877399-50-3|tert-Butyl 4-(4-bromo-1H-pyrazol-1-yl)piperidine-1-carboxylate| Ambeed

Structure of 877399-50-3

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Quality Control of [ 877399-50-3 ] Purity: 95% SDS Specification

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Product Details of [ 877399-50-3 ]

CAS No. :	877399-50-3
Formula :	C₁₃H₂₀BrN₃O₂
M.W :	330.22
SMILES Code :	BrC1=CN(C2CCN(C(OC(C)(C)C)=O)CC2)N=C1
MDL No. :	MFCD09831980
InChI Key :	IYNZAVDBHAQODX-UHFFFAOYSA-N
Pubchem ID :	45480278

Safety of [ 877399-50-3 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302
Precautionary Statements:	P280-P305+P351+P338

Computational Chemistry of [ 877399-50-3 ] Show Less

Physicochemical Properties

Num. heavy atoms	19
Num. arom. heavy atoms	5
Fraction Csp3	0.69
Num. rotatable bonds	4
Num. H-bond acceptors	3.0
Num. H-bond donors	0.0
Molar Refractivity	80.86
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	47.36 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	3.17
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	2.27
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.84
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	2.1
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	1.37
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.35

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.25
Solubility	0.186 mg/ml ; 0.000565 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-2.9
Solubility	0.414 mg/ml ; 0.00126 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-2.63
Solubility	0.776 mg/ml ; 0.00235 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	Yes
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	Yes
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.7 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<0.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	2.57

Application In Synthesis of [ 877399-50-3 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 877399-50-3 ]

[ 877399-50-3 ] Synthesis Path-Downstream 1~35

1
[ 877399-50-3 ]
[ 877399-49-0 ]
4-(4-{6-amino-5-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With nitrogen; sodium carbonate;Pd(PPh3)2Cl2; In 1,2-dimethoxyethane; water; ethyl acetate;	To a stirred solution of 3-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine (15.22 g, 35.64 mmol) and <strong>[877399-50-3]4-(4-bromo-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester</strong> (14.12 g, 42.77 mmol) in DME (143 mL) was added a solution of Na2CO3 (11.33 g, 10692 mmol) in water (36 mL). The solution was degassed and charged with nitrogen three times. To the solution was added Pd(PPh3)2Cl2 (1.25 mg, 1.782 mmol). The reaction solution was degassed and charged with nitrogen again three times. The reaction solution was stirred at 87° C. oil bath for about 16 hours (or until consumption of the borane pinacol ester), cooled to ambient temperature and diluted with EtOAc (600 mL). The reaction mixture was filtered through a pad of celite and washed with EtOAc. The EtOAc solution was washed with brine, dried over Na2SO4, and concentrated. The crude product was purified on a silica gel column eluding with EtOAc/Hexane system (Biotage 90+Column: equilibrium 600 mL 100percent Hexanes, segment 1: 2250 mL 50percent EtOAc/Hexanes Linear, segment 2: 4500 mL 75percent EtOAc/Hexanes Linear, segment 3: 4500 mL 100percent EtOAc) to afford 4-(4-{6-amino-5-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (11.8 g, 60percent yield, ~95percent purity) with a Rf of 0.15 (50percent EtOAc/Hexanes). MS m/e 550 (M+1)+.
65%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; ethyl acetate; at 87℃; for 16h;	To a stirred solution of 3-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine (4.2711 g, 10.0 mmol) and <strong>[877399-50-3]4-(4-bromo-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester</strong> (see procedure 11) (3.9628 g, 12.0 mmol) in DME (40 mL) was added a solution of Na2CO3 (3.1787 g, 30.0 mmol) in water (10 mL). The solution was degassed and charged with nitrogen three times. To the solution was added Pd(PPh3)2Cl2 (351 mg, 0.50 mmol). The reaction solution was degassed and charged with nitrogen again three times. The reaction solution was stirred at 87° C. oil bath for about 16 hours (or until consumption of the borane pinacol ester), cooled to ambient temperature and diluted with EtOAc (200 mL). The reaction mixture was filtered through a pad of celite and washed with EtOAc. The EtOAc solution was washed with brine, dried over Na2SO4, and concentrated. The crude product was purified on a silica gel column eluding with EtOAc/hexane system (0percent EtOAc to 100percent EtOAc) to afford 4-(4-{6-amino-5-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (3.4167 g, 65percent yield, 95percent purity) with a Rf of 0.15 (50percent EtOAc/Hexanes). MS m/e 550 (M+1)+.
65%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; at 87℃; for 16h;	To a stirred solution of 3-[(fl)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine (4.2711 g, 10.0 mmol) and <strong>[877399-50-3]4-(4-bromo-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester</strong> (see procedure 11) (3.9628 g, 12.0 mmol) in DME (40 mL) was added a solution of Na2CO3 (3.1787 g, 30.0 mmol) in water (10 mL). The solution was degassed and charged with nitrogen three times. To the solution was added Pd(PPh3)2CI2 (351 mg, 0.50 mmol). The reaction solution was degassed and charged with nitrogen again three times. The reaction solution was stirred at 87°C oil bath for about 16 hours (or until consumption of the borane pinacol ester), cooled to ambient temperature and diluted with EtOAc (200 mL). The reaction mixture was filtered through a pad of celite and washed with EtOAc. The EtOAc solution was washed with brine, dried over Na2SO4, and concentrated. The crude product was purified on a silica gel column eluting with EtOAc/hexane system (0percent EtOAc to 100percent EtOAc) to afford 4-(4-{6-amino-5-[(fl)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (3.4167 g, 65percent yield, -95percent purity) with a Rf of 0.15 (50percent EtOAc/Hexanes). MS m/e 550 (M+1)+.

65%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In 1,2-dimethoxyethane; water; at 87℃; for 16h;Inert atmosphere;	To a stirred solution of 3-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine (4.2711 g, 10.0 mmol) and <strong>[877399-50-3]4-(4-bromo-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester</strong> (3.9628 g, 12.0 mmol) in DME (40 mL) was added a solution of Na2CO3 (3.1787 g, 30.0 mmol) in water (10 mL). The solution was degassed and charged with nitrogen three times. To the solution was added Pd(PPh3J2CI2 (351 mg, 0.50 mmol). The reaction solution was degassed and charged with nitrogen again three times. The reaction solution was stirred at 87° C. oil bath for about 16 hours (or until consumption of the borane pinacol ester), cooled to ambient temperature and diluted with EtOAc (200 mL). The reaction mixture was filtered through a pad of celite and washed with EtOAc. The EtOAc solution was washed with brine, dried over Na2SO4, and concentrated. The crude product was purified on a silica gel column eluting with EtOAc/hexane system (0percent EtOAc to 100percent EtOAc) to afford 4-(4-{6-amino-5-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (3.4167 g, 65percent yield, ?95percent purity) with a Rf of 0.15 (50percent EtOAc/Hexanes). MS m/e 550 (M+1)+.
60%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; for 16h;Heating / reflux;	To a stirred solution of 3-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine (15.22 g, 35.64 mmol) and <strong>[877399-50-3]4-(4-bromo-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester</strong> (14.12 g, 42.77 mmol) in DME (143 mL) was added a solution of Na2CO3 (11.33 g, 10692 mmol) in water (36 mL). The solution was degassed and charged with nitrogen three times. To the solution was added Pd(PPh3)2Cl2 (1.25 g, 1.782 mmol). The reaction solution was degassed and charged with nitrogen again three times. The reaction solution was stirred at 87° C. oil bath for about 16 hours (or until consumption of the borane pinacol ester), cooled to ambient temperature and diluted with EtOAc (600 mL). The reaction mixture was filtered through a pad of celite and washed with EtOAc. The EtOAc solution was washed with brine, dried over Na2SO4, and concentrated. The crude product was purified on a silica gel column eluting with EtOAc/Hexane system (Biotage 90+ Column: equilibrium 600 mL 100percent Hexanes, segment 1:2250 mL 50percent EtOAc/Hexanes Linear, segment 2: 4500 mL 75percent EtOAc/Hexanes Linear, segment 3: 4500 mL 100percent EtOAc) to afford 4-(4-{6-amino-5-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (11.8 g, 60percent yield, 95percent purity) with a Rf of 0.15 (50percent EtOAc/Hexanes). MS m/e 550 (M+1)+.
60%		To a stirred solution of 3-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine (15.22 g, 35.64 mmol) and <strong>[877399-50-3]4-(4-bromo-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester</strong> (14.12 g, 42.77 mmol) in DME (143 mL) was added a solution of Na2CO3 (11.33 g, 10692 mmol) in water (36 mL). The solution was degassed and charged with nitrogen three times. To the solution was added Pd(PPh3)2Cl2 (1.25 mg, 1.782 mmol). The reaction solution was degassed and charged with nitrogen again three times. The reaction solution was stirred at 87° C. oil bath for about 16 hours (or until consumption of the borane pinacol ester), cooled to ambient temperature and diluted with EtOAc (600 mL). The reaction mixture was filtered through a pad of Celite® and washed with EtOAc. The EtOAc solution was washed with brine, dried over Na2SO4, and concentrated. The crude product was purified on a silica gel column eluting with EtOAc/Hexane system (Biotage 90+ Column: equilibrium 600 mL 100percent Hexanes, segment 1: 2250 mL 50percent EtOAc/Hexanes Linear, segment 2: 4500 mL 75percent EtOAc/Hexanes Linear, segment 3: 4500 mL 100percent EtOAc) to afford 4-(4-{6-amino-5-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (11.8 g, 60percent yield, ?95percent purity) with a Rf of 0.15 (50percent EtOAc/Hexanes). MS m/e 550 (M+1)+.

References: [1]Patent: US2008/300273,2008,A1 .
[2]Patent: US2006/46991,2006,A1 .Location in patent: Page/Page column 62-63.
[3]Patent: WO2006/21881,2006,A2 .Location in patent: Page/Page column 70-71; 72.
[4]Patent: US9375425,2016,B2 .Location in patent: Page/Page column 14-15.
[5]Patent: US2008/293769,2008,A1 .Location in patent: Page/Page column 7.
[6]Patent: US2016/206608,2016,A1 .Location in patent: Paragraph 0267; 0268.

2
[ 877399-50-3 ]
[ 877399-60-5 ]

Yield	Reaction Conditions	Operation in experiment
		A 4 M solution of HCI in 1 ,4-dioxane (13.5 ml, 54 mmol) is added to a solution of 4-(4- Bromo-pyrazol-1-yl)-piperidine -1-carboxylic acid tert-butyl ester (as obtained in preparation 62, 5.92 g , 17.94 mmol) in CH2CI2 (50 ml) and the reaction mixture is stirred at RT for 6h. The suspension is filtered on a Por. 4 Fritte and the cake dissolved in EtOAc. A saturated solution of NaHCO3 is added and the phases are separated. The aqueous phase is extracted 3chi with EtOAc. The combined organic layers are washed with NaHCO3, brine, dried over Na2SO4, filtered and the filtrate is concentrated in vacuo. The residue is used without further purification in the next step, and afford the title compound as pale orange solid, Rt = 0.582 min (Acquity UPLC BEH C18, 2.1x50mm, 1.7 micron, detection 215nM, 0.1 min 2percent CH3CN in H2O , 2percent to 100percent CH3CN in H2O in 1.5min, 0.4 min 100percent CH3CN + 0.1percent TFA, flow rate 1.0ml/min); MS: 330 (M+1 , 79Br)+
	With trifluoroacetic acid; In dichloromethane; at 20℃;	To a solution of <strong>[877399-50-3]4-(4-bromo-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester</strong> (500 mg, 1.515 mmol) in CH2Cl2 (3 mL) was added TFA (3 mL). The reaction was stirred at room temperature until LCMS indicated completion of the reaction. The solvents were removed in vacuo, and the residue was dissolved in MeOH (15 mL). The pH of the solution was adjusted to 9 with hydroxide resin to afford 4-(4-bromo-pyrazol-1-yl)-piperidine.
	With trifluoroacetic acid; In dichloromethane; at 20℃;	To a solution of <strong>[877399-50-3]4-(4-bromo-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester</strong> (500 mg, 1.515 mmol) in CH2CI2 (3 mL) was added TFA (3 mL). The reaction was stirred at room temperature until LCMS indicated completion of the reaction. The solvents were removed in vacuo, and the residue was dissolved in MeOH (15 mL). The pH of the solution was adjusted to 9 with hydroxide resin to afford 4-(4-bromo-pyrazol-1 -yl)-piperidine.

To a stirred solution of 4-(4-Bromo-pyrazol-1-yl)-pipehdine-1-carboxylic acid tert-butyl ester (1.2 g, 3.6 mmol) in CH2CI2 (4 ml) was added TFA (2 ml) and the reaction m ixture stirred at room temperature for 2 h. The volatiles were removed in vacuo and the residue partitioned between CH2CI2/NaHCO3(aq). The aqueous layer was extracted with CH2CI2 (x3), and the organic fractions combined, dried (using a phase separating cartridge) and the solvent removed in vacuo to give a solid. (0.49 g). 1 H NMR (400 MHz, CDCI3): 7.48 (1 H, s), 7.46 (1 H, s), 4.29-4.15 (1 H, m), 3.27 (2H, d), 2.99-2.75 (2H, m), 2.16 (2H, d), 2.05-1.81 (2H, m).

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 4092 - 4108.
[2]Patent: WO2008/148867,2008,A2 .Location in patent: Page/Page column 62.
[3]Patent: US2006/46991,2006,A1 .Location in patent: Page/Page column 64-65.
[4]Patent: WO2006/21881,2006,A2 .Location in patent: Page/Page column 74-75.
[5]Patent: WO2009/150240,2009,A1 .Location in patent: Page/Page column 120.

3
[ 2075-45-8 ]
[ 141699-59-4 ]
[ 877399-50-3 ]

Yield	Reaction Conditions	Operation in experiment
77%	With 1-methyl-pyrrolidin-2-one; caesium carbonate; at 80℃; for 12h;Large scale;	2.08 kg of cesium carbonate,0.78 kg of 4-bromopyrazole was dissolved in 4 liters of N-methylpyrrolidone,Heated to 80 degrees,A 5 liter solution of N-methylpyrrolidone was added to 1.8 kg of compound (CZT-7)Reaction for 12 hours.Cooled to room temperature,Add 50 litersMethyl tert-butyl etherwith50 liters of water,Stir for 1 hour.After dispensing,The organic phase was washed with 20 liters of * 4 water and dried 50percentLiter of hexane and stirred at room temperature for 2 hours. Filtered and dried to give 1.35 kg of compound (CZT-8) in a yield of 77percent
58%		B. To a cold solution (0 °C) of 4-bromo-lH-pyrazole (14.9 g, 0.10 mol) in 80 mL of dichloromethane was added sodium hydride (8.13 g, 0.20 mol) portion wise. The mixture was stirred at 0 °C for 1 hour, followed by the addition of a solution of tert-butyl 4-((methylsulfonyl)oxy)piperidine-l-carboxylate (34.0 g, 0.12 mol) in 30 mL of N,N-dimethylformamide. The resulting mixture was heated at 110 °C overnight. Purification by column chromatography afforded tert-butyl 4-(4-bromo-lH- pyrazol-l-yl)piperidine-l-carboxylate as a yellow oil in 58percent yield (19.5 g). 1H NMR (400 MHz, CDC13) delta 7.48 (s, 1H), 7.44 (s 1H), 4.35-4.20 (m, 3H), 2.95-2.85 (m, 2H), 2.15-2.05 (m, 2H), 1.92-1.81 (m, 2H), 1.48 (s, 9H).
45%		To a stirred solution of 4-bromo-pyrazole (10.44 g, 71.03 mmol) in anhydrous DMF (96 mL), cooled to 0° C., was slowly added NaH (60percent in mineral oil) (3.13 g, 78.133 mmol). The solution was stirred for 1 hour at 0° C. 4-Methanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester (19.82 g, 71.03 mmol) was added slowly and the reaction was heated to 100° C. overnight or until consumption of the pyrazole by NMR. The reaction was cooled to room temperature and water added (20 mL) followed by extraction with EtOAc. The combined extracts were washed with saturated aqueous NaCl (4*20 mL), dried with Na2SO4 and concentrated to afford 4-(4-bromo-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester as an orange oil. The oil was purified using silica gel chromatography eluding with 10percent EtOAc/hexanes to 25percent EtOAc/hexanes to provide 4-(4-bromo-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester as a white solid (10.55 g, 45percent yield) with a Rf=0.4 (25percent EtOAc/hexanes, using iodine as the stain). 1H NMR (CDCl3, 400 MHz) delta 7.46 (s, 1H), 7.43 (s, 1H), 4.23 (m, 3H), 2.88 (m, 2H), 2.10 (m, 2H), 1.88 (m, 2H), 1.47 (s, 9H).

45%		To a stirred solution of 4-bromo-pyrazole (10.44 g, 71.03 mmol) in anhydrous DMF (96 mL), cooled to 0°C, was slowly added NaH (60percent in mineral oil) (3.13 g, 78.133 mmol). The solution was stirred for 1 hour at 0°C. 4-Methanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester (19.82 g , 71.03 mmol) was added slowly and the reaction was heated to 100°C overnight or until consumption of the pyrazole by NMR. The reaction was cooled to room temperature and water added (20 mL) followed by extraction with EtOAc. The combined extracts were washed with saturated aqueous NaCI (4 x 20 mL), dried with Na2SO4 and concentrated to afford 4-(4-bromo-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester as an orange oil. The oil was purified using silica gel chromatography eluting with 10percent EtOAc/hexanes to 25percent EtOAc/hexanes to provide 4-(4-bromo-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester as a white solid (10.55 g, 45percent yield) with a R^= 0.4 (25percent EtOAc/hexanes, using iodine as the stain). 1H NMR (CDCI3, 400 MHz) 8 7.46 (s, 1H), 7.43 (s, 1H), 4.23 (m, 3H), 2.88 (m, 2H), 2.10 (m, 2H), 1.88(m, 2H), 1.47(s, 9H).
		NaH (60percent in mineral oil, 1.36 g, 34 mmol) is added portionwise to a stirred solution of 4- bromopyrazole (4.58 g, 30.9 mmol) in DMF (20 ml). The resulting mixture is stirred for 1h at O0C and 4-Methanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester (as obtained in preparation 61 , 8.62 g, 30.9 mmol) is added. The resulting pale suspension is heated at 1000C for 1h. The reaction is quenched with water and extracted with EtOAc several times. The combined organic layers are washed with brine, dried over Na2SO4, filtered and the filtrate is concentrated in vacuo. The residue is purified by chromatography on a 120 g silica gel column on a Combiflash Companion.(TM). (Isco Inc.) apparatus ( gradient hexanes: TBDME from 1 :0 => 0:1) to afford the title compound as a colorless solid, Rt = 1.213 min (Acquity UPLC BEH C18, 2.1x50mm, 1.7 micron, detection 215nM, 0.1 min 2percent CH3CN in H2O , 2percent to 100percent CH3CN in H2O in 1.5min, 0.4 min 100percent CH3CN + 0.1 percent TFA, flow rate 1.0ml/min); MS: 330 (M+1, 79Br)+.
		As shown in step 3-ii of Scheme 3, to a solution of 4-bromopyrazole (4.68 g, 31.83 mmol) in DMF (300 mL) at 00C was added sodium hydride (60percent on mineral oil, 1.27 g, 31.83 mmol). The solution was stirred at 00C for one hour, at which point a solution of Compound 1013 (9.78 g, 31.83 mmol) in DMF (50 mL) was added dropwise. The reaction mixture was stirred at room temperature for 1 hour and then refluxed for 16 hours. Disappearance of both starting materials was observed by TLC (1 : 1 EtOAc/hexanes). The reaction was cooled to room temperature, quenched by the addition of brine (300 mL), and extracted with ethyl acetate (3 x 200 mL). The combined organics were washed with 1percent aqueous LiCl (3 x 200 mL), dried over sodium sulfate, and concentrated under reduced pressure. The resulting crude bromide was purified by silica gel chromatography (0 - 25percent EtOAc/hexanes) to give Compound 1014.
	With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 80℃; for 12h;	c) tert-Butyl 4-(4-bromo- 1 H-pyrazol- 1 -yl)piperidine- 1 -carboxylateTo a cooled solution of the compound of Intermediate Example 5(b) (6.7 g, 23.9 mmol) in DMF (50 ml) was added NaH (2.8 g, 1 19 mmol, 5 eq.) and 4-bromo-lH-pyra- zole (2.8 g, 19.1 mmol, 0.8 eq.) and stirred at 80 °C for 12 h. The mixture was quenched and extracted with ethyl acetate (3 chi 100 ml). The combined organic layer was washed with water, brine and dried over sodium sulphate. The solvent was distilled off to afford the crude product (8.0 g).
		General procedure: To an ice-cooled solution of 4-bromo-1H-pyrazole (1.19 g, 8.07 mmol) in 10 mL of DMF was added portionwise sodium hydride (355 mg, 8.88 mmol, 60percent in oil). The resulting mixture was stirred for additional 1 h. Then to the mixture was added oxan-4-yl methanesulfonate (1.60 g, 8.88 mmol), which was prepared in a similar manner as described for 12. The resulting mixture was gradually heated to 100 °C and stirred for 10 h. After cooled to room temperature, the reaction was quenched with water. The mixture was extracted with EA. The organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated under vacuum. The crude product was purified by silica gel column chromatography (EA/PE, 1:6) to afford 26a as a white solid in 61percent yield.
	With sodium hydride; In N,N-dimethyl-formamide; at 80℃; for 12h;	To a cooled solution of the compound of Intermediate Example 5(b) (6.7 g, 23.9 mmol) in DMF (50 ml) was added NaH (2.8 g, 119 mmol, 5 eq.) and 4-bromo-1H-pyrazole (2.8 g, 19.1 mmol, 0.8 eq.) and stirred at 80° C. for 12 h. The mixture was quenched and extracted with ethyl acetate (3*100 ml). The combined organic layer was washed with water, brine and dried over sodium sulphate. The solvent was distilled off to afford the crude product (8.0 g).
	With sodium hydride; In N,N-dimethyl-formamide; at 20 - 110℃;Inert atmosphere;	Sodium hydride (400 mg, 60percent dispersion, 10 mmol) was added to a stirred solution of the bromopyrazole (1.47g, lOmmol) and 4-Methanesulfonyloxy-pipehdine-1-carboxylic acid tert-butyl ester (2.4 g, 8.6 mmol) in dry DMF (10 ml) at room temperature. After gas evolution had ceased, the reaction was stirred and heated at 110 0C under N2 for 4 h. The reaction mixture was allowed to cool to room temperature and stand at for 18 h before being partitioned between EtOAc and H2O. The organic layer was separated, washed with water H2O (x2), brine (x1 ), then dried (Na2SO4), filtered and the solvent removed in vacuo.The residue was purified using silica column chromatography running a 10-25percentEtOAc/petrol gradient to give a colourless oil (1.7 g, 5.15 mmol). 1 H NMR (400 MHz,CDCI3): 7.48 (1 H, s), 7.45 (1 H, s), 4.45-4.07 (3H, m), 2.90 (2H, t), 2.12 (2H, d), 1.97-1.79(2H, m), 1.50 (9H, s).

References: [1]Patent: CN106317024,2017,A .Location in patent: Paragraph 0060; 0061.
[2]Journal of Medicinal Chemistry,2011,vol. 54,p. 4092 - 4108.
[3]Patent: WO2015/81257,2015,A2 .Location in patent: Page/Page column 81.
[4]Tetrahedron Letters,2014,vol. 55,p. 1528 - 1531.
[5]Patent: US2006/46991,2006,A1 .Location in patent: Page/Page column 64-65.
[6]Patent: WO2006/21881,2006,A2 .Location in patent: Page/Page column 74; 75.
[7]Patent: WO2008/148867,2008,A2 .Location in patent: Page/Page column 51-52.
[8]Patent: WO2010/48131,2010,A1 .Location in patent: Page/Page column 54.
[9]Patent: WO2013/53983,2013,A1 .Location in patent: Page/Page column 31.
[10]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 6804 - 6820.
[11]Patent: US2015/11548,2015,A1 .Location in patent: Paragraph 0136.
[12]Bioorganic Chemistry,2016,vol. 65,p. 146 - 158.
[13]Patent: WO2009/150240,2009,A1 .Location in patent: Page/Page column 119.

4
[ 877399-50-3 ]
[ 68-12-2 ]
[ 1076224-00-4 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 5209 - 5212.

5
[ 877399-50-3 ]
4-(4-bromopyrazol-1-yl)piperidine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In ethyl acetate; at 20℃; for 2h;	To 4-(4-Bromo-pyrazol-1-yl)-pipehdine-1-carboxylic acid tert-butyl ester (1 g, 3. mmol) in ETOAc (4 ml) was added sat. ETOAc in HCI (5 ml) and the reaction mixture stirred at room temperature for 2 h. The solvent removed in vacuo and re-evaporated with toluene to give the product (0.68 g), which was used without further purification MS: [M+H]+ = 230

References: [1]Patent: WO2009/150240,2009,A1 .Location in patent: Page/Page column 135.

6
[ 877399-50-3 ]
[ 1036991-14-6 ]
C₂₉H₃₂F₃N₇O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate;tris-(dibenzylideneacetone)dipalladium(0); In 1,4-dioxane; at 120℃; for 0.5h;Inert atmosphere; Microwave irradiation;	To a mixture of 1-{3-[7-(4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolan-2-yl)-imidazo[1 ,2-a]pyhdin- 3-yl]-phenyl}-3-(2,2,2-thfluoro-ethyl)-urea (460 mg, 1.00 mmol), in a MW tube was added 4- (4-Bromo-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (500 mg, 1.5 mmol), SPHOS (41 mg, 0.1 mmol) and Pd2(dba)3 (45 mg, 0.05 mmol) in dioxane (6 ml) followed by a 1 M K3PO 4 (3 ml) in water. The reaction mixture was heated in a CEM discover m icrowave <n="109"/>synthesizer (300W) at 120 0C for 30 min. The mixture was allowed to cool, then partitioned between EtOAc /H2O, the organic layer was separated, extracted with EtOAc (x2), dried (Na2SO4), filtered and the solvent removed in vacuo. The residue was purified by silica column chromatography running a 0-3percent 2M methanolic NH3/CH2CI2 gradient. This afforded the crude product as a yellow gum (210mg), which was used directly in the next step.

References: [1]Patent: WO2009/150240,2009,A1 .Location in patent: Page/Page column 106-107.

7
[ 877399-50-3 ]
[ 73183-34-3 ]
[ 877399-74-1 ]

Yield	Reaction Conditions	Operation in experiment
81%	With isopropylmagnesium chloride; In tetrahydrofuran; at -10 - 30℃; for 9h;Inert atmosphere; Large scale;	1.3 kg of compound (CZT-8) was dissolved in 6.5 liters of dry tetrahydrofuran,Nitrogen protection,Down to -10 degrees,A solution of 3.2 liters of 2N isopropylmagnesium chloride in tetrahydrofuran was slowly added,After the completion of heating to 20 degrees,Add 1.0 publicjinEven boronic acid6.5 liters of tetrahydrofuran solution,Control the temperature between 20 degrees to 30 degrees,After the completion of the reaction at room temperature for 9 hours.Add 9 liters of ethyl acetate and 10 liters of water,Stir for 2 hours,Dispensing,Dried and concentrated.Recrystallization gave 1.2 kg of a white solid(CZT-9). Yield 81%
44%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In dimethyl sulfoxide; at 80℃; for 0.166667h;Inert atmosphere;	C. A mixture of tert-butyl 4-(4-bromo- lH-pyrazol- 1 -yl)piperidine- 1-carboxylate (20.0 g, 0.61 mmol), 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)-l,3,2-dioxaborolane (30.8 g, 0.12 mmol) and potassium acetate (17.8 g, 0.18 mol) in 50 mL of dimethyl sulfoxide was purged with nitrogen gas for 10 min. After the addition of [l, -bis(diphenylphosphino)ferrocene]dichloropalladium(II) (3.55 g, 4.85 mmol), the mixture was purged with nitrogen gas for another 10 minutes, heated at 80 C overnight under nitrogen atmosphere and filtered through celite and washed with ethyl acetate. The filtrate was extracted with ethyl acetate (2 x 200 mL). The organic layer was dried over anhydrous sodium sulfate. After filtration and removal of the solvent, the residue was purified by column chromatograph eluted with hexane to afford an oil which was recrystallized from hexane to afford tert-butyl 4-(4-(4,4,5,5- tetramethyl- 1 ,3 ,2-dioxaborolan-2-yl)- lH-pyrazol- 1 -yl)piperidine- 1 -carboxylate as a white solid in 44% yield (10 g). 1H NMR (400 MHz, CDC13) delta 7.79 (s, 1H), 7.72 (s, 1H), 4.32-4.13 (m, 3H), 2.95-2.80 (m, 2H), 2.15-2.05 (m, 2H), 1.93-1.82 (m, 2H), 1.47 (s, 9H), 1.31 (s, 12H).
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 90℃;Inert atmosphere;	As shown in step 3-iii of Scheme 3, tert-butyl 4-(4-bromo-lH-pyrazol-l- yl)piperidine-l-carboxylate (Compound 1014, 10.52 g, 31.86 mmol), 4,4,5, 5-tetramethyl-2- (4,4,5, 5-tetramethyl-l,3,2-dioxaborolan-2-yl)-l,3,2-dioxaborolane (9.71 g, 38.23 mmol), and potassium acetate (9.38 g, 95.58 mmol) were taken up in 105 mL of 1,4-dioxane. The mixture was flushed with nitrogen for 20 minutes and PdCl2(dppf) (1.3 g, 1.59 mmol) was added. The reaction was heated at 900C for 11 hours. The reaction was cooled to room temperature and filtered through a plug of Florisil, which was subsequently rinsed with ethyl acetate. The filtrate was concentrated under reduced pressure to afford a dark brown oil that was dissolved in hexanes and eluted through a second plug of Florisil with 1 :2 EtOAc/hexanes. The filtrate was concentrated under reduced pressure to give a tan oil, which was triturated with hexanes and stirred at 00C until a white precipitate formed. The precipitate was collected by vacuum filtration, washed with hexanes, and dried to afford 6.79 g of tert-butyl 4-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazol-l-yl)piperidine- 1-carboxylate (Compound 1015).

5.4 g	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 100℃; for 12h;Inert atmosphere; Sealed tube;	d) tert-Butyl 4-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazol-l- yl)piperidine- 1 -carboxylateTo a (N2 bubbling) solution of the compound of Intermediate Example 5(c) (8 g, 24.2 mmol) in 1,4-dioxane (100 ml) were added 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi- (1,3,2-dioxaborolane) (7.36 g, 29 mmol, 1.2 eq.), Pd(dppf)Cl2 (2 g, 2.42 mmol, 0.1 eq.) and potassium acetate (8 g, 82.4 mmol, 3.4 eq.) using the procedure of Intermediate Example 1(b). The solvent was distilled off and the residue was purified by column chromatography (60-120 silica gel, 10 % ethyl acetate in hexane) to give the product in 59 % yield (5.4 g). LC-MS (ESI): Calculated mass: 377.29; Observed mass: 378.3[(M+H]+ (RT: 1.83 min).
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In N,N-dimethyl-formamide; at 80℃; for 10h;Inert atmosphere;	General procedure: To a solution of 4-bromo-1-(oxan-4-yl)-1H-pyrazole 26a (1.00 g, 4.33 mmol) and 4,4,5,5-tetramethyl-2-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (1.32 g, 5.19 mmol) in 10 mL of DMF was added potassium acetate (1.27 g, 12.98 mmol), followed by 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (177 mg, 0.22 mmol) under argon. The resulting mixture was stirred at 80 C for 10 h and then diluted with 40 mL of water. The mixture was extracted with EA (3 × 30 mL). The combined organic phase was washed with water (3 × 30 mL), brine, dried over anhydrous Na2SO4 and concentrated under vacuum. The crude product was purified by silica gel column chromatography (EA/PE, 1:4) to afford 25c as white solid in 68% yield.
5.4 g	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 110℃; for 12h;Inert atmosphere;	To a (N2 bubbling) solution of the compound of Intermediate Example 5(c) (8 g, 24.2 mmol) in 1,4-dioxane (100 ml) were added 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-(1,3,2-dioxaborolane) (7.36 g, 29 mmol, 1.2 eq.), Pd(dppf)Cl2 (2 g, 2.42 mmol, 0.1 eq.) and potassium acetate (8 g, 82.4 mmol, 3.4 eq.) using the procedure of Intermediate Example 1(b). The solvent was distilled off and the residue was purified by column chromatography (60-120 silica gel, 10% ethyl acetate in hexane) to give the product in 59% yield (5.4 g). LC-MS (ESI): Calculated mass: 377.29; Observed mass: 378.3 [(M+H]' (RT: 1.83 min).

References: [1]Organic Letters,2019,vol. 21,p. 8158 - 8163.
[2]Patent: CN106317024,2017,A .Location in patent: Paragraph 0062; 0063; 0064; 0065'; 0066.
[3]Patent: WO2015/81257,2015,A2 .Location in patent: Page/Page column 81-82.
[4]Patent: WO2010/48131,2010,A1 .Location in patent: Page/Page column 54-55.
[5]Patent: WO2013/53983,2013,A1 .Location in patent: Page/Page column 31; 32.
[6]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 6804 - 6820.
[7]Patent: US2015/11548,2015,A1 .Location in patent: Paragraph 0137.
[8]Bioorganic Chemistry,2016,vol. 65,p. 146 - 158.

8
[ 877399-50-3 ]
[ 1309961-03-2 ]

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 4092 - 4108.

9
[ 877399-50-3 ]
[ 1309960-75-5 ]

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 4092 - 4108.

10
[ 877399-08-1 ]
[ 877399-50-3 ]
[ 877401-42-8 ]

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 6342 - 6363.

11
[ 877399-50-3 ]
potassiumhexacyanoferrate(II) trihydrate [ No CAS ]
[ 1361058-63-0 ]

Yield	Reaction Conditions	Operation in experiment
84.85%	With tetrakis(triphenylphosphine) palladium(0); 1,8-diazabicyclo[5.4.0]undec-7-ene; In water; tert-butyl alcohol; at 90℃; for 16h;Sealed tube;	To a stirred solution of tert-butyl 4-(4-bromopyrazol-l-yl)piperidine-l-carboxylate Sl-4 (1 g, 3.03 mmol) in tert- Butanol (7 rnL) and water (7 rnL) in a sealed tube was added Potassium ferrocyanide, trihydrate (511.65 mg, 1.21 mmol) and DBU (1 15.26 mg, 757.07 Ltmol) the reaction mixture was degassed with argon and then Palladium (0) tetrakis(triphenylphosphine) (174.97 mg, 151 .41 mhio) was added and the sealed tube was closed tightly and the reaction was allowed to stir at 90 C for 16 hours. The reaction mixture was filtered through a celite bed, washed with ethyl acetate and then concentrated. The crude residue was dissolved in ethyl acetate and washed with water, brine, dried over sodium sulphate and concentrated under reduced pressure. The crude product was then purified by column chromatography using (silica, gradient 25%-30% EtOAc/Hexane) to provide /erf-butyl 4-(4-cyanopyrazol-l-yl) piperidine- 1-carboxyiate Sl~5 (710 mg, 2.57 mmol, 84.85% yield). LCMS: ES+277.2. NMR (400 MHz, DMSO -ck) d 8 64 (s, 1H),8.07 (s, 1H), 4.42-4.48 (m, 1H), 4.00-4.05 (m, 2H), 2.90 (br, 2H), 2.00 (m, 2H), 1.71-1.80 (m, 2H),1.41 (s, 9H).

References: [1]Patent: WO2019/191112,2019,A1 .Location in patent: Page/Page column 206; 207.
[2]Chemical Communications,2012,vol. 48,p. 2909 - 2911.

12
[ 109384-19-2 ]
[ 877399-50-3 ]

References: [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 6804 - 6820.
[2]Tetrahedron Letters,2014,vol. 55,p. 1528 - 1531.
[3]Patent: US2015/11548,2015,A1 .
[4]Patent: WO2015/81257,2015,A2 .
[5]Bioorganic Chemistry,2016,vol. 65,p. 146 - 158.
[6]Patent: CN106317024,2017,A .
[7]Patent: WO2013/53983,2013,A1 .

13
[ 5382-16-1 ]
[ 877399-50-3 ]

References: [1]Patent: US2015/11548,2015,A1 .
[2]Patent: WO2013/53983,2013,A1 .

14
[ 24424-99-5 ]
[ 877399-50-3 ]

References: [1]Patent: US2015/11548,2015,A1 .
[2]Patent: WO2013/53983,2013,A1 .

15
[ 877399-50-3 ]
[ 1430727-71-1 ]

References: [1]Patent: US2015/11548,2015,A1 .
[2]Patent: WO2013/53983,2013,A1 .

16
[ 877399-50-3 ]
[ 1430723-67-3 ]

References: [1]Patent: US2015/11548,2015,A1 .
[2]Patent: WO2013/53983,2013,A1 .

17
[ 877399-50-3 ]
[ 1430728-12-3 ]

References: [1]Patent: US2015/11548,2015,A1 .
[2]Patent: WO2013/53983,2013,A1 .

18
[ 877399-50-3 ]
[ 1430724-58-5 ]

References: [1]Patent: US2015/11548,2015,A1 .
[2]Patent: WO2013/53983,2013,A1 .

19
[ 877399-50-3 ]
[ 1430724-59-6 ]

References: [1]Patent: US2015/11548,2015,A1 .
[2]Patent: WO2013/53983,2013,A1 .

20
[ 877399-50-3 ]
[ 1430728-20-3 ]

References: [1]Patent: US2015/11548,2015,A1 .
[2]Patent: WO2013/53983,2013,A1 .

21
[ 877399-50-3 ]
[ 1430724-66-5 ]

References: [1]Patent: US2015/11548,2015,A1 .
[2]Patent: WO2013/53983,2013,A1 .

22
[ 877399-50-3 ]
1-{4-[4-(6-amino-5-[1-(2,6-dichloro-3-fluorophenyl)ethyl]sulfanyl}pyridin-3-yl)-1H-pyrazol-1-yl]piperidin-1-yl}-2-hydroxyethanone [ No CAS ]