42182-27-4|2-Amino-4-cyanopyridine| Ambeed

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Quality Control of [ 42182-27-4 ] Purity: 98% SDS Specification

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Product Details of [ 42182-27-4 ]

CAS No. :	42182-27-4
Formula :	C₆H₅N₃
M.W :	119.12
SMILES Code :	C1=NC(=CC(=C1)C#N)N
MDL No. :	MFCD03791310
InChI Key :	GEEAYLFEIFJFGP-UHFFFAOYSA-N
Pubchem ID :	7015524

Safety of [ 42182-27-4 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H312-H315-H319-H332
Precautionary Statements:	P261-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P312-P332+P313-P337+P313

Computational Chemistry of [ 42182-27-4 ] Show Less

Physicochemical Properties

Num. heavy atoms	9
Num. arom. heavy atoms	6
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	2.0
Num. H-bond donors	1.0
Molar Refractivity	33.36
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	62.7 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.88
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	0.22
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	0.54
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.	-0.43
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	0.62
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.37

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.21
Solubility	7.34 mg/ml ; 0.0616 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-1.1
Solubility	9.55 mg/ml ; 0.0801 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very 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	-1.7
Solubility	2.37 mg/ml ; 0.0199 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	No
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	No
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	No
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.	-6.87 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	1.0
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<1.0
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)	1.56

Application In Synthesis of [ 42182-27-4 ]

* 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.

Upstream synthesis route of [ 42182-27-4 ]
Downstream synthetic route of [ 42182-27-4 ]

[ 42182-27-4 ] Synthesis Path-Upstream 1~1

1
[ 75-16-1 ]
[ 42182-27-4 ]
[ 42182-25-2 ]

References: [1] Patent: WO2011/14515, 2011, A1, . Location in patent: Page/Page column 123.

[ 42182-27-4 ] Synthesis Path-Downstream 1~35

1
[ 42182-27-4 ]
[ 84486-96-4 ]

References: [1]Australian Journal of Chemistry,1982,vol. 35,p. 2025 - 2034.

2
[ 42182-27-4 ]
[ 944401-72-3 ]

Yield	Reaction Conditions	Operation in experiment
78%	With N-Bromosuccinimide; In N,N-dimethyl-formamide; at -18℃; for 1h;	Step 2.1 : 2-Amino-5-bromo-isonicotinonitrile.A solution of <strong>[42182-27-4]2-amino-isonicotinonitrile</strong> (10.0 g, 83.9 mmol) in DMF (20 mL) was cooled to -18°C (ice / MeOH bath), treated with NBS (16.5 g, 92.3 mmol), and stirred at -18°C for 1 h. The reaction mixture was diluted in AcOEt (500 mL) and washed with water {200 mL). The aqueous phase was separated and extracted with AcOEt (2 x 500 ml). The combined organic fractions were dried over Na.sum.SO/t, filtered and evaporated. The residue was purified by Combi-Flash Companion.(TM). (Isco Inc.) column chromatography (SiO2; gradient elution, [hexane / DCM 1 :1] / TBME 98:2 --> 6:4) to yield the title compound (13.0 g, 65.6 mmol, 78percent) as a pale yellow solid. MS: 199 [M+1]+ ; HPLC: \\et = 1.13; TLC: RF 0.39 (hexane / DCM / TBME 1 :1 :2).
60%	With dihydrogen peroxide; 1-butylpyridinium bromide; toluene-4-sulfonic acid; In 1,2-dimethoxyethane; at 80℃; for 24h;Schlenk technique; Inert atmosphere; Green chemistry;	General procedure: To a mixture of 2-aminopyridine (0.5 mmol, 1 equiv), p-TSA (0.4 mmol,0.8 equiv), 1-butylpyridinium bromide (1.5 mmol, 3 equiv) in a 50 mL Schlenk tube were added 1,2-dimethoxyethane (2 mL) under air. Then H2O2 (1.2 mmol, 2.4 equiv) was added. The mixture was stirred at 80°C for 24 h. And then the mixture was purified by silica gel column chromatography (petroleum ether/ethyl acetate) to give the products.

References: [1]Patent: WO2007/113226,2007,A1 .Location in patent: Page/Page column 85-86.
[2]Tetrahedron Letters,2014,vol. 55,p. 5058 - 5061.
[3]ACS Medicinal Chemistry Letters,2015,vol. 6,p. 507 - 512.

3
[ 42182-27-4 ]
[ 930121-82-7 ]

Yield	Reaction Conditions	Operation in experiment
68%	With hydroxylamine hydrochloride; sodium carbonate; In ethanol; water; for 3h;Heating / reflux;	A stirred mixture of commercially available 2-amino-4-cyano-pyridine [CAS-No. 42182-27-4] (1.0 g, 8.39 mmol), hydroxylamine hydrochloride (1.17 g, 16.8 mmol) and sodium carbonate (0.89 g, 8.39 mol) in water (8 mL) and ethanol (16 mL) was heated under reflux conditions for 3 h. The reaction mixture was evaporated, water (10 mL) was added and the mixture stirred at room temperature for 1 h. The precipitate was collected by filtration to yield the title compound (0.87 g, 68percent) as an off-white solid. MS (EI) 152.0 [(M)+]; mp 188° C.

References: [1]Patent: US2007/232583,2007,A1 .Location in patent: Page/Page column 43.

4
[ 19798-80-2 ]
[ 557-21-1 ]
[ 42182-27-4 ]

References: [1]Organic Letters,2007,vol. 9,p. 1711 - 1714.

5
[ 42182-27-4 ]
2-amino-4-aminomethylpyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With hydrogen; triethylamine;palladium 10% on activated carbon; In ethanol; at 20℃; under 2585.81 Torr; for 12h;	Step 1.1 : 4-Aminomethvl-Dvridin-2-vlamine.In a sealed flask, a well stirred mixture of <strong>[42182-27-4]2-amino-isonicotinonitrile</strong> (12.6 g, 106.0 mmol), Et3N (98 mL) and Pd/C 10% (15.0 g) in EtOH (400 mL) was placed under an H2 atmosphere (50 psi) and hydrogenated at RT for 12h. The catalyst was filtered through a Celite pad and washed with MeOH. The filtrate was concentrated to dryness to yield the title compound (11.6 g, 94.2 mmol, 89%) as a white solid, which was used without further purification. MS: <n="84"/>122 [M-I]+ ; HPLC: V( = 0.16.
	With hydrogen; triethylamine;palladium 10% on activated carbon; In ethanol; under 2585.81 Torr; for 12h;	To a mixture of <strong>[42182-27-4]2-aminoisonicotinonitrile</strong> (0.043 mol) and Pd/C (10%, 6.00 g) was added Et3N (40.0 mL) and EtOH (160.0 mL) in a Parr bottle and hydrogenated at 50 psi for 12 h. Crude mixture was filtered through Celite, concentrated under vacuo and dried under high vacuum to yield compound.
1.82 g	With palladium 10% on activated carbon; hydrogen; triethylamine; In ethanol; at 20℃;	Step 1): Compound 46 (2.1 g, 17.6 mmol), Pd / C (250 mg, 10%, w / w = 50%) and triethylamine (16.3 mL) were added to ethanol (35 mL) at room temperature. Stir overnight at room temperature under hydrogen protection (50 psi).The reaction solution was filtered through celite and concentrated to dryness to obtain 1.82 g of a crude white solid which was directly used in the next synthesis.

References: [1]Patent: WO2007/113226,2007,A1 .Location in patent: Page/Page column 82-83.
[2]ChemMedChem,2017,vol. 12,p. 1953 - 1968.
[3]Patent: US2003/225106,2003,A1 .Location in patent: Page 96.
[4]Patent: CN110343089,2019,A .Location in patent: Paragraph 0347-0350.

6
[ 20099-90-5 ]
[ 42182-27-4 ]
4-(7-Cyanoimidazo[1,2-a]pyridin-2-yl)benzoic acid hydrobromide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol;	Example 5 8.5 g of <strong>[42182-27-4]2-amino-4-cyanopyridine</strong> and 27.5 g of 4-bromoacetylbenzoic acid are boiled in 260 ml of ethanol for 20 h. After cooling, the precipitate is filtered off with suction and subjected to the customary working-up. 4-(7-Cyanoimidazo[1,2-a]pyridin-2-yl)benzoic acid hydrobromide is obtained, m.p. >310°.

References: [1]Patent: US5614531,1997,A .

7
[ 42182-27-4 ]
[ 43219-50-7 ]
[ 66-25-1 ]
C₁₆H₂₂N₄O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid; In methanol; at 20℃;	To a solution of 4-cyano-2-aminopyridine (0.27 mg, 2.24 mmol) in MeOH (7.45 mL) was added the aldehyde (2.24 mmol), the isonitrile (2.24 mmol) and AcOH (260 muL, 4.48 mmol) at room temp. The reaction was stirred overnight and monitored by EPO <DP n="72"/>LCMS/TLC. When the reaction has completed, 1Lambda/ hydrochloric acid was added till pH ~ 1. The mixture was then evaporated. Saturated sodium bicarbonate solution was then added and ethyl acetate was used to extract. The combined organic extracts were then washed with brine, before drying in anhydrous sodium sulfate. The mixture was then filtered and concentrated. The crude product was used immediately without further purification (Tetrahedron Letters, 1998, 39, 3635).

References: [1]Patent: WO2006/101455,2006,A1 .Location in patent: Page/Page column 70-71.

8
[ 912673-53-1 ]
[ 42182-27-4 ]
S-6-methyl-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}-4-(4-cyanopyrid-2-ylamino)pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 60℃; for 18h;	Example 15; S-6-Methyl-2-{2-r3-(pyrid-2-vI)isoxazoI-5-yllpyrrolidin-l-vU-4-(4-cvanopyrid-2- gammalamino)pyrimidine; Tris(dibenzylideneacetone)dipalladium(0) (20mg, 0.022mmol), and 9,9-dimethyl-4,5- bis(diphenylphosphino)xanthene (20mg, 0.034mmol) were added to a mixture of 2-amino-4- cyanopyridine (60mg, 0.5mmol), S-4-chloro-6-methyl-2-{2-[3-(pyridin-2-yl)isoxazol-5- yl]pyrrolidin-l-yl}pyrimidine (188mg, 0.55mmol) and cesium carbonate (326mg, l.Ommol) in 1,4-dioxane (4ml) under nitrogen and the reaction mixture heated at 6O0C under nitrogen for 18 hours. The mixture was allowed to cool, the insoluble material removed by filtration, the solvent was removed from the filtrate by evaporation. The residue was purified by column chromatography on silica gel eluting with EtOAc / DCM (25:75) to give the title compound (140mg, 66percent) as a white solid; NMR Spectrum 1.95-2.32 (m, 6H), 2.32-2.47 (m, IH), 3.55-3.75 (m, IH), 3.75-3.95 (m, IH), 5.47-5.51 (d, IH), 6.46 (s, IH), 6.70 (s, IH), 7.32 (br s, IH), 7.42-7.54 (t, IH), 7.70-8.05 (m, 2H), 8.20-8.55 (br m, 2H), 10.12 (br slH); Mass Spectrum 425 [MH]+.

References: [1]Patent: WO2006/109026,2006,A1 .Location in patent: Page/Page column 95.

9
[ 42182-27-4 ]
[ 930121-82-7 ]

Yield	Reaction Conditions	Operation in experiment
68%	With hydroxylamine hydrochloride; sodium carbonate; In ethanol; water; for 3h;Heating / reflux;	Example B.6 2-Amino-N-hydroxy-pyridine-4-carboxamidine; A stirred mixture of commercially available 2-amino-4-cyano-pyridine [CAS-No. 42182-27-4] (1.0 g, 8.39 mmol), hydroxylamine hydrochloride (1.17 g, 16.8 mmol) and sodium carbonate (0.89 g, 8.39 mol) in water (8 ml) and ethanol (16 ml) was heated under reflux conditions for 3h. The reaction mixture was evaporated, water (10 ml) was added and the mixture stirred at room temperature for 1 h. The precipitate was collected by filtration to yield the title compound (0.87 g, 68percent) as an off-white solid. MS (EI) 152.0 [(M)+]; mp 188° C.

References: [1]Patent: US2007/72879,2007,A1 .Location in patent: Page/Page column 14.

10
[ 42182-27-4 ]
[ 75-36-5 ]
[ 939997-68-9 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 0℃; for 2h;	N-(4-Cyano-pyridin-2-yl)-acetamide 8 mmol of 2-Amino-isonicotinonitrile were dissolved in THF. 2 eq of DIPEA were added. The reaction mixture was cooled to 0° C. and 1.0 eq of acetylchloride in THF added dropwise and the reaction stirred for 2 h. The product was isolated by extraction from ethylacetate/water. MS(ISO): 162.2 (MH+)

References: [1]Patent: US2007/129544,2007,A1 .Location in patent: Page/Page column 42.

11
[ 42182-27-4 ]
[ 124-63-0 ]
[ 933989-22-1 ]

Yield	Reaction Conditions	Operation in experiment
66%	With pyridine; at 20℃; for 12h;	Example 76; 2-f3-Fluoro-phenyl)-pyrimidme-5-carboxylic acid (2-methanesulfonylamino-pyridin-4-ylmethyl)- amide; Step 1; A solution of <strong>[42182-27-4]2-amino-isonicotinonitrile</strong> (1 g, 8.4 mmol) and methanesulfonyl chloride (0.716 mL, 9.2 mmol) in pyridine (10 mL) is stirred at room temperature for 12 hours. The mixture is poured onto ice and stirred for 20 min. The mixture is filtered and washed with water (100 mL), followed by diethyl ether (100 mL). The solid is dried in vacuo to afford N-(4-cyanopyridin-2-yl)- methanesulfonamide (1.1 g, 66percent). MS: 198 (M+H); 1HNMR (300 MHz, DMSO-d6): delta 3.32 (s, 3H), 7.27 (s, IH), 7.48 (d, J= 5.1 Hz, IH), 8.53 (d, J= 5.3 Hz, IH).

References: [1]Patent: WO2007/41634,2007,A1 .Location in patent: Page/Page column 66.

12
[ 107-20-0 ]
[ 42182-27-4 ]
[ 952566-04-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In ethanol; at 20 - 80℃; for 18h;	Procedure W; Step 1: lmidazof1.2-aipyridine-7-carbonitrile; Chloroacetaldehyde (~50percent in H2O, 3.24 ml, 26 mmol) was added to a stirred mixture of 2- amino-isonicotinonitrile (1.6g, 3.4 mmol) and NaHCO3 (2.23g, 26.5 mmol) in ethanol (20ml) at RT under N2. The reaction was stirred and heated at 800C for 18 hours. After cooling to RT the volatiles were removed in vacuo and the residue was partitioned between EtOAc/H2O. This mixture was filtered to remove some dark insoluble residue. The solid was washed with MeOH. The aqueous layer was extracted with EtOAc (x2).The combined EtOAc extracts were dried (Na2SO4) and filtered. The MeOH washings were added and the volatiles were removed in vacuo. The residue was purified by chromatography on silica: 100percent DCM --> 1percent 2M NH3- <n="124"/>MeOH /DCM to give the title product. 1H NMR (400 MHz, DMSO-d6): 8.74 (1H1 dd), 8.35 (1H, s), 8.19 (1H, s), 7.86 (1H, s), 7.21 (1H, dd).

References: [1]Patent: WO2008/78100,2008,A2 .Location in patent: Page/Page column 122-123.

13
[ 1097180-24-9 ]
[ 42182-27-4 ]
[ 1097264-60-2 ]
C₁₉H₂₄N₄O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide; at 80℃; for 2.5h;	To a solution of 1,1-dimethylethyl (2S)-2-(3-bromo-2-oxopropyl)-1-piperidinecarboxylate D2 (0.27 mmol) in DMF (1 ml), 2-amino-4-pyridinecarbonitrile (0.032 g, 0.27 mmol) was added and the mixture heated at 80° C. for 2.5 h. The reaction was eluted through a SCX column. Collected fractions gave 0.049 g of an oil containing a mixture of the final compound, the corresponding N-Boc protected derivative and some residual 2-amino-4-pyridinecarbonitrile. [N-Boc derivative data: HPLC: rt=0.65 min, peak observed: 341 (M+1). C19H24N4O2 requires 340]. The crude was dissolved in DCM (2.50 ml) and the resulting solution cooled to 0° C. TFA (0.50 ml) was added dropwise, the reaction left under stirring for 1 h and then eluted through a SCX column. Collected fractions gave the title compound D15 (0.041 g, 0.17 mmol, 63percent yield from D2, two steps) contaminated with some residual 2-amino-4-pyridinecarbonitrile.UPLC: rt=0.38 min, peak observed: 241 (M+1). C14H16N4 requires 240.

References: [1]Patent: US2009/22670,2009,A1 .Location in patent: Page/Page column 14.

14
[ 1011803-53-4 ]
[ 42182-27-4 ]
[ 1011803-56-7 ]

Yield	Reaction Conditions	Operation in experiment
49%	In butan-1-ol;Heating / reflux;	Reference Example 2 2-tert-Butyl-3-cyclohexylmethylimidazo[1,2-a]pyridine-7-carbonitrile 2-Bromo-1-cyclohexyl-4,4-dimethylpentan-3-one (2.50 g, 9.08 mmol) obtained in Reference Example 1 was dissolved in n-butanol (15 mL). To this was added <strong>[42182-27-4]2-amino-4-cyanopyridine</strong> (1.30 g, 10.9 mmol), and then the mixture was stirred under reflux overnight. Then, the mixture was allowed to stand and cool to room temperature. After addition of aqueous sodium bicarbonate solution, the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was evaporated off in vacuo. The residue was purified by column chromatography on silica gel (hexane/ethyl acetate = 90/10) to give the title compound (1.31 g, 4.43 mmol, yield 49percent). 1H-NMR (delta ppm, CDCl3): 7.97-9.92 (m, 2H), 6.92-6.85 (m, 1H), 2.93 (d, J = 7.1 Hz, 2H), 1.75-1.50 (m, 6H), 1.48 (s, 9H), 1.31-1.03 (m, 5H). ESIMS m/z: 296 [M + H]+.

References: [1]Patent: EP2070927,2009,A1 .Location in patent: Page/Page column 28.

15
[ 42182-27-4 ]
[ 534-07-6 ]
[ 1201597-37-6 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; for 1.5h;Reflux;	Intermediate 172-(chloromethyl)imidazo[l ,2-alpha]pyridine-7-carbonitrile hydrochloride To an ethanol 5OmL solution of <strong>[42182-27-4]2-amino-isonicotinonitrile</strong> (5.0g, 42mmol) was added 1 ,3-dichloroacetone (6.93 g, 54.6mmol). The mixture was heated to reflux for 1.5hr and cooled to room temperature to give a suspension. The precipitate was collected by suction filtration, washed with dichloromethane and dried to give the title compound (7.2g). LC/MS: m/z 192(M+H).

References: [1]Patent: WO2009/152072,2009,A1 .Location in patent: Page/Page column 47.

16
[ 1207852-61-6 ]
[ 42182-27-4 ]
[ 1233086-94-6 ]

References: [1]Tetrahedron Letters,2010,vol. 51,p. 3528 - 3530.

17
[ 42182-27-4 ]
[ 88526-59-4 ]

Yield	Reaction Conditions	Operation in experiment
81%	With O,O-Diethyl hydrogen phosphorodithioate; In tetrahydrofuran; water; at 60℃; for 28h;	[00616] (i) Production of 2-aminopyridine-4-carbothioamide[00617] A mixture of <strong>[42182-27-4]2-aminopyridine-4-carbonitrile</strong> (6.0 g, 50 mmol), O,O' -diethyl dithiophosphate (11 mL, 60 mmol), tetrahydrofuran (25 mL) and water (25 mL) was stirred at 600C for 4 hr. To the reaction mixture was added O,O'-diethyl dithiophosphate (2.8 mL, 15 mmol) and the mixture was stirred at 600C for 1 day. To the reaction mixture was added aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The combined organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the obtained residue was washed with diisopropyl ether to give the title compound (6.2 g, 81percent) as a yellow solid.[00618] 1H-NMR (DMSO-dbeta, 300 MHz) delta 6.12 (2H, s), 6.73 (IH, dd, J = 1.7, 5.3 Hz), 6.77 - 6.81 (IH, m), 7.92 (IH, dd, J = 0.6, 5.3 Hz), 9.53 (IH, br s), 9.95 (IH, br s).
47%	With pyridine; diammonium sulfide; triethylamine; at 52℃; for 2h;	General procedure: 40?48wt.percent aqueous ammonium sulfide (8.27ml, 48.5mmol) was added to a mixture of 57 (5.3g, 44.1mmol), triethylamine (6.14ml, 44.1mmol), and pyridine (28.8ml, 353mmol) and the resulting suspension was stirred at 52°C for 2h. The mixture was concentrated under reduced pressure and H2O was added to the residue. The mixture was chilled to 0°C and the resulting precipitate was removed by filtration to deliver 2-aminopyrimidine-4-carbothioamide (5.5g, 35.7mmol, 80percent yield) as a yellow solid.

References: [1]Patent: WO2010/90716,2010,A1 .Location in patent: Page/Page column 251.
[2]European Journal of Medicinal Chemistry,2014,vol. 80,p. 364 - 382.

18
[ 1224708-12-6 ]
[ 42182-27-4 ]
[ 1224709-00-5 ]

References: [1]Tetrahedron Letters,2010,vol. 51,p. 4755 - 4758.

19
[ 75-16-1 ]
[ 42182-27-4 ]
[ 42182-25-2 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of <strong>[42182-27-4]2-aminoisonicotinonitrile</strong> (119.1 mg, 1.0 mmol) in Et2O (2 mL) was added dropwise a MeMgBr solution (3.0 M in Et2O, 2 mL, 6.0 mmol) at 0 °C. The mixture was refluxed overnight, cooled down, quenched with cold H2O, neutralized with concentrated HCl at 0 °C, and extracted with EtOAc. The combined organic layer was evaporated under reduced pressure to provide crude l-(2- aminopyridin-4-yl)ethanone.

References: [1]Patent: WO2011/14515,2011,A1 .Location in patent: Page/Page column 123.

20
[ 42182-27-4 ]
[ 885266-91-1 ]

References: [1]Patent: WO2011/14515,2011,A1 .

21
[ 42182-27-4 ]
[ 1263395-97-6 ]

References: [1]Patent: WO2011/14515,2011,A1 .

22
[ 42182-27-4 ]
[ 1266158-42-2 ]