66521-66-2|4-(Pyridin-3-yl)pyrimidin-2-amine| Ambeed

Structure of 66521-66-2

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

Synonyms: 4-(3-Pyridinyl)-2-aminopyrimidine

4.5 *For Research Use Only !

{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size	Price	VIP Price	US Stock	Global Stock	In Stock
{[ item.pr_size ]}		Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

{[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

Quality Control of [ 66521-66-2 ] Purity: 97% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of [ 66521-66-2 ]

CAS No. :	66521-66-2
Formula :	C₉H₈N₄
M.W :	172.19
SMILES Code :	NC1=NC=CC(C2=CC=CN=C2)=N1
Synonyms :	4-(3-Pyridinyl)-2-aminopyrimidine
MDL No. :	MFCD01317832
InChI Key :	LQHQKYWYKPLKCH-UHFFFAOYSA-N
Pubchem ID :	12450582

Safety of [ 66521-66-2 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H312-H332
Precautionary Statements:	P280

Computational Chemistry of [ 66521-66-2 ] Show Less

Physicochemical Properties

Num. heavy atoms	13
Num. arom. heavy atoms	12
Fraction Csp3	0.0
Num. rotatable bonds	1
Num. H-bond acceptors	3.0
Num. H-bond donors	1.0
Molar Refractivity	49.67
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	64.69 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.25
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	0.45
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.13
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.	-0.04
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	1.25
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.81

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.81
Solubility	2.68 mg/ml ; 0.0156 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.	-1.38
Solubility	7.23 mg/ml ; 0.042 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	-3.43
Solubility	0.0635 mg/ml ; 0.000369 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	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	Yes
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-7.03 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)	2.03

Application In Synthesis of [ 66521-66-2 ]

* 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 [ 66521-66-2 ]

[ 66521-66-2 ] Synthesis Path-Downstream 1~35

2
[ 55314-16-4 ]
[ 66521-66-2 ]

References: [1]Russian Journal of Organic Chemistry,2011,vol. 47,p. 1222 - 1226.
[2]Angewandte Chemie - International Edition,2013,vol. 52,p. 8551 - 8556.
Angew. Chem.,2013,vol. 125,p. 8713 - 8718,6.
[3]Synthesis,2007,p. 2121 - 2124.
[4]Russian Journal of Organic Chemistry,2011,vol. 47,p. 1222 - 1226.
[5]Russian Journal of Organic Chemistry,2011,vol. 47,p. 1222 - 1226.

3
[ 926922-18-1 ]
[ 66521-66-2 ]
[ 641571-10-0 ]

References: [1]Synthesis,2007,p. 2121 - 2124.
[2]Organic and Biomolecular Chemistry,2013,vol. 11,p. 1822 - 1839.

4
[ 7745-93-9 ]
[ 66521-66-2 ]
[ 152460-09-8 ]

Yield	Reaction Conditions	Operation in experiment
79%	With copper(l) iodide; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 120℃; for 0.5h;Microwave irradiation;	The mixture of 4-(Pyridin-3-yl) pyrimidin-2- amine (0.378 g,2.2 mmol), copper iodide (0.5 mmol) and anhydrous K2CO3(4 mmol), Dioxane (5 mL), 2-bromo-1-methyl-4- nitrobenzene(2 mmol), and DMEDA (0.5 mmol) was irradiated in the microwave synthesizer and heated at 120 C for 30 min. After completion of the reaction, ammonium hydroxide and brine solution was added andthen extracted with ethyl acetate. The organic layer was dried overanhydrous sodium sulphate, the solvent was evaporated in buchirotary evaporator and the resulting solid was dried under vacuum.The crude was purified by using silica gel column chromatographyusing ethyl acetate: chloroform (50:50) to yield 0.498 g (79.0percent) ofthe imatinib intermediate compound as yellowish powder. Melting point194-196 °C. ES-MS (M1) found (m/z): 308.1. 1H NMR (DMSOd6):2.49(S, 3H); 7.32-7.37 (m, 1H); 7.40-7.48 (m, 1H); 7.49e7.51(m, 1H); 7.85-7.88 (m, 1H); 8.02 (m, 1H); 8.48-8.51 (m, 1H);8.57-8.59 (m, 1H); 9.20(S, 1H); 9.29 (S, 1H).
60%	With copper(l) iodide; potassium carbonate; potassium iodide; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 110℃; for 24h;Inert atmosphere; Schlenk technique;	4-(Pyridine-3-yl) pyridine-2-amine (8.60 g, 0.05 mol), CuI (2.39 g, 0.0125 mmol), anhydrous K2CO3 (14.0 g, 0.1 mol), KI (2.08 g, 0.0125 mol) were added to a Schlenk-type three-neck flask fitted with a thermometer, magnetic stirbar, and septum. The flask was evacuated and back filled with N2 three times. Dioxane (250 mL) and 2-bromo-4-nitrotoluene (9.82 g, 0.045 mol) were added to the flask. Finally, N,N'-dimethylethylenediamine (1.10 g, 0.0125 mol) was added by syringe at room temperature with stirring. The reaction mixture was stirred at 110° C. under N2 for 24 hours and then cooled to room temperature. Ammonia (30percent, 100 mL) and saturated NaCl (400 mL), were added to the reaction mixture which was then extracted with ethyl acetate (500 mL*3). The organic phase was dried over Na2SO4 and a yellow solid was obtained after the solvent was removed under reduced pressure. The crude product was purified by column chromatography (biotage: DMC/Methanol, 1-8percent, 20 CV). The desired product was obtained as a yellow solid (8.3 g, yield: 60percent); 1H NMR (500 MHz, CDCl3) delta 2.49 (s, 3H), 7.36 (m, 1H), 7.15 (br., 1H), 7.35 (d, 1H), 7.38 (d, 1H), 7.52 (m, 1H), 7.88 (d, 1H), 8.55 (d, 1H), 8.60 (d, 1H), 8.76 (d, 1H), 9.28 (s, 1H), 9.50 (s, 1H). LC-MS (m/z) calculated, 307.3, found, 308.3 [M+H]+.
	With potassium tert-butylate; In dimethyl sulfoxide; at 120℃; for 12h;	2-bromo-1-methyl-4-nitrobenzene(0.63 g, 2.9 mmol), <strong>[66521-66-2]4-(pyridin-3-yl)pyrimidin-2-amine</strong> (1) (0.60 g, 3.5 mmol), and KOtBu(0.49 g, 4.40 mmol) was added flask containing PS-CuO (57.5 mg, 20 wtpercent of CuOin PS, 0.145 mmol based on Cu) in 15 mL DMSO. The resulting mixture was heatedto 120oC and stirred for 12 h. Aftercooling, the mixture was poured into EtOAc (20.0 mL) and washed with water (2 × 10.0 mL).The organic layer was separated and dried over MgSO4, and thenevaporated under reduced pressure. The resulting mixture was reacted with stannouschloride (1.64 g, 8.70 mmol) and 1.64 mL of Con. HCl in MeOH (10 mL) at at 50 oCfor 8 h. After completion the reaction mixture was poured into crushed ice followedby basification with sodium bicarbonate. The layer was separated and dried overanhydrous MgSO4, evaporated under reduced pressure to afford the crudeproduct which was purified by using column chromatography(hexane : EtOAc = 4:1) obtainedas yellow solid 67percent (0.54 g, 1.95 mmol).1HNMR (300 MHz, CDCl3) delta 9.25 (dd, J= 1.5 Hz, 1H), 8.71 (dd, J1= 3.3 Hz, J2 = 1.5 Hz,1H), 8.48 (d, J = 5.1 Hz, 1H), 8.35-8.31(m, 1H), 7.59 (d, J = 2.1 Hz, 1H), 7.43 ? 7.38 (m, 1H), 7.12 (d, J = 5.4Hz,1H) 7.03(bs, 1H), 6.98 (d, J = 8.1 Hz, 1H), 6.41 (dd, , J1 = 5.7 Hz, J2= 2.4 Hz, 1H), 3.59(bs, 2H), 2.24(s, 3H). 13C NMR (75 MHz, CDCl3): delta 162.5, 160.7, 159.0, 151.4, 148.5, 145.1,137.9, 134.4, 132.7, 131.0, 123.5, 118.1, 110.6, 108.4, 108.0 HRMS(ESI) calcd. for C16H16N5 [M+H]+ 278.1406, found 278.1400.

References: [1]RSC Advances,2015,vol. 5,p. 20516 - 20520.
[2]Organic and Biomolecular Chemistry,2009,vol. 7,p. 5129 - 5136.
[3]Chemical Communications,2010,vol. 46,p. 1118 - 1120.
[4]Angewandte Chemie - International Edition,2013,vol. 52,p. 8551 - 8556.
    Angew. Chem.,2013,vol. 125,p. 8713 - 8718,6.
[5]European Journal of Organic Chemistry,2007,p. 6084 - 6088.
[6]Organic Process Research and Development,2008,vol. 12,p. 490 - 495.
[7]Angewandte Chemie - International Edition,2015,vol. 54,p. 179 - 183.
    Angew. Chem.,2015,vol. 127,p. 181 - 185,5.
    Angewandte Chemie,2015,vol. 127,p. 181 - 185,5.
[8]Journal of Molecular Structure,2018,vol. 1171,p. 541 - 550.
[9]Patent: US9095622,2015,B2 .Location in patent: Page/Page column 32.
[10]Archiv der Pharmazie,2017,vol. 350.
[11]ChemMedChem,2011,vol. 6,p. 2009 - 2018.
[12]Tetrahedron Letters,2012,vol. 53,p. 6657 - 6661.

5
[ 104-92-7 ]
[ 66521-66-2 ]
[ 112675-67-9 ]

References: [1]Molecules,2008,vol. 13,p. 818 - 830.
[2]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 3860 - 3874.

6
[ 580-13-2 ]
[ 66521-66-2 ]
[ 1048003-96-8 ]

References: [1]Molecules,2008,vol. 13,p. 818 - 830.
[2]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 3860 - 3874.

7
[ 583-70-0 ]
[ 66521-66-2 ]
N-(2,4-dimethylphenyl)-4-(pyridin-3-yl)pyrimidin-2-amine [ No CAS ]

References: [1]Molecules,2008,vol. 13,p. 818 - 830.
[2]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 3860 - 3874.

8
[ 78831-87-5 ]
[ 66521-66-2 ]
[ 1048003-91-3 ]

References: [1]Molecules,2008,vol. 13,p. 818 - 830.
[2]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 3860 - 3874.

9
[ 50-01-1 ]
[ 55314-16-4 ]
[ 66521-66-2 ]

References: [1]Molecules,2008,vol. 13,p. 818 - 830.

10
[ 593-85-1 ]
[ 55314-16-4 ]
[ 66521-66-2 ]

Yield	Reaction Conditions	Operation in experiment
66%	With sodium hydroxide; In butan-1-ol; at 120℃; for 2h;	NaOH (0.78 g, 19.5 mmol) was added to a mixture of 3-(dimethylamino)-l-(pyridin-3- yl)prop-2-en-l-one (3.52 g, 20.0 mmol) and guanidine carbonate (1.80 g) in n-butanol (20 mL). The mixture was heated at 1200C for 2 h. After cooling, the precipitates formed was collected by filtration and dried under vacuum to afford the desired product (2.3g, 66percent). LCMS: (M+H)+= 173.2.
	In iso-butanol; for 24h;Heating / reflux;	4-Pyridin-3 - yl-pyrimidin-2- ylamine (7)[0042] A mixture of 3-acetylpyridine (20.72 g, 171.0 mmol) and N, N-dimethylformamide dimethyl acetal (60 mL, 450 mmol) is heated at 110 0C. After reaction overnight, the reaction mixture is cooled to room temperature and concentrated. Ethyl ether (20 mL) and hexanes (60 <n="17"/>P A T E N TGNF Docket No.: P1286PC10mL) are added to the residue. The resulting solid is collected by filtration, washed with hexanes, and dried to afford 3-dimethylamino-l-pyridin-3-yl-propenone which is used for next reaction without further purification. A mixture of 3-dimethylamino-l-pyridin-3-yl-propenone (17.6 g, 100 mmol) and guanidine carbonate (10.8 g, 60.0 mmol) in 2-butanol (100 mL) is heated at reflux. After 24 hours, the reaction mixture is cooled to room temperature and concentrated. The residue is triturated in water (50 mL). The solid is collected by filtration, washed with water and dried to afford the desired product 4-pyridin-3-yl-pyrimidin-2-ylamine as a white solid. C29H31N7O Exact MS: 172.07. Found MS m/z 173.1 (M+l). 1H NMR (DMSO-J6): delta 9.23 (s, IH), 8.69 (m, IH), 8.37 (m, 2H), 7.54 (d, IH), 7.20 (d, IH), 6.80 (s, 2H).

References: [1]Patent: WO2010/96395,2010,A1 .Location in patent: Page/Page column 36.
[2]Patent: WO2008/130944,2008,A1 .Location in patent: Page/Page column 15-16.

11
C₂₁H₂₅BrN₃OPol [ No CAS ]
[ 66521-66-2 ]
C₃₀H₃₂N₇OPol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 2,6-di-tert-butyl-4-methyl-phenol; sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100℃; for 17h;	Example 2; N-r4-Methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyll-4-(4-methyl-piperazin-l- ylmethylbenzamide resin (8b-l)[0043] Resin (6b-l) (0.2 g) is immersed in 1,4-dioxane (3 mL). Aminopyrimidine 7 (172 mg, 5 equiv.), tris(dibenzylideneacetone)-dipalladium(0) (Pd2dba3, 9 mg, 0.05 equiv.), 4,5- bis(diphenylphosphino)-9,9-dimethyl-xanthene (Xantphos, 14 mg, 0.12 equiv.), 2,6-di-tert- butyl-4-methylphenol (BHT, 264 mg, 6 equiv.) and sodium ?-butoxide (96 mg, 5 equiv.) are added into the reaction mixture. The reaction mixture is shaken at 100 0C for 17 hrs. Around 5 mg of resins are taken out, washed, dried, and cleaved by a mixture of TFA: H2O: DCM (45:5:50/v:v:v). LC-MS analysis of this cleavage solution revealed a complete conversion to product. LC-MS retention time: (UV254, t = 1.348 min).The rest of the resins are washed thoroughly with MeOH, DMF, and DCM, and dried in vacuo.

References: [1]Patent: WO2008/130944,2008,A1 .Location in patent: Page/Page column 16.

12
[ 1050619-26-5 ]
[ 66521-66-2 ]
[ 1224198-97-3 ]

References: [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 1806 - 1815.

13
[ 90347-66-3 ]
[ 66521-66-2 ]
[ 917392-54-2 ]

References: [1]Organic and Biomolecular Chemistry,2009,vol. 7,p. 5129 - 5136.

14
[ 50-01-1 ]
[ 55314-16-4 ]
[ 66521-66-2 ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium hydroxide; In tert-butyl alcohol; at 85℃;	The starting material was added 3-dimethylamino-1-(3-pyridyl)-2-propen-1-one (Compound 4) (1.76 g, 0.01 mol) in a three-neck flask.Guanidine hydrochloride (2.87 g, 0.03 mol)And sodium hydroxide (1.2g, 0.03mol), add 25ml of solvent t-butanol, stir, heated in a constant temperature oil bath to 85 C reflux reaction, 6-8h. After the reaction is completed, the solvent is spin-dried, an appropriate amount of water and ethyl acetate are added, the insoluble solid is filtered, and the filter cake is washed with water and dried to obtain a yellow solid; the filtrate is further subjected to extraction, the organic phase is collected, dried, and the solvent is dried and dried. The solid was subjected to column chromatography to give a pale yellow solid, Compound 5 (1.55 g, yield: 90%).
	With sodium hydroxide; In butan-1-ol; at 120℃;	To aflask 3-dimethylamino-1-(3-pyridyl)-2-propen-1-one(1.76 g, 10.0 mmol), guanidine hydrochloride (1.15 g, 12.0 mmol), NaOH (480 mg,12.0 mmol) and n-BuOH (20 mL) were added. The mixturewas heated to 120 oC.The resulting solid was collected, rinsed with water (50 mL) and dried overhigh vacuum to get the product as light yellow crystalline (1.51 g, 88% yield).1H NMR(400 MHz, DMSO) delta 9.23 (d, J = 2.0 Hz, 1H), 8.67 (dd, J = 4.7,1.3 Hz, 1H), 8.38 (dt, J = 8.0, 1.8 Hz, 1H), 8.36 (d, J = 5.1 Hz,1H), 7.52 (dd, J = 8.0, 4.8 Hz, 1H), 7.20 (d, J = 5.1 Hz, 1H),6.81 (s, 2H).13C NMR (101 MHz, DMSO) delta163.78, 161.53, 159.36, 151.11, 147.93, 134.11, 132.44, 123.72, 105.99
	With sodium hydroxide; In butan-1-ol; at 120℃;	3-dimethylamino-1-(3-pyridyl)-2-propenyl-1-one (1.76 g, 10.0 mmol) was suspended in n-butanol (20 mL), followed by the addition of guanidine hydrochloride (1.15 g, 12.0 mmol) and NaOH (480 mg, 12.0 mmol). The mixture was heated to 120 C for reacting overnight. The precipitated solid was collected and washed with water (50 mL), followed by vacuum drying to give a light yellow crystal (1.51g, 88% yield). 1H NMR (400 MHz, DMSO) delta 9.23 (d, J = 2.0 Hz, 1H), 8.67 (dd, J = 4.7, 1.3 Hz, 1H), 8.38 (dt, J = 8.0, 1.8 Hz, 1H),8.36 (d, J = 5.1 Hz, 1H), 7.52 (dd, J = 8.0, 4.8 Hz, 1H), 7.20 (d, J = 5.1 Hz, 1H), 6.81 (s, 2H). 13C NMR (101 MHz, DMSO) delta 163.78, 161.53, 159.36, 151.11, 147.93, 134.11, 132.44, 123.72, 105.99

References: [1]Patent: CN110078708,2019,A .Location in patent: Paragraph 0044; 0052-0056.
[2]RSC Advances,2016,vol. 6,p. 61458 - 61467.
[3]MedChemComm,2015,vol. 6,p. 1816 - 1825.
[4]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 3860 - 3874.
[5]Chemical Communications,2019,vol. 55,p. 1092 - 1095.
[6]Organic and Biomolecular Chemistry,2009,vol. 7,p. 5129 - 5136.
[7]Chemical Communications,2010,vol. 46,p. 1118 - 1120.
[8]Journal of the American Chemical Society,2012,vol. 134,p. 700 - 706.
[9]Journal of Heterocyclic Chemistry,2015,vol. 52,p. 1296 - 1301.
[10]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 3714 - 3718.
[11]Journal of Organic Chemistry,2016,vol. 81,p. 11788 - 11801.
[12]Archiv der Pharmazie,2017,vol. 350.
[13]Patent: EP3483155,2019,A1 .Location in patent: Paragraph 0077.

15
[ 581076-59-7 ]
[ 66521-66-2 ]
[ 152459-95-5 ]

Yield	Reaction Conditions	Operation in experiment
91%		Under nitrogen protection, 40 mg of N,N'-diisopropylselenourea was uniformly mixed with 10 g of chitosan.It was placed in a tubular reactor and calcined at 500 ° C for 5 hours under nitrogen to obtain selenium and nitrogen-doped nano-carbon fibers with selenium promoting large specific surface area. The material was immersed in 0.05 mol/L copper chloride aqueous solution for 18 hours. ,Filtration, washing with water, drying to obtain a catalyst.The above catalyst is determined by ICP, wherein the mass ratio of selenium is 0.01percent, and the mass ratio of copper is 0.12percent;The specific surface area is 28 cc/g.20 mg of the above catalyst with 1.72 g of <strong>[66521-66-2]4-(3-pyridyl)-2-aminopyrimidine</strong> (see I in the following reaction formula)And 4.02g of 4-(N-methylpiperazine)methylbenzoyl (3-bromo-4-methylphenyl)amine (see II in the following reaction formula) were mixed in 20 mL of ethanol under nitrogen protection. Heat at 60 ° C for 3 hours. The catalyst is recovered by centrifugation,Concentrate the supernatant to within 5 mL, that is, a large amount of crystals are precipitated, filtered, and washed with petroleum ether.Imadinib hydrobromide was obtained in a yield of 96percent.Dissolve the salt in 20 mL of water, adjust the pH to 8.7 with 0.2 mol/L NaOH, and extract with ethyl acetate.(3 extractions per 20 mL). The organic phases were combined and dried over anhydrous sodium sulfate. After filtering, the solvent is evaporated.That is, free imatinib was obtained, and the yield was 91percent. ICP analysis indicated that the copper residue in the product was less than 0.03 ppm.
72%	With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene; for 5.16667h;Inert atmosphere; Reflux; Sonication;	To a mixture of 4-(3-pyridyl)-2-pyrimidine-amine (172.2 mg, 1.0 mmol), N-(3-bromo-4-methyl-phenyl)-4-(4-methyl-piperazin-1-ylmethyl)-benzamide (402.4 mg, 1.0 mmol) and sodium tert.-butylate (144.2 mg, 1.5 mmol) is added a mixture of rac-BINAP (31.2 mg, 0.050 mmol) and Pd2(dba)3*CHCl3 (13 mg, 0.013 mmol) under argon. After addition of 3 ml of xylene the suspension is sonicated for 10 minutes then stirred for 5 hours under reflux. After cooling to room temperature, water (10 ml) is added to the dark brown oil and the product extracted 4 times with methylene chloride (10 ml each). The combined organic extracts are dried over MgSO4 and concentrated in vacuo. The brown oil is purified by flash-chromatography (SiO2, methanol). The product, a pale yellow solid is dissolved in methylene chloride, filtered and concentrated in vacuo. Yield: 484.3 mg of the title compound, 72percent of theory, (99.9percent area by HPLC). The product contains typically roughly 10percent of isomers which can be eliminated by preparative reversed phase chromatography.
71%	With copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 100℃; for 28h;Inert atmosphere; Autoclave;	To 20 L autoclave, 12 (189.4 g, 1.1 mol), 11 (402.3 g, 1 mol), CuI(47.8 g, 0.25 mol), and K2CO3 (276.4 g, 2 mol) were added. Theautoclave was then charged with N2, and a solution of DMEDA(26.8 mL) in 12 L of 1,4-dioxane was slowly dropped. Themixture was mechanically stirred at 100 °C for 28 h. Aftercooling to room temperature, it was poured into a mixture ofconcentrated NH3 (3.5 L) and cold sat. NaCl solution (15 L, 0?5°C) and extracted by EtOAc (3 × 14 L). The combined organiclayer was dried by Na2SO4 and led to white crystal after concentration.The crystal was washed by PE and dried under vacuumovernight to afford 350.5 g of imatinib base 1 in 71percent yield. Mp 207.4?209.2 °C. IR (KBr): 3410, 3290, 2967, 2964, 2932,2801, 1628, 1588, 1532, 1507, 1478, 1450, 1416, 1380, 1346,1007, 829, 761, 700 cm?1. 1H NMR (600 MHz, DMSO-d6, TMS):delta = 10.22 (s, 1 H), 9.30 (d, J = 1.8 Hz, 1 H), 9.02 (s, 1 H), 8.71?8.70(m, 1 H), 8.54?8.50 (m, 2 H), 8.12 (s, 1 H), 7.93 (d, J = 8.4 Hz, 2H), 7.55?7.44 (m, 5 H), 7.23 (d, J = 8.4 Hz, 1 H), 3.53 (s, 2 H),2.53?2.33 (br s, 8 H), 2.25 (s, 3 H), 2.16 (s, 3 H) ppm. 13C NMR(150 MHz, DMSO-d6): delta = 165.3, 161.6, 161.2, 159.4, 151.3,148.1, 142.1, 137.8, 137.2, 134.4, 133.7, 132.2, 130.0, 128.6,127.5, 123.8, 117.2, 116.8, 107.5, 61.6, 54.7, 52.5, 45.7, 17.6ppm. Known compound: CAS Reg. No. 152459-95-5.3

References: [1]Patent: CN108164505,2018,A .Location in patent: Paragraph 0015-0019; 0032.
[2]Patent: US9573928,2017,B2 .Location in patent: Page/Page column 15.
[3]Synlett,2016,vol. 27,p. 2233 - 2236.
[4]Chemical Communications,2010,vol. 46,p. 2450 - 2452.
[5]Tetrahedron Letters,2012,vol. 53,p. 6657 - 6661.
[6]Organic and Biomolecular Chemistry,2013,vol. 11,p. 1822 - 1839.
[7]Angewandte Chemie - International Edition,2016,vol. 55,p. 2531 - 2535.
Angew. Chem.,2016,vol. 128,p. 2577 - 2581,5.
[8]Journal of Organic Chemistry,2016,vol. 81,p. 11788 - 11801.

16
[ 506-93-4 ]
[ 55314-16-4 ]
[ 66521-66-2 ]

Yield	Reaction Conditions	Operation in experiment
85%	With sodium hydroxide; In butan-1-ol; for 16h;Reflux;	3-(Dimethylamino)-1-(pyridine-3-yl) prop-2-en-1-one (15.4 g, 0.088 mol), guanidine nitrate (10.7 g, 0.088 mol), and sodium hydroxide (3.5 g, 0.088 mol) were dissolved in n-butanol (120 mL). The mixture was heated to reflux with stirring and maintained for 16 hours. The reaction mixture was then cooled to room temperature. The solid was collected and washed with water (400 mL). The desired product was dried under vacuum for three days and 12.7 g of yellow crystals of desired product was obtained (yield: 85percent); 1H NMR (500 MHz, CDCl3) delta 5.15 (br., 2H), 7.09 (d, 1H), 7.44 (in, 1H), 8.33 (d, 1H), 8.42 (d, 1H), 8.73 (d, 1H), 9.22 (s, 1H). LC-MS (m/z) calculated, 172.2, found 173.2 [M+H]+.
1.18 g	With sodium hydroxide; In butan-1-ol; at 90℃; for 0.333333h;Microwave irradiation;	The obtained compound 3 followed by 3-(dimethylamino)-1-(pyridin-3-yl) prop-2-en-1-one (0.1 mol), guanidine nitrate(0.1 mol), sodium hydroxide (0.1 mol), and n-butanol (12.5 mL) was irradiated in the microwave synthesizer at 90 C for 20 min. Aftercompletion of the reaction mixture poured into ice-cold water andthe resulting solid was filtered and washed with water. The obtainedsolid of compound 4 (1.18 g) was dried under vacuum.Melting point 190-192 °C, ES-MS (M1) found (m/z): 173.1.

References: [1]Organic Process Research and Development,2008,vol. 12,p. 490 - 495.
[2]Patent: US9095622,2015,B2 .Location in patent: Page/Page column 31.
[3]Chemical Communications,2010,vol. 46,p. 2450 - 2452.
[4]Synlett,2016,vol. 27,p. 2233 - 2236.
[5]Journal of Molecular Structure,2018,vol. 1171,p. 541 - 550.

17
[ 328-70-1 ]
[ 66521-66-2 ]
[ 1234327-39-9 ]