3177-24-0|2,4-Dichloropyrimidine-5-carbonitrile| Ambeed

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 [ 3177-24-0 ] Purity: 95% 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 [ 3177-24-0 ]

CAS No. :	3177-24-0
Formula :	C₅HCl₂N₃
M.W :	173.99
SMILES Code :	ClC1=NC=C(C(=N1)Cl)C#N
MDL No. :	MFCD09746248
InChI Key :	KMHSUNDEGHRBNV-UHFFFAOYSA-N
Pubchem ID :	14026907

Safety of [ 3177-24-0 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 3177-24-0 ] Show Less

Physicochemical Properties

Num. heavy atoms	10
Num. arom. heavy atoms	6
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	3.0
Num. H-bond donors	0.0
Molar Refractivity	36.77
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	49.57 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.51
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	1.84
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.66
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.	0.19
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	2.19
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.48

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.52
Solubility	0.523 mg/ml ; 0.00301 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.	-2.5
Solubility	0.548 mg/ml ; 0.00315 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	-2.97
Solubility	0.188 mg/ml ; 0.00108 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	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.05 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)	1.77

Application In Synthesis of [ 3177-24-0 ]

* 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 [ 3177-24-0 ]

[ 3177-24-0 ] Synthesis Path-Downstream 1~35

1
[ 623-33-6 ]
[ 3177-24-0 ]
[ 120192-30-5 ]

References: [1]Chemistry of Heterocyclic Compounds,1988,p. 465.
Khimiya Geterotsiklicheskikh Soedinenii,1988,vol. 24,p. 560.

2
[ 3177-24-0 ]
[ 623-51-8 ]
[ 121400-39-3 ]

References: [1]Chemistry of Heterocyclic Compounds,1988,vol. 24,p. 1297 - 1300.
Khimiya Geterotsiklicheskikh Soedinenii,1988,vol. 24,p. 1559 - 1562.

3
[ 3177-24-0 ]
[ 623-51-8 ]
[ 121400-38-2 ]

References: [1]Chemistry of Heterocyclic Compounds,1988,vol. 24,p. 1297 - 1300.
Khimiya Geterotsiklicheskikh Soedinenii,1988,vol. 24,p. 1559 - 1562.

4
[ 3177-24-0 ]
[ 120192-31-6 ]

References: [1]Chemistry of Heterocyclic Compounds,1988,p. 465.
Khimiya Geterotsiklicheskikh Soedinenii,1988,vol. 24,p. 560.

5
[ 3177-24-0 ]
[ 121400-40-6 ]

References: [1]Chemistry of Heterocyclic Compounds,1988,vol. 24,p. 1297 - 1300.
Khimiya Geterotsiklicheskikh Soedinenii,1988,vol. 24,p. 1559 - 1562.

6
[ 3177-24-0 ]
2-(trifluoromethoxy)benzylamine [ No CAS ]
[ 874822-07-8 ]

Yield	Reaction Conditions	Operation in experiment
54%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 20h;	2,4-Dichloro-pyrimidine-5-carbonitrile (50 mg, 0.287 mmol) was dissolved in DMF (1 mL) and 2-(trifluoromethoxyl)benzylamine (57 mg, 0.287 mmol) was added to the solution followed by DIPEA (51 muL, 0.287 mmol). The reaction mixture was stirred at room temperature for 1 h. The solution was then diluted with EtOAc and washed with water (*4). The organic phase was then dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by silica gel prep TLC using CH2Cl2 as an eluent to afford 51 mg (54percent) of (4-chloro-5-nitrile-pyrimidin-2-yl)-(2-trifluoromethoxy-benzyl)-amine as a white solid.
42%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at -50℃;	To a solution of <strong>[3177-24-0]2,4-dichloropyrimidine-5-carbonitrile</strong> 10 (5.1 g,29 mmol) in DMF (50 mL), 2-(trifluoromethoxy)benzylamine (5.9 g,31 mmol) in DMF (13 mL) and DIPEA (6.1 mL, 35 mmol) were addedunder ?50 °C in dry ice-acetone bath and stirred at ?50 °C. The reactionmixture was diluted with EtOAc and washed with H2O, driedover MgSO4 and concentrated in vacuo. The residue was chromatographedon silica gel with elution using CHCl3 to give 11 (4.0 g, 42percent).1H NMR (DMSO?d6) delta ppm 4.58?4.69 (2H, m), 7.31?7.50 (4H, m), 8.75and 8.77 (1H, each s), 9.23?9.33 (1H, br); MS (ESI) m/z 351, 353 [M+Na]+.

References: [1]Patent: US2006/25433,2006,A1 .Location in patent: Page/Page column 104.
[2]Bioorganic and Medicinal Chemistry,2019,vol. 27,p. 790 - 799.

7
[ 4425-56-3 ]
[ 3177-24-0 ]

Yield	Reaction Conditions	Operation in experiment
	With N,N-diethylaniline; trichlorophosphate; at 25 - 115℃; for 3h;	To a mixture of the above uracil (15.41 g, 112.5 mmol) and phosphorus oxychloride (157.4 mL, 1.69 mol) was added N,N-diethylaniline (34.2 mL, 225 mmol), cautiously, at 25 C. The reaction was then heated at 115 C. for 3 h after which the mixture was cooled to 40 C. and concentrated in vacuo to remove excess POCl3. The remaining liquid was poured slowly onto ice-water with rapid stirring and the precipitated product was filtered. The aqueous layer was then extracted with chloroform and the extract was washed with 1 N HCl before concentrating in vacuo. This material was combined with the previously filtered material to afford 2,4-dichloro-pyrimidine-5-carbonitrile (15.36 g, 79%).

References: [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 6129 - 6152.
[2]Patent: US2006/25433,2006,A1 .Location in patent: Page/Page column 104.

8
[ 74900-81-5 ]
[ 3177-24-0 ]
[ 892413-66-0 ]

Yield	Reaction Conditions	Operation in experiment
33.4%	With N-ethyl-N,N-diisopropylamine; In acetonitrile; for 16h;Heating / reflux;	A mixture of 3-(2-propenyloxy)- benzenamine (max. 0.02 mol), 2,4-dichloro-5- pyrimidinecarbonitrile (0.009 mol) and DIPEA (0.03 mol) in acetonitrile (200 ml) was stirred and refluxed for 16 hours. The solvent was evaporated under reduced pressure. The residue was taken up into diglyme and stirred for 4 hours at 1000C, then stirred overnight at 1000C. The solvent was evaporated under reduced pressure. The residue was purified twice by column chromatography over silica gel (eluent: DCM/MeOEta from 99/1 to 97/3). The product fractions were collected and the solvent was evaporated under reduced pressure, yielding 1.2 g (33.4percent) of intermediate 1.

References: [1]Patent: WO2006/61415,2006,A1 .Location in patent: Page/Page column 72.

9
[ 5226-81-3 ]
[ 3177-24-0 ]
14,19-dioxa-2,4,8,26-tetraazatetracyclo[18.3.1.1(3,7).1(9,13)]hexacosa-1⁽²⁴⁾,3,5,7⁽²⁶⁾,9,11,13⁽²⁵⁾,16,20,22-nonaene-6-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
16%	In diethylene glycol dimethyl ether; at 90℃; for 16h;Heating / reflux;	A solution of <strong>[3177-24-0]2,4-dichloro-5-pyrimidinecarbonitrile</strong> (0.003 mol) in diglyme (100 ml) was added in one portion to a solution of 3,3'-[l,4-butanediylbis(oxy)]bis- benzenamine (0.003 mol) in diglyme (400 ml) at 900C. The reaction mixture was stirred and refluxed for 16 hours and then cooled. The solvent was evaporated under reduced pressure and the residue was purified on a silica gel filter (eluent: DCM/MeOH 99.5/0.5). The product fractions were collected and the solvent was evaporated under reduced pressure. The residue was stirred in DCM/MeOH (98/2), the resulting precipitate was filtered off and dried, yielding 0.1806 g (16 percent) of compound 2.

References: [1]Patent: WO2006/61415,2006,A1 .Location in patent: Page/Page column 103.

10
[ 943722-04-1 ]
[ 3177-24-0 ]
[ 943722-17-6 ]
C₂₅H₂₆ClN₅O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 70h;	Example 20. Synthesis of 2-([3'-(aminomethyl)-2-methyIbiphenyl-3- yIJmethyl}amino)-4-(4,5,7,8-tetrahydroimidazol4,5-dlazepn-6(lH)-yl)pyrmicline-5- carbonitrile; To a solution of (3'-aminomethyl-2'-methyl-biphenyl-3-ylmethyl)-carbamic acid tert-butyl ester (281 mg, 0.86 mmol) and diisopropylethylamine (0.165 mL, 0.95 mmol) in dichloromethane (5.0 mL) was added 2,4-dichloro-pyritnidine-5-carbonitrile (150 mg, 0.86 mmol). The ixn mixture was stirred at room temperature for 70 h, then adsorbed directly onto silica gel and purified by silica gel chromatography eluting with 20-45percent ethyl acetate in hcxancs to afford 254 mg of a colorless oil, identified as a 1:1 mixture of the desired product and the regioisomeric 4-addition product. This mixture was further purified by reverse phase semi-prep HPLC using 60percent acetonitrile/water (0.1percent TFA) as eluent to give 149 mg of {3'-[(4-chloro-5-cyano-pyrimidin-2-ylamino)-methyl]-2'-methyl-biphenyl-3- yhnethyl}-carbamic acid tert-butyl ester as an off-white solid, m/z 486.0 (M + Na)+.To a solution of l,4,5,6,7,8-hexahydro-imidazo[4,5-<f]azepine, di-HCl salt (41 mg, 0.19 mmol) and diisopropylethylamine (0.141 mL, 0.81 mmol) in 3:1 dichloromethane/N,iV- dimethylformamide (2.0 mL) was added {3'-[(4-chloro-5-cyano-pyrimidin-2-ylamino)- methyl]-2'-methyl-biphenyl-3-ylmethyl}-carbamic acid tert-butyl ester (75 mg, 0.16 mmol). The rxn mixture was stirred at room temperature for 84 h, then diluted with ethyl acetate (50 mL) and washed with 5percent NaCl solution (2x15 mL) and brine (15 mL), dried over Na2SO4, filtered and concentrated. The crude product was purified by silica gel chromatography eluting with 1-8percent MeOH in CH2Cl2 to give 67 mg (73percent) of (3'-[5- <n="58"/>cyano-4-(4,5,7,8-tetrahydro-lH-imidazo[4,5-c?]azepin-6-yl)-pyrimidin-2-ylamino]- methyl}-2'-methyl-biphenyl-3-ylmethyl)-carbamic acid tert-butyl ester, m/z 565.1 (M + H)+.A solution of (3'-[5-cyano-4-(4,5,7,8-tetrahydro-lH-imidazo[4,5-

References: [1]Patent: WO2007/76247,2007,A1 .Location in patent: Page/Page column 55-57.

11
[ 1036028-22-4 ]
[ 3177-24-0 ]
[ 1036028-04-2 ]

Yield	Reaction Conditions	Operation in experiment
19.7%	With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 90℃; for 18h;in a sealed tubein a sealed tubein a in a sealed tube;	[0240] <strong>[3177-24-0]2,4-dichloropyrimidine-5-carbonitrile</strong> (E. F. Godefroi, J. Org. Chem, 1962, 27(6), 2264-6) (0.1 Og, 0.57mmol), 2-amino-2-methyl-N-(2,2,2-trifluoroethyl)propanamide.lTFA (Meinke, Peter T.; Shih, Thomas L.; Fisher, Michael H., US 6,221,894 Bl) (0.171 g, 1.14 mmol) and DIPEA (0.39 mL, 2.29 mmol) were combined in anhydrous THF (5mL) in a <n="141"/>sealed tubeand heated to 90 0C for 18 hours, before cooling to room temperature. The solvent was evaporated in vacuo and the residue purified by flash chromatography (4Og SiO2, pentane/ethyl acetate, 30-70percent over 14 column volumes) to afford the title compound as a colorless waxy solid (0.036g, 19.7percent). MS(ES+) : 322.28. MS(ES-) : 320.39.

References: [1]Patent: WO2008/79346,2008,A1 .Location in patent: Page/Page column 139; 140.

12
[ 3731-51-9 ]
[ 3177-24-0 ]
[ 1141376-11-5 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 6071 - 6077.

13
[ 1240186-58-6 ]
[ 3177-24-0 ]
C₂₁H₁₉Cl₂N₇O [ No CAS ]
C₂₁H₁₉Cl₂N₇O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 20℃; for 72h;	A solution of Intermediate 43 (100 mg, 0.314 mmol), 2,4-dichloro-5-cyano- pyrimidine (81.9 mg, 0.471 mmol) and DIPEA (0.164 mL, 0.941 mmol) in rc-butanol (2 mL) was stirred at r.t. for 72 h. The mixture was dissolved in EtOAc (150 mL) and washed with saturated brine (3 x 30 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo. Purification by column chromatography (SiO2, 97:2:1 DCM/ MeOH/NH3 solution in MeOH) gave an off-white glass (60 mg, 42percent). LCMS (ES+) 456 (M+H)+ (mixture of regioisomers). The off-white glass (60 mg, 0.132 mmol), 7M NH3 in MeOH (1.5 mL) and NH4OH (1 mL) were combined and heated under microwave irradiation at 1200C for 1 h. After addition of saturated brine (20 mL) the reaction mixture was extracted with EtOAc (3 x 60 mL). The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo. Purification by preparative HPLC gave the title compounds (9.7 mg, 17percent; and 22.2 mg, 39percent) as white solids. deltaH (DMSO-de) 8.23 (IH, s), 8.01 (IH, s), 7.86 (IH, d, J 8.07 Hz), 7.73-7.64 (3H, m), 7.30-7.20 (IH, br s), 7.18 (2H, t, J7.76 Hz), 6.88 (IH, t, J5.30 Hz), 5.55-5.47 (IH, m), 3.98-3.92 (IH, m), 3.73-3.57 (2H, m), 2.22-1.96 (3H, m), 1.83-1.72 (IH, m), 1.63 (3H, d, J6.74 Hz). deltaH (DMSO-d6; T = 125°C) 8.23 (IH, s), 8.00 (IH, s), 7.65 (IH, s), 7.63 (IH, s), 7.45 (IH, d, J 8.00 Hz), 7.17 (IH, t, J 8.00 Hz), 7.09 (IH, br s), 6.70-6.57 (3H, m), 5.40-5.30 (IH, m), 4.02-3.95 (IH, m), 3.80-3.68 (2H, m), 2.25-2.10 (3H, m), 1.96-1.87 (IH, m), 1.63 (3H, d, J8.00 Hz). LCMS (ES+) 412 (M+H)+, 3.11 minutes {Method I). LCMS (ES+) 412 (M+H)+, 1.70 minutes {Method 2).

References: [1]Patent: WO2010/92340,2010,A1 .Location in patent: Page/Page column 85.

14
[ 1240186-58-6 ]
[ 3177-24-0 ]
[ 1350084-83-1 ]
[ 1349695-12-0 ]

Yield	Reaction Conditions	Operation in experiment
17%; 39%		A solution of Intermediate 43 (100 mg, 0.314 mmol), 2,4-dichloro-5-cyano- pyrimidine (81.9 mg, 0.471 mmol) and DIPEA (0.164 mL, 0.941 mmol) in rc-butanol (2 mL) was stirred at r.t. for 72 h. The mixture was dissolved in EtOAc (150 mL) and washed with saturated brine (3 x 30 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo. Purification by column chromatography (SiO2, 97:2:1 DCM/ MeOH/NH3 solution in MeOH) gave an off-white glass (60 mg, 42percent). LCMS (ES+) 456 (M+H)+ (mixture of regioisomers). The off-white glass (60 mg, 0.132 mmol), 7M NH3 in MeOH (1.5 mL) and NH4OH (1 mL) were combined and heated under microwave irradiation at 1200C for 1 h. After addition of saturated brine (20 mL) the reaction mixture was extracted with EtOAc (3 x 60 mL). The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo. Purification by preparative HPLC gave the title compounds (9.7 mg, 17percent; and 22.2 mg, 39percent) as white solids. deltaH (DMSO-de) 8.23 (IH, s), 8.01 (IH, s), 7.86 (IH, d, J 8.07 Hz), 7.73-7.64 (3H, m), 7.30-7.20 (IH, br s), 7.18 (2H, t, J7.76 Hz), 6.88 (IH, t, J5.30 Hz), 5.55-5.47 (IH, m), 3.98-3.92 (IH, m), 3.73-3.57 (2H, m), 2.22-1.96 (3H, m), 1.83-1.72 (IH, m), 1.63 (3H, d, J6.74 Hz). deltaH (DMSO-d6; T = 125°C) 8.23 (IH, s), 8.00 (IH, s), 7.65 (IH, s), 7.63 (IH, s), 7.45 (IH, d, J 8.00 Hz), 7.17 (IH, t, J 8.00 Hz), 7.09 (IH, br s), 6.70-6.57 (3H, m), 5.40-5.30 (IH, m), 4.02-3.95 (IH, m), 3.80-3.68 (2H, m), 2.25-2.10 (3H, m), 1.96-1.87 (IH, m), 1.63 (3H, d, J8.00 Hz). LCMS (ES+) 412 (M+H)+, 3.11 minutes {Method I). LCMS (ES+) 412 (M+H)+, 1.70 minutes {Method 2).

References: [1]Patent: WO2010/92340,2010,A1 .Location in patent: Page/Page column 85.

15
[ 57699-53-3 ]
[ 3177-24-0 ]
[ 1242262-97-0 ]

References: [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 6129 - 6152.

16
[ 57699-53-3 ]
[ 3177-24-0 ]
[ 1242262-98-1 ]
[ 1242262-97-0 ]

References: [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 6129 - 6152.

17
[ 1307298-96-9 ]
[ 3177-24-0 ]
C₂₀H₁₈ClFN₆OS [ No CAS ]
C₂₀H₁₈ClFN₆OS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20℃; for 4h;	A suspension of Intermediate 7 (500 mg, 1.48 mmol), K2C03 (204 mg, 1.48 mmol) and potassium thioacetate (590 mg, 5.16 mmol) in DMF (5.5 mL) was heated at 140°C under microwave irradiation for 3 h. After cooling, the mixture was dissolved in water (20 mL), neutralized to pH 6 with 1M HCl and extracted with EtOAc (3 x 50 mL). The organic layer was washed with saturated brine (3 x 30 mL), dried (MgS04) and concentrated in vacuo. Purification by column chromatography on silica, eluting with 5percent EtOAc in DCM, gave a yellow solid (127 mg, 26percent). LCMS (ES+) 337 (M+H)+. A suspension of this solid (114 mg, 0.339 mmol), K2C03 (46.8 mg, 0.339 mmol) and 2- chloro-N-methylacetamide (87 mg, 0.809 mmol) in DMF (3 mL) was heated at 120°C under microwave irradiation for 1 h. After cooling, the mixture was dissolved in a 1 : 1 mixture of EtOAc and Et20 (150 mL) and washed with saturated brine (3 x 30 mL). The organic layer was dried (MgS04) and concentrated in vacuo. Purification by column chromatography on silica, eluting with 40percent EtOAc in DCM, gave a white solid (119 mg, 86percent). LCMS (ES+) 408 (M+H)+. This solid (119 mg, 0.292 mmol) was dissolved in DCM (7.6 mL) and TFA (1.33 mL) was added. The reaction mixture was stirred at r.t. for 1.5 h and concentrated in vacuo. The residue obtained was basified with 0.8M aqueous NaOH (8 mL) and extracted with EtOAc (3 x 30 mL). The combined organic layers were dried (MgS04) and concentrated in vacuo to give a colourless glass (117 mg, 100percent). LCMS (ES+) 308 (M+H)+. A solution of this material (117 mg, 0.292 mmol), <strong>[3177-24-0]2,4-dichloro-5-cyanopyrimidine</strong> (76.2 mg, 0.438 mmol) and DIPEA (0.20 mL, 1.168 mmol) in THF (2 mL) was stirred at r.t. for 4 h. The mixture was dissolved in EtOAc (150 mL) and washed with saturated brine (3 x 30 mL). The organic layer was dried (MgS04) and concentrated in vacuo. Purification by column chromatography on silica, eluting with DCM/MeOH NH3 solution in MeOH (98: 1 :1), gave a pale brown foam (105 mg, 81percent). LCMS (ES+) 445, 447 (M+H)+ (mixture of regioisomers). A solution of this material (105 mg, 0.236 mmol) in a mixture of 7M NH3 solution in MeOH (2 mL) and NH4OH (1 mL) was heated at 120°C under microwave irradiation for 1 h. After cooling, the mixture was dissolved in saturated brine (40 mL) and extracted with EtOAc (3 x 100 mL). The organic layer was dried (MgS04) and concentrated in vacuo. Purification by preparative HPLC afforded the title compound (13.2 mg, 13percent) as an off-white solid, deltapi (DMSO-d6) 8.31 (1H, s), 8.25 (1H, s), 8.15 (1H, d, J5.33 Hz), 7.87-7.81 (2H, m), 7.40 (1H, t, J9.13 Hz), 7.15 (1H, br s), 6.97 (1H, br s), 5.55-5.46 (1H, m), 4.10 (1H, d, J 15.2 Hz), 4.04 (1H, d, J 15.2 Hz), 2.65 (3H, d, J4.59 Hz), 2.58 (3H, s), 1.61 (3H, d, J 6.82 Hz). LCMS (ES+) 426 (M+H)+, T 3.37 minutes {Method 1).

References: [1]Patent: WO2011/58113,2011,A1 .Location in patent: Page/Page column 33; 34.

18
[ 56004-83-2 ]
[ 3177-24-0 ]
[ 1214727-96-4 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 2h;Cooling with ice;	Preparation Example 54 Under ice-cooling, to a solution of <strong>[3177-24-0]2,4-dichloropyrimidine-5-carbonitrile</strong> (1.00 g) in DMF (15 ml) were added dropwise a solution of 2-(methylthio)benzylamine (881 mg) in DMF (5 ml) and DIPEA (1.2 ml), followed by stirring at the same temperature for 1 hour. A solution of 2-(methylthio)benzylamine (44 mg) in DMF (2 ml) was added thereto, followed by stirring at room temperature for additional 1 hour. To the reaction mixture were added EtOAc and water, followed by liquid separation. The organic layer was sequentially washed with water and saturated brine, and dried over anhydrous magnesium sulfate. After the desiccant was removed, the solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (chloroform) to obtain 709 mg of 4-chloro-2-[2-(methylsulfanyl)benzyl]amino}pyrimidine-5-carbonitrile.

References: [1]Patent: EP2325175,2011,A1 .Location in patent: Page/Page column 30-31.

19
[ 3177-24-0 ]
[ 25900-61-2 ]
[ 1332302-03-0 ]
[ 1332302-04-1 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In 1,2-dimethoxyethane; at 0 - 20℃; for 3h;	Step 1To 3-amino-N-methylbenzamide (353 mg, 2.351 mmol) in DME (8 mL) at 0 °C was added N-ethyl-N-isopropylpropan-2-amine (1.024 mL, 5.88 mmol) followed by 2,4- dichloropyrimidine-5-carbonitrile (450.0 mg, 2.59 mmol). The resulting reaction mixture was allowed to warm to RT (ice melt) over 3 h, concentrated, purified using MPLC (25 g cartridge, 40 g column, 0 to 100percent EtOAc-hexanes). Separation of 2- and 4-substitution products was not achieved. Fractions with both products were combined and concentrated giving about a 3 : 1 mixture of 3 -(2-chloro-5 -cyanopyrimidin-4-ylamino)-N-methylbenzamide and 3 -(4-chloro-5 - cyanopyrimidin-2-ylamino)-N-methylbenzamide (172.7 mg).

References: [1]Patent: WO2011/103196,2011,A1 .Location in patent: Page/Page column 98.

20
[ 3177-24-0 ]
[ 25900-61-2 ]
[ 1332300-63-6 ]

References: [1]Patent: WO2011/103196,2011,A1 .

21
[ 53084-60-9 ]
[ 3177-24-0 ]
(1R,3S)-ethyl 3-((4-chloro-5-cyanopyrimidin-2-yl)amino)cyclohexane-carboxylate [ No CAS ]
C₁₄H₁₇ClN₄O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20℃; for 1h;	Preparation of Compound 1-4Synthetic Scheme 14(a) iPr2NEt, THF; (b) 5-Trifluoromethyl-l -(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl- 1 ,3,2- dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine (64), Pd(Ph3P)4, 2M Na2C03, CH3CN, 120 °C; (c) LiOH, THF, H20, 130 °CFormation of (IR, 3S)-ethyl 3-((4-chloro-5-cyanopyrimidin-2-yI)amino)cyclohexane- carboxylate (63)To a solution of <strong>[3177-24-0]2,4-dichloropyrimidine-5-carbonitrile</strong> (0.56 g, 3.23 mmol) and ( \\R, 35)- ethyl 3-aminocyclohexanecarboxylate, 56, (0.60 g) in THF (50 mL) was added N,N- diisopropylethylamine ( 1 .40 mL, 8.07 mmol) in THF (l OmL). The reaction mixture was stirred at room temperature for 1 hour. The mixture was concentrated to dryness then dissolved in dichloromethane and washed with I N HC1. The product was absorbed onto silica-gel and purified via silica gel chromatography (0-20percent EtOAc/hexanes gradient) to afford 195 mg of the less polar (faster moving) product along with 542 mg of the more polar (slower moving) product, which was determined to be the desired product, 63.

References: [1]Patent: WO2012/83122,2012,A1 .Location in patent: Page/Page column 108.

22
[ 3177-24-0 ]
(1R,3S)-ethyl 3-((5-cyano-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-yl)amino)cyclohexanecarboxylate [ No CAS ]

References: [1]Patent: WO2012/83122,2012,A1 .

23
[ 3177-24-0 ]
[ 1383375-93-6 ]

References: [1]Patent: WO2012/83122,2012,A1 .

24
[ 3177-24-0 ]
[ 1351761-98-2 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 5536 - 5545.

25
[ 3177-24-0 ]
[ 74-89-5 ]
[ 389606-74-0 ]