5-Chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile → N-[2-[(3R)-3-aminopyrrolidin-1-yl]-5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]phenyl]acetamide

HRID 370

Reaction equation

HRID 370 reaction equation
CC(=O)Nc1cc(N)ccc1N1CC[C@@H](NC(=O)OC(C)(C)C)C1.N#Cc1cnn2c(NC3CC3)cc(Cl)nc12>CC(C)c1cc(C(C)C)c(-c2ccccc2P(C(C)(C)C)C(C)(C)C)c(C(C)C)c1.CN1CCCC1=O.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C([O-])[O-].[Cs+].[Cs+].[Pd].[Pd]>CC(=O)Nc1cc(Nc2cc(NC3CC3)n3ncc(C#N)c3n2)ccc1N1CC[C@@H](N)C1

Participants

7

Reactant 2

HCID 898271735-Chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrileHCID 178418201HCID 178418201, compound

Product 1

HCID 127045544N-[2-[(3R)-3-aminopyrrolidin-1-yl]-5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]phenyl]acetamideYield 17.82%

Reagents, catalysts & solvents 4

HCID 10796Cesium carbonateReagentHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
105 °C

Procedure

5-chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (300 mg, 1.28 mmol), (R)-tert-butyl 1-(2-acetamido-4-aminophenyl)pyrrolidin-3-ylcarbamate (429 mg, 1.28 mmol), CESIUM CARBONATE (837 mg, 2.57 mmol) and di-tert- butyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (54.5 mg, 0.13 mmol) were added into NMP (6 mL) in a 50mL round bottle. Pd2dba3 (58.8 mg, 0.06 mmol) was added to the solution. The solution was purged by nitrogen, then heated at 105°C overnight. Crude product was separarted between water and ethyl acetate. The organic layer was concentrated under reduced pressure. The crude product was purified on the ISCO(17g silica column, EA/hex 0-75%). Then the intermediate was put in 1N HCl in ether(5mL),. The solution was stirred at rt for2hrs. Crude product was purified on Gilson(0.1%TFA CH3CN/water 2-35%), 124.8mg final product was obtained as white solid

Sources & evidence

ORD record
ord-afce2c60bcdc4fe1bfc6b3962146067d
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Linked notes

Loading…