N-(5-amino-4-fluoro-2-methylphenyl)acetamide → N-[5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-4-fluoro-2-methylphenyl]acetamide

HRID 606

Reaction equation

HRID 606 reaction equation
CC(=O)Nc1cc(N)c(F)cc1C.N#Cc1cnn2c(NC3CC3)cc(Cl)nc12>C1COCCO1.CC(C)c1cc(C(C)C)c(-c2ccccc2P(C(C)(C)C)C(C)(C)C)c(C(C)C)c1.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)c(F)cc1C

Participants

7

Reactant 2

HCID 89099132N-(5-amino-4-fluoro-2-methylphenyl)acetamideHCID 898271735-Chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile

Product 1

HCID 72163926N-[5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-4-fluoro-2-methylphenyl]acetamideYield 20.63%

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 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

In 20 ml microwave vial were added 5-chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (200 mg, 0.86 mmol), N-(5-amino-4-fluoro-2-methylphenyl)acetamide (164 mg, 0.90 mmol), Pd2dba3 (39.2 mg, 0.04 mmol), di-tert- butyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (37.5 mg, 0.09 mmol) and Cs2CO3 (837 mg, 2.57 mmol). The vessel was fitted with septum, gas inlet and dioxane (8 mL) was added via syringe. The resulting suspension was stirred for 5 min. under N2. The septum and gas inlet quickly replaced with microwave vial cap and the mixture was heated to 150oC under microwave irradiation for 30 min. The reaction mixture filtered through celite, filtrate concentrated, combined with EN02368-53 experiment and purified by ISCO column (0-5% MeOH-CH2Cl2). The obtained compound triturated with CH3CN, filtered and dried to give light brown color solid. Conclusion: product isolated

Sources & evidence

ORD record
ord-71ad501d78264f9aa8b8fb6c66e7e044
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Linked notes

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