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

HRID 722

Reaction equation

HRID 722 reaction equation
CC(=O)Nc1cc(N)c(F)cc1C.N#Cc1cnn2c(NC3CCC3)cc(Cl)nc12>CC(=O)N(C)C.CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21.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(NC3CCC3)n3ncc(C#N)c3n2)c(F)cc1C

Participants

7

Reactant 2

HCID 89099132N-(5-amino-4-fluoro-2-methylphenyl)acetamideHCID 178418221HCID 178418221, compound

Product 1

HCID 72164043N-[5-[[3-cyano-7-(cyclobutylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-4-fluoro-2-methylphenyl]acetamideYield 5.51%

Reagents, catalysts & solvents 4

HCID 10796Cesium carbonateReagentHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
150 °C

Procedure

5-chloro-7-(cyclobutylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (80 mg, 0.32 mmol), N-(5-amino-4-fluoro-2-methylphenyl)acetamide (58.8 mg, 0.32 mmol), and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (18.69 mg, 0.03 mmol) in DMA (5 mL) were added to a microwave tube. Pd2(dba)3 (14.79 mg, 0.02 mmol) and cesium carbonate (210 mg, 0.65 mmol) were added. The solution was degassed, filled with N2, capped, then microwaved at 150C for 30 min. The organic solvent was removed. TLC showed two closely associated peaks, so product was purified via Gilson. Appropriate fractions were collected, concentrated by rotovap, and dried in the oven overnight. LCMS, HPLC, and NMR revealed desired product. See attachments.

Sources & evidence

ORD record
ord-b55c5711f803482494d33a05fbba3389
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Linked notes

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