N-(5-amino-2-cyclopropylphenyl)acetamide → N-[5-[[3-cyano-7-(oxetan-3-ylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2-cyclopropylphenyl]acetamide

HRID 738Notes

Reaction equation

HRID 738 reaction equation
CC(=O)Nc1cc(N)ccc1C1CC1.N#Cc1cnn2c(NC3COC3)cc(Cl)nc12>CC(=O)N(C)C.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(NC3COC3)n3ncc(C#N)c3n2)ccc1C1CC1

Participants

7

Reactant 2

HCID 89098640N-(5-amino-2-cyclopropylphenyl)acetamideHCID 178418222HCID 178418222, compound

Product 1

HCID 72164289N-[5-[[3-cyano-7-(oxetan-3-ylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2-cyclopropylphenyl]acetamideYield 8.66%

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 31374DimethylacetamideSolvent

Conditions

Temperature
145 °C

Procedure

In a microwave tube, was Cs2CO3 (0.522 g, 1.60 mmol), N-(5-amino-2-cyclopropylphenyl)acetamide (0.152 g, 0.80 mmol), Pd2dba3 (0.037 g, 0.04 mmol),5-chloro-7-(oxetan-3-ylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (0.200 g, 0.80 mmol),di-tert- butyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.034 g, 0.08 mmol). anhydrous DMA (1.0 mL) was added. The resulting mixture was bubbled through N2. Then the tube was capped. under microwave 145C for 25min. LCMS showed product and byproduct mass, did not showed SM The mixture was filtered through celite. The resulting black solution was concentrated to dryness by rotavapor. The crude product was purified by ISCO (40g, Hex to EtOAc:HEx=1;2 to 1;1 to EtOAcO) to give product (offwhite solid). HPLC showed some impurity. This offwhite solid was washed with warm EtOAc (1mL) to give N-(5-(3-cyano-7-(oxetan-3-ylamino)pyrazolo[1,5-a]pyrimidin-5-ylamino)-2-cyclopropylphenyl)acetamide (0.028 g, 8.66 %). LCMS and NMR were OK< see attachment.

Sources & evidence

ORD record
ord-475c89db99fe4f418713bc4636a30c0a
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Reaction notes

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