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

HRID 675

Reaction equation

HRID 675 reaction equation
CC(=O)Nc1cc(N)ccc1N1CC[C@H](N(C)C)C1.N#Cc1cnn2c(NC3CC3)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(NC3CC3)n3ncc(C#N)c3n2)ccc1N1CC[C@H](N(C)C)C1

Participants

7

Reactant 2

HCID 898271735-Chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrileHCID 166477480N-[5-amino-2-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]phenyl]acetamide

Product 1

HCID 127045538N-[5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]phenyl]acetamideYield 36.66%

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

in microwave tube was 5-chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (100mg, 0.43 mmol), [Reactants], and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (24.76 mg, 0.04 mmol) in DMA (1.0 mL).Pd2(dba)3 (19.60 mg, 0.02 mmol) and cesium carbonate (279 mg, 0.86 mmol) were added. degassed, filled with N2.capped. then microwave 150C for 30 min. filtered, then concentrated. The crude material was purified by ISC(Hex to Hex:EtOAc=1;1 to EtOAc to EtOAc:MeOH=10:1 to EtOAc:MeOH:Et3N=10:1:0.1)) to give no very pure product. collect the product fraction, concentrated to dryness. no pure enough, tried to form solid. it failed sent to ananlytic group for purification. came back. it was OK 1TFA salt. NMR LCMS are OK

Sources & evidence

ORD record
ord-6ca842b2903f47c19f42752e7a96ea52
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Linked notes

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