Potassium Cyanide → 5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidine-2-carbonitrile

HRID 1484990Notes

Reaction equation

Br[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:13]=[C:12]([CH:14]3[CH2:16][CH2:15]3)[NH:11][N:10]=2)[C:5]([Cl:17])=[CH:4][N:3]=1.[C-:18]#[N:19].[K+]>CS(C)=O.O>[Cl:17][C:5]1[C:6]([NH:8][C:9]2[CH:13]=[C:12]([CH:14]3[CH2:16][CH2:15]3)[NH:11][N:10]=2)=[N:7][C:2]([C:18]#[N:19])=[N:3][CH:4]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 2-bromo-5-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)pyrimidin-4-amine (3.0 g, 9.54 mmol, 1.0 eq), KCN (1.24 g, 19.07 mmol, 2.0 eq) and 1,4-diazobicyclo[2,2,2]octan (DABCO.6H2O) (4.20 g, 19.07 mmol, 2.0 eq) in DMSO (50 mL) and H2O (10 mL) was stirred at 80° C. for 4 h. The reaction mixture was diluted with H2O (50 mL) and extracted with EtOAc (3×100 mL). The combined organic phases were washed (brine), dried (Na2SO4), filtered and concentrated. The residue was purified by silica gel chromatography (CH2Cl2/MeOH 500:1 to 50:1 as eluent) to afford 5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidine-2-carbonitrile (1.9 g, 77%) as a solid. LC-MS (m/z)=261.0 [M+H]+.

Workup

extractionextracted with EtOAc (3×100 mL)
washThe combined organic phases were washed (brine)
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customThe residue was purified by silica gel chromatography (CH2Cl2/MeOH 500:1 to 50:1 as eluent)

Sources & evidence

ORD record: ord-a27ceb4ea0a742749b55e732d18cdceb
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09422271B2

Reaction notes

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