Water → 3-bromo-N-(5-cyanopyridin-2-yl)-N-methyl-6,7-dihydropyrazolo-[1,5-a]pyrazine-5(4H)-carboxamide

HRID 539583Notes

Reaction equation

[C:1]([C:3]1[CH:4]=[CH:5][C:6]([N:9]([CH3:13])[C:10](Cl)=[O:11])=[N:7][CH:8]=1)#[N:2].[Br:14][C:15]1[CH:16]=[N:17][N:18]2[CH2:23][CH2:22][NH:21][CH2:20][C:19]=12.C(N(CC)CC)C.O>C1COCC1.CN(C)C1C=CN=CC=1>[Br:14][C:15]1[CH:16]=[N:17][N:18]2[CH2:23][CH2:22][N:21]([C:10]([N:9]([C:6]3[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][N:7]=3)[CH3:13])=[O:11])[CH2:20][C:19]=12

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of (5-cyanopyridin-2-yl)(methyl)carbamic chloride (I-28) in THF (2.0 mL) were added 3-bromo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine (137 mg, 0.680 mmol), triethylamine (0.14 mL, 1.021 mmol) and 4-dimethylaminopyridine (2.0 mg, 0.017 mmol). The mixture was stirred at 60° C. for 1 h. Subsequently, water (25 mL) was added and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over Na2SO4 and the solvent was removed under reduced pressure. The resulting crude product was purified by preparative TLC to afford 60 mg (44%) of 3-bromo-N-(5-cyanopyridin-2-yl)-N-methyl-6,7-dihydropyrazolo-[1,5-a]pyrazine-5(4H)-carboxamide (I-29) as a off white solid. 1H NMR (400 MHz, DMSO) δ 8.64 (s, 1H), 8.07 (d, J=8.8 Hz, 1H), 7.60 (s, 1H), 7.18 (d, J=8.4 Hz, 1H), 4.53 (s, 2H), 4.16 (t, J=4.9 Hz, 2H), 3.84 (t, J=4.9 Hz, 2H), 3.26 (s, 3H); ESI-LC/MS (m/z): [M+H]+ 360.91, [(M+2)+H]+ 362.93, RT 1.63 min.

Workup

extractionthe mixture was extracted with ethyl acetate
washThe organic layer was washed with brine
dry with materialdried over Na2SO4
customthe solvent was removed under reduced pressure
customThe resulting crude product was purified by preparative TLC

Sources & evidence

ORD record: ord-aba3283e3bf044949c194ea845d48b74
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08871754B2

Reaction notes

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