Sodium hydride → 4-[(6-Cyclobutyl-5,6,7,8-tetrahydropyrazolo[3,4-d]azepin-2(4H)-yl)methyl]benzonitrile

HRID 1364169Notes

Reaction equation

[CH:1]1([N:5]2[CH2:11][CH2:10][C:9]3=[CH:12][NH:13][N:14]=[C:8]3[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Br[CH2:18][C:19]1[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=1>CN(C)C=O.CO>[CH:1]1([N:5]2[CH2:11][CH2:10][C:9]3=[CH:12][N:13]([CH2:18][C:19]4[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=4)[N:14]=[C:8]3[CH2:7][CH2:6]2)[CH2:2][CH2:3][CH2:4]1

Participants

Conditions

Temperature: 70 °C

Procedure

6-Cyclobutyl-2,4,5,6,7,8-hexahydropyrazolo[3,4-d]azepine (may be prepared as described in Description 31) (0.03, 0.16 mmol) in dimethylformamide (2 ml) was treated with sodium hydride (60% dispersion in oil) (0.007 g, 0.172 mmol). After 20 minutes 4-(bromomethyl)benzonitrile (0.037 g, 0.172 mmol) was added and the mixture was then heated at 70° C. for 18 hours. The reaction was then cooled to room temperature, diluted with methanol and applied to a SCX ion exchange cartridge and washed with methanol and then 2M solution of ammonia in methanol. The ammonia containing fractions were then combined and reduced and the resulting crude residue was chromatographed on silica gel eluting with a 2:98 mixture of 2M ammonia in methanol and dichloromethane to furnish the title compound (E46); (MS (ES+): [M+H]+ at m/z 307.1

Workup

temperatureThe reaction was then cooled to room temperature
washwashed with methanol
customthe resulting crude residue was chromatographed on silica gel eluting with a 2:98 mixture of 2M ammonia in methanol and dichloromethane

Sources & evidence

ORD record: ord-95faeb4c760346cdbb19af03768446e7
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07888347B2

Reaction notes

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