Water → (R)-[1-(2-cyano-ethyl)-4,5,6,7-tetrahydro-1H-indazol-4-yl]-carbamic acid benzyl ester

HRID 1645147Notes

Reaction equation

[CH2:1]([O:8][C:9]([NH:11][C@@H:12]1[CH2:20][CH2:19][CH2:18][C:17]2[N:16]([CH2:21][CH2:22]OS(C)(=O)=O)[N:15]=[CH:14][C:13]1=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C-:28]#[N:29].[Na+].O>CS(C)=O>[CH2:1]([O:8][C:9](=[O:10])[NH:11][C@@H:12]1[CH2:20][CH2:19][CH2:18][C:17]2[N:16]([CH2:21][CH2:22][C:28]#[N:29])[N:15]=[CH:14][C:13]1=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of methanesulfonic acid 2-((R)-4-benzyloxycarbonylamino-4,5,6,7-tetrahydroindazol-1-yl)-ethyl ester (850 mg, 2.16 mmol) in dimethyl sulfoxide (20 mL) was added sodium cyanide (540 mg, 10.8 mmol). The mixture was stirred at 55° C. for 4 hours. After cooling, to the mixture was added water, and the aqueous layer was extracted with ethyl acetate (20 mL×4). The combined organic layers were dried over sodium sulfate, filtered and then concentrated in vacuo. The residue was purified by flash column chromatography (10% methanol in dichloromethane) to afford (R)-[1-(2-cyano-ethyl)-4,5,6,7-tetrahydro-1H-indazol-4-yl]-carbamic acid benzyl ester (600 mg, 85%) as a white solid. MS calcd. for C18H20N4O2 324, obsd. (ESI+) [(M+H)+] 325.

Workup

temperatureAfter cooling, to the mixture
extractionthe aqueous layer was extracted with ethyl acetate (20 mL×4)
dry with materialThe combined organic layers were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by flash column chromatography (10% methanol in dichloromethane)

Sources & evidence

ORD record: ord-8cb25dc497d544479208995d38d8c8df
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08124641B2

Reaction notes

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