Dimethyl Sulfoxide → HCID 59754253, compound

HRID 751164Notes

Reaction equation

C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][C@@H:12]1[CH2:17][CH2:16][CH2:15][N:14]2[C:18](=[O:31])[N:19]([C:21]3[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[C:23]([Cl:29])[C:22]=3[CH3:30])[CH2:20][C@H:13]12.C(N(CC)CC)C>C(Cl)Cl>[O:31]=[C:18]1[N:14]2[CH2:15][CH2:16][CH2:17][C:12](=[O:11])[C@H:13]2[CH2:20][N:19]1[C:21]1[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[C:23]([Cl:29])[C:22]=1[CH3:30]

Participants

Conditions

Temperature: -78 °C

Procedure

A mixture of oxalyl chloride (94 μL, 0.19 mmol) in DCM (50 μL) was cooled to −78° C. and a solution of DMSO (26 μL, 0.37 mmol) in DCM (0.7 mL) was added. The resulting mixture was stirred at −78° C. for 15 min. A solution of 4-[(8R,8aR)-8-hydroxy-3-oxohexahydroimidazo[1,5-a]pyridin-2-yl]-2-chloro-3-methylbenzonitrile (77J) (16 mg, 0.052 mmol) in DCM (0.5 mL) was followed by DCM (0.5 mL) and stirred at −78° C. for 30 min. Triethylamine (120 μL, 0.86 mmol) was added and gradually warmed to rt over 1 h. The solvent was removed and the residue was purified by flash chromatography (silica gel, 30-50% EtOAc/hexane) to give the title compound 78A (12.9 mg) as a white solid: Chiral analytical HPLC (ChiralPak AD OD 4.6×250 mm, 35% IPA/hexane isocratic) retention time 13.8 min (100% ee); MS (ES) m/z 304.1 [M+1]+; HRMS calcd for C15H13ClN3O2 302.0696, Found 302.0681.

Workup

stirringstirred at −78° C. for 30 min
temperaturegradually warmed to rt over 1 h
customThe solvent was removed
customthe residue was purified by flash chromatography (silica gel, 30-50% EtOAc/hexane)

Sources & evidence

ORD record: ord-91bda0b901f74d14a6062d6da72b66c4
Source dataset: uspto-grants-2008_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07405234B2

Reaction notes

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