Water → HCID 66733797, compound

HRID 1929707Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([CH:18]([CH3:20])[CH3:19])=[N:15][C:16](I)=[C:10]2[CH:9]1[CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.O>C1COCC1.CCOCC>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([CH:18]([CH3:20])[CH3:19])=[N:15][CH:16]=[C:10]2[CH:9]1[CH2:21][CH2:22][C:23]1[CH:24]=[CH:25][C:26]([C:29]([F:30])([F:31])[F:32])=[CH:27][CH:28]=1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

Conditions

Temperature: -78 °C

Procedure

A cooled (−78° C.) solution of 1-iodo-3-isopropyl-8-[2-(4-trifluoromethyl-phenyl)-ethyl]-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester (379 mg; 0.673 mmol) in anhydrous THF (6 ml) was treated dropwise with a 1.6N butyllithium solution in hexanes (1.05 ml; 1.680 mmol). The resulting mixture was additionally stirred at −78° C., under nitrogen, for 15 min. Water (0.2 ml) was then added and the reaction mixture was allowed to warm-up to rt. The resulting solution was diluted with ether (30 ml), the organic layer was dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=25/1) gave the pure product 3-isopropyl-8-[2-(4-trifluoromethyl-phenyl)-ethyl]-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester as a yellow solid (229 mg; 78%). LC-MS: tR=0.92 min.; [M+H]+=438.43 g/mol.

Workup

temperatureto warm-up to rt
dry with materialthe organic layer was dried over anh. MgSO4
filtrationfiltered
concentrationconcentrated to dryness under reduced pressure
customPurification by FC (DCM/MeOH=25/1)

Sources & evidence

ORD record: ord-3d2b33b7a2104951b47dfb2fd30708da
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08188082B2

Reaction notes

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