Lithium Hexamethyldisilazide → 8-Chloro-3-(cyclopropylsulfonyl)-1-(2-fluoro-4-iodophenyl)-5-methyl-3,4a,5,7a-tetrahydrodiimidazo[4,5-b:4',5'-e]pyridin-2(1H)-one

HRID 558218Notes

Reaction equation

[Cl:1][C:2]1[C:7]2[N:8]=[CH:9][N:10]([CH3:11])[C:6]=2[N:5]=[C:4]2[NH:12][C:13](=[O:23])[N:14]([C:15]3[CH:20]=[CH:19][C:18]([I:21])=[CH:17][C:16]=3[F:22])[C:3]=12.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH:34]1([S:37](Cl)(=[O:39])=[O:38])[CH2:36][CH2:35]1>C1COCC1>[Cl:1][C:2]1[CH:7]2[N:8]=[CH:9][N:10]([CH3:11])[CH:6]2[N:5]=[C:4]2[N:12]([S:37]([CH:34]3[CH2:36][CH2:35]3)(=[O:39])=[O:38])[C:13](=[O:23])[N:14]([C:15]3[CH:20]=[CH:19][C:18]([I:21])=[CH:17][C:16]=3[F:22])[C:3]=12

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 8-chloro-1-(2-fluoro-4-iodophenyl)-5-methyl-3,5-dihydrodiimidazo[4,5-b:4′,5′-e]pyridin-2(1H)-one (200 mg, 0.36 mmol) in THF (6 ml) at −78° C. is added LiHMDS (0.54 ml, 1 M in THF, 0.54 mmol). The reaction mixture is stirred at −78° C. for 10 min and cyclopropylsulfonyl chloride (100 mg, 0.72 mmol) is added to the mixture. The reaction is slowly warmed to room temperature and stirred at the temperature for 3 h. The reaction is quenched with saturated aqueous NH4Cl solution (10 ml) and extracted with EtOAc (2×10 ml). The combined organic solution is washed with brine (10 ml), dried over MgSO4 and concentrated. Silica gel chromatography yields the title compound.

Workup

temperatureThe reaction is slowly warmed to room temperature
stirringstirred at the temperature for 3 h
customThe reaction is quenched with saturated aqueous NH4Cl solution (10 ml)
extractionextracted with EtOAc (2×10 ml)
washThe combined organic solution is washed with brine (10 ml)
dry with materialdried over MgSO4
concentrationconcentrated

Sources & evidence

ORD record: ord-198d68157d6e4ce4ac8aaa8d66ca3b98
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08063049B2

Reaction notes

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