Lithium Hexamethyldisilazide → HCID 89525863, compound

HRID 571423Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[CH:6][C:5]2[C:8]([CH:30]([NH:35][S:36]([C:39]([CH3:42])([CH3:41])[CH3:40])(=O)=[O:37])[C:31]([F:34])([F:33])[F:32])=[N:9][N:10]([C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:4]=2[CH:3]=1.[CH3:43][Si]([N-][Si](C)(C)C)(C)C.[Li+]>>[Cl:1][C:2]1[N:7]=[CH:6][C:5]2[C:8]([CH:30]([N:35]([CH3:43])[S:36]([C:39]([CH3:42])([CH3:40])[CH3:41])=[O:37])[C:31]([F:33])([F:34])[F:32])=[N:9][N:10]([C:11]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:4]=2[CH:3]=1

Participants

Reactant 2

HCID 2733832Lithium Hexamethyldisilazide

HCID 117601639HCID 117601639, compound

Product 1

HCID 89525863HCID 89525863, compoundYield 49.7%

Procedure

N-(1-(6-chloro-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-yl)-2,2,2-trifluoroethyl)-2-methylpropane-2-sulfonamide (108 mg, 0.181 mmol) was cooled to 0° C. and charged with lithium bis(trimethylsilyl)amide (0.217 ml, 0.217 mmol) followed by iodomethahe (0.011 ml, 0.181 mmol) (˜2 drops). The reaction was allowed to warm to rt overnight. Quenched excess LiHMDS with methanol and evaporated solvents on the V-10. The residue was purified on silica, 10-50% DCM/EtOAc to provide N-(1-(6-chloro-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-yl)-2,2,2-trifluoroethyl)-N,2-dimethylpropane-2-sulfinamide (53 mg, 0.09 mmol, 48% yield) MS ESI Calc'd for C32H30ClF3N4OS [M+H]+ 611, found 611.

Workup

customQuenched excess LiHMDS with methanol and evaporated solvents on the V-10
customThe residue was purified on silica, 10-50% DCM/EtOAc

Sources & evidence

ORD record: ord-2b70e45f53c1423cbbaba8a0a6accc19
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09023865B2

Reaction notes

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