Lithium Hexamethyldisilazide → HCID 86687520, compound

HRID 1473471Notes

Reaction equation

HRID 1473471 reaction equation
FC(F)(F)C(O)=O.[NH:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[C:22]2[C:17](=[CH:18][C:19]([S:23]([O:26]C3C(F)=C(F)C(F)=C(F)C=3F)(=[O:25])=O)=[CH:20][CH:21]=2)[CH:16]=[CH:15][N:14]=1.[CH3:38][O:39][C:40]1[CH:52]=[C:51]([O:53][CH3:54])[CH:50]=[CH:49][C:41]=1[CH2:42][NH:43][C:44]1[S:45][CH:46]=[CH:47][N:48]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>O1CCCC1>[CH3:38][O:39][C:40]1[CH:52]=[C:51]([O:53][CH3:54])[CH:50]=[CH:49][C:41]=1[CH2:42][N:43]([C:44]1[S:45][CH:46]=[CH:47][N:48]=1)[S:23]([C:19]1[CH:18]=[C:17]2[C:22](=[CH:21][CH:20]=1)[C:13]([CH:9]1[CH2:10][CH2:11][CH2:12][NH:8]1)=[N:14][CH:15]=[CH:16]2)(=[O:25])=[O:26]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 49931979N-(2,4-dimethoxybenzyl)thiazol-2-amineHCID 86687442HCID 86687442, compound

Product 1

HCID 86687520HCID 86687520, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of perfluorophenyl 1-(pyrrolidin-2-yl)isoquinoline-6-sulfonate 2,2,2-trifluoroacetate (Intermediate ZZZ; 0.350 g, 0.627 mmol) and N-(2,4-dimethoxybenzyl)thiazol-2-amine (0.173 g, 0.689 mmol) in tetrahydrofuran (6.27 ml) was cooled in a dry ice-acetone bath for 10 min. Lithium bis(trimethylsilyl)amide (1M in THF) (1.316 ml, 1.316 mmol) was added drop wise, then the reaction was stirred for 5 minutes. The cooling bath was removed and the reaction was stirred for 30 minutes. The reaction was warmed to room temperature and quenched with saturated ammonium chloride solution (aq), diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The filtrate was purified by chromatography on an 80-g silica gel column with 0-100% EtOAc/Heptane followed by a 20% 2.0M ammonia in MeOH/DCM flush to afford N-(2,4-dimethoxybenzyl)-1-(pyrrolidin-2-yl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as a light yellow solid. m/z (ESI) 511.3 (M+H)+.

Workup

  1. customThe cooling bath was removed
  2. stirringthe reaction was stirred for 30 minutes
  3. customquenched with saturated ammonium chloride solution (aq)
  4. additiondiluted with ethyl acetate
  5. washwashed with water
  6. extractionThe aqueous layer was extracted with ethyl acetate
  7. dry with materialthe combined organic layers were dried with sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe filtrate was purified by chromatography on an 80-g silica gel column with 0-100% EtOAc/Heptane
  11. customflush

Sources & evidence

ORD record
ord-da2349c0aca243f9a41064acf205c820
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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