Lithium Hexamethyldisilazide → N-(2,4-dimethoxybenzyl)-5-(pyrrolidin-2-yl)-N-(thiazol-2-yl)naphthalene-2-sulfonamide

HRID 1473356Notes

Reaction equation

HRID 1473356 reaction equation
FC(F)(F)C(O)=O.[NH:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[CH:22]=[CH:21][CH:20]=[C:19]2[C:14]=1[CH:15]=[CH:16][C:17]([S:23](OC1C(F)=C(F)C(F)=C(F)C=1F)(=[O:25])=[O:24])=[CH:18]2.[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+]>C1COCC1>[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:17]1[CH:16]=[CH:15][C:14]2[C:19](=[CH:20][CH:21]=[CH:22][C:13]=2[CH:9]2[CH2:10][CH2:11][CH2:12][NH:8]2)[CH:18]=1)(=[O:24])=[O:25]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 49931979N-(2,4-dimethoxybenzyl)thiazol-2-amineHCID 86687398Perfluorophenyl 5-(pyrrolidin-2-yl)naphthalene-2-sulfonate 2,2,2-trifluoroacetate

Product 1

HCID 86687404N-(2,4-dimethoxybenzyl)-5-(pyrrolidin-2-yl)-N-(thiazol-2-yl)naphthalene-2-sulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A round-bottom flask was charged with perfluorophenyl 5-(pyrrolidin-2-yl)naphthalene-2-sulfonate 2,2,2-trifluoroacetate (0.234 g, 0.420 mmol), N-(2,4-dimethoxybenzyl)thiazol-2-amine (0.126 g, 0.504 mmol), and THF (4.20 ml) to give a clear solution. The flask was cooled in an dry ice-acetone bath for 10 min, then lithium bis(trimethylsilyl)amide (1M in THF) (0.924 ml, 0.924 mmol) was added dropwise over 30 seconds. The reaction was stirred for 30 minutes, then the cooling bath was removed and the reaction was stirred for 30 minutes. The mixture was diluted with saturated aq. ammonium chloride solution, then extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (12-g, 0 to 10% MeOH/DCM) to give N-(2,4-dimethoxybenzyl)-5-(pyrrolidin-2-yl)-N-(thiazol-2-yl)naphthalene-2-sulfonamide as a white foam. (ESI) 510.2 (M+H)+.

Workup

  1. customto give a clear solution
  2. temperatureThe flask was cooled in an dry ice-acetone bath for 10 min
  3. customthe cooling bath was removed
  4. stirringthe reaction was stirred for 30 minutes
  5. additionThe mixture was diluted with saturated aq. ammonium chloride solution
  6. extractionextracted with EtOAc (2×)
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by chromatography on silica gel (12-g, 0 to 10% MeOH/DCM)

Sources & evidence

ORD record
ord-19902ca2a0bc45c79c61a10740776216
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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