Lithium Hexamethyldisilazide → HCID 86687447, compound

HRID 1473401Notes

Reaction equation

HRID 1473401 reaction equation
[CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][NH:6][C:7]1[S:8][CH:9]=[CH:10][N:11]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl:28][C:29]1[C:38]2[C:33](=[CH:34][C:35]([S:39](OC3C(F)=C(F)C(F)=C(F)C=3F)(=[O:41])=[O:40])=[CH:36][CH:37]=2)[CH:32]=[N:31][N:30]=1.C(=O)=O.CC(C)=O>C1COCC1.[Cl-].[NH4+].CCOC(C)=O>[Cl:28][C:29]1[C:38]2[C:33](=[CH:34][C:35]([S:39]([N:6]([CH2:5][C:4]3[CH:12]=[CH:13][C:14]([O:16][CH3:17])=[CH:15][C:3]=3[O:2][CH3:1])[C:7]3[S:8][CH:9]=[CH:10][N:11]=3)(=[O:41])=[O:40])=[CH:36][CH:37]=2)[CH:32]=[N:31][N:30]=1

Participants

8

Reactant 4

HCID 2733832Lithium HexamethyldisilazideHCID 18522661Acetone cardiceHCID 49931979N-(2,4-dimethoxybenzyl)thiazol-2-amineHCID 86687446HCID 86687446, compound

Product 1

HCID 86687447HCID 86687447, compoundYield 35.8%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

A round-bottom flask was charged with N-(2,4-dimethoxybenzyl)thiazol-2-amine (181 mg, 0.723 mmol) and THF (3287 μl) to give a clear solution. The flask was cooled in a dry ice-acetone bath for 5 min, then lithium bis(trimethylsilyl)amide (1M in THF) (723 μl, 0.723 mmol) was added. The flask was removed from the bath for 2 min, then resubmerged. After 5 min, a solution of perfluorophenyl 1-chlorophthalazine-6-sulfonate (270 mg, 0.657 mmol) in THF (0.7 mL with a 0.3 mL wash) was added drop wise. After 5 min, the dry ice-acetone bath was swapped out for an ice-water bath. After 1 h, the mixture was diluted with saturated aq ammonium chloride solution and EtOAc. The layers were separated, and the aq. layer was washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (40-g column, 20 to 70% EtOAc/Heptane) to give 1-chloro-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)phthalazine-6-sulfonamide (112 mg, 0.235 mmol, 35.7% yield) as a cream-colored solid: m/z (ESI) 477.2 (M+H)+.

Workup

  1. customto give a clear solution
  2. temperatureThe flask was cooled in a dry ice-acetone bath for 5 min
  3. customThe flask was removed from the bath for 2 min
  4. additionwas added drop wise
  5. waitAfter 5 min
  6. waitAfter 1 h
  7. customThe layers were separated
  8. washthe aq. layer was washed with brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by chromatography on silica gel (40-g column, 20 to 70% EtOAc/Heptane)

Sources & evidence

ORD record
ord-8cfed24b1eff4d5290eb31a8b4fc0ba6
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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