Lithium Hexamethyldisilazide → HCID 86687450, compound

HRID 1473404Notes

Reaction equation

HRID 1473404 reaction equation
[F:1][C:2]1[S:6][C:5]([NH:7][CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)=[N:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl:27][C:28]1[C:37]2[C:32](=[CH:33][C:34]([S:38](OC3C(F)=C(F)C(F)=C(F)C=3F)(=[O:40])=[O:39])=[CH:35][CH:36]=2)[CH:31]=[N:30][N:29]=1>C1COCC1.[Cl-].[NH4+]>[Cl:27][C:28]1[C:37]2[C:32](=[CH:33][C:34]([S:38]([N:7]([C:5]3[S:6][C:2]([F:1])=[CH:3][N:4]=3)[CH2:8][C:9]3[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=3)(=[O:40])=[O:39])=[CH:35][CH:36]=2)[CH:31]=[N:30][N:29]=1

Participants

6

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 86687419HCID 86687419, compoundHCID 86687446HCID 86687446, compound

Product 1

HCID 86687450HCID 86687450, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 25517Ammonium ChlorideSolvent

Procedure

A round-bottom flask was charged with 5-fluoro-N-(4-methoxybenzyl)thiazol-2-amine (Intermediate MMM) (184 mg, 0.774 mmol) and THF (1 mL) to give a clear, light-orange solution. The flask was cooled in a dry ice-acetone bath for 5 min to give a suspension. Lithium bis(trimethylsilyl)amide (1M in THF) (774 μl, 0.774 mmol) was added drop wise to give a clay-colored suspension. The mixture was stirred for 15 min, after which time it was a solution. A solution of perfluorophenyl 1-chlorophthalazine-6-sulfonate (from Intermediate AAAA, Step 2; 265 mg, 0.645 mmol) in THF (1 mL with a 0.25 mL syringe/vial wash) was added drop wise. After 45 min, the mixture was diluted with saturated aq ammonium chloride and extracted with EtOAc. The organic extract was 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-(5-fluorothiazol-2-yl)-N-(4-methoxybenzyl)phthalazine-6-sulfonamide (129 mg, 0.277 mmol, 43.0% yield) as a cream-colored solid: m/z (ESI) 465.2 (M+H)+.

Workup

  1. customto give a clear, light-orange solution
  2. temperatureThe flask was cooled in a dry ice-acetone bath for 5 min
  3. customto give a suspension
  4. customto give a clay-colored suspension
  5. additionwas added drop wise
  6. waitAfter 45 min
  7. extractionextracted with EtOAc
  8. extractionThe organic extract
  9. dry with materialwas dried 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-bf09f198a72c491ab84035e429126131
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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