Lithium Hexamethyldisilazide → 1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(1,2,5-thiadiazol-3-yl)isoquinoline-6-sulfonamide

HRID 1473598Notes

Reaction equation

HRID 1473598 reaction equation
[S:1]1[N:5]=[CH:4][C:3]([NH2:6])=[N:2]1.[CH3:7][O:8][C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:10]=1[C:19]1[C:28]2[C:23](=[CH:24][C:25]([S:29](OC3C(F)=C(F)C(F)=C(F)C=3F)(=[O:31])=[O:30])=[CH:26][CH:27]=2)[CH:22]=[CH:21][N:20]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[CH3:7][O:8][C:9]1[CH:14]=[C:13]([C:15]([F:16])([F:17])[F:18])[CH:12]=[CH:11][C:10]=1[C:19]1[C:28]2[C:23](=[CH:24][C:25]([S:29]([NH:6][C:3]3[CH:4]=[N:5][S:1][N:2]=3)(=[O:31])=[O:30])=[CH:26][CH:27]=2)[CH:22]=[CH:21][N:20]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 108986591,2,5-Thiadiazol-3-amineHCID 86687478Perfluorophenyl 1-(2-methoxy-4-(trifluoromethyl)phenyl)isoquinoline-6-sulfonate

Product 1

HCID 866876611-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(1,2,5-thiadiazol-3-yl)isoquinoline-6-sulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

1,2,5-thiadiazol-3-amine (28 mg, 0.273 mmol) (Aquila Pharmtech) and perfluorophenyl 1-(2-methoxy-4-(trifluoromethyl)phenyl)isoquinoline-6-sulfonate (Intermediate LLL; 100 mg, 0.182 mmol) were dissolved in THF (1 mL) in a round bottom flask and cooled to 0° C., then lithium bis(trimethylsilyl)amide (1 M in THF, 364 μl, 0.364 mmol) was added and the reaction was stirred for 30 min. The reaction was quenched with saturated ammonium chloride and extracted with EtOAc (3×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated via rotary evaporation. The residue was purified using reverse-phase HPLC with a Waters-Xbridge C18, 19×100 mm, 10 μm column with a gradient 5-95% acetonitrile and water with 0.1% ammonium hydroxide modifier to yield 1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(1,2,5-thiadiazol-3-yl)isoquinoline-6-sulfonamide. m/z (ESI) 467.0 (M+H)+.

Workup

  1. customThe reaction was quenched with saturated ammonium chloride
  2. extractionextracted with EtOAc (3×)
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated via rotary evaporation
  6. customThe residue was purified

Sources & evidence

ORD record
ord-a8d9c56790cf4795936eb0211d445183
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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