2-Aminothiazole → 1-chloro-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

HRID 1473330Notes

Reaction equation

HRID 1473330 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[NH2:6].[Cl:7][C:8]1[C:17]2[C:12](=[CH:13][C:14]([S:18](OC3C(F)=C(F)C(F)=C(F)C=3F)(=[O:20])=[O:19])=[CH:15][CH:16]=2)[CH:11]=[CH:10][N:9]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[Cl:7][C:8]1[C:17]2[C:12](=[CH:13][C:14]([S:18]([NH:6][C:2]3[S:1][CH:5]=[CH:4][N:3]=3)(=[O:20])=[O:19])=[CH:15][CH:16]=2)[CH:11]=[CH:10][N:9]=1

Participants

5

Reactant 3

HCID 21552-AminothiazoleHCID 2733832Lithium HexamethyldisilazideHCID 86687382Perfluorophenyl 1-chloroisoquinoline-6-sulfonate

Product 1

HCID 866873831-chloro-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A flask containing thiazol-2-amine (0.185 g, 1.843 mmol), perfluorophenyl 1-chloroisoquinoline-6-sulfonate (0.719 g, 1.755 mmol), and THF (0.163 mL) was cooled to 0° C. LHMDS (1.0 M in THF) (3.86 ml, 3.86 mmol) was added dropwise and the reaction was stirred for 5 minutes at 0° C. The reaction was quenched with saturated ammonium chloride solution, 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 material was triturated in DCM and loaded onto a silica gel cartridge. The tan solid remaining at the top of the cartridge was scraped into a flask and put aside. The remaining material was purified by silica gel chromatography (40 g column, gradient elution 0 to 100% EtOAc:Heptane with a 10% MeOH:DCM flush). The product fractions were combined with the previously isolated material to afford 1-chloro-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as a tan solid. m/z (ESI) 326.0 (M+H)+.

Workup

  1. customThe reaction was quenched with saturated ammonium chloride solution
  2. additiondiluted with ethyl acetate
  3. washwashed with water
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. dry with materialthe combined organic layers were dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe material was triturated in DCM
  9. customwas scraped into a flask
  10. customThe remaining material was purified by silica gel chromatography (
  11. wash40 g column, gradient elution 0 to 100% EtOAc
  12. customHeptane with a 10% MeOH:DCM flush)

Sources & evidence

ORD record
ord-6bea84c8dd0b4b58a06ee6105e3cd30a
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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