Dimethylformamide → 1-(4-chloro-2-methoxyphenyl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamide

HRID 1473564Notes

Reaction equation

HRID 1473564 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18](OC4C(F)=C(F)C(F)=C(F)C=4F)(=[O:20])=[O:19])=[CH:15][CH:16]=3)[CH:11]=[CH:10][N:9]=2)=[C:4]([O:33][CH3:34])[CH:3]=1.[S:35]1[CH:39]=[N:38][N:37]=[C:36]1[NH2:40].C(=O)([O-])[O-].[Cs+].[Cs+].CN(C=O)C>CCOC(C)=O.Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([NH:40][C:36]4[S:35][CH:39]=[N:38][N:37]=4)(=[O:19])=[O:20])=[CH:15][CH:16]=3)[CH:11]=[CH:10][N:9]=2)=[C:4]([O:33][CH3:34])[CH:3]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 199091,3,4-Thiadiazol-2-amineHCID 86687421Perfluorophenyl 1-(4-chloro-2-methoxyphenyl)isoquinoline-6-sulfonate

Product 1

HCID 866876261-(4-chloro-2-methoxyphenyl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamideYield 76%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

A round-bottom flask was charged with perfluorophenyl 1-(4-chloro-2-methoxyphenyl)isoquinoline-6-sulfonate (INTERMEDIATE NNN; 102.15 mg, 0.198 mmol), 1,3,4-thiadiazol-2-amine (40.1 mg, 0.396 mmol), cesium carbonate (194 mg, 0.594 mmol), and DMF (1 mL) (1:30 pm). The mixture was diluted with EtOAc and 0.5 N aq. HCl. The layers were separated, and the organic extract was washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-7% MeOH/DCM) to give 1-(4-chloro-2-methoxyphenyl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamide (64.78 mg, 0.150 mmol, 76% yield) as a white solid. m/z (ESI) 433.0 (M+H)+.

Workup

  1. customThe layers were separated
  2. extractionthe organic extract
  3. washwas washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-7% MeOH/DCM)

Sources & evidence

ORD record
ord-975029f9b5cd48e195f5c4c7b9060c8c
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

Loading…