Cesium carbonate → 1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(oxazol-4-yl)isoquinoline-6-sulfonamide

HRID 1473621Notes

Reaction equation

HRID 1473621 reaction equation
[O:1]1[CH:5]=[C:4]([NH:6]C(=O)OCC2C=CC(OC)=CC=2OC)[N:3]=[CH:2]1.[CH3:21][O:22][C:23]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][C:24]=1[C:33]1[C:42]2[C:37](=[CH:38][C:39]([S:43](OC3C(F)=C(F)C(F)=C(F)C=3F)(=[O:45])=[O:44])=[CH:40][CH:41]=2)[CH:36]=[CH:35][N:34]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.CCOC(C)=O>[CH3:21][O:22][C:23]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][C:24]=1[C:33]1[C:42]2[C:37](=[CH:38][C:39]([S:43]([NH:6][C:4]3[N:3]=[CH:2][O:1][CH:5]=3)(=[O:44])=[O:45])=[CH:40][CH:41]=2)[CH:36]=[CH:35][N:34]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 86687478Perfluorophenyl 1-(2-methoxy-4-(trifluoromethyl)phenyl)isoquinoline-6-sulfonateHCID 866876902,4-Dimethoxybenzyl oxazol-4-ylcarbamate

Product 1

HCID 866876891-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(oxazol-4-yl)isoquinoline-6-sulfonamideYield 9.29%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a 5-mL round bottom flask under N2 were dissolved 2,4-dimethoxybenzyl oxazol-4-ylcarbamate (100 mg, 0.359 mmol), perfluorophenyl 1-(2-methoxy-4-(trifluoromethyl)phenyl)isoquinoline-6-sulfonate (182 mg, 0.395 mmol) (Intermediate LLL) and cesium carbonate (351 mg, 1.078 mmol) in 1 mL of DMSO, and then the mixture was stirred at rt for 10 h. The reaction mixture was diluted with AcOEt then neutralized with NH4Cl/Ice. The aqueous phase was extracted 3× with AcOEt then the organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude mixture was purified by MPLC (ISCO) with Hexanes:AcOEt 100:0 to 0:100 to afforded 1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(oxazol-4-yl)isoquinoline-6-sulfonamide (15 mg, 0.033 mmol, 9.29%) as a white solid. MS (ESI, positive ion) [M+1]+: 450.0.

Workup

  1. extractionThe aqueous phase was extracted 3× with AcOEt
  2. dry with materialthe organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude mixture was purified by MPLC (ISCO) with Hexanes:AcOEt 100:0 to 0:100

Sources & evidence

ORD record
ord-25b5f5fb2a524662aa9296606a213a96
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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