Methanol → HCID 86687496, compound

HRID 1473450Notes

Reaction equation

HRID 1473450 reaction equation
Cl[C:2]1[N:3]=[C:4]([C:21]2[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][C:22]=2[O:31][CH3:32])[C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([S:12]([NH:15][C:16]1[S:17][CH:18]=[CH:19][N:20]=1)(=[O:14])=[O:13])=[CH:7][CH:6]=2.[CH3:33][O-:34].[Na+].CO>CS(C)=O.CCOC(C)=O>[CH3:33][O:34][C:2]1[N:3]=[C:4]([C:21]2[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][C:22]=2[O:31][CH3:32])[C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([S:12]([NH:15][C:16]1[S:17][CH:18]=[CH:19][N:20]=1)(=[O:14])=[O:13])=[CH:7][CH:6]=2

Participants

6

Reactant 3

HCID 887MethanolHCID 10942334Sodium Methoxide2×HCID 86687494HCID 86687494, compound

Product 1

HCID 86687496HCID 86687496, compoundYield 65.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A vial was charged with 3-chloro-1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (Example 249) (35.79 mg, 0.072 mmol), sodium methoxide (25.1 mg, 0.465 mmol), and MeOH (477 μl). The vial was sealed and heated in a 100° C. heating bath for 1 h. The mixture was diluted with DMSO (0.5 mL) to solubilize the solids, and an additional portion of sodium methoxide (25.1 mg, 0.465 mmol) was added. The vial was sealed and heated to 120° C. for 1.5 h. The mixture was cooled to room temperature and diluted with EtOAc, then washed with 1N aq. HCl, washed with water, washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (0 to 5% MeOH/DCM) to give 3-methoxy-1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (23.2 mg, 0.047 mmol, 65.4% yield) as an off-white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm=12.88 (s, 1H), 8.40 (s, 1H), 7.61-7.56 (m, 3H), 7.55-7.48 (m, 3H), 7.28 (d, J=4.6 Hz, 1H), 6.87 (d, J=4.6 Hz, 1H), 3.95 (s, 3H), 3.76 (s, 3H). m/z (ESI) 496.2 (M+H)+.

Workup

  1. customThe vial was sealed
  2. temperatureheating bath for 1 h
  3. customThe vial was sealed
  4. temperatureheated to 120° C. for 1.5 h
  5. temperatureThe mixture was cooled to room temperature
  6. washwashed with 1N aq. HCl
  7. washwashed with water
  8. washwashed with brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by chromatography on silica gel (0 to 5% MeOH/DCM)

Sources & evidence

ORD record
ord-6d3af5c7b7654631bbeac8d0554e98a6
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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