2-Aminothiazole → 1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

HRID 1473437Notes

Reaction equation

HRID 1473437 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1[C:13]1[C:22]2[C:17](=[CH:18][C:19]([S:23](OC3C(F)=C(F)C(F)=C(F)C=3F)(=[O:25])=[O:24])=[CH:20][CH:21]=2)[CH:16]=[CH:15][N:14]=1.[S:38]1[CH:42]=[CH:41][N:40]=[C:39]1[NH2:43].C1COCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:10])[F:11])[CH:6]=[CH:5][C:4]=1[C:13]1[C:22]2[C:17](=[CH:18][C:19]([S:23]([NH:43][C:39]3[S:38][CH:42]=[CH:41][N:40]=3)(=[O:24])=[O:25])=[CH:20][CH:21]=2)[CH:16]=[CH:15][N:14]=1

Participants

6

Reactant 4

HCID 21552-AminothiazoleHCID 8028TetrahydrofuranHCID 2733832Lithium HexamethyldisilazideHCID 86687478Perfluorophenyl 1-(2-methoxy-4-(trifluoromethyl)phenyl)isoquinoline-6-sulfonate

Product 1

HCID 866874821-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamideYield 75.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of perfluorophenyl 1-(2-methoxy-4-(trifluoromethyl)phenyl)isoquinoline-6-sulfonate (INTERMEDIATE LLL) (425.75 mg, 0.775 mmol), thiazol-2-amine (78 mg, 0.775 mmol), and THF (3875 μl) was cooled in an ice-water bath for 15 min, then lithium bis(trimethylsilyl)amide (1M in THF) (1627 μl, 1.627 mmol) was added drop wise. After 30 min, the mixture was warmed to room temperature and loaded onto a 25-g silica gel loading column with DCM. The column was dried under vacuum for 5 min then eluted onto a pre-equilibrated 40-g silica gel column with 0 to 10% MeOH/DCM to give a yellow solid. The mixture was concentrated from DCM (2×). The residue was then taken up in DCM, sonicated, filtered, washed with DCM (3×), and dried under a stream of N2 (g) to give a white solid. The white solid was crushed with a spatula then dried under high vacuum to give 1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (271 mg, 0.582 mmol, 75% yield) as a white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm=12.89 (br. s., 1H), 8.69 (d, J=5.7 Hz, 1H), 8.55 (d, J=1.8 Hz, 1H), 8.13 (d, J=5.7 Hz, 1H), 7.87 (dd, J=1.9, 8.9 Hz, 1H), 7.70 (d, J=8.9 Hz, 1H), 7.60-7.45 (m, 3H), 7.28 (d, J=4.6 Hz, 1H), 6.87 (d, J=4.6 Hz, 1H), 3.74 (s, 3H); m/z (ESI) 466.2 (M+H)+.

Workup

  1. customThe column was dried under vacuum for 5 min
  2. washthen eluted onto a pre-equilibrated 40-g silica gel column with 0 to 10% MeOH/DCM
  3. customto give a yellow solid
  4. concentrationThe mixture was concentrated from DCM (2×)
  5. customsonicated
  6. filtrationfiltered
  7. washwashed with DCM (3×)
  8. dry with materialdried under a stream of N2 (g)
  9. customto give a white solid
  10. customThe white solid was crushed with a spatula
  11. customthen dried under high vacuum

Sources & evidence

ORD record
ord-a293a62c39bf4c0ba4ae7b9b33dd9b98
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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