Imidazole → 1-(2-(1H-imidazol-1-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

HRID 1473458Notes

Reaction equation

HRID 1473458 reaction equation
F[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C:12]1[C:21]2[C:16](=[CH:17][C:18]([S:22]([NH:25][C:26]3[S:27][CH:28]=[CH:29][N:30]=3)(=[O:24])=[O:23])=[CH:19][CH:20]=2)[CH:15]=[CH:14][N:13]=1.[NH:31]1[CH:35]=[CH:34][N:33]=[CH:32]1.CC(C)([O-])C.[K+].CN(C=O)C>C(OCC)(=O)C>[N:31]1([C:2]2[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=2[C:12]2[C:21]3[C:16](=[CH:17][C:18]([S:22]([NH:25][C:26]4[S:27][CH:28]=[CH:29][N:30]=4)(=[O:23])=[O:24])=[CH:19][CH:20]=3)[CH:15]=[CH:14][N:13]=2)[CH:35]=[CH:34][N:33]=[CH:32]1

Participants

6

Reactant 4

HCID 795ImidazoleHCID 6228DimethylformamideHCID 23665647Potassium tert-butoxideHCID 866875021-(2-fluoro-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

Product 1

HCID 866875031-(2-(1H-imidazol-1-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

A microwave vial was charged with 1-(2-fluoro-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (0.090 g, 0.198 mmol), imidazole (0.054 g, 0.794 mmol), and potassium tert-butoxide (0.111 g, 0.992 mmol). DMF (0.992 ml) was added and the reaction was heated in a microwave reactor at 150° C. for one hour. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, then acidified with concentrated HCl solution and extracted twice with ethyl acetate. The aqueous layer was passed through an SCX ion exchange column (pre-wetted with methanol). The column was flushed several times with methanol, then the product was liberated by flushing the column several times with 2.0 M ammonia in methanol. The ammonia/methanol filtrate was combined with the previously isolated organic layers. The combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via silica gel column chromatography (12 g, gradient elution 0 to 10% MeOH:DCM) to afford 1-(2-(1H-imidazol-1-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm=12.90 (br. s., 1H), 8.66 (d, J=5.7 Hz, 1H), 8.50 (d, J=1.6 Hz, 1H), 8.13 (d, J=5.4 Hz, 1H), 8.08 (s, 1H), 8.03 (dd, J=1.2, 8.1 Hz, 1H), 7.88 (d, J=7.9 Hz, 1H), 7.79-7.73 (m, 1H), 7.70-7.63 (m, 1H), 7.48 (t, J=1.0 Hz, 1H), 7.26 (d, J=4.6 Hz, 1H), 6.89-6.81 (m, 2H), 6.62 (t, J=1.1 Hz, 1H). m/z (ESI) 502.2 (M+H)+.

Workup

  1. washwashed with water
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. extractionextracted twice with ethyl acetate
  4. customThe column was flushed several times with methanol
  5. customby flushing the column several times with 2.0 M ammonia in methanol
  6. dry with materialThe combined organic layers were dried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe material was purified via silica gel column chromatography (12 g, gradient elution 0 to 10% MeOH:DCM)

Sources & evidence

ORD record
ord-b977882d5d7548df92b0ff5d1d27e543
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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