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

HRID 1473458노트

반응식

HRID 1473458 반응식
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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

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온도
150 °C

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-b977882d5d7548df92b0ff5d1d27e543
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012443B2

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