Trifluoroacetic acid → methyl 2-(6-(N-(thiazol-2-yl)sulfamoyl)isoquinolin-1-yl)-5-(trifluoromethyl)benzimidate

HRID 1473453노트

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HRID 1473453 반응식
[C:1]([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]([N:26](CC3C=CC(OC)=CC=3OC)[C:27]3[S:28][CH:29]=[CH:30][N:31]=3)(=[O:25])=[O:24])=[CH:20][CH:21]=2)[CH:16]=[CH:15][N:14]=1)#[N:2].[C:43](O)(C(F)(F)F)=[O:44]>C(Cl)Cl>[S:28]1[CH:29]=[CH:30][N:31]=[C:27]1[NH:26][S:23]([C:19]1[CH:18]=[C:17]2[C:22](=[CH:21][CH:20]=1)[C:13]([C:4]1[CH:5]=[CH:6][C:7]([C:9]([F:11])([F:12])[F:10])=[CH:8][C:3]=1[C:1](=[NH:2])[O:44][CH3:43])=[N:14][CH:15]=[CH:16]2)(=[O:25])=[O:24]

참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acidHCID 866874981-(2-cyano-4-(trifluoromethyl)phenyl)-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

생성물 1

HCID 86687499methyl 2-(6-(N-(thiazol-2-yl)sulfamoyl)isoquinolin-1-yl)-5-(trifluoromethyl)benzimidate수율 88.9%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

1-(2-cyano-4-(trifluoromethyl)phenyl)-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (0.011 g, 0.018 mmol) was dissolved in 1 mL of DCM and TFA (0.1 ml, 1.298 mmol) was added. The reaction was stirred for 30 minutes at room temperature. The reaction was concentrated, dissolved in methanol, and 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 product-containing filtrate was concentrated to afford an orange solid. The material was purified via silica gel column chromatography (12 g silica gel column, gradient elution 0 to 10% MeOH:DCM) to afford methyl 2-(6-(N-(thiazol-2-yl)sulfamoyl)isoquinolin-1-yl)-5-(trifluoromethyl)benzimidate (0.008 g, 0.016 mmol, 9.10% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm=12.90 (br. s., 1H), 8.78 (br. s., 1H), 8.66 (d, J=5.6 Hz, 1H), 8.58 (s, 1H), 8.14 (d, J=5.0 Hz, 1H), 8.06 (br. s., 1H), 7.99 (d, J=7.5 Hz, 1H), 7.89-7.83 (m, 1H), 7.77 (d, J=8.5 Hz, 2H), 7.28 (d, J=4.6 Hz, 1H), 6.87 (d, J=4.6 Hz, 1H), 3.02 (s, 3H). m/z (ESI) 493.2 (M+H)+.

후처리

  1. concentrationThe reaction was concentrated
  2. dissolutiondissolved in methanol
  3. customThe column was flushed several times with methanol
  4. customby flushing the column several times with 2.0 M ammonia in methanol
  5. concentrationThe product-containing filtrate was concentrated
  6. customto afford an orange solid
  7. customThe material was purified via silica gel column chromatography (12 g silica gel column, gradient elution 0 to 10% MeOH:DCM)

출처 및 근거

ORD 기록
ord-7f03b8ae998c4314a911d6989f95ab66
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012443B2

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