Trifluoroacetic acid → N-(3-bromo-1,2,4-thiadiazol-5-yl)-1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1H-indole-6-sulfonamide

HRID 1524436노트

반응식

HRID 1524436 반응식
[Br:1][C:2]1[N:6]=[C:5]([N:7](CC2C=CC(OC)=CC=2)[S:8]([C:11]2[CH:19]=[C:18]3[C:14]([C:15]([C:21]4[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][C:22]=4[C:31]4[N:35]([CH3:36])[N:34]=[CH:33][CH:32]=4)=[CH:16][N:17]3[CH3:20])=[CH:13][CH:12]=2)(=[O:10])=[O:9])[S:4][N:3]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[Br:1][C:2]1[N:6]=[C:5]([NH:7][S:8]([C:11]2[CH:19]=[C:18]3[C:14]([C:15]([C:21]4[CH:26]=[CH:25][C:24]([C:27]([F:28])([F:29])[F:30])=[CH:23][C:22]=4[C:31]4[N:35]([CH3:36])[N:34]=[CH:33][CH:32]=4)=[CH:16][N:17]3[CH3:20])=[CH:13][CH:12]=2)(=[O:9])=[O:10])[S:4][N:3]=1

참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acid2회HCID 71259358N-(3-bromo-1,2,4-thiadiazol-5-yl)-N-(4-methoxybenzyl)-1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1H-indole-6-sulfonamide

생성물 1

HCID 71263830N-(3-bromo-1,2,4-thiadiazol-5-yl)-1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1H-indole-6-sulfonamide수율 85%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A 10-mL round-bottom flask was charged with N-(3-bromo-1,2,4-thiadiazol-5-yl)-N-(4-methoxybenzyl)-1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1H-indole-6-sulfonamide (28 mg, 0.039 mmol), DCM (1 mL), and trifluoroacetic acid (60.1 μl, 0.780 mmol). The flask was sealed, and the mixture was stirred for 2.5 h. An additional portion of TFA (0.15 mL) was added, and the resulting mixture was stirred for 48 h. The volatiles were removed in vacuo, and the residue was concentrated again from DCM. The crude product was purified by chromatography on silica gel (5 to 10% MeOH/DCM) to give N-(3-bromo-1,2,4-thiadiazol-5-yl)-1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1H-indole-6-sulfonamide (19.91 mg, 0.033 mmol, 85% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=7.94-7.83 (m, 3 H), 7.75 (s, 1 H), 7.55 (d, J=8.5 Hz, 1 H), 7.46-7.35 (m, 2 H), 7.05 (s, 1 H), 6.36 (d, J=1.9 Hz, 1 H), 3.78 (s, 3 H), 3.21 (s, 3 H). m/z (ESI) 597.0 (M+H)+.

후처리

  1. customThe flask was sealed
  2. stirringthe resulting mixture was stirred for 48 h
  3. customThe volatiles were removed in vacuo
  4. concentrationthe residue was concentrated again from DCM
  5. customThe crude product was purified by chromatography on silica gel (5 to 10% MeOH/DCM)

출처 및 근거

ORD 기록
ord-e25ed040420741b489602b11b12f489a
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09079902B2

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