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 1524436Notes

Reaction equation

HRID 1524436 reaction equation
[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

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 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

Product 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-sulfonamideYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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)+.

Workup

  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)

Sources & evidence

ORD record
ord-e25ed040420741b489602b11b12f489a
Source dataset
uspto-grants-2015_07
Patent number
US09079902B2

Reaction notes

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