Hydrochloric Acid → 3-(4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide 3-(4-chloro-2-(1-methyl-1H-pyrazol-3-yl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide

HRID 1524403Notes

Reaction equation

HRID 1524403 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[CH:12][C:13]([S:17]([N:20](CC4C=CC(OC)=CC=4OC)[C:21]4[S:25][N:24]=[CH:23][N:22]=4)(=[O:19])=[O:18])=[CH:14][CH:15]=3)[NH:10][CH:9]=2)=[C:4]([C:37]2[N:41]([CH3:42])[N:40]=[CH:39][CH:38]=2)[CH:3]=1.Cl.[CH3:44]O>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[CH:12][C:13]([S:17]([NH:20][C:21]4[S:25][N:24]=[CH:23][N:22]=4)(=[O:18])=[O:19])=[CH:14][CH:15]=3)[NH:10][CH:9]=2)=[C:4]([C:37]2[CH:38]=[CH:39][N:40]([CH3:44])[N:41]=2)[CH:3]=1.[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[CH:12][C:13]([S:17]([NH:20][C:21]4[S:25][N:24]=[CH:23][N:22]=4)(=[O:19])=[O:18])=[CH:14][CH:15]=3)[NH:10][CH:9]=2)=[C:4]([C:37]2[N:41]([CH3:42])[N:40]=[CH:39][CH:38]=2)[CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 712592093-(4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide2×

Product 1

HCID 894076863-(4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide 3-(4-chloro-2-(1-methyl-1H-pyrazol-3-yl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamideYield 90%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A vial was charged with 3-(4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (Intermediate A) (28.44 mg, 0.046 mmol) in methanol (0.5 mL). Hydrogen chloride (4M in 1,4-dioxane) (114 μl, 0.458 mmol) was added, and the resulting mixture was stirred for 30 min. The mixture was diluted with DCM and concentrated in vacuo. The residue was suspended in MeOH, then filtered through Celite® (diatomaceous earth). The filtrate was concentrated, and the residue was dissolved in methanol and loaded onto a 500 mg SCX-2 ion exchange column. The column was eluted with methanol, then with a solution of 2N ammonia in methanol. The basic fractions were concentrated to give 3-(4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide 3-(4-chloro-2-(1-methyl-1H-pyrazol-3-yl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (19.36 mg, 0.041 mmol, 90% yield) as a light-yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=11.57 (br. s., 1 H), 8.05 (s, 1 H), 7.85 (dd, J=0.5, 1.6 Hz, 1 H), 7.71-7.58 (m, 2 H), 7.54 (d, J=8.5 Hz, 1 H), 7.49 (d, J=2.2 Hz, 1 H), 7.43-7.33 (m, 2 H), 7.23-7.04 (m, 1 H), 6.93 (d, J=2.6 Hz, 1 H), 6.30 (d, J=1.9 Hz, 1 H), 3.19 (br. s., 1 H). m/z (ESI) 471.0 (M+H)+.

Workup

  1. concentrationconcentrated in vacuo
  2. filtrationfiltered through Celite® (diatomaceous earth)
  3. concentrationThe filtrate was concentrated
  4. dissolutionthe residue was dissolved in methanol
  5. washThe column was eluted with methanol
  6. concentrationThe basic fractions were concentrated

Sources & evidence

ORD record
ord-e663413906b146a29354bce62e0c6ac0
Source dataset
uspto-grants-2015_07
Patent number
US09079902B2

Reaction notes

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