Dichloromethane → 3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-6-sulfonamide

HRID 1524417Notes

Reaction equation

HRID 1524417 reaction equation
COC1C=C(OC)C=CC=1C[N:6]([C:35]1[S:39][N:38]=[CH:37][N:36]=1)[S:7]([C:10]1[N:15]=[C:14]2[NH:16][CH:17]=[C:18]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][C:20]=3[C:29]3[N:33]([CH3:34])[N:32]=[CH:31][CH:30]=3)[C:13]2=[CH:12][CH:11]=1)(=[O:9])=[O:8].C(Cl)Cl.C(O)(C(F)(F)F)=O>CO>[CH3:34][N:33]1[C:29]([C:20]2[CH:21]=[C:22]([C:25]([F:28])([F:27])[F:26])[CH:23]=[CH:24][C:19]=2[C:18]2[C:13]3[C:14](=[N:15][C:10]([S:7]([NH:6][C:35]4[S:39][N:38]=[CH:37][N:36]=4)(=[O:8])=[O:9])=[CH:11][CH:12]=3)[NH:16][CH:17]=2)=[CH:30][CH:31]=[N:32]1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 71259592N-(2,4-dimethoxybenzyl)-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-6-sulfonamide2×

Product 1

HCID 712594443-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-6-sulfonamideYield 50.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A vial was charged with N-(2,4-dimethoxybenzyl)-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-6-sulfonamide (Intermediate J) (46.47 mg, 0.071 mmol) and DCM (0.5 mL) to give a clear solution. TFA (0.1 mL) was added dropwise, and the resulting mixture was stirred for 30 min. The mixture was diluted with methanol, then filtered through Celite® (diatomaceous earth). The filtrate was concentrated, and the residue was triturated with diethyl ether to give a white solid. The diethyl ether was decanted, and the solid was put under vacuum again for 10 min. Diethyl ether was added, and the suspension was sonicated for 1 min to give a fine white precipitate. The mixture was filtered on a membrane filter, and the collected solid was washed with diethyl ether (3×), then dried under a stream of N2 to give 3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-6-sulfonamide (18.02 mg, 0.036 mmol, 50.3% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=12.49 (d, J=2.4 Hz, 1 H), 8.45 (s, 1 H), 8.01 (s, 1 H), 7.94-7.88 (m, 2 H), 7.79 (s, 1 H), 7.65 (d, J=8.3 Hz, 1 H), 7.40 (s, 1 H), 7.35 (d, J=2.7 Hz, 1 H), 6.37 (d, J=1.9 Hz, 1 H), 3.23 (s, 3 H). m/z (ESI) 506.0 (M+H)+.

Workup

  1. customto give a clear solution
  2. filtrationfiltered through Celite® (diatomaceous earth)
  3. concentrationThe filtrate was concentrated
  4. customthe residue was triturated with diethyl ether
  5. customto give a white solid
  6. customThe diethyl ether was decanted
  7. waitthe solid was put under vacuum again for 10 min
  8. additionDiethyl ether was added
  9. customthe suspension was sonicated for 1 min
  10. customto give a fine white precipitate
  11. filtrationThe mixture was filtered on a membrane
  12. filtrationfilter
  13. washthe collected solid was washed with diethyl ether (3×)
  14. dry with materialdried under a stream of N2

Sources & evidence

ORD record
ord-d85144b721cd4f0a8b19edae141ec38a
Source dataset
uspto-grants-2015_07
Patent number
US09079902B2

Reaction notes

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