2-Aminothiazole → 1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-1H-indole-6-sulfonamide

HRID 1524408Notes

Reaction equation

HRID 1524408 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([S:11](OC3C(F)=C(F)C(F)=C(F)C=3F)(=[O:13])=[O:12])[CH:9]=2)[C:4]([C:26]2[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][C:27]=2[C:36]2[N:40]([CH3:41])[N:39]=[CH:38][CH:37]=2)=[CH:3]1.[S:42]1[CH:46]=[CH:45][N:44]=[C:43]1[NH2:47].C1COCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C(Cl)Cl.CO.C(O)(=O)C>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([S:11]([NH:47][C:43]3[S:42][CH:46]=[CH:45][N:44]=3)(=[O:12])=[O:13])[CH:9]=2)[C:4]([C:26]2[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][C:27]=2[C:36]2[N:40]([CH3:41])[N:39]=[CH:38][CH:37]=2)=[CH:3]1

Participants

7

Reactant 4

HCID 21552-AminothiazoleHCID 8028TetrahydrofuranHCID 2733832Lithium HexamethyldisilazideHCID 89407674perfluorophenyl 1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1H-indole-6-sulfonate2×

Product 1

HCID 716078691-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-1H-indole-6-sulfonamideYield 72.7%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

A vial was charged with perfluorophenyl 1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1H-indole-6-sulfonate (Intermediate E) (32.98 mg, 0.055 mmol), thiazol-2-amine (7.14 mg, 0.071 mmol), and THF (0.4 mL) to give a clear solution. Lithium bis(trimethylsilyl)amide (1M in THF) (137 μl, 0.137 mmol) was added dropwise over 5 min, and the resulting solution was stirred overnight. In the morning, acetic acid (0.03 mL) was added, resulting in a viscous mixture. The mixture was diluted with DCM/MeOH, transferred to a flask, and concentrated in vacuo. The crude product was purified by chromatography on silica gel (0 to 5% MeOH/DCM) to give 1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-1H-indole-6-sulfonamide (20.6 mg, 0.040 mmol, 72.6% yield) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ=7.96-7.83 (m, 3 H), 7.78-7.71 (m, 1 H), 7.60-7.43 (m, 2 H), 7.40 (d, J=1.9 Hz, 1 H), 7.21 (s, 1 H), 7.12 (s, 1 H), 6.79 (d, J=4.6 Hz, 1 H), 6.36 (s, 1 H), 3.80 (s, 3 H), 3.22 (s, 3 H). m/z (ESI) 518.2 (M+H)+.

Workup

  1. customto give a clear solution
  2. customresulting in a viscous mixture
  3. customtransferred to a flask
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by chromatography on silica gel (0 to 5% MeOH/DCM)

Sources & evidence

ORD record
ord-1369706d9750499584cc7ef6b6d64980
Source dataset
uspto-grants-2015_07
Patent number
US09079902B2

Reaction notes

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