Triethylamine → 1-Methyl-3-trifluoromethyl-1H-pyrazole-4-sulfonic acid {1-[4-(5-fluoro-2-methoxy-pyridin-3-yl)-phenyl]-ethyl}-amide

HRID 2422889Notes

Reaction equation

HRID 2422889 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([CH:16]([NH2:18])[CH3:17])=[CH:12][CH:11]=2)[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.C(N(CC)CC)C.[CH3:26][N:27]1[CH:31]=[C:30]([S:32](Cl)(=[O:34])=[O:33])[C:29]([C:36]([F:39])([F:38])[F:37])=[N:28]1>ClCCl>[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([CH:16]([NH:18][S:32]([C:30]3[C:29]([C:36]([F:39])([F:37])[F:38])=[N:28][N:27]([CH3:26])[CH:31]=3)(=[O:34])=[O:33])[CH3:17])=[CH:12][CH:11]=2)[C:5]([O:8][CH3:9])=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27945611-Methyl-3-(trifluoromethyl)-1H-pyrazole-4-sulfonyl chlorideHCID 672445781-[4-(5-Fluoro-2-methoxy-pyridin-3-yl)-phenyl]-ethylamine

Product 1

HCID 672456941-Methyl-3-trifluoromethyl-1H-pyrazole-4-sulfonic acid {1-[4-(5-fluoro-2-methoxy-pyridin-3-yl)-phenyl]-ethyl}-amideYield 25%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The organic phase was washed with water, brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue chromatographed on silica gel to give to give 2-{1-[4-(5-fluoro-2-methoxy-pyridin-3-yl)-phenyl]-ethyl}-isoindole-1,3-dione (0.31 g, 0.82 mmol, 41%). To a solution of 2-{1-[4-(5-fluoro-2-methoxy-pyridin-3-yl)-phenyl]-ethyl}-isoindole-1,3-dione (0.31 g, 0.8 mmol) in dioxan/methanol (1:1, 10 ml) was added hydrazine hydrate (0.83 g, 46.5 mmol). The reaction was stirred at room temperature for 24 h. The solvent was evaporated and dichloromethane added. The resultant white solid was filtered off and dried to give 1-[4-(5-fluoro-2-methoxy-pyridin-3-yl)-phenyl]-ethylamine (0.21 g, 0.8 mmol, 100%) as a clear oil. To a solution of 1-[4-(5-fluoro-2-methoxy-pyridin-3-yl)-phenyl]-ethylamine (0.1 g, 0.4 mmol) in dichloromethane (2 ml) was added triethylamine (123 mg, 1.2 mmol) and 1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-sulfonylchloride (111 mg, 0.45 mmol). The reaction mixture was agitated for 16 h and quenched with saturated aqueuos sodium bicarbonate solution. The organic phase was washed with water, brine and dried over anhydrous magneium sulfate. The residue was chromatographed on silica gel to give the title compound (42 mg, 0.1 mmol, 25%). 1H NMR (400 MHz, CDCl3): δ 8.00 (d, 1H), 7.45 (m, 3H), 7.35 (dd, 1H), 7.21 (d, 2H), 4.86 (d, 1H), 4.60 (q, 1H), 3.96 (s, 3H), 3.75 (s, 3H), 1.50 (b, 3H) ppm; MS (ESI) m/z: 459.3 [M+H]+.

Workup

  1. customquenched with saturated aqueuos sodium bicarbonate solution
  2. washThe organic phase was washed with water, brine
  3. dry with materialdried over anhydrous magneium sulfate
  4. customThe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-48733df7de7f4c16bbcf34fd97a449d0
Source dataset
uspto-grants-2011_06
Patent number
US07960365B2

Reaction notes

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