4-(Trifluoromethylthio)benzoyl chloride → N-(2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(trifluoromethylthio)benzamide

HRID 1256427Notes

Reaction equation

HRID 1256427 reaction equation
[CH3:1][C:2]1[CH:17]=[C:5]2[N:6]=[C:7]([NH2:16])[CH:8]=[C:9]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[N:4]2[N:3]=1.[F:18][C:19]([F:31])([F:30])[S:20][C:21]1[CH:29]=[CH:28][C:24]([C:25](Cl)=[O:26])=[CH:23][CH:22]=1>N1C=CC=CC=1>[CH3:1][C:2]1[CH:17]=[C:5]2[N:6]=[C:7]([NH:16][C:25](=[O:26])[C:24]3[CH:28]=[CH:29][C:21]([S:20][C:19]([F:31])([F:18])[F:30])=[CH:22][CH:23]=3)[CH:8]=[C:9]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[N:4]2[N:3]=1

Participants

4

Reactant 2

HCID 27778654-(Trifluoromethylthio)benzoyl chlorideHCID 582071812-Methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-amine

Product 1

HCID 67064439N-(2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(trifluoromethylthio)benzamideYield 50%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A solution of 2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-amine (10A, 62 mg, 0.276 mmol) and pyridine (0.69 mL) in a 20 mL scintillation vial was cooled to 0° C. then treated with 4-(trifluoromethylthio)benzoyl chloride (100 mg, 0.415 mmol). The reaction mixture was stirred for 2 h, partitioned between saturated aqueous sodium bicarbonate and ethyl acetate, and the organic layer subsequently washed with water and then brine. The organic layer was then dried over sodium sulfate, filtered, concentrated under reduced pressure, diluted with methanol, filtered, and purified via preparative HPLC (80-80% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow solid (58.8 mg, 50%). Melting point (100.9-101.6° C.). 1H NMR (DMSO-d6) δ: 11.49 (s, 1H), 8.15 (d, J=8.6 Hz, 2H), 8.06 (dd, J=6.7, 2.9 Hz, 2H), 7.93 (s, 1H), 7.87 (d, J=8.3 Hz, 2H), 7.56-7.66 (m, 3H), 6.41 (s, 1H), 2.40 (s, 3H); ESI-MS: m/z 429.1 (M+H)+. Melting point (100.9-101.6° C.).

Workup

  1. custompartitioned between saturated aqueous sodium bicarbonate and ethyl acetate
  2. washthe organic layer subsequently washed with water
  3. dry with materialThe organic layer was then dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. additiondiluted with methanol
  7. filtrationfiltered
  8. custompurified via preparative HPLC (80-80% MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-c2effe32101a45e18fe9a6fdd8d423f6
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

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