Water → 1-[4-(5-Fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-[(5-phenyl-isoxazol-3-ylmethyl)-amino]-ethanone

HRID 1178155Notes

Reaction equation

HRID 1178155 reaction equation
C([O-])([O-])=O.[K+].[K+].[C:7]1([C:13]2[O:17][N:16]=[C:15]([CH2:18]OS(C)(=O)=O)[CH:14]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.Cl.[NH2:25][CH2:26][C:27]([N:29]1[CH2:34][CH2:33][N:32]([C:35](=[O:47])[C:36]2[CH:41]=[C:40]([F:42])[CH:39]=[CH:38][C:37]=2[C:43]([F:46])([F:45])[F:44])[CH2:31][CH2:30]1)=[O:28].O>CN(C=O)C>[F:42][C:40]1[CH:39]=[CH:38][C:37]([C:43]([F:45])([F:44])[F:46])=[C:36]([CH:41]=1)[C:35]([N:32]1[CH2:33][CH2:34][N:29]([C:27](=[O:28])[CH2:26][NH:25][CH2:18][C:15]2[CH:14]=[C:13]([C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=3)[O:17][N:16]=2)[CH2:30][CH2:31]1)=[O:47]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 23159221HCID 23159221, compoundHCID 669531292-Amino-1-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]ethanone hydrochloride

Product 1

HCID 251655271-[4-(5-Fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-[(5-phenyl-isoxazol-3-ylmethyl)-amino]-ethanoneYield 18%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

K2CO3 (121 mg, 0.87 mmol) was added to a stirred solution of methanesulfonic acid 5-phenyl-isoxazol-3-ylmethyl ester (120 mg, 0.43 mmol) and 2-amino-1-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone hydrochloride salt (162 mg, 0.43 mmol) in DMF (2 mL). The resulting mixture was heated at 40° C. for 1 hr. Cold water was then added and the resulting precipitate was isolated by filtration. The crude solid was purified by preparative HPLC [(Column-AV/SP/C18-25/003, mobile phase-0.1% TFA in water (A)/acetonitrile (B), flow: 6 mL/min, gradient: (Time): (% B)-0:20; 2:20; 10:70)]) to afford 38 mg (17.64% yield) of 1-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-[(5-phenyl-isoxazol-3-ylmethyl)-amino]-ethanone. LCMS Purity: 91.95%. 1H NMR (CDCl3): δ 7.94-7.64 (m, 3H), 7.56-7.4 (m, 3H), 7.2 (m, 1H), 7.3 (d, 1H), 6.64-6.48 (d, 1H), 4.0-3.9 (d, 2H), 3.9-3.8 (m, 1H), 3.76-3.56 (m, 2H), 3.56-3.4 (m, 4H), 3.56-3.26 (bs, 1H), 3.2 (d, 2H), 2.49-2.29 (bs, 1H).

Workup

  1. customthe resulting precipitate was isolated by filtration
  2. customThe crude solid was purified by preparative HPLC [(Column-AV/SP/C18-25/003, mobile phase-0.1% TFA in water (A)/acetonitrile (B), flow

Sources & evidence

ORD record
ord-86b43813f9c244eeb6fa992c9364ad48
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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