Triethylamine → (S)-N-[5-(4-Methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran-3-yl]-2,4-bis(trifluoromethyl)benzamide

HRID 131133

반응식

HRID 131133 반응식
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:9]=[CH:8][C:4]=1[C:5]([OH:7])=O.[NH2:18][C@H:19]1[CH2:24][C:23]2[C:25]([N:29]3[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]3)=[CH:26][CH:27]=[CH:28][C:22]=2[O:21][CH2:20]1.C(N(CC)CC)C>S(Cl)(Cl)=O.C(Cl)Cl>[CH3:35][N:32]1[CH2:33][CH2:34][N:29]([C:25]2[C:23]3[CH2:24][C@H:19]([NH:18][C:5](=[O:7])[C:4]4[CH:8]=[CH:9][C:10]([C:12]([F:15])([F:14])[F:13])=[CH:11][C:3]=4[C:2]([F:1])([F:17])[F:16])[CH2:20][O:21][C:22]=3[CH:28]=[CH:27][CH:26]=2)[CH2:30][CH2:31]1

참가 물질

6

반응물 3

HCID 8471TriethylamineHCID 1417522,4-Bis(trifluoromethyl)benzoic acidHCID 11139461(S)-3-amino-5-(4-methylpiperazin-1-yl)-1,4-dihydro-2H-1-benzopyran

생성물 1

HCID 54406700(S)-N-[5-(4-Methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran-3-yl]-2,4-bis(trifluoromethyl)benzamide수율 30%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 24386Thionyl Chloride용매

실험 절차

A solution of 2,4-bis(trifluoromethyl)benzoic acid (195 mg, 0.755 mmol) in thionyl chloride (4 mL) was heated at 55° C. for 45 min. The excess of thionyl chloride was removed in vacuo, and the residue was evaporated with two portions of toluene. The acid chloride was then dissolved in anhydrous methylene chloride (5 mL) and added to a solution of (S)-3-amino-5-(4-methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran (170 mg, 0.687 mmol) and triethylamine (144 μL, 1.03 mmol) in anhydrous methylene chloride (20 mL) with stirring. The reaction mixture was left overnight at room temperature and was washed with a 2 M NH3 solution (10 mL) followed by a portion of brine. The organic layer was dried (MgSO4), and the solvent was removed in vacuo. The residue was purified by column chromatography on silica (eluent: chloroform/ethanol; 92:8+0.5% conc. NH3) affording 100 mg (30% yield) of the title compound as a white powder: mp 202-203° C.; [α]21D −51° (c 1.0, chloroform); EIMS (70 eV) m/z (relative intensity) 487 (16, M+).

후처리

  1. customThe excess of thionyl chloride was removed in vacuo
  2. customthe residue was evaporated with two portions of toluene
  3. dissolutionThe acid chloride was then dissolved in anhydrous methylene chloride (5 mL)
  4. washwas washed with a 2 M NH3 solution (10 mL)
  5. dry with materialThe organic layer was dried (MgSO4)
  6. customthe solvent was removed in vacuo
  7. customThe residue was purified by column chromatography on silica (eluent: chloroform/ethanol; 92:8+0.5% conc. NH3)

출처 및 근거

ORD 기록
ord-f737d836cdfe418bbda096e0920cee74
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07384943B2

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