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

HRID 1827782Notes

Reaction equation

HRID 1827782 reaction equation
[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

Participants

6

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 24386Thionyl ChlorideSolvent

Procedure

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+).

Workup

  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)

Sources & evidence

ORD record
ord-002ae753429a4c66acb99ef85f1b82be
Source dataset
uspto-grants-2006_06
Patent number
US07056921B2

Reaction notes

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