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

HRID 1017602Notes

Reaction equation

HRID 1017602 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][CH:4]=1.[NH2:14][C@H:15]1[CH2:20][C:19]2[C:21]([N:25]3[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]3)=[CH:22][CH:23]=[CH:24][C:18]=2[O:17][CH2:16]1.C(N(CC)CC)C>S(Cl)(Cl)=O.C(Cl)Cl>[CH3:31][N:28]1[CH2:29][CH2:30][N:25]([C:21]2[C:19]3[CH2:20][C@H:15]([NH:14][C:7](=[O:9])[C:6]4[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:13])[F:12])=[CH:11][CH:10]=4)[CH2:16][O:17][C:18]=3[CH:24]=[CH:23][CH:22]=2)[CH2:26][CH2:27]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 99664-(Trifluoromethyl)benzoic acidHCID 11139461(S)-3-amino-5-(4-methylpiperazin-1-yl)-1,4-dihydro-2H-1-benzopyran

Product 1

HCID 57074391(S)-N-[5-(4-Methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran-3-yl]-4-trifluoromethylbenzamideYield 55%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 24386Thionyl ChlorideSolvent2×

Conditions

Temperature
50 °C

Procedure

A mixture of 4-trifluoromethylbenzoic acid (195 mg, 1.02 mmol) in thionyl chloride (5 mL) was heated at 50° C. for 20 min and then to reflux for 10 min. The mixture was allowed to cool after which 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 an ice-cooled solution of (S)-3-amino-5-(4-methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran (230 mg, 0.930 mmol) and triethylamine (194 μL, 1.39 mmol) in anhydrous methylene chloride (20 mL) with stirring. The reaction mixture was allowed to reach room temperature and was washed with a saturated NaHCO3 solution. After drying (MgSO4) and evaporation of the solvent in vacuo, a crude product was obtained which was purified by column chromatography on silica (eluent: chloroform/ethanol: 92:8+0.5% conc. NH3). This procedure gave 214 mg (55% yield) of the title compound as a white solid: m p 212-214° C.; [α]22D−73° (c 1.0, chloroform); EIMS (70 eV) m/z (relative intensity) 419 (100, M30 ).

Workup

  1. temperatureto reflux for 10 min
  2. customwas removed in vacuo
  3. customthe residue was evaporated with two portions of toluene
  4. dissolutionThe acid chloride was then dissolved in anhydrous methylene chloride (5 mL)
  5. additionadded to an ice-
  6. customto reach room temperature
  7. washwas washed with a saturated NaHCO3 solution
  8. customAfter drying
  9. custom(MgSO4) and evaporation of the solvent in vacuo
  10. customa crude product was obtained which
  11. customwas purified by column chromatography on silica (eluent: chloroform/ethanol: 92:8+0.5% conc. NH3)

Sources & evidence

ORD record
ord-9ee9b50e8324450994eda21d64285bbb
Source dataset
uspto-grants-2002_11
Patent number
US06479497B1

Reaction notes

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