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

HRID 1017607Notes

Reaction equation

HRID 1017607 reaction equation
[F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=1.[NH2:15][C@H:16]1[CH2:21][C:20]2[C:22]([N:26]3[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]3)=[CH:23][CH:24]=[CH:25][C:19]=2[O:18][CH2:17]1.C(N(CC)CC)C>S(Cl)(Cl)=O.C(Cl)Cl>[CH3:32][N:29]1[CH2:30][CH2:31][N:26]([C:22]2[C:20]3[CH2:21][C@H:16]([NH:15][C:8](=[O:10])[C:7]4[CH:6]=[CH:5][C:4]([O:3][C:2]([F:1])([F:14])[F:13])=[CH:12][CH:11]=4)[CH2:17][O:18][C:19]=3[CH:25]=[CH:24][CH:23]=2)[CH2:27][CH2:28]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 676134-(Trifluoromethoxy)benzoic acidHCID 11139461(S)-3-amino-5-(4-methylpiperazin-1-yl)-1,4-dihydro-2H-1-benzopyran

Product 1

HCID 69213151(S)-N-[5-(4-Methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran-3-yl]-4-trifluoromethoxybenzamideYield 51%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 4-trifluoromethoxybenzoic acid (254 mg, 1.23 mmol) in thionyl chloride (5 mL) was heated at 60° C. for 25 min. The excess of thionyl chloride was removed under reduced pressure, and the remains were evaporated with two portions of toluene. The acid chloride was then dissolved in anhydrous methylene chloride (5 mL) and added to a stirred solution of (S)-3-amino-5-(4-methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran (277 mg, 1.12 mmol) and triethylamine (234 μL, 1.68 mmol) in methylene chloride (10 mL). The reaction mixture was stirred for 2 h at room temperature and was washed with a saturated solution of NaHCO3. The organic layer was dried (MgSO4), and the solvent was removed in vacuo. The product was purified by column chromatography on silica (eluent: chloroform/ethanol, 92:8+0.5% conc. NH3) affording 248 mg (51% yield) of the title compound as a white solid: mp 192-193° C.; [α]21D−75° (c 1.0, chloroform); EIMS (70 eV) m/z (relative intensity) 435 (6, M30 ).

Workup

  1. customThe excess of thionyl chloride was removed under reduced pressure
  2. customthe remains were evaporated with two portions of toluene
  3. dissolutionThe acid chloride was then dissolved in anhydrous methylene chloride (5 mL)
  4. washwas washed with a saturated solution of NaHCO3
  5. dry with materialThe organic layer was dried (MgSO4)
  6. customthe solvent was removed in vacuo
  7. customThe product was purified by column chromatography on silica (eluent: chloroform/ethanol, 92:8+0.5% conc. NH3)

Sources & evidence

ORD record
ord-7d032b09fd064dc880b17fc7375e9000
Source dataset
uspto-grants-2002_11
Patent number
US06479497B1

Reaction notes

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