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

HRID 1017606

Reaction equation

HRID 1017606 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[C:5]([O:12]C(=O)C)[CH:4]=1.[NH2:16][C@H:17]1[CH2:22][C:21]2[C:23]([N:27]3[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]3)=[CH:24][CH:25]=[CH:26][C:20]=2[O:19][CH2:18]1.C(N(CC)CC)C>S(Cl)(Cl)=O.C(Cl)Cl>[CH3:33][N:30]1[CH2:31][CH2:32][N:27]([C:23]2[C:21]3[CH2:22][C@H:17]([NH:16][C:7](=[O:9])[C:6]4[CH:10]=[CH:11][C:3]([O:2][CH3:1])=[CH:4][C:5]=4[OH:12])[CH2:18][O:19][C:20]=3[CH:26]=[CH:25][CH:24]=2)[CH2:28][CH2:29]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 11139461(S)-3-amino-5-(4-methylpiperazin-1-yl)-1,4-dihydro-2H-1-benzopyranHCID 131293092-Acetoxy-4-methoxybenzoic acid

Product 1

HCID 56991280(S)-N-[5-(4-Methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran-3-yl]-2-hydroxy-4-methoxybenzamideYield 33%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 24386Thionyl ChlorideSolvent

Procedure

A solution of 4-methoxy-2-acetoxybenzoic acid (232 mg, 1.10 mmol; described in: Schonhofer, F. Ber Deutsch Chem Ges 1951, 84, 13) in thionyl chloride (5 mL) was heated at 55° C. for 30 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 stirred solution of (S)-3-amino-5-(4-methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran (248 mg, 1.00 mmol) and triethylamine (210 μL, 1.50 mmol) in anhydrous methylene chloride (20 mL). The reaction mixture was stirred at room temperature for 2.5 h after which the mixture was washed with a saturated NaHCO3 solution, dried (MgSO4), and the solvent was removed in vacuo. The residue was dissolved in absolute ethanol (20 mL), and conc. NH3 (5 mL) was added. The mixture was stirred overnight. The solvent was removed in vacuo, and the remains was purified by column chromatography on silica (eluent: chloroform/ethanol; 92:8+0.5% conc. NH3) affording 120 mg (33% yield) of the title compound as a white solid: mp sinters>80° C.; [α]21D−92° (c 1.0, chloroform); EIMS (70 eV) m/z (relative intensity) 397 (27, M30 ).

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 saturated NaHCO3 solution
  5. dry with materialdried (MgSO4)
  6. customthe solvent was removed in vacuo
  7. dissolutionThe residue was dissolved in absolute ethanol (20 mL)
  8. additionconc. NH3 (5 mL) was added
  9. stirringThe mixture was stirred overnight
  10. customThe solvent was removed in vacuo
  11. customthe remains was purified by column chromatography on silica (eluent: chloroform/ethanol; 92:8+0.5% conc. NH3)

Sources & evidence

ORD record
ord-35611b59a5724b2291ae11b9cd820964
Source dataset
uspto-grants-2002_11
Patent number
US06479497B1

Linked notes

Loading…