Réaction #218309

Équation de réaction

1,1′-carbonyldiimidazole

4-morpholinobenzoic acid

(S)-3-amino-5-(4-methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran

1,1′-carbonyldiimidazole

→

title compound

Rendement 68.0%

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

Rendement 68.0%

Solvants

N,N-dimethylformamide

N,N-dimethylformamide

Conditions de réaction

Traitement

1. 1
   workup.ADDITIONwas added
2. 2
   workup.STIRRINGthe mixture was stirred for an additional 3.5 h
3. 3
   AutreThe solvent was removed in vacuo
4. 4
   Autrethe residue was purified by column chromatography on silica (eluent: chloroform/ethanol; 93:7+0.5% NH3)

Mode opératoire

A solution of 4-morpholinobenzoic acid (380 mg, 1.83 mmol; described in: Degutis, J.; Rasteikiene, L.; Degutiene, A. Zh. Org. Khim. 1978, 14(10), 2060-2064) and 1,1′-carbonyldiimidazole (310 mg, 1.92 mmol) in anhydrous N,N-dimethylformamide (12 mL) was stirred at 75° C. for 30 min. The mixture was allowed to cool after which a solution of (S)-3-amino-5-(4-methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran (430 mg, 1.74 mmol) in N,N-dimethylformamide (8 mL) was added. The reaction mixture was stirred at room temperature for 3 days. Another portion of 1,1′-carbonyldiimidazole (57 mg, 0.35 mmol) was added, and the mixture was stirred for an additional 3.5 h. The solvent was removed in vacuo, and the residue was purified by column chromatography on silica (eluent: chloroform/ethanol; 93:7+0.5% NH3) affording 513 mg (68% yield) of the title compound as a white solid: mp 210-212° C.; [α]22D −145° (c 1.0, chloroform); EIMS (70 eV) m/z (relative intensity) 436 (65, M+).

Source