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

HRID 1017600Notes

Reaction equation

HRID 1017600 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:15]=[CH:14][C:10]([C:11]([OH:13])=O)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:28][C@H:29]1[CH2:34][C:33]2[C:35]([N:39]3[CH2:44][CH2:43][N:42]([CH3:45])[CH2:41][CH2:40]3)=[CH:36][CH:37]=[CH:38][C:32]=2[O:31][CH2:30]1>CN(C)C=O>[CH3:45][N:42]1[CH2:43][CH2:44][N:39]([C:35]2[C:33]3[CH2:34][C@H:29]([NH:28][C:11](=[O:13])[C:10]4[CH:9]=[CH:8][C:7]([N:4]5[CH2:3][CH2:2][O:1][CH2:6][CH2:5]5)=[CH:15][CH:14]=4)[CH2:30][O:31][C:32]=3[CH:38]=[CH:37][CH:36]=2)[CH2:40][CH2:41]1

Participants

5

Reactant 3

HCID 682631,1'-Carbonyldiimidazole2×HCID 3452784-(Morpholin-4-yl)benzoic acidHCID 11139461(S)-3-amino-5-(4-methylpiperazin-1-yl)-1,4-dihydro-2H-1-benzopyran

Product 1

HCID 9910906(S)-N-[5-(4-Methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran-3-yl]4-morpholinobenzamideYield 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

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′-carbonyldimidazole (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, M30 ).

Workup

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

Sources & evidence

ORD record
ord-dd0a2482f77e444090fa82996fe64dbe
Source dataset
uspto-grants-2002_11
Patent number
US06479497B1

Reaction notes

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