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

HRID 1017601Notes

Reaction equation

HRID 1017601 reaction equation
[N:1]1([C:7]2[CH:15]=[CH:14][C:10]([C:11]([OH:13])=O)=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][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:1]5[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]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'-Carbonyldiimidazole3×HCID 7645994-(Piperidin-1-yl)benzoic acidHCID 11139461(S)-3-amino-5-(4-methylpiperazin-1-yl)-1,4-dihydro-2H-1-benzopyran

Product 1

HCID 57315323(S)-N-[5-(4-Methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran-3-yl]-4-piperidinobenzamideYield 36.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
50 °C

Procedure

A suspension of 4-piperidinobenzoic acid (276 mg, 1.35 mmol; described in: Weringa, W. D.; Janssen, M. J. Recl. Trav. Chim. Pays-Bas 1968,87(12), 1372-1380) and 1,1′-carbonyldiimidazole (229 mg, 1.41 mmol) in anhydrous N,N-dimethylformamide (11 mL) was placed in an oil bath at 75° C. After 45 min of stirring, the mixture was allowed to cool. A solution of (S)-3-amino-5-(4-methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran (317 mg, 1.28 mmol) in N,N-dimethylformamide (5 mL) was added, and the mixture was stirred at room temperature for 40 h. Another portion of 1,1′-carbonyldiimidazole (83 mg, 0.51 mmol) was added, and the reaction was stirred for 3 days. At this time, the reaction was not complete and a final amount of 1,1′-carbonyldiimidazole (42 mg, 0.25 mmol) was added. The reaction mixture was heated for 3 h at 50° C. after which the solvent was removed in vacuo. The residue was purified by column chromatography on silica (eluent: chloroform/ethanol; 92:8+0.5% NH3) affording 202 mg (36% yield) of the title compound as a white solid: mp 178-180° C.; [α]22D−159° (c 1.0, chloroform); EIMS (70 eV) m/z (relative intensity) 434 (35, M30 ).

Workup

  1. customwas placed in an oil bath at 75° C
  2. temperatureto cool
  3. stirringthe mixture was stirred at room temperature for 40 h
  4. stirringthe reaction was stirred for 3 days
  5. customwas removed in vacuo
  6. customThe residue was purified by column chromatography on silica (eluent: chloroform/ethanol; 92:8+0.5% NH3)

Sources & evidence

ORD record
ord-a6c53ce9ab5d4ab39c03a307e526792d
Source dataset
uspto-grants-2002_11
Patent number
US06479497B1

Reaction notes

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