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

HRID 433902Notes

Reaction equation

HRID 433902 reaction equation
[CH3:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:23][C@H:24]1[CH2:29][C:28]2[C:30]([N:34]3[CH2:39][CH2:38][N:37]([CH3:40])[CH2:36][CH2:35]3)=[CH:31][CH:32]=[CH:33][C:27]=2[O:26][CH2:25]1>CN(C)C=O>[CH3:40][N:37]1[CH2:38][CH2:39][N:34]([C:30]2[C:28]3[CH2:29][C@H:24]([NH:23][C:7]([C:6]4[CH:5]=[N:4][CH:3]=[C:2]([CH3:1])[CH:10]=4)=[O:9])[CH2:25][O:26][C:27]=3[CH:33]=[CH:32][CH:31]=2)[CH2:35][CH2:36]1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 2562085-Methylnicotinic acidHCID 11139461(S)-3-amino-5-(4-methylpiperazin-1-yl)-1,4-dihydro-2H-1-benzopyran

Product 1

HCID 69207425(S)-N-[5-(4-Methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran-3-yl]-5-methylpyridine-3-carboxamideYield 35%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 5-methylnicotinic acid (141 mg, 1.03 mmol) and 1,1′-carbonyldiimidazole (183 mg, 1.13 mmol) in anhydrous N,N-dimethylformamide (5 mL) was stirred at 75° C. for 55 min. The mixture was allowed to cool, and a solution of (S)-3-amino-5-(4-methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran (232 mg, 0.94 mmol) in N,N-dimethylformamide (5 mL) was added. The reaction mixture was stirred at room temperature for 28 h. The solvent was removed in vacuo, and the residue was purified by column chromatography on silica (eluent: chloroform/ethanol; 87:13+0.5% NH3). The product was contaminated with a large amount of imidazole which could be removed by the following procedure: The mixture was dissolved in diethyl ether (100 mL), washed with water (2×20 mL) and treated with brine (10 mL). The ethereal layer was dried (MgSO4), and the solvent was removed in vacuo to give 119 mg (35% yield) of the title compound as a white solid: mp sinters >68° C.; [α]21D−82° (c 1.0, chloroform); EIMS (70 eV) m/z (relative intensity) 366 (21, M+).

Workup

  1. temperatureto cool
  2. customThe solvent was removed in vacuo
  3. customthe residue was purified by column chromatography on silica (eluent: chloroform/ethanol; 87:13+0.5% NH3)
  4. customcould be removed by the following procedure
  5. dissolutionThe mixture was dissolved in diethyl ether (100 mL)
  6. washwashed with water (2×20 mL)
  7. additiontreated with brine (10 mL)
  8. dry with materialThe ethereal layer was dried (MgSO4)
  9. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-a5403e29163c4a0f9ce960e334864789
Source dataset
uspto-grants-2003_12
Patent number
US06670359B2

Reaction notes

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