Cyanoacetic acid → 4-[[2-cyanomethyl-1H-benzimidazol-4-yl]carbonylamino]-3-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]benzamide

HRID 429674Notes

Reaction equation

HRID 429674 reaction equation
[NH2:1][C:2]1[C:44]([NH2:45])=[CH:43][CH:42]=[CH:41][C:3]=1[C:4]([NH:6][C:7]1[CH:38]=[CH:37][C:10]([C:11]([N:13]([CH3:36])[C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][C:15]=2[O:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([N:29]2[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]2)=[O:28])=[O:12])=[CH:9][C:8]=1[O:39][CH3:40])=[O:5].[C:46]([CH2:48][C:49](O)=O)#[N:47].C(=O)([O-])O.[Na+]>C(#N)C>[C:46]([CH2:48][C:49]1[NH:45][C:44]2[CH:43]=[CH:42][CH:41]=[C:3]([C:4]([NH:6][C:7]3[CH:38]=[CH:37][C:10]([C:11]([N:13]([CH3:36])[C:14]4[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][C:15]=4[O:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([N:29]4[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]4)=[O:28])=[O:12])=[CH:9][C:8]=3[O:39][CH3:40])=[O:5])[C:2]=2[N:1]=1)#[N:47]

Participants

5

Reactant 3

HCID 9740Cyanoacetic acidHCID 516892Sodium BicarbonateHCID 183547944-(2,3-diaminophenyl)carbonylamino-3-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]benzamide

Product 1

HCID 183551874-[[2-cyanomethyl-1H-benzimidazol-4-yl]carbonylamino]-3-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]benzamideYield 30.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-(2,3-diaminobenzoyl)amino-3-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]benzamide (240 mg) in acetonitrile (1 ml) was added cyanoacetic acid (662 mg). The solution was heated at 100° C. for 8 hours. After cooling, aqueous sodium hydrogen carbonate was added to the mixture and extracted with ethyl acetate. The extract was washed with brine and dried over sodium sulfate. After evaporation of the solvent, the residue was purified by silica gel column chromatography (7% methanol in chloroform) and preparative thin-layer chromatography (ethyl acetate:methanol=1:1) to give 4-[[2-cyanomethyl-1H-benzimidazol-4-yl]carbonylamino]-3-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]benzamide (80 mg).

Workup

  1. temperatureAfter cooling
  2. extractionextracted with ethyl acetate
  3. washThe extract was washed with brine
  4. dry with materialdried over sodium sulfate
  5. customAfter evaporation of the solvent
  6. customthe residue was purified by silica gel column chromatography (7% methanol in chloroform)

Sources & evidence

ORD record
ord-f6f76e47748d4dd3ae86c0715290d878
Source dataset
uspto-grants-2001_11
Patent number
US06316482B1

Reaction notes

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