Acetonitrile → 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 1533801Notes

Reaction equation

HRID 1533801 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][C:26](=[C:34]=[O:35])N2CCN(C)CC2)=[O:12])=[CH:9][C:8]=1OC)=[O:5].[C:46]([CH2:48][C:49](O)=O)#[N:47].[C:52](=[O:55])([O-])O.[Na+].[C:57](#[N:59])[CH3:58]>>[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:34]([N:59]4[CH2:3][CH2:4][N:6]([CH3:7])[CH2:58][CH2:57]4)=[O:35])=[O:12])=[CH:9][C:8]=3[O:55][CH3:52])=[O:5])[C:2]=2[N:1]=1)#[N:47]

Participants

5

Reactant 4

HCID 6342AcetonitrileHCID 9740Cyanoacetic acidHCID 516892Sodium BicarbonateHCID 88148813HCID 88148813, compound

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]benzamide

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-df56ced421644bffb26973060ec96bde
Source dataset
uspto-grants-2001_03
Patent number
US06207693B1

Reaction notes

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