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

HRID 1533803Notes

Reaction equation

HRID 1533803 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]1(=O)[O:50][CH2:49][CH2:48][CH2:47]1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(Cl)(Cl)Cl>[OH:50][CH2:49][CH2:48][CH2:47][C:46]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

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 7302Gamma-ButyrolactoneHCID 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 183549434-[2-(3-hydroxypropyl)-1H-benzimidazol-4-yl]carbonylamino-3-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]benzamideYield 42%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

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 (150 mg), butyrolactone (628 mg) and p-toluenesulfonic acid (139 mg) was heated at 100° C. for 4 hours. The reaction mixture was diluted with chloroform and washed with aqueous sodium hydrogen carbonate. The extract was dried over sodium sulfate. After evaporation of the solvent, the residue was purified by silica gel column chromatography (10% methanol in chloroform) and then preparative thin-layer chromatography (chloroform/methanol=20/3) to give 4-[2-(3-hydroxypropyl)-1H-benzimidazol-4-yl]carbonylamino-3-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]benzamide (70 mg).

Workup

  1. washwashed with aqueous sodium hydrogen carbonate
  2. dry with materialThe extract was dried over sodium sulfate
  3. customAfter evaporation of the solvent
  4. customthe residue was purified by silica gel column chromatography (10% methanol in chloroform)

Sources & evidence

ORD record
ord-a0d602fe57fa41168013d5b6d8451758
Source dataset
uspto-grants-2001_03
Patent number
US06207693B1

Reaction notes

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