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

HRID 429632Notes

Reaction equation

HRID 429632 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](OC)(OC)(OC)[O:47][CH3:48]>C(O)(=O)C>[CH3:46][O:47][C:48]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

4

Reactant 2

HCID 74613Tetramethyl orthocarbonateHCID 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 183548723-methoxy-4-(2-methoxy-1H-benzimidazol-4-yl)carbonylamino-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]benzamideYield 80.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

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 (200 mg) in acetic acid (1 ml) was added tetramethyl orthocarbonate (66 mg) at ambient temperature and the solution was allowed to stand at the same temperature for 3 days. After being concentrated in vacuo, the residue was diluted with chloroform and saturated sodium bicarbonate aqueous solution. The organic layer was separated and washed with water and brine. The solution was dried over magnesium sulfate and the solvent was evaporated in vacuo. The residue was purified by preparative thin-layer chromatography (chloroform-methanol=10:1) to give 4-(2-methoxy-1H-benzimidazol-4-yl)carbonylamino-3-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]benzamide (171 mg) as a powder.

Workup

  1. concentrationAfter being concentrated in vacuo
  2. additionthe residue was diluted with chloroform and saturated sodium bicarbonate aqueous solution
  3. customThe organic layer was separated
  4. washwashed with water and brine
  5. dry with materialThe solution was dried over magnesium sulfate
  6. customthe solvent was evaporated in vacuo
  7. customThe residue was purified by preparative thin-layer chromatography (chloroform-methanol=10:1)

Sources & evidence

ORD record
ord-164d8ea80db640ed8dcdc607ac73b022
Source dataset
uspto-grants-2001_11
Patent number
US06316482B1

Reaction notes

Loading…