Sodium Hydroxide → 3-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]-4-(3-nitro-2-trifluoroacetylaminobenzoyl)aminobenzamide

HRID 429623Notes

Reaction equation

HRID 429623 reaction equation
[NH2:1][C:2]1[CH:33]=[CH:32][C:5]([C:6]([N:8]([CH3:31])[C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][C:10]=2[O:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([N:24]2[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]2)=[O:23])=[O:7])=[CH:4][C:3]=1[O:34][CH3:35].[N+:36]([C:39]1[C:48]2[N:47]=[C:46]([C:49]([F:52])([F:51])[F:50])[O:45][C:44](=[O:53])[C:43]=2[CH:42]=[CH:41][CH:40]=1)([O-:38])=[O:37].[OH-].[Na+]>O1CCOCC1>[CH3:35][O:34][C:3]1[CH:4]=[C:5]([CH:32]=[CH:33][C:2]=1[NH:1][C:44](=[O:53])[C:43]1[CH:42]=[CH:41][CH:40]=[C:39]([N+:36]([O-:38])=[O:37])[C:48]=1[NH:47][C:46](=[O:45])[C:49]([F:51])([F:52])[F:50])[C:6]([N:8]([CH3:31])[C:9]1[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][C:10]=1[O:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([N:24]1[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]1)=[O:23])=[O:7]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 183549064-amino-3-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]benzamideHCID 183549908-Nitro-2-trifluoromethyl-3,1-benzoxazin-4-one2×

Product 1

HCID 183552993-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]-4-(3-nitro-2-trifluoroacetylaminobenzoyl)aminobenzamideYield 114.8%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-amino-3-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]benzamide (6.0 g) in 1,4-dioxane (200 ml) was added 8-nitro-2-trifluoromethyl-3,1-benzoxazin-4-one (3.24 g) and the mixture was stirred at 100° C. for 4 hours. To the mixture was added 8-nitro-2-trifluoromethyl-3,1-benzoxazin-4-one (3.24 g). and the solution was stirred at 100° C. for additional 3 hours. To the mixture was added 1N sodium hydroxide solution (90 ml) and the resulting solution was stirred at 60° C. for 1 hour. After being concentrated in vacuo, the residue was diluted with chloroform and the organic solution was washed with saturated aqueous sodium bicarbonate solution and brine. The organic layer was dried over magnesium sulfate and the solvent was concentrated in vacuo to give 3-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]-4-(3-nitro-2-trifluoroacetylaminobenzoyl)aminobenzamide as a yellow powder (10.6 g). The crude product was used for next step without further purification.

Workup

  1. stirringand the solution was stirred at 100° C. for additional 3 hours
  2. stirringthe resulting solution was stirred at 60° C. for 1 hour
  3. concentrationAfter being concentrated in vacuo
  4. additionthe residue was diluted with chloroform
  5. washthe organic solution was washed with saturated aqueous sodium bicarbonate solution and brine
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. concentrationthe solvent was concentrated in vacuo

Sources & evidence

ORD record
ord-6fb7eb27a99c4656a096906a7811d700
Source dataset
uspto-grants-2001_11
Patent number
US06316482B1

Reaction notes

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