Benzenamine, 4-(4-morpholinyl)- → 5-Acetyl-thiophene-2-carboxylic acid (3-{3-[(4-morpholin-4-yl-phenylamino)-methylene]-2-oxo-2,3-dihydro-1H-indole-6-carbonyl}-phenyl)-amide

HRID 640905Notes

Reaction equation

HRID 640905 reaction equation
O[CH:2]=[C:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([C:14]3[CH:15]=[C:16]([NH:20][C:21]([C:23]4[S:24][C:25]([C:28](=[O:30])[CH3:29])=[CH:26][CH:27]=4)=[O:22])[CH:17]=[CH:18][CH:19]=3)=[O:13])=[CH:9][CH:10]=2)[NH:5][C:4]1=[O:31].[NH2:32][C:33]1[CH:38]=[CH:37][C:36]([N:39]2[CH2:44][CH2:43][O:42][CH2:41][CH2:40]2)=[CH:35][CH:34]=1>C1COCC1>[N:39]1([C:36]2[CH:35]=[CH:34][C:33]([NH:32][CH:2]=[C:3]3[C:11]4[C:6](=[CH:7][C:8]([C:12]([C:14]5[CH:15]=[C:16]([NH:20][C:21]([C:23]6[S:24][C:25]([C:28](=[O:30])[CH3:29])=[CH:26][CH:27]=6)=[O:22])[CH:17]=[CH:18][CH:19]=5)=[O:13])=[CH:9][CH:10]=4)[NH:5][C:4]3=[O:31])=[CH:38][CH:37]=2)[CH2:40][CH2:41][O:42][CH2:43][CH2:44]1

Participants

4

Reactant 2

HCID 75655Benzenamine, 4-(4-morpholinyl)-HCID 178466653HCID 178466653, compound

Product 1

HCID 732247855-Acetyl-thiophene-2-carboxylic acid (3-{3-[(4-morpholin-4-yl-phenylamino)-methylene]-2-oxo-2,3-dihydro-1H-indole-6-carbonyl}-phenyl)-amideYield 69.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

A small screw cap test tube was charged with 5-Acetyl-thiophene-2-carboxylic acid [3-(3-hydroxymethylene-2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amide (as prepared in Example 54, 100 mg, 0.231 mmol) and THF (2 mL). To the resulting solution was added N-(4-aminophenyl)morpholine (45.34 mg, 0.254 mmol), and the mixture was stirred for 24 h at 65° C. Subsequently, the reaction mixture was cooled to room temperature. Hexanes (5 mL) were added to the reaction mixture. The crude mixture was concentrated in vacuo and then dissolved into hot EtOAc. Hexanes (˜5 mL) were added causing a precipitate to crash out. The precipitate was filtered and washed with ˜1 mL of i-prOH yielding 69% (95 mg, 0.160 mmol) of the title compound.

Workup

  1. customA small screw cap test tube
  2. temperatureSubsequently, the reaction mixture was cooled to room temperature
  3. concentrationThe crude mixture was concentrated in vacuo
  4. dissolutiondissolved into hot EtOAc
  5. additionHexanes (˜5 mL) were added
  6. filtrationThe precipitate was filtered

Sources & evidence

ORD record
ord-ce3d1bbdd6c84caab7c601fe5fbb28c8
Source dataset
uspto-grants-2010_04
Patent number
US07692005B2

Reaction notes

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