Triethylamine → 2-(4-(4-(2,5-Dichlorothiophene-3-carbonyl)piperazin-1-yl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one

HRID 591629Notes

Reaction equation

HRID 591629 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[C:9]2[C:4]=1[C:5](=[O:27])[NH:6][C:7]([C:15]1[CH:20]=[CH:19][C:18]([N:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)=[CH:17][CH:16]=1)=[N:8]2.[Cl:28][C:29]1[S:30][C:31]([Cl:37])=[CH:32][C:33]=1[C:34](Cl)=[O:35].CCN(CC)CC>C(Cl)Cl>[Cl:28][C:29]1[S:30][C:31]([Cl:37])=[CH:32][C:33]=1[C:34]([N:24]1[CH2:23][CH2:22][N:21]([C:18]2[CH:19]=[CH:20][C:15]([C:7]3[NH:6][C:5](=[O:27])[C:4]4[C:9](=[CH:10][C:11]([O:13][CH3:14])=[CH:12][C:3]=4[O:2][CH3:1])[N:8]=3)=[CH:16][CH:17]=2)[CH2:26][CH2:25]1)=[O:35]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27770842,5-Dichlorothiophene-3-carbonyl chlorideHCID 1359390885,7-dimethoxy-2-(4-(piperazin-1-yl)phenyl)quinazolin-4(3H)-one

Product 1

HCID 1359391042-(4-(4-(2,5-Dichlorothiophene-3-carbonyl)piperazin-1-yl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-oneYield 79.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 5,7-dimethoxy-2-(4-(piperazin-1-yl)phenyl)quinazolin-4(3H)-one (0.150 g, 0.41 mmol) and 2,5-dichlorothiophene-3-carbonyl chloride (0.088 g, 0.41 mmol) in CH2Cl2 was added Et3N (0.086 mL, 0.62 mmol) and the mixture stirred at room temperature under nitrogen for 30 minutes. The mixture was concentrated and purified by silica gel chromatography, eluting with 70% CH2Cl2/(92:7:1 CHCl3/MeOH/concentrated NH4OH) to 100% (92:7:1 CHCl3/MeOH/concentrated NH4OH), to afford the title compound as a light yellow solid (0.177 g, 79%). 1H NMR (300 MHz, DMSO-d6): δ 11.80 (s, 1H), 8.12 (d, J=9.0 Hz, 2H), 7.27 (s, 1H), 7.05 (d, J=9.0 Hz, 2H), 6.69 (d, J=2.3 Hz, 1H), 6.48 (d, J=2.3 Hz, 1H), 3.88 (s, 3H), 3.84 (s, 3H), 3.73-3.82 (m, 2H), 3.38-3.44 (m, 6H). APCI MS m/z 545 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated
  2. custompurified by silica gel chromatography
  3. washeluting with 70% CH2Cl2/(92:7:1 CHCl3/MeOH/concentrated NH4OH) to 100% (92:7:1 CHCl3/MeOH/concentrated NH4OH)

Sources & evidence

ORD record
ord-d6e5a7804e1c43f0b87eeaa45fae10f3
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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