p-Toluenesulfonic acid → 2-(4-(4-acetylpiperazin-1-yl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one

HRID 591602Notes

Reaction equation

[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:17]=[CH:16][C:13]([CH:14]=O)=[CH:12][CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[NH2:18][C:19]1[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[C:24]([O:30][CH3:31])[C:20]=1[C:21]([NH2:23])=[O:22].CC1C=CC(S(O)(=O)=O)=CC=1.OS([O-])=O.[Na+]>CC(N(C)C)=O.O>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:17]=[CH:16][C:13]([C:14]3[NH:23][C:21](=[O:22])[C:20]4[C:19](=[CH:27][C:26]([O:28][CH3:29])=[CH:25][C:24]=4[O:30][CH3:31])[N:18]=3)=[CH:12][CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 155 °C

Procedure

A mixture of 4-(4-acetylpiperazin-1-yl)benzaldehyde (1.34 g, 5.77 mmol) and 2-amino-4,6-dimethoxybenzamide (1.03 g, 5.24 mmol) in DMA (30 mL) was treated with p-TsOH (0.100 g, 0.524 mmol) and NaHSO3 (0.578 g, 5.55 mmol). The mixture was heated at 155° C. for 6 hours, cooled to room temperature, diluted with water (400 mL), and filtered to give brown solids. The filtrate was extracted with EtOAc (3×100 mL), concentrated, and combined with the brown solids from the filter cake. The combined solids were purified by silica gel chromatography, eluting with 92:7:1 CHCl3/MeOH/concentrated NH4OH to afford 2-(4-(4-acetylpiperazin-1-yl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one as a yellow solid (1.9 g, 90%).

Workup

temperaturecooled to room temperature
filtrationfiltered
customto give brown solids
extractionThe filtrate was extracted with EtOAc (3×100 mL)
concentrationconcentrated
customThe combined solids were purified by silica gel chromatography
washeluting with 92:7:1 CHCl3/MeOH/concentrated NH4OH

Sources & evidence

ORD record: ord-45bfc47eb8e6418fa6e915e5d58166d9
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238640B2

Reaction notes

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