p-Toluenesulfonic acid → 2-(4-(4-Isopropylpiperazin-1-yl)phenyl)-8-methoxyquinazolin-4(3H)-one

HRID 591651Notes

Reaction equation

[CH: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)([CH3:3])[CH3:2].OS([O-])=O.[Na+].CC1C=CC(S(O)(=O)=O)=CC=1.[NH2:34][C:35]1[C:43]([O:44][CH3:45])=[CH:42][CH:41]=[CH:40][C:36]=1[C:37]([NH2:39])=[O:38]>CC(N(C)C)=O.O.C([O-])(O)=O.[Na+]>[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:17]=[CH:16][C:13]([C:14]3[NH:39][C:37](=[O:38])[C:36]4[C:35](=[C:43]([O:44][CH3:45])[CH:42]=[CH:41][CH:40]=4)[N:34]=3)=[CH:12][CH:11]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 4-(4-isopropylpiperazin-1-yl)benzaldehyde (0.562 g, 2.40 mmol), NaHSO3 (0.310 g, 2.90 mmol), and p-TsOH (0.046 g, 0.24 mmol) was added to a solution of 2-amino-3-methoxybenzamide (0.400 g, 2.40 mmol) in DMA (15 mL). The reaction was stirred at 120° C. overnight. The mixture was diluted with H2O and saturated NaHCO3 and extracted with CH2Cl2. The organics were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. Purification by flash chromatography on silica gel eluting with 0% to 10% MeOH/CH2Cl2 afforded the title compound (0.140 g, 15%). 1H NMR (300 MHz, DMSO-d6): δ 12.27 (s, 1H), 8.10 (d, J=8.9 Hz, 2H), 7.64-7.70 (m, 1H), 7.31-7.39 (m, 2H), 7.03 (d, J=9.1 Hz, 2H), 3.93 (s, 3H), 3.27-3.32 (m, 4H), 2.64-2.75 (m, 1H), 2.56-2.59 (m, 4H), 1.00 (d, J=6.6 Hz, 6H). ESI MS m/z 379 [M+H]+.

Workup

extractionextracted with CH2Cl2
washThe organics were washed with brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customPurification by flash chromatography on silica gel eluting with 0% to 10% MeOH/CH2Cl2

Sources & evidence

ORD record: ord-6e0a8c79472a44e3bd3b2a802f527031
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238640B2

Reaction notes

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