p-Toluenesulfonic acid → HCID 136037978, compound

HRID 336712Notes

Reaction equation

[NH2:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([O:13][CH3:14])[C:3]=1[C:4]([NH2:6])=[O:5].[CH3:15][N:16]1[CH2:21][CH2:20][N:19]([CH2:22][C:23]2[CH:30]=[CH:29][C:26]([CH:27]=O)=[CH:25][CH:24]=2)[CH2:18][CH2:17]1.OS([O-])=O.[Na+].CC1C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>CN(C)C(=O)C.O>[CH3:14][O:13][C:7]1[CH:8]=[C:9]([O:11][CH3:12])[CH:10]=[C:2]2[C:3]=1[C:4](=[O:5])[NH:6][C:27]([C:26]1[CH:25]=[CH:24][C:23]([CH2:22][N:19]3[CH2:18][CH2:17][N:16]([CH3:15])[CH2:21][CH2:20]3)=[CH:30][CH:29]=1)=[N:1]2

Participants

Conditions

Temperature: 150 °C

Procedure

To a solution of 2-amino-4,6-dimethoxy-benzamide (150 mg, 0.76 mmol) and 4-(4-methyl piperazin-1-ylmethyl)benzaldehyde (166 mg, 0.76 mmol) in N,N-dimethyl acetamide (10 mL), NaHSO3 (149 mg, 0.84 mmol) and p-TSA (319 mg, 1.68 mmol) were added and the reaction mixture was heated at 150° C. for 3 h. The mixture was cooled to room temperature and water was added and neutralized by addition of NaHCO3. The solvent was removed under reduced pressure to give the crude product. The crude was purified by column chromatography (silica gel 230-400 mesh; 4% NH3 in methanol/CH2Cl2 as eluent) to give the product 5,7-dimethoxy-2-(4-((4-methylpiperazin-1-yl)methyl)phenyl)quinazolin-4(3H)-one as a free base, which was converted to the hydrochloride salt (115 mg, 35%). Selected data: MS (ES) m/z: 395.2; MP 275-277° C. (hydrochloride).

Workup

temperatureThe mixture was cooled to room temperature
customThe solvent was removed under reduced pressure
customto give the crude product
customThe crude was purified by column chromatography (silica gel 230-400 mesh; 4% NH3 in methanol/CH2Cl2 as eluent)

Sources & evidence

ORD record: ord-b38f7214731c4ae582eca638f4c3fad8
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889698B2

Reaction notes

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