Water → 2-(5-hydroxymethyl-3,4-dihydro-1H-isoquinolin-2-yl)-6,7-dimethoxy-3H-quinazolin-4-one

HRID 2183711Notes

Reaction equation

C(O[C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][C:14]=2[CH2:18][OH:19])[CH2:9]1)=O)(C)(C)C.ClC1[NH:30][C:29](=[O:31])[C:28]2[C:23](=[CH:24][C:25]([O:34][CH3:35])=[C:26]([O:32][CH3:33])[CH:27]=2)[N:22]=1.C(=O)(O)[O-].[Na+].O>FC(F)(F)C(O)=O.ClCCl.CS(C)=O>[OH:19][CH2:18][C:14]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:15]=1[CH2:16][CH2:17][N:8]([C:6]1[NH:30][C:29](=[O:31])[C:28]3[C:23](=[CH:24][C:25]([O:34][CH3:35])=[C:26]([O:32][CH3:33])[CH:27]=3)[N:22]=1)[CH2:9]2

Participants

Conditions

Temperature: 85 °C

Procedure

5-Hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester 21a (0.31 g, 1.17 mmol) was dissolved at room temperature in 10 mL of 10% trifluoroacetic acid in dichloromethane and stirred for 2 h. The volatiles were evaporated, the residue was suspended in toluene, evaporated again and dried under vacuum. The trifluoroacetic salt of the deprotected amine, was mixed with 2-chloro-6,7-dimethoxy-3H-quinazolin-4-one 1b (0.269 g, 1.11 mmol) and sodium bicarbonate (0.148 g, 1.76 mmol) in dimethyl sulfoxide (6 mL), and the mixture was heated to 85° C. with stirring for 28 h. After cooling to room temperature, water (20 mL) was added and the precipitated product was separated by filtration, rinsed with water, and dried to yield 0.2 g of 2-(5-hydroxymethyl-3,4-dihydro-1H-isoquinolin-2-yl)-6,7-dimethoxy-3H-quinazolin-4-one 22a, mp. 200.1-206.3° C.

Workup

customThe volatiles were evaporated
customevaporated again
customdried under vacuum
stirringwith stirring for 28 h
temperatureAfter cooling to room temperature
customthe precipitated product was separated by filtration
washrinsed with water
customdried

Sources & evidence

ORD record: ord-a4cb9cad1adc4053a193b3e5d39d09e5
Source dataset: uspto-grants-2005_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06900220B2

Reaction notes

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