Reference of 627-30-5 ,Some common heterocyclic compound, 627-30-5, molecular formula is C3H7ClO, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.
The 4-CHLORO-7- (3-CHLOROPROPOXY)-6-METHOXYQUINAZOLINE used as a starting material was prepared as follows:- Ammonium formate (45 g) was added portionwise over 1.25 hours to a stirred mixture of 7-benzyloxy-6-methoxy-3,4-dihydroquinazolin-4-one (International Patent Application WO 02/16352, Example 1 thereof; 20 g), 10% palladium-on-carbon catalyst (3.3 g) and DMF (530 ml) and the reaction mixture was stirred for an additional 30 minutes. The catalyst was removed by filtration and the solvent was evaporated. There was thus obtained 7-hydroxy- 6-methoxy-3,4-dihydroquinazolin-4-one (8.65 g); NMR Spectrum: (DMSOD6) 3.9 (s, 3H), 7.0 (s, 1H), 7.45 (s, 1H), 7.9 (s, 1H). A mixture of the material so obtained, acetic anhydride (63 ml) and pyridine (7.5 ml) was heated to 100C for 4.5 hours. The resultant mixture was allowed to stand at ambient temperature for 16 hours. The mixture was poured into a stirred mixture (400 ml) of ice and water. The resultant precipitate was isolated and dried under vacuum. Analysis revealed that hydrolysis of the acetate group on the 4 position of the quinazoline was incomplete. The mixture was therefore further hydrolysed with water (150 ml) and pyridine (a few drops) at 90C for 15 minutes. The resultant mixture was cooled to ambient temperature and the solid was collected by filtration, washed with water and dried under vacuum. There was thus obtained 7-ACETOXY-6-METHOXY-3, 4-dihydroquinazolin-4-one (7.4 g); NMR Spectrum: (DMSOD6) 2.3 (s, 3H), 3.9 (s, 3H), 7.45 (s, 1IN), 7.65 (s, 1H), 8. 05 (s, 1H). A mixture of A portion (2 g) of the material so obtained, thionyl chloride (32 ml) and DMF (5 drops) was stirred and heated to reflux for 1.5 hours. The mixture was cooled to ambient temperature and the excess of thionyl chloride was evaporated. Toluene was added to the residue and evaporated. The resultant residue was diluted with methylene chloride (15 ml) and a 10% ammonia solution in methanol (80 ml) was added and the mixture was heated to 80C for 10 minutes. The mixture was cooled to ambient temperature and evaporated. Water was added to the residue and the mixture was neutralised by the addition of dilute aqueous hydrochloric acid solution. The resultant precipitate was collected by filtration and dried under vacuum at 35C for 16 hours. There was thus obtained 4-chloro- 7-hydroxy-6-methoxyquinazoline (1.65 g); NMR Spectrum: (DMSOD6) 4.0 (s, 3H), 7.25 (s, 1H), 7.4 (s, 1H), 8.8 (s, 1H). Di-tert-butyl azodicarboxylate (2.3 g) was added portionwise over a few minutes to a stirred mixture of 4-chloro-7-hydroxy-6-methoxyquinazoline (1.65 g), 3-chloropropanol (0.7 ml), triphenylphosphine (2.6 g) and methylene chloride (100 ml) and the reaction mixture was stirred at ambient temperature for 2 hours. The mixture was concentrated to a volume of about 30 ml by evaporation and the residue was purified by column chromatography on silica using increasingly polar mixtures of petroleum ether (b. p 40-60C) and ethyl acetate as eluent. There was thus obtained 4-CHLORO-7- (3-CHLOROPROPOXY)-6-METHOXYQUINAZOLINE as a white solid (2 g); NMR Spectrum: (DMSOD6) 2.3 (m, 2H), 3. 8 (m, 2H), 4.05 (s, 3H), 4.4 (m, 2H), 7.45 (s, 1H), 7.55 (s, 1H), 8.9 (s, 1H).
In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles. 627-30-5, 3-Chloropropan-1-ol, other downstream synthetic routes, hurry up and to see.
Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2004/81000; (2004); A1;,
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