| 93% |
With pyridine; at 100℃; for 4h; |
Step 5. A mixture of 7-hydroxy-6-ethoxy-3,4-dihydroquinazolin-4-one (5.86 g, 30.5 mmol) and acetic anhydride (21.5 mL, 229 mmol) in pyridine (4.9 mL, 61 mmol) was heated to 100 C. for 4 h. After cooling to r.t., ice water (200 mL) was added and the mixture was vigorously stirred for 1 h. The precipitated 7-acetoxy-6-methoxy-3,4-dihydroquinazolin-4-one was filtered off, washed with water and dried (grey solid, 6.64 g, 28.3 mmol, 93%). LC/ESI-MS: m/z=235 M+H]+; m/z=233 [M-H]-; Rt=2.88 min. Cf. also WO 04/043472, page 32. |
| 93 - 96% |
With pyridine; at 100℃; for 4h; |
Step 5. A mixture of product step 4 (30.5 mmol), acetic anhydride (21.5 mL, 229 mmol) and pyridine (4.9 mL, 61 mmol) was heated to 100 C. for 4 h. After cooling to r.t., ice water (200 mL) was added and the mixture was vigorously stirred for 1 h. The precipitated 7-acetoxy-6-methoxy-3,4-dihydroquinazolin-4-one or 6-acetoxy-7-methoxy-3,4-dihydroquinazolin-4-one, respectively, was filtered off, washed with water and dried (93-96%). |
| 93 - 96% |
With pyridine; at 100℃; for 4h; |
Step 5. A mixture of product step 4 (30.5 mmol), acetic anhydride (21.5 mL, 229 mmol) and pyridine (4.9 mL, 61 mmol) was heated to 100C for 4 h. After cooling to r.t., ice water (200 mL) was added and the mixture was vigorously stirred for 1 h. The precipitated 7-acetoxy-6-methoxy-3,4-dihydroquinazolin-4-one or 6-acetoxy-7-methoxy-3,4-dihydroquinazolin-4-one, respectively, was filtered off, washed with water and dried (93-96%). |
| 93 - 96% |
With pyridine; at 100℃; for 4h; |
Step 5. A mixture of product step 4 (30.5 mmol), acetic anhydride (21.5 mL, 229 mmol) and pyridine (4.9 mL, 61 mmol) was heated to 100 C. for 4 h. After cooling to r.t., ice water (200 mL) was added and the mixture was vigorously stirred for 1 h. The precipitated 7-acetoxy-6-methoxy-3,4-dihydroquinazolin-4-one or 6-acetoxy-7-methoxy-3,4-dihydroquinazolin-4-one, respectively, was filtered off, washed with water and dried (93-96%). |
| 84% |
With pyridine; at 120℃; for 3h; |
Pyridine (20 ml) was added to a suspension of 7-hydroxy-6-methoxy-3, 4- dihydroquinazolin-4-one (20.5 g, 107 mmol) in acetic anhydride (150 ml, 1. 6 mol). The reaction mixture was heated to 120C for three hours, during which time the solid dissolved. The reaction mixture was allowed to cool then poured into ice-water (900 ml). The reaction mixture was stirred for one hour then the solid was removed by filtration and dried over phosphorus pentoxide yielding 7-acetoxy-6-methoxy-3,4-dihydroquinazolin-4-one as a white solid (20.98 g, 84%). H NMR Spectrum: (DMSOD6) 2.25 (s, 3H), 3.85 (s, 3H), 7.40 (s, 1H), 7.60 (s, 1H), 8.00 (s, 1H) MS-ESI: 235 [M+H] + |
| 84% |
With pyridine; at 120℃; for 3h;Heating; |
Pyridine (20 ml) was added to a suspension of 7-hydroxy-6-methoxy-3, 4- dihydroquinazolin-4-one (20.5 g, 107 mmol) in acetic anhydride (150 ml, 1.6 mol). The reaction mixture was heated to 120C for three hours, during which time the solid dissolved. The reaction mixture was allowed to cool then poured into ice-water (900 ml). The reaction mixture was stirred for one hour then the solid was removed by filtration and dried over phosphorus pentoxide yielding 7-ACETOXY-6-METHOXY-3, 4-DIHYDROQUINAZOLIN-4-ONE as a white solid (20.98 g, 84%). H NMR SPECTRUM : (DMSOD6) 2.25 (s, 3H), 3.85 (s, 3H), 7.40 (s, 1H), 7.60 (s, 1H), 8.00 (s, 1H) MS-ESI: 235 [M+H] + |
| 76% |
With pyridine; at 20 - 100℃; for 22.5h; |
b) A mixture of 7-HYDROXY-6-METHOXYQUINAZOLIN-4- (3H)-ONE (8. 0 g, 41.6 mmol), pyridine (7.5 ml) and acetic anhydride (63 ML) was heated at 100 C for 4.5 hours and left to cool to ambient temperature 18 hours. The reaction mixture was poured into ice/water (400 ml) and the resultant precipitate collected by filtration and dried IN VACUO. Analysis revealed that hydrolysis of the acetate group on the 4 position of the quinazoline was incomplete. The mixture was therefore treated with water (150 ml) and pyridine (0.5 ml) at 90 C for 15 minutes. The reaction was cooled and the solid was collected by filtration, washed with water and dried in vacuo to yield 7- (ACETOXY)-6-METHOXYQUINAZOLIN-4- (3H)-ONE (7.4 g, 76 % yield): 1H-NMR (DMSO D6) : 8.05 (s, 1H), 7.65 (s, 1H), 7.45 (s, 1H), 3.90 (s, 3H), 2.31 (s, 3H). |
| 76% |
|
A mixture of 7-HYDROXY-6-METHOXYQUINAZOLIN-4- (3H)-ONE (8.0 g, 41.6 mmol), pyridine (7.5 ml) and acetic anhydride (63 ml) was heated at 100C for 4.5 hours and left to cool to ambient temperature for 18 hours. The reaction mixture was poured into ice/water (400 ML) and the resultant precipitate collected by filtration and dried in vacuo. Analysis revealed that hydrolysis of the acetate group on the 4 position of the quinazoline was incomplete. The mixture was therefore treated with water (150 ml) and pyridine (0.5 ml) at 90 C for 15 minutes. The reaction was cooled and the solid was collected by filtration, washed with water and dried in vacuo to yield 7- (ACETOXY)-6-METHOXYQUINAZOLIN-4- (3H)-ONE (7.4 g, 76 % YIELD) : H-NMR (DMSO d6): 8.05 (s, 1H), 7.65 (s, 1H), 7.45 (s, 1H), 3.90 (s, 3H), 2.31 (s, 3H). |
| 55.4% |
With pyridine; at 120℃; for 3h; |
Pyridine (145 ml) was added to a suspension of 123 (148 g, 770.15 mmol) in acetic anhydride (800 ml). The reaction mixture was heated to 120 C. for 3 h, during which time the solid dissolved. The reaction mixture was allowed to cool, then poured into ice-water. The reaction mixture was stirred for 1 h, then the solid was removed by filtration and dried over to give 124 (100 g, yield=55.4%) as brown solid |
|
|
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, 1H), 7.65 (s, 1H), 8.05 (s, 1H) |
|
With pyridine; at 100℃; for 4h; |
A mixture of product step 4 (30.5 mmol), acetic anhydride (21.5 mL, 229 mmol) and pyridine (4.9 mL, 61 mmol) was heated to 100 C. for 4 h. After cooling to r.t., ice water (200 mL) was added and the mixture was vigorously stirred for 1 h. The precipitated 7-acetoxy-6-methoxy-3,4-dihydroquinazolin-4-one or 6-acetoxy-7-methoxy-3,4-dihydro-quinazolin-4-one, respectively, was filtered off, washed with water and dried (93-96%). |
|
In pyridine; water; at 20 - 100℃; for 20.75h; |
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 hydrolyse 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, 1H), 7.65 (s, 1H), 8.05 (s, 1H). |
|
|
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). |
|
With pyridine; at 100℃; for 4h; |
Step 5. A mixture of product step 4 (30.5 mmol), acetic anhydride (21.5 mL, 229 mmol) and pyridine (4.9 mL, 61 mmol) was heated to 100C for 4 h. After cooling to r.t., ice water (200 mL) was added and the mixture was vigorously stirred for 1 h. The precipitated 7-acetoxy-6-methoxy-3,4-dihydroquinazolin-4-one or 6-acetoxy-7-methoxy-3,4-dihydroquinazolin-4-one, respectively, was filtered off, washed with water and dried (93-96%). |
|
|
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 ambienttemperature for 16 hours. The mixture was poured into a stirred mixture (400 ml) of ice andwater. The resultant precipitate was isolated and dried under vacuum. Analysis revealed thathydrolysis of the acetate group on the 4 position of the quinazoline was incomplete. Themixture was therefore further hydrolysed with water (150 ml) and pyridine (a few drops) at90C for 15 minutes. The resultant mixture was cooled to ambient temperature and the solidwas collected by filtration, washed with water and dried under vacuum. There was thusobtained 7-acetoxy-6-methoxy-3,4-dihydroquinazolin-4-one (7.4 g); NMR Spectrum:(DMSOde) 2.3 (s, 3H), 3.9 (s, 3H), 7.45 (s, 1H), 7.65 (s, 1H), 8.05 (s, 1H). |
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
