Dimethyl Sulfoxide → 2-(4-Fluorobenzyl)-8-methyl-10-methoxy-1,9-dioxo-1,2,6,7,8,9-hexahydropyrazino[1',2':1,5]pyrrolo[2,3-d]pyridazine-4-carboxaldehyde

Temperature

-35 °C

To a cold (−78° C.) solution of oxalyl chloride (0.25 mL, 2.8 mmol) in anhydrous dichloromethane (15 mL) under an atmosphere of nitrogen, a solution of anhydrous DMSO (0.21 mL, 2.93 mmol) in anhydrous dichloromethane (5 mL) was added. The resultant mixture was stirred at the same temperature for 10 minutes. A solution of 2-(4-fluorobenzyl)-4-(hydroxymethyl)-10-methoxy-8-methyl-7,8-dihydropyrazino[1′,2′:1,5]pyrrolo[2,3-d]pyridazine-1,9(2H,6H)-dione (0.47 g, 1.22 mmol) in a mixture of anhydrous dichloromethane (3 mL) and DMSO (5 mL) was added. After stirring at the same temperature for 2 hours, the reaction mixture was allowed to warm to −35° C., and treated with triethylamine (8 mL). The reaction mixture was allowed to warm to room temperature and pour into water (40 mL). The product mixture was diluted with dichloromethane. The organic extract was dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residual oil was treated with hexane and cooled to 0° C. The solid precipitated was filtered and vacuum dried to provide the title compound.

1. additionwas added
2. temperatureto warm to room temperature
3. extractionThe organic extract
4. dry with materialwas dried over anhydrous magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated under vacuum
7. additionThe residual oil was treated with hexane
8. temperaturecooled to 0° C
9. customThe solid precipitated
10. filtrationwas filtered
11. customvacuum dried

ORD record

ord-8800c2e40e834a35927902fcb4c27c9f

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07538112B2