Morpholine → HCID 86667797, compound

Temperature

115 °C

To a mixture of 7-methyl-1H-pyrido[3′,2′:4,5]furo[3,2-d]pyrimidine-2.4-dione (1.6 g, 4.20 mmol, 1 eq) 17, and PCl5 (10.5 g, 50 mmol, 12 eq) was added at rt POCl3 (33.5 mL, 357 mmol, 85 eq) under Ar(g). The reaction mixture was refluxed at 115° C. overnight. Once cooled down to rt, the mixture was poured dropwise very slowly onto stirred crushed ice over 2 h, then warmed up to rt for 1 h. The resulting aqueous was extracted with EtOAc (3×100 mL) and CH2Cl2 (4×100 mL). The combined organics were dried over MgSO4 and the solvent was removed in vacuo. To this residue in dry MeOH (50 mL) was added at rt morpholine (0.92 mL, 10.5 mmol, 2.5 eq) under Ar(g). The reaction mixture was stirred for 3 h, then the solvent was removed in vacuo. The residue was further purified by silica gel column chromatography with hexane/EtOAc (1:1-0:1) to yield the product as a pale brown solid (384 mg, 30%).

1. temperatureOnce cooled down to rt
2. additionthe mixture was poured dropwise very slowly
3. customcrushed ice over 2 h
4. temperaturewarmed up to rt for 1 h
5. extractionThe resulting aqueous was extracted with EtOAc (3×100 mL) and CH2Cl2 (4×100 mL)
6. dry with materialThe combined organics were dried over MgSO4
7. customthe solvent was removed in vacuo
8. stirringThe reaction mixture was stirred for 3 h
9. customthe solvent was removed in vacuo
10. customThe residue was further purified by silica gel column chromatography with hexane/EtOAc (1:1-0:1)

ORD record

ord-bafa3c58a06d4ba7acc371dce632def9

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09200007B2