Diethyl Ether → 5,7-Dichloro-1,6-naphthyridine

N-(2,6-Dichloro-4-pyridinyl)-2,2-dimethylpropanamide (1 g, 4.05 mmol) was taken up in THF (10 ml) under nitrogen and cooled to <−70° C. n-Butyl lithium (4.05 ml, 10.12 mmol, 2.5M solution in hexanes) was added over 30 min keeping the temperature below −60° C. and then stirred at below −70° C. for 1 h. (2E)-3-(dimethylamino)-2-propenal (0.607 ml, 6.07 mmol) in THF (2 ml) was added over 30 min keeping the temperature below −60° C. The reaction was stirred at below −70° C. for 20 min and then allowed to warm to room temperature. LCMS showed that no starting material remained so the reaction was quenched with 5M HCl (5 ml) and refluxed overnight. LCMS showed good conversion to product so the reaction was cooled to room temperature. The reaction mixture was basified with solid K2CO3 and extracted with EtOAc (4×25 ml). The combined organics were dried with Na2SO4, filtered and concentrated to yield a brown solid. The crude product was applied to a samplet and columned using a 40+M eluting with 12% diethyl ether in cyclohexane for 2 CVs, then with 12%-63% diethyl ether in cyclohexane over 10 CVs then held at 63% for SCVs. Appropriate fractions were combined and evaporated to give the title compound as a yellow solid (0.42 g).

1. additionwas added over 30 min
2. customthe temperature below −60° C.
3. additionwas added over 30 min
4. customthe temperature below −60° C
5. customwas quenched with 5M HCl (5 ml)
6. temperaturerefluxed overnight
7. temperaturewas cooled to room temperature
8. extractionextracted with EtOAc (4×25 ml)
9. dry with materialThe combined organics were dried with Na2SO4
10. filtrationfiltered
11. concentrationconcentrated
12. customto yield a brown solid
13. customevaporated

ORD record

ord-d32a7f5759e34beead5c07f75b326240

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08633319B2