1-Methoxy-2-propanol → 6-Amino-4-(2-methoxy-1-methylethoxy)-3-pyridinecarbonitrile

Temperature

50 °C

1-methoxypropan-2-ol (329 mg, 3.65 mmol) was treated at room temperature with KHMDS (1M in THF, 1.82 ml, 1.82 mmol). The reaction mixture was stirred for 10 min. Then, the mixture was added to a solution of 6-amino-4-fluoronicotinonitrile (intermediate 21, 50 mg, 0.365 mmol) in NMP (0.5 ml). The solution was then heated at 50° C. for 1 h. The reaction mixture was quenched with water and diluted in EtOAc. The layers were separated and the aq. layer was extracted 3× with EtOAc. The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by normal phase chromatography (4 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100). The product containing fractions were concentrated; the obtained oil was dissolved in water and lyophilized to give the title compound as a white solid. (UPLC-MS 3) tR 0.57 min; ESI-MS 208.1 [M+H]+.

1. customThe reaction mixture was quenched with water
2. additiondiluted in EtOAc
3. customThe layers were separated
4. extractionthe aq. layer was extracted 3× with EtOAc
5. dry with materialThe combined organic layers were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe crude material was purified by normal phase chromatography (4 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100)
9. additionThe product containing fractions
10. concentrationwere concentrated
11. dissolutionthe obtained oil was dissolved in water

ORD record

ord-ce0581b1454f49ba9ca763d2d34dcd49

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266883B2