Propargyl alcohol → 3-(6-Aminopyridin-3-yl)prop-2-yn-1-ol

Temperature

80 °C

2-Amino5-bromopyridine (7-1), 10.0 g (57.8 mmol) was stirred in pyrrolidine (96.5 mL, 1.16 mol, 20 equiv) in a flame dried round bottom flask under argon. Propargyl alcohol (10.1 mL, 173 mmol) and tetrakis triphenylphosphine palladium(0) (1.34 g, 1.16 mmol) were added and the solution was degassed 3× by alternating vacuum/Ar. Heat to 80° C. After 18 h the bulk of the pyrrolidine was removed in vacuo and the residue was diluted with water. Extract with CH2Cl2 three times, and the extracts were dried over Na2SO4, filtered and concentrated to provide impure product. The aqueous layer was further extracted ten times with CH2Cl2/nBuOH (95:5). The extracts were dried over Na2SO4, filtered and concentrated. The two samples were combined and were purified in two batches by flash column chromatography (gradient: CH2Cl2 to CH2Cl2/MeOH, 90:10). The product was triurated with ice cold CH2Cl2, filtered, and washed with ice cold CH2Cl2. Afforded the titled compound as a pale yellow solid. 1H NMR (CD3OD) δ 7.96 (d, 1H, J=2.2 Hz), 7.45 (dd, 1H, J=2.4, 8.8 Hz), 6.51 (d, 1H, J=8.8 Hz), 4.36 (s, 2H).

1. customdried round bottom flask under argon
2. customthe solution was degassed 3×
3. customAfter 18 h the bulk of the pyrrolidine was removed in vacuo
4. additionthe residue was diluted with water
5. extractionExtract with CH2Cl2 three times
6. dry with materialthe extracts were dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customto provide impure product
10. extractionThe aqueous layer was further extracted ten times with CH2Cl2/nBuOH (95:5)
11. dry with materialThe extracts were dried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated
14. customwere purified in two batches by flash column chromatography (gradient: CH2Cl2 to CH2Cl2/MeOH, 90:10)
15. filtrationfiltered
16. washwashed with ice cold CH2Cl2

ORD record

ord-fdd8e96b47b048f184986589454680c0

Source dataset

uspto-grants-2003_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06586424B2