Formic Acid → HCID 67230991, compound

A mixture of Stereoisomers 1 and 2 of 2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-8-((trans)-5-fluoroazepan-4-yloxy)quinoline (0.023 g, 0.0511 mmol) was slurried in CH2Cl2 (3 mL). A saturated aqueous Na2CO3 solution (5 mL) was added and the mixture was stirred at ambient temperature for 0.5 hours. The layers were separated and the aqueous phase was extracted with CH2Cl2. The combined organic layers were washed with brine and dried over Na2SO4, filtered and concentrated. The crude residue was treated with formic acid (0.289 mL, 7.66 mmol) and formaldehyde (0.0380 mL, 0.511 mmol). The mixture was stirred at 90° C. for 4 hours. The mixture was cooled to ambient temperature and carefully treated with a saturated aqueous Na2CO3 solution to adjust the mixture to about pH 11. The mixture was extracted with CHCl3 and the combined organic phases were washed with brine and dried over Na2SO4, filtered and concentrated. The crude product was purified by Preparative TLC (0.5 mm, 10% MeOH/CH2Cl2 with 1% 7N NH3/MeOH) to provide the desired product (0.011 g, 55%) as a white solid. MS ESI (+) m/z 392.1 (M+1) detected.

1. customThe layers were separated
2. extractionthe aqueous phase was extracted with CH2Cl2
3. washThe combined organic layers were washed with brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. stirringThe mixture was stirred at 90° C. for 4 hours
8. temperatureThe mixture was cooled to ambient temperature
9. extractionThe mixture was extracted with CHCl3
10. washthe combined organic phases were washed with brine
11. dry with materialdried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated
14. customThe crude product was purified by Preparative TLC (0.5 mm, 10% MeOH/CH2Cl2 with 1% 7N NH3/MeOH)

ORD record

ord-23b6a775d7174b36aae76d40262e05bd

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987251B2