Hydrochloric Acid → HCID 89790880, compound

Temperature

90 °C

A stirred solution of (S)-N-(8-((2-amino-4-methylpentyl)oxy)-5H-chromeno[3,4-c]pyridin-2-yl)acetamide (40 mg, 0.113 mmol) and NaOH (45.0 mg, 1.125 mmol) in a mixture of ethanol (10 mL) and water (4 mL) was heated to 90° C. for 18 h. The volatiles were removed under reduced pressure and the residue was partitioned between water (20 mL) and dichloromethane (15 mL). The layers were separated and the aqueous layer was extracted with dichloromethane (15 mL). The combined organic layers were dried over sodium sulphate and concentrated under reduced to pressure to afford crude (S)-8-((2-amino-4-methylpentyl)oxy)-5H-chromeno[3,4-c]pyridin-2-amine (23 mg, 0.068 mmol, 60% crude yield) which was taken in MeOH (2 mL) and cooled to 0° C. The resultant solution was treated with 1M HCl in diethyl ether (15 mL, 0.068 mmol) and the reaction was stirred at room temperature for 14 h. The reaction mixture was then cooled to 0° C. to afford a solid which was filtered, washed with diethyl ether (10 mL) and dried under vacuum to afford (S)-8-((2-amino-4-methylpentyl)oxy)-5H-chromeno[3,4-c]pyridin-2-amine dihydrochloride (11 mg, 0.025 mmol, 37% yield for two steps) as a brown solid. 1H NMR (400 MHz, MeOD) δ 7.88 (d, J=6.9 Hz, 1 H), 7.78 (s, 1 H), 7.17 (s, 1 H), 6.89 (m, 1 H), 6.75 (d, J=2.1 Hz, 1 H), 5.07 (s, 2 H), 4.84-4.34 (m, 1 H), 4.17-4.13 (m, 1 H), 3.71 (m, 1 H), 1.82-1.75 (m, 1 H), 1.73-1.66 (m, 2 H), 1.04 (m, 6 H). LCMS (ESI) m/e 314.2 [(M+H)+, calcd for C18H24N3O2 314.2]; LC/MS retention time (Method D): tR=1.1 min; HPLC retention time (method A): tR=5.16 min; HPLC retention time (method B): tR=8.96 min.

1. customThe volatiles were removed under reduced pressure
2. customthe residue was partitioned between water (20 mL) and dichloromethane (15 mL)
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with dichloromethane (15 mL)
5. dry with materialThe combined organic layers were dried over sodium sulphate
6. concentrationconcentrated
7. customto afford crude (S)-8-((2-amino-4-methylpentyl)oxy)-5H-chromeno[3,4-c]pyridin-2-amine (23 mg, 0.068 mmol, 60% crude yield) which
8. temperaturecooled to 0° C
9. temperatureThe reaction mixture was then cooled to 0° C.
10. customto afford a solid which
11. filtrationwas filtered
12. washwashed with diethyl ether (10 mL)
13. customdried under vacuum

ORD record

ord-2ece9b0607584df287eb7c72cb38b356

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08703953B2