Hydrochloric Acid → HCID 89463409, compound

Temperature

140 °C

A suspension of 2-(9-(4-fluorobenzyl)-2-methyl-1-oxo-4-(p-tolyl)-2,9-dihydro-1H-pyrido[3,4-b]indol-3-yl)acetonitrile (45 mg, 0.103 mmol) in Ethanol (3 mL) and Water (1 mL) was treated with KOH (5.80 mg, 0.103 mmol) and heated in a sealed tube at 140° C. for 3 days. The mixture was cooled to 0° C. and then treated with 4N HCl until pH<2. The mixture was partly concentrated and then extracted with ethyl acetate. The combined extracts were washed with brine and then concentrated. The residue was dissolved AcOH and concentrated HCl (37%) and irradiated in microwave at 120° C. for 1 hour. The mixture was concentrated to dryness. The residue was diluted with Ethyl acetate, washed with brine, dried over Na2SO4, filtered and concentrated. The resultant was dissolved in Methanol (3.00 mL), cooled to 0° C., treated with TMS-diazomethane (59.0 mg, 0.517 mmol) and then stirred at 0° C. for 20 minutes. The mixture was concentrated and the residue purified on silica gel (0-100% ethyl acetate/hexanes) to afford methyl 2-(9-(4-fluorobenzyl)-2-methyl-1-oxo-4-(p-tolyl)-2,9-dihydro-1H-pyrido[3,4-b]indol-3-yl)acetate (45 mg, 0.096 mmol, 93% yield) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) ppm 7.31-7.42 (m, 4H) 7.22-7.27 (m, 3H) 6.92-7.00 (m, 3H) 6.87-6.92 (m, 1H) 6.61-6.66 (m, 1H) 6.16 (s, 2H) 3.73 (s, 3H) 3.70 (s, 3H) 2.48 (s, 3H); LCMS (m/z) ES+=469 (M+1).

1. temperatureThe mixture was cooled to 0° C.
2. concentrationThe mixture was partly concentrated
3. extractionextracted with ethyl acetate
4. washThe combined extracts were washed with brine
5. concentrationconcentrated
6. dissolutionThe residue was dissolved AcOH and concentrated HCl (37%)
7. customirradiated in microwave at 120° C. for 1 hour
8. concentrationThe mixture was concentrated to dryness
9. additionThe residue was diluted with Ethyl acetate
10. washwashed with brine
11. dry with materialdried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated
14. dissolutionThe resultant was dissolved in Methanol (3.00 mL)
15. temperaturecooled to 0° C.
16. concentrationThe mixture was concentrated
17. customthe residue purified on silica gel (0-100% ethyl acetate/hexanes)

ORD record

ord-3e196dafc8d0447fb14d68b13d224fac

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012642B2