Nitrogen → HCID 86601188, compound

4-Methylphenyl 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-6-yl sulfide hydrochloride (prepared in Example 1, 331 mg, 1.0 mmol) was suspended in TFA (17 mL) at rt. This mixture was cooled in an ice bath. A stream of N2 was introduced through the solution while solid NaCNBH3 (202 mg, 3.3 mmol) was added in 4 portions over 10 min. maintaining an internal temperature of <7° C. The resultant solution was maintained at ˜0° C. for 5 h at which time it was poured over ice chips. With vigorous stirring, 50% NaOH was added portionwise to pH 12. This mixture was extracted with CHCl3 (3×100 mL). The organic extracts were combined, dried (MgSO4) and concentrated in vacuo. The residue (265 mg, 90%) was treated with Et2O (5 mL) and filtered. The filtrate was treated with a MeOH solution (1 mL) of fumaric acid (116 mg, 1.0 mmol). The resultant solution was concentrated in vacuo. The solid residue was recrystallized from EtOAc-Et2O to afford the title compound (298 mg, 67%) as a crystalline sample. 1H NMR (300 MHz, CDCl3) δ 7.18 (d, J=7.7 Hz, 1H), 7.09 (d, J=7.0 Hz, 1H), 7.29 (s, 4H), 6.72 (t, J=7.3 Hz, 1H), 4.09 (t, J=8.3 Hz, 1H), 3.83 (q, J=5.5 Hz, 1H), 3.2-2.8 (m, 3H), 2.72-2.60 (m, 1H), 2.28 (s, 3H), 1.78-1.63 (m, 2H), 1.57-1.44 (m, 2H) ppm.

1. temperatureThis mixture was cooled in an ice bath
2. additionwas added in 4 portions over 10 min.
3. temperaturemaintaining an internal temperature of <7° C
4. additionwas poured over ice chips
5. extractionThis mixture was extracted with CHCl3 (3×100 mL)
6. dry with materialdried (MgSO4)
7. concentrationconcentrated in vacuo
8. additionThe residue (265 mg, 90%) was treated with Et2O (5 mL)
9. filtrationfiltered
10. concentrationThe resultant solution was concentrated in vacuo
11. customThe solid residue was recrystallized from EtOAc-Et2O

ORD record

ord-77512e7f47bf4343994cf008dda621e2

Source dataset

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07592454B2