Potassium Phosphate, Tribasic → (E)-8-chloro-2,3-dimethyl-5-(2-(pyridin-4-yl)prop-1-enyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Temperature

140 °C

8-Chloro-2,3-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (117 mg, 0.5 mmol) and potassium phosphate (212 mg, 1 mmol) were mixed in DMF and the suspension was purged with nitrogen. The suspension was heated at 140° C. for 10 min. In a separate round bottomed flask, 4-(1-bromoprop-1-en-2-yl)pyridine (107.83 mg, 0.55 mmol), L-proline (11.5 mg, 0.1 mmol) and Copper (I) iodide (9.5 mg, 0.05 mmol) were mixed in DMF, the suspension was purged with nitrogen, and heated at 90° C. for 5 min. at which point it became a clear solution. The contents in the two reaction flasks were mixed and the reaction mixture was heated overnight at 90° C. The contents were cooled to RT and poured into water The precipitate obtained was filtered, dried and purified by silica gel chromatography (100-200 mesh, neutralized with aqueous ammonia) eluting with 0-10% MeOH-DCM as eluent. Compound was further purified by HPLC. 1H NMR (CD3OD, freebase) δ (ppm): 8.60 (d, 2H), 7.70 (d, 2H), 7.45 (s, 1H), 7.30 (s, 1H), 7.10 (s, 2H), 4.05 (d, 1H), 3.80 (d, 1H), 3.10 (m, 1H), 2.95 (m, 1H), 2.65 (m, 1H), 2.60 (s, 3H), 2.0 (s, 3H), 1.30 (d, 3H).

1. customthe suspension was purged with nitrogen
2. customthe suspension was purged with nitrogen
3. temperatureheated at 90° C. for 5 min. at which point it
4. customThe contents in the two reaction flasks
5. additionwere mixed
6. temperaturethe reaction mixture was heated overnight at 90° C
7. temperatureThe contents were cooled to RT
8. customobtained
9. filtrationwas filtered
10. customdried
11. custompurified by silica gel chromatography (100-200 mesh, neutralized with aqueous ammonia)
12. washeluting with 0-10% MeOH-DCM as eluent
13. customCompound was further purified by HPLC

ORD record

ord-a0c55f6478c64a9e8147de3fcc426346

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08907097B2