1H-Indole-3-propanoic acid → N-(4-Dimethylamino-4-phenylcyclohexylmethyl)-2-(1H-indol-3-yl)propionamide hydrochloride

The non-polar diastereoisomer of (4-aminomethyl-1-phenylcyclohexyl)dimethylamine (232 mg, 1.0 mmol.) and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (415 mg, 1.5 mmol.) were added to a solution of 3-(1H-indol-3-yl)propionic acid (189 mg, 1.0 mmol.) in abs. methanol, and stirring was carried out for 20 h at RT. For working up, the mixture was concentrated, the residue was taken up in water (10 ml) and ether (10 ml), and the phases were separated. The aqueous phase was adjusted to pH 11 with 5M NaOH and extracted with EE (4×10 ml). The combined organic extracts were washed with 1M NaOH (2×3 ml), dried, filtered and concentrated. For the preparation of the hydrochloride, the resulting non-polar diastereoisomer of N-(4-dimethylamino-4-phenylcyclohexylmethyl)-2-(1H-indol-3-yl)propionamide (220 mg, 0.54 mmol.) was dissolved in 2-butanone; chlorotrimethylsilane (104 μl, 0.82 mmol.) was added thereto, and stirring was carried out for 1 h at RT. After 1 h at 4° C., the resulting precipitate was filtered off with suction, washed with cold 2-butanone (1 ml) and cold ether (2×1 ml) and dried in vacuo. The target compound was obtained in a yield of 168 mg (colourless solid, m.p. 163–168° C. with decomposition).

1. concentrationthe mixture was concentrated
2. customether (10 ml), and the phases were separated
3. extractionextracted with EE (4×10 ml)
4. washThe combined organic extracts were washed with 1M NaOH (2×3 ml)
5. customdried
6. filtrationfiltered
7. concentrationconcentrated
8. customFor the preparation of the hydrochloride
9. waitwas carried out for 1 h at RT
10. waitAfter 1 h at 4° C.
11. filtrationthe resulting precipitate was filtered off with suction
12. washwashed with cold 2-butanone (1 ml) and cold ether (2×1 ml)
13. customdried in vacuo
14. customThe target compound was obtained in a yield of 168 mg (colourless solid, m.p. 163–168° C. with decomposition)

ORD record

ord-26cc5f7d9a1e44df8fee5daf1b530e31

Source dataset

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07173045B2