REDUCTIVE ALKYLATION PROCESS FOR THE PREPARATION N-(2-(R)-HYDROXY-1-(S)-INDANYL)-2(R)-PHENYLMETHYL-4(S)-HYDROXY-5-(1-(4-(3-PYRIDYLMETHYL)-2(S)-N'-(T-BUTYLCARBOXAMIDO)-PIPERAZINYL))-PENTANEAMIDE (=COMPOUND J OR L-735,524)

摘要

1. A process for reductive alkylation for the preparation N-(2-(R)-hydroxyY-1-(S)-indanyl)-2(R)-phenylmethyl-4(S)-hydroxy-5-(1-(4-(3-pyrididylmethyl)-2(S)-N'-(t-butylcarboxamido)-piperazinyl))-pentaneamide having the structure: or hydrates thereof wherein reacting is carried out for at least 5 minutes in suitable solvent one equivalent of the compound having the structure: with excess 3-pyridine carboxaldehyde in the presence of excess reducing agent, at a temperature range of between about 78 degree C and about 90 degree C; 2. A process of Claim 1, wherein the suitable solvent is selected from an ester, an ether, an alcohol, a formamide, a hydrocarbon, and 1,2-dichloroethane, and any mixture of these solvents. 3. The process of Claim I, wherein the suitable solvent is selected from an ester and an alcohol or both. 4. The process of Claim 1, wherein the suitable solvent is selected from isopropyil acetate and ethyl acetate. 5. The process of Claim 1, wherein the reducing agent comprises a catalytic hydrogenation agent. 6. The process of Claim 1, wherein the reducing agent comprises a reducing agent selected from NaBH4, NaCNBH3, NaBH(OAc)3, Zn/HCl, Fe(CO)5/KOH-EtOH, formic acid and selenophenol. 7. The process of Claim 5 wherein the reducing agent comprises a reducing agent selected from NaCNBH3, NaBH(OAc)3 and formic acid. 8. The process of Claim 6, wherein the reducing agent comprises a reducing agent selected from NaBN(OAc)3 and formic acid. 9. The process of Claim 1, wherein the temperatures range of the reaction is carried out between about -40 degree C and about 70 degree C. 10. The process of Claim 8, wherein the temperatures range of the reaction is carried out between about 20 degree C and about 60 degree C. 11. The process of Claim 1, wherein reacting is carried out for at least 5 minutes in a solvent selected from isopropyl acetate and ethyl acetate, one equivalent of the compound having the structure: with between about one equivalent and about two equivalents of 3-pyridine carboxaldehyde in the presence of a reducing agent selected from NaBH(OAc)3 and formic acid the temperature range between about 20 degree C and about 60 degree C to give compound J or hydrate thereof. 12. A process 0f Claim 1, wherein mixing in a solvent selected from isopropyl acetate and ethyl acetate, one equivalent of a compound having the structure with between about one equivalent and about two equivalents of 3-pyridine carboxaldehyde; adding a reducing agent selected from NaBH(OAc)3 and formic acid, and maintaining for at least 5 minutes the resulting mixture at a temperature range between about 20 degree C to about 60 degree C to obtain a compound J or hydrate thereof.