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US 6,297,380 B1Granted
Process and intermediates for growth hormone secretagogues
AssigneePfizer Inc.
InventorsCharles K. Chiu, David A. Griffith
Life of this patent
Estimating the term…
Abstract
This invention relates to a process for preparing compounds of the Formula I, wherein R1, R2 and Pt are as defined in the specification, which are intermediates in the synthesis of certain growth hormone secretagogue compounds. This invention further relates to processes for preparing the growth hormone secretagogues. The invention also relates to the compound of Formula I wherein R1 is H, R2 is 2,2,2-trifluoromethyl and Pt is Boc.
Claims15
A process for preparing a compound of Formula I,
- wherein
- R1 is —(CH2)q—A1;
- q is 1;
- R2 is methyl, ethyl or 2,2,2-trifluoroethyl;
- A1 is phenyl, pyridyl or thiazolyl;
- A1 is optionally substituted with one to three substituents, each substituent independently selected from the group consisting of F, Cl, OCF3, OCF2H, CF3, CH3, or OCH3;
- and
- Pt is an amine protecting group wherein Pt is tert-butyloxycarbonyl, benzyloxycarbonyl, or benzyl;
- comprising reacting a compound of Formula III,
- wherein Pt and R2 are as defined hereinabove,
- with an alkylating agent of formula R1—Z, wherein R1 is as defined hereinabove and Z is a leaving group, in the presence of a suitable base and a reaction inert solvent;
- Z in said alkylating agent is p-toluenesulfonyloxy, methanesulfonyloxy, Cl, Br or I;
- said base is alkaline metal bis(trimethylsilyl)amide or alkaline alkoxide;
- and said reaction inert solvent is N,N-dimethylformamide, tetrahydrofuran, toluene, isopropyl ether, MTBE or a mixture thereof.
11 more elements
A process for preparing a compound of Formula V,
- wherein
- R1 is —(CH2)q—A1;
- q is 1;
- R2 is methyl, ethyl or 2,2,2-trifluoroethyl;
- A1 is phenyl, pyridyl or thiazolyl;
- A1 is independently optionally substituted with one to three substituents, each substituent independently selected from the group consisting of F, Cl, OCF3, OCF2H, CF3, CH3, or OCH3;
- comprising reacting a compound of Formula I,
- wherein
- Pt is an amine protecting group and R1 and R2 are as defined hereinabove;
- with an acid in the presence of a reaction inert solvent;
- wherein said Pt is t-butyloxycarbonyl;
- said acid is methanesulfonic acid, trifluoroacetic acid or hydrochloric acid;
- and said reaction inert solvent is methylene chloride, methanol or ethanol.
10 more elements
A process of claim 7 wherein said benzyl is optionally substituted with up to two fluoro.
Dependencies are inferred from the claim text.