US 2004/0002609 A1 · Synthesis of 3,3,4,4-tetrafluoropyrrolidine and novel dipeptidyl peptidase-IV inhibitor compounds

Abstract

The present invention relates to a method of making novel dipeptidyl peptidase-IV (“DPP-IV’) inhibitor compounds useful for treating, inter alia, diseases that are associated with proteins that are subject to processing by DPP-IV, such as Type 2 diabetes mellitus, metabolic syndrome (Syndrome X or insulin resistance syndrome), hyperglycemia, impaired glucose tolerance, glucosuria, metabolic acidosis, cataracts, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, Type 1 diabetes, obesity, hypertension, hyperlipidemia, atherosclerosis, osteoporosis, osteopenia, frailty, bone loss, bone fracture, acute coronary syndrome, infertility due to polycystic ovary syndrome, short bowel syndrome and to prevent disease progression in Type 2 diabetes. The invention also relates to a method of making 3,3,4,4-tetrafluoropyrrolidine, a starting material utilized in the afore-mentioned method for preparing DPP-IV compounds.

Claims39

Dependent claims

A process for preparing a compound of Formula I,

8
wherein R7 is (c1-C8)alkyl or (c3-C8)cycloalkyl, comprising:
(a) treating an N-protected amino acid of the formula II,
9
wherein R7 is (C1-C8)alkyl or (C3-C8)cycloalkyl and R10 is a nitrogen-protecting group, with a base and 2,2,3,3,-tetrafluoropyrrolidine hydrochloride in the presence of a coupling agent to form a coupled amino acid intermediate;
and
(b) deprotecting the coupled amino acid intermediate to form a compound of Formula I.

4 more elements

Dependencies are inferred from the claim text.

Synthesis of 3,3,4,4-tetrafluoropyrrolidine and novel dipeptidyl peptidase-IV inhibitor compounds

Life of this patent

Synthesis of 3,3,4,4-tetrafluoropyrrolidine and novel dipeptidyl peptidase-IV inhibitor compounds

Life of this patent

Abstract

Claims39