US 6,211,367 B1Granted

Methods of Synthesing Purine Compounds Having PDE Iv Inhibitory Activity

AssigneeEuro-Celtique S.A.

InventorsDavid J. Cavalla, Mark Chasin, Peter Hofer

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Abstract

The present invention comprises compounds having the general formula I: wherein: Y, is N or CH Z is selected from the group consisting of alkyl groups such as alkylene groups such as CH2, CH2CH2, CH(CH3); alkenyl groups such as CH═CH; alkynyl groups such as C≡C; and NH, N(C1-C3 alkyl), O, S, C(O)CH2 and OCH2; R1 and R2 are selected from the group consisting of hydrogen and a C1-C8 straight or branched alkyl or a C3-C8 cycloalkyl; R3 is a C3-C12 straight or branched alkyl; R4 is a C3-C10 cycloalkyl optionally substituted with OH or C3-C10 cycloalkenyl optionally substituted with OH; and R8 is a C1-C8 straight or branched alkyl or a C3-C8 cycloalkyl, optionally substituted with OH; and methods of synthesis.

Claims12

Dependent claims

A method of forming a compound having the formula I

wherein:
Y1 is N and Y2 is CH
Z is CH2;
R1 and R2 are independently selected from the group consisting of hydrogen and a C1-C8 straight or branched alkyl or a C3-C8 cycloalkyl;
R3 is a C1-C12 straight or branched alkyl;
R4is a C3-C10 cycloalkyl optionally substituted with OH, or a C3-C10 cycloalkenyl optionally substituted with OH;
and
R8 is a C1-C8 straight or branched alkyl or a C3-C8 cycloalkyl, optionally substituted with OH;
said method comprising the steps of;
(a) reacting a compound of the formula II
wherein X1 is a carboxamide and X2 is an amino group;
with the benzaldehyde of compound (III)
wherein R3 and R4 are as defined above;
followed by reduction of the resultant compound with a reducing agent to yield compound (IV)
wherein Z, X1, R3, R4 and R8 are as defined above;
(b) reacting compound (IV) with triethylorthoformate to cause cyclization to compound (V) as set forth below
wherein Y1, Y2, Z, R3, R4 and R8 are as defined above;
(c) transforming said compound (V) to an amine by successive halogenation with a halogenating agent and displacement of the resultant halogen with an amine of the formula NR1R2 wherein R1R2 are as defined above, to yield compound (I).

15 more elements

Dependencies are inferred from the claim text.