Patent CA-1243313-A (CA)
Inventor: JONES ROBERT L
IPC: C07C59/62
Filed: 1985-10-18
Granted: 1988-10-18
Abstract: ABSTRACT PROSTAGLANDINS A process for the preparation of a compound of formula (I) (I)   wherein represents one of the cyclic groups shown below:-    the letters a and b indicating in each case the points of attachment of the substituents R1 and Z, respectively;  R1 is a 6-carboxyhex-2-enyl group or a modification thereof in which the group is altered by one, or an appropriate combination of two or more, of the follow-ing:  (a) alteration of the position of the double bond, (b) reduction of the double bond optionally accompanied by replacement of a methylene group at any of positions 1 to 5 by an oxygen or sulphur atom, (c) alteration of the chain length through a decrease or an increase of one or two methylene groups, and (d) formation of an amide, ester or salt derivative of the carboxy group;  and Z is either (a) a group ANHR2 in which A is an aliphatic hydrocarbon group with a chain length between the points of attachment to the divalent cyclic group and to the group NHR1 of 1 to 5 carbon atoms or such a group substituted by an aromatic group Ar, where Ar represents a phenyl, napthyl, fluorenyl, dibenzocyclohexyl, dibenzocycloheptyl, pyridyl, benzthiazolyl, dihydrobenzthiazolyl, N-methyldihydrobenzthiazolyl, benzoxazolyl, dihydrobenzoxazolyl or N-methyldihydrobenzoxazolyl group or such a group substituted by one or more substituents selected from C1-10 alkoxy, halogen, C1-10 halogen-substituted alkyl, sulphamoyl, amino, hydroxyl, nitro and C1-10 alkyl groups;  and R2 is hydrogen, a C1-10 aliphatic hydrocarbon group, a group or or a C1-10 aliphatic hydrocarbon group substituted by one or more groups Ar;  or (b) a group B'=O in which B' is a saturated aliphatic hydrocarbon group with a chain length between the points of attachment to the divalent cyclic group and to the oxygen atom of 2 to 5 carbon atoms or such a group substituted on the carbon atom attached to the divalent cyclic group, or in a branch formed at said carbon atom from the chain of carbon atoms linking the divalent cyclic group and the oxygen atom, by a group Ar;  comprises reacting a compound of formula (II)                            (II) in which Y represents R1 or a precursor therefor, X is as defined for (I), and W represents (a) a group B=O wherein B is a trivalent aliphatic hydrocarbon group corresponding to the divalent group A but with the replacement by a free valency of a hydrogen atom attached to that carbon atom of the group A which is nitrogen-bonded, or a group ANH2 in which A is as defined for (I); or (b) a group CHO or CR"'O in which R"' represents a C1-10 aliphatic hydrocarbon group, a group Ar or a C1-10 aliphatic hydrocarbon group substituted by a group Ar;  the said reaction consisting of (a) reductive amination of the group B=O to form a group ANHR2  in which R2 is hydrogen, or treatment of the group B=O with an amine R2NH2 or alkylation of the group ANH2 by a C1-10 alkyl group to form a group ANHR2 in which R2 is other than hydrogen;  or (b) chain extension of the group CHO or CR"'O to form a group B'=O;  and where appropriate converting the group Y in the resultant product into the group R1 of compound (I).  The compounds prepared by this process are of value for the production of biologically active prostaglandin compounds.