초록 ▼

This invention provides an improved process for the preparation of compounds of formula (I): [Figure] (I) wherein: n is 0, 1 or 2; each R1 is independently halo or lower alkyl; R2 is nitro or －N(R3)R4 where R3 is hydrogen or lower alkyl; R4 is hydrogen, lower alkyl, lower alkylsulfonyl or －C(Y)R5 wh

This invention provides an improved process for the preparation of compounds of formula (I): [Figure] (I) wherein: n is 0, 1 or 2; each R1 is independently halo or lower alkyl; R2 is nitro or －N(R3)R4 where R3 is hydrogen or lower alkyl; R4 is hydrogen, lower alkyl, lower alkylsulfonyl or －C(Y)R5 where Y is oxygen or sulfur and R5 is hydrogen, lower alkyl, lower alkoxy or －N(R6)R7 where R6 is hydrogen or lower alkyl and R7 is hydrogen, lower alkyl or lower alkoxycarbonyl; or R3 and R4 together with N is pyrrolidino, piperidino, morpholino, thiomorpholino or piperazino, wherein the piperazino is optionally substituted at the 4-position by －C(O)R8 where R8 is hydrogen, lower alkyl, lower alkoxy or amino; or pharmaceutically acceptable salts thereof. These compounds are useful in treating disease-states characterized by hypercholesterolemia.

대표청구항 ▼

A process for the preparation of compounds of formula (I): [Figure] (I) wherein: n is 0; R2 is －N(R3)R4 where R3 is hydrogen and R4 is hydrogen or －C(Y)R5 where Y is oxygen and R5 is methyl, or a pharmaceutically acceptable salt thereof; which process comprises the following steps: (1) reacting the

A process for the preparation of compounds of formula (I): [Figure] (I) wherein: n is 0; R2 is －N(R3)R4 where R3 is hydrogen and R4 is hydrogen or －C(Y)R5 where Y is oxygen and R5 is methyl, or a pharmaceutically acceptable salt thereof; which process comprises the following steps: (1) reacting the compound of formula (B): [Figure] (B) with a compound of formula (D): [Figure] (D) wherein R9 is tosylate, in the presence of methanesulfonic acid, to yield a mixture of stereoisomers represented by the following formula (E): [Figure] (E) wherein R9 is tosylate; (2) dissolving the mixture of stereoisomers represented by formula (E), as defined above, in a suitable solvent and treating the resulting solution with about 0.8 to about 1.0 molar equivalents of concentrated nitric acid to yield a compound of formula (Eb): [Figure] (Eb) wherein R9 is tosylate, as a precipitate; (3) treating the mother liquor resulting from the preparation of the compound of formula (Eb) with sodium hydroxide and then allowing the resulting mixture to crystallize from isopropanol to yield a compound of formula (Ea): [Figure] (Ea) wherein R9 is tosylate; (4) treating a compound of formula (Ea), as defined above, with a compound of formula (F): [Figure] (F) wherein n is 0; and R2 is －N(R3)R4 where R4 is hydrogen and R4 is hydrogen or －C(Y)R5 where Y is oxygen and R5 is methyl; in the presence of potassium carbonate to yield a compound of formula (I), as defined above. A process for separating a compound of formula (Ea): [Figure] (Ea) wherein R9 is halo, tosylate or mesylate, from a mixture of stereoisomers represented by the following formula (E): [Figure] (E) wherein R9 is halo, tosylate or mesylate; which process comprises the following steps: (a) dissolving the mixture of stereoisomers represented by formula (E), as defined above, in a suitable solvent and treating the resulting solution with about 0.5 to about 1.5 molar equivalents of concentrated nitric acid to yield a compound of formula (Eb): [Figure] (Eb) wherein R9 is halo, tosylate or mesylate, as a precipitate; (b) treating the mother liquor resulting from the preparation of the compound of formula (Eb) with a suitable base and allowing the resulting mixture to crystallize from a suitable solvent to yield a compound of formula (Ea), as defined above.