| 主权项 |
1. A process for producing aliskiren represented by the formula (I), comprising the following operations: A) converting (R)-2[4-methoxy-3-(3-methoxypropxy)benzyl]-3-methyl-butanal of formula (II) or a compound of formula (II′) into a beta-dicarbonyl compound of formula (V) by treatment with a beta-keto ester of formula (III): wherein R is selected from hydrogen, alkyl or alkyl-substituted, aryl or aryl-substituted; and Y is selected from: an —OR1 group, in which R1 has the same meanings above defined for R; radical (S)-4-benzyloxazolidin-2-on-3-yl; or radical 2-carbamoyl-2-methylpropylamino; and X is a leaving group; B) transforming the compound (V) into the intermediate of formula (VII): wherein P is selected from radicals hydrogen; acyl, R2C(O)—, in which R2 has the same meanings above defined for R; silyl, R33Si—, in which R3 has the same meanings above defined for R; and carbamoyl, R42NC(O)—, in which R4 has the same meanings above defined for R; C) transforming the intermediate (VII) into a cyclic carbamate or an amino-lactone, respectively represented by the formula (VIII) or (IX″), wherein W is hydrogen or —C(O)OR5 and in which R5 has the same meanings above defined for R: D) transforming the cyclic carbamate (VIII) or the amino-lactone (IX″) into aliskiren of formula (I) by reaction with 3-amino-2,2-dimethylpropanamide, of formula and subsequent hydrolysis of the cyclic carbamate or deprotection of the amino group. |
