Process for the production of tert-butyl (E)-(6-[2-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]vinyl](4R,6S)-2, 2-dimethyl[1, 3]dioxan-4-yl)acetate
AssigneeAstraZeneca AB
InventorsNigel P Taylor, Loius J Diorazio, Haruo Koike, Mikio Kabaki
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Abstract
The invention concerns a process for the manufacture of tert-butyl (E)-(6-[2-4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]vinyl)-(4R, 6S)-2,2-dimethyl(1,3-dioxan-4-yl) acetate, the novel starting material used in said process and the use of the process in the manufacture of a pharmaceutical.
Claims11
A compound of the Formula VI
- wherein
- P1 and P2 are
- alcohol protecting groups, or
- P1 and P2, taken together, form a 1,3-diol protecting group;
- and
- P3 is
- a carboxylic acid protecting group.
A process for the manufacture of a compound of the Formula IV
- in which R1 is hydrogen or a pharmaceutically acceptable cation which comprises
- (1) cleavage of the P1 and P2 alcohol or 1,3-diol protecting groups from a compound of Formula VI;
- (2) cleavage of the P3 carboxylic acid protecting group from the product of step (1) to form a compound of the Formula IV in which R1 is a pharmaceutically acceptable cation;
- optionally followed by neutralization to give a compound of the Formula IV in which R1 is hydrogen;
- and/or optionally followed by conversion to another compound of the Formula IV which R1 is a pharmaceutically acceptable cation.
A process for the manufacture of a compound of the formula III
- which comprises:
- (1) reaction of an alkyl 4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)axnino]pyrimidine5carboxylate with a reducing agent;
- (2) reaction of the product of step (1) with a halogenating agent;
- (3) reaction of the product of step (2) with an alkyldiarylphosphinite.
A process for the manufacture of methyl 4-(4-fluorophenyl)-6-isopropyl-2-[(methyl(methylsulfonyl)amino)pyrimidine-5-carboxylate which comprises:
- (1) reaction of methyl 2-amino-4-(4-fluorophenyl)-6-isopropyl-pyrimidine-5-carboxylate with methanesulfonyl chloride in the presence of strong base;
- and
- (2) reaction of the product of step (1) with a methylating agent in the presence of strong base.
Dependencies are inferred from the claim text.