Azetidinyloxyphenylpyrrolidine compounds

Abstract

The invention provides certain azetidinyloxyphenylpyrrolidine compounds, particularly compounds of formula I wherein R is hydrogen or methyl, and pharmaceutical compositions thereof. The invention further provides methods of using a compound of formula I to treat overactive bladder. ##STR00001##

Claims

1. A compound of the formula ##STR00014## wherein R is hydrogen or methyl.

2. The compound of claim 1 which is (1R)-1-[(3S,4S)-1-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]carbony}-4-(4-methoxy-3-{[1-(5-methylpyridin-2-yl)azetidin-3-yl]oxy}phenyl)-3-methylpyrrolidin-3-yl]ethanol which can be structurally represented by the formula ##STR00015##

3. A process for preparing a compound of the formula ##STR00016## wherein R is hydrogen or methyl; comprising reacting a compound of the formula ##STR00017## wherein R is hydrogen or methyl; with an acid selected from the group consisting of hydrochloric acid and acetic acid.

4. The process according to claim 3 wherein the acid is hydrochloric acid.

Description

Example 1

Synthesis of (2S)-3-[(3S,4S)-3-[(1R)-1-hydroxyethyl]-4-{4-methoxy-3-[(1-pyridin-2-ylazetidin-3-yl)oxy]phenyl}-3-methylpyrrolidin-1-yl]-3-oxopropane-1,2-diol

(1) ##STR00012##

(2) To a solution of (1R)-1-[(3S,4S)-1-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]carbonyl}-4-(4-methoxy-3-{[1-pyridin-2-ylazetidin-3-yl]oxy}phenyl)-3-methylpyrrolidin-3-yl]ethanol (22.1 mg) in tetrahydrofuran (2 mL) is added aqueous 1.0 M HCl (1 mL). Stir overnight at room temperature. Add aqueous 1.0 M HCl (1 mL) and stir for additional 8 hours. Neutralize with aqueous 1.0 M NaOH, extract with ethyl acetate, dry and evaporate to provide the title compound (18.2 mg). MS (ES+)=472 (M+1).

Example 2

Synthesis of (2S)-3-[(3S,4S)-3-[(1R)-1-hydroxyethyl]-4-(4-methoxy-3-{[1-(5-methylpyridin-2-yl)azetidin-3-yl]oxy}phenyl)-3-methylpyrrolidin-1-yl]-3-oxopropane-1,2-diol

(3) ##STR00013##

(4) The title compound is prepared essentially by the method of Example 1. MS (ES+)=486 (M+1).