2-pyrrolidin-1-ylphenol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from (2S)-3-[4-(2-bromo-ethoxy)-phenyl]-2-methoxy-propionic acid ethyl ester (Example 283, Step 2) and 2-pyrrolidin-1-yl-phenol via the same procedure used for the preparation of (2S)-2-methoxy-3-[4-(3-phenoxy-propoxy)-phenyl]-propionic acid (Example 285, Step 1), to produce a yellow oil. to produce a yellow oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In an analogous manner to the stepwise sequence outlined in intermediate 19, starting from 4,5-dichloro-2-(tetrahydropyran-2-yl)-2H-pyridazin-3-one (Intermediate 20) and 2-pyrrolidin-1-yl-phenol and alkylating with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10) afforded 3-cyclopentyl-2-[6-oxo-4-(2-pyrrolidin-1-yl-phenoxy)-6H-pyridazin-1-yl]propionic acid (9 g, 57%) as a yellow solid; LC-MS 398 [M+H+]; HPLC [acetonitrile (0.1% trifluoroacetic acid) in water (0.1% trifluoroacetic acid)=100%˜50%, gradient, 1 mL/min, Venusil MP-C18, C18-15 cm×4.6 mm-5 μm], 254 nm, 97%, 214 nm, 96%. 1H-NMR (300 MHz, CDCl3): δ 7.82 (s, 1H), 7.15 (t, J=7.2 Hz, 1H), 6.95 (d, J=7.5 Hz, 1H), 6.75-6.82 (m, 2H), 5.92 (s, 1H), 5.49 (s, 1H), 3.25 (s, 4H), 2.31 (s, 1H), 2.15 (s, 1H), 1.25-1.87 (m, 11H), 1.08-1.16 (m, 2H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a similar manner to that described in Reference Example 27, a reaction was carried out using 2-pyrrolidinophenol (1.88 g), t-butyl N-(5-chloro-2-nitrophenyl)-N-methylcarbamate (3.34 g), sodium hydride (55 wt. %, 0.52 g) and anhydrous N,N-dimethylformamide (22 ml) and the reaction mixture was purified to afford t-butyl N-[2-nitro-5-(2-pyrrolidinophenoxy)phenyl]-N-methylcarbamate, of which Rf value was 0.25 in thin layer chromatography on a silica gel plate using c-hexane/ethyl acetate=10/1. In a similar manner to that described in Reference Example 27, a reaction was carried out using this product, palladium on carbon (10%, 0.45 g) and toluene/methanol=7/3 (50 ml) and the reaction mixture was purified to give the title compound (3.0 g). the reaction mixture was purified

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a similar manner to that described in Reference Example 27, a reaction was carried out using 2-pyrrolidinophenol (1.88 g), t-butyl N-(5-chloro-2-nitrophenyl)-N-methylcarbamate (3.34 g), sodium hydride (55 wt. %, 0.52 g) and anhydrous N,N-dimethylformamide (22 ml) and the reaction mixture was purified to afford t-butyl N-[2-nitro-5-(2-pyrrolidinophenoxy)phenyl]-N-methylcarbamate, of which Rf value was 0.25 in thin layer chromatography on a silica gel plate using c-hexane/ethyl acetate=10/1. In a similar manner to that described in Reference Example 27, a reaction was carried out using this product, palladium on carbon (10%, 0.45 g) and toluene/methanol=7/3 (50 ml) and the reaction mixture was purified to give the title compound (3.0 g). the reaction mixture was purified

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from (2S)-3-[4-(2-bromo-ethoxy)-phenyl]-2-methoxy-propionic acid ethyl ester (Example 283, Step 2) and 2-pyrrolidin-1-yl-phenol via the same procedure used for the preparation of (2S)-2-methoxy-3-[4-(3-phenoxy-propoxy)-phenyl]-propionic acid (Example 285, Step 1), to produce a yellow oil. to produce a yellow oil