2-morpholin-4-ylphenol

反応条件: temp:70.01; pressure:0.00; stir:

実験手順: Dilution of the aliquot (2 uL) with DMSO (200 uL).

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2.78 ml (16.4 mmol) of trifluoromethanesulphonic anhydride are slowly added dropwise to a solution, cooled to −10° C., of 2 g (10.9 mmol) of 2-(4-morpholinyl)-phenol and 4.57 ml (32.8 mmol) of triethylamine in 15 ml of dichloromethane. The mixture is stirred at −10° C. for 30 min and then at 0° C. for 30 min. It is washed successively with 10% strength sodium bicarbonate solution, water and saturated sodium chloride solution, dried over sodium sulphate and concentrated in vacuo, and the residue is dried under high vacuum. 3.48 g (87.6% of theory) of the title compound are obtained. at 0° C. for 30 min It is washed successively with 10% strength sodium bicarbonate solution, water and saturated sodium chloride solution dried over sodium sulphate concentrated in vacuo the residue is dried under high vacuum

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2.78 ml (16.4 mmol) of trifluoromethanesulphonic anhydride are slowly added dropwise to a solution, cooled to −10° C., of 2 g (10.9 mmol) of 2-(4-morpholinyl)-phenol and 4.57 ml (32.8 mmol) of triethylamine in 15 ml of dichloromethane. The mixture is stirred at −10° C. for 30 min and then at 0° C. for 30 min. It is washed successively with 10% strength sodium bicarbonate solution, water and saturated sodium chloride solution, dried over sodium sulphate and concentrated in vacuo, and the residue is dried under high vacuum. 3.48 g (87.6% of theory) of the title compound are obtained. at 0° C. for 30 min It is washed successively with 10% strength sodium bicarbonate solution, water and saturated sodium chloride solution dried over sodium sulphate concentrated in vacuo the residue is dried under high vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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-morpholin-4-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 colorless oil. to produce a colorless oil

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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-morpholin-4-yl-phenol and alkylating with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10) afforded 3-cyclopentyl-2-[4-(2-morpholin-4-yl-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid (8.5 g, 64%) as a white solid; LC-MS: 414 [M+H+]. HPLC: >99% (purity). 1H-NMR (300 MHz, DMSO-d6): δ 12.9 (s, 1H), 8.00 (s, 1H), 7.1-7.3 (m, 4H), 5.76 (s, 1H), 5.3 (m, 1H); 3.3 (m, 4H), 2.9 (m, 4H), 1.0-2.2 (m, 11H).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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-morpholin-4-yl-phenol and alkylating with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10) afforded 3-cyclopentyl-2-[4-(2-morpholin-4-yl-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid (8.5 g, 64%) as a white solid; LC-MS: 414 [M+H+]. HPLC: >99% (purity). 1H-NMR (300 MHz, DMSO-d6): δ 12.9 (s, 1H), 8.00 (s, 1H), 7.1-7.3 (m, 4H), 5.76 (s, 1H), 5.3 (m, 1H); 3.3 (m, 4H), 2.9 (m, 4H), 1.0-2.2 (m, 11H).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: By using 0.72 g of 2-(4-morpholino)phenol, 1.15 g of t-butyl N-(5-chloro-2-nitrophenyl)-N-methylcarbamate, 0.17 g of sodium hydride (55% by weight) and 10 ml of anhydrous N,N-dimethylformamide, reaction and purification were carried out in a similar manner to that described in Reference Example 6, whereby 1.44 g of the title compound were obtained.

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2.78 ml (16.4 mmol) of trifluoromethanesulphonic anhydride are slowly added dropwise to a solution, cooled to −10° C., of 2 g (10.9 mmol) of 2-(4-morpholinyl)-phenol and 4.57 ml (32.8 mmol) of triethylamine in 15 ml of dichloromethane. The mixture is stirred at −10° C. for 30 min and then at 0° C. for 30 min. It is washed successively with 10% strength sodium bicarbonate solution, water and saturated sodium chloride solution, dried over sodium sulphate and concentrated in vacuo, and the residue is dried under high vacuum. 3.48 g (87.6% of theory) of the title compound are obtained. at 0° C. for 30 min It is washed successively with 10% strength sodium bicarbonate solution, water and saturated sodium chloride solution dried over sodium sulphate concentrated in vacuo the residue is dried under high vacuum

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-morpholinophenol (100 mg, 0.56 mmol) and ethyl 2-bromoacetate (200 mg, 0.672 mmol) in CH3CN (10 mL) was added K2CO3 (772.8 mg, 5.6 mmol). The reaction mixture was stirred at 80° C. for 4 h. The solid was removed by filtration and the filtrate concentrated to give a crude material, which was used in the next step without further purification. (130 mg, Yield 90%). The solid was removed by filtration the filtrate concentrated

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-(2-methoxyphenyl)morpholine (200 mg, 1.02 mmol) in CH2Cl2 (20 mL) was added BBr3 (1 mL) at 0° C. The mixture was stirred for 2 h at 0° C. The mixture was then added drop wise to ice-water (50 mL) and the mixture treated with CH2Cl2 (2×20 mL). The combined organic layers were washed with brine (30 mL), dried over Na2SO4 and concentrated to give the yellow solid which was used in next step without further purification (165 mg Yield 80%). LCMS (m/z): 180.1 (M+1). The combined organic layers were washed with brine (30 mL) dried over Na2SO4 concentrated to give the yellow solid which was used in next step without further purification (165 mg Yield 80%)