methyl 7-aminoheptanoate;hydrochloride

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

実験手順: The procedure described in Example 1 was repeated, except that dihydropyran (1.93 ml) and methyl 7-aminoheptanate hydrochloride (1.679 g) were successively reacted with (RS)-2-(4-chlorobenzenesulfonylamino)-3-hydroxypropanoic acid (2 g) to obtain (RS)-2-(4-chlorobenzenesulfonylamino)-N-(6-methoxycarbonylhexyl)-3-(tetrahydropyran-2-yloxy)propanamide (1. 497 g).

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

実験手順: The procedure described in Example 1 was repeated, except that dihydropyran (1.93 ml) and methyl 7-aminoheptanate hydrochloride (1.679 g) were successively reacted with (RS)-2-(4-chlorobenzenesulfonylamino)-3-hydroxypropanoic acid (2 g) to obtain (RS)-2-(4-chlorobenzenesulfonylamino)-N-(6-methoxycarbonylhexyl)-3-(tetrahydropyran-2-yloxy)propanamide (1. 497 g).

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

実験手順: A solution of 72 mg (0.18 mmol) of cyclopentyl{4-[(5-oxo-2-phenyl-5,6-dihydro-4H-1,3,4-oxa-diazin-4-yl)methyl]phenyl}acetic acid (enantiomer 2), 30 mg (0.15 mmol) of methyl 7-amino-heptanoate hydrochloride, 87 mg (0.23 mmol) of HATU and 0.8 ml of pyridine in 3.2 ml of DMF was stirred at room temperature overnight. After the reaction had ended, the mixture was poured into ice-water, the phases were separated and the aqueous phase was extracted three times with tert-butyl methyl ether. The combined organic phases were dried over sodium sulfate, and, after filtration, the solvent was removed to dryness under reduced pressure. The crude product obtained was purified by preparative RP-HPLC. This gave 13 mg (0.02 mmol, 13% of theory) of the title compound as a colorless oil. the phases were separated the aqueous phase was extracted three times with tert-butyl methyl ether The combined organic phases were dried over sodium sulfate after filtration the solvent was removed to dryness under reduced pressure

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

実験手順: Following the procedure described in Step A of Example 68, reductive amination of 4-butyl-benzaldehyde (1.50 g, 9.26 mmol) with 7-aminoheptanoic methyl ester hydrochloride (1.51 g, 7.72 mmol) provided the title compound (955 mg). 1H NMR (300 MHz, CDCl3) δ 7.29 (d, 2H), 7.16 (d, 2H), 3.85 (s, 2H), 3.67 (s, 3H), 3.54 (m, 1H), 2.70 (t, 2H), 2.59 (t, 2H), 2.29 (t, 2H), 1.60 (m, 6H), 1.32 (m, 6H), 0.92 (t, 3H); MS 306 (M+1).

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

実験手順: Following the procedure described in Step A of Example 68, reductive amination of 4-butyl-benzaldehyde (1.50 g, 9.26 mmol) with 7-aminoheptanoic methyl ester hydrochloride (1.51 g, 7.72 mmol) provided the title compound (955 mg). 1H NMR (300 MHz, CDCl3) δ 7.29 (d, 2H), 7.16 (d, 2H), 3.85 (s, 2H), 3.67 (s, 3H), 3.54 (m, 1H), 2.70 (t, 2H), 2.59 (t, 2H), 2.29 (t, 2H), 1.60 (m, 6H), 1.32 (m, 6H), 0.92 (t, 3H); MS 306 (M+1).

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

実験手順: Following the procedure described in Step A of Example 68, reductive amination of 4-butyl-benzaldehyde (1.50 g, 9.26 mmol) with 7-aminoheptanoic methyl ester hydrochloride (1.51 g, 7.72 mmol) provided the title compound (955 mg). 1H NMR (300 MHz, CDCl3) δ 7.29 (d, 2H), 7.16 (d, 2H), 3.85 (s, 2H), 3.67 (s, 3H), 3.54 (m, 1H), 2.70 (t, 2H), 2.59 (t, 2H), 2.29 (t, 2H), 1.60 (m, 6H), 1.32 (m, 6H), 0.92 (t, 3H); MS 306 (M+1).

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

実験手順: The procedure described in Example 1 was repeated, except that dihydropyran (1.93 ml) and methyl 7-aminoheptanate hydrochloride (1.679 g) were successively reacted with (RS)-2-(4-chlorobenzenesulfonylamino)-3-hydroxypropanoic acid (2 g) to obtain (RS)-2-(4-chlorobenzenesulfonylamino)-N-(6-methoxycarbonylhexyl)-3-(tetrahydropyran-2-yloxy)propanamide (1. 497 g).

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

実験手順: A solution of 72 mg (0.18 mmol) of cyclopentyl{4-[(5-oxo-2-phenyl-5,6-dihydro-4H-1,3,4-oxa-diazin-4-yl)methyl]phenyl}acetic acid (enantiomer 2), 30 mg (0.15 mmol) of methyl 7-amino-heptanoate hydrochloride, 87 mg (0.23 mmol) of HATU and 0.8 ml of pyridine in 3.2 ml of DMF was stirred at room temperature overnight. After the reaction had ended, the mixture was poured into ice-water, the phases were separated and the aqueous phase was extracted three times with tert-butyl methyl ether. The combined organic phases were dried over sodium sulfate, and, after filtration, the solvent was removed to dryness under reduced pressure. The crude product obtained was purified by preparative RP-HPLC. This gave 13 mg (0.02 mmol, 13% of theory) of the title compound as a colorless oil. the phases were separated the aqueous phase was extracted three times with tert-butyl methyl ether The combined organic phases were dried over sodium sulfate after filtration the solvent was removed to dryness under reduced pressure

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

実験手順: A solution of 7-amino-heptanoic acid (3.0 g, 21.0 mmol), in 25 mL MeOH and 2.4 mL concentrated HCl was heated at reflux for 4 hours and was stirred at room temperature for 60 h. The mixture was concentrated in vacuo to afford the title compound (3.3 g). 1H NMR (400 MHz, CD3OD) δ 3.62 (s, 3H), 2.89 (m, 2H), 2.31 (t, 2H), 1.62 (m, 4H), 1.37 (m, 4H). at reflux for 4 hours The mixture was concentrated in vacuo

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

実験手順: The title compound of Step A was prepared from 7-amino-heptanoic acid methyl ester hydrochloride, of Preparation 1, and 4-pyrazin-2-yl-benzaldehyde, of Preparation 27, using the method described in Example 1, Step A. 1H NMR (400 MHz, CDCl3) δ 9.01 (d, 1H), 8.61 (m, 1H), 8.48 (d, 1H), 7.97 (d, 2H), 7.46 (d, 2H), 3.85 (s, 2H), 3.65 (s, 3H), 2.63 (t, 2H), 2.29 (t, 2H), 1.62 (m, 2H), 1.54 (m, 2H), 1.33 (m, 4H); MS 328 (M+1).

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

実験手順: The title compound of Step A was prepared from 7-amino-heptanoic acid methyl ester hydrochloride, of Preparation 1, and 4-thiazol-2-yl-benzaldehyde, of Preparation 25, using the method described in Example 1, Step A. 1H NMR (400 MHz, CDCl3) δ 7.91 (d, 2H), 7.84 (d, 1H), 7.38 (d, 2H), 7.30 (d, 1H), 3.82 (s, 2H), 3.65 (s, 3H), 2.62 (t, 2H), 2.29 (t, 2H), 1.61 (m, 2H), 1.51 (m, 2H), 1.33 (m, 4H); MS 333 (M+1).

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

実験手順: The title compound of Step A was prepared from 7-amino-heptanoic acid methyl ester hydrochloride, of Preparation 1, and 4-pyrimidin-2-yl-benzaldehyde, of Preparation 21, using the method described in Example 1, Step A. 1H NMR (400 MHz, CDCl3) δ 8.78 (d, 2H), 8.37 (d, 2H), 7.42 (d, 2H), 7.16 (t, 1H), 3.85 (s, 2H), 3.64 (s, 3H), 2.62 (t, 2H), 2.28 (t, 2H), 1.55 (m, 4H), 1.32 (m, 4H); MS 328 (M+1).