D,L-丙氨酸乙酯盐酸盐

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: As described for example 15, 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (100 mg, 0.32 mmol) was converted, using DL-alanine ethylester hydrochloride instead of 3-methoxypropylamine, to the title compound (23 mg, 17%) which was obtained as a light yellow gum. MS: m/e=410.1 [M+H]+.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: As described for example 15, 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (100 mg, 0.32 mmol) was converted, using DL-alanine ethylester hydrochloride instead of 3-methoxypropylamine, to the title compound (23 mg, 17%) which was obtained as a light yellow gum. MS: m/e=410.1 [M+H]+.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Example 224 was prepared in a similar manner as described for the preparation of Example 221 with the exceptions that 2-aminobutyric acid methyl ester hydrochloride was substituted for DL-alanine ethyl ester hydrochloride in Step 1, 4-chlorobenzoic acid was substituted for 3-chlorobenzoic acid in Step 2, and 4-(4-chlorophenyl)-4-hydroxypiperidine was substituted for 4-(4-chlorophenyl)piperidine hydrochloride in Step 4. Example 224 was provided by elimination during Step 5. MS found: (M+H)+=417. Example 224 was prepared in a similar manner Example 224 was provided by elimination during Step 5

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of 4-chloro-5,6,7,8-tetrahydroquinazoline-2-ylamine (100 mg, 0.545 mmol), triethylamine (221 mg, 2.18 mmol) and dimethylformamide (4 ml) was added 2-aminopropionic acid ethyl ester hydrochloride (167 mg, 1.09 mmol) at room temperature. After the mixture was stirred for 2.5 hours at 100° C., the reaction mixture was poured into water and extracted with chloroform. The organic layer was washed with saturated brine, dried over sodium sulfate, filtered and the solvent in the filtrate was removed in vacuo. The residue was purified by silica gel chromatography (5% MeOH/CHCl3) to give the object compound (42.1 mg, 29.3%). extracted with chloroform The organic layer was washed with saturated brine dried over sodium sulfate filtered the solvent in the filtrate was removed in vacuo The residue was purified by silica gel chromatography (5% MeOH/CHCl3)

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of 4-chloro-5,6,7,8-tetrahydroquinazoline-2-ylamine (100 mg, 0.545 mmol), triethylamine (221 mg, 2.18 mmol) and dimethylformamide (4 ml) was added 2-aminopropionic acid ethyl ester hydrochloride (167 mg, 1.09 mmol) at room temperature. After the mixture was stirred for 2.5 hours at 100° C., the reaction mixture was poured into water and extracted with chloroform. The organic layer was washed with saturated brine, dried over sodium sulfate, filtered and the solvent in the filtrate was removed in vacuo. The residue was purified by silica gel chromatography (5% MeOH/CHCl3) to give the object compound (42.1 mg, 29.3%). extracted with chloroform The organic layer was washed with saturated brine dried over sodium sulfate filtered the solvent in the filtrate was removed in vacuo The residue was purified by silica gel chromatography (5% MeOH/CHCl3)

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of 4-chloro-5,6,7,8-tetrahydroquinazoline-2-ylamine (100 mg, 0.545 mmol), triethylamine (221 mg, 2.18 mmol) and dimethylformamide (4 ml) was added 2-aminopropionic acid ethyl ester hydrochloride (167 mg, 1.09 mmol) at room temperature. After the mixture was stirred for 2.5 hours at 100° C., the reaction mixture was poured into water and extracted with chloroform. The organic layer was washed with saturated brine, dried over sodium sulfate, filtered and the solvent in the filtrate was removed in vacuo. The residue was purified by silica gel chromatography (5% MeOH/CHCl3) to give the object compound (42.1 mg, 29.3%). extracted with chloroform The organic layer was washed with saturated brine dried over sodium sulfate filtered the solvent in the filtrate was removed in vacuo The residue was purified by silica gel chromatography (5% MeOH/CHCl3)

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of 4-chloro-5,6,7,8-tetrahydroquinazoline-2-ylamine (100 mg, 0.545 mmol), triethylamine (221 mg, 2.18 mmol) and dimethylformamide (4 ml) was added 2-aminopropionic acid ethyl ester hydrochloride (167 mg, 1.09 mmol) at room temperature. After the mixture was stirred for 2.5 hours at 100° C., the reaction mixture was poured into water and extracted with chloroform. The organic layer was washed with saturated brine, dried over sodium sulfate, filtered and the solvent in the filtrate was removed in vacuo. The residue was purified by silica gel chromatography (5% MeOH/CHCl3) to give the object compound (42.1 mg, 29.3%). extracted with chloroform The organic layer was washed with saturated brine dried over sodium sulfate filtered the solvent in the filtrate was removed in vacuo The residue was purified by silica gel chromatography (5% MeOH/CHCl3)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of DL-alanine ethyl ester hydrochloride (913 mg, 5.9 mmol) in DCE (15 mL) was added TEA (1.2 mL, 8.8 mmol) followed by benzaldehyde (0.538 mL), 5.3 mmol) and Na(OAc)3BH (2.0 g, 9.4 mmol). The mixture was stirred at room temperature overnight and then quenched with saturated aqueous NaHCO3 solution. The layers were separated and the aqueous layer extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. Chromatography on SiO2 eluting EtOAc/Hex afforded the desired compound as a colorless liquid (798 mg, 73%). MS (ESI) mass calcd. C12H17NO2, 207.1. m/z found 208.2 [M+H]+. 1H NMR (500 MHz, CDCl3): 7.39-7.23 (m, 5H), 4.23-4.16 (m, 2H), 3.83-3.65 (m, 2H), 3.37 (q, J=7.0 Hz, 1H), 1.34-1.27 (m, 6H). quenched with saturated aqueous NaHCO3 solution The layers were separated the aqueous layer extracted with DCM The combined organic layers were dried over Na2SO4 filtered concentrated in vacuo Chromatography on SiO2 eluting EtOAc/Hex

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: As described for example 15, 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (100 mg, 0.32 mmol) was converted, using DL-alanine ethylester hydrochloride instead of 3-methoxypropylamine, to the title compound (23 mg, 17%) which was obtained as a light yellow gum. MS: m/e=410.1 [M+H]+.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: As described for example 15, 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (100 mg, 0.32 mmol) was converted, using DL-alanine ethylester hydrochloride instead of 3-methoxypropylamine, to the title compound (23 mg, 17%) which was obtained as a light yellow gum. MS: m/e=410.1 [M+H]+.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: As described for example 15, 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (100 mg, 0.32 mmol) was converted, using DL-alanine ethylester hydrochloride instead of 3-methoxypropylamine, to the title compound (23 mg, 17%) which was obtained as a light yellow gum. MS: m/e=410.1 [M+H]+.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: According to the procedure of Example 20, 1.00 g (6.51 mmol) of D,L-alanine ethyl ester hydrochloride reacted with 1.75 g (7.16 mmol) of 4-but-2-ynyloxy-benzenesulfonyl chloride to provide 1.22 g (58%) of the sulfonamide as a white solid. Electrospray Mass Spec: 325.9 (M+H)+