甘氨酸叔丁酯 盐酸盐

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

实验步骤: tert-Butyl 2-(5-hydroxy-8-methyl-7-oxo-3-(piperidin-1-yl)-7,8-dihydropyrido[2,3-c]pyridazine-6-carboxamido)acetate. The title compound is prepared by reaction of methyl 5-hydroxy-8-methyl-7-oxo-3-(piperidin-1-yl)-7,8-dihydropyrido[2,3-c]pyridazine-6-carboxylate and tert-butyl 2-aminoacetate hydrochloride according to Method 3(a).

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

实验步骤: tert-Butyl 2-(5-hydroxy-3-methoxy-8-methyl-7-oxo-7,8-dihydropyrido[2,3-c]pyridazine-6-carboxamido)acetate. The title compound is prepared from methyl 5-hydroxy-3-methoxy-8-methyl-7-oxo-7,8-dihydropyrido[2,3-c]pyridazine-6-carboxylate and tert-butyl 2-aminoacetate hydrochloride according to Method 3(a).

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

实验步骤: To a solution of 4-chloro-3-nitrobenzonitrile (33.87 g) and glycine tert-butyl ester hydrochloride (55.98 g) in ethanol (400 ml) was added triethylamine (77.6 ml), and the mixture was stirred at room temperature for 15 hours and then at 50° C. for 3 hours. After completion of the reaction, the solvent was evaporated and the obtained residue was extracted with ethyl acetate. The extract was washed with 10% aqueous citric acid solution and saturated brine. The organic layer was dried over anhydrous magnesium sulfate and the solvent was evaporated. The obtained residue was washed with diisopropyl ether and collected by filtration to give the title compound (38.419 g). at 50° C. for 3 hours After completion of the reaction the solvent was evaporated the obtained residue was extracted with ethyl acetate The extract was washed with 10% aqueous citric acid solution and saturated brine The organic layer was dried over anhydrous magnesium sulfate the solvent was evaporated The obtained residue was washed with diisopropyl ether collected by filtration

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

实验步骤: Starting from 1-(4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-(4-oxopiperidin-1-yl)-1,3,5-triazin-2-yl)phenyl)-3-(pyridin-4-yl)urea.TFA (60 mg) and glycine tert-butyl ester hydrochloride (33 mg) and triethylamine (10 drops) and following the procedure as outlined in example 118, the title compound was isolated as its di-TFA salt after HPLC purification; MS (ES+) 616.9 (M+H)+.

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

实验步骤: A solution of glycine tert-butyl ester hydrochloride (300 mg, 1.79 mmol) (Aldrich), Et3N (250 μL, 1.79 mmol), and 4-(fluorosulfonyl)benzoyl chloride (400 mg, 1.79 mmol) (Aldrich) in 9 mL of dry N,N-dimethylformamide was stirred at room temperature under a nitrogen atmosphere for 12 h. The reaction mixture was diluted with ethyl acetate. The organic phase was washed with distilled water, dried over sodium sulfate, filtered, and concentrated in vacuo to provide crude (4-fluorosulfonyl-benzoylamino)-acetic acid tert-butyl ester (541 mg, 95%) as an oil that solidified upon sitting at room temperature. The crude (4-fluorosulfonyl-benzoylamino)-acetic acid tert-butyl ester was used without further purification. The organic phase was washed with distilled water dried over sodium sulfate filtered concentrated in vacuo

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

实验步骤: To a mixture of glycine t-butyl ester hydrochloride (0.84 g, 5 mmol), and 4-benzyloxy-benzaldehyde (0.53 g, 2.5 mmol) in CH2Cl2 (25 mL) at 0° C. was added sodium triacetoxyborohydride (0.81 g, 3.8 mmol). The mixture was allowed to warm to room temperature and stirred overnight. Aqueous NaHCO3 was added, and the mixture was stirred for 30 minutes. The aqueous layer was extracted 3 times with CH2Cl2. The combined organic extracts were washed with brine, dried over MgSO4, and concentrated. Flash chromatography (ethyl acetate) gave 0.38 g (59%) of the title compound as a white solid. the mixture was stirred for 30 minutes The aqueous layer was extracted 3 times with CH2Cl2 The combined organic extracts were washed with brine dried over MgSO4 concentrated

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

实验步骤: 4-Nitrobenzenesulfonyl chloride (46.3 g) was added to a solution of glycine t-butyl ester hydrochloride (35 g) in pyridine (200 ml). The mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated. The residue was washed with water and then a mixture of hexane and ethyl acetate (9:1) and dried to give the title compound (61.4 g) having the following physical data. The reaction mixture was concentrated The residue was washed with water a mixture of hexane and ethyl acetate (9:1) dried

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

实验步骤: To a solution of 2-[1-(4-(ethoxycarbonyl)piperazin-1-yl)carbonyl-3-carboxypropyl]aminocarbonyl-4-methoxyquinoline (142 mg, 0.30 mmol) in tetrahydrofuran (THF) (5 mL) was added glycine t-butyl ester hydrochloride (44 mg, 0.33 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCl) (64 mg, 0.33 mmol), 1-hydroxybenzotriazole (HOBT) (45 mg, 0.33 mmol) and diisopropylethylamine (DIEA) (0.43 g, 0.33 mmol). The reaction was stirred at ambient temperature overnight. The resultant solution was partitioned between water and ethyl acetate. The organic layer was concentrated in vacuo to afford an oil. The crude product was purified by elution through silica gel with 20:1 methylene chloride-methanol to afford 2-[1-(4-(ethoxycarbonyl)piperazin-1-yl)carbonyl-3-(((1,1-dimethylethoxycarbonyl)methyl)aminocarbonyl)propyl]aminocarbonyl-4-methoxyquinoline (62 mg, 35%); NMR (CDCl3) 1.25 (t, 3), 1.50 (s, 9), 2.00 (m, 1), 2.15–2.50 (m, 3), 3.31–3.95 (m, 9), 4.10–4.32 (m, 7), 5.40 (m, 1), 759 (t, 1), 7.63 (s, 1), 7.75 (t, 1), 8.14 (d, 1), 8.22 (d, 1), 9.41 (d, 1) ppm. The resultant solution was partitioned between water and ethyl acetate The organic layer was concentrated in vacuo to afford an oil The crude product was purified by elution through silica gel with 20:1 methylene chloride-methanol

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 glycine tert-butylester hydrochloride instead of 3-methoxypropylamine, to the title compound (111 mg, 81%) which was obtained as an off white foam. MS: m/e=424.3 [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 glycine tert-butylester hydrochloride instead of 3-methoxypropylamine, to the title compound (111 mg, 81%) which was obtained as an off white foam. MS: m/e=424.3 [M+H]+.

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

实验步骤: Sodium cyanoborohydride(1.9 g) was added portionwise to a stirred mixture of cyclopentanone(2.1 g), glycine tert-butyl ester hydrochloride(5.0 g), water(12 ml) and methanol(25 ml) during 15 min at water-bath temperature. The resulting mixture was stirred for 4 hr, diluted with 20% H3PO4 (40 ml) and water(20 ml), and extracted with ether(80 ml). The aqueous layer was made alkaline(pH 10) with 20% NaOH and extracted with CHCl3 (50 ml). The extract was dried(Na2SO4) and concentrated in vacuo to give an oily residue, which was purified by silica gel column chromatography(ethyl acetate:hexane=3:1) to yield N-cyclopentylglycine tert-butyl ester(4.5 g) as a pale yellow oil. extracted with ether(80 ml) extracted with CHCl3 (50 ml) concentrated in vacuo to give an oily residue, which was purified by silica gel column chromatography(ethyl acetate:hexane=3:1)

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

实验步骤: 14.4 ml of triethylamine are added dropwise to 6.91 g of glycine t-butyl ester hydrochloride and 12.1 g of 2-naphthylsulfonyl chloride in 70 ml of methylene chloride. The reaction mixture is subsequently diluted with 200 ml of ether. The organic phase is washed with 1N hydrochloric acid and with water. After drying and evaporation the residue is suspended in ether and suction filtered. After drying the crystals there are obtained 11.57 g of N-(2-naphthylsulfonyl)-glycine t-butyl ester, Rf=0.49 (ether/hexane 2:1). The organic phase is washed with 1N hydrochloric acid and with water After drying evaporation the residue suction filtered After drying the crystals