ethyl 3-aminobutanoate

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

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

Procedure: Triethylamine (12.8 mL, 91.8 mmol) was added to a solution of 4-chloro-3-nitroquinoline (8.0 g, 38 mmol) in DMF (100 mL). The resulting solution was stirred for five minutes at room temperature, and then ethyl 3-aminobutyrate (6.2 mL, 42 mmol) was added. The reaction was stirred overnight at room temperature and poured into deionized water (320 mL). The mixture was extracted with ethyl acetate (1×125 mL and 2×100 mL). The combined extracts were washed with brine (3×120 mL), dried over magnesium sulfate, filtered through a layer of CELITE filter agent, concentrated under reduced pressure, and further dried under high vacuum to provide 11.5 g of ethyl 3-[(3-nitroquinolin-4-yl)amino]butanoate as a yellow solid. The reaction was stirred overnight at room temperature The mixture was extracted with ethyl acetate (1×125 mL and 2×100 mL) The combined extracts were washed with brine (3×120 mL) dried over magnesium sulfate filtered through a layer of CELITE filter agent concentrated under reduced pressure further dried under high vacuum

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

Procedure: Triethylamine (12.8 mL, 91.8 mmol) was added to a solution of 4-chloro-3-nitroquinoline (8.0 g, 38 mmol) in DMF (100 mL). The resulting solution was stirred for five minutes at room temperature, and then ethyl 3-aminobutyrate (6.2 mL, 42 mmol) was added. The reaction was stirred overnight at room temperature and poured into deionized water (320 mL). The mixture was extracted with ethyl acetate (1×125 mL and 2×100 mL). The combined extracts were washed with brine (3×120 mL), dried over magnesium sulfate, filtered through a layer of CELITE filter agent, concentrated under reduced pressure, and further dried under high vacuum to provide 11.5 g of ethyl 3-[(3-nitroquinolin-4-yl)amino]butanoate as a yellow solid. The reaction was stirred overnight at room temperature The mixture was extracted with ethyl acetate (1×125 mL and 2×100 mL) The combined extracts were washed with brine (3×120 mL) dried over magnesium sulfate filtered through a layer of CELITE filter agent concentrated under reduced pressure further dried under high vacuum

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

Procedure: 6-(trans-4-tert-butylcyclohexyloxy)-2-naphthaldehyde (30 mg, 0.097 mmol), ethyl 3-aminobutanoate (CAS no. 5303-65-1) (19 mg, 0.145 mmol), and acetic acid (17 mg, 0.291 mmol) were dissolved in dichloroethane (2 mL). The mixture was stirred at r.t. for 10 min under nitrogen atmosphere. Then NaBH(OAc)3 (41 mg, 0.194 mmol) was added to the mixture and the mixture was stirred at r.t. for 15 h. Then saturated NaHCO3 was added to the mixture to adjust the pH to 8. The mixture was extracted with ethyl acetate and the organic layer was purified by silica gel column chromatography using dichloromethane:methanol 10:1 to give produce ethyl 3-((6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)methylamino)butanoate (40 mg, 88%) as a slight yellow solid. ESI-MS: 426.1 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 7.70-7.65 (m, 3H), 7.41 (d, 1H), 7.13-7.09 (m, 2H), 4.28-4.23 (m, 1H), 4.12 (q, 2H), 3.98-3.88 (m, 2H), 3.22-3.18 (m, 1H), 2.53-2.42 (m, 2H), 2.28-2.25 (m, 2H), 1.90-1.87 (m, 2H), 1.45-1.42 (m, 2H), 1.26-1.09 (m, 9H), 0.90 (s, 9H). the mixture was stirred at r.t. for 15 h The mixture was extracted with ethyl acetate the organic layer was purified by silica gel column chromatography to give

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

Procedure: A solution of ethyl 3-aminobutanoate (4.2 g) and of ethyl 2-propenoate (3.83 mL) in EtOH (20 mL) was stirred at room temperature for 8 h. The solvent was evaporated under reduced pressure and the residue purified by chromatography on NH column eluting with a gradient from 100% cyclohexane to 90% ethyl acetate/cyclohexane. The title compound was isolated as a colourless oil, 3.9 g (MS (m/z): 232 [MH]+. The solvent was evaporated under reduced pressure the residue purified by chromatography on NH column eluting with a gradient from 100% cyclohexane to 90% ethyl acetate/cyclohexane

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

Procedure: A solution of ethyl 3-aminobutanoate (4.2 g) and of ethyl 2-propenoate (3.83 mL) in EtOH (20 mL) was stirred at room temperature for 8 h. The solvent was evaporated under reduced pressure and the residue purified by chromatography on NH column eluting with a gradient from 100% cyclohexane to 90% ethyl acetate/cyclohexane. The title compound was isolated as a colourless oil, 3.9 g (MS (m/z): 232 [MH]+. The solvent was evaporated under reduced pressure the residue purified by chromatography on NH column eluting with a gradient from 100% cyclohexane to 90% ethyl acetate/cyclohexane

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

Procedure: Triethylamine (12.8 mL, 91.8 mmol) was added to a solution of 4-chloro-3-nitroquinoline (8.0 g, 38 mmol) in DMF (100 mL). The resulting solution was stirred for five minutes at room temperature, and then ethyl 3-aminobutyrate (6.2 mL, 42 mmol) was added. The reaction was stirred overnight at room temperature and poured into deionized water (320 mL). The mixture was extracted with ethyl acetate (1×125 mL and 2×100 mL). The combined extracts were washed with brine (3×120 mL), dried over magnesium sulfate, filtered through a layer of CELITE filter agent, concentrated under reduced pressure, and further dried under high vacuum to provide 11.5 g of ethyl 3-[(3-nitroquinolin-4-yl)amino]butanoate as a yellow solid. The reaction was stirred overnight at room temperature The mixture was extracted with ethyl acetate (1×125 mL and 2×100 mL) The combined extracts were washed with brine (3×120 mL) dried over magnesium sulfate filtered through a layer of CELITE filter agent concentrated under reduced pressure further dried under high vacuum

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

Procedure: Triethylamine (12.8 mL, 91.8 mmol) was added to a solution of 4-chloro-3-nitroquinoline (8.0 g, 38 mmol) in DMF (100 mL). The resulting solution was stirred for five minutes at room temperature, and then ethyl 3-aminobutyrate (6.2 mL, 42 mmol) was added. The reaction was stirred overnight at room temperature and poured into deionized water (320 mL). The mixture was extracted with ethyl acetate (1×125 mL and 2×100 mL). The combined extracts were washed with brine (3×120 mL), dried over magnesium sulfate, filtered through a layer of CELITE filter agent, concentrated under reduced pressure, and further dried under high vacuum to provide 11.5 g of ethyl 3-[(3-nitroquinolin-4-yl)amino]butanoate as a yellow solid. The reaction was stirred overnight at room temperature The mixture was extracted with ethyl acetate (1×125 mL and 2×100 mL) The combined extracts were washed with brine (3×120 mL) dried over magnesium sulfate filtered through a layer of CELITE filter agent concentrated under reduced pressure further dried under high vacuum

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

Procedure: To a solution of 3-amino-butyric acid ethyl ester (5.00 g, 34.3 mmol), benzaldehyde (4.1 mL, 40 mmol) and acetic acid (1.9 mL, 34 mmol) in 1,2-dichloroethane (120 mL) was added sodium triacetoxyborohydride (17 g, 80 mmol) at room temperature and the mixture was stirred for 20 hours. The reaction mixture was poured into sodium bicarbonate saturated aqueous solution and extracted with chloroform. The organic phase was dried over anhydrous sodium sulfate and concentrated. The resulting residue was purified by flash column chromatography on silica gel (chloroform/methanol=10/1 as an eluant) to afford 3-benzylamino-butyric acid ethyl ester (2.1 g, 9.5 mmol, 28%) as colorless oil. extracted with chloroform The organic phase was dried over anhydrous sodium sulfate concentrated The resulting residue was purified by flash column chromatography on silica gel (chloroform/methanol=10/1 as an eluant)

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

Procedure: Methyl chloroformate (0.071 mL, 0.91 mmol) was added to a solution of ethyl 3-aminobutanoate (0.10 g, 0.76 mmol) (Aldrich, Cat. #E10556) and triethylamine (0.16 mL, 1.1 mmol) in tetrahydrofuran (2.0 mL) at r.t. After stirring at r.t. for 30 min, the mixture was diluted with water, and extracted with ethyl acetate (3×10 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The residue was dissolved in methanol (3.0 mL) and water (1.0 mL). To the solution was added lithium hydroxide monohydrate (0.049 g, 1.2 mmol). The reaction mixture was stirred at r.t. overnight. The mixture was adjusted to pH=2 with aqueous HCl, and extracted with ethyl acetate (3×10 mL). The combined organic layers were dried over MgSO4, filtered and concentrated to afford the desired product. extracted with ethyl acetate (3×10 mL) The combined organic layers were dried over MgSO4 filtered concentrated under reduced pressure The residue was dissolved in methanol (3.0 mL) The reaction mixture was stirred at r.t. overnight extracted with ethyl acetate (3×10 mL) The combined organic layers were dried over MgSO4 filtered concentrated

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

Procedure: Triethylamine (12.8 mL, 91.8 mmol) was added to a solution of 4-chloro-3-nitroquinoline (8.0 g, 38 mmol) in DMF (100 mL). The resulting solution was stirred for five minutes at room temperature, and then ethyl 3-aminobutyrate (6.2 mL, 42 mmol) was added. The reaction was stirred overnight at room temperature and poured into deionized water (320 mL). The mixture was extracted with ethyl acetate (1×125 mL and 2×100 mL). The combined extracts were washed with brine (3×120 mL), dried over magnesium sulfate, filtered through a layer of CELITE filter agent, concentrated under reduced pressure, and further dried under high vacuum to provide 11.5 g of ethyl 3-[(3-nitroquinolin-4-yl)amino]butanoate as a yellow solid. The reaction was stirred overnight at room temperature The mixture was extracted with ethyl acetate (1×125 mL and 2×100 mL) The combined extracts were washed with brine (3×120 mL) dried over magnesium sulfate filtered through a layer of CELITE filter agent concentrated under reduced pressure further dried under high vacuum

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

Procedure: To a solution of 2-fluoro-4-{5-[2-(methoxymethyl)-2′-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoyl chloride, prepared as in example 116 (75 mg; 0.17 mmol) in dry THF, DIEA (103 μl; 0.60 mmol) was added followed by ethyl-3-aminobutyrate (45 mg; 0.34 mmol) and the reaction mixture stirred for 2 h30 at RT. The solvent was then removed under vacuum and the crude material purified by flash chromatography (EtOAc/cHex) to afford the title compound as a colorless oil (82 mg, 89%). 1H NMR: (CDCl3, 300 MHz) δ 8.42 (m, 1H), 8.23 (t, J=8 Hz, 1H), 8.16 (dd, J=1.9, 8 Hz. 1H), 8.09 (dd, J=1.5, 8.1 Hz, 1H), 7.96 (dd, J=1.3, 12.4 Hz, 1H), 7.47 (m, 1H), 7.38-7.22 (m, 5H), 7.12 (m, 1H), 4.62 (m, 1H), 4.21 (m, 2H), 4.19 (q, J=7.1 Hz, 2H), 3.33 (s, 3H), 2.65 (m, 2H), 2.07 (s, 3H), 1.37 (d, J=6.8 Hz, 3H), 1.28 (t, J=7.1 Hz, 3H). UPLC/MS: 532.3 (M+H)+ 530.3 (M−H)−. HPLC (Method A) Rt: 5.52 min (purity: 98.5%). was added The solvent was then removed under vacuum the crude material purified by flash chromatography (EtOAc/cHex)