4-(dimethylamino)-4-oxobutanoic acid

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: The title compound, off-white solid (87 mg, 77%), MS (ISP) m/z=456.3 [(M+H)+], mp 205° C., was prepared in accordance with the general method of example 1 from trans-4-{2-[4-(2,3-dihydro-benzofuran-4-yl)-piperidin-1-yl]-ethyl}-cyclohexylamine dihydrochloride (intermediate B) (100 mg, 0.25 mmol) and 4-(dimethylamino)-4-oxobutanoic acid.

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

実験手順: From N,N-dimethylsuccinamic acid, HATU and N-ethyldiisopropylamine in THF, then treatment with (+)-7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-ylamine. [α]D20=+21.9° (c=1.04, CHCl3), ES-MS m/e (%): 394 (M+H+, 100).

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

実験手順: From N,N-dimethylsuccinamic acid, HATU and N-ethyldiisopropylamine in THF, then treatment with (+)-7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-ylamine. [α]D20=+21.9° (c=1.04, CHCl3), ES-MS m/e (%): 394 (M+H+, 100).

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

実験手順: To an ice cold solution of 4-(dimethylamino)-4-oxobutanoic acid (0.174 g, 1.20 mmol) in CH2Cl2 (2 mL) was added DIPEA (0.208 mL, 1.120 mmol) followed by isobutyl chloroformate (0.138 mL, 1.06 mmol). The mixture was stirred for 10 minutes, and the resulting mixed anhydride was added to a solution of N,3-dimethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine (0.100 g, 0.531 mmol) in CH2Cl2 (0.66 mL). The reaction mixture was stirred at room temperature (about 22° C.) for one hour. The crude reaction mixture was concentrated and purified via reverse phase column chromatography (0%-100% acetonitrile (MeCN)/water) to give the desired product F62 as a white solid (0.155 g, 83%). The reaction mixture was stirred at room temperature (about 22° C.) for one hour The crude reaction mixture was concentrated purified via reverse phase column chromatography (0%-100% acetonitrile (MeCN)/water)

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

実験手順: The title compound, off-white solid (87 mg, 77%), MS (ISP) m/z=456.3 [(M+H)+], mp 205° C., was prepared in accordance with the general method of example 1 from trans-4-{2-[4-(2,3-dihydro-benzofuran-4-yl)-piperidin-1-yl]-ethyl}-cyclohexylamine dihydrochloride (intermediate B) (100 mg, 0.25 mmol) and 4-(dimethylamino)-4-oxobutanoic acid.

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

実験手順: Synthesis in analogy to the General Method 1 starting from (3aS,4R,7aS)-4-hydroxy-4-m-tolylethynyl-octahydro-indole-1-carboxylic acid methyl ester and N,N-dimethylsuccinamic acid to yield (3aR,4S,7aR)-methyl 4-(4-(dimethylamino)-4-oxobutanoyloxy)-4-(m-tolylethynyl)octahydro-1H-indole-1-carboxylate. MS [2M+NH4]=898; RT=1.15 min; UPLC Method I

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

実験手順: The title compound, white solid (48 mg, 52%), MS (ISP) m/z=458.6 [(M+H)+], mp 188° C., was prepared in accordance with the general method of example 32 from trans-4-{2-[4-(2,3-dihydrofuro[3,2-c]pyridin-4-yl)-piperazin-1-yl]-ethyl}-cyclohexanamine trihydrochloride (intermediate C) (88 mg, 0.2 mmol) and 4-(dimethylamino)-4-oxobutanoic acid.

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

実験手順: The title compound, off-white solid (55 mg, 48%), MS (ISP) m/z=454.4 [(M+H)+], mp 167° C., was prepared in accordance with the general method of example 1 from trans-4-[2-(4-benzofuran-3-yl-piperidin-1-yl)-ethyl]-cyclohexylamine dihydrochloride (intermediate A) (100 mg, 0.25 mmol) and 4-(dimethylamino)-4-oxobutanoic acid.

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

実験手順: The title compound, white solid (103 mg, 90%), MS (ISP) m/z=458.6 [(M+H)+], mp 177.5° C., was prepared in accordance with the general method of example 6 from trans-4-{2-[4-(2,3-dihydro-furo[2,3-c]pyridin-7-yl)-piperazin-1-yl]-ethyl}-cyclohexylamine trihydrochloride (intermediate B) (110 mg, 0.25 mmol) and 4-(dimethylamino)-4-oxobutanoic acid.

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

実験手順: From N,N-dimethylsuccinamic acid, HATU and N-ethyldiisopropylamine in THF, then treatment with (+)-7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-ylamine. [α]D20=+21.9° (c=1.04, CHCl3), ES-MS m/e (%): 394 (M+H+, 100).

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

実験手順: To an ice cold solution of 4-(dimethylamino)-4-oxobutanoic acid (0.174 g, 1.20 mmol) in CH2Cl2 (2 mL) was added DIPEA (0.208 mL, 1.120 mmol) followed by isobutyl chloroformate (0.138 mL, 1.06 mmol). The mixture was stirred for 10 minutes, and the resulting mixed anhydride was added to a solution of N,3-dimethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine (0.100 g, 0.531 mmol) in CH2Cl2 (0.66 mL). The reaction mixture was stirred at room temperature (about 22° C.) for one hour. The crude reaction mixture was concentrated and purified via reverse phase column chromatography (0%-100% acetonitrile (MeCN)/water) to give the desired product F62 as a white solid (0.155 g, 83%). The reaction mixture was stirred at room temperature (about 22° C.) for one hour The crude reaction mixture was concentrated purified via reverse phase column chromatography (0%-100% acetonitrile (MeCN)/water)