D-2-氨基-2-苯基乙酰胺盐酸盐

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

实验步骤: A solution of 3,5-dichloropyrazine-2-carbonitrile (150 mg, 0.862 mmol), (R)-2-amino-2-phenylacetamide hydrochloride (160 mg, 0.858 mmol) and DIEA (0.400 mL, 2.30 mmol) in DMF (5 mL) was stirred at room temperature for 6 h. Water and EtOAc were added. Organic phase was separated, washed with 1N HCl, then with 5% NaHCO3, dried over Na2SO4, concentrated in vacuo to give (R)-2-(6-chloro-5-cyanopyrazin-2-ylamino)-2-phenylacetamide (245 mg). Organic phase was separated washed with 1N HCl with 5% NaHCO3, dried over Na2SO4 concentrated in vacuo

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

实验步骤: The solid (R)-tert-butyl 2-amino-2-oxo-1-phenylethylcarbamate (446 mg) was dissolved in dioxane (5 mL), aq. 6N HCl (8 mL) was added. After being stirred at room temperature for 20 h, the mixture was concentrated in vacuo to give (R)-2-amino-2-phenylacetamide hydrochloride as a solid (329 mg). the mixture was concentrated in vacuo

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

实验步骤: The title compound was synthesized in analogy to Example 1, using 5-cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid (Example 42 a) and (αR)-α-amino-benzeneacetamide hydrochloride (1:1) (CAN 63291-39-4) as starting materials, LC-MS (UV peak area/ESI) 100%, 366.1808 (M+H)+.

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

实验步骤: The title compound was synthesized in analogy to Example 1, using 5-cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid (Example 42 a) and (αR)-α-amino-benzeneacetamide hydrochloride (1:1) (CAN 63291-39-4) as starting materials, LC-MS (UV peak area/ESI) 100%, 366.1808 (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 3,5-dichloropyrazine-2-carbonitrile (150 mg, 0.862 mmol), (R)-2-amino-2-phenylacetamide hydrochloride (160 mg, 0.858 mmol) and DIEA (0.400 mL, 2.30 mmol) in DMF (5 mL) was stirred at room temperature for 6 h. Water and EtOAc were added. Organic phase was separated, washed with 1N HCl, then with 5% NaHCO3, dried over Na2SO4, concentrated in vacuo to give (R)-2-(6-chloro-5-cyanopyrazin-2-ylamino)-2-phenylacetamide (245 mg). Organic phase was separated washed with 1N HCl with 5% NaHCO3, dried over Na2SO4 concentrated in vacuo

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

实验步骤: The solid (R)-tert-butyl 2-amino-2-oxo-1-phenylethylcarbamate (446 mg) was dissolved in dioxane (5 mL), aq. 6N HCl (8 mL) was added. After being stirred at room temperature for 20 h, the mixture was concentrated in vacuo to give (R)-2-amino-2-phenylacetamide hydrochloride as a solid (329 mg). the mixture was concentrated in vacuo

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

实验步骤: 3-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenylamino)-3-oxopropanoic acid (Compound C of Example 102, 30 mg, 0.10 mmol) was coupled with (R)-2-amino-2-phenylacetamide hydrochloride (Bachem, 28 mg, 0.15 mmol) in a manner similar to that which is described in Step C of Example 1 to give (R)-N1-(2-amino-2-oxo-1-phenylethyl)-N3-(4-(2-aminopyridin-4-yloxy)-3-fluorophenyl)malonamide, hydrochloride salt (14 mg, 30% yield). 1H NMR (DMSO-d6) δ 10.65 (s, 1H), 8.76 (d, 1H, J=8.0 Hz), 7.92 (d, 1H, J=7.0 Hz), 7.75-7.88 (m, 4H), 7.20-7.43 (m, 8H), 6.66 (m, 1H), 6.09 (s, 1H), 5.35 (d, 1H, J=8.0 Hz), 3.45 (d, 1H, J=15.0 Hz), 3.37 (d, 1H, J=15.0 Hz); MS(ESI+) m/z 438.23 (M+H)+.

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

实验步骤: 3-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenylamino)-3-oxopropanoic acid (Compound C of Example 102, 30 mg, 0.10 mmol) was coupled with (R)-2-amino-2-phenylacetamide hydrochloride (Bachem, 28 mg, 0.15 mmol) in a manner similar to that which is described in Step C of Example 1 to give (R)-N1-(2-amino-2-oxo-1-phenylethyl)-N3-(4-(2-aminopyridin-4-yloxy)-3-fluorophenyl)malonamide, hydrochloride salt (14 mg, 30% yield). 1H NMR (DMSO-d6) δ 10.65 (s, 1H), 8.76 (d, 1H, J=8.0 Hz), 7.92 (d, 1H, J=7.0 Hz), 7.75-7.88 (m, 4H), 7.20-7.43 (m, 8H), 6.66 (m, 1H), 6.09 (s, 1H), 5.35 (d, 1H, J=8.0 Hz), 3.45 (d, 1H, J=15.0 Hz), 3.37 (d, 1H, J=15.0 Hz); MS(ESI+) m/z 438.23 (M+H)+.

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

实验步骤: 3-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenylamino)-3-oxopropanoic acid (Compound C of Example 102, 30 mg, 0.10 mmol) was coupled with (R)-2-amino-2-phenylacetamide hydrochloride (Bachem, 28 mg, 0.15 mmol) in a manner similar to that which is described in Step C of Example 1 to give (R)—N1-(2-amino-2-oxo-1-phenylethyl)-N3-(4-(2-aminopyridin-4-yloxy)-3-fluorophenyl)malonamide, hydrochloride salt (14 mg, 30% yield). 1H NMR (DMSO-d6) δ 10.65 (s, 1H), 8.76 (d, 1H, J=8.0 Hz), 7.92 (d, 1H, J=7.0 Hz), 7.75-7.88 (m, 4H), 7.20-7.43 (m, 8H), 6.66 (m, 1H), 6.09 (s, 1H), 5.35 (d, 1H, J=8.0 Hz), 3.45 (d, 1H, J=15.0 Hz), 3.37 (d, 1H, J=15.0 Hz); MS(ESI+) m/z 438.23 (M+H)+.

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

实验步骤: 3-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenylamino)-3-oxopropanoic acid (Compound C of Example 102, 30 mg, 0.10 mmol) was coupled with (R)-2-amino-2-phenylacetamide hydrochloride (Bachem, 28 mg, 0.15 mmol) in a manner similar to that which is described in Step C of Example 1 to give (R)—N1-(2-amino-2-oxo-1-phenylethyl)-N3-(4-(2-aminopyridin-4-yloxy)-3-fluorophenyl)malonamide, hydrochloride salt (14 mg, 30% yield). 1H NMR (DMSO-d6) δ 10.65 (s, 1H), 8.76 (d, 1H, J=8.0 Hz), 7.92 (d, 1H, J=7.0 Hz), 7.75-7.88 (m, 4H), 7.20-7.43 (m, 8H), 6.66 (m, 1H), 6.09 (s, 1H), 5.35 (d, 1H, J=8.0 Hz), 3.45 (d, 1H, J=15.0 Hz), 3.37 (d, 1H, J=15.0 Hz); MS(ESI+) m/z 438.23 (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 3,5-dichloropyrazine-2-carbonitrile (150 mg, 0.862 mmol), (R)-2-amino-2-phenylacetamide hydrochloride (160 mg, 0.858 mmol) and DIEA (0.400 mL, 2.30 mmol) in DMF (5 mL) was stirred at room temperature for 6 h. Water and EtOAc were added. Organic phase was separated, washed with 1N HCl, then with 5% NaHCO3, dried over Na2SO4, concentrated in vacuo to give (R)-2-(6-chloro-5-cyanopyrazin-2-ylamino)-2-phenylacetamide (245 mg). Organic phase was separated washed with 1N HCl with 5% NaHCO3, dried over Na2SO4 concentrated in vacuo

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

实验步骤: The solid (R)-tert-butyl 2-amino-2-oxo-1-phenylethylcarbamate (446 mg) was dissolved in dioxane (5 mL), aq. 6N HCl (8 mL) was added. After being stirred at room temperature for 20 h, the mixture was concentrated in vacuo to give (R)-2-amino-2-phenylacetamide hydrochloride as a solid (329 mg). the mixture was concentrated in vacuo