2-(三氟甲氧基)乙胺盐酸盐

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

实验步骤: 1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-trifluoromethoxy-ethyl)-amide (87 mg) was prepared by following General Procedure F starting from 1-methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (100 mg), 2-(trifluoromethoxy)ethylamine hydrochloride (45 mg), HBTU (112 mg), and DIEA (65 uL). LC/MS: m/z 520.8. 1H NMR (DMSO-d6, 400 MHz): δ 12.41 (bs, 1H), 8.72 (s, 1H), 8.10 (s, 1H), 7.92 (s, 1H), 7.78 (d, 1H), 7.74 (d, 1H), 7.51 (d, 1H), 7.36 (d, 1H), 4.23 (t, 2H), 3.81-3.55 (m, 5H).

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

实验步骤: The title compound was prepared in a manner similar to Example 227 using 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and 2-(trifluoromethoxy)ethanamine hydrochloride. 1H NMR (400 MHz, DMSO-d6) δ 2.36 (s, 3 H) 3.55 (q, J=5.3 Hz, 2 H) 4.16 (t, J=5.3 Hz, 2 H) 7.59 (d, J=7.8 Hz, 1 H) 7.66 (s, 1 H) 7.71 (br. s., 1 H) 8.14 (br. s., 1 H) 8.36 (d, J=7.3 Hz, 1 H) 8.84-8.88 (m, 1 H) 8.93 (t, J=4.4 Hz, 1 H) 13.18 (br. s., 1 H). MS m/z [M+H]+ 432.4.

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

实验步骤: The title compound was prepared in a manner similar to Example 227 using 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and 2-(trifluoromethoxy)ethanamine hydrochloride. 1H NMR (400 MHz, DMSO-d6) δ 2.36 (s, 3H) 3.55 (q, J=5.3 Hz, 2H) 4.16 (t, J=5.3 Hz, 2H) 7.59 (d, J=7.8 Hz, 1H) 7.66 (s, 1H) 7.71 (br. s., 1H) 8.14 (br. s., 1H) 8.36 (d, J=7.3 Hz, 1H) 8.84-8.88 (m, 1H) 8.93 (t, J=4.4 Hz, 1H) 13.18 (br. s., 1H). MS m/z [M+H]+ 432.4.

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

实验步骤: 1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-trifluoromethoxy-ethyl)-amide (87 mg) was prepared by following General Procedure F starting from 1-methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (100 mg), 2-(trifluoromethoxy)ethylamine hydrochloride (45 mg), HBTU (112 mg), and DIEA (65 uL). LC/MS: m/z 520.8. 1H NMR (DMSO-d6, 400 MHz): δ 12.41 (bs, 1H), 8.72 (s, 1H), 8.10 (s, 1H), 7.92 (s, 1H), 7.78 (d, 1H), 7.74 (d, 1H), 7.51 (d, 1H), 7.36 (d, 1H), 4.23 (t, 2H), 3.81-3.55 (m, 5H).

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

实验步骤: 1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-trifluoromethoxy-ethyl)-amide (87 mg) was prepared by following General Procedure F starting from 1-methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (100 mg), 2-(trifluoromethoxy)ethylamine hydrochloride (45 mg), HBTU (112 mg), and DIEA (65 uL). LC/MS: m/z 520.8. 1H NMR (DMSO-d6, 400 MHz): δ 12.41 (bs, 1H), 8.72 (s, 1H), 8.10 (s, 1H), 7.92 (s, 1H), 7.78 (d, 1H), 7.74 (d, 1H), 7.51 (d, 1H), 7.36 (d, 1H), 4.23 (t, 2H), 3.81-3.55 (m, 5H).

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 0° C. suspension of 2-(trifluoromethoxy)ethylamine hydrochloride (0.308 g, 1.861 mmol) in THF (10 mL) was treated with NaH (60% in mineral oil, 0.082 g, 2.047 mmol), stirred at 0° C. for 0.5 h, treated drop-wise with 2-chloroethyl isocyanate (0.175 mL, 2.047 mmol), allowed to warm to RT and stirred overnight. The mixture was treated with EtOAc, the solids removed via filtration and the filtrate concentrated to dryness to afford 1-(2-chloroethyl)-3-(2-(trifluoromethoxy)ethyl)urea (610 mg, 140%) containing EtOAc. 1H NMR (400 MHz, DMSO-d6): δ 6.29 (br s, 2 H), 4.04-3.97 (m, 2 H), 3.55 (t, J=6.2 Hz, 2 H), 3.33-3.24 (m, 4 H). to warm to RT stirred overnight the solids removed via filtration the filtrate concentrated to dryness

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

实验步骤: The title compound was prepared according to the procedure described in Step A of Example 5 from 2-(trifluoromethoxy)ethanamine hydrochloride (J. Org. Chem. 2001, 66, 1061-1063), 4-bromo-1-fluoro-2-nitrobenzene (Wako Pure Chemical Industries, Ltd.) and N,N-diisopropylethylamine.

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

实验步骤: The title compound was prepared according to the procedure described in Step A of Example 5 from 1-chloro-4-(ethylsulfonyl)-2-nitrobenzene (Step C of Example 2), 2-(trifluoromethoxy)ethanamine hydrochloride (J. Org. Chem. 2001, 66, 1061-1063.) and triethylamine.

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

实验步骤: See FIG. 21(c). 1-((6-methoxy-5-methylpyrimidin-4-yl)methyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxylic acid (40 mg, 0.13 mmol) was taken in a 50 ml single necked flask equipped with an air condenser connected to nitrogen source. NMP (3 ml, 31.17 mmol) was added to get a solution. Triethyl amine (0.056 ml, 0.40 mmol) was added followed by the addition of 2-(trifluoromethoxy)ethanamine hydrochloride (44.4 mg, 0.27 mmol). The reaction mass was stirred at RT for 5 minutes. HATU (61.2 mg, 0.16 mmol) was added and stirred at RT for 30 min. After the completion of the reaction, few drops of methanol was added and clear solution was subjected for reverse phase HPLC purification to get 1-((6-methoxy-5-methylpyrimidin-4-yl)methyl)-N-(2-(trifluoromethoxy)ethyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide (15.00 mg, 27.3%). ES+MS m/z: 410 (M+1). 1H NMR (300 MHz, DMSO-d6) δ ppm 2.25 (s, 3 H ) 3.68-3.80 (m, 2 H ) 3.93 (s, 3 H ) 4.24 (t, J=5.27 Hz, 2 H ) 5.69 (s, 2 H ) 7.26 (dd, J=8.29, 4.71 Hz, 1 H ) 7.94 (d, J=7.35 Hz, 1 H ) 8.28 (s, 1 H ) 8.38-8.54 (m, 2 H ) 8.96 (s, 1 H). equipped with an air condenser to get a solution stirred at RT for 30 min was added clear solution was subjected for reverse phase HPLC purification

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

实验步骤: The title compound was prepared in a manner similar to Example 227 using 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and 2-(trifluoromethoxy)ethanamine hydrochloride. 1H NMR (400 MHz, DMSO-d6) δ 2.36 (s, 3 H) 3.55 (q, J=5.3 Hz, 2 H) 4.16 (t, J=5.3 Hz, 2 H) 7.59 (d, J=7.8 Hz, 1 H) 7.66 (s, 1 H) 7.71 (br. s., 1 H) 8.14 (br. s., 1 H) 8.36 (d, J=7.3 Hz, 1 H) 8.84-8.88 (m, 1 H) 8.93 (t, J=4.4 Hz, 1 H) 13.18 (br. s., 1 H). MS m/z [M+H]+ 432.4.

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

实验步骤: The title compound was prepared in a manner similar to Example 227 using 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and 2-(trifluoromethoxy)ethanamine hydrochloride. 1H NMR (400 MHz, DMSO-d6) δ 2.36 (s, 3H) 3.55 (q, J=5.3 Hz, 2H) 4.16 (t, J=5.3 Hz, 2H) 7.59 (d, J=7.8 Hz, 1H) 7.66 (s, 1H) 7.71 (br. s., 1H) 8.14 (br. s., 1H) 8.36 (d, J=7.3 Hz, 1H) 8.84-8.88 (m, 1H) 8.93 (t, J=4.4 Hz, 1H) 13.18 (br. s., 1H). MS m/z [M+H]+ 432.4.

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

实验步骤: 1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-trifluoromethoxy-ethyl)-amide (87 mg) was prepared by following General Procedure F starting from 1-methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (100 mg), 2-(trifluoromethoxy)ethylamine hydrochloride (45 mg), HBTU (112 mg), and DIEA (65 uL). LC/MS: m/z 520.8. 1H NMR (DMSO-d6, 400 MHz): δ 12.41 (bs, 1H), 8.72 (s, 1H), 8.10 (s, 1H), 7.92 (s, 1H), 7.78 (d, 1H), 7.74 (d, 1H), 7.51 (d, 1H), 7.36 (d, 1H), 4.23 (t, 2H), 3.81-3.55 (m, 5H).