N-乙基-3-氟苯胺

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: To a solution of (3-fluorophenyl)-ethylamine (3.06 g, 22 mmol) and rhodanine (2.66 g, 20 mmol) in acetonitrile (70 mL) was added DIEA (7.66 mL, 44 mmol) at room temperature. Then, this solution was cooled to 0° C. and mercuric chloride (5.97 g, 22 mmol) was added in two portions. After addition, the suspension was allowed to warm to room temperature and stirred for 3 days. The resulting black solids were filtered through a plug of celite and washed with dichloromethane (500 mL) and methanol (250 mL). The combined solvents were removed under the vacuum and the crude residue was dissolved in ethyl acetate (25 mL) at hot condition and stored in the refrigerator overnight. Then, the solids were collected by filtration and washed with ethyl acetate. After drying in air, 3.65 g (76.6% yield) of 2-[(3-fluorophenyl)-ethylamino]-thiazol-4-one was isolated as a white amorphous solid: HRES(+) m/e calcd for C11H11FN2OS (M+H)+239.0649, found 239.0647. After addition to warm to room temperature The resulting black solids were filtered through a plug of celite washed with dichloromethane (500 mL) and methanol (250 mL) The combined solvents were removed under the vacuum the crude residue was dissolved in ethyl acetate (25 mL) at hot condition stored in the refrigerator overnight Then, the solids were collected by filtration washed with ethyl acetate After drying in air

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

实验步骤: 3-Fluoro-N-ethylaniline [NMR (DMSO-d6, 200 MHz): δ1.18 (t, J=7.2 Hz, 3H); 3.02 (dq, J1 =7.2 Hz, J2 =7.2 Hz, 2H); 5.86 (br m, 1H); 6.24-6.42 (m, 3H); 7.07 (q, J=7.8 Hz, 1H)] was prepared from 3-fluoroaniline and acetic anhydride, coupled with 3-((αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-(tert-butyldimethylsilyloxy)benzyl)benzoyl chloride, deprotected and purified by the methods described in Example 10 to give (+)-3-((αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-ethyl-N-(3-fluorophenyl)benzamide as a white solid. NMR (DMSO-d6, 200 MHz): δ0.92 (d, J=6 Hz, 3H); 0.96 (d, J=6 Hz, 3H); 1.05 (t, J=7 Hz, 3H); 1.7 (m, 1H); 2.05 (m, 1H); 2.3 (m, 1H); 2.5 (m, 2H); 2.7 (m, 1H); 2.9 (m, 1H); 3.2 (m, 1H); 3.9 (q, J=7 Hz, 2H); 4.8 (s, 1H); 5.1 (d, J=10 Hz, 1H); 5.2 (d, J=16 Hz, 1H); 5.8 (m, 1H); 6.45 (d, J=8 Hz, 1H); 6.6 (s, 1H); 6.65 (d, J=8 Hz, 1H); 6.9 (d, J=8 Hz, 1H); 7.0-7.2 (m, 3H); 7.2-7.4 (m, 5H); 9.35 (s, 1H). [α]D20 =+4.3° (abs EtOH, c=3.9). Calc. for C31H36FN3O2HCl 0.5 H2O: C, 68.06; H, 7.00: N, 7.68; Cl, 6.48. Found C, 68.10;H, 7.04; N, 7.63; Cl, 6.42. Mass spectrum (CI--CH4) m/e: 502 (M+1, 39%), 501 (M, 9%), 348 (29%), 153 (100%). purified by the methods

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: 3-Fluoro-N-ethylaniline [NMR (DMSO-d6, 200 MHz): δ1.18 (t, J=7.2 Hz, 3H); 3.02 (dq, J1 =7.2 Hz, J2 =7.2 Hz, 2H); 5.86 (br m, 1H); 6.24-6.42 (m, 3H); 7.07 (q, J=7.8 Hz, 1H)] was prepared from 3-fluoroaniline and acetic anhydride, coupled with 3-((αR)-α-((2S, 5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-(tert-butyldimethylsilyloxy)benzyl)benzoyl chloride, deprotected and purified by the methods described in Example 10 to give (+)-3-((αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-ethyl-N-(3-fluorophenyl)benzamide as a white solid. NMR (DMSO-d6, 200 MHz): δ0.92 (d, J=6 Hz, 3H); 0.96 (d, J=6 Hz, 3H); 1.05 (t, J=7 Hz, 3H); 1.7 (m, 1H); 2.05 (m, 1H); 2.3 (m, 1H); 2.5 (m, 2H); 2.7 (m, 1H); 2.9 (m, 1H); 3.2 (m, 1H); 3.9 (q, J=7 Hz, 2H); 4.8 (s, 1H); 5.1 (d, J=10 Hz, 1H); 5.2 (d, J=16 Hz, 1H); 5.8 (m, 1H); 6.45 (d, J=8 Hz, 1H); 6.6 (s, 1H); 6.65 (d, J=8 Hz, 1H); 6.9 (d, J=8 Hz, 1H); 7.0-7.2 (m, 3H); 7.2-7.4 (m, 5H); 9.35 (s, 1H). [α]D20 =+4.3° (abs EtOH, c=3.9). purified by the methods

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

实验步骤: To a solution of (3-fluorophenyl)-ethylamine (3.06 g, 22 mmol) and rhodanine (2.66 g, 20 mmol) in acetonitrile (70 mL) was added DIEA (7.66 mL, 44 mmol) at room temperature. Then, this solution was cooled to 0° C. and mercuric chloride (5.97 g, 22 mmol) was added in two portions. After addition, the suspension was allowed to warm to room temperature and stirred for 3 days. The resulting black solids were filtered through a plug of celite and washed with dichloromethane (500 mL) and methanol (250 mL). The combined solvents were removed under the vacuum and the crude residue was dissolved in ethyl acetate (25 mL) at hot condition and stored in the refrigerator overnight. Then, the solids were collected by filtration and washed with ethyl acetate. After drying in air, 3.65 g (76.6% yield) of 2-[(3-fluorophenyl)-ethylamino]-thiazol-4-one was isolated as a white amorphous solid: HRES(+) m/e calcd for C11H11FN2OS (M+H)+ 239.0649, found 239.0647. After addition to warm to room temperature The resulting black solids were filtered through a plug of celite washed with dichloromethane (500 mL) and methanol (250 mL) The combined solvents were removed under the vacuum the crude residue was dissolved in ethyl acetate (25 mL) at hot condition stored in the refrigerator overnight Then, the solids were collected by filtration washed with ethyl acetate After drying in air

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

实验步骤: To a solution of (3-fluorophenyl)-ethylamine (3.06 g, 22 mmol) and rhodanine (2.66 g, 20 mmol) in acetonitrile (70 mL) was added DIEA (7.66 mL, 44 mmol) at room temperature. Then, this solution was cooled to 0° C. and mercuric chloride (5.97 g, 22 mmol) was added in two portions. After addition, the suspension was allowed to warm to room temperature and stirred for 3 days. The resulting black solids were filtered through a plug of celite and washed with dichloromethane (500 mL) and methanol (250 mL). The combined solvents were removed under the vacuum and the crude residue was dissolved in ethyl acetate (25 mL) at hot condition and stored in the refrigerator overnight. Then, the solids were collected by filtration and washed with ethyl acetate. After drying in air, 3.65 g (76.6% yield) of 2-[(3-fluorophenyl)-ethylamino]-thiazol-4-one was isolated as a white amorphous solid: HRES(+) m/e calcd for C11H11FN2OS (M+H)+239.0649, found 239.0647. After addition to warm to room temperature The resulting black solids were filtered through a plug of celite washed with dichloromethane (500 mL) and methanol (250 mL) The combined solvents were removed under the vacuum the crude residue was dissolved in ethyl acetate (25 mL) at hot condition stored in the refrigerator overnight Then, the solids were collected by filtration washed with ethyl acetate After drying in air

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

实验步骤: 3-Fluoro-N-ethylaniline [NMR (DMSO-d6, 200 MHz): δ1.18 (t, J=7.2 Hz, 3H); 3.02 (dq, J1 =7.2 Hz, J2 =7.2 Hz, 2H); 5.86 (br m, 1H); 6.24-6.42 (m, 3H); 7.07 (q, J=7.8 Hz, 1H)] was prepared from 3-fluoroaniline and acetic anhydride, coupled with 3-((αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-(tert-butyldimethylsilyloxy)benzyl)benzoyl chloride, deprotected and purified by the methods described in Example 10 to give (+)-3-((αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-ethyl-N-(3-fluorophenyl)benzamide as a white solid. NMR (DMSO-d6, 200 MHz): δ0.92 (d, J=6 Hz, 3H); 0.96 (d, J=6 Hz, 3H); 1.05 (t, J=7 Hz, 3H); 1.7 (m, 1H); 2.05 (m, 1H); 2.3 (m, 1H); 2.5 (m, 2H); 2.7 (m, 1H); 2.9 (m, 1H); 3.2 (m, 1H); 3.9 (q, J=7 Hz, 2H); 4.8 (s, 1H); 5.1 (d, J=10 Hz, 1H); 5.2 (d, J=16 Hz, 1H); 5.8 (m, 1H); 6.45 (d, J=8 Hz, 1H); 6.6 (s, 1H); 6.65 (d, J=8 Hz, 1H); 6.9 (d, J=8 Hz, 1H); 7.0-7.2 (m, 3H); 7.2-7.4 (m, 5H); 9.35 (s, 1H). [α]D20 =+4.3° (abs EtOH, c=3.9). Calc. for C31H36FN3O2HCl 0.5 H2O: C, 68.06; H, 7.00: N, 7.68; Cl, 6.48. Found C, 68.10;H, 7.04; N, 7.63; Cl, 6.42. Mass spectrum (CI--CH4) m/e: 502 (M+1, 39%), 501 (M, 9%), 348 (29%), 153 (100%). purified by the methods