N-ethyl-2-fluoroaniline

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

実験手順: 2M Oxalyl chloride solution in dichloromethane (0.080 ml) and DMF (0.001 ml) were added to a suspension of 3-[2-(tert-butoxycarbonyl-pyridin-4-yl-amino)-ethoxy]-5-chloro-benzoic acid (0.050 g) in anhydrous dichloromethane (1 ml). The reaction was stirred at room temperature for 2 h then a solution of N-ethyl-2-fluoroaniline (0.029 g) DMAP (0.001 g) and DIPEA (0.070 ml) were added. The reaction mixture was stirred at room temperature for 16 h and then triflouroacetic acid (1 ml) was added. The solvent was removed in vacuo, the residue was subjected to preparative hplc and the required fraction dried by repetitive addition of acetonitrile and concentration under reduced pressure to give the title compound (0.020 g) as a colourless gum. The reaction mixture was stirred at room temperature for 16 h The solvent was removed in vacuo the required fraction dried by repetitive addition of acetonitrile and concentration under reduced pressure

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

実験手順: 2-Fluoro-N-ethylaniline [NMR (DMSO-d6, 200 MHz): δ1.16 (t, J=7.1 Hz, 3H); 3.11 (dq, J1 =7.2 Hz, J2 =6.5 Hz, 2H); 5.30 (br m, 1H); 6.48-6.59 (m, 1H); 6.70 (t, J=8.5 Hz, 1H); 6.92-7.06 (m, 2H)] was prepared from 2-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-(2-fluorophenyl)benzamide as a light yellow wax. NMR (DMSO-d6, 200 MHz): δ0.9 (d, J=6 Hz, 3H); 0.95 (d, J=6 Hz, 3H); 1.1 (t, J=7 Hz, 3H); 1.7 (m, 1H); 2.1 (m, 1H); 2.3 (m, 1H); 2.5 (m, 2H); 2.7 (m, 1H); 2.85 (m, 1H); 3.8 (br m, 2H); 4.8 (br s, 1H); 5.1 (d, J=10 Hz, 1H); 5.2 (d, J=17 Hz, 1H); 5.8 (m, 1H); 6.45 (m, 1H); 6.5 (s, 1H); 6.65 (m, 1H); 7.0-7.4 (m, 9H); 9.35 (s, 1H). [α]D20 =+3.4° (abs ethanol, c=2.04). Calc. for C31H36FN3O2HCl H2O: C, 66.95; H, 7.07; N, 7.56; Cl, 6.38. Found: C, 66.61; H, 7.14; N, 7.53; Cl, 6.40. Mass spectrum (CI-CH4) m/e: 502 (M+1, 89%), 501 (M, 17%), 348 (36%), 153 (100%). purified by the methods

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

実験手順: 2-Fluoro-N-ethylaniline [NMR (DMSO-d6, 200 MHz): δ 1.16 (t, J=7.1 Hz, 3H); 3.11 (dq, J1 =7.2 Hz, J2 =6.5 Hz, 2H); 5.30 (br m, 1H); 6.48-6.59 (m, 1H); 6.70 (t, J=8.5 Hz, 1H); 6.92-7.06 (m, 2H)] was prepared from 2-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-(2-fluorophenyl)benzamide as a light yellow wax. NMR (DMSO-d6, 200 MHz): δ 0.9 (d, J=6 Hz, 3H); 0.95 (d, J=6 Hz, 3H); 1.1 (t, J=7 Hz, 1H); 2.1 (m, 1H); 2.3 (m, 1H); 2.5 (m, 2H); 2.7 (m, 1H); 2.85 (m, 1H); 3.8 (br m, 2H); 4.8 (br s, 1H); 5.1 (d, J=10 Hz, 1H); 5.2 (d, J=17 Hz, 1H); 5.8 (m, 1H); 6.45 (m, 1H); 6.5 (s, 1H); 6.65 (m, 1H); 7.0-7.4 (m, 9H); 9.35 (s, 1H). [α]D20 =+3.4° (abs ethanol, c=2.04). Calc. for C31H36FN3O2HCl H2O: C, 66.95; H, 7.07; N, 7.56; Cl, 6.38. Found: C, 66.61; H, 7.14; N, 7.53; Cl, 6.40. Mass spectrum (CI--CH4) m/e: 502 (M+1, 89%), 501 (M, 17%), 348 (36%), 153 (100%). purified by the methods