N-propylaniline

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The reaction procedure of Example 57 was followed except that 1.763 g (11.2 mmol) of 2-chloronicotinic acid, 15 ml of thionyl chloride, two droplets of DMF, 894 mg of ammonium thiocyanate, 15 ml of acetone, 1.59 g of N-propylaniline and 10 ml of acetone were used. The product was then recrystallized from ethanol to obtain 2.68 g of 2-(N-phenyl-N-propylamino)-4H-pyrido[3,2-e]-1,3-thiazin-4-one. The reaction procedure of Example 57 The product was then recrystallized from ethanol

Conditions: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of N-propylaniline (24 parts), 2-ethylhexyl bromide (58 parts), anhydrous potassium carbonate (42 parts) and dry N,N-dimethylformamide (50 parts) was stirred at 125° C. for 16 hours. The cooled reaction mixture was poured into water (250 parts), the organic phase separated and washed with water (2×200 parts) and dried at 90° C. and 15 mmHg to yield N-(2-ethylhexyl)-N-propylaniline (49 parts, 89%). Acetic anhydride was added to this to make a total of 69.5 parts. The cooled reaction mixture the organic phase separated washed with water (2×200 parts) dried at 90° C.

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Propylaniline was prepared from aniline and propionic 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-phenyl-N-propylbenzamide as a light yellow solid. NMR (200 MHz, DMSO-d6): δ0.87 (t, J=7.4 Hz, 3H); 0.91 (d, J=5.9 Hz, 3H); 0.98 (d, J=6.0 Hz, 3H); 1.51 (m, 2H); 1.69 (dd, J1 =7.2 Hz, J2 =10.9 Hz, 1H); 2.06 (dd, J1 =7.0 Hz, J2 =10.5 Hz, 1H); 2.30 (d, J=10.3 Hz, 1H); 2.39-2.54 (m, 2H); 2.65 (br d, J=10.3 Hz, 1H); 2.85 (dd, J1 =7.4 Hz, J2 =14.5 Hz, 1H); 3.16 (dd, J1 =5.1 Hz. J2 =14.2 Hz, 1H); 3.79 (t, J=7.6 Hz, 2H); 4.77 (s, 1H); 5.12 (d, J=10.2 Hz, 1H); 5.18 (d, J=16.0 Hz, 1H); 5.71-5.84 (m, 1H); 6.43 (d, J=7.6 Hz, 1H); 6.57 (s, 1H); 6.64 (d, J=8.0 Hz, 1H); 7.02-7.33 (m, 10H); 9.32 (s, 1H). Mass spectrum (CI--CH4) m/e: 498 (M+1,100%), 344 (23%), 153 (80%), [α]D20 =+8.9° (ethanol, c=1.1). The free amine (0.585 g) was dissolved in ethanol and titrated with ethanolic hydrogen chloride to pH 4.0 followed by precipitation with diethyl ether from dichloromethane to give 0.479 g of the monohydrochloride salt as a hygroscopic off-white powder. Calc. for C32H39N3O2HCl 0.75 H2O: C, 70.18; H, 7.64; N, 7.67; Cl, 6.47. Found: C, 70.16; H, 7.73; N, 7.59; Cl, 6.51. purified by the methods

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture consisting of 100 mg of 4-[N-methyl-N-(3,5-bistrifluoromethyl-benzoyl)-amino]-5-(naphth-2-yl)-pentanoic acid, 29.9 mg of N-propyl-aniline, 85.3 mg of propanephosphonic acid anhydride, 154 νl of triethylamine and 2 ml of methylene chloride is left to stand at room temperature for 18 hours. 0.5 ml of 1N potassium carbonate solution is then added and the mixture is shaken vigorously. After separation of the phases, the organic phase is separated off and concentrated by evaporation. Chromatography of the residue over silica gel with methylene chloride/methanol 19:1 yields the title compound in the form of a yellow foam. Rf value=0.63 (methylene chloride/methanol 19:1). is left After separation of the phases the organic phase is separated off concentrated by evaporation

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture consisting of 100 mg of 4-[N-methyl-N-(3,5-bistrifluoromethyl-benzoyl)-amino]-5-(naphth-2-yl)-pentanoic acid, 29.9 mg of N-propyl-aniline, 85.3 mg of propanephosphonic acid anhydride, 154 νl of triethylamine and 2 ml of methylene chloride is left to stand at room temperature for 18 hours. 0.5 ml of 1N potassium carbonate solution is then added and the mixture is shaken vigorously. After separation of the phases, the organic phase is separated off and concentrated by evaporation. Chromatography of the residue over silica gel with methylene chloride/methanol 19:1 yields the title compound in the form of a yellow foam. Rf value=0.63 (methylene chloride/methanol 19:1). is left After separation of the phases the organic phase is separated off concentrated by evaporation

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The reaction procedure of Example 57 was followed except that 1.763 g (11.2 mmol) of 2-chloronicotinic acid, 15 ml of thionyl chloride, two droplets of DMF, 894 mg of ammonium thiocyanate, 15 ml of acetone, 1.59 g of N-propylaniline and 10 ml of acetone were used. The product was then recrystallized from ethanol to obtain 2.68 g of 2-(N-phenyl-N-propylamino)-4H-pyrido[3,2-e]-1,3-thiazin-4-one. The reaction procedure of Example 57 The product was then recrystallized from ethanol