cycloheptylmethanamine

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: Synthesised similar to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is 2-chloroethylmalonate, and Z is cycloheptylmethyl amine. The resulting product XYZ is stirred for 30 minutes at −10° C. in methanol and NaBH4 and then slowly warmed to room temperature and stirred for 2 hour. The reaction mixture is then treated with a 1N aqueous HCl solution (pH ˜8) and concentrated to obtain a residue that is taken up in water and acidified with 1N aqueous HCl solution (pH ˜6.5 to 7). The formed precipitate is then collected by filtration, washed with water, pet ether, ethyl acetate and finally with n-Pentane, then dried under vacuum. Formula: C20H27ClN2O3; Molecular Weight: 378.89; Mass/charge ratio: 378.17 (100.0%), 380.17 (32.1%), 379.17 (22.4%), 381.17 (7.3%), 380.18 (2.9%); Elemental analysis: C, 63.40; H, 7.18; Cl, 9.36; N, 7.39; O, 12.67. Synthesised similar to the procedure concentrated to obtain a residue that The formed precipitate is then collected by filtration washed with water, pet ether, ethyl acetate and finally with n-Pentane dried under vacuum Mass/charge ratio

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

Procedure: Synthesised similar to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is 2-chloroethylmalonate, and Z is cycloheptylmethyl amine. The resulting product XYZ is stirred for 30 minutes at −10° C. in methanol and NaBH4 and then slowly warmed to room temperature and stirred for 2 hour. The reaction mixture is then treated with a 1N aqueous HCl solution (pH ˜8) and concentrated to obtain a residue that is taken up in water and acidified with 1N aqueous HCl solution (pH ˜6.5 to 7). The formed precipitate is then collected by filtration, washed with water, pet ether, ethyl acetate and finally with n-Pentane, then dried under vacuum. Formula: C20H27ClN2O3; Molecular Weight: 378.89; Mass/charge ratio: 378.17 (100.0%), 380.17 (32.1%), 379.17 (22.4%), 381.17 (7.3%), 380.18 (2.9%); Elemental analysis: C, 63.40; H, 7.18; Cl, 9.36; N, 7.39; O, 12.67. Synthesised similar to the procedure concentrated to obtain a residue that The formed precipitate is then collected by filtration washed with water, pet ether, ethyl acetate and finally with n-Pentane dried under vacuum Mass/charge ratio

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

Procedure: Synthesised similar to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is 2-chloroethylmalonate, and Z is cycloheptylmethyl amine. The resulting product XYZ is stirred for 30 minutes at −10° C. in methanol and NaBH4 and then slowly warmed to room temperature and stirred for 2 hour. The reaction mixture is then treated with a 1N aqueous HCl solution (pH ˜8) and concentrated to obtain a residue that is taken up in water and acidified with 1N aqueous HCl solution (pH ˜6.5 to 7). The formed precipitate is then collected by filtration, washed with water, pet ether, ethyl acetate and finally with n-Pentane, then dried under vacuum. Formula: C20H27ClN2O3; Molecular Weight: 378.89; Mass/charge ratio: 378.17 (100.0%), 380.17 (32.1%), 379.17 (22.4%), 381.17 (7.3%), 380.18 (2.9%); Elemental analysis: C, 63.40; H, 7.18; Cl, 9.36; N, 7.39; O, 12.67. Synthesised similar to the procedure concentrated to obtain a residue that The formed precipitate is then collected by filtration washed with water, pet ether, ethyl acetate and finally with n-Pentane dried under vacuum Mass/charge ratio

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

Procedure: In a manner analogous to the method described in example 163, {1-[(4S,5R)-2-(6-tert-butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperidin-4-yl}-acetic acid was reacted with N-cycloheptylmethyl-amine (Aldrich) to give the title compound. HR-MS (ES, m/z) calculated for C44H58Cl2N5O3 [(M+H)+] 774.391 1, observed 774.3909.

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

Procedure: The title compound was prepared from (3-{2-[((2R)-2-[4-(benzyloxy)-3-(hydroxymethyl)phenyl]-2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)amino]-2-methyl propyl}phenyl)acetic acid (preparation 148) and cycloheptane methylamine, using a similar method to that of preparation 38, as a white solid in 97% yield. 1H NMR (400 MHz, CD3OD) δ: 7.72 (1H, dd), 7.44 (1H, d), 7.42 (2H, m), 7.38-7.21 (5H, m), 7.19 (1H, d), 7.07 (1H, d), 7.02 (1H, m), 5.08 (2H, d), 5.03 (1H, m), 4.71 (2H, d), 3.51 (2H, d), 3.03-2.96 (4H, m), 1.77-1.34 (13H, m), 1.28 (6H, m), 1.07 (2H, m), 0.93 (9H, s), 0.07 (3H, s), −0.92 (3H, s) ppm; LRMS ESI m/z 688 [M+H]+ of preparation 38

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 5-mL process vial was charged with 2-cyclopropyl-5-iodoisoquinolin-1(2H)-one (100 mg, 0.0004 mol), cycloheptylmethanamine (100 mg, 0.001 mol), molybdenum hexacarbonyl (90 mg, 0.0004 mol), palladium acetate (8 mg, 0.00004 mol), 1,8-diazabicyclo[5.4.0]undec-7-ene (200 mg, 0.001 mol) and 1,4-dioxane (2 mL, 0.02 mol). The vessel was sealed under air and exposed to microwave heating for 15 min at 110° C. The reaction tube was thereafter cooled to room temperature, and the mixture was concentrated and dissolved in a small volume of dichloromethane. The crude product was purified via flash column chromatography (12 g of silica gel, 30% EtOAC/Hexane) to give the desired product as a white solid. The vessel was sealed under air The reaction tube was thereafter cooled to room temperature the mixture was concentrated dissolved in a small volume of dichloromethane The crude product was purified via flash column chromatography (12 g of silica gel, 30% EtOAC/Hexane)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 5 ml microwave reaction vessel was combined 2-(2-hydroxyethyl)-5-iodoisoquinolin-1(2H)-one (0.100 g, 0.000317 mol), cycloheptylmethanamine (100 mg, 0.0008 mol), molybdenum hexacarbonyl (80 mg, 0.0003 mol), palladium acetate (7 mg, 0.00003 mol), 1,8-diazabicyclo[5.4.0]undec-7-ene (0.1 mL, 0.001 mol) and 1,4-dioxane (1 mL, 0.02 mol). The vessel was exposed to microwave heating for 15 min at 110° C. The reaction tube was cooled to room temperature and the volatiles removed under educed pressure. The mixture was purified directly by column chromatography using an methanol:methylene chloride (0-10%) gradient. The combined pure fractions were reduced in vacuo to yield a white solid which was purified again by HPLC to afford the title compound as a white solid. 1H NMR (DMSO-d6) δ: 8.55 (t, 1H), 8.31 (d, 1H), 7.72 (dd, 1H), 7.517 (t, 1H), 7.446 (d, 1H), 6.76 (d, 1H), 4.88 (t, 1H) 4.014 (t 2H), 3.66 (q, 2H) 3.123 (t, 2H), 1.79-1.34 (m, 11H), 1.2615-1.149 (m, 2H) Into a 5 ml microwave reaction vessel was combined The reaction tube was cooled to room temperature the volatiles removed under educed pressure The mixture was purified directly by column chromatography to yield a white solid which was purified again by HPLC