1-ethylpiperidin-4-amine

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:

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

Procedure: As described for example 34, 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (100 mg, 0.32 mmol) was converted, using 1-ethylpiperidin-4-amine instead of 1-methylpiperidin-4-amine, to the title compound (99 mg, 73%) which was obtained as an off white solid. MS: m/e=421.1 [M+H]+.

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

Procedure: As described for example 34, 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (100 mg, 0.32 mmol) was converted, using 1-ethylpiperidin-4-amine instead of 1-methylpiperidin-4-amine, to the title compound (99 mg, 73%) which was obtained as an off white solid. MS: m/e=421.1 [M+H]+.

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

Procedure: 6.50 Grams (0.05 mole) of 4-amino-N-ethyl piperidine and 9.65 grams (0.05 mole) of 4-nitrophthalic anhydride were dissolved in 150 milliliters of chloroform and the solution was stirred for an hour at room temperature. The chloroform was evaporated and the solid dissolved in 50 milliliters of acetic anhydride and the solution was refluxed for an hour. The acetic anhydride was evaporated off and the dark red residue treated with isopropyl alcohol and the solvent evaporated. The residue which was a gum was repeatly subjected to treatment with isopropyl alcohol and evaporation of the solvent until a crystalline solid was produced. The solid was taken up in chloroform and this was washed with sodium bicarbonate solution, then water and then brine until the aqueous layer was neutral. The chloroform extract was dried with magnesium sulphate, filtered and evaporated to give a solid. Microanalysis showed this to be impure and the bicarbonate washing was repeated as outlined above. The dried chloroform extract was evaporated off and the residue treated with ether to give 2.5 grams of the title compound as a yellow solid, m.p. 153°-155°. The chloroform was evaporated the solid dissolved in 50 milliliters of acetic anhydride the solution was refluxed for an hour The acetic anhydride was evaporated off the dark red residue treated with isopropyl alcohol the solvent evaporated was repeatly subjected to treatment with isopropyl alcohol and evaporation of the solvent until a crystalline solid was produced this was washed with sodium bicarbonate solution The chloroform extract was dried with magnesium sulphate filtered evaporated to give a solid The dried chloroform extract was evaporated off the residue treated with ether

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

Procedure: The title compound was synthesized from (R)-4-(9-cyclohexyl-7-fluoro-7-vinyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid as described in the General procedure for amide bond synthesis using HATU and 4-amino 1-N-ethyl piperidine. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.47-2.04 (m, 16H) 2.32 (q, J=7.07 Hz, 3H) 2.88 (d, J=11.62 Hz, 2H) 3.28 (s, 3H) 3.67-3.87 (m, 3H) 3.94 (s, 3H) 4.87 (d, J=8.34 Hz, 1H) 5.30-5.45 (m, 2H) 6.01 (ddd, J=17.43, 12.88, 10.86 Hz, 1H) 7.46 (d, J=1.77 Hz, 2H) 7.82 (s, 1H) 8.12 (s, 2H) 8.30 (d, J=8.08 Hz, 1H). [M+H] calc'd for C30H40FN7O3, 566. found 566. as described in the General procedure for amide bond synthesis

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

Procedure: The title compound was synthesized from (R)-4-(9-cyclohexyl-7-fluoro-7-vinyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid as described in the General procedure for amide bond synthesis using HATU and 4-amino 1-N-ethyl piperidine. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.47-2.04 (m, 16H) 2.32 (q, J=7.07 Hz, 3H) 2.88 (d, J=11.62 Hz, 2H) 3.28 (s, 3H) 3.67-3.87 (m, 3H) 3.94 (s, 3H) 4.87 (d, J=8.34 Hz, 1H) 5.30-5.45 (m, 2H) 6.01 (ddd, J=17.43, 12.88, 10.86 Hz, 1H) 7.46 (d, J=1.77 Hz, 2H) 7.82 (s, 1H) 8.12 (s, 2H) 8.30 (d, J=8.08 Hz, 1H). [M+H] calc'd for C30H40FN7O3, 566. found 566. as described in the General procedure for amide bond synthesis

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

Procedure: Synthesized according to the method of reagent preparation 9 by using acetaldehyde and 1,1-dimethylethyl piperidin-4-ylcarbamate. MS (EI) for C7H16N2: 131 (MH+). Synthesized according to the method of reagent preparation 9

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

Procedure: The title compound, as a TFA salt, was prepared in a manner similar to Example 74 using 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and 1-ethylpiperidin-4-amine 1H NMR (400 MHz, DMSO-d6) δ ppm 1.13-1.31 (m, 3 H) 1.71-1.88 (m, 2 H) 1.91-2.20 (m, 2 H) 2.44 (s, 3 H) 3.01-3.18 (m, 3 H) 3.23-3.43 (m, 1 H) 3.55 (d, J=12.13 Hz, 2 H) 3.99-4.28 (m, 1 H) 7.67 (d, J=7.83 Hz, 1 H) 7.70-7.86 (m, 2 H) 8.07-8.31 (m, 1 H) 8.32-8.64 (m, 2 H) 8.73 (d, J=6.32 Hz, 1 H) 8.84-8.99 (m, 1 H) 9.24 (br. s., 1H) 12.78-13.45 (m, 1 H). MS m/z [M+H]+ 431.2.