5-aMino-1-cyclohexyl-1h-pyrazole-4-carboxaMide synthesis

Yield:21254-07-9 72%

Reaction Conditions:

Stage #1: 5-amino-1-cyclohexyl-1H-pyrazol-4-carbonitrilewith sulfuric acid at 0 - 25; for 3 h;
Stage #2: with ammonia;water pH=8 - 9;

Steps:

1.2

Step 2: 5-Amino-l -cyclohexyl-lH-pyrazole-4-carboxylic acid amide; [00266] Concentrated sulfuric acid (98 %, 100 mL) was cooled to 0 - 5 ⁰C, and 5-amino-l- cyclohexyl-lH-pyrazole-4-carbonitrile (14.0 g, 73.6 mmol) was added portionwise with vigorous stirring whilst maintaining the temperature below 10 ⁰C . The mixture was stirred at 0 - 5 ⁰C for 2 h, then allowed to warm to 25 ⁰C and stirred at this temperature for 1 h. The mixture was poured onto crushed ice and basified to pη 8-9 by cautious addition of ammonium hydroxide solution. The EPO precipitate was collected by filtration and the filtrate was extracted with EtOAc (4 x 150 mL). The combined organic phases were washed with brine (100 mL), dried (MgSO/i) and concentrated to dryness. The resulting solid was mixed with the previously obtained precipitate and the mixture was triturated with diethyl ether and petroleum ether 40-60 ⁰C (1 :20) and the solid was collected by filtration. The title compound was isolated as a yellow solid (11.0 g, 72 %) that was used without further purification. ¹H NMR (400MHz, dg-DMSO): δ 7.65 (IH, s), 7.16 (2H, br s), 6.19 (2H, s), 4.06 - 3.98 (IH, m), 1.83 - 1.66 (7H, m), 1.42 - 1.33 (2H, m), 1.23 - 1.14 (IH, m).

References:

WO2008/55959,2008,A1 Location in patent:Page/Page column 62-63