TRANS-2-AMINOCYCLOHEXANOL HYDROCHLORIDE

white or beige to light brown crystalline powder

To a suspension of l-(2-fluoro-4-(l-methyl-lH-pyrazol-4-yl)benzyl)-lH-pyrrolo[3, 2-b]pyridine- 3-carbonyl chloride hydrochloride (Example A4) (100 mg, 247 muiotaetaomicron) in N, N- dimethylformamide (1.00 ml) under nitrogen at room temperature, was added triethylamine (99.9 mg, 137 mu, 987 muiotaetaomicron). After 5 minutes, a) 5-Bromo-N-((ilS, R, 2RlS, )-2-hydroxy-cyclohexyl)-6-(2, 2, 2-trifluoro-ethoxy)-nicotinamide5-Bromo-6-(2, 2, 2-trifluoro-ethoxy)-nicotinic acid (75.0 g, 0.25 mol) was dissolved in DMF (850 mL). To the solution was added TBTU (91.0 g, 0.275 mol), N, N-diisopropylethyl amine (214 mL, 1.25 mol) and (7SR, 2RS)-2-amino-cyclohexanol hydrochloride (41.7 g, 0.275 mol). The reaction mixture was stirred for 1.5 h at room temperature. The solvent wasevaporated in vacuo, the residue was partitioned between ethyl acetate (2500 mL) and 1 N sodium hydroxide solution (2000 mL), the water phase was separated, extracted once more with ethyl acetate (1000 mL) and the organic phases were washed 2 times with water (2x1500 mL). Organic phases were pooled, dried with MgS04 and concentrated to about 900 mL. The product precipitated upon stirring and cooling to 0°C. Filtration, washing with ethyl acetate/n-heptane (1: 1) and drying in vacuo gave the title compound (81.1 g) as a white solid; MS (ISP) 397, 399 (M)+.a)5-Bromo-N-((1SR, 2RS)-2-hydroxy-cyclohexyl)-6-(2, 2, 2-trifluoro-ethoxy)-nicotinamide5-Bromo-6-(2, 2, 2-trifluoro-ethoxy)-nicotinic acid (75.0 g, 0.25 mol) was dissolved in DMF (850 mL).To the solution was added TBTU (91.0 g, 0.275 mol), N, N-diisopropylethyl amine (214 mL, 1.25 mol) and

NSC 21550 is used in preparation of Benzoxazinone derivatives.