2-(trans-4-Aminocyclohexyl)propan-2-ol

Description

2-(trans-4-Aminocyclohexyl)propan-2-ol is a white solid organic heterocyclic compound and a pharmaceutical intermediate component for the synthesis of PIM Kinase Inhibitor TP-3654, which is an orally available second-generation PIM Kinase Inhibitor TP-3654 is an orally available second-generation selective ATP-competitive proviral integration site inhibitor for the treatment of Moloney murine leukaemia virus (PIM) kinase, with potential anti-tumour activity.

The Uses of 2-(trans-4-Aminocyclohexyl)propan-2-ol

trans-2-(4-Aminocyclohexyl)-2-hydroxypropane can be used as organic synthesis intermediate and pharmaceutical intermediate, mainly used in laboratory research and development process and chemical production process.

Synthesis

Step 1
To a solution of trans-benzyl 4-(dibenzylamino)cyclohexanecarboxylate (290 g X 5, 3.6 mol) in 2 L of THF under N2 at 0 °C, MeMgBr (800 mL) was added. The mixture was stirred at room temperature overnight and then quenched with 1.5 L of saturated NH4Cl. The resulting mixture was extracted wtih EtOAc. The product was extracted with 1 M HCl to the aqueous phase, which was then wash with EtOAc. The aqueous phase was then neutralized with NaOH, extracted with EtOAc, washed with brine, dried with Na2SO4 and concentrated in vacuo to give the 2-(trans-4-(dibenzylamino)cyclohexyl)propan-2-ol. White solid, yield 950 g, 78.3%.
Step 2
A mixture of 2-(trans-4-(dibenzylamino)cyclohexyl)propan-2-ol (120 g X 8,356mmol) and Pd(OH)2 (15g X 8) in methanol (1000 mL) and MeOH/NH3(100 mL) was stirred under H2 (50 psi) at 50 °C for 72 hrs, then the catalyst was removed and the filtrate was concentrated in vacuo and The crude product was chromatographed on silica gel (DCM/MeOH 20:1 - DCM/MeOH/NH3 5:4:1) to give the 2-(trans-4-aminocyclohexyl)propan-2-ol. Yield 210 g, 47.5%, pale yellow solid.