1-(Cyclopropylmethyl)piperazine hydrochloride synthesis

Yield:-

Reaction Conditions:

with hydrogenchloride in methanol;dichloromethane;

Steps:

2A

6-(4-Cyclopropylmethyl-piperazin-l-ylmethylV2-(lH-mdazol-4-ylV4-morpholin-4- yl-thienor3,2-d1pyrimidine (88) .Prepared via 2-Chloro-6-(4-cyclopropylmethyl-piperazin- 1 -ylmethyl)-4- morpholin-4-yl-thieno[3,2-d]pyrimidine, prepared from 1-cyclopropylmethyl- piperazine.Amine preparation: A mixture of BOC-piperazine (887mgg), (bromomethyl)cyclopropane (0.5mL) and potassium carbonate (779mg) in MeCN(1OmL) was heated to reflux for 16h. The reaction mixture was cooled, diluted with chloroform, washed with brine, dried (MgSO₄) and the solvent removed in vacuo.The residue was purified using flash chromatography to yield 4-yclopropylmethyl- piperazine-1-carboxylic acid tert-butyl ester (1.05g). Treatment of this compound EPO with HCl in DCM/MeOH yielded the desired compound, which was isolated as the hydrochloride salt.¹H NMR (400MHz, CDCl₃): 0.07-0.14 (m, 2H, 2 x CH₂), 0.48-0.51 (m, 2H, 2 x CH), 0.8-0.95 (m, H, CH), 2.28-2.32 (m, 2H, CH₂), 2.5-2.7 (m, 8H, 4 x CH₂), 3.86 (s, 2H, CH₂), 3.90-3.93 (m, 4 H, 2 x CH₂), 4.07-4.11 (m, 4H, 2 x CH₂), 7.38 (s, H, ArH), 7.50 (t, H, ArH, J=7.79Hz), 7.58 (d, H, ArH, J=8.28Hz), 8.28 (d, H, ArH, J=7.57Hz), 9.02 (s, H, ArH), 10.15 (sbr, H, NH); MS (ESl⁺) 490.19 (MH⁺).

References:

WO2006/46031,2006,A1 Location in patent:Page/Page column 45-46