Btk Kinase inhibitor synthesis

Yield:-

Steps:

Multi-step reaction with 6 steps
1: zinc; ammonium chloride; water / ethyl acetate / 2 h / 20 °C / Cooling with ice
2: tetrahydrofuran / 15 h / 60 °C
3: hydrogen; 10 wt% Pd(OH)2 on carbon / ethyl acetate; methanol / 7.5 h / 60 °C
4: copper diacetate; pyridine / dichloromethane / 21 h / Molecular sieve
5: hydrogenchloride / 1,4-dioxane; methanol / 1 h / 20 °C
6: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; triethylamine / N,N-dimethyl-formamide / 3 h / 20 °C

References:

EP2786996,2014,A1