Hydrochloric Acid → HCID 178482658, compound

A solution of HCl in MeOH (1:1, 3 ml) was added to 7-[(3aS,4R,6R,6aR)-2,2-dimethyl-6-({methyl[(3-{[5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]methyl}cyclobutyl)methyl]amino}methyl)-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine at 0° C. and stirred. This was then immediately stirred at 40° C. for 4 h (reaction monitored by LCMS) The reaction was continued for a further 1 h. LCMS still showed 30% acetal deprotected SM. A further 1 ml of HCl (36% aq) was added to the reaction mixture and continued at 40° C. for a further 1 h. The reaction mixture was then evaporated in vacuo. The residue was dissolve in DCM (100 ml)+MeOH (1 ml) and washed with sat. NaHCO3 (2×50 ml), dried over Na2SO4, filtered and evaporated. Purification by prep.TLC, eluting with 7N NH3 in MeOH:DCM (1:9); MS (ESI+) for C27H32F3N7O2 m/z 544 [M+H]+; HPLC purity 96% (ret. time, 2.03 min); 1H NMR (500 MHz, MeOD) δH ppm 1.47-1.58 (1 H, m), 1.58-1.69 (1 H, m), 1.87-2.12 (1 H, m), 2.12-2.54 (10 H, m), 2.53-2.91 (3 H, m), 2.93-3.15 (2 H, m), 3.88-4.08 (1 H, m), 4.32 (1 H, dd, J=7.57, 6.15 Hz), 4.88-5.01 (1 H, m), 6.59 (1 H, d, J=3.63 Hz), 7.20 (1 H, d, J=3.63 Hz), 7.42-7.53 (1 H, m), 7.63 (1 H, d, J=8.20 Hz), 7.79 (1 H, s), 7.95-8.22 (1 H, m).

1. stirringThis was then immediately stirred at 40° C. for 4 h
2. custom(reaction monitored by LCMS) The reaction
3. waitcontinued at 40° C. for a further 1 h
4. customThe reaction mixture was then evaporated in vacuo
5. dissolutionThe residue was dissolve in DCM (100 ml)+MeOH (1 ml)
6. washwashed with sat. NaHCO3 (2×50 ml)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. customevaporated
10. customPurification by prep.TLC,
11. washeluting with 7N NH3 in MeOH:DCM (1:9)
12. customHPLC purity 96% (ret. time, 2.03 min)

ORD record

ord-04f2faff3032476b8b0f675e3c5bd677

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08580762B2