Hydrochloric Acid → 7-(3-azetidinyl)-5-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Participants

Reaction Conditions

Reaction Steps

To 1,1-dimethylethyl 3-(4-amino-5-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-azetidinecarboxylate (198 mg, 0.368 mmol) was added 4N HCl in dioxane (4 mL, 16.00 mmol). The starting material was oiling out of solution and even heating to 50 degrees C. overnight did not effect conversion. The reaction was then concentrated and DCM (4 mL) and TFA (2 ml) was added. The SM dissolved into solution and after 1 hr the reaction was complete. The reaction was concentrated then diluted with EtOAc (20 mL) and then washed with Sat. Na2CO3. A precipitate cashed out of solution and the mixture was extracted with a mixture of 20% isoproyl alcohol in DCM (3×50 ml). The organics were pooled and dried over Na2SO4, filtered and concentrated to give a yellow oil. The oil was dissolved in 1 ml of DMF and then loaded on to a 10 g Biotage column with 0 to 100% DCM in 95:5:1 mixture of DCM:MeOH:1NH4OH for 15 min then 100% 95:5:1 mixture of DCM:MeOH:1NH4OH for 15 minutes to isolate 7-(3-azetidinyl)-5-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7H-pyrrolo[2,3-d]pyrimidin-4-amine (103 mg, 0.235 mmol, 63.9% yield) as a clear oil. LC-MS (ES) m/z=439.4 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 8.15 (d, J=8.34 Hz, 1H), 8.13 (s, 1H), 7.62 (s, 1H), 7.36 (s, 1H), 7.25-7.30 (m, 1H), 7.23 (d, J=7.33 Hz, 1H), 7.06-7.14 (m, 3H), 6.09 (br. s., 2H), 5.50 (t, J=7.45 Hz, 1H), 4.22 (t, J=8.34 Hz, 2H), 3.91-3.96 (m, 2H), 3.78-3.85 (m, 4H), 3.18-3.25 (m, 2H), 2.31 (s, 3H).

Provenance & Evidence