Hydrochloric Acid → HCID 68109783, compound

Participants

Reaction Steps

Into a 50-mL round-bottom flask, a solution of tert-butyl N-(4-[[(3R)-3-(2-cyano-2-methoxyethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamate (100 mg, 0.21 mmol, 1.00 equiv) in dichloromethane (10 mL) was added hydrochloric acid (12 M, 0.5 mL) in a water/ice bath and stirred for 4 h. After completion and concentration in vacuo, the residue was neutralised with saturated aqueous sodium bicarbonate, extracted with 3×50 mL of DCM. The combined organic layers were concentrated under vacuum and the crude product (80 mg) was purified by preparative HPLC under the following conditions: (SHIMADZU): column: Xbridge Prep C18 5 um, 19*150 mm; mobile phase: water with 0.05% NH4HCO3 and CH3CN (6.0% CH3CN up to 56.0% in 15 min); flow rate: 20 mL/min; UV detection at 254/220 nm. The product-containing fractions were collected and partially evaporated to remove water and CH3CN under reduced pressure. The residue was lyophilized overnight to give the corresponding (2S)-2-methoxy-3-[(3R)-12-[[4-(methylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]propanenitrile (12.5 mg) as a off-white semi-solid and (2R)-2-methoxy-3-[(3R)-12-[[4-(methylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]propanenitrile (3.5 mg) as a light yellow semi-solid, respectively.

Provenance & Evidence