Water → HCID 56655590, compound

Participants

Reaction Steps

In a 100 mL round-bottomed flask, (S)-6-tert-butyl-2-(3-(5-(5-(2-(tert-butyldimethylsilyloxy)-3-methoxypropoxy)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)-2-(hydroxymethyl)phenyl)-8-fluorophthalazin-1(2H)-one (214 mg, 287 mmol, Eq: 1.00) was combined with THF (6.0 ml) to give a yellow solution. TBAF (500 μl of a 1M solution in THF, 500 μmol) was added and the resultant solution was stirred at 25° C. for 1 h. The reaction was complete by LCMS. The reaction mixture was poured into 75 mL H2O and extracted with EtOAc (1×75 mL). An emulsion resulted. Saturated NaCl was added and the EtOAc layer was separated. Extracted 2 times with DCM. No product left in aqueous phase by LCMS. The organic layers were combined, dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 24 g, 0.5% to 4% MeOH in DCM) to afford a glass. The glass was taken up in EtOAc/hexane and conc. to give a semisolid, which was triturated with ether. The resulting white solid was washed with ether/hexanes to give 112 mg of pure product as a white powder. (M+H)+=631 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.44 (s, 9H) 3.44 (s, 3H) 3.53-3.64 (m, 2H) 3.91 (s, 3H) 4.03-4.11 (m, 2H) 4.13-4.22 (m, 1H) 4.42 (s, 2H) 6.98 (d, J=8.69 Hz, 1H) 7.28-7.35 (m, 1H) 7.43-7.62 (m, 4H) 7.64-7.69 (m, 1H) 8.06 (d, J=3.02 Hz, 1H) 8.27-8.32 (m, 2H) 8.48 (s, 1H)

Provenance & Evidence