1,4-Dioxane → N-[1-{[3-(Aminomethyl)phenyl]methyl}-4-(1-hydroxy-1-methylethyl)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide

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Reaction Steps

Methylmagnesium bromide (3M solution in diethyl ether) (0.730 mL, 2.191 mmol) was added slowly dropwise to a stirring solution of 1,1-dimethylethyl({3-[(4-acetyl-3-{[(5-chloro-2-thienyl)sulfonyl]amino}-1H-indazol-1-yl)methyl]phenyl}methyl)carbamate (for a preparation see Intermediate 76) (210 mg, 0.365 mmol) in THF (3 mL) at room temp. The reaction was stirred for 2 h and then more methylmagnesium bromide (3M solution in diethyl ether) (0.730 mL, 2.191 mmol) was added and stirred overnight. LCMS indicated molecular ion 592 [M+1] corresponding to the desired alcohol and that the starting material co-eluted with the product. 1N HCl (5 mL) was added and the product was extracted with EtOAc (15 mL×3). The combined organic layers were dried by passing through a hydrophobic frit and concentrated in vacuo. The residue was dissolved in 4N HCl in Dioxane (2 mL, 8.00 mmol) and the reaction was stirred at room temp over 1 h. The reaction mixture was loaded on an SCX-2 ion-exchange 20 g cartridge eluting with methanol and 2M ammonia in methanol. The appropriate ammoniacal fractions were combined and evaporated in vacuo to give the title compound (168 mg, 76%) as a brown oil. LCMS (System A) RT=0.79 min, ES+ve m/z 491/493 (M+H)+.

Provenance & Evidence