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

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)+.

1. customat room temp
2. stirringstirred overnight
3. extractionthe product was extracted with EtOAc (15 mL×3)
4. customThe combined organic layers were dried
5. concentrationconcentrated in vacuo
6. stirringthe reaction was stirred at room temp over 1 h
7. washeluting with methanol and 2M ammonia in methanol
8. customevaporated in vacuo

ORDレコード

ord-4b9c19ab43ec4e2483777d0f31f9ce56

出典データセット

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08357716B2