Hydrochloric Acid → N-[1-{[3-(Aminomethyl)phenyl]methyl}-4-(1-hydroxyethyl)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide

Sodium borohydride (20.52 mg, 0.543 mmol) was added 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 75) (260 mg, 0.452 mmol) in MeOH (5 mL) at 25° C. under N2. The reaction mixture was stirred at room temp for 2 h. About ˜⅔ of the methanol was evaporated in vacuo and the residue was treated slowly with 1M HCl (5 mL). The product was extracted with EtOAc (2×40 mL) and the combined organic layers were dried by passing through a hydrophobic frit and concentrated to afford a yellow oil. 4N HCl in Dioxane (2 mL, 8.00 mmol) was added to the residue at 25° C. and the reaction mixture was stirred for 30 min. The crude sample was loaded straight on to a pre-washed (MeOH)SPE sulphonic acid (SCX-2) cartridge (20 g). The SCX cartridge was washed with 2 column volumes of MeOH and the product was collected by washing with 3 column volumes of 2N Ammonia in MeOH. The appropriate fractions were combined and evaporated in vacuo to give the title compound (235 mg, 91) %. LCMS (System A) RT=0.77 min, ES+ve m/z 477/479 (M+H)+.

1. customat 25° C.
2. customAbout ˜⅔ of the methanol was evaporated in vacuo
3. additionthe residue was treated slowly with 1M HCl (5 mL)
4. extractionThe product was extracted with EtOAc (2×40 mL)
5. customthe combined organic layers were dried
6. concentrationconcentrated
7. customto afford a yellow oil
8. stirringthe reaction mixture was stirred for 30 min
9. washThe SCX cartridge was washed with 2 column volumes of MeOH
10. customthe product was collected
11. washby washing with 3 column volumes of 2N Ammonia in MeOH
12. customevaporated in vacuo

ORDレコード

ord-4dd7130289674063823944182b5b95a1

出典データセット

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08507543B2