Acetic Acid → HCID 59456019, Verbindung

A solution of N-[1-{[3-(aminomethyl)phenyl]methyl}-5-fluoro-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide (for a preparation see Intermediate 61) (49 mg, 0.10 mmol) in dry DMF (4 mL) was treated with HATU (38.7 mg, 0.10 mmol) and stirred under nitrogen for 3 min prior to the addition of DIPEA (0.018 mL, 0.10 mmol). The reaction mixture was stirred for a further 3 min prior to the addition of acetic acid (6.12 mg, 0.10 mmol) and stirring continued for a further 3 h. The reaction mixture was concentrated by nitrogen in a blowdown unit and the sample was loaded in dichloromethane onto aminopropyl ion-exchange cartridge (1 g) pre-equilibrated with DCM. The sample was eluted with methanol/dichloromethane and dried under a stream of nitrogen in the Radleys blowdown apparatus to give the crude product. The sample was dissolved in 1:1 MeOH-DMSO (1 mL) and purified by Mass Directed AutoPrep on Xbridge column using Acetonitrile Water with an ammonium carbonate modifier (Method C). The solvent was evaporated in vacuo using the Genevac to give the title compound (14.5 mg, 27%): LCMS (System A) RT=1.06 min, ES+ve m/z 523/525 (M+H)+.

1. stirringThe reaction mixture was stirred for a further 3 min
2. stirringstirring
3. waitcontinued for a further 3 h
4. concentrationThe reaction mixture was concentrated by nitrogen in a blowdown unit
5. washThe sample was eluted with methanol/dichloromethane
6. customdried under a stream of nitrogen in the Radleys blowdown apparatus
7. customto give the crude product
8. custompurified by Mass Directed AutoPrep on Xbridge column
9. customThe solvent was evaporated in vacuo

ORD-Eintrag

ord-92ebc03df48c4aa797bb3121c4485a9a

Quelldatensatz

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08357716B2