Acetic Acid → N-[(4-{[3-{[(5-Chloro-2-thienyl)sulfonyl]amino}-4-(methyloxy)-1H-indazol-1-yl]methyl}phenyl)methyl]acetamide

A solution of N-[1-{[4-(aminomethyl)phenyl]methyl}-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide formate salt for a preparation see Intermediate 30) (15 mg, 0.03 mmol) and acetic acid (0.001 mL, 0.03 mmol) in acetonitrile (2 mL) and DIPEA (0.046 mL, 0.26 mmol) was treated with HATU (37.0 mg, 0.097 mmol) and the resulting mixture was stirred for 2 h and 15 min at ambient temperature. The reaction mixture was diluted with DCM (2 mL) and water (3 mL). The organic was separated and the aqueous layer was further extracted with DCM (2 mL). The combined organic solutions were dried through an hydrophobic frit and concentrated under reduced pressure. The residue was dissolved in 1:1 MeOH-DMSO (1 mL) and purified by Mass Directed AutoPrep on (supelcosil ABZ+Plus column) eluting with solvents A/B (A: Water+0.1% Formic acid, B: MeCN:Water 95:5+0.05% Formic acid). The solvent was removed under a stream of nitrogen in a Radleys blowdown apparatus to give the title compound (13 mg, 87%) as a gum. LCMS (System A) RT=1.11 min, ES+ve m/z 505/507 (M+H)+.

1. customThe organic was separated
2. extractionthe aqueous layer was further extracted with DCM (2 mL)
3. customThe combined organic solutions were dried through an hydrophobic frit
4. concentrationconcentrated under reduced pressure
5. dissolutionThe residue was dissolved in 1:1 MeOH-DMSO (1 mL)
6. custompurified by Mass Directed AutoPrep on (supelcosil ABZ+Plus column)
7. washeluting with solvents A/B (A: Water+0.1% Formic acid, B
8. customThe solvent was removed under a stream of nitrogen in a Radleys blowdown apparatus

ORD-Eintrag

ord-a2700346d4514487a76c55d89a1acdce

Quelldatensatz

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08357716B2