Reaktion #41493

ord-e4fda28d383d4f0894603e5dff2c1df9

Reaktionsgleichung

CCOC(=O)C(C)(F)F
Ethyl 2,2-difluoropropanoate
COc1cccc([C@@H](Oc2ccc3c(cnn3-c3ccc(F)cc3)c2)[C@H](C)N)c1
(1R,2S)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-amine
COc1cccc([C@@H](Oc2ccc3c(cnn3-c3ccc(F)cc3)c2)[C@H](C)N)c1
(1R,2S)-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-(3-methoxyphenyl)propan-2-amine
→
COc1cccc([C@@H](Oc2ccc3c(cnn3-c3ccc(F)cc3)c2)[C@H](C)NC(=O)C(C)(F)F)c1
2,2-difluoro-N-((1R,2S)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-yl)propanamide

Edukte

CCOC(=O)C(C)(F)F
Ethyl 2,2-difluoropropanoate
COc1cccc([C@@H](Oc2ccc3c(cnn3-c3ccc(F)cc3)c2)[C@H](C)N)c1
(1R,2S)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-amine
COc1cccc([C@@H](Oc2ccc3c(cnn3-c3ccc(F)cc3)c2)[C@H](C)N)c1
(1R,2S)-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-(3-methoxyphenyl)propan-2-amine

Reagenzien

Keine

Lösungsmittel

CC#N
acetonitrile

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    Sonstigepurified by semiprep HPLC

Vorschrift

Ethyl 2,2-difluoropropanoate (400 μl) and (1R,2S)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-amine (6a, 135 mg, 0.34 mmol) was heated to 150° C. for 30 min. Then it was diluted with acetonitrile and purified by semiprep HPLC followed by flash chromatography on silica gel (n-heptane/ethyl acetate, 4:1) Yield 60 mg (36%).

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US07728030B2uspto-grants-2010_06