Bromodifluoromethyl diethylphosphonate → N-(7-(Difluoromethoxy)isoquinolin-3-yl)cyclopropanecarboxamide

HRID 468800

Reaktionsgleichung

[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:17][CH2:16]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1.Br[C:19](P(=O)(OCC)OCC)([F:21])[F:20]>C(#N)C.O.C(OCC)(=O)C>[F:20][CH:19]([F:21])[O:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:16][CH2:17]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1

Komponenten

Reaktionsbedingungen

Temperatur: -78 °C

Versuchsvorschrift

A solution of N-(7-hydroxyisoquinolin-3-yl)cyclopropanecarboxamide (91.2 mg, 0.40 mmol), diethyl bromodifluoromethylphosphonate (212 mg, 0.80 mmol) in acetonitrile/water (1:1, 5 mL) was mixed and stirred at −78° C. After the reaction mixture was warmed to room temperature and stirred for 20 minutes, the reaction mixture was diluted with ethyl acetate, and the organic phase was separated. The water phase was extracted with ethyl acetate, and the combined organic layer was dried, concentrated and purified by prep-HPLC to give product (42.8 mg, 26%). LCMS (ESI): RT (min)=0.994, M+H+=279.0, method=A. 1H NMR (400 MHz, DMSO-d6) δ 8.92 (s, 1H), 8.54 (s, 1H), 8.37 (s, 1H), 7.79 (d, J=8.8 Hz, 1H), 7.54 (s, 1H), 7.43 (dd, J=2.4, 8.8 Hz, 1H), 6.61 (t, J=73.2 Hz, 1H), 1.71-1.57 (m, 1H), 1.15-1.11 (m, 2H), 0.95-0.89 (m, 2H).

Aufarbeitung

temperatureAfter the reaction mixture was warmed to room temperature
stirringstirred for 20 minutes
customthe organic phase was separated
extractionThe water phase was extracted with ethyl acetate
customthe combined organic layer was dried
concentrationconcentrated
custompurified by prep-HPLC

Quellen und Nachweise

ORD-Eintrag: ord-aef7cf60683146efa12c723ea2853134
Quelldatensatz: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08623889B2

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