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

HRID 1502318

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-0bbbeff3f63a4a57a25309ee8e400795
Quelldatensatz: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US09206175B2

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