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

HRID 1502318

반응식

HRID 1502318 반응식
[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

참가 물질

5

반응물 2

HCID 144101Bromodifluoromethyl diethylphosphonateHCID 67975011N-(7-hydroxyisoquinolin-3-yl)cyclopropanecarboxamide

생성물 1

HCID 67976733N-(7-(Difluoromethoxy)isoquinolin-3-yl)cyclopropanecarboxamide수율 38.5%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 18373917Acetonitrile--water (1/1)용매

반응 조건

온도
-78 °C

실험 절차

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).

후처리

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

출처 및 근거

ORD 기록
ord-0bbbeff3f63a4a57a25309ee8e400795
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09206175B2

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