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

HRID 1502318

反応式

HRID 1502318 の反応式
[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

参加物

5

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 18373917Acetonitrile--water (1/1)溶媒

反応条件

温度
-78 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-0bbbeff3f63a4a57a25309ee8e400795
出典データセット
uspto-grants-2015_12
特許番号
US09206175B2

関連ノート

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