Phenol → N-(7-phenoxyisoquinolin-3-yl)cyclopropanecarboxamide

HRID 468796

Reaction equation

HRID 468796 reaction equation
Br[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.[C:18]1([OH:24])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.CC1C=NC2C(C=1C)=CC=C1C=2N=CC(C)=C1C.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1CCCC1=O.ClCCl.[Cu]I>[O:24]([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)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

8

Reactant 4

HCID 996PhenolHCID 10796Cesium carbonateHCID 742653,4,7,8-Tetramethyl-1,10-phenanthrolineHCID 67974626N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide

Product 1

HCID 67975080N-(7-phenoxyisoquinolin-3-yl)cyclopropanecarboxamideYield 32.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide (89 mg, 0.30 mmol), phenol (86.5 mg, 0.92 mmol, 3 eq), 3, 4,7,8-tetramethyl-1,10-phenanthrolin (35.4 mg, 0.15 mmol, 0.5 eq), copper(I) iodide (57.3 mg, 0.3 mmol, 1 eq) and cesium carbonate (293.2 mg, 0.9 mmol, 3 eq) in 1-methyl-2-pyrrolidinone (2.5 ml) were stirred under microwave irradiation at 180° C. for 99 min under nitrogen. The mixture was diluted with dichloromethane and filtered through a pad of Celite. The filer cake was washed with dichloromethane and the combined filtrate was concentrated and purified by prep-HPLC to give product (30 mg, 26%). LCMS (ESI): RT (min)=1.107, M+H+=305.0, method=A. 1H NMR (400 MHz, CDCl3) δ 8.76 (s, 1H), 8.46 (s, 1H), 8.24 (s, 1H), 7.72 (d, J=9.2 Hz, 1H), 7.38-7.00 (m, 5H), 1.55-1.52 (m, 1H), 1.10-1.06 (m, 2H), 0.87-0.82 (m, 2H).

Workup

  1. filtrationfiltered through a pad of Celite
  2. washThe filer cake was washed with dichloromethane
  3. concentrationthe combined filtrate was concentrated
  4. custompurified by prep-HPLC

Sources & evidence

ORD record
ord-5958112bbeeb487b926dbf700165028a
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Linked notes

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