3-Chlorophenol → HCID 68095475, compound

HRID 1502315Notes

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.[Cl:18][C:19]1[CH:20]=[C:21]([OH:25])[CH:22]=[CH:23][CH:24]=1.CC(C)(C(=O)CC(=O)C(C)(C)C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1CCCC1=O.ClCCl.[Cu]Cl>[Cl:18][C:19]1[CH:20]=[C:21]([CH:22]=[CH:23][CH:24]=1)[O:25][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

Participants

Conditions

Temperature: 180 °C

Procedure

A mixture of N-(7-Bromoisoquinolin-3-yl)cyclopropanecarboxamide (89 mg, 0.30 mmol), 3-chlorophenol (115.2 mg, 0.90 mmol), 2,2,6,6-tetramethylheptane-3,5-dione (27.6 mg, 0.15 mmol), copper(I) chloride (30 mg, 0.30 mmol) and cesium carbonate (292.5 mg, 0.90 mmol) in 1-methyl-2-pyrrolidinone (2.5 mL) was stirred under microwave irradiation at 180° C. for 99 minutes 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 filtrates were concentrated and purified by prep-HPLC to give the product (28.5 mg, 13%). LCMS (ESI): RT (min)=1.237, M+H+=338.8, method=A; 1H NMR (400 MHz, DMSO-d6) δ 10.93 (s, 1H), 9.06 (s, 1H), 8.41 (s, 1H), 8.02 (t, J=0.8 Hz, 1H), 7.84 (d, J=8.8 Hz, 1H), 7.53 (dd, J=1.6, 8.4 Hz, 1H), 7.38-7.31 (m, 5H), 2.09-1.99 (m, 1H), 0.83-0.79 (m, 4H).

Workup

filtrationfiltered through a pad of Celite
washThe filer cake was washed with dichloromethane
concentrationthe combined filtrates were concentrated
custompurified by prep-HPLC

Sources & evidence

ORD record: ord-2099945d594a4a908eabbc81200d394a
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09206175B2

Reaction notes

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