Cesium carbonate → 7-(5-Fluoro-2-methylphenyl)isoquinolin-3-amine

HRID 1502239Notes

Reaction equation

HRID 1502239 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH2:12])[N:8]=[CH:9]2)=[CH:4][CH:3]=1.[F:13][C:14]1[CH:15]=[CH:16][C:17]([CH3:23])=[C:18](B(O)O)[CH:19]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CC#N.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:13][C:14]1[CH:19]=[CH:18][C:17]([CH3:23])=[C:16]([C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[C:7]([NH2:12])[N:8]=[CH:9]3)=[CH:4][CH:3]=2)[CH:15]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27831905-Fluoro-2-methylphenylboronic acidHCID 529877577-Bromoisoquinolin-3-amine

Product 1

HCID 574102447-(5-Fluoro-2-methylphenyl)isoquinolin-3-amineYield 79.4%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

7-Bromoisoquinolin-3-amine (15.0 g, 67.4 mmol), 5-fluoro-2-methylphenylboronic acid (12.4 g, 81.0 mmol), Pd(dppf)Cl2 (2.76 g, 3.38 mmol) and Cs2CO3 (26.4 g, 81.0 mmol) in MeCN/H2O (10:1, 150 mL) was stirred at 120° C. for 6 h under N2. After the reaction mixture was filtered, the filtrate was concentrated and purified by chromatography on silica gel to give the desired product (13.5 g, 79.4%). LCMS (ESI): RT (Min)=0.869, M+H+=252.8, method=A. 1H NMR (400 MHz, DMSO-d6) δ 8.84 (s, 1H), 7.75 (s, 1H), 7.55 (d, J=8.8 Hz, 1H), 7.44 (d, J=8.4 Hz, 1H), 7.34-7.30 (m, 1H), 7.11-7.07 (m, 2H), 6.64 (s, 1H), 6.00 (s, 2H), 2.22 (s, 3H).

Workup

  1. filtrationAfter the reaction mixture was filtered
  2. concentrationthe filtrate was concentrated
  3. custompurified by chromatography on silica gel

Sources & evidence

ORD record
ord-bc7ca472dc884741b3b374fae49848af
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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