Water → 7-(5-Fluoro-4-methylpyridin-3-yl)isoquinolin-3-amine

HRID 1502451Notes

Reaction equation

[F:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6](B2OC(C)(C)C(C)(C)O2)[C:7]=1[CH3:8].Br[C:19]1[CH:28]=[C:27]2[C:22]([CH:23]=[C:24]([NH2:29])[N:25]=[CH:26]2)=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+].C(#N)C.O>C(OCC)(=O)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[F:1][C:2]1[C:7]([CH3:8])=[C:6]([C:19]2[CH:28]=[C:27]3[C:22]([CH:23]=[C:24]([NH2:29])[N:25]=[CH:26]3)=[CH:21][CH:20]=2)[CH:5]=[N:4][CH:3]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (261 mg; 0.7706 mmol), 7-bromoisoquinolin-3-amine (233.1 mg; 1.045 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (52.8 mg; 0.0746 mmol), potassium carbonate (338 mg; 2.44566 mmol), acetonitrile (3.0 mL; 57 mmol) and water (0.30 mL; 17 mmol) was heated at 120° C. for 40 minutes. The reaction mixture was diluted with ethyl acetate, washed with water and brine, dried over magnesium sulfate, filtered, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (25 g silica, solvent gradient: 0-5% methanol in dichloromethane) to yield 162.4 mg (83%) of the title compound. LCMS (ESI): M+H=254.2; 1H NMR (400 MHz, DMSO) δ 8.88 (s, 1H), 8.50 (s, 1H), 8.37 (s, 1H), 7.86 (s, 1H), 7.63 (d, J=8.6 Hz, 1H), 7.51 (dd, J=8.6, 1.6 Hz, 1H), 6.67 (s, 1H), 6.04 (s, 2H), 2.25 (d, J=2.0 Hz, 3H).

Workup

washwashed with water and brine
dry with materialdried over magnesium sulfate
filtrationfiltered
customevaporated in vacuo
customThe crude product was purified via flash chromatography on silica gel (25 g silica, solvent gradient: 0-5% methanol in dichloromethane)

Sources & evidence

ORD record: ord-26f1010559da499ea7ead0136d1e3b2a
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09206175B2

Reaction notes

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