Water → 7-(4-Methylpyridin-3-yl)isoquinolin-3-amine

HRID 468761Notes

Reaction equation

HRID 468761 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.[CH3:13][C:14]1[CH:19]=[CH:18][N:17]=[CH:16][C:15]=1B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+].COCCOC.O>ClCCl.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>[CH3:13][C:14]1[CH:19]=[CH:18][N:17]=[CH:16][C:15]=1[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

Participants

8

Reactant 5

HCID 962WaterHCID 80711,2-DimethoxyethaneHCID 10796Cesium carbonateHCID 27627114-Methylpyridine-3-Boronic Acid2×HCID 529877577-Bromoisoquinolin-3-amine

Product 1

HCID 679741997-(4-Methylpyridin-3-yl)isoquinolin-3-amineYield 42%

Reagents, catalysts & solvents 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 7-bromoisoquinolin-3-amine (253.2 mg, 1.135 mmol), 4-methylpyridine-3-boronic acid (188.8 mg, 1.379 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (81.0 mg, 0.114 mmol), and cesium carbonate (0.7432 g, 2.281 mmol) was added 1,2-dimethoxyethane (5 mL, 50 mmol) and water (0.5 mL, 30 mmol). The reaction mixture was subjected to microwave irradiation at 130° C. for 30 minutes. 4-Methylpyridine-3-boronic acid (197.2 mg, 1.440 mmol) was added and the reaction mixture was subjected to microwave irradiation at 130° C. for 45 min. The reaction mixture was diluted with dichloromethane, washed with saturated aqueous NaHCO3, dried over MgSO4, and evaporated in vacuo. The crude material was purified via flash chromatography on silica gel (25 g silica, solvent gradient: 0-10% methanol in dichloromethane) to yield 111.1 mg (42%) of 7-(4-methylpyridin-3-yl)isoquinolin-3-amine. LCMS (ESI): M+H=236.2; 1H NMR (400 MHz, DMSO-d6) δ 8.87 (s, 1H), 8.43 (d, J=6.4 Hz, 2H), 7.81 (s, 1H), 7.60 (d, J=8.5 Hz, 1H), 7.49 (dd, J=8.6, 1.7 Hz, 1H), 7.35 (d, J=5.0 Hz, 1H), 6.67 (s, 1H), 5.99 (s, 2H), 2.31 (s, 3H).

Workup

  1. customirradiation at 130° C. for 30 minutes
  2. customirradiation at 130° C. for 45 min
  3. washwashed with saturated aqueous NaHCO3
  4. dry with materialdried over MgSO4
  5. customevaporated in vacuo
  6. customThe crude material was purified via flash chromatography on silica gel (25 g silica, solvent gradient: 0-10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-ccb5fc8f167f45c2ab75369c9a9f7078
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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