Dimethylacetamide → 7-(4-Methyl-6-(methylthio)pyridin-3-yl)isoquinolin-3-amine

HRID 1502444Notes

Reaction equation

HRID 1502444 reaction equation
F[C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([NH2:18])[N:14]=[CH:15]3)=[CH:10][CH:9]=2)=[C:4]([CH3:19])[CH:3]=1.[CH3:20][S-:21].[Na+].CN(C)C(=O)C>>[CH3:19][C:4]1[CH:3]=[C:2]([S:21][CH3:20])[N:7]=[CH:6][C:5]=1[C:8]1[CH:17]=[C:16]2[C:11]([CH:12]=[C:13]([NH2:18])[N:14]=[CH:15]2)=[CH:10][CH:9]=1

Participants

4

Reactant 3

HCID 31374DimethylacetamideHCID 4378561Sodium methanethiolateHCID 711151637-(6-Fluoro-4-methylpyridin-3-yl)isoquinolin-3-amine

Product 1

HCID 679748647-(4-Methyl-6-(methylthio)pyridin-3-yl)isoquinolin-3-amine

Procedure

A mixture of 7-(6-fluoro-4-methylpyridin-3-yl)isoquinolin-3-amine (389 mg; 1.536 mmol) and sodium thiomethoxide (344 mg; 4.66253 mmol) in N,N-dimethylacetamide (3.0 mL; 32 mmol) was subjected to microwave irradiation at 150° C. for 30 minutes to produce a mixture of the desired product and the demethylated thiol product. To the reaction mixture was added a 10 mol/L solution sodium hydroxide in water (1.5 mL; 15 mmol) followed by iodomethane (0.10 mL; 1.6 mmol). The reaction mixture was stirred at room temperature for 4 hours, and then additional iodomethane (0.05 mL; 0.8 mmol) was added. After an additional 4 hours, the reaction mixture was diluted with ethyl acetate, washed with water and brine, dried over magnesium sulfate, filtered, and evaporated in vacuo to yield 419.9 mg of the title compound, which was carried forward without purification. LCMS (ESI): M+H=282.2; 1H NMR (400 MHz, DMSO) δ 8.85 (s, 1H), 8.30 (s, 1H), 7.79 (s, 1H), 7.59 (d, J=8.6 Hz, 1H), 7.47 (d, J=8.6 Hz, 1H), 7.27 (s, 1H), 6.66 (s, 1H), 5.98 (s, 2H), 2.54 (s, 3H), 2.27 (s, 3H).

Workup

  1. customirradiation at 150° C. for 30 minutes
  2. customto produce

Sources & evidence

ORD record
ord-59f1237f4a2742d08291a92b97cc640a
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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