6-Methoxy-3-pyridinylamine → N-(6-methoxypyridin-3-yl)-3-(2-methyl-6-(methylthio)pyrimidin-4-yl)pyrazin-2-amine

HRID 1811922Notes

Reaction equation

HRID 1811922 reaction equation
F[C:2]1[C:3]([C:8]2[CH:13]=[C:12]([S:14][CH3:15])[N:11]=[C:10]([CH3:16])[N:9]=2)=[N:4][CH:5]=[CH:6][N:7]=1.[NH2:17][C:18]1[CH:19]=[CH:20][C:21]([O:24][CH3:25])=[N:22][CH:23]=1.C(N(C(C)C)C(C)C)C>O1CCOCC1.O.[Cu]I>[CH3:25][O:24][C:21]1[N:22]=[CH:23][C:18]([NH:17][C:2]2[C:3]([C:8]3[CH:13]=[C:12]([S:14][CH3:15])[N:11]=[C:10]([CH3:16])[N:9]=3)=[N:4][CH:5]=[CH:6][N:7]=2)=[CH:19][CH:20]=1

Participants

7

Reactant 3

HCID 811216-Methoxy-3-pyridinylamineHCID 81531DiisopropylethylamineHCID 666002204-(3-Fluoropyrazin-2-yl)-2-methyl-6-(methylthio)pyrimidine

Product 1

HCID 66599972N-(6-methoxypyridin-3-yl)-3-(2-methyl-6-(methylthio)pyrimidin-4-yl)pyrazin-2-amineYield 46.3%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A glass microwave reaction vessel was charged with 4-(3-fluoropyrazin-2-yl)-2-methyl-6-(methylthio)pyrimidine (21 mg, 0.089 mmol), 5-amino-2-methoxypyridine (0.022 mL, 0.178 mmol), copper(I) iodide (2 mg, 8.89 μmol) and N-ethyl-N-isopropylpropan-2-amine (22.97 mg, 0.178 mmol) in dioxane (1 mL). The reaction mixture was stirred and heated in an oil bath at 100° C. for 24 h. The reaction mixture was diluted with water (5 mL) and extracted with EtOAc (2×20 mL). The organic extract was washed with saturated NaCl (5 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as a light-yellow solid. The crude product was purified by silica gel chromatography, eluting with 30% EtOAc/hexanes to give N-(6-methoxypyridin-3-yl)-3-(2-methyl-6-(methylthio)pyrimidin-4-yl)pyrazin-2-amine (14 mg, 0.041 mmol, 46.3% yield). 1H NMR (300 MHz, CDCl3) δ 12.20 (s, 1H); 8.42 (d, J=2.05 Hz, 1H); 8.22 (s, 1H); 8.18 (s, 1H); 8.09 (dd, J=8.92, 2.63 Hz, 1H); 8.02 (d, J=1.90 Hz, 1H); 6.79 (d, J=8.77 Hz, 1H); 3.95 (s, 3H); 2.78 (s, 3H); 2.63 (s, 3H). m/z (ESI, +ve ion) 341.0 (M+H)+.

Workup

  1. customA glass microwave reaction vessel
  2. extractionextracted with EtOAc (2×20 mL)
  3. extractionThe organic extract
  4. washwas washed with saturated NaCl (5 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated in vacuo
  8. customto give the crude material as a light-yellow solid
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 30% EtOAc/hexanes

Sources & evidence

ORD record
ord-ea324a10013e4a2bb8a8903ccca46b2e
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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