Potassium Carbonate → 3-(3-Methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-6-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridine

HRID 2178330Notes

Reaction equation

HRID 2178330 reaction equation
I[C:2]1[CH:3]=[C:4]2[N:10]=[CH:9][N:8]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]4[CH:21]=[N:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=4)=[C:14]([O:28][CH3:29])[CH:13]=3)[C:5]2=[N:6][CH:7]=1.[CH3:30][N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.N1CCC[C@H]1C(O)=O.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Cu]I>[CH3:29][O:28][C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][C:15]=1[O:18][CH2:19][C:20]1[CH:21]=[N:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=1)[CH2:11][N:8]1[C:5]2=[N:6][CH:7]=[C:2]([N:34]3[CH2:35][CH2:36][N:31]([CH3:30])[CH2:32][CH2:33]3)[CH:3]=[C:4]2[N:10]=[CH:9]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 531671-MethylpiperazineHCID 145742L-ProlineHCID 1181140026-iodo-3-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-3H-imidazo[4,5-b]pyridine

Product 1

HCID 1180097893-(3-Methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-6-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-b]pyridineYield 134.4%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

To a stirred suspension of 6-iodo-3-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-3H-imidazo[4,5-b]pyridine (1.40 g, 2.79 mmol) in dimethylsulfoxide (15 mL) was added 1-methylpiperazine (0.44 g, 4.40 mmol), copper(I) iodide (0.16 g, 0.84 mmol), L-proline (0.19 g, 1.67 mmol), and potassium carbonate (0.96 g, 6.97 mmol). The mixture was degassed under vacuum/backfilled with N2 (×3), and then it was heated to 120° C. As the mixture warmed, it became dark blue/black in color. After 19 h, the brown mixture was allowed to cool to room temperature and was diluted with 5N ammonium hydroxide solution (100 mL). The mixture was extracted with dichloromethane (3×50 mL). The combined organic phases were dried over magnesium sulfate, filtered, and concentrated to provide 1.78 g of a brown oil. Chromatographic purification (Combi-Flash, 40 g SiO2 gold column, 1-10% 2M ammonia in methanol/dichloromethane elute) afforded 0.60 g (45%) of the product as a tan solid: 1H NMR (400 MHz, CDCl3) δ 8.26 (d, J=2.4 Hz, 1H), 8.18 (d, J=2.4 Hz, 1H), 7.92 (s, 1H), 7.69-7.61 (m, 2H), 6.91-6.84 (m, 2H), 6.80 (dd, J=8.2, 2.0 Hz, 1H), 6.74 (dd, J=8.5 Hz, 1H), 5.34 (s, 2H), 5.02 (s, 2H), 3.93 (s, 3H), 3.80 (s, 3H), 3.25-3.18 (m, 4H), 2.68-2.61 (m, 4H), 2.38 (s, 3H) ppm; (M+1)=475.

Workup

  1. customThe mixture was degassed under vacuum/backfilled with N2 (×3)
  2. temperatureAs the mixture warmed
  3. temperatureto cool to room temperature
  4. additionwas diluted with 5N ammonium hydroxide solution (100 mL)
  5. extractionThe mixture was extracted with dichloromethane (3×50 mL)
  6. dry with materialThe combined organic phases were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-f5f09449289e4f7d985d96ee40dca21d
Source dataset
uspto-grants-2015_06
Patent number
US09067914B1

Reaction notes

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