Sodium Iodide → 3-{1-[2-(1-(3,4-Dichlorophenyl)-5-methyl-1H-pyrazol-3-yloxy)ethyl]piperidin-4-yl}-3H-imidazo[4,5-b]pyridine

HRID 220001Notes

Reaction equation

HRID 220001 reaction equation
Cl[CH2:2][CH2:3][O:4][C:5]1[CH:9]=[C:8]([CH3:10])[N:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[N:6]=1.[NH:19]1[CH2:24][CH2:23][CH:22]([N:25]2[C:29]3=[N:30][CH:31]=[CH:32][CH:33]=[C:28]3[N:27]=[CH:26]2)[CH2:21][CH2:20]1.C([O-])([O-])=O.[K+].[K+].[Na+].[I-]>CN(C)C=O>[Cl:18][C:13]1[CH:12]=[C:11]([N:7]2[C:8]([CH3:10])=[CH:9][C:5]([O:4][CH2:3][CH2:2][N:19]3[CH2:20][CH2:21][CH:22]([N:25]4[C:29]5=[N:30][CH:31]=[CH:32][CH:33]=[C:28]5[N:27]=[CH:26]4)[CH2:23][CH2:24]3)=[N:6]2)[CH:16]=[CH:15][C:14]=1[Cl:17]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 114470113-(Piperidin-4-yl)-3H-imidazo[4,5-b]pyridineHCID 250231333-(2-chloroethoxy)-1-(3,4-dichlorophenyl)-5-methyl-1H-pyrazole

Product 1

HCID 115329203-{1-[2-(1-(3,4-Dichlorophenyl)-5-methyl-1H-pyrazol-3-yloxy)ethyl]piperidin-4-yl}-3H-imidazo[4,5-b]pyridineYield 43.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(2-chloroethoxy)-1-(3,4-dichlorophenyl)-5-methyl-1H-pyrazole (0.2 g, 0.65 mmol), 3-(piperidin-4-yl)-3H-imidazo[4,5-b]pyridine (0.145 g, 0.72 mmol), K2CO3 (270 mg, 1.96 mmol) and NaI (98 mg, 0.65 mmol) in dry dimethylformamide (6 ml) was warmed overnight at 85° C., and then an additionally 16 hrs at 95° C., in a dry nitrogen atmosphere. Solvents were evaporated in vacuo and the crude residue partitioned in water/ethyl acetate. The combined organic extracts were washed with water, dried on Na2SO4 and concentrated in vacuo to obtain a yellow crude oil, which was purified by column chromatography on silica gel (eluent: ethyl acetate 100% and ethyl acetate/MeOH 98/2 and 95/5) yielding 134 mg of 3-{1-[2-(1-(3,4-Dichlorophenyl)-5-methyl-1H-pyrazol-3-yloxy)ethyl]piperidin-4-yl}-3H-imidazo[4,5-b]pyridine as a white solid with m.p.=104-107° C.

Workup

  1. customan additionally 16 hrs
  2. customat 95° C.
  3. customSolvents were evaporated in vacuo
  4. customthe crude residue partitioned in water/ethyl acetate
  5. washThe combined organic extracts were washed with water
  6. customdried on Na2SO4
  7. concentrationconcentrated in vacuo
  8. customto obtain a yellow crude oil, which
  9. customwas purified by column chromatography on silica gel (eluent: ethyl acetate 100% and ethyl acetate/MeOH 98/2 and 95/5)

Sources & evidence

ORD record
ord-d2c64015124c4f99a663a45f98856494
Source dataset
uspto-grants-2012_06
Patent number
US08202872B2

Reaction notes

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