Sodium Carbonate → 5-methoxy-1-methyl-2-[5-(1H-pyrazol-4-yl)pyridin-3-yl]-1H-benzimidazole

HRID 1048989Notes

Reaction equation

HRID 1048989 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[N:12]([CH3:13])[C:11]3[CH:14]=[CH:15][C:16]([O:18][CH3:19])=[CH:17][C:10]=3[N:9]=2)[CH:5]=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:28]2[CH:29]=[N:30][NH:31][CH:32]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O.C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:19][O:18][C:16]1[CH:15]=[CH:14][C:11]2[N:12]([CH3:13])[C:8]([C:4]3[CH:5]=[N:6][CH:7]=[C:2]([C:28]4[CH:29]=[N:30][NH:31][CH:32]=4)[CH:3]=3)=[N:9][C:10]=2[CH:17]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 666927982-(5-bromo-pyridin-3-yl)-5-methoxy-1-methyl-1H-benzoimidazole

Product 1

HCID 666923245-methoxy-1-methyl-2-[5-(1H-pyrazol-4-yl)pyridin-3-yl]-1H-benzimidazole

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 86587398Ethanol toluene waterSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-(5-bromo-pyridin-3-yl)-5-methoxy-1-methyl-1H-benzoimidazole (0.15 g, 0.00047 mol) in ethanol toluene water (6 ml, 3 ml, 1.5 ml, respectively) mixture in a sealed tube was added 4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.18 g, 0.000942 mol) and Na2CO3 (0.14 g, 0.0014 mol) and argon was purged for 15 min. Then Pd (PPh3)4 (0.027 g, 0.000023 mol) was added and heated at 100° C. for 24 h. The solvent was evaporated and the resulting residue was added water. The aqueous layer was extracted with ethyl acetate (3×20 ml). The combined organic layers were washed with brine dried over Na2SO4 and concentrated under vacuum to afford the crude compound which was purified by column chromatography to obtain title compound 5-methoxy-1-methyl-2-[5-(1H-pyrazol-4-yl)pyridin-3-yl]-1H-benzimidazole as an off white solid. 1H NMR (400 MHz, DMSO-d6), δ: 13.11 (s, 1H), 9.01 (s, 1H), 8.79 (s, 1H), 8.44 (s, 1H), 8.38 (s, 1H), 8.13 (s, 1H), 7.54 (d, J=8.8 Hz, 1H), 7.22 (s, 1H), 6.95 (d, J=8.8 Hz, 1H), 3.89 (s, 3H), 3.79 (s, 3H). MS (M+1): 306.1, Purity 99.0%.

Workup

  1. customwas purged for 15 min
  2. customThe solvent was evaporated
  3. additionthe resulting residue was added water
  4. extractionThe aqueous layer was extracted with ethyl acetate (3×20 ml)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under vacuum
  8. customto afford the crude compound which
  9. customwas purified by column chromatography

Sources & evidence

ORD record
ord-e068fb0010964c17adfa4674a4b5a86f
Source dataset
uspto-grants-2016_07
Patent number
US09382226B2

Reaction notes

Loading…