Sodium Carbonate → HCID 178506243, compound

HRID 1048969Notes

Reaction equation

HRID 1048969 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C:10]3[CH:11]=[N:12][CH:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:15]=3)[N:7]([CH:20]3[CH2:22][CH2:21]3)[C:6]=2[CH:23]=1.CC1(C)C(C)(C)OB([C:32]2[CH:36]=[CH:35][NH:34][N:33]=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>[CH:20]1([N:7]2[C:6]3[CH:23]=[C:2]([C:32]4[CH:36]=[CH:35][NH:34][N:33]=4)[CH:3]=[CH:4][C:5]=3[N:9]=[C:8]2[C:10]2[CH:11]=[N:12][CH:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:15]=2)[CH2:22][CH2:21]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 666926766-bromo-1-cyclopropyl-2-(5-trifluoromethyl-pyridin-3-yl)-1H-benzoimidazoleHCID 178431094HCID 178431094, compound

Product 1

HCID 178506243HCID 178506243, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 86587398Ethanol toluene waterSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 6-bromo-1-cyclopropyl-2-(5-trifluoromethyl-pyridin-3-yl)-1H-benzoimidazole (0.15 g, 0.00026 mol) in ethanol toluene water (6 ml 3 ml 1.5 ml respectively) mixture in a sealed tube was added 3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.1 g, 0.00052 mol) and Na2CO3 (0.082 g, 0.000785 mol) and argon was purged for 15 min. Then Pd (PPh3)4 (0.015 g, 0.000013 mol) was added and heated at 80° C. for 5 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 1-cyclopropyl-6-(1H-pyrazol-3-yl)-2-[5-(trifluoromethyl)pyridin-3-yl]-1H-benzimidazole (321) as an off white solid. NMR (400 MHz, DMSO-d6), δ: 12.85 (s, 1H), 9.49 (s, 1H), 9.12 (s, 1H), 8.75 (s, 1H), 8.09 (s, 1H), 7.79-7.67 (m, 3H), 7.54-7.52 (m, 1H), 6.79 (s, 1H), 3.96 (bs, 1H), 1.15 (d, J=5.6 Hz, 2H), 0.73 (bs, 2H). MS (M+1): 370.6, Purity 99.94%.

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-6c5331d22ef9473c8d6d52559d86c631
Source dataset
uspto-grants-2016_07
Patent number
US09382226B2

Reaction notes

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