(6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazol-4-yl)(pyridin 2-yl)methanone → 6-(3,5-dimethylisoxazol-4-yl)-4-(4,4,4-trifluoro-1-hydroxy-1-(pyridin-2-yl)butyl)-1H-benzo[d]imidazol-2(3H)-one

HRID 1773734Notes

Reaction equation

HRID 1773734 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]([C:19]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)=[O:20])[C:10]3[N:14]=[C:13]([O:15]CC)[NH:12][C:11]=3[CH:18]=2)=[C:5]([CH3:27])[O:4][N:3]=1.[F:28][C:29]([F:35])([F:34])[CH2:30][CH2:31][Mg]Br>C1COCC1>[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]([C:19]([OH:20])([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)[CH2:31][CH2:30][C:29]([F:35])([F:34])[F:28])[C:10]3[NH:14][C:13](=[O:15])[NH:12][C:11]=3[CH:18]=2)=[C:5]([CH3:27])[O:4][N:3]=1

Participants

4

Reactant 2

HCID 117601753(6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazol-4-yl)(pyridin 2-yl)methanoneHCID 178506320HCID 178506320, compound

Product 1

HCID 862971586-(3,5-dimethylisoxazol-4-yl)-4-(4,4,4-trifluoro-1-hydroxy-1-(pyridin-2-yl)butyl)-1H-benzo[d]imidazol-2(3H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

(6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazol-4-yl)(pyridin-2-yl)methanone (50 mg, 0.14 mmol) was dissolved in dry THF (1.4 mL) and cooled to 0° C. (3,3,3-trifluoropropyl)magnesium bromide (0.5 M, 0.55 mL, 0.28 mmol) was added dropwise and the reaction was allowed to stir for 10 mins and then quenched with water. Reaction was extracted three times with EtOAc and combined organic layers were washed once with water and concentrated. Residue was taken up in EtOH (1.5 mL) and 4.0M HCl/dioxane (0.75 mL), heated to 65° C. for two hours, concentrated, then purified by reverse-phase HPLC to afford the desired product as a white powder.

Workup

  1. additionwas added dropwise
  2. customquenched with water
  3. customReaction
  4. extractionwas extracted three times with EtOAc
  5. washwere washed once with water
  6. concentrationconcentrated
  7. concentrationconcentrated
  8. custompurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-0577bacb57ba4048ba4ab4031fb3f822
Source dataset
uspto-grants-2016_02
Patent number
US09255089B2

Reaction notes

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