Bromomethylcyclopropane → 6-(3,5-dimethylisoxazol-4-yl)-4-(1-hydroxy-1-(pyridin-2-yl)pent-4-en-1-yl)-1H-benzo[d]imidazol-2(3H)-one

HRID 1773733Notes

Reaction equation

HRID 1773733 reaction equation
[Mg].Br[CH2:3][CH:4]1[CH2:6][CH2:5]1.C1(C[Mg]Br)CC1.[CH3:13][C:14]1[C:18]([C:19]2[CH:20]=[C:21]([C:31]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=3)=[O:32])[C:22]3[N:26]=[C:25]([O:27]CC)[NH:24][C:23]=3[CH:30]=2)=[C:17]([CH3:39])[O:16][N:15]=1>C1COCC1>[CH3:13][C:14]1[C:18]([C:19]2[CH:20]=[C:21]([C:31]([OH:32])([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=3)[CH2:6][CH2:5][CH:4]=[CH2:3])[C:22]3[NH:26][C:25](=[O:27])[NH:24][C:23]=3[CH:30]=2)=[C:17]([CH3:39])[O:16][N:15]=1

Participants

6

Reactant 4

HCID 81503BromomethylcyclopropaneHCID 5462224MagnesiumHCID 117601753(6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazol-4-yl)(pyridin 2-yl)methanoneHCID 178419657HCID 178419657, compound

Product 1

HCID 1176020206-(3,5-dimethylisoxazol-4-yl)-4-(1-hydroxy-1-(pyridin-2-yl)pent-4-en-1-yl)-1H-benzo[d]imidazol-2(3H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
65 °C

Procedure

Magnesium metal (20 mg, 0.82 mmol) was taken up in THF (1.5 mL) and (bromomethyl)cyclopropane (100 mg, 0.71 mmol) was added dropwise and the reaction was heated to 65° C. for 1 hr. (Cyclopropylmethyl)magnesium bromide (0.5 M, 0.83 mL, 0.41 mmol) was then added dropwise to a solution of (6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazol-4-yl)(pyridin-2-yl)methanone (50 mg, 0.14 mmol) in dry THF (1.4 mL) which was cooled to 0° C. Reaction mixture was allowed to stir for 10 mins, quenched with water and extracted three times with EtOAc. Combined organic layers were washed once with water and concentrated. Residue was dissolved in a mixture of EtOH (1.5 mL) and 4.0M HCl/dioxane (0.75 mL) and heated for 2 hours at 65° C. Reaction was then concentrated and purified by reverse-phase HPLC to afford the desired product as a white powder.

Workup

  1. temperaturewas cooled to 0° C
  2. customReaction mixture
  3. customquenched with water
  4. extractionextracted three times with EtOAc
  5. washCombined organic layers were washed once with water
  6. concentrationconcentrated
  7. dissolutionResidue was dissolved in a mixture of EtOH (1.5 mL) and 4.0M HCl/dioxane (0.75 mL)
  8. temperatureheated for 2 hours at 65° C
  9. customReaction
  10. concentrationwas then concentrated
  11. custompurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-3d639c6ad4244238bd6b37d45e6bca7e
Source dataset
uspto-grants-2016_02
Patent number
US09255089B2

Reaction notes

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