Ethyl Acetate → (1H-benzoimidazol-2-yl)-{3-[3-(4-hydroxy-4-methyl-piperidin-1-yl)-pyrazin-2-yl]-azetidin-1-yl}-methanone

HRID 1850336Notes

Reaction equation

HRID 1850336 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([N:12]1[CH2:15][CH:14]([C:16]2[C:17]([N:22]3[CH2:27][CH2:26][C:25](=[O:28])[CH2:24][CH2:23]3)=[N:18][CH:19]=[CH:20][N:21]=2)[CH2:13]1)=[O:11].C[Mg+].[Br-].[CH3:32]COC(C)=O>C1COCC1>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([N:12]1[CH2:13][CH:14]([C:16]2[C:17]([N:22]3[CH2:27][CH2:26][C:25]([OH:28])([CH3:32])[CH2:24][CH2:23]3)=[N:18][CH:19]=[CH:20][N:21]=2)[CH2:15]1)=[O:11]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 585473681-{3-[1-(1H-benzoimidazole-2-carbonyl)-azetidin-3-yl]-pyrazin-2-yl}-piperidin-4-oneHCID 178418689HCID 178418689, compound

Product 1

HCID 58546758(1H-benzoimidazol-2-yl)-{3-[3-(4-hydroxy-4-methyl-piperidin-1-yl)-pyrazin-2-yl]-azetidin-1-yl}-methanoneYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-{3-[1-(1H-benzoimidazole-2-carbonyl)-azetidin-3-yl]-pyrazin-2-yl}-piperidin-4-one (150 mg, 0.40 mol, SCHEME 13, Ex. 13.1) in 20 mL of THF was added CH3MgBr (0.60 mol, 3 M in ether) dropwise at 0° C. The mixture was stirred for 1 h at RT and then quenched with saturated aqueous NH4Cl. The resulting mixture was extracted with EtOAc (2×20 mL) and the combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated to give crude product which was purified by prep. TLC (EtOAc:Petrol ether=1:1) to give (1H-benzoimidazol-2-yl)-{3-[3-(4-hydroxy-4-methyl-piperidin-1-yl)-pyrazin-2-yl]-azetidin-1-yl}-methanone (0.109 g, 0.28 mmol, 70% yield) as a white solid.

Workup

  1. customquenched with saturated aqueous NH4Cl
  2. extractionThe resulting mixture was extracted with EtOAc (2×20 mL)
  3. dry with materialthe combined organic layers were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give crude product which
  7. customwas purified by prep

Sources & evidence

ORD record
ord-a6d5d75f77684761b491e9d09c00862b
Source dataset
uspto-grants-2015_02
Patent number
US08957073B2

Reaction notes

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