Ethyl Acetate → HCID 66678614, compound

HRID 1025988Notes

Reaction equation

HRID 1025988 reaction equation
[NH:1]1[CH:5]=[CH:4][C:3]([CH2:6][N:7]2[C:15](=[O:16])[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:8]2=[O:17])=[N:2]1.[H-].[Na+].[CH:20]1([CH2:23]Br)[CH2:22][CH2:21]1.C(OCC)(=O)C>CN(C=O)C>[CH:20]1([CH2:23][N:1]2[CH:5]=[CH:4][C:3]([CH2:6][N:7]3[C:15](=[O:16])[C:14]4[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=4)[C:8]3=[O:17])=[N:2]2)[CH2:22][CH2:21]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 178514967HCID 178514967, compound

Product 1

HCID 66678614HCID 66678614, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a colorless solution of 2-(1H-pyrazol-3-ylmethyl)-1H-Isoindole-1,3(2H)-dione (CAN 95533-75-8; 3.66 g, 16.1 mmol) in DMF (80 mL) at 0° C. was added in 4 portions sodium hydride (1.29 g, 32.2 mmol) within 15 min. After warming to room temperature the mixture was stirred for 30 min and cyclopropylmethyl bromide (21.7 g, 15.6 mL, 161 mmol) in DMF (20 mL) was added within 30 min. The mixture was stirred for 22 h at room temperature, poured into ethyl acetate (200 mL) and extracted with water (3×100 mL). Water phases were washed with ethyl acetate (200 mL), organic phases were combined, dried with MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 80 g, 0% to 100% EtOAc in heptane) and finally by preparative HPLC to give 1.63 g (36%) of the title compound as a white solid; MS (EI): 282.2 (M+H)+.

Workup

  1. stirringThe mixture was stirred for 22 h at room temperature
  2. extractionextracted with water (3×100 mL)
  3. washWater phases were washed with ethyl acetate (200 mL), organic phases
  4. dry with materialdried with MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography (silica gel, 80 g, 0% to 100% EtOAc in heptane) and finally by preparative HPLC

Sources & evidence

ORD record
ord-ae3cff9ec4b842dd80a9baf008c5eea7
Source dataset
uspto-grants-2014_05
Patent number
US08729105B2

Reaction notes

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