Ethyl diazoacetate → Ethyl (1R,2R)-2-[1-(2,2-dimethylpropyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl]cyclopropanecarboxylate

HRID 629905Notes

Reaction equation

HRID 629905 reaction equation
[CH3:1][C:2]([CH3:18])([CH3:17])[CH2:3][N:4]1[C:12]2[C:7](=[N:8][C:9]([CH:13]=[CH2:14])=[CH:10][CH:11]=2)[N:6]([CH3:15])[C:5]1=[O:16].[N+](=[CH:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])=[N-]>C1(C)C=CC=CC=1>[CH3:17][C:2]([CH3:1])([CH3:18])[CH2:3][N:4]1[C:12]2[C:7](=[N:8][C:9]([C@@H:13]3[CH2:14][C@H:21]3[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:10][CH:11]=2)[N:6]([CH3:15])[C:5]1=[O:16]

Participants

4

Reactant 2

HCID 12192Ethyl diazoacetateHCID 893046641-(2,2-Dimethylpropyl)-5-ethenyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

Product 1

HCID 117718204Ethyl (1R,2R)-2-[1-(2,2-dimethylpropyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl]cyclopropanecarboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

1-(2,2-Dimethylpropyl)-5-ethenyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (31-2, 636.4 mg, 2.6 mmol, 1.0 equiv) was added to anhydrous toluene (5.5 mL). Ethyl diazoacetate (807 μL, 7.8 mmol, 3.0 equiv) was added and the resulting solution was heated to 100° C. for 18 h. Following this duration, LCMS showed complete consumption of 31-2. The reaction mixture was diluted with ethyl acetate (50 mL) and saturated NaHCO3 (25 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (3×10 mL). The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to give an orange oil. Purification by normal-phase HPLC (0-40% EtOAc:hexanes) provided 31-3 as a white solid. MS m/z (M+H): calculated=332.1969; observed=332.1971.

Workup

  1. customconsumption of 31-2
  2. additionThe reaction mixture was diluted with ethyl acetate (50 mL) and saturated NaHCO3 (25 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (3×10 mL)
  5. dry with materialThe combined organics were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give an orange oil
  9. customPurification by normal-phase HPLC (0-40% EtOAc:hexanes)

Sources & evidence

ORD record
ord-2bc9e9a506bc49aa93ed5c02fe20df35
Source dataset
uspto-grants-2016_04
Patent number
US09315518B2

Reaction notes

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