Propionic Acid → HCID 178493983, compound

HRID 707247Notes

Reaction equation

HRID 707247 reaction equation
[C:1]([O:5][C:6](=[O:20])[NH:7][C@H:8]1[CH2:11][C@H:10]([NH:12][C:13]2[C:18]([NH2:19])=[CH:17][CH:16]=[CH:15][N:14]=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[C:21](OC)(OC)(OC)[O:22][CH3:23].C(O)(=O)CC>O>[C:1]([O:5][C:6](=[O:20])[NH:7][C@H:8]1[CH2:11][C@H:10]([N:12]2[C:13]3=[N:14][CH:15]=[CH:16][CH:17]=[C:18]3[N:19]=[C:21]2[O:22][CH3:23])[CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 1032Propionic AcidHCID 74613Tetramethyl orthocarbonateHCID 178454116HCID 178454116, compound2×

Product 1

HCID 178493983HCID 178493983, compoundYield 48.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a glass microwave vial was added tert-butyl(trans-3-((3-aminopyridin-2-yl)amino)cyclobutyl)carbamate (intermediate 12, step 2, 1.7367 g, 6.24 mmol), tetramethyl orthocarbonate (16.66 ml, 125 mmol), and propionic acid (0.233 ml, 3.12 mmol). The reaction mixture was heated at 100° C. for 5 hours then was allowed to cool to room temperature. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic extract was washed with water, brine, and dried over magnesium sulfate before evaporating to dryness under reduced pressure. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage SNAP HP-silica gel column (50 g), eluting with a gradient of 10% to 100% ethyl acetate in hexane, to provide tert-butyl(trans-3-(2-methoxy-3H-imidazo[4,5-b]pyridin-3-yl)cyclobutyl)carbamate (0.968 g, 3.04 mmol, 48.7% yield).

Workup

  1. temperatureto cool to room temperature
  2. extractionextracted with ethyl acetate
  3. extractionThe organic extract
  4. washwas washed with water, brine
  5. dry with materialdried over magnesium sulfate
  6. custombefore evaporating to dryness under reduced pressure
  7. customchromatographed through a Biotage SNAP HP-silica gel column (50 g)
  8. washeluting with a gradient of 10% to 100% ethyl acetate in hexane

Sources & evidence

ORD record
ord-b63d8aecb3f94d9c86c03a8aec8e1567
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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