HCID 68157677, compound → HCID 68157387, compound

HRID 242895Notes

Reaction equation

HRID 242895 reaction equation
[C:1]([O:5][C:6](=[O:27])[NH:7][C@H:8]([C:10](=O)[NH:11][C:12]1[C:13]([NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH3:25])=[N:14][CH:15]=[CH:16][CH:17]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]>CC(O)=O>[C:1]([O:5][C:6](=[O:27])[NH:7][C@H:8]([C:10]1[N:18]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH3:25])[C:13]2=[N:14][CH:15]=[CH:16][CH:17]=[C:12]2[N:11]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]

Participants

3

Reactant 1

HCID 68157677HCID 68157677, compound

Product 1

HCID 68157387HCID 68157387, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of [(S)-1-(2-o-tolylaminopyridin-3-ylcarbamoyl)ethyl]carbamic acid tert-butyl ester (2.51 mmol) in AcOH (20 mL) was heated at 70° C. for 6 h. After cooling to RT, the volatiles were removed under reduced pressure and the residue partitioned between DCM and a saturated aqueous solution of NaHCO3. The aqueous phase was extracted with DCM and the combined organic fractions washed with water, dried (Na2SO4) and concentrated in vacuo to afford [(S)-1-(3-o-tolyl-3H-imidazo[4,5-b]pyridin-2-yl)ethyl]carbamic acid tert-butyl ester as a brown oil (quantitative). To a solution of the compound thus obtained (2.51 mmol) in DCM (25 mL) was added TFA (10 mL) and the mixture stirred at RT for 15 min. The volatiles were removed in vacuo and the resulting residue dissolved in DCM and washed with a saturated aqueous solution of NaHCO3 (40 mL). The aqueous phase was further extracted with DCM (×3) and the combined organic fractions dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-8% 2M NH3/MeOH in DCM) to afford the title compound as an oil (340 mg, 54% over 3 steps). 1H NMR (CDCl3, 400 MHz): δ 8.33 (1H, d, J=4.83 Hz), 8.09 (1H, d, J=8.00 Hz), 7.52-7.37 (3H, m), 7.33-7.21 (2H, m), 4.08 (0.5H, q, J=6.75 Hz), 3.99 (0.5H, q, J=6.72 Hz), 2.02 (3H, s), 1.50 (1.5H, d, J=6.75 Hz), 1.41 (1.5H, d, J=6.75 Hz). Signals split due to presence of rotamers/tautomers.

Workup

  1. customthe volatiles were removed under reduced pressure
  2. customthe residue partitioned between DCM
  3. extractionThe aqueous phase was extracted with DCM
  4. washthe combined organic fractions washed with water
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-534bbf9dd61b4519a3250e3dc9c777a8
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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