HCID 67433863, compound → HCID 58459367, compound

HRID 2036673Notes

Reaction equation

HRID 2036673 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([F:9])=[CH:4][C:3]=1[NH:10][C:11](=O)[C@@H:12]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH3:13]>CC(O)=O>[F:9][C:5]1[C:6]([F:8])=[CH:7][C:2]2[NH:1][C:11]([C@@H:12]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH3:13])=[N:10][C:3]=2[CH:4]=1

Participants

3

Reactant 1

HCID 67433863HCID 67433863, compound

Product 1

HCID 58459367HCID 58459367, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of (S)-tert-butyl 1-(2-amino-4,5-difluorophenylamino)-1-oxopropan-2-ylcarbamate (3.454 g, 10.96 mmol) in AcOH (21.91 mL) was heated at 75° C. After 50 min, the mixture was concentrated in vacuo. The residue was dissolved in DCM (100 mL), washed with satd. sodium bicarbonate solution (50 mL×2), water (100 mL×1), and brine (100 mL×1). The product was precipitated from DCM. In order to dissolve the precipitate, EtOAc (100 mL) was added. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (80 g), eluting with a gradient of 0% to 100% EtOAc in hexane, to provide (S)-tert-butyl 1-(5,6-difluoro-1H-benzo[d]imidazol-2-yl)ethylcarbamate (2.5025 g, 8.42 mmol, 77% yield) as orange solid. The orange solid was suspended in DCM-hexane (1:1) and filtered to give (S)-tert-butyl 1-(5,6-difluoro-1H-benzo[d]imidazol-2-yl)ethylcarbamate (2.0003 g, 6.73 mmol, 61.4% yield) as a pink solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.34 (1H, br. s.), 7.47-7.57 (2H, m), 7.38 (1H, d, J=7.2 Hz), 4.83 (1H, quin, J=6.6 Hz), 1.45 (3H, d, J=7.0 Hz), 1.40 (9H, s); LC-MS (ESI) m/z 298.1 [M+H]+.

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolved in DCM (100 mL)
  3. washwashed with satd
  4. customThe product was precipitated from DCM
  5. dissolutionIn order to dissolve the precipitate, EtOAc (100 mL)
  6. additionwas added
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was absorbed onto a plug of silica gel
  11. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (80 g)
  12. washeluting with a gradient of 0% to 100% EtOAc in hexane

Sources & evidence

ORD record
ord-1b92c8447381491d89f4ecb9a45f036c
Source dataset
uspto-grants-2013_11
Patent number
US08575183B2

Reaction notes

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