Propionyl chloride → HCID 21875678, compound

HRID 858477Notes

Reaction equation

HRID 858477 reaction equation
[NH2:1][C:2]1[C:3]([Cl:26])=[N:4][C:5]([CH3:25])=[CH:6][C:7]=1[NH:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:11][CH:10]=1.[C:27](Cl)(=O)[CH2:28][CH3:29].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.ClCCl.C(OCC)(=O)C>[Cl:26][C:3]1[C:2]2[N:1]=[C:27]([CH2:28][CH3:29])[N:8]([C:9]3[CH:10]=[CH:11][C:12]([CH2:15][CH2:16][NH:17][C:18](=[O:24])[O:19][C:20]([CH3:22])([CH3:23])[CH3:21])=[CH:13][CH:14]=3)[C:7]=2[CH:6]=[C:5]([CH3:25])[N:4]=1

Participants

7

Reactant 3

HCID 62324Propionyl chlorideHCID 521998p-Toluenesulfonic acid monohydrateHCID 21875720HCID 21875720, compound

Product 1

HCID 21875678HCID 21875678, compoundYield 34.4%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolvent2×HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of tert-butyl 2-{4-[(3-amino-2-chloro-6-methyl-4-pyridinyl)amino]phenyl}ethylcarbamate (step 2, 238 mg, 0.63 mmol), propionyl chloride (70 mg, 0.76 mmol) in toluene (4.6 ml) and dichloromethane (0.6 ml) was heated at reflux temperature for 1 h. After cooling, the mixture was diluted with ethyl acetate (100 ml) and washed with IN aqueous NaOH solution (30 ml×2) and brine (30 ml). The organic layer was dried (MgSO4), and concentrated. The residue and p-toluenesulfonic acid monohydrate (5 mg, 0.026 mmol) in toluene (5.0 ml) was heated at reflux temperature for 16 h. After cooling, the mixture was diluted with dichloromethane (100 ml) and washed with saturated aqueous NaHCO3 solution (30 ml) and brine (30 ml). The organic layer was dried (MgSO4), and concentrated. Purification by PTLC eluting with hexane/ethyl acetate (1:1) to afford 90 mg (34%) of the title compound as a brown oil.

Workup

  1. temperaturewas heated
  2. temperatureat reflux temperature for 1 h
  3. temperatureAfter cooling
  4. washwashed with IN aqueous NaOH solution (30 ml×2) and brine (30 ml)
  5. dry with materialThe organic layer was dried (MgSO4)
  6. concentrationconcentrated
  7. temperatureat reflux temperature for 16 h
  8. temperatureAfter cooling
  9. washwashed with saturated aqueous NaHCO3 solution (30 ml) and brine (30 ml)
  10. dry with materialThe organic layer was dried (MgSO4)
  11. concentrationconcentrated
  12. customPurification by PTLC
  13. washeluting with hexane/ethyl acetate (1:1)

Sources & evidence

ORD record
ord-cd7d571db3b441e2be472edbd4e32b5f
Source dataset
uspto-grants-2006_12
Patent number
US07148234B2

Reaction notes

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