4-Methylmorpholine → HCID 68157811, compound

HRID 243071Notes

Reaction equation

HRID 243071 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([NH2:9])[C:3]=1[NH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C1C=N[C:20]2N(O)N=[N:25][C:19]=2[CH:18]=1.CN1CC[O:31][CH2:30]C1.CCN=C=NCCCN(C)C.[ClH:45]>C(Cl)Cl.O>[ClH:45].[ClH:45].[F:8][C:7]1[CH:6]=[CH:5][C:4]2[N:9]=[C:20]([C@@H:19]([NH2:25])[CH2:18][O:31][CH3:30])[N:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:3]=2[C:2]=1[F:1]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 62534008HCID 62534008, compound

Product 1

HCID 68157811HCID 68157811, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 3,4-difluoro-N2-phenylbenzene-1,2-diamine (400 mg, 1.8 mmol), Boc-ser(OMe)-OH (800 mg, 2.0 mmol), HOAT (340 mg, 2.0 mmol) and N-methylmorpholine (500 μL, 4.0 mmol) in DCM (5 mL) was added N-(3-dimethylaminopropyl)-n′-ethylcarbodiimide hydrochloride (480 mg, 2.0 mmol) and the reaction mixture stirred at RT for 16 h. The reaction mixture was diluted with water and extracted with DCM (3×10 mL). The combined organic fractions were washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was dissolved in HCl in dioxane (10 mL, 4 M) and the reaction mixture heated at 80° C. for 4 h. The reaction mixture was concentrated in vacuo and the resultant residue dissolved in EtOAc (10 mL). The solution was washed with sat. aq. NaHCO3 and the product extracted with EtOAc (3×10 mL). The combined organic extracts were washed with brine, dried (MgSO4), concentrated in vacuo and the resultant residue subjected to flash chromatography (SiO2, eluting with 0-10% methanol in DCM) to give the title compound as an off white solid (207 mg, 38%). LCMS (Method C): RT=2.27 min, [M+H]+=304.

Workup

  1. extractionextracted with DCM (3×10 mL)
  2. washThe combined organic fractions were washed with brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in HCl in dioxane (10 mL, 4 M)
  6. temperaturethe reaction mixture heated at 80° C. for 4 h
  7. concentrationThe reaction mixture was concentrated in vacuo
  8. dissolutionthe resultant residue dissolved in EtOAc (10 mL)
  9. washThe solution was washed with sat. aq. NaHCO3
  10. extractionthe product extracted with EtOAc (3×10 mL)
  11. washThe combined organic extracts were washed with brine
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated in vacuo
  14. washthe resultant residue subjected to flash chromatography (SiO2, eluting with 0-10% methanol in DCM)

Sources & evidence

ORD record
ord-6c0e4420bd6249fc9f93cdff1f220e0e
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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