4-Methylmorpholine → HCID 68157891, compound

HRID 242948Notes

Reaction equation

HRID 242948 reaction equation
[CH:1]1([NH:5][C:6]2[C:7]([NH2:13])=[CH:8][CH:9]=[C:10]([F:12])[CH:11]=2)[CH2:4][CH2:3][CH2:2]1.[C:14]([O:18][C:19]([NH:21][C@@H:22]([CH3:26])[C:23](O)=[O:24])=[O:20])([CH3:17])([CH3:16])[CH3:15].C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[C:14]([O:18][C:19](=[O:20])[NH:21][C@H:22]([C:23](=[O:24])[NH:13][C:7]1[CH:8]=[CH:9][C:10]([F:12])=[CH:11][C:6]=1[NH:5][CH:1]1[CH2:2][CH2:3][CH2:4]1)[CH3:26])([CH3:15])([CH3:16])[CH3:17]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 85082Tert-butoxycarbonylalanineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 62415716HCID 62415716, compound

Product 1

HCID 68157891HCID 68157891, compoundYield 69.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of N2-cyclobutyl-4-fluorobenzene-1,2-diamine (0.63 g, 3.5 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (0.73 g, 3.9 mmol), HOAt (0.53 g, 3.9 mmol), 4-methylmorpholine (0.85 mL, 7.7 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.75 g, 3.9 mmol) in DCM (12 mL) was stirred at RT for 18 h. The reaction mixture was partitioned between DCM and a saturated aqueous solution of NaHCO3. The organic fraction was washed with brine, dried (MgSO4), concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cyclohexane) to afford [(S)-1-(2-cyclobutylamino-4-fluorophenylcarbamoyl)ethyl]carbamic acid tert-butyl ester (853 mg, 69%). LCMS (Method J): RT 3.54 min [M+H]+ 352.2.

Workup

  1. customThe reaction mixture was partitioned between DCM
  2. washThe organic fraction was washed with brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-c6edad281db94e0d808ac230db7304ae
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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