4-Methylmorpholine → HCID 68157104, compound

HRID 242813Notes

Reaction equation

HRID 242813 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH2:15])[C:5]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:6][CH:7]=1.[C:16]([O:20][C:21]([NH:23][C@@H:24]([CH3:28])[C:25](O)=O)=[O:22])([CH3:19])([CH3:18])[CH3:17].C1C=NC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC.CN1CCOCC1>C(Cl)Cl>[C:16]([O:20][C:21](=[O:22])[NH:23][C@H:24]([C:25]1[N:8]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:5]2[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][C:4]=2[N:15]=1)[CH3:28])([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 85082Tert-butoxycarbonylalanineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10535968HCID 10535968, compound

Product 1

HCID 68157104HCID 68157104, compoundYield 103%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 4-methyl-N1-phenylbenzene-1,2-diamine (500 mg, 2.52 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (524 mg, 2.77 mmol), HOAt (377 mg, 2.77 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (532 mg, 2.77 mmol) and 4-methylmorpholine (0.609 mL, 5.54 mmol) in anhydrous DCM (20 mL) was stirred at RT for 20 h. The reaction mixture was diluted with DCM (100 mL) and washed with a saturated solution of NaHCO3. The organic layer was then dried and concentrated in vacuo. The resulting residue was dissolved in AcOH (10 mL) and heated to 70° C. for 20 h. After cooling to RT, volatiles were removed in vacuo and the residue was dissolved in EtOAc and washed with a saturated solution of NaHCO3 (2×100 mL). The organic layer was then washed with brine, dried (Na2SO4) and then concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 10-60% EtOAc in cyclohexane) affording [(S)-1-(5-Methyl-1-phenyl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tertbutyl ester (912 mg, quantitative). LCMS: RT 3.02 min [M+H-tBu]+ 352.1.

Workup

  1. washwashed with a saturated solution of NaHCO3
  2. customThe organic layer was then dried
  3. concentrationconcentrated in vacuo
  4. dissolutionThe resulting residue was dissolved in AcOH (10 mL)
  5. temperatureheated to 70° C. for 20 h
  6. temperatureAfter cooling to RT
  7. customvolatiles were removed in vacuo
  8. dissolutionthe residue was dissolved in EtOAc
  9. washwashed with a saturated solution of NaHCO3 (2×100 mL)
  10. washThe organic layer was then washed with brine
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated in vacuo
  13. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 10-60% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-67ac6b65363847c582f05b94ecc85dfc
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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