4-Methylmorpholine → HCID 68157577, compound

HRID 242809Notes

Reaction equation

HRID 242809 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:5]([NH2:8])=[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:9]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:4]2[CH:3]=[C:2]([CH3:1])[CH:7]=[CH:6][C:5]=2[N:8]=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 10512174HCID 10512174, compound

Product 1

HCID 68157577HCID 68157577, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-methyl-N2-phenylbenzene-1,2-diamine (600 mg, 3.03 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (861 mg, 4.55 mmol), HOAt (453 mg, 3.33 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (874 mg, 4.55 mmol) and 4-methylmorpholine (0.74 mL, 6.67 mmol) in anhydrous DCM (20 mL) was stirred at RT for 1.5 h. Volatiles were removed under reduced pressure and 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 (100 mL) 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 absorbed onto HM-N and the solvent was removed in vacuo. The product was purified by column chromatography (Si—PCC, gradient 10-60% EtOAc in cyclohexane) affording [(S)-1-(6-Methyl-1-phenyl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tertbutyl ester (969 mg, 92%). LCMS: RT 3.10 min [M+H-tBu]+ 352.1.

Workup

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

Sources & evidence

ORD record
ord-0565f82970c44a32a035b573a4331eb7
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

Loading…