4-Methylmorpholine → (R)-1-(6-Fluoro-7-methyl-1-phenyl-1H-benzoimidazol-2-yl)-2-methoxyethylamine

HRID 242984

Reaction equation

HRID 242984 reaction equation
[F:1][C:2]1[C:3]([CH3:16])=[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(OC([NH:24][C@@H:25]([CH2:29][O:30][CH3:31])[C:26](O)=O)=O)(C)(C)C.C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]2[N:8]=[C:26]([C@@H:25]([NH2:24])[CH2:29][O:30][CH3:31])[N:9]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:4]=2[C:3]=1[CH3:16]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7016354(2S)-2-(((tert-butoxy)carbonyl)amino)-3-methoxypropanoic acidHCID 681575494-Fluoro-3-methyl-N2-phenylbenzene-1,2-diamine

Product 1

HCID 68157044(R)-1-(6-Fluoro-7-methyl-1-phenyl-1H-benzoimidazol-2-yl)-2-methoxyethylamineYield 70.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-fluoro-3-methyl-N2-phenylbenzene-1,2-diamine (560 mg, 2.59 mmol), (S)-2-tertbutoxycarbonylamino-3-methoxypropionic acid (624 mg, 2.85 mmol), HOAt (388 mg, 2.85 mmol), 4-methylmorpholine (626 μL, 5.69 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (547 mg, 2.85 mmol) in DCM (10 mL) was stirred at RT for 1 h. The reaction mixture was partitioned between DCM and water. The aqueous phase was further extracted with DCM and the combined organic fractions washed with brine, dried (MgSO4) and concentrated in vacuo. The resulting residue was dissolved in 4N HCl in dioxane (5 mL) and the mixture heated at 70° C. for 2 h. The volatiles were removed in vacuo and the resulting residue partitioned between EtOAc and a saturated aqueous solution of NaHCO3. The aqueous phase was further extracted with EtOAc and the combined organic fractions were washed with brine, dried (MgSO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM) to afford the title compound (545 mg, 70%). LCMS (Method C): RT 3.95 min [M+H]+ 300.2.

Workup

  1. customThe reaction mixture was partitioned between DCM and water
  2. extractionThe aqueous phase was further extracted with DCM
  3. washthe combined organic fractions washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. dissolutionThe resulting residue was dissolved in 4N HCl in dioxane (5 mL)
  7. temperaturethe mixture heated at 70° C. for 2 h
  8. customThe volatiles were removed in vacuo
  9. customthe resulting residue partitioned between EtOAc
  10. extractionThe aqueous phase was further extracted with EtOAc
  11. washthe combined organic fractions were washed with brine
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated in vacuo
  14. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-17fe5dfa2bf54527a0680f7c92c569be
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Linked notes

Loading…