4-Methylmorpholine → (S)-tert-butyl 1-(6-fluoro-1-phenyl-1H-benzo[d]imidazol-2-yl)propylcarbamate

HRID 242864노트

반응식

HRID 242864 반응식
[F: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]([CH2:28][CH3:29])[C:25](O)=O)=[O:22])([CH3:19])([CH3:18])[CH3:17].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:25]([C@@H:24]([NH:23][C:21](=[O:22])[O:20][C:16]([CH3:17])([CH3:19])[CH3:18])[CH2:28][CH3:29])[N:9]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:4]=2[CH:3]=1

참가 물질

7

반응물 5

HCID 79724-MethylmorpholineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2755934(S)-2-((tert)-Butoxycarbonyl)amino)butanoic acidHCID 214506204-Fluoro-2-phenylaminoaniline

생성물 1

HCID 68158046(S)-tert-butyl 1-(6-fluoro-1-phenyl-1H-benzo[d]imidazol-2-yl)propylcarbamate수율 64.4%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A mixture of 4-fluoro-N2-phenylbenzene-1,2-diamine from Example 8 (199 mg, 0.984 mmol), (S)-2-tertbutoxycarbonylaminobutyric acid (219 mg, 1.08 mmol), HOAt (147 mg, 1.08 mmol), 4-methylmorpholine (0.238 mL, 2.16 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (207 mg, 1.08 mmol) in DCM (5 mL) was stirred at RT for 2 h. The reaction mixture was then partitioned between DCM (50 mL) and a saturated solution of NaHCO3. The organic layer was dried (Na2SO4) and concentrated in vacuo and the resulting residue was dissolved in AcOH (10 mL) and stirred for 18 h at 70° C. After cooling to RT, volatiles were evaporated in vacuo and the residue was partitioned between DCM (50 mL) and a saturated solution of NaHCO3. The organic layer was washed with brine, dried (Na2SO4) and then concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-50% EtOAc in cyclohexane) affording (S)-tert-butyl 1-(6-fluoro-1-phenyl-1H-benzo[d]imidazol-2-yl)propylcarbamate as a beige solid (234 mg, 64%). LCMS: RT 3.82 min [M+H]+ 370.5

후처리

  1. customThe reaction mixture was then partitioned between DCM (50 mL)
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. dissolutionthe resulting residue was dissolved in AcOH (10 mL)
  5. stirringstirred for 18 h at 70° C
  6. temperatureAfter cooling to RT
  7. customvolatiles were evaporated in vacuo
  8. customthe residue was partitioned between DCM (50 mL)
  9. washThe organic layer was washed with brine
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated in vacuo
  12. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-50% EtOAc in cyclohexane)

출처 및 근거

ORD 기록
ord-587d4ae1700e43f18576078384f216b7
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08653089B2

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