Pyridine → N-(5-((2-chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide

HRID 2278969노트

반응식

HRID 2278969 반응식
[C:1](Cl)(Cl)=[O:2].[O:5]1[CH2:10][CH2:9][CH:8]([N:11]2[CH2:15][CH2:14][NH:13][C:12]2=[O:16])[CH2:7][CH2:6]1.N1C=CC=CC=1.[Cl:23][C:24]1[CH:29]=[C:28]([O:30][C:31]2[CH:32]=[CH:33][C:34]([NH2:38])=[N:35][C:36]=2[CH3:37])[CH:27]=[CH:26][N:25]=1>C(Cl)Cl>[Cl:23][C:24]1[CH:29]=[C:28]([O:30][C:31]2[CH:32]=[CH:33][C:34]([NH:38][C:1]([N:13]3[CH2:14][CH2:15][N:11]([CH:8]4[CH2:7][CH2:6][O:5][CH2:10][CH2:9]4)[C:12]3=[O:16])=[O:2])=[N:35][C:36]=2[CH3:37])[CH:27]=[CH:26][N:25]=1

참가 물질

6

반응물 4

HCID 1049PyridineHCID 6371PhosgeneHCID 904029725-((2-Chloropyridin-4-yl)oxy)-6-methylpyridin-2-amineHCID 904259751-(Oxan-4-yl)imidazolidin-2-one

생성물 1

HCID 90426065N-(5-((2-chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide수율 52.4%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

Phosgene (20% in toluene, 2.62 g, 5.3 mmol) was treated with a solution of Example B1 (0.27 g, 1.59 mmol) and pyridine (0.43 mL, 5.3 mmol) in DCM (5 mL), stirred for 15 min, then concentrated to dryness. The residue was dissolved in DCM (5 mL), treated with a solution of Example A7 (0.25 g, 1.06 mmol) and TEA (0.74 mL, 5.3 mmol) in DCM (5 mL) and stirred at RT for 1 h. The mixture was treated with satd. NaHCO3, extracted with EtOAc (2×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (EtOAc/Hex) to afford N-(5-((2-chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (0.24 g, 52%). 1H NMR (400 MHz, DMSO-d6): δ 10.91 (s, 1 H), 8.27 (d, J=5.8 Hz, 1 H), 7.90 (d, J=8.8 Hz, 1 H), 7.65 (d, J=8.8 Hz, 1 H), 7.02 (d, J=2.3 Hz, 1 H), 6.92 (dd, J=5.8, 2.3 Hz, 1 H), 3.94-3.84 (m, 5 H), 3.48-3.35 (m, 4 H), 2.21 (s, 3 H), 1.74-1.66 (m, 2 H), 1.60 (d, J=12.5 Hz, 2 H); MS (ESI) m/z: 432.1 (M+H+).

후처리

  1. concentrationconcentrated to dryness
  2. dissolutionThe residue was dissolved in DCM (5 mL)
  3. stirringstirred at RT for 1 h
  4. additionThe mixture was treated with satd
  5. extractionNaHCO3, extracted with EtOAc (2×)
  6. washthe combined organics were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated to dryness
  9. custompurified via silica gel chromatography (EtOAc/Hex)

출처 및 근거

ORD 기록
ord-231a34df98fa43c48509a972f93b54f0
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09133183B2

반응 노트

불러오는 중…