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

HRID 2278992
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HRID 2278992 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.[CH3:23][C:24]1[N:29]=[C:28]([NH2:30])[CH:27]=[CH:26][C:25]=1[O:31][C:32]1[CH:37]=[CH:36][N:35]=[C:34]([C:38]2[O:42][N:41]=[C:40]([CH3:43])[CH:39]=2)[CH:33]=1>C(Cl)Cl>[CH3:23][C:24]1[N:29]=[C:28]([NH:30][C:1]([N:13]2[CH2:14][CH2:15][N:11]([CH:8]3[CH2:7][CH2:6][O:5][CH2:10][CH2:9]3)[C:12]2=[O:16])=[O:2])[CH:27]=[CH:26][C:25]=1[O:31][C:32]1[CH:37]=[CH:36][N:35]=[C:34]([C:38]2[O:42][N:41]=[C:40]([CH3:43])[CH:39]=2)[CH:33]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 4

HCID 1049PyridineHCID 6371PhosgeneHCID 904036286-Methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-amineHCID 904259751-(Oxan-4-yl)imidazolidin-2-one

생성물 1

HCID 86270405N-(6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide수율 63%

시약·촉매·용매

1
HCID 6344Dichloromethane용매2회

실험 절차

Phosgene (20% in toluene, 0.613 g, 1.24 mmol) was treated with a solution of Example B1 (0.063 g, 0.37 mmol) and pyridine (0.1 mL, 1.24 mmol) in DCM (2 mL), stirred for 15 min, then concentrated to dryness. The residue was dissolved in DCM (2 mL), treated with a solution of 6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-amine (0.07 g, 0.25 mmol) and TEA (0.17 mL, 1.24 mmol) in DCM (2 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 (MeOH/DCM) to afford N-(6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (75 mg, 63%). 1H NMR (400 MHz, DMSO-d6): δ 10.92 (s, 1 H), 8.55 (d, J=5.7 Hz, 1 H), 7.92 (d, J=8.8 Hz, 1 H), 7.67 (d, J=8.8 Hz, 1 H), 7.34 (d, J=2.5 Hz, 1 H), 6.98 (s, 1 H), 6.96 (dd, J=5.7, 2.5 Hz, 1 H), 3.95-3.77 (m, 5 H), 3.48-3.35 (m, 4 H), 2.28 (s, 3 H), 2.24 (s, 3 H), 1.71-1.70 (m, 2 H), 1.60 (d, J=12.5 Hz, 2 H); MS (ESI) m/z: 479.2 (M+H+).

후처리

  1. concentrationconcentrated to dryness
  2. dissolutionThe residue was dissolved in DCM (2 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 (MeOH/DCM)

출처 및 근거

ORD 기록
ord-92f96f7d22714fc4bae30eb94c0db024
출처 데이터셋
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09133183B2

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