Water → N-((5-((2-acetamidopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)tetrahydrofuran-3-carboxamide

HRID 626556노트

반응식

HRID 626556 반응식
[O:1]1[CH2:5][CH2:4][CH:3]([C:6]([NH2:8])=[O:7])[CH2:2]1.C(Cl)(=O)[C:10](Cl)=[O:11].[NH2:15][C:16]1[N:21]=[CH:20][C:19]([O:22][C:23]2[CH:28]=[CH:27][N:26]=[C:25]([NH:29][C:30](=[O:32])[CH3:31])[CH:24]=2)=[CH:18][CH:17]=1.O>ClCCCl.C1COCC1>[C:30]([NH:29][C:25]1[CH:24]=[C:23]([O:22][C:19]2[CH:18]=[CH:17][C:16]([NH:15][C:10]([NH:8][C:6]([CH:3]3[CH2:4][CH2:5][O:1][CH2:2]3)=[O:7])=[O:11])=[N:21][CH:20]=2)[CH:28]=[CH:27][N:26]=1)(=[O:32])[CH3:31]

참가 물질

7

반응물 4

HCID 962WaterHCID 65578Oxalyl chlorideHCID 21982383Oxolane-3-carboxamideHCID 90410482N-(4-((6-aminopyridin-3-yl)oxy)pyridin-2-yl)acetamide

생성물 1

HCID 86272978N-((5-((2-acetamidopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)tetrahydrofuran-3-carboxamide수율 24.2%

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매HCID 8028Tetrahydrofuran용매

실험 절차

A solution of Example B2 (0.104 g, 0.901 mmol) in DCE (3 mL) was treated with oxalyl chloride (0.079 mL, 0.901 mmol), stirred at RT for 1 h, then heated at 75° C. for 1 h. The mixture was cooled to RT, treated with a solution of Example A2 (0.11 g, 0.450 mmol) and TEA (0.188 mL, 1.351 mmol) in THF (4 mL) and stirred at RT for 1 h. The mixture was treated with water, extracted with 10% MeOH/DCM (1×), then DCM (1×) 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-((5-((2-acetamidopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)tetrahydrofuran-3-carboxamide (42 mg, 24%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.98 (s, 2H), 10.56 (s, 1H), 8.24 (d, J=2.9 Hz, 1H), 8.18 (d, J=5.7 Hz, 1H), 8.08 (d, J=9.0 Hz, 1H), 7.72 (dd, J=9.0, 2.9 Hz, 1H), 7.64 (d, J=2.4 Hz, 1H), 6.69 (dd, J=5.7, 2.4 Hz, 1H), 3.87 (t, J=8.3 Hz, 1H), 3.76-3.75 (m, 2H), 3.67-3.66 (m, 1H), 3.28-3.26 (m, 1H), 2.08-2.06 (m, 2H), 2.03 (s, 3H); MS (ESI) m/z: 386.2 (M+H+).

후처리

  1. temperatureheated at 75° C. for 1 h
  2. temperatureThe mixture was cooled to RT
  3. stirringstirred at RT for 1 h
  4. extractionextracted with 10% MeOH/DCM (1×)
  5. washDCM (1×) and the combined organics were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness
  8. custompurified via silica gel chromatography (MeOH/DCM)

출처 및 근거

ORD 기록
ord-e5fa81dcbd3b42e98711431db7d10be9
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309224B2

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