Oxalyl chloride → N-((5-((2-acetamidopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)tetrahydro-2H-pyran-4-carboxamide

HRID 626546노트

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HRID 626546 반응식
[O:1]1[CH2:6][CH2:5][CH:4]([C:7]([NH2:9])=[O:8])[CH2:3][CH2:2]1.C(Cl)(=O)[C:11](Cl)=[O:12].[NH2:16][C:17]1[N:22]=[CH:21][C:20]([O:23][C:24]2[CH:29]=[CH:28][N:27]=[C:26]([NH:30][C:31](=[O:33])[CH3:32])[CH:25]=2)=[CH:19][CH:18]=1>ClCCCl.C1COCC1>[C:31]([NH:30][C:26]1[CH:25]=[C:24]([O:23][C:20]2[CH:19]=[CH:18][C:17]([NH:16][C:11]([NH:9][C:7]([CH:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)=[O:8])=[O:12])=[N:22][CH:21]=2)[CH:29]=[CH:28][N:27]=1)(=[O:33])[CH3:32]

참가 물질

6

반응물 3

HCID 65578Oxalyl chlorideHCID 13197203Oxane-4-carboxamideHCID 90410482N-(4-((6-aminopyridin-3-yl)oxy)pyridin-2-yl)acetamide

생성물 1

HCID 86272277N-((5-((2-acetamidopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)tetrahydro-2H-pyran-4-carboxamide수율 52.4%

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매HCID 8028Tetrahydrofuran용매

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온도
80 °C

실험 절차

A solution of Example B5 (0.095 g, 0.737 mmol) in DCE (3 mL) was treated with oxalyl chloride (0.129 mL, 1.474 mmol) and heated at 80° C. for 3 h. The mixture was cooled to RT, concentrated to dryness, treated with a solution of Example A2 (0.09 g, 0.368 mmol) and TEA (0.205 mL, 1.474 mmol) in THF (4 mL) and stirred at RT for 0.5 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). The material was suspended in MeCN/H2O, frozen and lyophilized to afford N-((5-((2-acetamidopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)tetrahydro-2H-pyran-4-carboxamide (77 mg, 52%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.05 (s, 1H), 10.88 (s, 1H), 10.56 (s, 1H), 8.24 (d, J=2.9 Hz, 1H), 8.18 (d, J=5.7 Hz, 1H), 8.07 (d, J=9.0 Hz, 1H), 7.72 (dd, J=9.0, 2.9 Hz, 1H), 7.64 (d, J=2.4 Hz, 1H), 6.68 (dd, J=5.7, 2.4 Hz, 1H), 3.87 (m, 2H), 3.29-3.25 (m, 2H), 2.72-2.64 (m, 1H), 2.02 (s, 3H), 1.71 (m, 2H), 1.66-1.54 (m, 2H); MS (ESI) m/z: 400.2 (M+H+).

후처리

  1. temperatureThe mixture was cooled to RT
  2. concentrationconcentrated to dryness
  3. additionThe mixture was treated with satd
  4. extractionNaHCO3, extracted with EtOAc (2×)
  5. washthe combined organics were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness
  8. custompurified via silica gel chromatography (MeOH/DCM)
  9. temperaturefrozen

출처 및 근거

ORD 기록
ord-4af7ef639ad744528129e59a9be4276a
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309224B2

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