Sodium hydride → Ethyl 1-[(6-chloropyridin-3-yl)methyl]-4-oxo-1,4-dihydropyrido[2,3-c]pyridazine-3-carboxylate

HRID 2067104노트

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HRID 2067104 반응식
[O:1]=[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[N:6][NH:5][C:4]2[N:13]=[CH:14][CH:15]=[CH:16][C:3]1=2.[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24]Cl)=[CH:20][N:19]=1.[H-].[Na+].C(=O)(O)[O-].[Na+]>CN(C)C=O>[Cl:17][C:18]1[N:19]=[CH:20][C:21]([CH2:24][N:5]2[C:4]3[N:13]=[CH:14][CH:15]=[CH:16][C:3]=3[C:2](=[O:1])[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[N:6]2)=[CH:22][CH:23]=1

참가 물질

6

반응물 4

HCID 24758Sodium hydrideHCID 1554792-Chloro-5-(chloromethyl)pyridineHCID 516892Sodium BicarbonateHCID 66745620Ethyl 4-oxo-1,4-dihydropyrido[2,3-c]pyridazine-3-carboxylate

생성물 1

HCID 86662098Ethyl 1-[(6-chloropyridin-3-yl)methyl]-4-oxo-1,4-dihydropyrido[2,3-c]pyridazine-3-carboxylate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
0 °C

실험 절차

Ethyl 4-oxo-1,4-dihydropyrido[2,3-c]pyridazine-3-carboxylate (1.00 g, 4.56 mmol) and 2-chloro-5-(chloromethyl)pyridine (813 mg, 5.02 mmol, 1.1 equiv) were combined in degassed N,N-dimethylformamide and cooled to 0° C. Sodium hydride (219 mg, 5.47 mmol, 1.2 equiv) was added portionwise over 5 minutes and the mixture was stirred for an additional 1 hour at 0° C. The mixture was warmed to ambient temperature, stirred for 1 hour and poured into sodium bicarbonate (150 mL, aqueous saturated). The aqueous layer was extracted with ethyl acetate (2×150 mL) and the combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate), providing the titled compound as a white solid.

후처리

  1. temperatureThe mixture was warmed to ambient temperature
  2. stirringstirred for 1 hour
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×150 mL)
  4. dry with materialthe combined organic extracts were dried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate)

출처 및 근거

ORD 기록
ord-5f77da195d5f46c1a5b698d2e4d4a833
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08293744B2

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