Hydrochloric Acid → Pyridazine

HRID 1432691

반응식

HRID 1432691 반응식
[CH3:1][C:2]1[CH:6]=[CH:5][O:4][CH:3]=1.[Li]CCCC.[CH2:12]([CH:14]([C:17]1[C:18]2[N:19]([C:24](I)=[C:25]([CH3:27])[N:26]=2)[N:20]=[C:21]([CH3:23])[CH:22]=1)[CH2:15][CH3:16])[CH3:13].Cl>[Cl-].[Cl-].[Zn+2].C1COCC1>[N:19]1[CH:18]=[CH:17][CH:22]=[CH:21][N:20]=1.[CH2:12]([CH:14]([C:17]1[C:18]2[N:19]([C:24]([C:3]3[O:4][CH:5]=[CH:6][C:2]=3[CH3:1])=[C:25]([CH3:27])[N:26]=2)[N:20]=[C:21]([CH3:23])[CH:22]=1)[CH2:15][CH3:16])[CH3:13]

참가 물질

8

반응물 4

HCID 313Hydrochloric AcidHCID 135873-MethylfuranHCID 577526818-(1-Ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 178418339Butyllithium2회

생성물 2

HCID 9259Pyridazine수율 318%HCID 57932919HCID 57932919, 화합물

시약·촉매·용매 2

HCID 3007855Zincchloride촉매HCID 8028Tetrahydrofuran용매

반응 조건

온도
0 °C

실험 절차

A THF solution (5 mL) of 3-methylfuran (Acros, 232 mg, 2.83 mmol) is cooled to −78° C. under N2 then treated with nBuLi (1.6 M in hexane, 1.8 mL, 2.9 mmol). After addition of the nBuLi, the solution is warmed to 0° C. for 15 minutes, then to room temperature for an additional 5 minutes. The reaction mixture is then cooled to −78° C. and treated with ZnCl2 (Aldrich, 0.5 M in THF, 5.8 mL, 2.9 mmol). The resulting mixture is warmed to room temperature and treated with 8-(1-ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazine (400 mg, 1.17 mmol) and PdCl2(dppf)-CH2Cl2 complex (Aldrich, 95 mg, 0.12 mmol). The mixture is heated to 60° C. for 4 hours, then poured into 1 N HCl (60 mL) and extracted with ethyl acetate (2×60 mL). The combined organic extracts are washed with aq. brine, dried over Na2SO4, filtered, and concentrated. The crude residue is purified by chromatography using hexane-ethyl acetate gradient (100% hexane to 20% ethyl acetate in hexane) to elute the title compound as an oil pyridazine (149 mg, 43% yield). ES-MS (m/z): calc'd for C18H23N3O: 297.2; found: 298.5 (M+H); 1H NMR (400 mHz, CDCl3): δ 7.59 (d, J=1.8 Hz, 1H), 6.71 (s, 1H), 6.47 (d, J=1.8 Hz, 1H), 3.36 (m, 1H), 2.55 (s, 3H), 2.50 (s, 3H), 2.10 (s, 3H), 1.92-1.79 (m, 4H), 0.90 (t, J=7.5 Hz, 6H).

후처리

  1. temperatureThe reaction mixture is then cooled to −78° C.
  2. temperatureThe resulting mixture is warmed to room temperature
  3. temperatureThe mixture is heated to 60° C. for 4 hours
  4. extractionextracted with ethyl acetate (2×60 mL)
  5. washThe combined organic extracts are washed with aq. brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue is purified by chromatography

출처 및 근거

ORD 기록
ord-2d0203f01736484085763576b38a3fc0
출처 데이터셋
uspto-grants-2009_11
특허 번호
US07612067B2

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