Cesium carbonate → 3-Chloro-4-methyl-6-phenylpyridazine

HRID 219123

반응식

HRID 219123 반응식
[Cl:1][C:2]1[N:3]=[N:4][C:5](Cl)=[CH:6][C:7]=1[CH3:8].[C:10]1(B(O)O)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O>[Cl:1][C:2]1[N:3]=[N:4][C:5]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:6][C:7]=1[CH3:8]

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 66827Phenylboronic AcidHCID 879233,6-Dichloro-4-methylpyridazine

생성물 1

HCID 1199993-Chloro-4-methyl-6-phenylpyridazine

시약·촉매·용매 2

HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
80 °C

실험 절차

3,6-Dichloro-4-methylpyridazine (1.00 g, 6.1 mmol) was mostly dissolved in dioxane (22.5 mL) then added phenylboronic acid (0.82 g, 6.7 mmol), PdCl2(dppf)-CH2Cl2Adduct (0.25 g, 0.31 mmol) and a solution of cesium carbonate (6.0 g, 18 mmol) in water (7.5 mL). The reaction mixture was heated at 80° C. for 6 hours. The reaction mixture was concentrated under vacuum and the remaining solid was triturated with water. The solid was collected on a glass frit, washing well with water. The sample was purified by flash chromatography eluting with 1:4 ethyl acetate/hexane to afford 3-chloro-4-methyl-6-phenylpyridazine as an off-white solid. MS (ESI pos. ion) m/z: 205.2 (MH+). Step 2. 3-Chloro-4-methyl-6-phenylpyridazine (0.510 g, 2.49 mmol) was dissolved in hydrazine (1.56 ml, 49.8 mmol) then the reaction mixture was heated at 100° C. for 1.5 hours. The precipitate that had formed in the mixture was collected and washed with iPrOH. The solid was dried under high vacuum to afford 1-(4-methyl-6-phenylpyridazin-3-yl)hydrazine as a pale yellow solid. MS (ESI pos. ion) m/z: 201.1 (MH+). The remaining synthesis of 7-methoxy-N-((8-methyl-6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)-1,5-naphthyridin-4-amine was conducted as described in general Method B.

후처리

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. customthe remaining solid was triturated with water
  3. customThe solid was collected on a glass frit
  4. washwashing well with water
  5. customThe sample was purified by flash chromatography
  6. washeluting with 1:4 ethyl acetate/hexane

출처 및 근거

ORD 기록
ord-dc76c7f48b6f44e18fe60431ec6daacd
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08198448B2

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