Cesium carbonate → 3-(4,5-dibromo-2-methyl-2H-pyrazol-3-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

HRID 1432696노트

반응식

HRID 1432696 반응식
[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([CH:13]=[C:14]([CH3:16])[N:15]=2)[N:9]=[C:10]([CH3:12])[CH:11]=1)[CH2:4][CH3:5])[CH3:2].[Br:17][C:18]1[C:22]([Br:23])=[C:21](Br)[N:20]([CH3:25])[N:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[Br:23][C:22]1[C:18]([Br:17])=[N:19][N:20]([CH3:25])[C:21]=1[C:13]1[N:8]2[N:9]=[C:10]([CH3:12])[CH:11]=[C:6]([CH:3]([CH2:4][CH3:5])[CH2:1][CH3:2])[C:7]2=[N:15][C:14]=1[CH3:16]

참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 133340543,4,5-Tribromo-1-methyl-1H-pyrazoleHCID 688412672,6-Dimethyl-8-(pentan-3-yl)imidazo[1,2-b]pyridazine

생성물 1

HCID 579329713-(4,5-dibromo-2-methyl-2H-pyrazol-3-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine수율 32%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
130 °C

실험 절차

8-(1-Ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (300 mg, 1.4 mmol), 3,4,5-tribromo-1-methyl-1H-pyrazole (700 mg, 2.1 mmol) and cesium carbonate (900 mg, 2.8 mmol) are stirred in DMF (5 ml) and degassed by bubbling a stream of nitrogen through the mixture. PdCl2(PPh3)2 (14 mg) is added and the mixture heated to 130° C. overnight. The mixture is added to water and extracted twice with EtOAc. The combined organic extracts are washed with brine, dried over Na2SO4, filtered and concentrated. The crude product is purified by chromatography using a hexane-ethyl acetate gradient (100% hexane to 20% ethyl acetate in hexane) to elute the title product (204 mg, 32% yield). ES-MS (m/z): calc'd for C17H21Br2N5: 455.2. found 455.9 (M+H)+. 1H NMR (400 mHz, CDCl3): δ 6.75 (s, 1H), 3.72 (s, 3H), 3.33 (m, 1H), 2.51 (s, 3H), 2.45 (s, 3H), 1.84 (m, 4H), 0.88 (t, 6H).

후처리

  1. customdegassed
  2. customby bubbling a stream of nitrogen through the mixture
  3. additionPdCl2(PPh3)2 (14 mg) is added
  4. additionThe mixture is added to water
  5. extractionextracted twice with EtOAc
  6. washThe combined organic extracts are washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product is purified by chromatography

출처 및 근거

ORD 기록
ord-006bcd88790c4f5797b2c9ff0f673125
출처 데이터셋
uspto-grants-2009_11
특허 번호
US07612067B2

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