Potassium Carbonate → 3-(4-Chloro-2-fluorobenzyl)-N-(1-(4-methoxybenzyl)-5-methyl-1H-pyrazol-3-yl)-2-methyl-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine

HRID 597862노트

반응식

HRID 597862 반응식
Cl[C:2]1[CH:3]=[C:4]([CH2:21][N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:5]2[N:6]([C:8]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[F:20])=[C:9]([CH3:11])[N:10]=2)[N:7]=1.[CH3:28][O:29][C:30]1[CH:43]=[CH:42][C:33]([CH2:34][N:35]2[C:39]([CH3:40])=[CH:38][C:37]([NH2:41])=[N:36]2)=[CH:32][CH:31]=1.C(=O)([O-])[O-].[K+].[K+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].O1CCOCC1.O>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]([CH2:12][C:8]2[N:6]3[N:7]=[C:2]([NH:41][C:37]4[CH:38]=[C:39]([CH3:40])[N:35]([CH2:34][C:33]5[CH:42]=[CH:43][C:30]([O:29][CH3:28])=[CH:31][CH:32]=5)[N:36]=4)[CH:3]=[C:4]([CH2:21][N:22]4[CH2:23][CH2:24][O:25][CH2:26][CH2:27]4)[C:5]3=[N:10][C:9]=2[CH3:11])=[C:14]([F:20])[CH:15]=1

참가 물질

8

반응물 4

HCID 11430Potassium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 674274551-(4-methoxybenzyl)-5-methyl-1H-pyrazol-3-amineHCID 715739154-[[6-Chloro-3-(4-chloro-2-fluorobenzyl)-2-methylimidazo[1,2-b]pyridazin-8-yl]methyl]morpholine

생성물 1

HCID 674350193-(4-Chloro-2-fluorobenzyl)-N-(1-(4-methoxybenzyl)-5-methyl-1H-pyrazol-3-yl)-2-methyl-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine수율 86.1%

시약·촉매·용매 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium촉매HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

Combine 4-((6-chloro-3-(4-chloro-2-fluorobenzyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)methyl)morpholin (0.36 g, 0.88 mmol), 1-(4-methoxybenzyl)-5-methyl-1H-pyrazol-3-amine (0.248 g, 1.3 equiv.), potassium carbonate (0.30 g, 2.5 equiv.), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.076 g, 0.15 equiv.), water (2 mL), and 1,4-dioxane (20 mL) in a round bottom flask. Degas thoroughly with nitrogen then add bis(dibenzylideneacetone)palladium (0.10 g, 0.2 equiv.). Attach a reflux condenser and place under nitrogen. Heat the reaction at reflux overnight. Pass reaction through a Celite plug. Wash the plug with EA. Transfer to a separatory funnel and wash with water. Wash the organic layer with aqueous sodium chloride, and dry over anhydrous magnesium sulfate. Filter and concentrate in vacuo. Purify on silica gel (EA→10% methanol:EA) to give the title compound (0.447 g, 86%) as a pale yellow solid. LCMS (4 min)=590.2, 591.2, M+1.

후처리

  1. customDegas thoroughly with nitrogen
  2. temperatureHeat
  3. customthe reaction
  4. temperatureat reflux overnight
  5. customPass reaction through a Celite plug
  6. washWash the plug with EA
  7. washTransfer to a separatory funnel and wash with water
  8. washWash the organic layer with aqueous sodium chloride
  9. dry with materialdry over anhydrous magnesium sulfate
  10. filtrationFilter
  11. concentrationconcentrate in vacuo
  12. customPurify on silica gel (EA→10% methanol:EA)

출처 및 근거

ORD 기록
ord-4492c40f18ff48c3ba42ed913be5582c
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07897600B2

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