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 597862ノート

反応式

HRID 597862 の反応式
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

参加物

8

反応物 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

生成物 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-amine収率 86.1%

試薬・触媒・溶媒 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-4492c40f18ff48c3ba42ed913be5582c
出典データセット
uspto-grants-2011_03
特許番号
US07897600B2

反応ノート

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