Cesium carbonate → [7-(2-Chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-yl]-[4-(3-pyrrolidin-1-yl-propane-1-sulfonyl)-phenyl]-amine

HRID 449221ノート

反応式

HRID 449221 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:20]=[C:19]([CH3:21])[C:13]2[N:14]=[C:15]([NH2:18])[N:16]=[N:17][C:12]=2[CH:11]=1.Br[C:23]1[CH:28]=[CH:27][C:26]([S:29]([CH2:32][CH2:33][CH2:34][N:35]2[CH2:39][CH2:38][CH2:37][CH2:36]2)(=[O:31])=[O:30])=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+].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>C(Cl)Cl.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:20]=[C:19]([CH3:21])[C:13]2[N:14]=[C:15]([NH:18][C:23]3[CH:28]=[CH:27][C:26]([S:29]([CH2:32][CH2:33][CH2:34][N:35]4[CH2:36][CH2:37][CH2:38][CH2:39]4)(=[O:31])=[O:30])=[CH:25][CH:24]=3)[N:16]=[N:17][C:12]=2[CH:11]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 248227537-(2-Chloro-5-methoxyphenyl)-5-methylbenzo[e][1,2,4]triazin-3-amineHCID 529828661-(3-(4-Bromophenylsulfonyl)propyl)pyrrolidine

生成物 1

HCID 59837755[7-(2-Chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-yl]-[4-(3-pyrrolidin-1-yl-propane-1-sulfonyl)-phenyl]-amine収率 91%

試薬・触媒・溶媒 2

HCID 9832798Tris(dibenzylideneacetone) dipalladium触媒HCID 6344Dichloromethane溶媒

実験手順

In a dry 25 mL round bottom flask, 7-(2-chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamine (0.0361 g, 0.122 mmol, 1 equiv), 1-[3-(4-bromo-benzenesulfonyl)-propyl]-pyrrolidine (0.061 g, 0.184 mmol, 1.5 equiv), cesium carbonate (0.120 g, 0.367 mmol, 3 equiv), 4,5-bis(diphenylphosphino)-9,9-dimethyl xanthene (0.014 g, 0.0244 mmol, 0.2 equiv) and tris(dibenzylideneacetone) dipalladium (0.012 g, 0.0122 mmol, 0.1 equiv) were combined. The reactants were flushed with argon, diluted with dioxane (6 mL) and outfitted with reflux condenser. The reaction was heated to reflux for 18 hours, filtered hot, diluted with ethyl acetate and washed with brine. The brine layer was back extracted once with fresh ethyl acetate. The organic phases were combined and dried over sodium sulfate (Na2SO4). Filtration followed by evaporation provided crude product, which was dissolved in minimum amount of DCM and precipitated out with excess hexanes. Solids were filtered off and dried to yield a yellow powder (0.06 g, 91% yield).

後処理

  1. customThe reactants were flushed with argon
  2. additiondiluted with dioxane (6 mL)
  3. temperaturewith reflux condenser
  4. temperatureThe reaction was heated
  5. temperatureto reflux for 18 hours
  6. filtrationfiltered hot
  7. additiondiluted with ethyl acetate
  8. washwashed with brine
  9. extractionThe brine layer was back extracted once with fresh ethyl acetate
  10. dry with materialdried over sodium sulfate (Na2SO4)
  11. filtrationFiltration
  12. customfollowed by evaporation
  13. customprovided crude product, which
  14. customprecipitated out with excess hexanes
  15. filtrationSolids were filtered off
  16. customdried

出典と根拠

ORDレコード
ord-8ee467da33a74c46b9c4ff36ac8f88a5
出典データセット
uspto-grants-2013_07
特許番号
US08481536B2

反応ノート

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