Cesium carbonate → 5-(Benzyloxy)-6-(6-methylpyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1661999ノート

反応式

HRID 1661999 の反応式
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][C:17]=1Br)[N:14]([CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)[N:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.CC([O-])=O.[K+].Br[C:49]1[CH:50]=[CH:51][C:52]([CH3:55])=[N:53][CH:54]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(C)=O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][C:17]=1[C:49]1[CH:54]=[N:53][C:52]([CH3:55])=[CH:51][CH:50]=1)[N:14]([CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)[N:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

11

反応物 5

HCID 10796Cesium carbonateHCID 517044Potassium AcetateHCID 12010205-Bromo-2-methylpyridineHCID 2733548Bis(pinacolato)diboraneHCID 667670665-(Benzyloxy)-6-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

生成物 1

HCID 667671245-(Benzyloxy)-6-(6-methylpyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole収率 46.2%

試薬・触媒・溶媒 5

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 178418397HCID 178418397、化合物触媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

実験手順

To a solution of 5-(benzyloxy)-6-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (4 g, 10.3 mmol) in 1,4-dioxane (25 mL) is added bis(pinacolato)diboron (3 g, 11.8 mmol), dppf (0.3 g, 541 μmol), PdCl2(dppf) (0.42 g, 514 μmol) and KOAc (2 g, 20.4 mmol) under N2. After the reaction mixture is stirred at reflux for 5 hours, 5-bromo-2-methylpyridine (2.1 g, 12.2 mmol), tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) (0.6 g, 519 μmol) and Cs2CO3 (4 g, 12.3 mmol) are added and the mixture is stirred at reflux overnight. The reaction mixture is cooled and filtered, the filtrate is concentrated. The residue is purified by silica gel column chromatography eluting with PE:EtOAc (2:1) to give the product (1.9 g, 46.0% yield). MS (m/z): 400.1 (M+H).

後処理

  1. temperatureat reflux for 5 hours
  2. stirringthe mixture is stirred
  3. temperatureat reflux overnight
  4. temperatureThe reaction mixture is cooled
  5. filtrationfiltered
  6. concentrationthe filtrate is concentrated
  7. customThe residue is purified by silica gel column chromatography
  8. washeluting with PE

出典と根拠

ORDレコード
ord-3b136d0de8584be19934fae2556c9d03
出典データセット
uspto-grants-2011_10
特許番号
US08030302B2

反応ノート

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