2-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl → 6-morpholin-4-ylbenzo[d]isothiazole-3-carboxylic acid ((3R)-1-azabicyclo[2.2.2]oct-3-yl)amide

HRID 889121

反応式

HRID 889121 の反応式
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([NH:9][C:10]([C:12]1[C:16]3[CH:17]=[C:18](Br)[CH:19]=[CH:20][C:15]=3[S:14][N:13]=1)=[O:11])[CH2:2]2.[C:22](=[O:25])(O)[O-].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2[C:40]2C=CC=C[C:41]=2[N:46](C)[CH3:47])CCCCC1>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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([NH:9][C:10]([C:12]1[C:16]3[CH:17]=[CH:18][C:19]([N:46]4[CH2:47][CH2:22][O:25][CH2:40][CH2:41]4)=[CH:20][C:15]=3[S:14][N:13]=1)=[O:11])[CH2:2]2

参加物

5

反応物 3

HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 2734983Cesium bicarbonateHCID 9976134N-((3R)-1-azabicyclo[2.2.2]oct-3-yl)-5-(bromo)benzo[d]isothiazole-3-carboxamide

生成物 1

HCID 103419666-morpholin-4-ylbenzo[d]isothiazole-3-carboxylic acid ((3R)-1-azabicyclo[2.2.2]oct-3-yl)amide収率 180.3%

試薬・触媒・溶媒 1

HCID 9811564Bis(dibenzylideneacetone)palladium触媒

実験手順

In a 5 mL microwave reaction vessel was added N-((3R)-1-azabicyclo[2.2.2]oct-3-yl)-5-(bromo)benzo[d]isothiazole-3-carboxamide (133 mg, 0.37 mmol), tris(dibenzylideneacetone)dipalladium (0) (34 mg, 0.04 mmol), caesium bicarbonate (213 mg, 1.1 mmol), and (2′-dicyclohexylphosphanylbiphenyl-2-yl)dimethylamine (30 mg, 0.07 mmol). The vial was then evacuated and back-filled with argon gas. The mixture of solids was then diluted with morpholine (0.7 mL), dioxane (1 mL), and triethylamine (0.5 mL) and the reaction vessel was sealed. The reaction mixture was subjected to microwave irradiation at 120° C. for 1800 s. The reaction mixture was filtered through a plug of celite and concentrated in vacuo. The crude product was purified by chromatography (90/10/1 dichloromethane/methanol/ammonium hydroxide) to provide 47 mg (34%) of 6-morpholin-4-ylbenzo[d]isothiazole-3-carboxylic acid ((3R)-1-azabicyclo[2.2.2]oct-3-yl)amide as a colorless solid.

後処理

  1. customThe vial was then evacuated
  2. additionback-filled with argon gas
  3. additionThe mixture of solids
  4. additionwas then diluted with morpholine (0.7 mL), dioxane (1 mL), and triethylamine (0.5 mL)
  5. customthe reaction vessel was sealed
  6. customirradiation at 120° C. for 1800 s
  7. filtrationThe reaction mixture was filtered through a plug of celite and
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by chromatography (90/10/1 dichloromethane/methanol/ammonium hydroxide)

出典と根拠

ORDレコード
ord-5b8eef39b7e94748a68be248fda01dbb
出典データセット
uspto-grants-2012_08
特許番号
US08252811B2

関連ノート

読み込み中…