1,4-Diazabicyclo(3.2.2)nonane → 7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-3-(3-chlorophenyl)-2-methylisoquinolin-1(2H)-one

HRID 77404

反応式

HRID 77404 の反応式
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=3)[N:8]([CH3:13])[C:9]2=[O:12])=[CH:4][CH:3]=1.[N:21]12[CH2:29][CH2:28][CH:25]([CH2:26][CH2:27]1)[NH:24][CH2:23][CH2:22]2.CC(C)([O-])C.[Na+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.O.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:21]12[CH2:29][CH2:28][CH:25]([CH2:26][CH2:27]1)[N:24]([C:2]1[CH:11]=[C:10]3[C:5]([CH:6]=[C:7]([C:14]4[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=4)[N:8]([CH3:13])[C:9]3=[O:12])=[CH:4][CH:3]=1)[CH2:23][CH2:22]2

参加物

8

反応物 4

HCID 3984071,4-Diazabicyclo(3.2.2)nonaneHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 699285487-bromo-3-(3-chlorophenyl)-2-methylisoquinolin-1(2H)-one2 回

生成物 1

HCID 513534447-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-3-(3-chlorophenyl)-2-methylisoquinolin-1(2H)-one収率 35%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
85 °C

実験手順

A mixture of 7-bromo-3-(3-chlorophenyl)-2-methylisoquinolin-1(2H)-one (Intermediate 24A) (50 mg, 0.143 mmol), 1,4-diazabicyclo[3.2.2]nonane (27.2 mg, 0.215 mmol), sodium t-butoxide (55.1 mg, 0.574 mmol), tris(dibenzylideneacetone)dipalladium(0) (13.13 mg, 0.014 mmol) and (+/−) BINAP (26.8 mg, 0.043 mmol) in degassed dioxane (1 mL) was heated to 85° C. under N2 in a sealed vessel overnight. Reaction mixture allowed to cool to room temperature, diluted with water and the product extracted into ethyl acetate. Organics washed several times with water, dried (MgSO4), filtered and then evaporated to dryness. The crude product was added to a silica gel column (25 g) and was eluted with 0-50% 2M ammonia in methanol in ethylacetate to afford 7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-3-(3-chlorophenyl)-2-methylisoquinolin-1(2H)-one (19.4 mg, 0.05 mmol).

後処理

  1. customReaction mixture
  2. temperatureto cool to room temperature
  3. extractionthe product extracted into ethyl acetate
  4. dry with materialOrganics washed several times with water, dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated to dryness
  7. additionThe crude product was added to a silica gel column (25 g)
  8. washwas eluted with 0-50% 2M ammonia in methanol in ethylacetate

出典と根拠

ORDレコード
ord-c1d1c04561374a87909533458de57e09
出典データセット
uspto-grants-2014_09
特許番号
US08841289B2

関連ノート

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