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

반응식

HRID 77404 반응식
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

참가 물질

8

반응물 4

HCID 3984071,4-Diazabicyclo(3.2.2)nonaneHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 699285487-bromo-3-(3-chlorophenyl)-2-methylisoquinolin-1(2H)-one2회

생성물 1

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

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
85 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-c1d1c04561374a87909533458de57e09
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841289B2

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