Benzyl mercaptan → 7-(benzylthio)-4-chloro-2-(4-methoxybenzyl)isoquinolin-1(2H)-one

HRID 1473698ノート

反応式

HRID 1473698 の反応式
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([Cl:22])=[CH:7][N:8]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[C:9]2=[O:12])=[CH:4][CH:3]=1.O1CCOCC1.[CH2:29]([SH:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>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].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH2:29]([S:36][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([Cl:22])=[CH:7][N:8]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[C:9]2=[O:12])=[CH:4][CH:3]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

参加物

7

反応物 3

HCID 7509Benzyl mercaptanHCID 312751,4-DioxaneHCID 866877827-bromo-4-chloro-2-(4-methoxybenzyl)isoquinolin-1(2H)-one

生成物 1

HCID 866877837-(benzylthio)-4-chloro-2-(4-methoxybenzyl)isoquinolin-1(2H)-one収率 89.7%

試薬・触媒・溶媒 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒

反応条件

温度
80 °C

実験手順

A screw cap vial was charged with 7-bromo-4-chloro-2-(4-methoxybenzyl)isoquinolin-1(2H)-one (3.6 g, 9.51 mmol), Xantphos (0.275 g, 0.475 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.218 g, 0.238 mmol), 1,4-Dioxane (9.51 ml) and dipea (3.31 ml, 19.02 mmol). The vial was purged with Argon, sealed and heated to 80° C. for 10 minutes. The reaction was cooled to room temperature and benzyl mercaptan (1.18 ml, 9.98 mmol) was added and the reaction was continued heating at 80° C. for an additional 30 minutes. The reaction was cooled to room temperature, diluted with water and extracted with DCM (3×). The combined organics were washed with water and brine, dried over magnesium sulfate, filtered and concentrated. The resulting material was concentrated, dissolved in minimal DCM and purified via column chromatography (silica gel 40 g, gradient elution 0 to 50% EtOAc:Heptane) to afford 3.60 g of 7-(benzylthio)-4-chloro-2-(4-methoxybenzyl)isoquinolin-1(2H)-one. m/z (ESI) 442.1 (M+H)+.

後処理

  1. customA screw cap vial
  2. customThe vial was purged with Argon
  3. customsealed
  4. temperatureThe reaction was cooled to room temperature
  5. temperaturethe reaction was continued heating at 80° C. for an additional 30 minutes
  6. temperatureThe reaction was cooled to room temperature
  7. extractionextracted with DCM (3×)
  8. washThe combined organics were washed with water and brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. concentrationThe resulting material was concentrated
  13. dissolutiondissolved in minimal DCM
  14. custompurified via column chromatography (silica gel 40 g, gradient elution 0 to 50% EtOAc:Heptane)

出典と根拠

ORDレコード
ord-2f83e8e334574d8c9f0a9ec2cb21a62b
出典データセット
uspto-grants-2015_04
特許番号
US09012443B2

反応ノート

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