Sodium Carbonate → 2-chloro-6-{4-[(4-methoxybenzyl)oxy]-3-(trifluoromethyl)phenyl}-9-methyl-9H-purine

HRID 522281ノート

反応式

HRID 522281 の反応式
B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:25]1[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=2)=[C:27]([C:41]([F:44])([F:43])[F:42])[CH:26]=1.[Cl:45][C:46]1[N:54]=[C:53]2[C:49]([N:50]=[CH:51][N:52]2[CH3:55])=[C:48](Cl)[N:47]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.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.O>[Cl:45][C:46]1[N:54]=[C:53]2[C:49]([N:50]=[CH:51][N:52]2[CH3:55])=[C:48]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=3)=[C:27]([C:41]([F:44])([F:43])[F:42])[CH:26]=2)[N:47]=1

参加物

11

反応物 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 17125532,6-dichloro-9-methyl-9H-purineHCID 2733548Bis(pinacolato)diboraneHCID 900657114-Bromo-1-[(4-methoxybenzyl)oxy]-2-(trifluoromethyl)benzene

生成物 1

HCID 1178996942-chloro-6-{4-[(4-methoxybenzyl)oxy]-3-(trifluoromethyl)phenyl}-9-methyl-9H-purine収率 16.6%

試薬・触媒・溶媒 5

HCID 178418397HCID 178418397、化合物触媒HCID 178418476HCID 178418476、化合物触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

Bis(pinacolato)diboron (4.12 g), potassium acetate (4.35 g), and dichlorobis(triphenylphosphine)palladium (II) (1.04 g) were added to a solution of 4-bromo-1-[(4-methoxybenzyl)oxy]-2-(trifluoromethyl)benzene (5.87 g) in dioxane (90 mL) at room temperature in an argon atmosphere, and the mixture was stirred at 100° C. for 2 hours. After the reaction mixture was cooled to room temperature, 2,6-dichloro-9-methyl-9H-purine (3 g), Na2CO3 (4.7 g), tetrakis(triphenylphosphine)palladium (0) (854 mg), and water (15 mL) were added thereto. The reaction mixture was stirred at 100° C. for 4 hours. After the reaction mixture was cooled to room temperature, EtOAc was added thereto, followed by stirring, and the insoluble material was separated by filtration using Celite. Extraction was performed on the filtrate using EtOAc, and the extract was washed with water. The organic layer was dried over MgSO4 and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hex:EtOAc=4:1 to 1:1), whereby 2-chloro-6-{4-[(4-methoxybenzyl)oxy]-3-(trifluoromethyl)phenyl}-9-methyl-9H-purine (1.1 g) was obtained as a white solid.

後処理

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. stirringThe reaction mixture was stirred at 100° C. for 4 hours
  3. temperatureAfter the reaction mixture was cooled to room temperature
  4. stirringby stirring
  5. customthe insoluble material was separated by filtration
  6. extractionExtraction
  7. washthe extract was washed with water
  8. dry with materialThe organic layer was dried over MgSO4
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (Hex:EtOAc=4:1 to 1:1)

出典と根拠

ORDレコード
ord-40b906f201ca4b50b130da7cb23af559
出典データセット
uspto-grants-2016_05
特許番号
US09328118B2

反応ノート

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