Dimethylformamide → ethyl 1-[({5'-chloro-4-methyl-6'-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]-methyl}-1H-imidazol-2-yl]-3,3'-bipyridin-6-yl}oxy)methyl]cyclobutanecarboxylate

HRID 623918노트

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HRID 623918 반응식
CN(C)C=O.Br[C:7]1[CH:8]=[C:9]([Cl:30])[C:10]([C:13]2[N:14]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[N:17]=2)=[N:11][CH:12]=1.[CH3:31][C:32]1[C:37](B2OC(C)(C)C(C)(C)O2)=[CH:36][N:35]=[C:34]([O:47][CH2:48][C:49]2([C:53]([O:55][CH2:56][CH3:57])=[O:54])[CH2:52][CH2:51][CH2:50]2)[CH:33]=1.C(=O)([O-])[O-].[Na+].[Na+]>O>[Cl:30][C:9]1[CH:8]=[C:7]([C:37]2[CH:36]=[N:35][C:34]([O:47][CH2:48][C:49]3([C:53]([O:55][CH2:56][CH3:57])=[O:54])[CH2:52][CH2:51][CH2:50]3)=[CH:33][C:32]=2[CH3:31])[CH:12]=[N:11][C:10]=1[C:13]1[N:14]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[N:17]=1

참가 물질

6

반응물 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 679736045-bromo-3-chloro-2-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]pyridineHCID 67975298Ethyl 1-(((4-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridin-2-yl)oxy)methyl)cyclobutanecarboxylate

생성물 1

HCID 86698180ethyl 1-[({5'-chloro-4-methyl-6'-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]-methyl}-1H-imidazol-2-yl]-3,3'-bipyridin-6-yl}oxy)methyl]cyclobutanecarboxylate수율 63.7%

시약·촉매·용매 1

HCID 962Water용매

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온도
65 °C

실험 절차

N,N-dimethylformamide (3 mL) was added to 5-bromo-3-chloro-2-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]pyridine (365 mg), ethyl 1-({[4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]-oxy}methyl)cyclobutanecarboxylate (300 mg) and palladium chloride (dppf) methylene chloride complex (33 mg), and after adding 2N aqueous sodium carbonate solution (1.2 mL) to the mixture, the atmosphere was replaced with nitrogen and the mixture was stirred at 65° C. for 2 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated brine, concentrated under reduced pressure and the obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=100:0 to 90:10) to obtain ethyl 1-[({5′-chloro-4-methyl-6′-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]-3,3′-bipyridin-6-yl}oxy)methyl]cyclobutanecarboxylate (318 mg).

후처리

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with a saturated brine
  3. concentrationconcentrated under reduced pressure
  4. customthe obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=100:0 to 90:10)

출처 및 근거

ORD 기록
ord-dae217b89e614e82bb625741f42c36ec
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09302996B2

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