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Potassium Carbonate → Methyl 7-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-quinolinecarboxylate

HRID 2423395
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HRID 2423395 반응식
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:12]([O:14][CH3:15])=[O:13])[CH:8]=[N:9]2)=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:24]2[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=2)O1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Cl[CH2:60][C:61]1[C:62]([C:69]2[C:74]([Cl:75])=[CH:73][CH:72]=[CH:71][C:70]=2[Cl:76])=[N:63][O:64][C:65]=1[CH:66]([CH3:68])[CH3:67].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOC(C)=O.CN(C=O)C.O>[Cl:75][C:74]1[CH:73]=[CH:72][CH:71]=[C:70]([Cl:76])[C:69]=1[C:62]1[C:61]([CH2:60][O:30][C:27]2[CH:26]=[CH:25][C:24]([C:2]3[CH:11]=[C:10]4[C:5]([CH:6]=[C:7]([C:12]([O:14][CH3:15])=[O:13])[CH:8]=[N:9]4)=[CH:4][CH:3]=3)=[CH:29][CH:28]=2)=[C:65]([CH:66]([CH3:68])[CH3:67])[O:64][N:63]=1
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참가 물질

12

반응물 6

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 62657Potassium Phosphate, TribasicHCID 27346244-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 592648754-(Chloromethyl)-3-(2,6-dichlorophenyl)-5-isopropylisoxazoleHCID 59321547Methyl 7-bromoquinoline-3-carboxylate

생성물 1

HCID 59321510Methyl 7-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-quinolinecarboxylate수율 40.9%

시약·촉매·용매 5

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매2회HCID 312751,4-Dioxane용매

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온도
60 °C

실험 절차

A solution of 78 mg (0.29 mmol) of methyl 7-bromo-3-quinolinecarboxylate, 97 mg (0.44 mmol) of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol, 3 mg (0.01 mmol) of palladium acetate, 8 mg (0.03 mmol) of triphenylphosphine, 218 mg (1.03 mmol) of K3PO4 and 25 μL of H2O in 1.0 mL of dioxane was stirred at 60° C. for 1 hr. EtOAc was added and the organics were washed with water and brine then concentrated. To the residue was added 65 mg (0.21 mmol) of 4-(chloromethyl)-3-(2,6-dichlorophenyl)-5-(1-methylethyl)isoxazole, 74 mg (0.54 mmol) of K2CO3 and 1.5 mL of DMF and the mixture was then stirred at 60° C. for 1 hr. EtOAc was added and the organics were washed with three portions of water, then brine. The solution was concentrated and the residue purified by silica gel chromatography (12 g of silica gel eluting with 0-40% EtOAc in hexanes over 45 minutes) to give 47 mg (30%) of methyl 7-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-quinolinecarboxylate as a clear glass. 1H NMR (400 MHz, CDCl3): δ 9.44 (s, 1H), 8.83 (s, 1H), 8.28 (s, 1H), 7.96 (d, J=9 Hz, 1H), 7.82 (d, J=9 Hz, 1H), 7.64 (d, J=9 Hz, 2H), 7.41 (d, J=8 Hz, 2H), 7.35-7.31 (m, 1H), 6.92 (d, J=9 Hz, 2H), 4.79 (s, 2H), 4.02 (s, 3H), 3.38-3.34 (m, 1H), 1.45 (d, J=7 Hz, 6H). ESI-LCMS m/z 548 (M+H)+.

후처리

  1. washthe organics were washed with water and brine
  2. concentrationthen concentrated
  3. washthe organics were washed with three portions of water
  4. concentrationThe solution was concentrated
  5. customthe residue purified by silica gel chromatography (12 g of silica gel eluting with 0-40% EtOAc in hexanes over 45 minutes)

출처 및 근거

ORD 기록
ord-27ec22573b4c4f218385e03196a04c0a
출처 데이터셋
uspto-grants-2011_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07960552B2

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