Toluene → 1-methylethyl ((cis)-1-acetyl-6-{1-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-1H-pyrazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

HRID 2366836

반응식

HRID 2366836 반응식
Br[C:2]1[CH:3]=[N:4][N:5]([CH2:7][CH2:8][N:9]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]2=[O:19])[CH:6]=1.[CH3:20][CH:21]([O:23][C:24](=[O:49])[NH:25][CH:26]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33](B3OC(C)(C)C(C)(C)O3)[CH:34]=2)[N:29]([C:45](=[O:47])[CH3:46])[CH:28]([CH3:48])[CH2:27]1)[CH3:22].C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1>C(O)C.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>[CH3:22][CH:21]([O:23][C:24](=[O:49])[NH:25][C@H:26]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([C:2]3[CH:3]=[N:4][N:5]([CH2:7][CH2:8][N:9]4[C:17](=[O:18])[C:16]5[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=5)[C:10]4=[O:19])[CH:6]=3)[CH:34]=2)[N:29]([C:45](=[O:47])[CH3:46])[C@@H:28]([CH3:48])[CH2:27]1)[CH3:20]

참가 물질

7

반응물 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 53216871N-(2-(4-Bromopyrazol-1-yl)ethyl)phthalimideHCID 774200021-Methylethyl [1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate2회

생성물 1

HCID 671987031-methylethyl ((cis)-1-acetyl-6-{1-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-1H-pyrazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 702Ethanol용매

실험 절차

2-[2-(4-bromo-1H-pyrazol-1-yl)ethyl]-1H-isoindole-1,3(2H)-dione (for a preparation see Intermediate 28) (80 mg, 0.250 mmol) and 1-methylethyl[1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (Intermediate 12, 150 mg, 0.360 mmol) were mixed with potassium carbonate (69.1 mg, 0.500 mmol) and tetrakis(triphenylphosphine)palladium(0) (14.44 mg, 0.012 mmol), dissolved in ethanol (1 mL) and toluene (1 mL) and stirred under nitrogen at 90° C. for 1 hour. The mixture was partitioned between distilled water (20 mL) and EtOAc (60 mL). The aqueous layer was extracted with EtOAc (60 mL) and the organic fractions were combined, washed (brine, 30 mL), dried (MgSO4), filtered and evaporated to dryness to give a yellow solid which was loaded on to a 12+M Biotage silica column and eluted with cyclohexane:ethyl acetate (3:1 to 1:2). Product-containing fractions were evaporated to dryness to give a solid (39 mg). LCMS (Method C): Rt=0.95, MH+=530

후처리

  1. customThe mixture was partitioned
  2. distillationbetween distilled water (20 mL) and EtOAc (60 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (60 mL)
  4. washwashed (brine, 30 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customto give a yellow solid which
  9. washeluted with cyclohexane:ethyl acetate (3:1 to 1:2)
  10. customProduct-containing fractions were evaporated to dryness

출처 및 근거

ORD 기록
ord-da7f7019cf4c407d86333f19583d6083
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08697725B2

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