Potassium Carbonate → HCID 178502495, 화합물

HRID 1509755노트

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HRID 1509755 반응식
[CH3:1][CH:2]([CH3:46])[C@H:3]([NH:42][C:43](=[O:45])[O-:44])[C:4]([N:6]1[C@H:10]([C:11]2[NH:15][C:14]3[C:16]4[C:21]([CH:22]=[CH:23][C:13]=3[N:12]=2)=[CH:20][C:19]2[C:24]3[C:29]([CH2:30][O:31][C:18]=2[CH:17]=4)=[CH:28][C:27](B2OC(C)(C)C(C)(C)O2)=[CH:26][CH:25]=3)[CH2:9][CH2:8][C@@H:7]1[CH3:41])=[O:5].Br[C:48]1[NH:52][C:51]([C@@H:53]2[CH2:57][C@H:56]([CH3:58])[CH2:55][N:54]2[C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])=[N:50][CH:49]=1.[C:66](=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:66][O:44][C:43]([NH:42][C@H:3]([C:4]([N:6]1[C@@H:7]([CH3:41])[CH2:8][CH2:9][C@H:10]1[C:11]1[NH:15][C:14]2[C:16]3[C:21]([CH:22]=[CH:23][C:13]=2[N:12]=1)=[CH:20][C:19]1[C:24]2[C:29]([CH2:30][O:31][C:18]=1[CH:17]=3)=[CH:28][C:27]([C:48]1[NH:52][C:51]([C@@H:53]3[CH2:57][C@H:56]([CH3:58])[CH2:55][N:54]3[C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])=[N:50][CH:49]=1)=[CH:26][CH:25]=2)=[O:5])[CH:2]([CH3:1])[CH3:46])=[O:45]

참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 69675472HCID 69675472, 화합물HCID 178448384HCID 178448384, 화합물

생성물 1

HCID 178502495HCID 178502495, 화합물수율 63.1%

시약·촉매·용매 3

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 679Dimethyl Sulfoxide용매

반응 조건

온도
95 °C

실험 절차

To a solution of [(2S)-3-methyl-1-{(2S,5S)-2-methyl-5-[9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl]pyrrolidin-1-yl}-1-oxobutan-2-yl]carbamate (269 mg, 0.42 mmol), (2S,4S)-tert-butyl 2-(5-bromo-1H-imidazol-2-yl)-4-methylpyrrolidine-1-carboxylate (206 mg, 0.54 mmol), tetrakis(triphenylphosphine) palladium(0) (49 mg, 0.042 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (31 mg, 0.042 mmol) in DMSO (3 mL) and dioxanes (3 mL) was added a solution of potassium carbonate (2M in water, 0.69 mL, 1.39 mmol). The resulting mixture was degassed and then heated to 95° C. for 2h. After cooling to room temperature, the reaction was diluted with ethyl acetate. The organics were washed with saturated sodium bicarbonate and brine, dried over Na2SO4 and concentrated. The crude residue was purified by flash chromatography (1 to 20% MeOH/EtOAc) to yield tert-butyl (2S,4S)-2-[5-(2-{(2S,5S)-1-[N-(methoxycarbonyl)-L-valyl]-5-methylpyrrolidin-2-yl}-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-9-yl)-1H-imidazol-2-yl]-4-methylpyrrolidine-1-carboxylate (202 mg, 63%).

후처리

  1. customThe resulting mixture was degassed
  2. temperatureAfter cooling to room temperature
  3. additionthe reaction was diluted with ethyl acetate
  4. washThe organics were washed with saturated sodium bicarbonate and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe crude residue was purified by flash chromatography (1 to 20% MeOH/EtOAc)

출처 및 근거

ORD 기록
ord-7b45cb7a73a64b4c9872dc3ce653b4a9
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221833B2

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