Potassium Carbonate → HCID 178502495、化合物

HRID 1413028ノート

反応式

HRID 1413028 の反応式
[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]

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 69675472HCID 69675472、化合物HCID 178448384HCID 178448384、化合物

生成物 1

HCID 178502495HCID 178502495、化合物収率 63.1%

試薬・触媒・溶媒 3

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
95 °C

実験手順

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 2 h. 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,5 S)-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%).

後処理

  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)

出典と根拠

ORDレコード
ord-1109d8eef1ba45589d0822dac62e492c
出典データセット
uspto-grants-2014_12
特許番号
US08921341B2

反応ノート

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