Potassium Carbonate → HCID 67682424、化合物

HRID 1412939ノート

反応式

HRID 1412939 の反応式
[CH3:1][O:2][CH2:3][C@@H:4]1[CH2:8][N:7]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C@H:6]([C:16]2[NH:20][C:19]3[C:21]4[C:26]([CH:27]=[CH:28][C:18]=3[N:17]=2)=[CH:25][C:24]2[C:29]3[C:34]([CH2:35][O:36][C:23]=2[CH:22]=4)=[CH:33][C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][CH:30]=3)[CH2:5]1.Br[C:47]1[NH:51][C:50]([C@@H:52]2[CH2:56][C@H:55]([CH3:57])[CH2:54][N:53]2[C:58](=[O:68])[C@@H:59]([NH:63][C:64](=[O:67])[O:65][CH3:66])[CH:60]([CH3:62])[CH3:61])=[N:49][CH:48]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.CN(C)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:65][C:64]([NH:63][C@H:59]([C:58]([N:53]1[CH2:54][C@@H:55]([CH3:57])[CH2:56][C@H:52]1[C:50]1[NH:51][C:47]([C:32]2[CH:33]=[C:34]3[CH2:35][O:36][C:23]4[CH:22]=[C:21]5[C:26]([CH:27]=[CH:28][C:18]6[NH:17][C:16]([C@@H:6]7[CH2:5][C@H:4]([CH2:3][O:2][CH3:1])[CH2:8][N:7]7[C:9]([O:11][C:12]([CH3:13])([CH3:14])[CH3:15])=[O:10])=[N:20][C:19]=65)=[CH:25][C:24]=4[C:29]3=[CH:30][CH:31]=2)=[CH:48][N:49]=1)=[O:68])[CH:60]([CH3:62])[CH3:61])=[O:67]

参加物

8

反応物 3

HCID 11430Potassium CarbonateHCID 67683076HCID 67683076、化合物HCID 178495650HCID 178495650、化合物

生成物 1

HCID 67682424HCID 67682424、化合物収率 32%

試薬・触媒・溶媒 4

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 6228Dimethylformamide溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
85 °C

実験手順

To a solution of (2S,4S)-tert-butyl 4-(methoxymethyl)-2-(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)pyrrolidine-1-carboxylate (438 mg, 0.72 mmol), methyl(S)-1-((2S,4S)-2-(5-bromo-1H-imidazol-2-yl)-4-methylpyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (276 mg, 0.72 mmol), tetrakis(triphenylphosphine) palladium(0) (41 mg, 0.04 mmol) and dichloro[1,1′-bis(diphenylphosphino) ferrocene]palladium(II) (52 mg, 0.07 mmol) in a mixture of 1,2-dimethoxyethane (8.6 mL) and dimethylformamide (1.5 mL) was added a solution of potassium carbonate (2M in water, 1.07 mL, 2.15 mmol). The resulting mixture was degassed and then heated to 85° C. under argon for 18 hours. After cooling to room temperature, the reaction was diluted with ethyl acetate. The organics were washed with water and brine, dried (Na2SO4), and concentrated. The crude residue was purified by flash chromatography to yield tert-butyl(2S,4S)-2-[9-(2-{(2S,4S)-1-[N-(methoxycarbonyl)-L-valyl]-4-methylpyrrolidin-2-yl}-1H-imidazol-5-yl)-3,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl]-4-(methoxymethyl)pyrrolidine-1-carboxylate (182 mg, 32%).

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 water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude residue was purified by flash chromatography

出典と根拠

ORDレコード
ord-e14fdf198b084e3fa128170c46220ab1
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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