Triphenylphosphine → HCID 67682549、化合物

HRID 1751591ノート

反応式

HRID 1751591 の反応式
[CH3:1][CH:2]([CH3:36])[C@H:3]([NH:31][C:32](=[O:35])[O:33][CH3:34])[C:4](=[O:30])[N:5]1[C@H:10]([C:11]2[NH:15][C:14]3[CH:16]=[C:17](B4OC(C)(C)C(C)(C)O4)[CH:18]=[CH:19][C:13]=3[N:12]=2)[C@@H:9]2[CH2:29][C@H:6]1[CH2:7][CH2:8]2.Br[C:38]1[CH:50]=[C:49]2[C:41]([C:42]3[CH:43]=[CH:44][C:45]([C:53]4[NH:57][C:56]([C@@H:58]5[CH2:62][CH2:61][CH2:60][N:59]5[C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])=[N:55][CH:54]=4)=[CH:46][C:47]=3[C:48]2([F:52])[F:51])=[CH:40][CH:39]=1.C(=O)(O)[O-].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(COC)OC>[F:52][C:48]1([F:51])[C:47]2[CH:46]=[C:45]([C:53]3[NH:57][C:56]([C@@H:58]4[CH2:62][CH2:61][CH2:60][N:59]4[C:63]([O:65][C:66]([CH3:68])([CH3:67])[CH3:69])=[O:64])=[N:55][CH:54]=3)[CH:44]=[CH:43][C:42]=2[C:41]2[C:49]1=[CH:50][C:38]([C:17]1[CH:18]=[CH:19][C:13]3[N:12]=[C:11]([C@@H:10]4[C@@H:9]5[CH2:29][C@@H:6]([CH2:7][CH2:8]5)[N:5]4[C:4](=[O:30])[C@@H:3]([NH:31][C:32]([O:33][CH3:34])=[O:35])[CH:2]([CH3:36])[CH3:1])[NH:15][C:14]=3[CH:16]=1)=[CH:39][CH:40]=2

参加物

7

反応物 4

HCID 11776TriphenylphosphineHCID 516892Sodium BicarbonateHCID 59610218HCID 59610218、化合物HCID 67682542HCID 67682542、化合物

生成物 1

HCID 67682549HCID 67682549、化合物収率 54%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
95 °C

実験手順

A mixture of methyl (S)-3-methyl-1-oxo-1-((1R,3S,4S)-3-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptan-2-yl)butan-2-ylcarbamate (122 mg, 0.25 mmol), (S)-tert-butyl 2-(5-(7-bromo-9,9-difluoro-9H-fluoren-2-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (127 mg, 0.25 mmol), 1M aqueous sodium bicarbonate solution (0.93 mL, 0.93 mmol), triphenylphosphine (13 mg, 0.05 mmol), palladium(II) acetate (5.5 mg, 0.02 mmol) and dimethoxyethane (2.5 mL) was degassed with a stream of argon for twenty minutes. The reaction was heated to 95° C. After four hours, the reaction was cooled to room temperature and diluted with ethyl acetate. The organic phase was washed with saturated aqueous NaHCO3 solution and brine, dried (Na2SO4) and concentrated. The crude material was purified by flash column chromatography to yield (S)-tert-butyl 2-(5-(9,9-difluoro-7-(2-((1R,3S,4S)-2-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-2-azabicyclo[2.2.1]heptan-3-yl)-1H-benzo[d]imidazol-6-yl)-9H-fluoren-2-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (106 mg, 54%).

後処理

  1. customwas degassed with a stream of argon for twenty minutes
  2. temperaturethe reaction was cooled to room temperature
  3. additiondiluted with ethyl acetate
  4. washThe organic phase was washed with saturated aqueous NaHCO3 solution and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude material was purified by flash column chromatography

出典と根拠

ORDレコード
ord-2ee67e528a32408892aa47a55a440dbc
出典データセット
uspto-grants-2015_10
特許番号
US09156823B2

反応ノート

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