Triphenylphosphine → HCID 67682397、化合物

HRID 1751589ノート

反応式

HRID 1751589 の反応式
Br[C:2]1[CH:14]=[C:13]2[C:5]([C:6]3[CH:7]=[CH:8][C:9]([C:17]4[NH:21][C:20]([C@@H:22]5[CH2:26][CH2:25][CH2:24][N:23]5[C:27](=[O:37])[C@@H:28]([NH:32][C:33](=[O:36])[O:34][CH3:35])[CH:29]([CH3:31])[CH3:30])=[N:19][CH:18]=4)=[CH:10][C:11]=3[C:12]2([F:16])[F:15])=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:46]2[CH:47]=[CH:48][C:49]3[N:53]=[C:52]([C@@H:54]4[C@@H:59]5[CH2:60][C@@H:56]([CH2:57][CH2:58]5)[N:55]4[C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[NH:51][C:50]=3[CH:68]=2)O1.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:16][C:12]1([F:15])[C:13]2[CH:14]=[C:2]([C:47]3[CH:46]=[CH:68][C:50]4[N:51]=[C:52]([C@@H:54]5[C@@H:59]6[CH2:60][C@@H:56]([CH2:57][CH2:58]6)[N:55]5[C:61]([O:63][C:64]([CH3:66])([CH3:65])[CH3:67])=[O:62])[NH:53][C:49]=4[CH:48]=3)[CH:3]=[CH:4][C:5]=2[C:6]2[C:11]1=[CH:10][C:9]([C:17]1[NH:21][C:20]([C@@H:22]3[CH2:26][CH2:25][CH2:24][N:23]3[C:27](=[O:37])[C@@H:28]([NH:32][C:33]([O:34][CH3:35])=[O:36])[CH:29]([CH3:30])[CH3:31])=[N:19][CH:18]=1)=[CH:8][CH:7]=2

参加物

7

反応物 4

HCID 11776TriphenylphosphineHCID 516892Sodium BicarbonateHCID 67506198(1R,3S,4S)-tert-butyl 3-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylateHCID 67522673HCID 67522673、化合物

生成物 1

HCID 67682397HCID 67682397、化合物収率 76.7%

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)-1-((S)-2-(5-(7-bromo-9,9-difluoro-9H-fluoren-2-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (192 mg, 0.33 mmol), (1R,3S,4S)-tert-butyl 3-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate (177 mg, 0.40 mmol), 1M aqueous sodium bicarbonate solution (1.27 mL, 1.27 mmol), triphenylphosphine (9 mg, 0.03 mmol), palladium(II) acetate (4 mg, 0.02 mmol) and dimethoxyethane (3.5 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 (1R,3S,4S)-tert-butyl 3-(6-(9,9-difluoro-7-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-9H-fluoren-2-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate (204 mg, 76%).

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-aaba04296d0642ef8938977f7771ac19
出典データセット
uspto-grants-2015_10
特許番号
US09156823B2

反応ノート

読み込み中…