Triphenylphosphine → HCID 67682397, 화합물

HRID 1751589노트

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HRID 1751589 반응식
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

참가 물질

7

반응물 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, 화합물

생성물 1

HCID 67682397HCID 67682397, 화합물수율 76.7%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 80711,2-Dimethoxyethane용매

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온도
95 °C

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-aaba04296d0642ef8938977f7771ac19
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09156823B2

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