Triphenylphosphine → HCID 67682397, compound

HRID 1751589Notes

Reaction equation

HRID 1751589 reaction equation
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

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 516892Sodium BicarbonateHCID 67506198HCID 67506198, compoundHCID 67522673HCID 67522673, compound

Product 1

HCID 67682397HCID 67682397, compoundYield 76.7%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
95 °C

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-aaba04296d0642ef8938977f7771ac19
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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