Triphenylphosphine → HCID 67682549, compound

HRID 1751591Notes

Reaction equation

HRID 1751591 reaction equation
[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

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 516892Sodium BicarbonateHCID 59610218HCID 59610218, compoundHCID 67682542HCID 67682542, compound

Product 1

HCID 67682549HCID 67682549, compoundYield 54%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
95 °C

Procedure

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%).

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-2ee67e528a32408892aa47a55a440dbc
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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