Potassium Carbonate → HCID 86708757, compound

HRID 1751531Notes

Reaction equation

HRID 1751531 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:14]3[C:9](=[C:10]4[CH:18]=[CH:17][C:16]([C:19]5[NH:23][C:22]([C@@H:24]6[CH2:28][CH2:27][CH2:26][N:25]6[C:29](=[O:39])[C@@H:30]([NH:34][C:35](=[O:38])[O:36][CH3:37])[CH:31]([CH3:33])[CH3:32])=[N:21][CH:20]=5)=[CH:15][C:11]4=[CH:12][CH:13]=3)[O:8][CH2:7][C:6]=2[CH:40]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:65]1[NH:69][C:68]([C@@H:70]2[CH2:74][CH2:73][CH2:72][N:71]2[C:75]([O:77][C:78]([CH3:81])([CH3:80])[CH3:79])=[O:76])=[N:67][CH:66]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.CS(C)=O>[CH3:37][O:36][C:35]([NH:34][C@@H:30]([CH:31]([CH3:32])[CH3:33])[C:29]([N:25]1[CH2:26][CH2:27][CH2:28][C@H:24]1[C:22]1[NH:23][C:19]([C:16]2[CH:17]=[CH:18][C:10]3[C:11]([CH:15]=2)=[CH:12][CH:13]=[C:14]2[C:9]=3[O:8][CH2:7][C:6]3[CH:40]=[C:2]([C:65]4[NH:69][C:68]([C@@H:70]5[CH2:74][CH2:73][CH2:72][N:71]5[C:75]([O:77][C:78]([CH3:81])([CH3:80])[CH3:79])=[O:76])=[N:67][CH:66]=4)[CH:3]=[CH:4][C:5]2=3)=[CH:20][N:21]=1)=[O:39])=[O:38]

Participants

11

Reactant 5

HCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 56605192tert-Butyl (2S)-2-(5-bromo-1H-imidazol-2-yl)pyrrolidine-1-carboxylateHCID 86708755HCID 86708755, compound

Product 1

HCID 86708757HCID 86708757, compoundYield 25%

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of methyl (S)-1-((S)-2-(5-(8-bromo-6H-dibenzo[c,h]chromen-2-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (466 mg, 0.77 mmol), bis(pinacolato)diboron (235 mg, 0.93 mmol) and potassium acetate (227 mg, 2.3 mmol) in dioxane (4 mL) was degassed with a stream of argon for fifteen minutes. To this mixture was added PdCl2(dppf) (56 mg, 0.08 mmol) and the reaction was heated to 90° C. After 14 hours, the mixture was cooled to room temperature. To the reaction was added (S)-tert-butyl 2-(5-bromo-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (341 mg, 1.1 mmol), 2M aqueous potassium carbonate solution (1.54 mL, 3.1 mmol) and DMSO (3.9 mL). The reaction was degassed with a stream of argon for fifteen minutes. Tetrakis(triphenylphosphine)palladium(0) (89 mg, 0.08 mmol) was added and the reaction was heated to 90° C. After 4.5 hours, the reaction was poured into water. The aqueous phase was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried (Na2SO4) and concentrated. The crude material was purified by flash column chromatography to yield (S)-tert-butyl 2-(5-(2-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-6H-dibenzo[c,h]-chromen-8-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (145 mg, 25%).

Workup

  1. customwas degassed with a stream of argon for fifteen minutes
  2. temperaturethe mixture was cooled to room temperature
  3. customThe reaction was degassed with a stream of argon for fifteen minutes
  4. temperaturethe reaction was heated to 90° C
  5. waitAfter 4.5 hours
  6. extractionThe aqueous phase was extracted twice with ethyl acetate
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customThe crude material was purified by flash column chromatography

Sources & evidence

ORD record
ord-8e588d44dd194bac80c7148b9d1afc0e
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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