Potassium Carbonate → HCID 178502495, compound

HRID 2172522Notes

Reaction equation

HRID 2172522 reaction equation
[CH3:1][CH:2]([CH3:46])[C@H:3]([NH:42][C:43](=[O:45])[O-:44])[C:4]([N:6]1[C@H:10]([C:11]2[NH:15][C:14]3[C:16]4[C:21]([CH:22]=[CH:23][C:13]=3[N:12]=2)=[CH:20][C:19]2[C:24]3[C:29]([CH2:30][O:31][C:18]=2[CH:17]=4)=[CH:28][C:27](B2OC(C)(C)C(C)(C)O2)=[CH:26][CH:25]=3)[CH2:9][CH2:8][C@@H:7]1[CH3:41])=[O:5].Br[C:48]1[NH:52][C:51]([C@@H:53]2[CH2:57][C@H:56]([CH3:58])[CH2:55][N:54]2[C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])=[N:50][CH:49]=1.[C:66](=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.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]>[CH3:66][O:44][C:43]([NH:42][C@H:3]([C:4]([N:6]1[C@@H:7]([CH3:41])[CH2:8][CH2:9][C@H:10]1[C:11]1[NH:15][C:14]2[C:16]3[C:21]([CH:22]=[CH:23][C:13]=2[N:12]=1)=[CH:20][C:19]1[C:24]2[C:29]([CH2:30][O:31][C:18]=1[CH:17]=3)=[CH:28][C:27]([C:48]1[NH:52][C:51]([C@@H:53]3[CH2:57][C@H:56]([CH3:58])[CH2:55][N:54]3[C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])=[N:50][CH:49]=1)=[CH:26][CH:25]=2)=[O:5])[CH:2]([CH3:1])[CH3:46])=[O:45]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 69675472HCID 69675472, compoundHCID 178448384HCID 178448384, compound

Product 1

HCID 178502495HCID 178502495, compoundYield 63.1%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of [(2S)-3-methyl-1-{(2S,5S)-2-methyl-5-[9-[4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl]pyrrolidin-1-yl}-1-oxobutan-2-yl]carbamate (269 mg, 0.42 mmol), (2S,4S)-tert-butyl 2-(5-bromo-1H-imidazol-2-yl)-4-methylpyrrolidine-1-carboxylate (206 mg, 0.54 mmol), tetrakis(triphenylphosphine) palladium(0) (49 mg, 0.042 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (31 mg, 0.042 mmol) in DMSO (3 mL) and dioxanes (3 mL) was added a solution of potassium carbonate (2M in water, 0.69 mL, 1.39 mmol). The resulting mixture was degassed and then heated to 95° C. for 2 h. After cooling to room temperature, the reaction was diluted with ethyl acetate. The organics were washed with saturated sodium bicarbonate and brine, dried over Na2SO4 and concentrated. The crude residue was purified by flash chromatography (1 to 20% MeOH/EtOAc) to yield tert-butyl (2S,4S)-2-[5-(2-{(2S,5S)-1-[N-(methoxycarbonyl)-L-valyl]-5-methylpyrrolidin-2-yl}-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-9-yl)-1H-imidazol-2-yl]-4-methylpyrrolidine-1-carboxylate (202 mg, 63%).

Workup

  1. customThe resulting mixture was degassed
  2. temperatureAfter cooling to room temperature
  3. additionthe reaction was diluted with ethyl acetate
  4. washThe organics were washed with saturated sodium bicarbonate and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe crude residue was purified by flash chromatography (1 to 20% MeOH/EtOAc)

Sources & evidence

ORD record
ord-dbf7c4537f6c4ffdbe0f20868df12c88
Source dataset
uspto-grants-2015_06
Patent number
US09051340B2

Reaction notes

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