Potassium Carbonate → HCID 178494530, compound

HRID 1509674Notes

Reaction equation

HRID 1509674 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:13]([C:14]2[NH:18][C:17]3[C:19]4[C:24]([CH:25]=[CH:26][C:16]=3[N:15]=2)=[CH:23][C:22]2[C:27]3[C:32]([CH2:33][O:34][C:21]=2[CH:20]=4)=[CH:31][C:30](B2OC(C)(C)C(C)(C)O2)=[CH:29][CH:28]=3)[CH2:12][C@@H:11]2[C@H:9]1[CH2:10]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:45]1[NH:49][C:48]([C@@H:50]2[CH2:54][C@H:53]([CH2:55][O:56][CH3:57])[CH2:52][N:51]2[C:58](=[O:68])[C@@H:59]([NH:63][C:64](=[O:67])[O:65][CH3:66])[CH:60]([CH3:62])[CH3:61])=[N:47][CH:46]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.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]>[C:1]([O:5][C:6]([N:8]1[C@H:13]([C:14]2[NH:18][C:17]3[C:19]4[C:24]([CH:25]=[CH:26][C:16]=3[N:15]=2)=[CH:23][C:22]2[C:27]3[C:32]([CH2:33][O:34][C:21]=2[CH:20]=4)=[CH:31][C:30]([C:45]2[NH:49][C:48]([C@@H:50]4[CH2:54][CH:53]([CH2:55][O:56][CH3:57])[CH2:52][N:51]4[C:58](=[O:68])[C@@H:59]([NH:63][C:64]([O:65][CH3:66])=[O:67])[CH:60]([CH3:62])[CH3:61])=[N:47][CH:46]=2)=[CH:29][CH:28]=3)[CH2:12][C@@H:11]2[C@H:9]1[CH2:10]2)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 86688341HCID 86688341, compoundHCID 178452514HCID 178452514, compound

Product 1

HCID 178494530HCID 178494530, compound

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 679Dimethyl SulfoxideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of (1R,3 S,5R)-tert-butyl-3-(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)-2-azabicyclo[3.1.0]hexane-2-carboxylate (213 mg, 0.37 mmol), methyl (S)-1-((2S,4S)-2-(5-bromo-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (142 mg, 0.31 mmol), tetrakis (triphenylphosphine) palladium(0) (35 mg, 0.03 mmol) and dichloro[1,1′-bis (diphenylphosphino) ferrocene]palladium(II) (22 mg, 0.03 mmol) in a mixture of 1,4-dioxane (3.0 mL) and dimethylsulfoxide (3.0 mL) was added a solution of potassium carbonate (2M in water, 0.46 mL, 0.9 mmol). The resulting mixture was degassed and then heated to 95° C. under argon for 7 hours. After cooling to room temperature, the reaction was diluted with ethyl acetate. The organics were washed with water and brine, dried (Na2SO4), and concentrated. The crude residue was purified by flash chromatography to (1R,3S,5R)-tert-butyl 3-(9-(2-((S)-1-((S)-2-(methoxycarbonyl amino)-3-methylbutanoyl)-4-methoxymethylpyrrolidin-2-yl)-1H-imidazol-5-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (101 mg, 42%).

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 water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude residue was purified by flash chromatography to (1R,3S,5R)-tert-butyl 3-(9-(2-((S)-1-((S)-2-(methoxycarbonyl amino)-3-methylbutanoyl)-4-methoxymethylpyrrolidin-2-yl)-1H-imidazol-5-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (101 mg, 42%)

Sources & evidence

ORD record
ord-89fa861a710946ffbb48038e70376304
Source dataset
uspto-grants-2015_12
Patent number
US09221833B2

Reaction notes

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