Potassium Carbonate → HCID 178495697, compound

HRID 1412962Notes

Reaction equation

HRID 1412962 reaction equation
[CH3:1][O:2][C:3](=[O:47])[NH:4][C@@H:5]([CH:44]([CH3:46])[CH3:45])[C:6]([N:8]1[CH2:12][C@@H:11]([CH3:13])[CH2:10][C@H:9]1[C:14]1[NH:18][C:17]2[C:19]3[C:24]([CH:25]=[CH:26][C:16]=2[N:15]=1)=[CH:23][C:22]1[C:27]2[C:32]([CH2:33][O:34][C:21]=1[CH:20]=3)=[CH:31][C:30](B1OC(C)(C)C(C)(C)O1)=[CH:29][CH:28]=2)=[O:7].I[C:49]1[NH:53][C:52]([C@@H:54]2[CH2:58][C@H:57]([CH2:59][O:60][CH3:61])[CH2:56][N:55]2C(=O)[C@@H](NC(=O)OC)C(C)C)=[N:51][CH:50]=1.[C:73]([O-:76])([O-])=[O:74].[K+].[K+]>CS(C)=O.O1CCOCC1.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.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]>[CH3:1][O:2][C:3]([NH:4][C@H:5]([C:6]([N:8]1[CH2:12][C@@H:11]([CH3:13])[CH2:10][C@H:9]1[C:14]1[NH:18][C:17]2[C:19]3[C:24]([CH:25]=[CH:26][C:16]=2[N:15]=1)=[CH:23][C:22]1[C:27]2[C:32]([CH2:33][O:34][C:21]=1[CH:20]=3)=[CH:31][C:30]([C:50]1[NH:51][C:52]([C@@H:54]3[CH2:58][C@H:57]([CH2:59][O:60][CH3:61])[CH2:56][N:55]3[C:73]([O:76][C:11]([CH3:13])([CH3:12])[CH3:10])=[O:74])=[N:53][CH:49]=1)=[CH:29][CH:28]=2)=[O:7])[CH:44]([CH3:45])[CH3:46])=[O:47]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 131731033methyl(S)-1-((2S,4S)-2-(5-iodo-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamateHCID 178502425Methyl [(2S)-3-methyl-1-{(2S,4S)-4-methyl-2-[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

Product 1

HCID 178495697HCID 178495697, compoundYield 43%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
95 °C

Procedure

Methyl[(2S)-3-methyl-1-{(2S,4S)-4-methyl-2-[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 (312 mg, 0.49 mmol), methyl(S)-1-((2S,4S)-2-(5-iodo-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (219 mg, 0.54 mmol), Pd(PPh3)4 (58 mg, 0.05 mmol), PdCl2(dppf)2 (36 mg, 0.05 mmol), and K2CO3 (2M in H2O, 0.8 mL, 1.6 mmoL) were combined in DMSO (5 mL) and dioxane (5 mL). The mixture was degassed with bubbling N2 for 10 min then heated to 95° C. for 5 h. After cooling, the reaction mixture was diluted with EtOAc, and washed successively with saturated aqueous NaHCO3 and brine. The organics were dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (0%-30% MeOH/EtOAc) to afford tert-butyl(2S,4S)-2-[5-(2-{(2S,4S)-1-[N-(methoxycarbonyl)-L-valyl]-4-methylpyrrolidin-2-yl}-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-9-yl)-1H-imidazol-2-yl]-4-(methoxymethyl)pyrrolidine-1-carboxylate (166 mg, 43%).

Workup

  1. customThe mixture was degassed with bubbling N2 for 10 min
  2. temperatureAfter cooling
  3. additionthe reaction mixture was diluted with EtOAc
  4. washwashed successively with saturated aqueous NaHCO3 and brine
  5. dry with materialThe organics were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue was purified by silica column chromatography (0%-30% MeOH/EtOAc)

Sources & evidence

ORD record
ord-64e2944083564f81b692c53603e81e39
Source dataset
uspto-grants-2014_12
Patent number
US08921341B2

Reaction notes

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