Potassium Carbonate → HCID 178502450, compound

HRID 1509680Notes

Reaction equation

HRID 1509680 reaction equation
[CH3:1][C@@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([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)[CH2:3]1.I[C:45]1[NH:49][C:48]([C@@H:50]2[CH2:54][C@H:53]([CH3:55])[CH2:52][N:51]2[C:56](=[O:66])[C@@H:57]([NH:61][C:62](=[O:65])[O:63][CH3:64])[CH:58]([CH3:60])[CH3:59])=[N:47][CH:46]=1.C([O-])([O-])=O.[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]>[CH3:64][O:63][C:62]([NH:61][C@H:57]([C:56]([N:51]1[CH2:52][C@@H:53]([CH3:55])[CH2:54][C@H:50]1[C:48]1[NH:49][C:45]([C:30]2[CH:31]=[C:32]3[CH2:33][O:34][C:21]4[CH:20]=[C:19]5[C:24]([CH:25]=[CH:26][C:16]6[N:15]=[C:14]([C@@H:4]7[CH2:3][C@H:2]([CH3:1])[CH2:6][N:5]7[C:7]([O:9][C:10]([CH3:12])([CH3:11])[CH3:13])=[O:8])[NH:18][C:17]=65)=[CH:23][C:22]=4[C:27]3=[CH:28][CH:29]=2)=[CH:46][N:47]=1)=[O:66])[CH:58]([CH3:60])[CH3:59])=[O:65]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 53261948methyl N-[(1S)-1-[(2S,4S)-2-(4-iodo-1H-imidazol-2-yl)-4-methyl-pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamateHCID 178461438HCID 178461438, compound

Product 1

HCID 178502450HCID 178502450, compoundYield 35.1%

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

(2S,4S)-tert-butyl 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)pyrrolidine-1-carboxylate (558 mg, 0.96 mmol), methyl (S)-1-((2S,4S)-2-(5-iodo-1H-imidazol-2-yl)-4-methylpyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (501 mg, 1.15 mmol), Pd(PPh3)4 (111 mg, 0.096 mmol), PdCl2(dppf)2 (70 mg, 0.096 mmol), and K2CO3 (2M in H2O, 1.6 mL, 3.17 mmoL) were combined in DMSO (6 mL) and dioxane (6 mL). The mixture was degassed with bubbling N2 for 10 min then heated to 95° C. for 14 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-[9-(2-{(2S,4S)-1-[N-(methoxycarbonyl)-L-valyl]-4-methylpyrrolidin-2-yl}-1H-imidazol-5-yl)-1,11-dihydroisochromeno[4′,3′: 6,7]naphtho[1,2-d]imidazol-2-yl]-4-methylpyrrolidine-1-carboxylate (257 mg, 35%).

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-32da0700c13341428a230099d14ac9b3
Source dataset
uspto-grants-2015_12
Patent number
US09221833B2

Reaction notes

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