Potassium Carbonate → HCID 86708798, compound

HRID 1751645Notes

Reaction equation

HRID 1751645 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]([C@@H:13]3[CH2:17][C@H:16]([CH2:18][O:19][CH3:20])[CH2:15][N:14]3[C:21](=[O:31])[C@@H:22]([NH:26][C:27](=[O:30])[O:28][CH3:29])[CH:23]([CH3:25])[CH3:24])=[N:10][CH:9]=2)=[CH:4][CH:3]=1.[CH3:32][C@@H:33]1[CH2:37][N:36]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[C@H:35]([C:45]2[NH:46][C:47]([C:50]3[CH:55]=[CH:54][C:53](B4OC(C)(C)C(C)(C)O4)=[CH:52][CH:51]=3)=[CH:48][N:49]=2)[CH2:34]1.C([O-])([O-])=O.[K+].[K+]>COCCOC.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>[CH3:29][O:28][C:27]([NH:26][C@@H:22]([CH:23]([CH3:25])[CH3:24])[C:21]([N:14]1[CH2:15][C@@H:16]([CH2:18][O:19][CH3:20])[CH2:17][C@H:13]1[C:11]1[NH:12][C:8]([C:5]2[CH:6]=[CH:7][C:2]([C:53]3[CH:52]=[CH:51][C:50]([C:47]4[NH:46][C:45]([C@@H:35]5[CH2:34][C@H:33]([CH3:32])[CH2:37][N:36]5[C:38]([O:40][C:41]([CH3:42])([CH3:44])[CH3:43])=[O:39])=[N:49][CH:48]=4)=[CH:55][CH:54]=3)=[CH:3][CH:4]=2)=[CH:9][N:10]=1)=[O:31])=[O:30]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 58501718HCID 58501718, compoundHCID 59610786HCID 59610786, compound

Product 1

HCID 86708798HCID 86708798, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

Methyl (S)-1-((2S,4S)-2-(5-(4-bromophenyl)-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (621 mg, 1.26 mmol), (2S,4S)-tert-butyl 4-methyl-2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (628 mg, 1.39 mmol), Pd(PPh3)4 (145 mg, 0.13 mmol), and K2CO3 (2M in H2O, 2.0 mL, 4.16 mmoL) were combined in DME (13 mL). The mixture was degassed with bubbling N2 for 10 min the heated to 85° C. for 16 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% to 30% MeOH/EtOAc) to afford (2S,4S)-tert-butyl 2-(5-(4′-(2-((2S,4S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-4-(methoxymethyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-methylpyrrolidine-1-carboxylate (342 mg, 37%).

Workup

  1. customThe mixture was degassed with bubbling N2 for 10 min the
  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% to 30% MeOH/EtOAc)

Sources & evidence

ORD record
ord-ca6899d086eb40be94b6a44d111fd5b9
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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