Potassium Carbonate → (S)-benzyl 2-(5-(4'-(2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1H-benzo[d]imidazol-6-yl)biphenyl-4-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate

HRID 1751372Notes

Reaction equation

HRID 1751372 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[NH:25][C:24]([C@@H:26]5[CH2:30][CH2:29][CH2:28][N:27]5[C:31]([O:33][CH2:34][C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)=[O:32])=[N:23][CH:22]=4)=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)O1.Br[C:43]1[CH:44]=[CH:45][C:46]2[N:50]=[C:49]([C@@H:51]3[CH2:55][CH2:54][CH2:53][N:52]3[C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])[NH:48][C:47]=2[CH:63]=1.C(=O)([O-])[O-].[K+].[K+]>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.C(COC)OC>[C:59]([O:58][C:56]([N:52]1[CH2:53][CH2:54][CH2:55][C@H:51]1[C:49]1[NH:48][C:47]2[CH:63]=[C:43]([C:9]3[CH:10]=[CH:11][C:12]([C:15]4[CH:16]=[CH:17][C:18]([C:21]5[NH:25][C:24]([C@@H:26]6[CH2:30][CH2:29][CH2:28][N:27]6[C:31]([O:33][CH2:34][C:35]6[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=6)=[O:32])=[N:23][CH:22]=5)=[CH:19][CH:20]=4)=[CH:13][CH:14]=3)[CH:44]=[CH:45][C:46]=2[N:50]=1)=[O:57])([CH3:62])([CH3:60])[CH3:61]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 56605032(S)-tert-butyl 2-(6-bromo-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylateHCID 67681665(S)-benzyl 2-(5-(4'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)biphenyl-4-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate

Product 1

HCID 86708716(S)-benzyl 2-(5-(4'-(2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1H-benzo[d]imidazol-6-yl)biphenyl-4-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylateYield 44.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of (S)-benzyl 2-(5-(4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)biphenyl-4-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (2.1 g, 3.8 mmol), (S)-tert-butyl 2-(6-bromo-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate (1.6 g, 4.3 mmol), tetrakis(triphenylphosphine)palladium(0) (0.44 mg, 0.38 mmol), 2M aqueous potassium carbonate solution (7.7 mL, 15.4 mmol) and dimethoxyethane (26 mL) was degassed under a stream of argon for 15 minutes. The reaction was heated to 85° C. for 14 hours. Upon completion, the reaction was cooled to room temperature, diluted with ethyl acetate and filtered through Celite. The filtrate was washed with water and brine, dried (MgSO4) and concentrated. The resulting crude material was purified by flash column chromatography to yield (S)-benzyl 2-(5-(4′-(2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1H-benzo[d]imidazol-6-yl)biphenyl-4-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (1.2 g, 44%). LCMS-ESI+: calculated for C43H44N6O4: 708.85; observed [M+1]+: 709.41.

Workup

  1. customwas degassed under a stream of argon for 15 minutes
  2. temperatureUpon completion, the reaction was cooled to room temperature
  3. additiondiluted with ethyl acetate
  4. filtrationfiltered through Celite
  5. washThe filtrate was washed with water and brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe resulting crude material was purified by flash column chromatography

Sources & evidence

ORD record
ord-0f64c7b6337f4f73a659bcba36a45a14
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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