Potassium Carbonate → 2-(5-{4'-[2-(1-tert-butoxycarbonylamino-cyclobutyl)-3H-imidazol-4-yl]-biphenyl-4-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 79745Notes

Reaction equation

HRID 79745 reaction equation
B(O)O.[C:4]([O:8][C:9](=[O:11])[NH2:10])([CH3:7])([CH3:6])[CH3:5].[C:12]([O:16][C:17]([N:19]1[CH2:23][CH2:22][CH2:21][CH:20]1[C:24]1[NH:25][C:26]([C:29]2[CH:34]=[CH:33][C:32](Br)=[CH:31][CH:30]=2)=[CH:27][N:28]=1)=[O:18])([CH3:15])([CH3:14])[CH3:13].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.COCCOC.O>[C:4]([O:8][C:9]([N:10]1[CH2:23][CH2:22][CH2:21][CH:20]1[C:24]1[NH:25][C:26]([C:29]2[CH:34]=[CH:33][C:32]([C:32]3[CH:31]=[CH:30][C:29]([C:26]4[NH:25][C:24]([C:20]5([NH:19][C:17]([O:16][C:12]([CH3:14])([CH3:15])[CH3:13])=[O:18])[CH2:21][CH2:22][CH2:23]5)=[N:28][CH:27]=4)=[CH:34][CH:33]=3)=[CH:31][CH:30]=2)=[CH:27][N:28]=1)=[O:11])([CH3:7])([CH3:6])[CH3:5]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 547756232-[5-(4-bromo-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 178450614HCID 178450614, compound

Product 1

HCID 666200892-(5-{4'-[2-(1-tert-butoxycarbonylamino-cyclobutyl)-3H-imidazol-4-yl]-biphenyl-4-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 9.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

1-[1H-Imidazol-2-yl]-cyclobutyl}-carbamic acid tert-butyl ester boronic acid (60 mg, 0.17 mmol) and 2-[5-(4-bromo-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (65 mg, 17 mmol) in 3:1 DME/H2O (1.5 mL) were treated with Pd(PPh3)4 (10 mg, 0.0084 mmol) and K2CO3 (2 M solution, 0.25 mL, 0.50 mmol). The mixture was stirred in a sealed tube at 80° C. for 18 hours. The mixture was filtered through a fritted glass funnel and concentrated. The mixture was subjected to a reverse phase HPLC column (5-95% MeCN—H2O; 0.1% TFA modifier) to afford 2-(5-{4′-[2-(1-tert-butoxycarbonylamino-cyclobutyl)-3H-imidazol-4-yl]-biphenyl-4-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (10 mg, 9%): MS (ESI) m/z 625 [M+H]+.

Workup

  1. filtrationThe mixture was filtered through a fritted glass funnel
  2. concentrationconcentrated

Sources & evidence

ORD record
ord-6e4340ad544248eaa928ef3315419330
Source dataset
uspto-grants-2014_09
Patent number
US08841278B2

Reaction notes

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