Sodium Bicarbonate → 4,4'-Bis-[2-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-biphenyl-2,2'-dicarboxylic acid dimethyl ester

HRID 71696Notes

Reaction equation

HRID 71696 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([C:18]2[CH:23]=[CH:22][C:21](Br)=[C:20]([C:25]([O:27][CH3:28])=[O:26])[CH:19]=2)=[CH:16][N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:29]([O:33][C:34]([N:36]1[CH2:40][CH2:39][CH2:38][CH:37]1[C:41]1[NH:42][C:43]([C:46]2[CH:51]=[CH:50][C:49](B3OC(C)(C)C(C)(C)O3)=[C:48]([C:61]([O:63][CH3:64])=[O:62])[CH:47]=2)=[CH:44][N:45]=1)=[O:35])([CH3:32])([CH3:31])[CH3:30].C(=O)(O)[O-].[Na+]>O.CCOC(C)=O.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>[CH3:28][O:27][C:25]([C:20]1[C:21]([C:49]2[C:48]([C:61]([O:63][CH3:64])=[O:62])=[CH:47][C:46]([C:43]3[NH:42][C:41]([CH:37]4[CH2:38][CH2:39][CH2:40][N:36]4[C:34]([O:33][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:35])=[N:45][CH:44]=3)=[CH:51][CH:50]=2)=[CH:22][CH:23]=[C:18]([C:15]2[NH:14][C:13]([CH:9]3[CH2:10][CH2:11][CH2:12][N:8]3[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[N:17][CH:16]=2)[CH:19]=1)=[O:26]

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 666201422-{5-[3-Methoxycarbonyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 666202292-[5-(4-bromo-3-methoxycarbonyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 666202834,4'-Bis-[2-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-biphenyl-2,2'-dicarboxylic acid dimethyl esterYield 34.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To the solution of 2-[5-(4-bromo-3-methoxycarbonyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (158 mg, 0.35 mmol) and 2-{5-[3-Methoxycarbonyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (166 mg, 0.33 mmol) in 1,2-dimethoxyether (3 ml) and water (1 ml) was added sodium bicarbonate (91 mg, 1.1 mmol), followed by Pd(PPh3)4 (15 mg) and PdCl2(dppf)CH2Cl2 (15 mg). The mixture was heated at 80° C. for 7 hours. The mixture was diluted with EtOAc, and was washed with water and brine, and was dried with sodium sulfate. Concentration and purification by flash column chromatography (EtOAc) gave 4,4′-Bis-[2-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-biphenyl-2,2′-dicarboxylic acid dimethyl ester (85 mg). m/z: 741.0 (M+H)+, 370.9 (M+2H)+/2.

Workup

  1. washwas washed with water and brine
  2. dry with materialwas dried with sodium sulfate
  3. concentrationConcentration and purification by flash column chromatography (EtOAc)

Sources & evidence

ORD record
ord-63fe024afdcd4aa7be7b88b8c8f26d9e
Source dataset
uspto-grants-2014_09
Patent number
US08822430B2

Reaction notes

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