1,2-Dimethoxyethane → 2-(5-{4'-[3-(2-Trimethylsilanyl-ethoxymethyl)-3H-imidazol-4-yl]-biphenyl-4-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 71731Notes

Reaction equation

HRID 71731 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[CH:11]=[N:10][CH:9]=2)=[CH:4][CH:3]=1.Br[C:22]1[CH:27]=[CH:26][C:25]([C:28]2[N:29]=[CH:30][N:31]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[CH:32]=2)=[CH:24][CH:23]=1.[C:41]([O:45][C:46]([N:48]1[CH2:52][CH2:51][CH2:50][CH:49]1[C:53]1[NH:54][C:55]([C:58]2[CH:63]=[CH:62][C:61](B3OC(C)(C)C(C)(C)O3)=[CH:60][CH:59]=2)=[CH:56][N:57]=1)=[O:47])([CH3:44])([CH3:43])[CH3:42].C(COC)OC>C([O-])([O-])=O.[K+].[K+].C(OCC)(=O)C.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:41]([O:45][C:46]([N:48]1[CH2:52][CH2:51][CH2:50][CH:49]1[C:53]1[NH:54][C:55]([C:58]2[CH:63]=[CH:62][C:61]([C:2]3[CH:7]=[CH:6][C:5]([C:8]4[N:12]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[CH:11]=[N:10][CH:9]=4)=[CH:4][CH:3]=3)=[CH:60][CH:59]=2)=[CH:56][N:57]=1)=[O:47])([CH3:44])([CH3:42])[CH3:43].[C:41]([O:45][C:46]([N:48]1[CH2:52][CH2:51][CH2:50][CH:49]1[C:53]1[NH:54][C:55]([C:58]2[CH:63]=[CH:62][C:61]([C:22]3[CH:27]=[CH:26][C:25]([C:28]4[N:29]=[CH:30][N:31]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[CH:32]=4)=[CH:24][CH:23]=3)=[CH:60][CH:59]=2)=[CH:56][N:57]=1)=[O:47])([CH3:44])([CH3:42])[CH3:43]

Participants

9

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 574497592-{4-[4-(4,4,5,5-Tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]-1h-imidazol-2-yl}pyrrolidine-1-carboxylic acid tert-butyl esterHCID 666203455-(4-Bromo-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazoleHCID 666204954-(4-Bromo-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole

Product 2

HCID 666208032-(5-{4'-[3-(2-Trimethylsilanyl-ethoxymethyl)-3H-imidazol-4-yl]-biphenyl-4-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 666208752-(5-{4'-[1-(2-Trimethylsilanyl-ethoxymethyl)-1H-imidazol-4-yl]-biphenyl-4-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 11430Potassium CarbonateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 1:1 mixture of 5-(4-Bromo-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole and 4-(4-Bromo-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole (0.145 g), 2-{5-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (0.150 g, prepared according to WO2008021927 A2) and Pd(PPh3)4 (0.020 g) in aq. K2CO3 solution (0.51 mL)/dimethoxyethane (1.5 mL) was heated at 80° C. for 18 hours. Reaction mixture was cooled, diluted with ethyl acetate, washed with brine, dried (MgSO4) and concentrated. The residue was purified by flash column chromatography (silica gel, 50 to 100% ethyl acetate/hexanes) to give a 1:1 mixture 2-(5-{4′-[3-(2-Trimethylsilanyl-ethoxymethyl)-3H-imidazol-4-yl]-biphenyl-4-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester and 2-(5-{4′-[1-(2-Trimethylsilanyl-ethoxymethyl)-1H-imidazol-4-yl]-biphenyl-4-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.0998 g): LCMS-ESI+: calc'd for C33H44N5O3Si: 586.82 (M+H+). Found: 586.0 (M+H+).

Workup

  1. customReaction mixture
  2. temperaturewas cooled
  3. washwashed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography (silica gel, 50 to 100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-8a74d97f51b541e4ae04acc3c18c5250
Source dataset
uspto-grants-2014_09
Patent number
US08822430B2

Reaction notes

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