1,2-Dimethoxyethane → 2-{5-[4-(2-Benzyloxy-pyridin-4-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 71725Notes

Reaction equation

HRID 71725 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[C:13](Br)[CH:12]=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:16]([O:20][C:21]([N:23]1[CH2:27][CH2:26][CH2:25][CH:24]1[C:28]1[NH:29][C:30]([C:33]2[CH:38]=[CH:37][C:36](B3OC(C)(C)C(C)(C)O3)=[CH:35][CH:34]=2)=[CH:31][N:32]=1)=[O:22])([CH3:19])([CH3:18])[CH3:17].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:16]([O:20][C:21]([N:23]1[CH2:27][CH2:26][CH2:25][CH:24]1[C:28]1[NH:29][C:30]([C:33]2[CH:38]=[CH:37][C:36]([C:13]3[CH:12]=[CH:11][N:10]=[C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[CH:14]=3)=[CH:35][CH:34]=2)=[CH:31][N:32]=1)=[O:22])([CH3:19])([CH3:17])[CH3:18]

Participants

7

Reactant 3

HCID 80711,2-DimethoxyethaneHCID 532173892-(Benzyloxy)-4-bromopyridineHCID 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 ester

Product 1

HCID 666202502-{5-[4-(2-Benzyloxy-pyridin-4-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl esterYield 96.5%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
85 °C

Procedure

A mixture of 2-Benzyloxy-4-bromo-pyridine (0.292 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 (0.533 g, prepared according to WO2008021927 A2) and Pd(PPh3)4 (0.064 g) in aq. K2CO3 solution/dimethoxyethane (1.82 mL/5.0 mL) was heated at 80-90° C. for 8 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, 20 to 80% ethyl acetate/hexanes) to give 2-{5-[4-(2-Benzyloxy-pyridin-4-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (0.530 g): LCMS-ESI+: calc'd for C30H33N4O3: 497.6 (M+H+). Found: 497.0 (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, 20 to 80% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-e734d634c4264ffdb6fd2f67f550f264
Source dataset
uspto-grants-2014_09
Patent number
US08822430B2

Reaction notes

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