Potassium Acetate → 2-[5-(4-{6-[2-(1-tert-Butoxycarbonyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-naphthalen-2-yl}-phenyl)-1H-imidazol-2-yl]-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 2039298Notes

Reaction equation

HRID 2039298 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([C:13]#[N:14])[CH2:10][CH:9]1[C:15]1[NH:16][C:17]([C:20]2[CH:25]=[CH:24][C:23](Br)=[CH:22][CH:21]=2)=[CH:18][N:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:27]([O:31][C:32]([N:34]1[CH2:38][CH2:37][CH2:36][CH:35]1[C:39]1[NH:40][C:41]([C:44]2[CH:53]=[CH:52][C:51]3[C:46](=[CH:47][CH:48]=[C:49](B4OC(C)(C)C(C)(C)O4)[CH:50]=3)[CH:45]=2)=[CH:42][N:43]=1)=[O:33])([CH3:30])([CH3:29])[CH3:28].C([O-])(=O)C.[K+]>COCCOC.O.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:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([C:13]#[N:14])[CH2:10][CH:9]1[C:15]1[NH:16][C:17]([C:20]2[CH:25]=[CH:24][C:23]([C:49]3[CH:48]=[CH:47][C:46]4[C:51](=[CH:52][CH:53]=[C:44]([C:41]5[NH:40][C:39]([CH:35]6[CH2:36][CH2:37][CH2:38][N:34]6[C:32]([O:31][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:33])=[N:43][CH:42]=5)[CH:45]=4)[CH:50]=3)=[CH:22][CH:21]=2)=[CH:18][N:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 3

HCID 517044Potassium AcetateHCID 666205222-{5-[6-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-naphthalen-2-yl]-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 666205592-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 666206472-[5-(4-{6-[2-(1-tert-Butoxycarbonyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-naphthalen-2-yl}-phenyl)-1H-imidazol-2-yl]-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl esterYield 33.6%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

The mixture of 2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl ester (356 mg, 0.85 mmol), 2-{5-[6-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-naphthalen-2-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (501 mg, 1.02 mmol), tetrakis(triphenylphosphine)palladium (99 mg, 0.08 mmol) and potassium acetate (425 mg, 3.07 mmol) in 7 mL 1,2-dimethoxyethane and 2 mL water was heated to 90° C. for 2 hour. The reaction mixture was cooled and dissolved in ethyl acetate and washed with saturated sodium bicarbonate solution. The organic layer dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 20 to 80% ethyl acetate/hexane) to give 2-[5-(4-{6-[2-(1-tert-Butoxycarbonyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-naphthalen-2-yl}-phenyl)-1H-imidazol-2-yl]-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl ester (200 mg, yield 33%) and the amide product. LCMS-ESI−: calc'd for C41H45N7O4: 699.84; Found: 700.2 (M+H+).

Workup

  1. temperatureThe reaction mixture was cooled
  2. washwashed with saturated sodium bicarbonate solution
  3. dry with materialThe organic layer dried (MgSO4)
  4. concentrationconcentrated
  5. custompurified by flash column chromatography (silica gel, 20 to 80% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-f421e7b4ea8146c4adc9af68d387e7d1
Source dataset
uspto-grants-2013_11
Patent number
US08575118B2

Reaction notes

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