Sodium Carbonate → HCID 66990281, compound

HRID 1627233Notes

Reaction equation

HRID 1627233 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:15][C:9]2=[N:10][CH:11]=[C:12](Br)[CH:13]=[C:8]2[CH:7]=1)=[O:5])[CH3:2].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C([O-])(=O)C.[K+].[N:58]1[CH:63]=[CH:62][C:61]([CH2:64][NH:65][C:66]([C:68]2[N:69]([CH2:75][O:76][CH2:77][CH2:78][Si:79]([CH3:82])([CH3:81])[CH3:80])[C:70]([CH3:74])=[C:71](Br)[N:72]=2)=[O:67])=[CH:60][CH:59]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.CO.ClCCl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[CH2:1]([O:3][C:4]([C:6]1[NH:15][C:9]2=[N:10][CH:11]=[C:12]([C:71]3[NH:72][C:68]([C:66](=[O:67])[NH:65][CH2:64][C:61]4[CH:62]=[CH:63][N:58]=[CH:59][CH:60]=4)=[N:69][C:70]=3[CH3:74])[CH:13]=[C:8]2[CH:7]=1)=[O:5])[CH3:2].[CH2:1]([O:3][C:4]([C:6]1[NH:15][C:9]2=[N:10][CH:11]=[C:12]([C:71]3[N:72]=[C:68]([C:66](=[O:67])[NH:65][CH2:64][C:61]4[CH:62]=[CH:63][N:58]=[CH:59][CH:60]=4)[N:69]([CH2:75][O:76][CH2:77][CH2:78][Si:79]([CH3:80])([CH3:82])[CH3:81])[C:70]=3[CH3:74])[CH:13]=[C:8]2[CH:7]=1)=[O:5])[CH3:2]

Participants

11

Reactant 6

HCID 10340Sodium CarbonateHCID 75806TricyclohexylphosphineHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 46941896Ethyl 5-bromo-1H-pyrrolo[2,3-b]pyridine-2-carboxylateHCID 66989223HCID 66989223, compound

Product 2

HCID 66990281HCID 66990281, compoundYield 105.9%HCID 178468485HCID 178468485, compound

Reagents, catalysts & solvents 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 312751,4-DioxaneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 5-Bromo-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid ethyl ester (143 mg, 0.53 mmol), bis(pinacolato)diboron (202 mg, 0.79 mmol), tricyclohexylphosphine (15 mg, 0.053 mmol), potassium acetate (105 mg, 1.07 mmol) and Pd(dba)2 (15 mg, 0.027 mmol) in 1,4-dioxane (5 ml) is heated to 110° C. in an oil bath for 1 hour under argon. 4-Bromo-5-methyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid(pyridin-4-ylmethyl)-amide (225 mg, 0.53 mmol) and (Bis(di-t-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (38 mg, 0.053 mmol) and aqueous Na2CO3 (2M, 1.33 ml, 2.65 mmol) are added, and the reaction mixture is heated at 110° C. for 1 hour. The mixture is cooled to room temperature, diluted with 5% methanol/dichloromethane and filtered through celite. The filtrate is evaporated in vacuo, and the crude product is purified by reverse phase HPLC to give the title compound 5-[5-Methyl-2-[(pyridin-4-ylmethyl)-carbamoyl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-4-yl]-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid ethyl ester as a light yellow solid 150 mg, 53%, LC/MS ESI m/z (M+H)+=535.61.

Workup

  1. temperaturethe reaction mixture is heated at 110° C. for 1 hour
  2. temperatureThe mixture is cooled to room temperature
  3. filtrationfiltered through celite
  4. customThe filtrate is evaporated in vacuo
  5. customthe crude product is purified by reverse phase HPLC

Sources & evidence

ORD record
ord-592e2c03285f4db9ba0a0123b1a379ac
Source dataset
uspto-grants-2014_07
Patent number
US08785489B2

Reaction notes

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