3-Bromopyridine → 2-(3-Ethyl-ureido)-7-pyridin-3-yl-[1,2,4]triazolo[1,5-a]pyridine-5-carboxylic acid methyl ester

HRID 2112932Notes

Reaction equation

HRID 2112932 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:11]2[N:12]=[C:13]([NH:15][C:16]([NH:18][CH2:19][CH3:20])=[O:17])[N:14]=[C:10]2[CH:9]=[C:8](Br)[CH:7]=1)=[O:5])C.[N:22]1[CH:27]=[CH:26][CH:25]=[C:24]([Sn](C)(C)C)[CH:23]=1.BrC1C=NC=CC=1.[Li+].[Cl-]>C1(C)C=CC=CC=1.CO.C(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH3:1][O:3][C:4]([C:6]1[N:11]2[N:12]=[C:13]([NH:15][C:16]([NH:18][CH2:19][CH3:20])=[O:17])[N:14]=[C:10]2[CH:9]=[C:8]([C:24]2[CH:23]=[N:22][CH:27]=[CH:26][CH:25]=2)[CH:7]=1)=[O:5]

Participants

9

Reactant 4

HCID 122863-BromopyridineHCID 433294Lithium ChlorideHCID 108684453-(Trimethylstannyl)pyridineHCID 576430687-Bromo-2-(3-ethyl-ureido)-[1,2,4]triazolo[1,5-a]pyridine-5-carboxylic acid ethyl ester

Product 1

HCID 445719542-(3-Ethyl-ureido)-7-pyridin-3-yl-[1,2,4]triazolo[1,5-a]pyridine-5-carboxylic acid methyl ester

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 1140TolueneSolvent2×HCID 21226129Dichloromethane methanolSolvent

Procedure

A mixture of 7-bromo-2-(3-ethyl-ureido)-[1,2,4]triazolo[1,5-a]pyridine-5-carboxylic acid ethyl ester (8)(240 mg, 0.67 mmol), (Ph3P)2PdCl2 (24 mg, 0.03 mmol) and CuI (13 mg, 0.07 mg) were suspended in dry toluene (5 mL). A solution of 3-pyridyltrimethylstannane [195 mg, 0.81 mmol; prepared from 3-bromopyridine according to the procedure of J. Org. Chem., 64(19), 6999-7008 (1999)] in toluene (5 mL) was added, followed by LiCl (143 mg, 3.37 mmol) as a single portion. The entire mixture was heated at reflux under nitrogen for 2 h. The reaction mixture was allowed to cool, then diluted with 10% MeOH/CH2Cl2 (80 mL). This organic solution was washed with water (80 mL), 1 M KF solution (80 mL) and brine (80 mL). The organic layer was filtered to remove inorganic solids, dried (Na2SO4), and the solvent removed under reduced pressure to give a solid which was purified by chromatography on silica (2% MeOH/CH2Cl2 as eluant). Transesterification from the ethyl to the methyl ester occurred during workup and chromatography. 2-(3-Ethyl-ureido)-7-pyridin-3-yl-[1,2,4]triazolo[1,5-a]pyridine-5-carboxylic acid methyl ester was isolated; mp. 211-213° C. LCMS (APCI+) 341. HRMS (FAB+) calcd C16H17N6O3 (MH+) 341.1362, found 341.1358.

Workup

  1. temperatureThe entire mixture was heated
  2. temperatureat reflux under nitrogen for 2 h
  3. temperatureto cool
  4. washThis organic solution was washed with water (80 mL), 1 M KF solution (80 mL) and brine (80 mL)
  5. filtrationThe organic layer was filtered
  6. customto remove inorganic solids
  7. dry with materialdried (Na2SO4)
  8. customthe solvent removed under reduced pressure
  9. customto give a solid which
  10. customwas purified by chromatography on silica (2% MeOH/CH2Cl2 as eluant)

Sources & evidence

ORD record
ord-3e73b08e732348ec9e66c337985fe7c1
Source dataset
uspto-grants-2009_04
Patent number
US07524860B2

Reaction notes

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