Citric Acid → HCID 18404005, compound

HRID 1017635Notes

Reaction equation

HRID 1017635 reaction equation
BrCCBr.[CH2:5](I)[C:6]([CH3:9])([CH3:8])[CH3:7].[F:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[N:18]1[C:22]2=[N:23][C:24]([O:28][CH2:29][C:30]3[N:31]([CH3:35])[N:32]=[CH:33][N:34]=3)=[C:25](Br)[CH:26]=[C:21]2[N:20]=[N:19]1.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C.O.[Zn].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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[N:18]1[C:22]2=[N:23][C:24]([O:28][CH2:29][C:30]3[N:31]([CH3:35])[N:32]=[CH:33][N:34]=3)=[C:25]([CH2:5][C:6]([CH3:9])([CH3:8])[CH3:7])[CH:26]=[C:21]2[N:20]=[N:19]1

Participants

10

Reactant 5

HCID 311Citric AcidHCID 78391,2-DibromoethaneHCID 84953Propane, 1-iodo-2,2-dimethyl-HCID 521585Tris(furan-2-yl)phosphaneHCID 18404041HCID 18404041, compound

Product 1

HCID 18404005HCID 18404005, compoundYield 41%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

A suspension of acid washed zinc dust (0.12 g, 1.80 mmol) and 1,2-dibromoethane (0.015 ml, 10 mol %) in dry DMF (3 ml) was stirred at room temperature under nitrogen for 5 min then warmed to 40° C. A solution of neopentyl iodide (0.25 ml, 1.85 mmol) in dry DMF (1 ml) was added and the mixture was stirred at 40° C. for 3 h. A solution of 3-(2-fluorophenyl)-5-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-6-bromo-1,2,3-triazolo[4,5-b]pyridine (0.15 g, 0.37 mmol) (Example 3, step c), tris(dibenzylideneacetone)dipalladium(0) (0.008 g, 2.5 mol %) and tri-2-furylphosphine (0.017 g, 20 mol %) in dry DMF (2 ml) was stirred at 40° C. under nitrogen for 10 min followed by addition of the organozinc reagent via syringe. The mixture was stirred for 18 h at 40° C. then cooled, diluted with water (60 ml), acidified with 1M aqueous citric acid and extracted with dichloromethane (2×30 ml). The extracts were dried (Na2SO4), filtered and concentrated. Preparative thin layer chromatography on silica gel, eluting with 2% methanol-dichloromethane, and trituration of the product with diethyl ether gave 3-(2-fluorophenyl)-5-(2-methyl-2H-1,2,4triazol-3-ylmethoxy)-6-(2,2-dimethylpropyl)-1,2,3-triazolo[4,5-b]pyridine (0.060 g, 41%) as a white solid, m.p. 130-133° C. Found: C, 60.03; H, 5.51; N, 24.37. C20H22N7OF.0.25(H2O) requires C, 60.06; H, 5.67; N, 24.52%. δH (360 MHz; CDCl3) 0.93 (9H, s), 2.68 (2H, s), 3.82 (3H, s),5.52 (2H, s), 7.36-7.42 (2H, m), 7.54-7.61 (1H, m), 7.69 (1H, dd, J=7 and 7), 7.86 (1H, s) and 8.10 (1H, s); m/z (ES+) 396 (M+H+).

Workup

  1. additionA suspension of acid
  2. temperaturethen warmed to 40° C
  3. stirringthe mixture was stirred at 40° C. for 3 h
  4. stirringThe mixture was stirred for 18 h at 40° C.
  5. temperaturethen cooled
  6. extractionextracted with dichloromethane (2×30 ml)
  7. dry with materialThe extracts were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. washPreparative thin layer chromatography on silica gel, eluting with 2% methanol-dichloromethane, and trituration of the product with diethyl ether

Sources & evidence

ORD record
ord-ae0d3a80dcb24a0aacacdd474fc35e5f
Source dataset
uspto-grants-2002_11
Patent number
US06479506B1

Reaction notes

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