Methyl dichlorophosphate → HCID 66839224, compound

HRID 546760Notes

Reaction equation

HRID 546760 reaction equation
P(Cl)(Cl)(OC)=O.[CH3:7][O:8][C:9]1[N:14]=[C:13](/[CH:15]=[CH:16]/[C:17]([NH2:19])=O)[CH:12]=[CH:11][C:10]=1[N:20]1[CH:24]=[C:23]([CH3:25])[N:22]=[CH:21]1.C1CCN2C(=NCCC2)CC1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.O>[CH3:7][O:8][C:9]1[N:14]=[C:13](/[CH:15]=[CH:16]/[C:17]#[N:19])[CH:12]=[CH:11][C:10]=1[N:20]1[CH:24]=[C:23]([CH3:25])[N:22]=[CH:21]1

Participants

7

Reactant 4

HCID 69611Methyl dichlorophosphateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 516892Sodium BicarbonateHCID 66839442(E)-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]acrylamide

Product 1

HCID 66839224HCID 66839224, compoundYield 85.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Methyl dichlorophosphate (33 ml) was added dropwise to a suspension of (E)-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]acrylamide (42.96 g) and 1,8-diazabicyclo[5,4,0]-7-undecene (112 ml) in methylene chloride (400 ml) under ice-cooling over 20 minutes. The reaction solution was stirred at the same temperature for 10 minutes and at room temperature for further 35 minutes. Then, a saturated sodium bicarbonate solution (200 ml) was added to the reaction solution, and the reaction solution was stirred at room temperature for 10 minutes. Water was added to the reaction solution. Then, the reaction solution was filtered and the organic layer in the filtrate was separated. The aqueous layer was reextracted with methylene chloride (twice). The combined organic layers were dried over anhydrous magnesium sulfate and purified by short silica gel column chromatography (carrier: Chromatorex NH; elution solvent: methylene chloride). The eluted fraction was concentrated. The resulting residue was triturated with ethyl acetate and tert-butyl methyl ether and dried under reduced pressure overnight to obtain 34.28 g of the title compound.

Workup

  1. temperaturecooling over 20 minutes
  2. stirringthe reaction solution was stirred at room temperature for 10 minutes
  3. filtrationThen, the reaction solution was filtered
  4. customthe organic layer in the filtrate was separated
  5. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  6. custompurified by short silica gel column chromatography (carrier: Chromatorex NH; elution solvent: methylene chloride)
  7. concentrationThe eluted fraction was concentrated
  8. customThe resulting residue was triturated with ethyl acetate and tert-butyl methyl ether
  9. customdried under reduced pressure overnight

Sources & evidence

ORD record
ord-31d2dfc1ca334a3ea71a9f969922da65
Source dataset
uspto-grants-2011_05
Patent number
US07935815B2

Reaction notes

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