Phosgene → 2,3-Dimethyl-8-{2-[(2-methylsulfanylethoxy)carbonylamino]-6-methylbenzylamino}imidazo[1,2-a]-pyridine hemifumarate

HRID 1870242Notes

Reaction equation

HRID 1870242 reaction equation
[C:1](Cl)(Cl)=[O:2].[CH3:5][S:6][CH2:7][CH2:8][OH:9].CN1CC[O:14][CH2:13]C1.[NH2:17][C:18]1[CH:36]=[CH:35][CH:34]=[C:33]([CH3:37])[C:19]=1[CH2:20][NH:21][C:22]1[C:23]2[N:24]([C:28]([CH3:32])=[C:29]([CH3:31])[N:30]=2)[CH:25]=[CH:26][CH:27]=1.[C:38](=[O:41])(O)[O-:39].[Na+]>C1(C)C=CC=CC=1.ClCCl.C(N(CC)CC)C>[C:1]([OH:2])(=[O:14])/[CH:7]=[CH:8]/[C:38]([OH:39])=[O:41].[CH3:31][C:29]1[N:30]=[C:23]2[C:22]([NH:21][CH2:20][C:19]3[C:33]([CH3:37])=[CH:34][CH:35]=[CH:36][C:18]=3[NH:17][C:13]([O:9][CH2:8][CH2:7][S:6][CH3:5])=[O:14])=[CH:27][CH:26]=[CH:25][N:24]2[C:28]=1[CH3:32].[CH3:31][C:29]1[N:30]=[C:23]2[C:22]([NH:21][CH2:20][C:19]3[C:33]([CH3:37])=[CH:34][CH:35]=[CH:36][C:18]=3[NH:17][C:1]([O:9][CH2:8][CH2:7][S:6][CH3:5])=[O:2])=[CH:27][CH:26]=[CH:25][N:24]2[C:28]=1[CH3:32]

Participants

9

Reactant 5

HCID 6371PhosgeneHCID 79724-MethylmorpholineHCID 789252-(Methylthio)ethanolHCID 516892Sodium BicarbonateHCID 109896268-(2-Amino-6-methylbenzylamino)-2,3-dimethylimidazo[1,2-a]pyridine

Product 1

HCID 1317219282,3-Dimethyl-8-{2-[(2-methylsulfanylethoxy)carbonylamino]-6-methylbenzylamino}imidazo[1,2-a]-pyridine hemifumarateYield 47%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent3×HCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

A 20% strength solution of phosgene in toluene (2.8 ml) is diluted with anhydrous dichloromethane (15 ml) and cooled to 0° C. A solution of 2-methylsulfanylethanol (0.46 ml) and N-methylmorpholine (0.59 ml) in anhydrous dichloromethane (10 ml) is then added dropwise. The mixture is kept at 0° C. for a further 15 min, then warmed to RT and stirred for a further 30 min. A suspension of 8-(2-amino-6-methylbenzylamino)-2,3-dimethylimidazo[1,2-a]pyridine (1.0 g) and triethylamine (0.49 ml) in anhydrous dichloromethane (30 ml) is then added dropwise to the solution and it is additionally stirred at RT for 1 h. Aqueous sodium bicarbonate solution (70 ml) is then added and the mixture is stirred for a further 30 min. The organic phase is separated off and the aqueous phase is extracted with dichloromethane (3×50 ml). The combined organic phases are washed with water (50 ml), dried over magnesium sulfate and concentrated. The residue is taken up in a hot solution of fumaric acid (400 mg) in acetone (30 ml) and cooled to 4° C. The precipitate is filtered off and additionally precipitated from a little hot acetone by stirring. After drying in a high vacuum, 0.65 g (47%) of the title compound is isolated as a pale beige crystallizate. M.p. 174-176° C.

Workup

  1. temperaturewarmed to RT
  2. additionis then added dropwise to the solution and it
  3. stirringis additionally stirred at RT for 1 h
  4. stirringthe mixture is stirred for a further 30 min
  5. customThe organic phase is separated off
  6. extractionthe aqueous phase is extracted with dichloromethane (3×50 ml)
  7. washThe combined organic phases are washed with water (50 ml)
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. temperaturecooled to 4° C
  11. filtrationThe precipitate is filtered off
  12. customadditionally precipitated from a little hot acetone
  13. stirringby stirring
  14. customAfter drying in a high vacuum

Sources & evidence

ORD record
ord-3bfa7021f2fb42e9b5b514f4233e4e6d
Source dataset
uspto-grants-2000_08
Patent number
US06096758

Reaction notes

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