1,1-Dichloroethane → HCID 118308702, compound

HRID 923506Notes

Reaction equation

HRID 923506 reaction equation
[NH2:1][C:2]1([C:10]#[N:11])[CH2:7][O:6][C:5]([CH3:9])([CH3:8])[O:4][CH2:3]1.ClC(Cl)C.Cl.[F:17][C:18]1[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[C:19]=1[CH2:20][O:21][C:22]1[C:23]2[N:24]([C:28]([C:32](Cl)=[O:33])=[C:29]([CH3:31])[N:30]=2)[CH:25]=[CH:26][CH:27]=1>C(N(CC)CC)C>[C:10]([C:2]1([NH:1][C:32]([C:28]2[N:24]3[CH:25]=[CH:26][CH:27]=[C:22]([O:21][CH2:20][C:19]4[C:18]([F:17])=[CH:38][CH:37]=[CH:36][C:35]=4[F:39])[C:23]3=[N:30][C:29]=2[CH3:31])=[O:33])[CH2:7][O:6][C:5]([CH3:8])([CH3:9])[O:4][CH2:3]1)#[N:11]

Participants

5

Reactant 3

HCID 63651,1-Dichloroethane2×HCID 86717885HCID 86717885, compoundHCID 118308686HCID 118308686, compound

Product 1

HCID 118308702HCID 118308702, compoundYield 91.1%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
70 °C

Procedure

Under an argon gas flow, to a mixture of 10.4 g of 5-amino-2,2-dimethyl-1,3-dioxane-5-carbonitrile, 27.8 ml of triethylamine, and 280 ml of dichloroethane were added 27.2 g of 8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carbonyl chloride hydrochloride and 12 ml of dichloroethane at room temperature, followed by stirring at 70° C. for 2 hours. After leaving to be cooled to room temperature, the insoluble materials were separated by filtration and washed with dichloroethane. The filtrate was washed with a 10% aqueous citric acid solution three times, and the aqueous layer was extracted with chloroform. The organic layer was combined, washed with water, a saturated aqueous sodium hydrogen carbonate solution, and a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure. The obtained residue was azeotropic distilled with ethyl acetate twice. To the obtained residue was added THF, and the insoluble materials were separated by filtration and washed with THF. The filtrate was concentrated and the residue was purified by silica gel column chromatography to obtain 27.7 g of N-(5-cyano-2,2-dimethyl-1,3-dioxan-5-yl)-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxamide.

Workup

  1. customAfter leaving
  2. temperatureto be cooled to room temperature
  3. customthe insoluble materials were separated by filtration
  4. washwashed with dichloroethane
  5. washThe filtrate was washed with a 10% aqueous citric acid solution three times
  6. extractionthe aqueous layer was extracted with chloroform
  7. washwashed with water
  8. dry with materiala saturated aqueous sodium hydrogen carbonate solution, and a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate
  9. customthe solvent was then evaporated under reduced pressure
  10. distillationThe obtained residue was azeotropic distilled with ethyl acetate twice
  11. additionTo the obtained residue was added THF
  12. customthe insoluble materials were separated by filtration
  13. washwashed with THF
  14. concentrationThe filtrate was concentrated
  15. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-23664713f2a94bd0ad8350723fc0df20
Source dataset
uspto-grants-2016_03
Patent number
US09278968B2

Reaction notes

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