Hydrochloric Acid → HCID 51353726, compound

HRID 2367515Notes

Reaction equation

HRID 2367515 reaction equation
[CH3:1][C@H:2]1[NH:7][CH2:6][C@@H:5]([CH2:8][OH:9])[O:4][CH2:3]1.[Cl:10][C:11]1[CH:16]=[C:15](Cl)[N:14]=[C:13]([NH:18][CH3:19])[N:12]=1.C([O-])([O-])=O.[K+].[K+].Cl>CCO.CCOCC.O>[Cl:10][C:11]1[N:12]=[C:13]([NH:18][CH3:19])[N:14]=[C:15]([N:7]2[C@H:2]([CH3:1])[CH2:3][O:4][C@H:5]([CH2:8][OH:9])[CH2:6]2)[CH:16]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 2598804,6-Dichloro-n-methylpyrimidin-2-amineHCID 51357960HCID 51357960, compound

Product 1

HCID 51353726HCID 51353726, compoundYield 55.9%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

A mixture of [(2S,5R)-5-methyl-2-morpholinyl]methanol (11.50 g, 65.2 mmol), 4,6-dichloro-N-methyl-2-pyrimidinamine (11.38 g, 63.9 mmol), and K2CO3 (19.87 g, 144 mmol) in EtOH (250 mL) was stirred at reflux under nitrogen for 23 hours. The mixture was cooled, poured into water (500 mL), and extracted with CH2Cl2 (3×400 mL). The extracts were dried (Na2SO4), filtered, and concentrated in vacuo to give a cream solid. The residue was purified by flash chromatography (400 g SiO2, 10-60% EtOAc in hexanes gradient). The product was collected and concentrated in vacuo to give a very sticky foam. The residue was taken up in Et2O (250 mL) and HCl (4.0 M in 1,4-dioxane, 10 mL) was added dropwise while the mixture was swirled. The solid that formed was collected by vacuum filtration and dried in the vacuum oven overnight to give a hydrochloride salt of the title compound (9.75 g) as a white solid. LC-MS (ES) m/z=273, 275 [M+H]+.

Workup

  1. temperatureat reflux under nitrogen for 23 hours
  2. temperatureThe mixture was cooled
  3. extractionextracted with CH2Cl2 (3×400 mL)
  4. dry with materialThe extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a cream solid
  8. customThe residue was purified by flash chromatography (400 g SiO2, 10-60% EtOAc in hexanes gradient)
  9. customThe product was collected
  10. concentrationconcentrated in vacuo
  11. customto give a very sticky foam
  12. customThe solid that formed
  13. filtrationwas collected by vacuum filtration
  14. customdried in the vacuum oven overnight

Sources & evidence

ORD record
ord-787b5b9ad3e14e95bc935d401bea1917
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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