4,6-Dichloropyrimidine → HCID 58940650, compound

HRID 548934Notes

Reaction equation

HRID 548934 reaction equation
[C:1]([O:5][C:6](=[O:13])[N:7]([CH:9]1[CH2:12][NH:11][CH2:10]1)[CH3:8])([CH3:4])([CH3:3])[CH3:2].[Cl:14][C:15]1[CH:20]=[C:19](Cl)[N:18]=[CH:17][N:16]=1>CC(O)C>[Cl:14][C:15]1[N:16]=[CH:17][N:18]=[C:19]([N:11]2[CH2:12][CH:9]([N:7]([CH3:8])[C:6](=[O:13])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])[CH2:10]2)[CH:20]=1

Participants

4

Reactant 2

HCID 709434,6-DichloropyrimidineHCID 23033645tert-Butyl azetidin-3-yl(methyl)carbamate

Product 1

HCID 58940650HCID 58940650, compoundYield 64.6%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent2×

Conditions

Temperature
80 °C

Procedure

Azetidin-3-yl-methyl-carbamic acid tert-butyl ester (1.97 g, 11 mmol) in IPA (5 mL) was added dropwise to a stirred solution of 4,6-dichloropyrimidine (1.49 g, 10 mmol) in IPA (20 mL) followed by dropwise addition of TEA (2.11 mL, 15.1 mmol) at ambient temperature under N2. The resulting milky yellow solution was heated to 80° C. and maintained at 80° C. for 2 hours. The solution was allowed to cool and evaporated to give a yellow oil. The crude material was partitioned between DCM (70 mL) and water (30 aqueous extract was re-extracted with DCM (70 mL). The combined organic extract was washed with saturated aqueous sodium bicarbonate (30 mL), dried (MgSO4), filtered and evaporated to give a coloured oil. The crude oil was purified by flash column chromatography on silica gel eluting with DCM:MeOH (99:1 changing to 96:4 by volume) to yield the title compound as a solid (1.93 g, 64%).

Workup

  1. temperaturemaintained at 80° C. for 2 hours
  2. temperatureto cool
  3. customevaporated
  4. customto give a yellow oil
  5. customThe crude material was partitioned between DCM (70 mL) and water (30
  6. extractionaqueous extract
  7. extractionwas re-extracted with DCM (70 mL)
  8. extractionThe combined organic extract
  9. washwas washed with saturated aqueous sodium bicarbonate (30 mL)
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. customevaporated
  13. customto give a coloured oil
  14. customThe crude oil was purified by flash column chromatography on silica gel eluting with DCM:MeOH (99:1 changing to 96:4 by volume)

Sources & evidence

ORD record
ord-2b3e615683a543daaedf44ac0c9895af
Source dataset
uspto-grants-2011_05
Patent number
US07943628B2

Reaction notes

Loading…