2,4-Dichloropyrimidine → (2R,3R)-2-((2-chloropyrimidin-4-yl)amino)-3-methoxybutan-1-ol

HRID 57346Notes

Reaction equation

HRID 57346 reaction equation
[NH2:1][C@@H:2]([C@H:5]([O:7][CH3:8])[CH3:6])[CH2:3][OH:4].[Cl:9][C:10]1[N:15]=[C:14](Cl)[CH:13]=[CH:12][N:11]=1.CCN(C(C)C)C(C)C>C(#N)C>[Cl:9][C:10]1[N:15]=[C:14]([NH:1][C@@H:2]([C@H:5]([O:7][CH3:8])[CH3:6])[CH2:3][OH:4])[CH:13]=[CH:12][N:11]=1

Participants

5

Reactant 3

HCID 775312,4-DichloropyrimidineHCID 81531DiisopropylethylamineHCID 55284136(2R,3R)-2-amino-3-methoxybutan-1-ol

Product 1

HCID 90416988(2R,3R)-2-((2-chloropyrimidin-4-yl)amino)-3-methoxybutan-1-olYield 40.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a round bottom flask containing (2R,3R)-2-amino-3-methoxybutan-1-ol (2.1 g, 9.0 mmol) and a stir bar was added acetonitrile (100 mL) followed by the addition of 2,4-dichloropyrimidine (1.34 g, 9.0 mmol) and DIEA (4.7 mL, 27.0 mmol). Resulting reaction mixture allowed to stir 18 hr at room temperature. Volatiles were then removed. Residue was partitioned between EtOAc and water. Aqueous layer extracted with EtOAc. Organic phases combined, washed with water, brine, dried (Na2SO4), filtered and concentrated to afford (2R,3R)-2-((2-chloropyrimidin-4-yl)amino)-3-methoxybutan-1-ol (1.68 g, 3.63 mmol, 40% yield) which contains some unreacted 2,4-dichloropyrimidine. LCMS m/z 232.0 (M+H)+, Rt 0.38 min.

Workup

  1. customResulting
  2. customreaction mixture
  3. customVolatiles were then removed
  4. customResidue was partitioned between EtOAc and water
  5. extractionAqueous layer extracted with EtOAc
  6. washwashed with water, brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-913ed8b6e8c8448c9fa0e85f4bad2c8b
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

Loading…