Chloroacetaldehyde → 7-chloro-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine

HRID 1852951Notes

Reaction equation

HRID 1852951 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[CH:12]=2)[N:5]=[C:4]([NH2:21])[CH:3]=1.P([O-])([O-])([O-])=O.[C:27]([O-])(=O)[CH3:28].[Na+].ClCC=O>C(O)C.C(=O)(O)[O-].[Na+]>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:18])([CH3:20])[CH3:19])[CH:12]=2)[N:5]2[CH:27]=[CH:28][N:21]=[C:4]2[CH:3]=1

Participants

7

Reactant 4

HCID 33Chloroacetaldehyde2×HCID 1061PhosphateHCID 517045Sodium Acetate2×HCID 866852946-chloro-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)pyrimidin-4-amine

Product 1

HCID 866852957-chloro-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidineYield 39.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of 6-chloro-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)pyrimidin-4-amine (2.750 g, 8.439 mmol) in 60 mL of 1:1 absolute ethanol: pH=7 phosphate buffer were added sodium acetate (1.385 g, 16.88 mmol) and 2-chloroacetaldehyde (1.905 mL, 14.77 mmol) and the reaction mixture was then fitted with a condenser and heated to 95° C. overnight. The reaction was not complete so sodium acetate (1.385 g, 16.88 mmol) and 2-chloroacetaldehyde (1.905 mL, 14.77 mmol) were added and the reaction mixture was heated to 95° C. for four hours. After this time the reaction was allowed to cool to ambient temperature and was then diluted with aqueous saturated sodium bicarbonate (50 mL) and extracted with ethyl acetate. The organic layers were combined, dried over MgSO4, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography eluting with 30-45% ethyl acetate in hexanes (1 L) to afford the title compound (1.16 g, 3.315 mmol, 39.29% yield). MS (apci) m/z=350.1 (M+H).

Workup

  1. customthe reaction mixture was then fitted with a condenser
  2. additionwere added
  3. temperaturethe reaction mixture was heated to 95° C. for four hours
  4. temperatureto cool to ambient temperature
  5. extractionextracted with ethyl acetate
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by silica gel chromatography
  10. washeluting with 30-45% ethyl acetate in hexanes (1 L)

Sources & evidence

ORD record
ord-67d63515ab9b45899887d6269679104e
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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