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

HRID 1852959Notes

Reaction equation

HRID 1852959 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[N:12]=[C:11]([C:13]3[CH:14]=[N:15][N:16]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:17]=3)[N:10]=[C:9]([NH2:26])[CH:8]=2)[CH:4]=[N:3]1.[CH3:27][C:28]([O-])=O.[Na+].ClCC=O.C([O-])(O)=O.[Na+]>P([O-])([O-])([O-])=O.CCO.CCOC(C)=O>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[N:12]=[C:11]([C:13]3[CH:14]=[N:15][N:16]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:23])([CH3:25])[CH3:24])[CH:17]=3)[N:10]3[CH:27]=[CH:28][N:26]=[C:9]3[CH:8]=2)[CH:4]=[N:3]1

Participants

8

Reactant 4

HCID 33Chloroacetaldehyde2×HCID 516892Sodium BicarbonateHCID 517045Sodium AcetateHCID 674585736-(1-methyl-1H-pyrazol-4-yl)-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)pyrimidin-4-amine

Product 1

HCID 674576157-(1-Methyl-1H-pyrazol-4-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidineYield 41.2%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 1061PhosphateSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

6-(1-methyl-1H-pyrazol-4-yl)-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)pyrimidin-4-amine (2.0 g, 5.4 mmol) was suspended in a mixture of 40 mL of pH 7 phosphate buffer and 16 mL of EtOH. To the milky white mixture was added NaOAc (0.79 g, 9.7 mmol) followed by 2-chloroacetaldehyde (1.0 mL, 8.1 mmol). The reaction mixture was then heated to 95° C. After 5 hours, the reaction was incomplete and another portion of 2-chloroacetaldehyde (0.10 mL, 0.81 mmol) was added and stirred for another 1 hour. After cooling, the reaction mixture was diluted in EtOAc and saturated NaHCO3. After separation, the organic layer was washed with brine, dried with MgSO4, filtered and concentrated in vacuo. The residue was diluted in diethyl ether, sonicated, and filtered to afford 0.88 g of 7-(1-methyl-1H-pyrazol-4-yl)-5-(1-((2-(trimethylsilyl)ethoxy)-methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine as an off-white solid. Additional product was obtained by concentration of the filtrate and purification by silica chromatography using 0-10% MeOH/EtOAc. This afforded another 0.80 g of the intermediate. MS (apci) m/z=396.2 (M+H).

Workup

  1. temperatureAfter cooling
  2. customAfter separation
  3. washthe organic layer was washed with brine
  4. dry with materialdried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. additionThe residue was diluted in diethyl ether
  8. customsonicated
  9. filtrationfiltered

Sources & evidence

ORD record
ord-faad69cbac0d4b9db54e7e03b25d1a94
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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