Hydrochloric Acid → 4-(4-(5-chloro-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)-2,5-dimethylphenyl)cyclohexanone

HRID 2093809Notes

Reaction equation

HRID 2093809 reaction equation
[CH3:1][C:2]1[CH:8]=[C:7]([CH:9]2[CH2:18][CH2:17][C:12]3([O:16]CCO3)[CH2:11][CH2:10]2)[C:6]([CH3:19])=[CH:5][C:3]=1[NH2:4].Cl[C:21]1[N:26]=[C:25]([NH:27][C:28]2[CH:32]=[C:31]([CH3:33])[NH:30][N:29]=2)[C:24]([Cl:34])=[CH:23][N:22]=1.Cl>CC(O)C>[Cl:34][C:24]1[C:25]([NH:27][C:28]2[CH:32]=[C:31]([CH3:33])[NH:30][N:29]=2)=[N:26][C:21]([NH:4][C:3]2[C:2]([CH3:1])=[CH:8][C:7]([CH:9]3[CH2:10][CH2:11][C:12](=[O:16])[CH2:17][CH2:18]3)=[C:6]([CH3:19])[CH:5]=2)=[N:22][CH:23]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 114022722,5-Dichloro-N-(5-methyl-1H-pyrazol-3-yl)-4-pyrimidinamineHCID 582571202,5-Dimethyl-4-(1,4-dioxaspiro[4.5]decan-8-yl)aniline

Product 1

HCID 671668434-(4-(5-chloro-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)-2,5-dimethylphenyl)cyclohexanone

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 2,5-dimethyl-4-(1,4-dioxaspiro[4.5]decan-8-yl)aniline (86 mg, 0.33 mmol) and 2,5-dichloro-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine (104 mg, 0.43 mmol) in iPrOH (3 mL) was treated with HCl (82 μL, 4N in dioxane, 0.33 mmol) and heated to 125° C. in a sealed tube for 14 h. After cooling down to room temperature, the mixture was concentrated and was treated with acetone (2 mL) and HCl (330 μL, 4N in dioxane) at room temperature for 5 h. The mixture was then treated with saturated NaHCO3 aqueous solution (10 mL) and extracted with EtOAc (3×10 mL). The organic layers were combined, concentrated and purified by flash column chromatography (silica gel, 0%-100% EtOAc in hexanes gradient) to provide 4-(4-(5-chloro-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)-2,5-dimethylphenyl)cyclohexanone as white solid; ESMS m/z 425.2 (M+H+).

Workup

  1. temperatureAfter cooling down to room temperature
  2. concentrationthe mixture was concentrated
  3. additionwas treated with acetone (2 mL) and HCl (330 μL, 4N in dioxane) at room temperature for 5 h
  4. additionThe mixture was then treated with saturated NaHCO3 aqueous solution (10 mL)
  5. extractionextracted with EtOAc (3×10 mL)
  6. concentrationconcentrated
  7. custompurified by flash column chromatography (silica gel, 0%-100% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-1bef40e7d2bd475e9e5690c6bfd4a298
Source dataset
uspto-grants-2013_05
Patent number
US08445505B2

Reaction notes

Loading…