p-Toluenesulfonic acid → N2-(4-bromo-2,5-dimethylphenyl)-5-chloro-N4-(5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

HRID 2093802Notes

Reaction equation

HRID 2093802 reaction equation
[Br:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([NH:9][C:10]2[N:15]=[C:14]([NH:16][C:17]3[CH:21]=[C:20]([CH3:22])[NH:19][N:18]=3)[C:13]([Cl:23])=[CH:12][N:11]=2)=[C:4]([CH3:24])[CH:3]=1.CC1C=CC(S(O)(=O)=O)=CC=1.[O:36]1[CH:41]=[CH:40][CH2:39][CH2:38][CH2:37]1.C([O-])(O)=O.[Na+]>C1COCC1>[Br:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([NH:9][C:10]2[N:15]=[C:14]([NH:16][C:17]3[CH:21]=[C:20]([CH3:22])[N:19]([CH:37]4[CH2:38][CH2:39][CH2:40][CH2:41][O:36]4)[N:18]=3)[C:13]([Cl:23])=[CH:12][N:11]=2)=[C:4]([CH3:24])[CH:3]=1

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 80803,4-dihydro-2H-pyranHCID 516892Sodium BicarbonateHCID 86653324N2-(4-bromo-2,5-dimethylphenyl)-5-chloro-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

Product 1

HCID 86653323N2-(4-bromo-2,5-dimethylphenyl)-5-chloro-N4-(5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N2-(4-bromo-2,5-dimethylphenyl)-5-chloro-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (280 mg, 0.69 mmol) in THF (3 mL) was added p-TSA (119 mg, 0.69 mmol) and 3,4-dihydro-2H-pyran (348 mg, 2.86 mmol). The mixture was stirred at room temperature for 14 h and then poured into saturated aqueous NaHCO3 solution (10 mL). The resulting mixture was extracted with EtOAc (3×10 mL) and the combined organic layers were concentrated. The resulting residue was purified by flash column chromatography (silica gel, 0-50% EtOAc in hexanes gradient) to provide N2-(4-bromo-2,5-dimethylphenyl)-5-chloro-N4-(5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)pyrimidine-2,4-diamine as a white solid; ESMS m/z 491.1 (M+H+).

Workup

  1. extractionThe resulting mixture was extracted with EtOAc (3×10 mL)
  2. concentrationthe combined organic layers were concentrated
  3. customThe resulting residue was purified by flash column chromatography (silica gel, 0-50% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-2b182d0892be4d98a1e17edeb8552048
Source dataset
uspto-grants-2013_05
Patent number
US08445505B2

Reaction notes

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