Cesium carbonate → 5-chloro-N2-(2,5-dimethyl-4-(1-(tetrahydro-2H-thiopyran-4-yl)piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

HRID 536366Notes

Reaction equation

HRID 536366 reaction equation
[Cl:1][C:2]1[C:3]([NH:23][C:24]2[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[CH:11][C:10]=2[CH3:22])=[N:6][CH:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].I[CH:37]1[CH2:42][CH2:41][S:40][CH2:39][CH2:38]1.[NH4+].[Cl-]>C(#N)C>[Cl:1][C:2]1[C:3]([NH:23][C:24]2[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([CH:16]3[CH2:21][CH2:20][N:19]([CH:37]4[CH2:42][CH2:41][S:40][CH2:39][CH2:38]4)[CH2:18][CH2:17]3)=[CH:11][C:10]=2[CH3:22])=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 185259114-IodothianeHCID 582549005-chloro-N-(2,5-dimethyl-4-(piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

Product 1

HCID 446111005-chloro-N2-(2,5-dimethyl-4-(1-(tetrahydro-2H-thiopyran-4-yl)piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-chloro-N2-(2,5-dimethyl-4-(piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (30 mg, 0.073 mmol) in acetonitrile (1 mL) was added Cs2CO3 (47 mg, 0.15 mmol) and 4-iodotetrahydro-2H-thiopyran (48 mg, 0.22 mmol). This mixture was then stirred at 80° C. for 16 hr. After cooling down to room temperature, the mixture was treated with saturated aqueous NH4Cl solution (3 mL) and extracted with EtOAc (3×3 mL). The organic layers were combined and concentrated. The residue was purified by silica gel chromatography (Gradient 0˜8% MeOH/CH2Cl2 with NH3) to provide 5-chloro-N2-(2,5-dimethyl-4-(1-(tetrahydro-2H-thiopyran-4-yl)piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine as a white solid. ESMS m/z 512.2 (M+H+).

Workup

  1. temperatureAfter cooling down to room temperature
  2. extractionextracted with EtOAc (3×3 mL)
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel chromatography (Gradient 0˜8% MeOH/CH2Cl2 with NH3)

Sources & evidence

ORD record
ord-338c3a76b2e54aacb0611f76936c8ef4
Source dataset
uspto-grants-2014_10
Patent number
US08859574B2

Reaction notes

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