Dimethylformamide → 4-(2-chloropyridin-3-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine

HRID 446291Notes

Reaction equation

HRID 446291 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([NH2:14])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O.[Cl:26][C:27]1[C:32]([C:33]2[CH:38]=[CH:37][N:36]=[C:35](S(C)(=O)=O)[N:34]=2)=[CH:31][CH:30]=[CH:29][N:28]=1>O>[Cl:26][C:27]1[C:32]([C:33]2[CH:38]=[CH:37][N:36]=[C:35]([NH:14][C:11]3[CH:12]=[CH:13][C:8]([N:5]4[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]4)=[CH:9][CH:10]=3)[N:34]=2)=[CH:31][CH:30]=[CH:29][N:28]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 7372534-(4-Methylpiperazin-1-yl)anilineHCID 866025914-(2-Chloropyridin-3-yl)-2-(methylsulfonyl)pyrimidine

Product 1

HCID 585881954-(2-chloropyridin-3-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

In a 48 mL sealed pressure vessel, was added 4-(4-methylpiperazin-1-yl)benzenamine (0.851 g, 4.45 mmol), potassium carbonate (1.03 g, 7.42 mmol), N,N-dimethylformamide (10 mL) and 4-(2-chloropyridin-3-yl)-2-(methylsulfonyl)pyrimidine (Step 1, 1.0 g). the vessel was heated to 70° C. for 22 hours, cooled to room temperature, diluted with water, extracted into ethyl acetate, washed 1× with water and 1× with NaCl solution. The organics were dried over magnesium sulfate, filtered through fritted Buchner funnel, and concentrated. The crude was chromatographed on silica gel using 15-60% 90:10:1 (CH2Cl2:MeOH:NH4OH/CH2Cl2) as a gradient. Concentrated the product fractions to yield 4-(2-chloropyridin-3-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine as a brown solid. MS (M+H)+=381. Calc'd 380.87 for C20H21ClN6.

Workup

  1. customIn a 48 mL sealed pressure vessel
  2. temperaturecooled to room temperature
  3. extractionextracted into ethyl acetate
  4. washwashed 1× with water and 1× with NaCl solution
  5. dry with materialThe organics were dried over magnesium sulfate
  6. filtrationfiltered through fritted Buchner funnel
  7. concentrationconcentrated
  8. customThe crude was chromatographed on silica gel using 15-60% 90:10:1 (CH2Cl2:MeOH:NH4OH/CH2Cl2) as a gradient
  9. concentrationConcentrated the product fractions

Sources & evidence

ORD record
ord-514303c9b6b04330826dfc19439d6df6
Source dataset
uspto-grants-2013_07
Patent number
US08476434B2

Reaction notes

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