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Cesium carbonate → 4-Chloro-6-[4-(2-trifluoromethyl-phenyl)-piperidin-1-yl]-pyrimidin-2-ylamine

HRID 469869
Notes
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Reaction equation

HRID 469869 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[C:4](Cl)[N:3]=1.Cl.[F:11][C:12]([F:26])([F:25])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O>[Cl:8][C:6]1[CH:5]=[C:4]([N:22]2[CH2:23][CH2:24][CH:19]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[C:12]([F:11])([F:25])[F:26])[CH2:20][CH2:21]2)[N:3]=[C:2]([NH2:1])[N:7]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 655222-Amino-4,6-dichloropyrimidineHCID 219369704-[2-(Trifluoromethyl)phenyl]piperidine hydrochloride

Product 1

HCID 866143044-Chloro-6-[4-(2-trifluoromethyl-phenyl)-piperidin-1-yl]-pyrimidin-2-ylamineYield 117.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent
HCID 312751,4-DioxaneSolvent

Conditions

Temperature
210 °C

Procedure

2-Amino 4,6-dichloro pyrimidine (0.164 g, 1 mmol), 4-(2-trifluoromethyl-phenyl)-piperidine hydrochloride (0.266 g, 1 mmol), and cesium carbonate (0.684 g, 2.1 mmol) were dissolved in a mixture of 1,4-dioxane (5 ml) and H2O (5 ml) in a 20 ml microwave vial. The mixture was stirred at 210° C. for 20 minutes in a microwave reactor. Solvent was removed and the residue was dissolved in 5% methanol in CH2Cl2 (20 ml), dried over Na2SO4 and concentrated to get the crude intermediate, 4-chloro-6-[4-(2-trifluoromethyl-phenyl)-piperidin-1-yl]-pyrimidin-2-ylamine (0.42 g) which was directly used in the following step.

Workup

  1. customSolvent was removed
  2. dissolutionthe residue was dissolved in 5% methanol in CH2Cl2 (20 ml)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-21556f874ea947f8938d161b6d50f959
Source dataset
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08629156B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes