Acetonitrile → 9-methyl-6-{6-[2-(piperidin-4-yl)ethoxy]-5-(trifluoromethyl)pyridin-3-yl}-9H-purine-2-carbonitrile monohydrochloride

HRID 522302Notes

Reaction equation

HRID 522302 reaction equation
FC(F)(F)C(O)=O.[C:8]([C:10]1[N:18]=[C:17]2[C:13]([N:14]=[CH:15][N:16]2[CH3:19])=[C:12]([C:20]2[CH:21]=[C:22]([C:42]([F:45])([F:44])[F:43])[C:23]([O:26][CH2:27][CH2:28][CH:29]3[CH2:34][CH2:33][N:32](C(OC(C)(C)C)=O)[CH2:31][CH2:30]3)=[N:24][CH:25]=2)[N:11]=1)#[N:9].C(#N)C.C(Cl)[Cl:50]>>[ClH:50].[CH3:19][N:16]1[CH:15]=[N:14][C:13]2[C:17]1=[N:18][C:10]([C:8]#[N:9])=[N:11][C:12]=2[C:20]1[CH:25]=[N:24][C:23]([O:26][CH2:27][CH2:28][CH:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)=[C:22]([C:42]([F:45])([F:43])[F:44])[CH:21]=1

Participants

5

Reactant 4

HCID 6342AcetonitrileHCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 117899570tert-butyl 4-(2-{[5-(2-cyano-9-methyl-9H-purin-6-yl)-3-(trifluoromethyl)pyridin-2-yl]oxy}ethyl)piperidine-1-carboxylate

Product 1

HCID 1178996109-methyl-6-{6-[2-(piperidin-4-yl)ethoxy]-5-(trifluoromethyl)pyridin-3-yl}-9H-purine-2-carbonitrile monohydrochloride

Procedure

Trifluoroacetic acid (40 mL) was added to a solution of tert-butyl 4-(2-{[5-(2-cyano-9-methyl-9H-purin-6-yl)-3-(trifluoromethyl)pyridin-2-yl]oxy}ethyl)piperidine-1-carboxylate (5.8 g) in CH2Cl2 (80 mL)-acetonitrile (20 mL) at room temperature, and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and CH2Cl2 (10 mL) was added to the residue. A 4 M solution of hydrogen chloride in EtOAc (10 mL) was added to the mixture at room temperature, and the resultant mixture was stirred at the same temperature for 10 minutes. EtOAc (5 mL) and disiopropyl ether (150 mL) were added to the reaction mixture at room temperature, and the resultant mixture was stirred for 30 minutes. The precipitate was collected by filtration, whereby 9-methyl-6-{6-[2-(piperidin-4-yl)ethoxy]-5-(trifluoromethyl)pyridin-3-yl}-9H-purine-2-carbonitrile monohydrochloride (5.1 g) was obtained as a solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, and CH2Cl2 (10 mL)
  2. additionwas added to the residue
  3. additionA 4 M solution of hydrogen chloride in EtOAc (10 mL) was added to the mixture at room temperature
  4. stirringthe resultant mixture was stirred at the same temperature for 10 minutes
  5. additionEtOAc (5 mL) and disiopropyl ether (150 mL) were added to the reaction mixture at room temperature
  6. stirringthe resultant mixture was stirred for 30 minutes
  7. filtrationThe precipitate was collected by filtration

Sources & evidence

ORD record
ord-e60dbfbb925e43a79cc4873832530ade
Source dataset
uspto-grants-2016_05
Patent number
US09328118B2

Reaction notes

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