p-Toluenesulfonic acid monohydrate → 1-[2-(4-Chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine-4-yl]piperidine-4-one hydrochloride

HRID 225481Notes

Reaction equation

HRID 225481 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9]2[N:10]=[C:11]([N:18]3[CH2:27][CH2:26][C:21]4(OCC[O:22]4)[CH2:20][CH2:19]3)[C:12]3[S:17][CH:16]=[CH:15][C:13]=3[N:14]=2)=[C:4]([F:28])[CH:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(#N)C.CC(C)=O>O>[ClH:1].[Cl:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9]2[N:10]=[C:11]([N:18]3[CH2:19][CH2:20][C:21](=[O:22])[CH2:26][CH2:27]3)[C:12]3[S:17][CH:16]=[CH:15][C:13]=3[N:14]=2)=[C:4]([F:28])[CH:3]=1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 21918305Acetone acetonitrileHCID 690793598-[2-(4-Chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine-4-yl]-1,4-dioxa-8-azaspiro[4,5]decane

Product 1

HCID 690722011-[2-(4-Chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine-4-yl]piperidine-4-one hydrochlorideYield 140%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 451 mg of 8-[2-(4-chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine-4-yl]-1,4-dioxa-8-azaspiro[4.5]decane, 20 mg of p-toluenesulfonic acid monohydrate and 8 ml of acetonitrile-acetone (1:1) was stirred for 5 hours heated to reflux. The reaction mixture was allowed to cool to room temperature and was added to 200 ml of water. After the precipitate was filtered and washed with water, it was dried at 50° C. under reduced pressure. The obtained solid was dissolved in 12 ml of THF and added 2 ml of 4M HCl-dioxane solution. The resultant was concentrated under reduced pressure to give a solid. This solid washed with acetonitrile-ether to give 310 mg of 1-[2-(4-chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine-4-yl]piperidine-4-one hydrochloride.

Workup

  1. temperatureheated to reflux
  2. filtrationAfter the precipitate was filtered
  3. washwashed with water, it
  4. customwas dried at 50° C. under reduced pressure
  5. dissolutionThe obtained solid was dissolved in 12 ml of THF
  6. additionadded 2 ml of 4M HCl-dioxane solution
  7. concentrationThe resultant was concentrated under reduced pressure
  8. customto give a solid
  9. washThis solid washed with acetonitrile-ether

Sources & evidence

ORD record
ord-7179fcf09f8b431782a8651293ae7372
Source dataset
uspto-grants-2009_07
Patent number
US07557112B2

Reaction notes

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