N-methyl-2-pyrrolidone → HCID 178478942, compound

HRID 225491Notes

Reaction equation

HRID 225491 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[CH2:23][CH2:22][CH:21]([CH2:24][C:25]#[N:26])[CH2:20][CH2:19]3)[C:12]3[S:17][CH:16]=[CH:15][C:13]=3[N:14]=2)=[C:4]([F:27])[CH:3]=1.CN1CCCC1=O.[N-:35]=[N+:36]=[N-:37].[Na+].Cl.O1CCOCC1>C1COCC1.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[CH2:23][CH2:22][CH:21]([CH2:24][C:25]4[NH:37][N:36]=[N:35][N:26]=4)[CH2:20][CH2:19]3)[C:12]3[S:17][CH:16]=[CH:15][C:13]=3[N:14]=2)=[C:4]([F:27])[CH:3]=1

Participants

7

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 33557Sodium AzideHCID 204431481,4-Dioxane hydrochlorideHCID 66673743HCID 66673743, compound

Product 1

HCID 178478942HCID 178478942, compoundYield 175.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 825 mg of {1-[2-(4-chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine-4-yl]piperidine-4-yl}acetonitrile, 15 ml of N-methylpyrrolidinone, 1.32 g of sodium azide and 2.81 g of triethylamide hydrochloride was stirred for 8 hours at 150° C. After the reaction mixture was allowed to cool to room temperature, 50 ml of water was added and the resultant was extracted with EtOAc. After the organic layer washed with a saturated saline solution and dried over anhydrous magnesium sulfate, the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform-MeOH) to give an oily substance. After the obtained oily substance was dissolved in 10 ml of THF and 4 ml of 4M HCl-dioxane solution was added, the resultant was concentrated under reduced pressure to give a solid. The obtained solid was recrystallized from iPrOH-EtOAc-ether to give 868 mg of 2-(4-chloro-2,5-difluorophenyl)-4-[4-(1H-tetrazole-5-ylmethyl)piperidine-1-yl]thieno[3,2-d]pyrimidine hydrochloride.

Workup

  1. temperatureto cool to room temperature
  2. extractionthe resultant was extracted with EtOAc
  3. washAfter the organic layer washed with a saturated saline solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was removed under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (chloroform-MeOH)
  7. customto give an oily substance
  8. concentrationthe resultant was concentrated under reduced pressure
  9. customto give a solid
  10. customThe obtained solid was recrystallized from iPrOH-EtOAc-ether

Sources & evidence

ORD record
ord-31ba183a33d14c75b48c09ba53c9cbac
Source dataset
uspto-grants-2009_07
Patent number
US07557112B2

Reaction notes

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