Tetrahydrofuran → (S)-3-{4-[2-(4-chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine-4-yl]piperazine-1-yl}propane-1,2-diol dihydrochloride

HRID 225485Notes

Reaction equation

HRID 225485 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][NH:21][CH2:20][CH2:19]3)[C:12]3[S:17][CH:16]=[CH:15][C:13]=3[N:14]=2)=[C:4]([F:24])[CH:3]=1.[CH2:25]1[O:27][C@@H:26]1[CH2:28][OH:29].C1COCC1.[ClH:35].O1CCOCC1>CCO>[ClH:1].[ClH:35].[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][N:21]([CH2:25][C@H:26]([OH:27])[CH2:28][OH:29])[CH2:22][CH2:23]3)[C:12]3[S:17][CH:16]=[CH:15][C:13]=3[N:14]=2)=[C:4]([F:24])[CH:3]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 5460455(+)-GlycidolHCID 204431481,4-Dioxane hydrochlorideHCID 666735982-(4-Chloro-2,5-difluorophenyl)-4-piperazine-1-ylthieno[3,2-d]pyrimidine

Product 1

HCID 69073054(S)-3-{4-[2-(4-chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine-4-yl]piperazine-1-yl}propane-1,2-diol dihydrochloride

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 870 mg of 2-(4-chloro-2,5-difluorophenyl)-4-piperazine-1-ylthieno[3,2-d]pyrimidine, 1.08 ml of (R)-glycidol and 15 ml of THF was stirred for 21 hours heated to reflux. The reaction mixture was concentrated under reduced pressure and the obtained residue was purified by silica gel column chromatography (chloroform-MeOH) to give a foam-like substance. After the obtained foam-like substance was dissolved in 10 ml of EtOH and was added to 2 ml of 4M HCl-dioxane solution, it was concentrated under reduced pressure to give a solid. This solid was recrystallized from ethanol to give 898 mg of (S)-3-{4-[2-(4-chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine-4-yl]piperazine-1-yl}propane-1,2-diol dihydrochloride.

Workup

  1. temperatureheated to reflux
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customthe obtained residue was purified by silica gel column chromatography (chloroform-MeOH)
  4. customto give a foam-like substance
  5. concentrationwas concentrated under reduced pressure
  6. customto give a solid
  7. customThis solid was recrystallized from ethanol

Sources & evidence

ORD record
ord-e12e18643c7d4eb5a0174fae6cc7e81c
Source dataset
uspto-grants-2009_07
Patent number
US07557112B2

Reaction notes

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