Methyl morpholine oxide → (4RS,5SR)-1-[2-(4-chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine-4-yl]azepane-4,5-diol hydrochloride

HRID 225488Notes

Reaction equation

HRID 225488 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9]2[N:10]=[C:11]([N:18]3CCC=C[CH2:20][CH2:19]3)[C:12]3[S:17][CH:16]=[CH:15][C:13]=3[N:14]=2)=[C:4]([F:25])[CH:3]=1.C[N+]1([O-])CC[O:30]CC1.[CH2:34]1[CH2:38][O:37][CH2:36][CH2:35]1.O.Cl.CCOC(C)=O>C1COCC1.[Os](=O)(=O)(=O)=O.C(O)(C)(C)C.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[CH2:38][CH2:34][CH:35]([OH:30])[CH:36]([OH:37])[CH2:20][CH2:19]3)[C:12]3[S:17][CH:16]=[CH:15][C:13]=3[N:14]=2)=[C:4]([F:25])[CH:3]=1

Participants

8

Reactant 4

HCID 82029Methyl morpholine oxideHCID 21866389Hydrogen chloride-ethyl acetateHCID 21881883Oxolane--water (1/1)HCID 690759792-(4-chloro-2,5-difluorophenyl)-4-(2,3,6,7-tetrahydro-1H-azepine-1-yl)thieno[3,2-d]pyrimidine

Product 1

HCID 69079363(4RS,5SR)-1-[2-(4-chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine-4-yl]azepane-4,5-diol hydrochloride

Reagents, catalysts & solvents 3

HCID 87401860HCID 87401860, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 582 mg of 2-(4-chloro-2,5-difluorophenyl)-4-(2,3,6,7-tetrahydro-1H-azepine-1-yl)thieno[3,2-d]pyrimidine, 235 mg of N-methylmorpholine-N-oxide, 1.30 ml of 2.5 w % osmium tetroxide-tert-butanol solution and 10 ml of THF-water (4:1) was stirred for 20 hours at room temperature. After 50 ml of water was added to the reaction mixture and extracted with EtOAc, the resultant washed with a saturated saline solution. After the organic layer was 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 a foam-like substance. After the obtained foam-like substance was dissolved in 20 ml of THF and 2 ml of 4M HCl-EtOAc solution was added, it was concentrated under reduced pressure to give a solid. This solid was recrystallized from EtOH-ether to give 618 mg of (4RS,5SR)-1-[2-(4-chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine-4-yl]azepane-4,5-diol hydrochloride.

Workup

  1. extractionextracted with EtOAc
  2. washthe resultant washed with a saturated saline solution
  3. dry with materialAfter the organic layer was dried over anhydrous magnesium sulfate
  4. customthe solvent was removed under reduced pressure
  5. customthe obtained residue was purified by silica gel column chromatography (chloroform-MeOH)
  6. customto give a foam-like substance
  7. concentrationit was concentrated under reduced pressure
  8. customto give a solid
  9. customThis solid was recrystallized from EtOH-ether

Sources & evidence

ORD record
ord-2fc93ec8becc49c9ad23730716f1cdf3
Source dataset
uspto-grants-2009_07
Patent number
US07557112B2

Reaction notes

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