Methanol → HCID 69071071, compound

HRID 225492Notes

Reaction equation

HRID 225492 reaction equation
[N:1]1([C:8]2[C:9]3[S:25][CH:24]=[CH:23][C:10]=3[N:11]=[C:12]([C:14]3[CH:19]=[C:18]([F:20])[C:17]([Cl:21])=[CH:16][C:15]=3F)[N:13]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C[O-].[Na+].CO.Cl.[O:32]1CCOC[CH2:33]1>C(Cl)(Cl)Cl.CO>[ClH:21].[N:1]1([C:8]2[C:9]3[S:25][CH:24]=[CH:23][C:10]=3[N:11]=[C:12]([C:14]3[CH:19]=[C:18]([F:20])[C:17]([Cl:21])=[CH:16][C:15]=3[O:32][CH3:33])[N:13]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 887MethanolHCID 10942334Sodium MethoxideHCID 204431481,4-Dioxane hydrochlorideHCID 66674077HCID 66674077, compound

Product 1

HCID 69071071HCID 69071071, compound

Reagents, catalysts & solvents 1

HCID 21584188Chloroform methanolSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 514 mg of 4-azepane-1-yl-2-(4-chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine, 300 mg of sodium methoxide and 10 ml of MeOH was stirred in a sealed tube for 5 days at 120° C. After the reaction mixture was concentrated under reduced pressure, 40 ml of water was added to the obtained residue and extracted twice with 40 ml of chloroform. 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 a solid. After 0.6 ml of 4M HCl-dioxane solution was added to 10 ml of chloroform-MeOH with this solid, the resultant was concentrated under reduced pressure to give a solid. After the obtained solid was recrystallized three times from EtOAc and EtOH, the crystal generated was filtered and washed with EtOAc to give 223 mg of 4-azepane-1-yl-2-(4-chloro-5-fluoro-2-methoxyphenyl)thieno[3,2-d]pyrimidine hydrochloride.

Workup

  1. concentrationAfter the reaction mixture was concentrated under reduced pressure, 40 ml of water
  2. additionwas added to the obtained residue
  3. extractionextracted twice with 40 ml of chloroform
  4. washAfter the organic layer washed with a saturated saline solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was removed under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (chloroform-MeOH)
  8. customto give a solid
  9. concentrationthe resultant was concentrated under reduced pressure
  10. customto give a solid
  11. customAfter the obtained solid was recrystallized three times from EtOAc and EtOH
  12. filtrationthe crystal generated was filtered
  13. washwashed with EtOAc

Sources & evidence

ORD record
ord-f483dab19cb1433db165dc699a060af2
Source dataset
uspto-grants-2009_07
Patent number
US07557112B2

Reaction notes

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