Sodium Hydroxide → HCID 67366072, compound

HRID 245688Notes

Reaction equation

HRID 245688 reaction equation
[O:1]1[CH2:6][CH2:5][C:4](=O)[CH2:3][CH2:2]1.[NH:8]1[CH2:11][CH:10]([C:12]2[N:16]3[CH:17]=[CH:18][N:19]=[C:20]([CH3:21])[C:15]3=[C:14]([Br:22])[N:13]=2)[CH2:9]1.C([BH3-])#N.[Na+].[OH-].[Na+]>ClCCl.C(O)(=O)C>[Br:22][C:14]1[N:13]=[C:12]([CH:10]2[CH2:9][N:8]([CH:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)[CH2:11]2)[N:16]2[CH:17]=[CH:18][N:19]=[C:20]([CH3:21])[C:15]=12

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 121599Tetrahydro-4H-pyran-4-oneHCID 5003444Sodium cyanoborohydrideHCID 67364087HCID 67364087, compound

Product 1

HCID 67366072HCID 67366072, compoundYield 5.8%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent2×

Procedure

To tetrahydro-4-h-pyran-4-one (3.74 mmol, 0.346 ml) in dichloromethane (5 ml) and acetic acid (0.306 ml) was added 3-(azetidin-3-yl)-1-bromo-8-methylimidazo[1,5-a]pyrazine (1.872 mmol, 500 mg) in dichloromethane (10 ml) and after stirring for 20 minutes under a nitrogen atmosphere at room temperature sodium cyanoborohydride (3.74 mmol, 235 mg) was added in portions. After one hour the reaction mixture was quenched with water, a saturated aqueous sodium hydrogencarbonate solution was added (pH of reaction mixture ˜7) followed by 2M sodium hydroxide until the pH reached 11 and extracted three times with dichloromethane. The organic layers were combined, filtered through a phase separation filter and concentrated in vacuo. Purification by column chromatography (silica gel; dichloromethane with gradient 0 to 10% methanol) gave 1-bromo-8-methyl-3-(1-(tetrahydro-2H-pyran-4-yl)azetidin-3-yl)imidazo[1,5-a]pyrazine (38 mg).

Workup

  1. additionwas added in portions
  2. customAfter one hour the reaction mixture was quenched with water
  3. additiona saturated aqueous sodium hydrogencarbonate solution was added
  4. custom(pH of reaction mixture ˜7)
  5. extractionextracted three times with dichloromethane
  6. filtrationfiltered through a phase separation
  7. filtrationfilter
  8. concentrationconcentrated in vacuo
  9. customPurification by column chromatography (silica gel; dichloromethane with gradient 0 to 10% methanol)

Sources & evidence

ORD record
ord-e4f6d439b2b2497c811c46a1bcd4bea3
Source dataset
uspto-grants-2014_02
Patent number
US08658794B2

Reaction notes

Loading…