Acetaldehyde → 6-{6-[2-(1-ethylpiperidin-4-yl)ethoxy]-5-(trifluoromethyl)pyridin-3-yl}-9-methyl-9H-purine-2-carbonitrile

HRID 522303Notes

Reaction equation

HRID 522303 reaction equation
Cl.[CH3:2][N:3]1[CH:11]=[N:10][C:9]2[C:4]1=[N:5][C:6]([C:31]#[N:32])=[N:7][C:8]=2[C:12]1[CH:13]=[N:14][C:15]([O:22][CH2:23][CH2:24][CH:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:17]=1.[C:33](O[BH-](OC(=O)C)OC(=O)C)(=O)[CH3:34].[Na+].C(=O)C.C([O-])(O)=O.[Na+]>ClC(Cl)C.C(Cl)(Cl)Cl.C(O)(=O)C.C(N(CC)CC)C>[CH2:33]([N:28]1[CH2:29][CH2:30][CH:25]([CH2:24][CH2:23][O:22][C:15]2[N:14]=[CH:13][C:12]([C:8]3[N:7]=[C:6]([C:31]#[N:32])[N:5]=[C:4]4[C:9]=3[N:10]=[CH:11][N:3]4[CH3:2])=[CH:17][C:16]=2[C:18]([F:21])([F:19])[F:20])[CH2:26][CH2:27]1)[CH3:34]

Participants

9

Reactant 4

HCID 177AcetaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 1178996109-methyl-6-{6-[2-(piperidin-4-yl)ethoxy]-5-(trifluoromethyl)pyridin-3-yl}-9H-purine-2-carbonitrile monohydrochloride

Product 1

HCID 717616296-{6-[2-(1-ethylpiperidin-4-yl)ethoxy]-5-(trifluoromethyl)pyridin-3-yl}-9-methyl-9H-purine-2-carbonitrileYield 61.1%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 6212ChloroformSolventHCID 63651,1-DichloroethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

Triethylamine (2.7 mL) was added to a suspension of 9-methyl-6-{6-[2-(piperidin-4-yl)ethoxy]-5-(trifluoromethyl)pyridin-3-yl}-9H-purine-2-carbonitrile monohydrochloride (3.0 g) in dichloroethane (60 mL) at room temperature, and the mixture was stirred at the same temperature for 20 minutes. After the reaction mixture was ice-cooled, acetic acid (1.8 mL), sodium triacetoxyborohydride (2.7 g) were added thereto, and a solution of acetaldehyde (1.1 mL) in dichloroethane (5 mL) was added thereto. The mixture was stirred for 1 hour under ice-cooling. After a saturated aqueous NaHCO3 solution was added to the reaction mixture, extraction thereof was performed using CHCl3, and the extract was washed with saturated brine. The organic layer was dried over Na2SO4 and filtered, and the filtrate was concentrated under reduced pressure. The residue was suspended in EtOH (80 mL), and the suspension was dissolved by stirring for 30 minutes while heating to reflux. The mixture was cooled to room temperature, and the precipitate was collected by filtration, whereby 6-{6-[2-(1-ethylpiperidin-4-yl)ethoxy]-5-(trifluoromethyl)pyridin-3-yl}-9-methyl-9H-purine-2-carbonitrile (1.8 g) was obtained as a crystal (heat absorption peak temperature obtained by a TG/DTA analysis: near 191° C.).

Workup

  1. temperaturecooled
  2. stirringThe mixture was stirred for 1 hour under ice-
  3. temperaturecooling
  4. washthe extract was washed with saturated brine
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. dissolutionthe suspension was dissolved
  9. stirringby stirring for 30 minutes
  10. temperaturewhile heating to reflux
  11. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-40e682a8485a413f93e5d28d7f3afd1e
Source dataset
uspto-grants-2016_05
Patent number
US09328118B2

Reaction notes

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