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

HRID 522306Notes

Reaction equation

HRID 522306 reaction equation
N1(CO)C2C=CC=C[C:4]=2N=N1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl.[CH3:27][N:28]1[CH:36]=[N:35][C:34]2[C:29]1=[N:30][C:31]([C:56]#[N:57])=[N:32][C:33]=2[C:37]1[CH:38]=[N:39][C:40]([O:47][CH2:48][CH2:49][CH:50]2[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]2)=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:42]=1.C([O-])(O)=O.[Na+]>C1COCC1.CCOC(C)=O.CCO.C(N(CC)CC)C>[CH3:27][N:28]1[CH:36]=[N:35][C:34]2[C:29]1=[N:30][C:31]([C:56]#[N:57])=[N:32][C:33]=2[C:37]1[CH:38]=[N:39][C:40]([O:47][CH2:48][CH2:49][CH:50]2[CH2:55][CH2:54][N:53]([CH3:4])[CH2:52][CH2:51]2)=[C:41]([C:43]([F:46])([F:44])[F:45])[CH:42]=1

Participants

9

Reactant 4

HCID 2241691H-Benzotriazole-1-methanolHCID 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 1178995429-methyl-6-{6-[2-(1-methylpiperidin-4-yl)ethoxy]-5-(trifluoromethyl)pyridin-3-yl}-9H-purine-2-carbonitrileYield 59.9%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Triethylamine (30 μL), 1H-benzotriazole-1-methanol (48 mg), and sodium triacetoxyborohydride (91 mg) were added to a solution of 9-methyl-6-{6-[2-(piperidin-4-yl)ethoxy]-5-(trifluoromethyl)pyridin-3-yl}-9H-purine-2-carbonitrile monohydrochloride (100 mg) in THF (1.5 mL)-EtOH (1.5 mL), and the mixture was stirred at room temperature for 16 hours. After a saturated aqueous NaHCO3 solution and EtOAc were added to the reaction mixture, extraction thereof was performed using EtOAc, and the extract was washed with saturated brine. The organic layer was dried over MgSO4 and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (CHCl3:MeOH=100:0 to 80:20), whereby 9-methyl-6-{6-[2-(1-methylpiperidin-4-yl)ethoxy]-5-(trifluoromethyl)pyridin-3-yl}-9H-purine-2-carbonitrile (57 mg) was obtained as a solid.

Workup

  1. washthe extract was washed with saturated brine
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (CHCl3:MeOH=100:0 to 80:20)

Sources & evidence

ORD record
ord-cd272b1aa9cf434094edbe3dda900169
Source dataset
uspto-grants-2016_05
Patent number
US09328118B2

Reaction notes

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