Triethylamine → 6-((2,2-Diphenylethyl)amino)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine-2-carbonitrile

HRID 2184268Notes

Reaction equation

HRID 2184268 reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[C:4]([NH:17][CH2:18][CH:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:3]=1.[CH2:32]([N:34](CC)CC)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CN(C)C=O>[C:20]1([CH:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:18][NH:17][C:4]2[N:3]=[C:2]([C:32]#[N:34])[N:10]=[C:9]3[C:5]=2[N:6]=[CH:7][N:8]3[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

7

Reactant 2

HCID 8471TriethylamineHCID 101813352-Chloro-N-(2,2-diphenylethyl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

Product 1

HCID 101593916-((2,2-Diphenylethyl)amino)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine-2-carbonitrileYield 40.8%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 15220664Palladium--triphenylphosphane (1/1)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 2-chloro-N-(2,2-diphenylethyl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (Preparation 9) (1.0 g. 2.31 mmol), zinc cyanide (0.162 g, 1.38 mmol), triethylamine (0.28 g, 2.77 mmol), tetrakis(triphenylphosphine palladium(0) (0.133 g, 0.12 mmol) and N,N-dimethylformamide (3 ml) was heated under a nitrogen atmosphere at 100° C. for 6 hours. The reaction mixture was allowed to cool and partitioned between ethyl acetate (100 ml) and 2 M aqueous sodium hydroxide solution (100 ml). The organic layer was separated, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The resulting 1:1 mixture of 6-[(2,2-diphenylethyl)amino]-9-(tetrahydro-2H-pyran-2-yl)-9H-purine-2-carbonitrile and 6-[(2,2-diphenylethyl)amino]-9H-purine-2-carbonitrile (e.g. see Preparation 15) was separated by column chromatography on silica gel eluting with a gradient system of ethyl acetate:hexane (40:60, by volume) gradually changing to ethyl acetate:hexane (60:40, by volume) to give the title compound as a white solid (0.4 g).

Workup

  1. temperatureto cool
  2. custompartitioned between ethyl acetate (100 ml) and 2 M aqueous sodium hydroxide solution (100 ml)
  3. customThe organic layer was separated
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customevaporated under reduced pressure
  6. additionThe resulting 1:1 mixture of 6-[(2,2-diphenylethyl)amino]-9-(tetrahydro-2H-pyran-2-yl)-9H-purine-2-carbonitrile and 6-[(2,2-diphenylethyl)amino]-9H-purine-2-carbonitrile (e.g. see Preparation 15)
  7. customwas separated by column chromatography on silica gel eluting with a gradient system of ethyl acetate:hexane (40:60, by volume)

Sources & evidence

ORD record
ord-207de1150037494091374de954f5dc54
Source dataset
uspto-grants-2005_05
Patent number
US06900309B1

Reaction notes

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