Ethyl Acetate → 6-[(1-naphthylmethyl)amino]-9H-purine-2-carbonitrile

HRID 897095Notes

Reaction equation

HRID 897095 reaction equation
ClC1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2C2CCCCO2)=[C:4]([NH:17][CH2:18][C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=[CH:21][CH:20]=2)[N:3]=1.C([N:31](C(C)C)C(C)C)C.C(O[CH2:42][CH3:43])(=O)C>[C-]#N.[Zn+2].[C-]#N>[C:19]1([CH2:18][NH:17][C:4]2[N:3]=[C:43]([C:42]#[N:31])[N:10]=[C:9]3[C:5]=2[N:6]=[CH:7][NH:8]3)[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 208168032-Chloro-N-(1-naphthylmethyl)-9-tetrahydro-2H-pyran-2-yl-9H-purin-6-amine

Product 1

HCID 1785105996-[(1-naphthylmethyl)amino]-9H-purine-2-carbonitrile

Reagents, catalysts & solvents 1

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst

Conditions

Temperature
100 °C

Procedure

Tetrakistriphenylphosphine palladium (1.1 g, 0.95 mmol) was added to a solution of 2-chloro-N-(1-naphthylmethyl)-9-tetrahydro-2H-pyran-2-yl-9H-purin-6-amine (7.5 g, 19 mmol) (Preparation 9) , zinc cyanide (1.4 g, 11.9 mmol) and N-ethyl-N-isopropyl-2-propanamine (4 ml, 23 mmol) in N′N′-dimethylformamide (80 ml). The reaction mixture was heated to 100° C. for 16 hours. The reaction mixture was allowed to cool to room temperature and ethyl acetate (250 ml) was added. The resulting mixture was extracted with aqueous sodium hydroxide solution (2M, 100 ml). The sodium hydroxide layer was extracted with more ethyl acetate (50 ml). The ethyl acetate layers were combined and washed with water (50 ml) and then dried over anhydrous magnesium sulphate. The solvent was removed under reduced pressure, the residue was dissolved in dichloromethane (100 ml) and the solvent was removed under reduced pressure again. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol (99:2 by volume) increasing in polarity to dichloromethane:methanol (90:10 by volume). The solvent was removed under reduced pressure to give the title compound (1.8 g) as a foam. The major product of this reaction was actually 6-[(1-naphthylmethyl)amino]-9-tetrahydro-2H-pyran-2-yl-9H-purine-2-carbonitrile (2.7 g).

Workup

  1. temperatureto cool to room temperature
  2. extractionThe resulting mixture was extracted with aqueous sodium hydroxide solution (2M, 100 ml)
  3. extractionThe sodium hydroxide layer was extracted with more ethyl acetate (50 ml)
  4. washwashed with water (50 ml)
  5. dry with materialdried over anhydrous magnesium sulphate
  6. customThe solvent was removed under reduced pressure
  7. dissolutionthe residue was dissolved in dichloromethane (100 ml)
  8. customthe solvent was removed under reduced pressure again
  9. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol (99:2 by volume)
  10. temperatureincreasing in polarity to dichloromethane:methanol (90:10 by volume)
  11. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-32b964cf06ec4e4eb84fc957f19eef6e
Source dataset
uspto-grants-2005_07
Patent number
US06921753B2

Reaction notes

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