Tetrahydrofuran → 6-[(2,2-diphenylethyl)amino]-9-(tetrahydro-2H-pyran-2-yl) 9H-purine-2-carboxylic acid

HRID 2184278Notes

Reaction equation

HRID 2184278 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.[OH-:32].[Na+].[O:34]1[CH2:38]CCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[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:38]([OH:34])=[O:32])[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

6

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 101813352-Chloro-N-(2,2-diphenylethyl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

Product 1

HCID 224759666-[(2,2-diphenylethyl)amino]-9-(tetrahydro-2H-pyran-2-yl) 9H-purine-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst

Conditions

Temperature
140 °C

Procedure

A mixture of 2-chloro-N-(2,2-diphenylethyl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (0.87 g, 2 mmol) (Preparation 9), palladium (II) acetate (0.002 g. 0.009 mmol), 1,1′-bis(diphenylphosphino)ferrocene (0.033 g, 0.06 mmol), 10 M aqueous sodium hydroxide solution (0.6 ml, 6 mmol) and tetrahydrofuran (4 ml) was heated at 140° C. under an atmosphere of carbon monoxide at 1725 kPa (250 psi) for 12 hours. The mixture was allowed to cool and to stand at ambient temperature for 16 days during which time a suspension formed. The solid was collected by filtration and washed with tetrahydrofuran (10 ml). This material was added to a mixture of dichloromethane (35 ml) and water (25 ml) and the pH of the mixture was adjusted to 1 by the addition of dilute aqueous hydrochloric acid solution with stirring. The layers were separated and the aqueous phase was extracted with dichloromethane (25 ml). The combined organic phases were dried (MgSO4) and the solvent was removed under reduced pressure to give a the title compound as an amber foam (0.45 g) that was identical by 1H-NMR, high performance liquid chromatography, mass spectrometry and thin-layer chromatography to the compound prepared in Preparation 21.

Workup

  1. temperatureto cool
  2. customa suspension formed
  3. filtrationThe solid was collected by filtration
  4. washwashed with tetrahydrofuran (10 ml)
  5. additionThis material was added to a mixture of dichloromethane (35 ml) and water (25 ml)
  6. additionthe pH of the mixture was adjusted to 1 by the addition of dilute aqueous hydrochloric acid solution
  7. customThe layers were separated
  8. extractionthe aqueous phase was extracted with dichloromethane (25 ml)
  9. dry with materialThe combined organic phases were dried (MgSO4)
  10. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-63fc6cc7e3d844dd83fd3f6b93c8389c
Source dataset
uspto-grants-2005_05
Patent number
US06900309B1

Reaction notes

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