2,2,2-trifluoro-N,N-bis(trimethylsilyl)acetamide

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The sub-title compound was prepared from 5-iodo-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-1H-pyrrolo[3,4 -d]pyrimidine-2,4(3H,6H)-dione, and 4-pentynoic acid in the presence of bistrimethylsilyltrifluoroacetamide in a manner analogous to the method of Example 13 above.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of [1-allyl-4-amino-4-(4-bromo-2-thienyl)pyrrolidin-3-yl]methanol 4 g, 12.6 mmol) in tetrahydrofuran (180 mL) is added bis(trimethylsilyl)trifluoroacetamide (3.2 g, 12.6 mmol) and the reaction is stirred at room temperature for 1 hr. Benzoyl isothiocyanate (2.5 g, 15.1 mmol) is added in one portion, stirred for 1 hour at room temperature, and then quenched with 1 N hydrochloric acid (20 mL). After stirring for 1 hour the pH of the reaction is adjusted to >8 using saturated sodium bicarbonate and extracted with dichloromethane. The organic phases are combined, concentrated under reduced pressure, and triturated with hexane/ethyl acetate (4:1) to give the title compound (5.9 g, >95%). ES/MS (m/e) (79Br/81Br) 480/482 (M+H). stirred for 1 hour at room temperature quenched with 1 N hydrochloric acid (20 mL) After stirring for 1 hour the pH of the reaction extracted with dichloromethane concentrated under reduced pressure triturated with hexane/ethyl acetate (4:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a slurry of the product of step (vii) (1.42 g) in dry 1,2-dichloroethane (15 ml) was added bis(trimethylsilyl)trifluoroacetamide (3.4 ml). The mixture was heated at reflux for 2 hours until the mixture became a homogeneous solution. The solution was allowed to cool to room temperature and a solution of 5-[bromomethyl]-2-furancarboxylic acid ethyl ester (J. Chem. Soc. Perkin Trans. 1, 1981, 1125, Bull. Chem. Soc. Jpn., 1987, 60, 1807) (1.1 g) in dry acetonitrile (15 ml) was added. The solution was then heated at reflux for 14 hours. The reaction mixture was allowed to cool and methanol (15 ml) was added. The solvents were evaporated under reduced pressure and the residue was triturated with diethyl ether. The resultant solid was collected by filtration and partitioned between saturated aqueous sodium bicarbonate and ethyl acetate. The organic phase was dried (MgSO4) and the solvent was evaporated under reduced pressure. Purification was by chromatography eluting with ethyl acetate. The mixture was heated at reflux for 2 hours until the mixture The solution was then heated at reflux for 14 hours to cool The solvents were evaporated under reduced pressure the residue was triturated with diethyl ether The resultant solid was collected by filtration partitioned between saturated aqueous sodium bicarbonate and ethyl acetate The organic phase was dried (MgSO4) the solvent was evaporated under reduced pressure Purification eluting with ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The sub-title compound was prepared from 5-iodo-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione, and 4-pentynoic acid in the presence of bistrimethylsilyltrifluoroacetamide in a manner analogous to the method of Example 13 above.

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The sub-title compound was prepared from 5-iodo-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione, and 4-pentynoic acid in the presence of bistrimethylsilyltrifluoroacetamide in a manner analogous to the method of Example 13 above.