2-cyanoacetyl chloride

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:

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 76.6 g (0.455 mol) of 2,4-dimethyl-5-nitroaniline and 64 ml (0.46 mol) triethylamine in 500 ml abs. tetrahydrofurane is added dropwise within 1 h 47.2 g (0.455 mol) cyanoacetyl chloride in 100 ml tetrahydrofurane. After stirring for 2 h at 25° C. and 3 h at 80° C. and cooling to 25° C. the reaction mixture is filtered and poured into water. The precipitate is separated, washed with water and toluene/petrolether and dried. Yield: 84 g (78%) N-cyanoacetyl-2,4-dimethyl-5-nitroaniline, mp. 229°-230° C. cooling to 25° C. the reaction mixture is filtered poured into water The precipitate is separated washed with water and toluene/petrolether dried

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

Procedure: A 2-amino-4-oxo-5-cyanopyrrolo[2,3-d]pyrimidine(III) was prepared according to the method reported by Migawa, et al., “A Two Step Synthesis of the Nucleoside q Precursor 2-amino-5-cyanopyrrolo[2-3-d]pyrimidine-4-one” Syn. Comm. 26:3317(1996) which involved the synthesis of chloroformylacetonitrile (110) from chloroacetonitrile (109) and methyl formate as shown in FIG. 19. Cyclocon-densation of compound 10 with 2,6-diamino-4-oxopyrimidine afforded to the key intermediate in 65-70% overall yield. Reductive amination of the 5-nitrile with the appropriate anilines or ethyl-p-aminobenzoyl-L-glutamate in the presence of Raney nickel and hydrogen at 50 psi for 5-6 hours afforded the desired analogues which were purified by column chromatography and were obtained in 20-62% yield. This yielded the product generally represented by compound 112. For the classical analogue, compound 407, which is the compound 112 where R2 is p-benzoyl-L-glutamate, saponification of the chromatographically purified ester afforded the desired product. This method was used to synthesize compounds 407-415, which are generally represented by compound 112 in FIG. 19 with the following substitutions: A 2-amino-4-oxo-5-cyanopyrrolo[2,3-d]pyrimidine(III) was prepared

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

Procedure: A 2-amino-4-oxo-5-cyanopyrrolo[2,3-d]pyrimidine(III) was prepared according to the method reported by Migawa, et al., “A Two Step Synthesis of the Nucleoside q Precursor 2-amino-5-cyanopyrrolo[2-3-d]pyrimidine-4-one” Syn. Comm. 26:3317(1996) which involved the synthesis of chloroformylacetonitrile (110) from chloroacetonitrile (109) and methyl formate as shown in FIG. 19. Cyclocon-densation of compound 10 with 2,6-diamino-4-oxopyrimidine afforded to the key intermediate in 65-70% overall yield. Reductive amination of the 5-nitrile with the appropriate anilines or ethyl-p-aminobenzoyl-L-glutamate in the presence of Raney nickel and hydrogen at 50 psi for 5-6 hours afforded the desired analogues which were purified by column chromatography and were obtained in 20-62% yield. This yielded the product generally represented by compound 112. For the classical analogue, compound 407, which is the compound 112 where R2 is p-benzoyl-L-glutamate, saponification of the chromatographically purified ester afforded the desired product. This method was used to synthesize compounds 407-415, which are generally represented by compound 112 in FIG. 19 with the following substitutions: A 2-amino-4-oxo-5-cyanopyrrolo[2,3-d]pyrimidine(III) was prepared

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

Procedure: A 2-amino-4-oxo-5-cyanopyrrolo[2,3-d]pyrimidine(III) was prepared according to the method reported by Migawa, et al., "A Two Step Synthesis of the Nucleoside q Precursor 2-amino-5-cyanopyrrolo[2-3-dpyrimidine-4-one" Syn. Comm. 26:3317(1996) which involved the synthesis of chloroformylacetonitrile (110) from chloroacetonitrile (109) and methyl formate as shown in FIG. 19. Cyclocon-densation of compound 10 with 2,6-diamino-4-oxopyrimidine afforded to the key intermediate in 65-70% overall yield. Reductive amination of the 5-nitrile with the appropriate anilines or ethyl-p-aminobenzoyl-L-glutamate in the presence of Raney nickel and hydrogen at 50 psi for 5-6 hours afforded the desired analogues which were purified by column chromatograpy and were obtained in 20-62% yield. This yielded the product generally represented by compound 112. For the classical analogue, compound 407, which is the compound 112 where R2 is p-benzoyl-L-glutamate, saponification of the chromatographically purified ester afforded the desired product. This method was used to synthesize compounds 407-415, which are generally represented by compound 112 in FIG. 19 with the following substitutions: A 2-amino-4-oxo-5-cyanopyrrolo[2,3-d]pyrimidine(III) was prepared

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

Procedure: A 2-amino-4-oxo-5-cyanopyrrolo[2,3-d]pyrimidine(III) was prepared according to the method reported by Migawa, et al., "A Two Step Synthesis of the Nucleoside q Precursor 2-amino-5-cyanopyrrolo[2-3-dpyrimidine-4-one" Syn. Comm. 26:3317(1996) which involved the synthesis of chloroformylacetonitrile (110) from chloroacetonitrile (109) and methyl formate as shown in FIG. 19. Cyclocon-densation of compound 10 with 2,6-diamino-4-oxopyrimidine afforded to the key intermediate in 65-70% overall yield. Reductive amination of the 5-nitrile with the appropriate anilines or ethyl-p-aminobenzoyl-L-glutamate in the presence of Raney nickel and hydrogen at 50 psi for 5-6 hours afforded the desired analogues which were purified by column chromatograpy and were obtained in 20-62% yield. This yielded the product generally represented by compound 112. For the classical analogue, compound 407, which is the compound 112 where R2 is p-benzoyl-L-glutamate, saponification of the chromatographically purified ester afforded the desired product. This method was used to synthesize compounds 407-415, which are generally represented by compound 112 in FIG. 19 with the following substitutions: A 2-amino-4-oxo-5-cyanopyrrolo[2,3-d]pyrimidine(III) was prepared

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

Procedure: In 40 ml of dimethylformamide was dissolved 1.82 g of 2-amino-6-ethyl-4-oxo-4H-1-benzopyran-3-carboxaldehyde, followed by the addition of 3.5 g of cyanoacetyl chloride. The mixture was reacted at 60° C. for 3 hours, with constant stirring. The solvent was then distilled off under reduced pressure and the residue was chromatographed on silica gel. The desired product was recovered from the chloroform eluate and recrystallized from acetonitrile. By the above procedure was obtained 1.03 g of 7-ethyl-3-cyano-1-azaxanthone, m.p. 183°-185° C. The mixture was reacted at 60° C. for 3 hours, with constant stirring The solvent was then distilled off under reduced pressure the residue was chromatographed on silica gel The desired product was recovered from the chloroform eluate recrystallized from acetonitrile