HL-725 has been synthesized in a variety of ways: 1) 1-Carbamoylmethylene-6,7-methoxy-1,2,3,4-tetrahydroisoquinoline (I) was cyclized on treatment with diethylcarbonate (A) to give 9,10-dimethoxy-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinoline-2,4-dione (II). Methylation of (II) with methyliodide in dimethylformamide in the presence of sodium hydride afforded (III). The N-methyl compound (III) was treated with phosphorous pentasulfide to give the thio compound (IV). Reaction of (IV) with mesidine (C) afforded HL-725. 2) Alternately, the compound (II) was reacted with phosphorous oxychloride to yield the chloro compound (V), which was then reacted with mesidine to give the mesitylino derivative (VI). Methylation of (VI) with methyliodide afforded HL-725 and the exo-N-methyl isomer (VII), which were separated chromatographcally. 3) 3,4-Dimethoxy-beta-phenethyl bromide (VIII) was reacted with barbituric acid (B) to give the alkylated product (IX). Bischler-Napieralski-type cyclization afforded (II), which was then converted to HL-725 by the appropriate route.

HL-725 has been synthesized in a variety of ways: 1) 1-Carbamoylmethylene-6,7-methoxy-1,2,3,4-tetrahydroisoquinoline (I) was cyclized on treatment with diethylcarbonate (A) to give 9,10-dimethoxy-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinoline-2,4-dione (II). Methylation of (II) with methyliodide in dimethylformamide in the presence of sodium hydride afforded (III). The N-methyl compound (III) was treated with phosphorous pentasulfide to give the thio compound (IV). Reaction of (IV) with mesidine (C) afforded HL-725. 2) Alternately, the compound (II) was reacted with phosphorous oxychloride to yield the chloro compound (V), which was then reacted with mesidine to give the mesitylino derivative (VI). Methylation of (VI) with methyliodide afforded HL-725 and the exo-N-methyl isomer (VII), which were separated chromatographcally. 3) 3,4-Dimethoxy-beta-phenethyl bromide (VIII) was reacted with barbituric acid (B) to give the alkylated product (IX). Bischler-Napieralski-type cyclization afforded (II), which was then converted to HL-725 by the appropriate route.

HL-725 has been synthesized in a variety of ways: 1) 1-Carbamoylmethylene-6,7-methoxy-1,2,3,4-tetrahydroisoquinoline (I) was cyclized on treatment with diethylcarbonate (A) to give 9,10-dimethoxy-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinoline-2,4-dione (II). Methylation of (II) with methyliodide in dimethylformamide in the presence of sodium hydride afforded (III). The N-methyl compound (III) was treated with phosphorous pentasulfide to give the thio compound (IV). Reaction of (IV) with mesidine (C) afforded HL-725. 2) Alternately, the compound (II) was reacted with phosphorous oxychloride to yield the chloro compound (V), which was then reacted with mesidine to give the mesitylino derivative (VI). Methylation of (VI) with methyliodide afforded HL-725 and the exo-N-methyl isomer (VII), which were separated chromatographcally. 3) 3,4-Dimethoxy-beta-phenethyl bromide (VIII) was reacted with barbituric acid (B) to give the alkylated product (IX). Bischler-Napieralski-type cyclization afforded (II), which was then converted to HL-725 by the appropriate route.

HL-725 has been synthesized in a variety of ways: 1) 1-Carbamoylmethylene-6,7-methoxy-1,2,3,4-tetrahydroisoquinoline (I) was cyclized on treatment with diethylcarbonate (A) to give 9,10-dimethoxy-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinoline-2,4-dione (II). Methylation of (II) with methyliodide in dimethylformamide in the presence of sodium hydride afforded (III). The N-methyl compound (III) was treated with phosphorous pentasulfide to give the thio compound (IV). Reaction of (IV) with mesidine (C) afforded HL-725. 2) Alternately, the compound (II) was reacted with phosphorous oxychloride to yield the chloro compound (V), which was then reacted with mesidine to give the mesitylino derivative (VI). Methylation of (VI) with methyliodide afforded HL-725 and the exo-N-methyl isomer (VII), which were separated chromatographcally. 3) 3,4-Dimethoxy-beta-phenethyl bromide (VIII) was reacted with barbituric acid (B) to give the alkylated product (IX). Bischler-Napieralski-type cyclization afforded (II), which was then converted to HL-725 by the appropriate route.

HL-725 has been synthesized in a variety of ways: 1) 1-Carbamoylmethylene-6,7-methoxy-1,2,3,4-tetrahydroisoquinoline (I) was cyclized on treatment with diethylcarbonate (A) to give 9,10-dimethoxy-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinoline-2,4-dione (II). Methylation of (II) with methyliodide in dimethylformamide in the presence of sodium hydride afforded (III). The N-methyl compound (III) was treated with phosphorous pentasulfide to give the thio compound (IV). Reaction of (IV) with mesidine (C) afforded HL-725. 2) Alternately, the compound (II) was reacted with phosphorous oxychloride to yield the chloro compound (V), which was then reacted with mesidine to give the mesitylino derivative (VI). Methylation of (VI) with methyliodide afforded HL-725 and the exo-N-methyl isomer (VII), which were separated chromatographcally. 3) 3,4-Dimethoxy-beta-phenethyl bromide (VIII) was reacted with barbituric acid (B) to give the alkylated product (IX). Bischler-Napieralski-type cyclization afforded (II), which was then converted to HL-725 by the appropriate route.