ethyl pentanimidate;hydrochloride

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

Procedure: A mixture of 3,4-diaminothiophene (116 mg, 1.01 mmol) and ethyl valeroimidate hydrochloride (504 mg, 3.05 mmol) in absolute ethanol (20 mL) was heated to reflux for 1 hour, cooled to room temperature and stirred for 15 hours. The mixture was concentrated and purified by flash chromatography (SiO2, 25% EtOAc/hexanes) to give 140 mg (78%) of 2-n-butyl-1H-thieno[3,4-d]imidazole as a tan solid: 1H NMR (300 MHz, CDCl3)δ 6.70 (s, 2H), 2.81 (t, 2H, J=7.5 Hz), 1.88-1.74 (m, 2H), 1.48-1.35 (m, 2H), 0.90 (t, 3H, J=7.2 Hz); FAB-MS: 181 (M+ +1). was heated to reflux for 1 hour The mixture was concentrated purified by flash chromatography (SiO2, 25% EtOAc/hexanes)

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

Procedure: A 12.7 g (76.7 mmol) sample of ethyl valerimidate hydrochloride (prepared from valeronitrile, ethanol, and hydrogen chloride gas as described by A. J. Hill and I. Rabinowitz, J. Am. Chem. Soc., 1926, 48, 734) was dissolved in 33% (w/w) potassium carbonate solution (made by dissolving 15 g of K2CO3 in 30 mL of H2O) and immediately extracted with either (3×40 mL). The combined ether layers were dried over Na2SO4, filtered, and concentrated in vacuo to give 7.09 g (72%) of the product as a clear oil, which was used directly in the next step. 1H NMR (300 MHz, CDCl3, ppm): δ0.88 (t, J=7 Hz, 3H), 1.24 (t, J=7 Hz, 3H), 1.31 (m, 2H), 1.50 (m, 2H), 2.19 (t, J=7.5 Hz, 2H), 4.06 (q, J=7 Hz, 2H), 6.84 (br s, 1H). immediately extracted with either (3×40 mL) The combined ether layers were dried over Na2SO4 filtered concentrated in vacuo

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

Procedure: A mixture of 3,4-diaminothiophene (116 mg, 1.01 mmol ) and ethyl valeroimidate hydrochloride (504 mg, 3.05 mmol) in absolute ethanol (20 mL) was heated to reflux for 1 hour, cooled to room temperature and stirred for 15 hours. The mixture was concentrated and purified by flash chromatography (SiO2, 25% EtOAc/hexanes) to give 140 mg (78%) of 2-n-butyl-1H-thieno[3,4-d]imidazole as a tan solid: 1H NMR (300 MHz, CDCl3)δ 6.70 (s, 2H), 2.81 (t, 2H, J=7.5 Hz), 1.88-1.74 (m, 2H), 1.48-1.35 (m, 2H), 0.90 (t, 3H, J=7.2 Hz); FAB-MS: 181 (M+ +1). was heated to reflux for 1 hour The mixture was concentrated purified by flash chromatography (SiO2, 25% EtOAc/hexanes)

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

Procedure: A mixture of 3,4-diaminothiophene (116 mg, 1.01 mmol ) and ethyl valeroimidate hydrochloride (504 mg, 3.05 mmol) in absolute ethanol (20 mL) was heated to reflux for 1 hour, cooled to room temperature and stirred for 15 hours. The mixture was concentrated and purified by flash chromatography (SiO2, 25% EtOAc/hexanes) to give 140 mg (78%) of 2-n-butyl-1H-thieno[3,4-d]imidazole as a tan solid: 1H NMR (300 MHz, CDCl3)δ 6.70 (s, 2H), 2.81 (t, 2H, J=7.5 Hz), 1.88-1.74 (m, 2H), 1.48-1.35 (m, 2H), 0.90 (t, 3H, J=7.2 Hz); FAB-MS: 181 (M+ +1). was heated to reflux for 1 hour The mixture was concentrated purified by flash chromatography (SiO2, 25% EtOAc/hexanes)

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

Procedure: Using the procedure of Step A of Example 1, 2.04 g of 4,5-dimethyl-1,2-phenylene diamine and 3.73 g of ethyl pentanimidoate hydrochloride [J.A.C.S., Vol. 64, p. 1827 (1942)] were reacted to obtain 3.48 g of crude product which was chromatographed on silica (eluant: methylene chloride-methanol (9-1)) to obtain 2.27 g of the expected compound melting at 110° C. An analytical sample was prepared by crystallization of 120 mg of the product from isopropyl ether to obtain 88 mg of product melting at 110° C. were reacted to obtain 3.48 g of crude product which was chromatographed on silica (eluant: methylene chloride-methanol (9-1))

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

Procedure: Using the procedure of Step A of Example 1, 2.04 g of 4,5-dimethyl-1,2-phenylene diamine and 3.73 g of ethyl pentanimidoate hydrochloride [J.A.C.S., Vol. 64, p. 1827 (1942)] were reacted to obtain 3.48 g of crude product which was chromatographed on silica (eluant: methylene chloride-methanol (9-1)) to obtain 2.27 g of the expected compound melting at 110° C. An analytical sample was prepared by crystallization of 120 mg of the product from isopropyl ether to obtain 88 mg of product melting at 110° C. were reacted to obtain 3.48 g of crude product which was chromatographed on silica (eluant: methylene chloride-methanol (9-1))

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

Procedure: Using the procedure of Example 1, 5 g of 4,5-diaminopyrimidine and 10 g of ethyl pentanimidoate hydrochloride [J.A.C.S., Vol. 64, p 1827 (1942)] using dimethylformamide as solvent were reacted to obtain 2.1 g of the desired product which after crystallization from ethyl acetate melted at 166° C. The product was crystallized from ethyl acetate to obtain 1.8 g of the expected product melting at 168° C. 200 mg of an analytical sample was obtained by an additional crystallization of 300 mg of the product from ethyl acetate melting at 168° C. were reacted

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

Procedure: Using the procedure of Example 1, 5 g of 4,5-diaminopyrimidine and 10 g of ethyl pentanimidoate hydrochloride [J.A.C.S., Vol. 64, p 1827 (1942)] using dimethylformamide as solvent were reacted to obtain 2.1 g of the desired product which after crystallization from ethyl acetate melted at 166° C. The product was crystallized from ethyl acetate to obtain 1.8 g of the expected product melting at 168° C. 200 mg of an analytical sample was obtained by an additional crystallization of 300 mg of the product from ethyl acetate melting at 168° C. were reacted

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

Procedure: Using the procedure of Step A of Example 1, 2.5 g of methyl 2,3-diaminobenzoate [J. Chem. Soc., Vol. 117 (1920) p 775 and CAN. J. Chem., Vol. 55 (1977), p. 1653 to 1657] and 2.73 g of ethyl pentanimidoate hydrochloride [J.A.C.S., Vol. 64, p. 1827 (1942)] were reacted to obtain 3.05 g of the desired product which after crystallization from essence G melted at approximately 85° C. The analytical sample was obtained by two successive crystallizations of 280 mg of product from isopropyl ether to obtain 100 mg of the product melting at 97° C. were reacted

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

Procedure: Using the procedure of Step A of Example 1, 2.5 g of methyl 2,3-diaminobenzoate [J. Chem. Soc., Vol. 117 (1920) p 775 and CAN. J. Chem., Vol. 55 (1977), p. 1653 to 1657] and 2.73 g of ethyl pentanimidoate hydrochloride [J.A.C.S., Vol. 64, p. 1827 (1942)] were reacted to obtain 3.05 g of the desired product which after crystallization from essence G melted at approximately 85° C. The analytical sample was obtained by two successive crystallizations of 280 mg of product from isopropyl ether to obtain 100 mg of the product melting at 97° C. were reacted

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5.47 g of ethyl pentanimidoate hydrochloride (J.A.C.S., Vol. 64, p. 1827 (1942)) were added to a solution of 5 g of methyl 3,4-diaminobenzoate in 60 ml of tetrahydrofuran, and the mixture was stirred for 3 hours and 30 minutes at 90° C. The tetrahydrofuran was evaporated off and 50 ml of a saturated solution of sodium bicarbonate were added. The mixture was extracted with methylene chloride and the extracts were washed with water, dried and evaporated to dryness under reduced pressure to obtain 9 g of product which was crystallized from isopropyl ether to obtain 6.65 g of the desired product melting at 114° C. The tetrahydrofuran was evaporated off 50 ml of a saturated solution of sodium bicarbonate were added The mixture was extracted with methylene chloride the extracts were washed with water dried evaporated to dryness under reduced pressure

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5.47 g of ethyl pentanimidoate hydrochloride (J.A.C.S., Vol. 64, p. 1827 (1942)) were added to a solution of 5 g of methyl 3,4-diaminobenzoate in 60 ml of tetrahydrofuran, and the mixture was stirred for 3 hours and 30 minutes at 90° C. The tetrahydrofuran was evaporated off and 50 ml of a saturated solution of sodium bicarbonate were added. The mixture was extracted with methylene chloride and the extracts were washed with water, dried and evaporated to dryness under reduced pressure to obtain 9 g of product which was crystallized from isopropyl ether to obtain 6.65 g of the desired product melting at 114° C. The tetrahydrofuran was evaporated off 50 ml of a saturated solution of sodium bicarbonate were added The mixture was extracted with methylene chloride the extracts were washed with water dried evaporated to dryness under reduced pressure