3-methylbut-2-enoyl isothiocyanate

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

Procedure: To a solution of 3-methylbut-2-enoyl isothiocyanate (2 g, 14.2 mmol, Eq: 1.00) in benzene (40.0 ml) was added a solution of piperidine (1.21 g, 1.4 ml, 14.2 mmol, Eq: 1.00) in benzene (20.0 ml). The mixture was stirred for 2 hours. The mixture was evaporated affording 3-methyl-but-2-enoic acid (piperidine-1-carbothioyl)-amide (3.32 g, 104%) as a yellow oil. MS: m/z=227.2 (M+H+) The mixture was evaporated

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

Procedure: To a solution of 3-methylbut-2-enoyl isothiocyanate (2 g, 14.2 mmol, Eq: 1.00) in benzene (40.0 ml) was added a solution of piperidine (1.21 g, 1.4 ml, 14.2 mmol, Eq: 1.00) in benzene (20.0 ml). The mixture was stirred for 2 hours. The mixture was evaporated affording 3-methyl-but-2-enoic acid (piperidine-1-carbothioyl)-amide (3.32 g, 104%) as a yellow oil. MS: m/z=227.2 (M+H+) The mixture was evaporated

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

Procedure: To a solution of 3-methylbut-2-enoyl isothiocyanate (500 mg, 3.54 mmol, Eq: 1.00) in Tetrahydrofuran (3.5 ml) was added a solution of N-methylcyclopropanamine (264 mg, 3.72 mmol, Eq: 1.05) in Tetrahydrofuran (3.5 ml). The mixture was stirred for 30 minutes. Sodium carbonate (394 mg, 3.72 mmol, Eq: 1.05) and iodomethane (1.01 g, 443 μl, 7.08 mmol, Eq: 2) was added and stirred overnight at 70° C. The solvent was evaporated. Methylhydrazine (1.63 g, 1.86 ml, 35.4 mmol, Eq: 10) was added and the mixture was stirred for 2 hours at 100° C. MS showed just product peak. The crude material was applied on silica gel and purified by column chromatography using heptane/ethyl acetate (0-40% ethyl acetate) as eluent affording stirred overnight at 70° C The solvent was evaporated the mixture was stirred for 2 hours at 100° C purified by column chromatography affording

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

Procedure: Was prepared in the same manner as described in General Procedure Example 1b) using 3-methylbut-2-enoyl isothiocyanate (2 g, 14.2 mmol, Eq: 1.00) and dimethylamine solution 2M in THF (7.08 ml, 14.2 mmol, Eq: 1.00). Evaporation of the solvent afforded 1,1-dimethyl-3-(3-methyl-but-2-enoyl)-thiourea (2.239 g/84.9%) as a yellow oil which was used without further purification in the next step. MS: m/e=187.4 (M+H+) Was prepared in the same manner Evaporation of the solvent

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

Procedure: To a solution of 3-methylbut-2-enoyl isothiocyanate (500 mg, 3.54 mmol, Eq: 1.00) in benzene (10.0 ml) was added a solution of pyrrolidine (252 mg, 293 μl, 3.54 mmol, Eq: 1.00) in benzene (5.00 ml). The mixture was stirred for 30 minutes. The solvent was evaporated affording 3-methyl-but-2-enoic acid (pyrrolidine-1-carbothioyl)-amide (824 mg/110%) as a light yellow solid. MS: m/e=213.1 (M+H+) The solvent was evaporated

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

Procedure: To a solution of 3-methylbut-2-enoyl isothiocyanate (500 mg, 3.54 mmol, Eq: 1.00) in benzene (10.0 ml) was added a solution of pyrrolidine (252 mg, 293 μl, 3.54 mmol, Eq: 1.00) in benzene (5.00 ml). The mixture was stirred for 30 minutes. The solvent was evaporated affording 3-methyl-but-2-enoic acid (pyrrolidine-1-carbothioyl)-amide (824 mg/110%) as a light yellow solid. MS: m/e=213.1 (M+H+) The solvent was evaporated

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of potassium thiocyanate (10 g, 101 mmol, Eq: 1.00) and hexaethylene glycol monomethyl ether (896 mg, 830 μl, 3.02 mmol, Eq: 0.03) in dry dichloromethane (120 ml) was added dropwise at 0° C. a solution of 3-methylbut-2-enoyl chloride (12.0 g, 11.2 ml, 101 mmol, Eq: 1.00) in dry dichloromethane (20.0 ml) over 1 hour under argon atmosphere. After the addition was completed, the mixture (now light brown & turbid) was allowed to warm to 25° C. and was stirred for additional 3 hours. The mixture was filtrated, the filtrate was evaporated the residue was distilled under reduced pressure affording 3-methyl-but-2-enoyl isothiocyanate (9.989 g/70.2%) as a yellow liquid. GC-MS: m/ei=141 (M)/bp: 86° C./2 mbar After the addition The mixture was filtrated the filtrate was evaporated the residue was distilled under reduced pressure

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

Procedure: To a solution of 3-methylbut-2-enoyl isothiocyanate (2 g, 14.2 mmol, Eq: 1.00) in benzene (40.0 ml) was added a solution of piperidine (1.21 g, 1.4 ml, 14.2 mmol, Eq: 1.00) in benzene (20.0 ml). The mixture was stirred for 2 hours. The mixture was evaporated affording 3-methyl-but-2-enoic acid (piperidine-1-carbothioyl)-amide (3.32 g, 104%) as a yellow oil. MS: m/z=227.2 (M+H+) The mixture was evaporated

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

Procedure: To a solution of 3-methylbut-2-enoyl isothiocyanate (500 mg, 3.54 mmol, Eq: 1.00) in Tetrahydrofuran (3.5 ml) was added a solution of N-methylcyclopropanamine (264 mg, 3.72 mmol, Eq: 1.05) in Tetrahydrofuran (3.5 ml). The mixture was stirred for 30 minutes. Sodium carbonate (394 mg, 3.72 mmol, Eq: 1.05) and iodomethane (1.01 g, 443 μl, 7.08 mmol, Eq: 2) was added and stirred overnight at 70° C. The solvent was evaporated. Methylhydrazine (1.63 g, 1.86 ml, 35.4 mmol, Eq: 10) was added and the mixture was stirred for 2 hours at 100° C. MS showed just product peak. The crude material was applied on silica gel and purified by column chromatography using heptane/ethyl acetate (0-40% ethyl acetate) as eluent affording stirred overnight at 70° C The solvent was evaporated the mixture was stirred for 2 hours at 100° C purified by column chromatography affording

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

Procedure: Was prepared in the same manner as described in General Procedure Example 1b) using 3-methylbut-2-enoyl isothiocyanate (2 g, 14.2 mmol, Eq: 1.00) and dimethylamine solution 2M in THF (7.08 ml, 14.2 mmol, Eq: 1.00). Evaporation of the solvent afforded 1,1-dimethyl-3-(3-methyl-but-2-enoyl)-thiourea (2.239 g/84.9%) as a yellow oil which was used without further purification in the next step. MS: m/e=187.4 (M+H+) Was prepared in the same manner Evaporation of the solvent

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

Procedure: To a solution of 3-methylbut-2-enoyl isothiocyanate (500 mg, 3.54 mmol, Eq: 1.00) in benzene (10.0 ml) was added a solution of pyrrolidine (252 mg, 293 μl, 3.54 mmol, Eq: 1.00) in benzene (5.00 ml). The mixture was stirred for 30 minutes. The solvent was evaporated affording 3-methyl-but-2-enoic acid (pyrrolidine-1-carbothioyl)-amide (824 mg/110%) as a light yellow solid. MS: m/e=213.1 (M+H+) The solvent was evaporated

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of potassium thiocyanate (10 g, 101 mmol, Eq: 1.00) and hexaethylene glycol monomethyl ether (896 mg, 830 μl, 3.02 mmol, Eq: 0.03) in dry dichloromethane (120 ml) was added dropwise at 0° C. a solution of 3-methylbut-2-enoyl chloride (12.0 g, 11.2 ml, 101 mmol, Eq: 1.00) in dry dichloromethane (20.0 ml) over 1 hour under argon atmosphere. After the addition was completed, the mixture (now light brown & turbid) was allowed to warm to 25° C. and was stirred for additional 3 hours. The mixture was filtrated, the filtrate was evaporated the residue was distilled under reduced pressure affording 3-methyl-but-2-enoyl isothiocyanate (9.989 g/70.2%) as a yellow liquid. GC-MS: m/ei=141 (M)/bp: 86° C./2 mbar After the addition The mixture was filtrated the filtrate was evaporated the residue was distilled under reduced pressure