methyl 2-methyl-3-oxopropanoate

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

Procedure: 2.0 g 5-Chlorothiophene-2-carboxamidine hydrochloride and 1.7 g methyl 2-formylpropionate are added to a 25% solution of potassium methoxide in methanol containing 6.2 g of KOMe. The mixture is stirred for 6 days, then the methanol is evaporated and the residue dissolved in water. Upon addition of hydrochloric acid the product precipitates as a white solid (m.p.>250° C.). the methanol is evaporated the residue dissolved in water Upon addition of hydrochloric acid the product precipitates as a white solid (m.p.>250° C.)

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

Procedure: Into an apparatus similar to that in Example 1, were charged 103.1 g (1 mole) of diethylenetriamine and 116.1 g (1 mole) of methyl 2-formylpropionate. At 130° to 135° C., 18 g of water and 32 g of methanol were distilled off. Then, after addition of 200.3 g (1 mole) of lauric acid, the amide formation was effected at 200° to 210° C. to distil off 18 g of water, leaving behind 4-lauramidoethyl-6-methyl-3,6-dihydro-2H-1,4-diazepin-5-one. At 130° to 135° C., 18 g of water and 32 g of methanol were distilled off was effected at 200° to 210° C. to distil off 18 g of water

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

Procedure: Into an apparatus similar to that in Example 1, were charged 299.5 g (1 mole) of N-tetradecyldiethylenetriamine and 116.1 g (1 mole) of methyl 2-formylpropionate. At 130° to 135° C., 18 g of water and 32 g of methanol were distilled off to obtain 4-tetradecylaminoethyl-6-methyl-3,6-dihydro-2H-1,4-diazepin-5-one. At 130° to 135° C., 18 g of water and 32 g of methanol were distilled off

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

Procedure: Into an apparatus similar to that in Example 1, were charged 103.1 g (1 mole) of diethylenetriamine and 116.1 g (1 mole) of methyl 2-formylpropionate. At 130° to 135° C., 18 g of water and 32 g of methanol were distilled off. Then, after addition of 200.3 g (1 mole) of lauric acid, the amide formation was effected at 200° to 210° C. to distil off 18 g of water, leaving behind 4-lauramidoethyl-6-methyl-3,6-dihydro-2H-1,4-diazepin-5-one. At 130° to 135° C., 18 g of water and 32 g of methanol were distilled off was effected at 200° to 210° C. to distil off 18 g of water

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

Procedure: Into an apparatus similar to that in Example 1, were charged 299.5 g (1 mole) of N-tetradecyldiethylenetriamine and 116.1 g (1 mole) of methyl 2-formylpropionate. At 130° to 135° C., 18 g of water and 32 g of methanol were distilled off to obtain 4-tetradecylaminoethyl-6-methyl-3,6-dihydro-2H-1,4-diazepin-5-one. At 130° to 135° C., 18 g of water and 32 g of methanol were distilled off

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of [2-(2,5-dichloro-phenoxy)-5-fluoro-pyridin-3-yl]-(3,4-dihydro-2H-quinoxalin-1-yl)-methanone (25.1 mg, 0.06 mmol, 1.0 equiv; Example 147) in a 1:1 mixture of THF and water (1 mL) was added 2-methyl-3-oxo-propionic acid methyl ester (27.9 mg, 0.24 mmol, 4.0 equiv; [CAS RN 51673-64-4]), dibutyltin dichloride (1.8 mg, 0.006 mmol, 0.1 equiv; [CAS RN 683-18-1]) and phenylsilane (13.0 mg, 15 μL, 0.12 mmol, 2.0 equiv; [CAS RN 694-53-1]). The reaction mixture was heated by microwave irradiation to 150° C. for 1.5 h. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water provided 2.2 mg (7%) of the title compound as a light yellow solid. MS (ISP): 504.0 [M+H]+. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water

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

Procedure: Sodium hydride (0.52 g, 13 mmol) is added to 20 mL of anhydrous ethanol and stirred for 30 minutes at ambient temperature. To this, 4-fluorobenzamidine hydrochloride (1.47 g, 8.5 mmol) (from example 40) is added and the mixture is stirred for further 30 minutes. Methyl 2-formylpropionate (1 g, 10.6 mmol) is added dropwise and the reaction mixture is left for 4 days under stirring at ambient temperature. the mixture is stirred for further 30 minutes the reaction mixture is left for 4 days under stirring at ambient temperature

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

Procedure: 55 g (0.3 mole) of 4,8-dimethyl-deca-1,6-dien-3-ol and 46 g (0.4 mole) of α-formyl-propionic acid methyl ester are heated at from 140° to 200° C, whilst stirring, the methanol thereby eliminated is distilled off through a column, and the carbon dioxide eliminated is recorded by a gas flow meter. When the reaction has ceased, the contents of the flask are fractionated. 51 g of 2,6,10-trimethyl-dodeca-4,8-dien-1-al (yield, 77% of theory) are obtained. B.p. = 72° - 75° C at 0.01 mm Hg; nD25 = 1.4566. Odor: sweet, fruity, orange scent. the methanol thereby eliminated is distilled off through a column

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

Procedure: 57 g (0.5 mole) of 4-methyl-hex-1-en-3-ol and 70 g of α-formylpropionic acid methyl ester (0.6 mole) are heated at from 140° to 200° C whilst stirring; at the same time the methanol liberated is distilled off through a 20 cm column and the carbon dioxide is measured using a gas flow meter. 11.5 liters of carbon dioxide are liberated in the course of three hours. When the elimination of methanol and carbon dioxide has ceased, the mixture is fractionated. 58 g of the above aldehyde (yield: 75% of theory) are obtained. B.p. = 75° - 80° C at 11 mm Hg. at the same time the methanol liberated is distilled off through a 20 cm column are liberated in the course of three hours

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

Procedure: 2.0 g 5-Chlorothiophene-2-carboxamidine hydrochloride and 1.7 g methyl 2-formylpropionate are added to a 25% solution of potassium methoxide in methanol containing 6.2 g of KOMe. The mixture is stirred for 6 days, then the methanol is evaporated and the residue dissolved in water. Upon addition of hydrochloric acid the product precipitates as a white solid (m.p.>250° C.). the methanol is evaporated the residue dissolved in water Upon addition of hydrochloric acid the product precipitates as a white solid (m.p.>250° C.)

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

Procedure: 2.0 g 5-Chlorothiophene-2-carboxamidine hydrochloride and 1.7 g methyl 2-formylpropionate are added to a 25% solution of potassium methoxide in methanol containing 6.2 g of KOMe. The mixture is stirred for 6 days, then the methanol is evaporated and the residue dissolved in water. Upon addition of hydrochloric acid the product precipitates as a white solid (m.p.>250° C.). the methanol is evaporated the residue dissolved in water Upon addition of hydrochloric acid the product precipitates as a white solid (m.p.>250° C.)

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

Procedure: Into an apparatus similar to that in Example 1, were charged 103.1 g (1 mole) of diethylenetriamine and 116.1 g (1 mole) of methyl 2-formylpropionate. At 130° to 135° C., 18 g of water and 32 g of methanol were distilled off. Then, after addition of 200.3 g (1 mole) of lauric acid, the amide formation was effected at 200° to 210° C. to distil off 18 g of water, leaving behind 4-lauramidoethyl-6-methyl-3,6-dihydro-2H-1,4-diazepin-5-one. At 130° to 135° C., 18 g of water and 32 g of methanol were distilled off was effected at 200° to 210° C. to distil off 18 g of water