methyl morpholine-3-carboxylate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Intermediate I was prepared in the same manner as Intermediate B, using 3-morpholinecarboxylic acid as the starting material instead of (R)-2-aminobutanoic acid. No reductive amination step, such as that used for the conversion of compound II to compound III, was required. Rather, methylmorpholine-3-carboxylate was reacted directly with 2,4-dichloro-5-nitropyrimidine in the same manner as is described for the conversion of compound III to Intermediate A. LCMS: 254.9 m/z (M+H)+.

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 4-(2-bromo-4-fluorophenyl)-6-(bromomethyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate (1.1 g, 2.2 mmol) was reacted with methyl morpholine-3-carboxylate (0.4 g, 2.2 mmol) according to the procedure as described in Example 24 to give the title compound as a yellow solid (0.62 g, 50%). The compound was characterized by the following spectroscopic data:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 4-(2-bromo-4-fluorophenyl)-6-(bromomethyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate (1.1 g, 2.2 mmol) was reacted with methyl morpholine-3-carboxylate (0.4 g, 2.2 mmol) according to the procedure as described in Example 24 to give the title compound as a yellow solid (0.62 g, 50%). The compound was characterized by the following spectroscopic data:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Intermediate I was prepared in the same manner as Intermediate B, using 3-morpholinecarboxylic acid as the starting material instead of (R)-2-aminobutanoic acid. No reductive amination step, such as that used for the conversion of compound II to compound III, was required. Rather, methylmorpholine-3-carboxylate was reacted directly with 2,4-dichloro-5-nitropyrimidine in the same manner as is described for the conversion of compound III to Intermediate A. LCMS: 254.9 m/z (M+H)+.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Intermediate I was prepared in the same manner as Intermediate B, using 3-morpholinecarboxylic acid as the starting material instead of (R)-2-aminobutanoic acid. No reductive amination step, such as that used for the conversion of compound II to compound III, was required. Rather, methylmorpholine-3-carboxylate was reacted directly with 2,4-dichloro-5-nitropyrimidine in the same manner as is described for the conversion of compound III to Intermediate A. LCMS: 254.9 m/z (M+H)+.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Intermediate I was prepared in the same manner as Intermediate B, using 3-morpholinecarboxylic acid as the starting material instead of (R)-2-aminobutanoic acid. No reductive amination step, such as that used for the conversion of compound II to compound III, was required. Rather, methylmorpholine-3-carboxylate was reacted directly with 2,4-dichloro-5-nitropyrimidine in the same manner as is described for the conversion of compound III to Intermediate A. LCMS: 254.9 m/z (M+H)+.

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4-([4-2-butynyloxy)phenyl]sulfonyl}-morpholine-3-carboxylic acid, methyl ester (0.1 g, 0.28 mmol) in 2.4 mL of THF:methanol:water [4:1:1] was cooled in an ice bath and 2N LiOH (0.3 mL, 0.59 mmol) was added. The reaction was stirred at 0° C. for 30 minutes and at room temperature for 2 hours. After evaporating the solvent, the residue was diluted with ether and filtered. The solid was dissolved in water, neutralized with 1N HCl to pH˜3 and extracted with dichloromethane. The organic layer was washed with water and brine, dried over sodium sulfate, filtered and concentrated to give 0.06 g of 4-[4-(2-butynyloxy)phenyl]sulfonyl}-morpholine-3-carboxylic acid. Yield˜69.8%. mp 40-42° C. Electrospray Mass Spec 338.1(M−H)−. After evaporating the solvent the residue was diluted with ether filtered The solid was dissolved in water extracted with dichloromethane The organic layer was washed with water and brine dried over sodium sulfate filtered concentrated

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Morpholine-3-carboxylic acid hydrochloride (1.04 g) was dissolved in methanol (20 ml) and the solution cooled to -20° C. Thionyl chloride (1 ml) was added dropwise to the stirred reaction mixture such that the temperature did not rise above -10°. After the addition was complete the reaction mixture was stirred at room temperature for 16 h. The solvent was removed in vacuo and the resultant pale grey residue was partitioned between 2N Na2CO3 and dichloromethane. The organic phase was separated, dried, and the solvent was removed in vacuo to give the title compound as an oil (220 mg). did not rise above -10° After the addition The solvent was removed in vacuo the resultant pale grey residue was partitioned between 2N Na2CO3 and dichloromethane The organic phase was separated dried the solvent was removed in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 4-(2-bromo-4-fluorophenyl)-6-(bromomethyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate (1.1 g, 2.2 mmol) was reacted with methyl morpholine-3-carboxylate (0.4 g, 2.2 mmol) according to the procedure as described in Example 24 to give the title compound as a yellow solid (0.62 g, 50%). The compound was characterized by the following spectroscopic data: