2-morpholin-4-ylethylhydrazine

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

実験手順: Following the procedure for 8-Bromo-2-[2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene, 8-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide 25 was reacted with (2-morpholin-4-yl-ethyl)-hydrazine to give 8-bromo-2-[2-(2-morpholin-4-yl-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene. MS(ESI+) 462.1/464.1.

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

実験手順: H2SO4 (conc., 0.98 g, 10 mmol) was added dropwise into a suspension of diethyloxalacetate sodium salt (10 mmol) in 100 mL anhydrous ethyl ether. Na2SO4 was filtered off after the addition. Excess acid was removed by 30 ml KHCO3 (sat.) to give diethyl oxacetate. 2-(N-morpholinyl)ethylhydrazine (1.45 g, 10 mmol) in 2 ml EtOH was added, and the mixture was refluxed for 45 min. The solvent was removed under vacuum to yield 2.1 g of the crude pyrazole-based compound A. Na2SO4 was filtered off after the addition Excess acid was removed by 30 ml KHCO3 (sat.) to give diethyl oxacetate the mixture was refluxed for 45 min The solvent was removed under vacuum

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

実験手順: Following the procedure for 8-Bromo-2-[2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene, 8-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide 25 was reacted with (2-morpholin-4-yl-ethyl)-hydrazine to give 8-bromo-2-[2-(2-morpholin-4-yl-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene. MS (ESI+) 462.1/464.1.

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

実験手順: Following the procedure for 8-Bromo-2-[2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene, 8-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide 25 was reacted with (2-morpholin-4-yl-ethyl)-hydrazine to give 8-bromo-2-[2-(2-morpholin-4-yl-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene. MS(ESI+) 462.1/464.1.

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

実験手順: Compound 28 was synthesised following similar procedures outlined in Example 31 (Compound 18), using 4-(2-hydrazinylethyl)morpholine instead of ethyl hydrazine in Step 3. As a slightly modified procedure, Step 3 was performed at 60° C. for 16 h. The reaction mixture was concentrated in vacuo and the crude residue was purified by column chromatography (silica gel, gradient 50 to 100% ethyl acetate/isohexane), followed by preparative HPLC, yielding Compound 28 as a solid. Compound 28 was synthesised The reaction mixture was concentrated in vacuo the crude residue was purified by column chromatography (silica gel, gradient 50 to 100% ethyl acetate/isohexane)

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

実験手順: (2S,4R)-4-(2-Chlorophenylsulfonyl)-1-(3-methyl-1-(2-morpholinoethyl)-1H-pyrazol-5-yl)pyrrolidine-2-carboxylic acid methyl ester. In analogy to the procedure described in example 192 h, (2S,4R)-methyl 4-(2-chlorophenylsulfonyl)-1-(3-oxobutanethioyl)pyrrolidine-2-carboxylate (example 253c) was reacted with 4-(2-hydrazinoethyl)morpholine (CAS Reg. No. 2154-24-7) to give the title compound as yellow oil. MS (ESI): m/z=497.3 [M+H]+.

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

実験手順: Compound 28 was synthesised following similar procedures outlined in Example 31 (Compound 18), using 4-(2-hydrazinylethyl)morpholine instead of ethyl hydrazine in Step 3. As a slightly modified procedure, Step 3 was performed at 60° C. for 16 h. The reaction mixture was concentrated in vacuo and the crude residue was purified by column chromatography (silica gel, gradient 50 to 100% ethyl acetate/isohexane), followed by preparative HPLC, yielding Compound 28 as a solid. Compound 28 was synthesised The reaction mixture was concentrated in vacuo the crude residue was purified by column chromatography (silica gel, gradient 50 to 100% ethyl acetate/isohexane)

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

実験手順: Following the procedure for 8-Bromo-2-[2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene, 8-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide 25 was reacted with (2-morpholin-4-yl-ethyl)-hydrazine to give 8-bromo-2-[2-(2-morpholin-4-yl-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene. MS (ESI+) 462.1/464.1.

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

実験手順: Following the procedure for 8-Bromo-2-[2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene, 8-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide 25 was reacted with (2-morpholin-4-yl-ethyl)-hydrazine to give 8-bromo-2-[2-(2-morpholin-4-yl-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene. MS(ESI+) 462.1/464.1.

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

実験手順: H2SO4 (conc., 0.98 g, 10 mmol) was added dropwise into a suspension of diethyloxalacetate sodium salt (10 mmol) in 100 mL anhydrous ethyl ether. Na2SO4 was filtered off after the addition. Excess acid was removed by 30 ml KHCO3 (sat.) to give diethyl oxacetate. 2-(N-morpholinyl)ethylhydrazine (1.45 g, 10 mmol) in 2 ml EtOH was added, and the mixture was refluxed for 45 min. The solvent was removed under vacuum to yield 2.1 g of the crude pyrazole-based compound A. Na2SO4 was filtered off after the addition Excess acid was removed by 30 ml KHCO3 (sat.) to give diethyl oxacetate the mixture was refluxed for 45 min The solvent was removed under vacuum