4-[(1,1-dioxo-1,4-thiazinan-4-yl)methyl]aniline

反応条件: temp:0.00; pressure:0.00; stir:

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: 4-(4-Nitro-benzyl)-thiomorpholine 1,1-dioxide (110 mg, 0.41 mmol) is dissolved in MeOH (7 mL). To this solution is added FeCl3.6H2O (−20 mg, 0.07 mmol) and active Charcoal (12 mg, 1.0 mmol). The suspension is heated to reflux. Hydrazine hydrate (0.5 mL) is added, and reflux is continued for 4 h until full conversion, the active Charcoal is filtered off through Celite, and the MeOH is removed under reduced pressure. The residue (85 mg, 86%) is directly used in the next step. The suspension is heated to reflux reflux the active Charcoal is filtered off through Celite the MeOH is removed under reduced pressure

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

実験手順: 4-(4-Nitro-benzyl)-thiomorpholine 1,1-dioxide (110 mg, 0.41 mmol) is dissolved in MeOH (7 mL). To this solution is added FeCl3.6H2O (−20 mg, 0.07 mmol) and active Charcoal (12 mg, 1.0 mmol). The suspension is heated to reflux. Hydrazine hydrate (0.5 mL) is added, and reflux is continued for 4 h until full conversion, the active Charcoal is filtered off through Celite, and the MeOH is removed under reduced pressure. The residue (85 mg, 86%) is directly used in the next step. The suspension is heated to reflux reflux the active Charcoal is filtered off through Celite the MeOH is removed under reduced pressure

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

実験手順: Prepared from 1-acetyl-3-(1-ethoxy-1-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(1,1-dioxo-thiomorpholin-4-yl-methyl)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol=10:1) C28H27N3O5S

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

実験手順: A mixture of 3-bromo-4-methoxy-benzoic acid (500 mg), 4-(1,1-dioxo-1lambda*6*-thiomorpholin-4-ylmethyl)-phenylamine (519 mg), EDAC (830 mg), HOBT (585 mg) and N-methylmorpholine (712 μl) in DMF (3 ml) was stirred at room temperature for 18 h. The mixture was then diluted with water (30 ml) and the resulting solid collected by filtration and dried (882 mg) the resulting solid collected by filtration dried (882 mg)

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

実験手順: A mixture of 5′-cyano-2′-methyl-biphenyl-4-carboxylic acid (100 mg), 4-(1,1-dioxo-1lambda*6*-thiomorpholin-4-ylmethyl)-phenylamine (101 mg), EDAC (81 mg), HOBT (57 mg) and N-methylmorpholine (0.09 ml) in dry DMF (2 ml) was stirred at 20 C for 18 h. Water (8 ml) was then added and the resulting solid collected by filtration and dried (160 mg). the resulting solid collected by filtration dried (160 mg)

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

実験手順: A mixture of 5′-(cyclohexanecarbonyl-amino)-2′-chloro-biphenyl-4-carboxylic acid (100 mg), 4-(1,1-dioxo-1lambda*6*-thiomorpholin-4-ylmethyl)-phenylamine (67 mg), triethylamine (0.098 ml) and HBTU (159 mg) in dry DMF (5 ml) was stirred at 20 C for 18 h. The mixture was then evaporated to dryness and purified via reversed-phase preparative HPLC (eluting with acetonitrile/water) to afford the title compound as an orange solid (35 mg). The mixture was then evaporated to dryness purified via reversed-phase preparative HPLC (eluting with acetonitrile/water)

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

実験手順: A mixture of 5′-(cyclopropanecarbonyl-amino)-2′-methoxy-biphenyl-4-carboxylic acid (50 mg), 4-(1,1-dioxo-1lambda*6*-thiomorpholin-4-ylmethyl)-phenylamine (38 mg), N-methylmorpholine (0.03 ml), 1-hydroxybenzotriazole (21 mg) and 1-ethyl-3-(3-(dimethylaminopropyl)carbodiimide hydrochloride (30 mg) in dry DMF (1 ml) was stirred at 20 C for 18 h. The mixture was then added to water and the resulting colourless precipitate collected by filtration and dried (38 mg). the resulting colourless precipitate collected by filtration dried (38 mg)

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

実験手順: 2′-Methyl-5′-[(thiophene-2-carbonyl)-amino]-biphenyl-4-carboxylic acid (45 mg), 4-(1,1-dioxo-1lambda*6*-thiomorpholin-4-ylmethyl)-phenylamine (32 mg), EDAC (25 mg), HOBT (18 mg) and N-methylmorpholine (27 mg) in dry DMF (0.5 ml) was stirred at 20 C for 18 h. The mixture was then diluted with water (6 ml) and the resulting colourless solid collected by filtration and dried (62 mg). the resulting colourless solid collected by filtration dried (62 mg)

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

実験手順: A mixture of 2′-methyl-5′-[(morpholine-4-carbonyl)-amino]-biphenyl-4-carboxylic acid (40 mg), 4-(1,1-Dioxo-1lambda*6*-thiomorpholin-4-ylmethyl)-phenylamine (28 mg), triethylamine (0.033 ml) and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (67 mg) in dry DMF (3 ml) was stirred at 20 C for 18 h. The mixture was then partitioned between water and dichloromethane. The dried extracts were evaporated and the residue purified on silica gel. Elution with dichloromethane:ethanol:0.880 ammonia; 200:8:1 gave an off-white solid (32 mg). The mixture was then partitioned between water and dichloromethane The dried extracts were evaporated the residue purified on silica gel Elution with dichloromethane

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

実験手順: A mixture of 5′-tert-butoxycarbonylamino-2′-methyl-biphenyl-4-carboxylic acid (500 mg), 4-(1,1-dioxo-1lambda*6*-thiomorpholin-4-ylmethyl) -phenylamine (367 mg), triethylamine (0.64 ml) and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (869 mg) in dry DMF (20 ml) was stirred at 20 C for 118 h. The mixture was then partitioned between water and dichloromethane. The dried extracts were evaporated and the residue purified on silica gel. Elution with ethyl acetate:petrol; 1:1 removed high Rf impurities and further elution with ethyl acetate gave the title compound as a pale yellow solid (693 mg). The mixture was then partitioned between water and dichloromethane The dried extracts were evaporated the residue purified on silica gel Elution with ethyl acetate 1:1 removed high Rf impurities and further elution with ethyl acetate