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Chemical Structure| 324737-10-2

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Product Details of [ 324737-10-2 ]

CAS No. :324737-10-2
Formula : C9H10N2O3
M.W : 194.19
SMILES Code : O=C(OC)C(C)C(C1=NC=CN=C1)=O
MDL No. :MFCD06245585

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Application In Synthesis of [ 324737-10-2 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 324737-10-2 ]

[ 324737-10-2 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 324737-10-2 ]
  • [ 64224-21-1 ]
YieldReaction ConditionsOperation in experiment
14% With tetraphosphorus decasulfide; In 5,5-dimethyl-1,3-cyclohexadiene; toluene; at 135℃; for 4h; General procedure: P4S10 (12 g, 27.0 mmol), toluene (90 ml) and xylene (90 ml)were added to a reactor and heated to a temperature of 120 C.Compound 5a (8.1 g, 45.1 mmol) was added to the reactor. Thereaction mixture was allowed to proceed under reflux at 135 Cfor 4 h and then cooled to 20 C and filtered through Celite. The solventwas then removed under reduced pressure and the resultantred solid was extracted with CH2Cl2. The organic layer was washedwith aqueous K2CO3 solution, dried over Na2SO4, and filtered. Thesolvent was removed under reduced pressure and the crude solidwas dried in vacuo. The dried solid was washed with cold EtOAc,and then recrystallized in acetonitrile to give 1a (0.9 g, 10percent) as ared solid.
13.6% With phosphorous (V) sulfide; In toluene; xylene; at 135℃; for 4h; Example 3; Synthesis and recrystallization of oltipraz. 300 mL of toluene, 350 mL of xylene, and 48.0 g (216 mmole) of phosphorus pentasulfide were added to a reactor and heated to a temperature of 120 to 122°C. 40.0 g (206 mmole) of methyl 2-metbyl-3-(pyrazin-2-yl)-3-oxopropionate prepared in Example 2 was dissolved in 100 mL of toluene and then dropwise added to the reactor. The reaction solution was allowed to proceed under reflux at 135°C for 4 hours and then cooled to 20 C. After addition of 500 mL of distilled water and 500 mL of methanol, the pH of the resultant reaction solution was adjusted to 8.5 with adding a 28percent ammonia solution (about 51 mL). An organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. 150 mL of methanol was added to the resultant concentrate, stirred for one hour, and filtered. A filtrate was washed with 100 mL of methanol to give a humid oltipraz crude crystal (12.0 to 13.0 g). The oltipraz crude crystal was placed in a reactor. 400 mL of acetonitrile was added and dissolved at 80 °C. 1.4 g of activated carbon was added and stirred for 30 minutes. The resultant solution was filtered, washed with 100 mL of acetonitrile, crystallized with stirring at a temperature of 20 to 25°C for 2 hours, and again stirred at 10°C for one hour. The obtained crystal was filtered, washed with 20 mL of acetonitrile, and vacuum dried at 40 °C to give 6.37 g of oltipraz (13.6percent yield, >99.5percent purity). NMR (6 CDC13) : 2.51 (s, 3H), 8.70 (d, 1H), 8.80 (d, 1H), 9.21 (s, 1H)
With diphosphorus pentasulfide; Step 3 (treatment of methyl-2-methyl-3-(pyrazin-2-yl)-3-oxopropionate with phosphorus pentasulfide to form oltipraz):
With tetraphosphorus decasulfide; In toluene; at 95 - 97℃; for 36h; ? Charged ST-602 in toluene (-3.5 L; 3-4 vol) to P2S5 (1931 g) in toluene (10 L; 10 vol). Rinsed with toluene (1 L; 1 vol). No exothermic effect, yellow slurry. (0184) ? Reaction over after 36 h at 95-97 °C (0185) 36 h, -95 °C, IPC HPLC lot2463-54-l: 95.2percent of ST-617 at 6.85 min and 4.8percent of ST-602 at 4.79 min (0186) ? Work-up (after 36 h at -95 °C): Cooled to RT over 20 mins (0187) ? Charged the slurry via a transfer line to a mixture of Na2C03 (2686 g; 3.5 eq), water (15 L; 15 vol) and THF (5 L; 5 vol) at 15/30 °C over a minimum of 1 h - weak exothermic effect and no gas evolution observed. (0188) ? The resulting mixture was slowly transferred back to the parent flask - some gas evolution observed. Minor insolubles were observed. (0189) ? The resulting mixture was stirred at RT for 65 h (shouldn't need more than 12 h) to complete gas evolution/quench of the reaction mixture (0190) ? The resulting mixture was passed through a 0.5" celite bed to remove fine insolubles. ? The organic layer was separated, dried with Na2S04 (200 g; 0.2 g/g SM) and concentrated under reduced pressure at (0191) ? The resulting slurry was diluted with MeOH (1.5 L; 1.5 vol) and stirred at RT for 2 h. · The solids were collected by filtration, rinsed with MeOH (2x500 mL; 2x 0.5 vol) followed by heptane (1 L + 0.5 L; 1 + 0.5 vol). (0192) ? Dried in air to yield constant weight. (0193) Isolated material: ST-603 (crude ST-617) (0194) Lot No.: 2463-55- 1 (0195) Appearance: red solid powder (crystals not uniform) (0196) Yield: 223 g (14percent) (0197) HPLC: 99percent by R&D method

  • 2
  • [ 7440-44-0 ]
  • [ 324737-10-2 ]
  • [ 64224-21-1 ]
YieldReaction ConditionsOperation in experiment
With P2S5; conc. ammonia; In methanol; water; toluene; acetonitrile; To a 3L 3-neck round-bottomed flask fitted with pressure-equalising dropping funnel with N2 inlet, condenser with N2 outlet and mechanical stirrer and under a nitrogen atmosphere was charged P2S5 (168.83 g, 759.58 mmol). Toluene (500 mL) was charged to the flask and the slurry was stirred at 20° C. Methyl-2-methyl-3-(pyrazin-2-yl)-3-oxopropionate in toluene (400 mL) (from step 2 of the process) was charged to the slurry in one portion. The resulting yellow slurry was heated to reflux temperature (110° C.) (external oil bath at;135° C.) and stirred at this temperature for 18 hours. The resulting deep red-coloured slurry was cooled to 0-5° C., water was added and the resulting suspension brought to pH 8-8.5 by the addition of conc. ammonia solution (270 mL). The resulting biphasic solution was filtered to remove solid particulates, the black lower aqueous phase was removed and the deep red-coloured upper organic phase (approx. 1L) was retained and combined with the toluene extracts (2*400 mL) of the aqueous phase. The organic phase was dried over magnesium sulphate (30 g) and concentrated in vacuo at;45° C. to a volume of 100 mL. Methanol (100 mL) was added and the resulting slurry was stirred for 20 minutes, then filtered through a sintered funnel and washed with methanol (2*20 mL). The dark red solid was dissolved in acetonitrile (approx. 400 mL) at;78° C., 1.4 g of decolorizing charcoal was added, the solution was filtered and a red precipitate was formed by cooling to 0-5° C. The precipitate was filtered and washed with ice cold acetonitrile (1*40 mL) to afford Oltipraz as bright red needles, (approx. 6.5 g, 10percent), m.p. 167-168° C., structure confirmed by 1H NMR.
 

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