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Chemical Structure| 265121-04-8
Chemical Structure| 265121-04-8
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Product Details of [ 265121-04-8 ]

CAS No. :265121-04-8 MDL No. :MFCD23102059
Formula : C37H56F7N6O16P Boiling Point : -
Linear Structure Formula :- InChI Key :VRQHBYGYXDWZDL-OOZCZQCLSA-N
M.W : 1004.83 Pubchem ID :135564864
Synonyms :
MK-0517;L785298;Fosaprepitant dimeglumine salt

Safety of [ 265121-04-8 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 265121-04-8 ]

* 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 [ 265121-04-8 ]

[ 265121-04-8 ] Synthesis Path-Downstream   1~16

  • 1
  • [ 6284-40-8 ]
  • [ 265121-01-5 ]
  • Fosaprepitant dimeglumine [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With palladium on activated charcoal; hydrogen; In methanol; at 20 - 30℃; under 2250.23 Torr; for 48h; To the autoclave, the compound of formula II (30g), methanol (240m1), N-methyl Dglucamine (14.75m1) and Pd/C (1.5g) were charged and the reaction mass was hydrogenated at 3.0 kg/cm2 hydrogen pressure at 20-30C for 24 h. After completion of the reaction, the catalyst was filtered through hyflo. To the filtrate smopex 234 (1.5g) wasadded and reaction mixture was stirred for 24 hours at 20-30C. The reaction mixture was filtered through hyflo. To the filtrate triphenyl phosphine (1. 5g) was added and reaction mixture was stirred for 24 hours at 20-30C. The reaction mixture was filtered through 0.4 micron. The filtrate was collected and concentrated under vacuum up to 2 to 3 volume to obtain concentrated solution. To the concentrated solution 11% orthophosphuric acidsolution (5.5m1) was added to maintain the pH 6.5-7.5. To the reaction mixture methanol(80m1) was added. The resulting reaction mixture was added to the isopropyl alcohol(750m1) to precipitate a solid. The precipitated solid was then filtered and washed with30% methanol- isopropyl alcohol solution (30m1) followed by acetone (90m1). The solidwas then dried under vacuum at a temperature of 20-30C to yield dimeglumine salt of thecompound of formula I having Pd content less than 1 ppm. Yield 80%, purity 99%, Pdcontent 0.3 ppm.
With hydrogen;palladium 10% on activated carbon; In methanol; under 5171.62 Torr; for 1h;Product distribution / selectivity; EXAMPLE 2: PREPARATION OF FOSAPREPITANT DIMEGLUMINE; 200 ml of methanol, 10 g of dibenzyl ester fosaprepitant of formula 11 obtained in EXAMPLE 1 and 6.0 gm of N-methyl -D- glucamine were charged in a clean and dry 4 neck round bottom flask. 2.0gm of palladium-carbon ( 10%) was charged and 100 psi of anhydrous hydrogen pressure was passed for about 60 minutes under agitation. The reaction progress was monitored by HPLC. Monobenzyl impurity of formula (III) should be less than 0.1 %. After completion of the reaction, the reaction suspension was filtered on celite and the celite was washed with 20ml of methanol. The filtrate was distilled completely at about 65C under vacuum and 100ml of methanol was charged. The resultant residual suspension was stirred for about 1 5 minutes and the solution obtained was added to 200ml of isopropyl alcohol over about 10 minutes. The resultant reaction suspension was stirred for about 30 minutes. The separated solid was filtered and dried (Formula (I)) at about 300C under vacuum for about 1 hour to yield 8.2 gms of the title compound in crude form. Purity by HPLC: 94.5% with dibenzyl fosaprepitant (I I) : Not detected, monobenzyl fosaprepitant (II I): Not detected, aprepitant: 0.2%, desflouroaprepitant: 0.08%.; EXAMPLE 3: PURIFICATION OF FOSAPREPITANTDIMEGLUMINE; 10 gms of crude Fosaprepitant dimeglumine, as obtained in Example 2 and 100 ml of methanol were charged into a clean and dry 4 neck round bottom flask under nitrogen followed by stirring at about 300C for about 10 minutes. 300 ml of acetone(prefiltered) was charged into another clean and dry 4 neck round bottom flask. The above solution of fosaprepitant dimeglumine in methanol was added to acetone at about25C over about 15 minutes under nitrogen atmosphere. The resultant reaction suspension was stirred for about 30 minutes. The separated solid was filtered under nitrogen atmosphere and the solid was washed with 50 ml of acetone. The solid (Formula(I)) obtained was dried at about 300C under vacuum for about 1 hour to yield 8 gms of the title compound in pure form.Purity by chiral HPLC: 99.76% with Aprepitant: 0.05%; desflouro fosaprepitant: 0.06%, monobenzyl fosaprepitant (II I): below detection limit, desflouro aprepitant: below detection limit, diastereomer of fosaprepitant: below detection limit.All other individual impurities are below 0.05%.Assay (on anhydrous basis): 100.5%w/wPalladium content: below detection limit.Content of N-methyl-D-glucamine (on anhydrous basis): 39.7%w/w. Water content by KF: 3.2%w/w; heavy metals: less than 20ppm.
With hydrogen;palladium 10% on activated carbon; In methanol; under 5171.62 Torr; for 1h;Product distribution / selectivity; Example 2Preparation of Fosaprepitant Dimeglumine200 ml of methanol, 10 gm of dibenzyl ester fosaprepitant of formula II obtained in example 1 and 6.0 gm of N-methyl-D-glucamine were charged in a clean and dry 4 neck round bottom flask. 2.0 gm of palladium-carbon (10%) was charged and 100 psi of anhydrous hydrogen pressure was passed for about 60 minutes under agitation. The reaction progress was monitored by HPLC. Monobenzyl impurity of formula (III) should be less than 0.1%. After completion of the reaction, the reaction suspension was filtered on celite and the celite was washed with 20 ml of methanol. The filtrate was distilled completely at about 65 C. under vacuum and 100 ml of methanol was charged. The resultant residual suspension was stirred for about 15 minutes and the solution obtained was added to 200 ml of isopropyl alcohol over about 10 minutes. The resultant reaction suspension was stirred for about 30 minutes. The separated solid was filtered and dried (Formula I) at about 30 C. under vacuum for about 1 hour to yield 8.2 gm of the title compound in crude form.Purity by HPLC: 94.5% with dibenzyl fosaprepitant (II): Not detected, monobenzyl fosaprepitant (III): Not detected, aprepitant: 0.2%, desfluoroaprepitant: 0.08%.
Dibenzyl fosaprepitant (50 gm), N-methyl-D-glucamine (25 gm), palladium carbon (10 gm) and methanol (410 gm) were added at room temperature and then applied 40 percent hydrogen pressure for 5 hours. The reaction mass was filtered through hyflow- bed. To the filtrate thus obtained was added SiliaBond dimercaptotriazine (5 gm) and maintained for 15 hours at room temperature. The reaction mass was filtered through hyflow-bed and the solvent was distilled off under vacuum pressure at 30 to 35C to obtain a residual solid. The residual solid obtained was co-distilled with isopropyl alcohol and acetonitrile. To the reaction mass was added acetonitrile (200 ml) under nitrogen atmosphere and stirred for 15 hours at room temperature. The solid obtained was collected by filtration and dried to obtain 28 gm of fosaprepitant dimeglumine (Palladium content: 3 ppm).
To fosaprepitant dibenzyl ester (110 g) of formula II as an oil obtained in example-1, methanol (800 mL) added and stirred for a while followed by addition of 5 % Pd/C and methanol (110mL). Hydrogen pressure 2.5kg /cm2 to 3.0 kg /cm2 was applied and stirred at 20-30 C for 4 h. Nmethyl D-glucamine (55 g) and methanol (200 mL) was added into the reaction mixture and hydrogen pressure 2.5kg /cm2 to 3.0 kg /cm2 was applied. The reaction mixture was stirred at 20- 30C for 20 h. Pd/C was filtered from the reaction mixture and fresh methanol (220 mL) was added into it followed by addition of tributyl phosphine (6.6 mL), methanol (220 mL) and stirred for about 20-23 h under nitrogen at 20-30 C. To the reaction mixture activated carbon (11 g) was added and stirred for about 1 h. The reaction mixture was filtered and concentrated under vacuum up to -2.0-3.5 volume at 20-30 C. Then after 11 % orthophosphoric acid solution wasadded to adjust the pH reaction mass to 7.5-8.5 followed by addition of methanol (300 mL) and isopropyl alcohol (2750 mL) to the reaction mixture. The reaction mixture was stirred for 1 h, filtered and washed with mixture of methanol and isopropyl alcohol solution, acetone and methyl tert-butyl ether followed by drying at under vacuum below 25 C for 3-4 h to yield fosaprepitant dimeglumine (50-64 %) having purity more than 99 %.

  • 3
  • [ 265121-04-8 ]
  • [ 172673-20-0 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride In methanol; water at 0 - 5℃; for 0.0833333h; 4.C C). CONVERSION OF FOSAPREPITANT DIMEGLUMINE INTO FOSAPREPITANT; 6.0 gm of fosaprepitant dimeglumine salt, prepared as in Part B, 120 ml of water and 120 ml of methanol were charged in a clean and dry round bottom flask followed by cooling to about O0C. The pH of the reaction mixture was adjusted to about 1 by the addition of I N hydrochloric acid solution at about 0°C-5°C. The resultant reaction mixture was stirred for about 5 minutes. The separated solid was filtered and the solid was washed with copious amount of water to neutral pH. Finally, the solid was washed with 12 ml of methanol followed by drying the solid obtained at about 35°C-40°C under vacuum to afford 2.9 gm of fosaprepitant, neutral form, having the XRPD pattern, which is substantially in accordance with Fig. 3; and a DSC thermogram, which is substantially in accordance with Fig. 4.
With hydrogenchloride In methanol; water at 0 - 5℃; for 0.0833333h; 4.C C) Conversion of Fosaprepitant Dimeglumine into Fosaprepitant6.0 gm of fosaprepitant dimeglumine salt, prepared as in Part B, 120 ml of water and 120 ml of methanol were charged in a clean and dry round bottom flask followed by cooling to about 0° C. The pH of the reaction mixture was adjusted to about 1 by the addition of 1N hydrochloric acid solution at about 0° C.-5° C. The resultant reaction mixture was stirred for about 5 minutes. The separated solid was filtered and the solid was washed with copious amount of water to neutral pH. Finally, the solid was washed with 12 ml of methanol followed by drying the solid obtained at about 35° C.-40° C. under vacuum to afford 2.9 gm of fosaprepitant, neutral form, having the XRPD pattern, which is substantially in accordance with FIG. 3; and a DSC thermogram, which is substantially in accordance with FIG. 4.
  • 4
  • [ 265121-04-8 ]
  • [ 170729-80-3 ]
YieldReaction ConditionsOperation in experiment
With water at 90℃; Neat (no solvent);
  • 5
  • [ CAS Unavailable ]
  • [ 90191-92-7 ]
  • [ 265121-04-8 ]
YieldReaction ConditionsOperation in experiment
75% Stage #1: dibenzyl fosaprepitant With 6-methylamino-hexane-1,2,3,4,5-pentaol; hydrogen In methanol Stage #2: 6-methylamino-hexane-1,2,3,4,5-pentaol In methanol 11 Process for the Preparation of Fosaprepitant Dimeglumine.50 gm of Dibenzyl Fosaprepitant was dissolved in about 1.0 litre of methanol. The reaction mixture is subjected to the hydrogenation using Pd/C catalyst and monitored the reaction by HPLC till its completion. The reaction mixture is filtered and residue washed with methanol containing N-methyl-D-glucamine. The clear filtrate of methanol is added slowly to Isopropyl alcohol, filtered the precipitated slurry and dried under vacuum to get pure fosaprepitant dimeglumine salt with any individual impurities less than 0.05%.
YieldReaction ConditionsOperation in experiment
In methanol; acetone at 25 - 30℃; for 0.916667h; Inert atmosphere; 3 Example 3Purification of Fosaprepitant Dimeglumine10 gm of crude Fosaprepitant dimeglumine, as obtained in example 2 and 100 ml of methanol were charged into a clean and dry 4 neck round bottom flask under nitrogen followed by stirring at about 30° C. for about 10 minutes. 300 ml of acetone (prefiltered) was charged into another clean and dry 4 neck round bottom flask. The above solution of fosaprepitant dimeglumine in methanol was added to acetone at about 25° C. over about 15 minutes under nitrogen atmosphere. The resultant reaction suspension was stirred for about 30 minutes. The separated solid was filtered under nitrogen atmosphere and the solid was washed with 50 ml of acetone. The solid (Formula I) obtained was dried at about 30° C. under vacuum for about 1 hour to yield 8 gms of the title compound in pure form.Purity by chiral HPLC: 99.76% with Aprepitant: 0.05%; desfluoro fosaprepitant: 0.06%, monobenzyl fosaprepitant (III): below detection limit, desfluoro aprepitant: below detection limit, diastereomer of fosaprepitant: below detection limit.All other individual impurities are below 0.05%.Assay (on anhydrous basis): 100.5% w/wPalladium content: below detection limit.Content of N-methyl-D-glucamine (on anhydrous basis): 39.7% w/w.Water content by KF: 3.2% w/w; heavy metals: less than 20 ppm
Stage #1: Fosaprepitant dimeglumine With SiliaBond dimercaptotriazine In methanol at 25 - 35℃; for 16h; Stage #2: In methanol; isopropyl alcohol at 20 - 25℃; for 2h; Stage #3: In methanol; ethyl acetate; isopropyl alcohol for 1h; 1 Fosaprepitant dimeglumine (10 gm; Palladium content: 30 ppm) as obtained in preparative example 2 was dissolved in methanol (100 ml) and stirred for 15 minutes to obtain a solution. To the solution was added SiliaBond dimercaptotriazine (1 gm) and then maintained for 16 hours at room temperature. The reaction mass was filtered through hyflow-bed and washed with methanol. To the filtrate thus obtained was added isopropyl alcohol (375 ml) slowly for 1 hour. The reaction mass was stirred for 1 hour at 20 to 25°C and filtered. To the wet solid thus obtained was added ethyl acetate (100 ml) and maintained for 1 hour. The separated solid was filtered and dried to obtain 8 gm of fosaprepitant dimeglumine (Palladium content: 2 ppm).
  • 7
  • C23H20F7N4O6P(2-)*2C4H12N(1+) [ No CAS ]
  • [ 6284-40-8 ]
  • Fosaprepitant dimeglumine [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% Fosapinidine dibenzyl ester (3 g, 3.78 mmole, 1 equiv) was added at 20-30 & lt; 0 &Diethylamine (0.55 g, 7.56 mmole, 2 equiv) And methanol (60 mL) were added to a three-necked round bottom flask containing a stir bar. The mixture was stirred at 20-30 & lt; 0 & gt; C for about 10 minutes to form a homogeneous solution. 10% Pd / C (90 mg, 3 wt%) was added followed by a hydrogenation reaction (about 15 psi) at 20-30 & lt; 0 & gt; C for 1 h. The mixture was filtered through a bed of celite and the filter cake was washed with MeOH (12 mL). Si-Thiourea (0.9 g, 30 wt%) was added to the mixed filtrate and washings at 20 to 30 C, and the mixture was stirred at this temperature for about 15 hours. The mixture was filtered and the filter cake was washed with methanol (12 mL). N-Methyl-D-glucamine (1.62 g, 8.32 mmole, 2.2 equiv) was added to the mixed filtrate and washings at 20 to 30 C, and the mixture was stirred at this temperature for about 1 hour. The solution was concentrated to a volume of about 15 mL at a temperature of not more than 35C and 20 to 30 torr. This concentrated solution was added dropwise to isopropanol (60 mL) at 20-30 & lt; 0 & gt; C, and the resulting mixture was stirred at this temperature for about 1 hour. The mixture was filtered and the filter cake was washed with isopropanol (15 mL). Fosapentin (3.23 g) was obtained in 85% yield with a purity of greater than 99%, a white powder containing less than 0.3 ppm of palladium
  • 8
  • C31H30F7N4O8P [ No CAS ]
  • [ 6284-40-8 ]
  • Fosaprepitant dimeglumine [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% Fosapentin dihydrofuran ester was added at 20-30 & lt; 0 & gt; C(5 g, 6.29 mmole, 1 equiv) and methanol (37.5 mL) were added to a three-neck round bottom flask containing a stir bar. The mixture was stirred at 20-30 & lt; 0 & gt; C for about 10 minutes to form a homogeneous solution. After addition of N-methyl-D-glucamine (2.70 g, 2.2 equiv) and 10% Pd / C (0.15 g, 3 wt%), the mixture was subjected to a hydrogenation reaction (about 15 psi) at 20-30 C for 16 hours. The mixture was filtered through a bed of celite and the filter cake was washed with MeOH (10 mL). The mixed filtrate and washings were concentrated to a volume of about 20 mL at a temperature of not more than 35 C and 20 to 30 torr. The concentrated solution was added dropwise to isopropanol (100 mL) at 20 to 30 C, and the resulting mixture was stirred at this temperature for about 1 hour. The mixture was filtered,And the filter cake was washed with isopropanol (10 mL). (5.56 g) was obtained in 88% yield with purity greater than 99% and was a white powder containing less than 30.6 ppm of palladium.
  • 9
  • [ 265121-01-5 ]
  • [ 265121-04-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: methanol / 0.17 h / 20 - 30 °C 1.2: 1 h / 20 - 30 °C 2.1: Si-Thiol / 15 h / 20 - 30 °C 2.2: 1 h / 20 - 30 °C
  • 10
  • C23H20F7N4O6P(2-)*2C6H16N(1+) [ No CAS ]
  • [ 6284-40-8 ]
  • Fosaprepitant dimeglumine [ No CAS ]
YieldReaction ConditionsOperation in experiment
91.6% For 20-30 C will luck Sha Bitan two animal pen ester (2g, 2.52mmole, 1 equiv), triethylamine (0.51g, 5 . 04mmole, 2 equiv) and methanol (40 ml) containing the sample to a three-necked round-bottom flask. In 20-30 C stirring this mixture under about 10 minutes to form a homogeneous solution. Adding 10% Pd/C (60 mg, 3 wt %), then this mixture in 20-30 C to carry out hydrogenation reaction under (about 15psi) 1 hour. Silicon, through a filter bed filtering the mixture, and to MeOH (8 ml) to wash the filter cake. In 20-30 C has been mixed in is added to the filtrate and wash liquid Si-Thiol (0.2g, 10 wt %), then the mixture is stirred at this temperature for about 15 hours. Filtering the mixture, and in MeOH (4 ml) to wash the filter cake. In 20-30 C has been mixed in is added to the filtrate and wash liquid N-methyl-D- grape amine (1.08g, 5 . 54mmole, 2.2 equiv), then the mixture is stirred at this temperature for about 1 hour. In the solution does not exceed 35 C, 20-30torr volume under the concentrated to about 10 ml. In 20-30 C instillment to of this concentrated solution of isopropanol (40 ml), then the generated mixture stirring at this temperature for about 1 hour. Filtering the mixture, and in isopropanol (10 ml) to wash the filter cake. Obtain fosaprepitant diformic cyclophosphadenosine (2.25g), the yield is 90%, the purity is greater than 99%, to contains less than 0.3 PPM palladium white powder.In addition to using Si-Thiol outside (0.6g, 30 wt %), a new round of duplication of the embodiment of the embodiment 1 to the stated condition. Obtain fosaprepitant diformic cyclophosphadenosine (2.29g), its yield of 91.6%, the purity is greater than 99%, to contains less than 0.3 PPM palladium white powder.
  • 11
  • [ 2054311-37-2 ]
  • [ 6284-40-8 ]
  • [ 265121-04-8 ]
YieldReaction ConditionsOperation in experiment
66.48% Stage #1: fosaprepitant di(dicyclohexylamine) With hydrogenchloride In methanol; water Stage #2: 1-deoxy-1-(methylamino)-D-glucitol In methanol 3 Synthesis of Fosaprepitant Dimeglumine (Ia) 10057] To a solution of dibenzyl fosaprepitant (prepared as per prior art processes) in ethyl acetate (1000 mL), dicyclohexyl amine (74.64 g, 0.41 mol), 10% Pd/C (50% wet) (25 g), basic alumina (20 g), and 20 mL of water were added and were stirred under a hydrogen pressure at a temperature of about 25° C. to 30° C. until reaction completion. The reaction mass was filtered through hyflow and removed the solvent from the filtrate by distillation to obtain residue of fosaprepitant DCHA (II). The residue was dissolved in 1000 mL of Methanol. Aqueous HC1 was added to adjust pH about 2.0 and stirred to precipitate the solid fosaprepitant (I). The fosaprepitant solid was filtered and added in 400 mL of Methanol, N-Methyl-D-glucamine (70 g, 0.358 mol) was added. The resulting reaction mixture was stirred for about 20 to 30 minutes and filtered. The filtrate was added into a mixture of acetonitrile (3500 mL) and isopropyl alcohol (1700 mL) to crystallize fosaprepitant dimeglumine (Ia). The fosaprepitant dimeglumine solid was filtered, dried under vacuum at a temperature from about 25° C. to about 35° C. to obtain fosaprepitant dimeglumine (Ia) (125 g, 66.48% yield) having a HPLC purity of 99.5%.
  • 12
  • [ 6284-40-8 ]
  • [ 170729-80-3 ]
  • Fosaprepitant dimeglumine [ No CAS ]
YieldReaction ConditionsOperation in experiment
98% Step The formula V compound 5 - [[2 (R) - [1 (R) - [3,5- bis (trifluoromethyl) phenyl] ethoxy] -3 (S) - (4- fluorophenyl ) -4-morpholinyl] methyl] -1,2-dihydro--3H-1,2,4- triazol-3-(5.3g, 10mmol), pyrophosphoric acid tetrabenzyl ester (7.0g, 13mmol ) was dissolved in THF (60ml), ice-water bath, a solution of NaHMDS 2.0M (12ml, 24mmol), controlling the reaction temperature at about -3 . Dropwise to a stirred for 2h the reaction was complete, methyl tert-butyl ether was added (150ml) and saturated sodium bicarbonate solution (150ml), separated, saturated sodium bicarbonate solution (150ml), sodium bisulfite solution (150ml), water ( 150ml) washed, and concentrated to dryness, dried to obtain 5.9 g of a white solid, a yield of 86.7%. Step B The resulting product from the previous step (5.9g, 8.4mmol), N- methyl-glucamine -D- (2.2g, 11.3mmol) was dissolved in methanol (25ml) / water (1ml), was added 10% Pd / C (0.1 g), to atmospheric hydrogenation 4h the reaction was complete. Filtered and washed with methanol, concentrated to dryness, methanol (15ml), tributylphosphine (0.03 ml of), stirred overnight, isopropanol precipitated solid was filtered and washed with methanol (1ml). Added dropwise to ethanol (30ml) / acetonitrile (30ml), stirred IH, filtered and washed with acetonitrile, and dried in vacuo to give a white solid 7.5g. The solid was dissolved in methanol (50ml), added dropwise to acetone (150ml), stirred for 2h, filtered, washed with acetone and dried in vacuo to give a white solid 5.7g, yield 98%, proven a compound of formula I, the purity of the product 99.9%.
  • 13
  • C49H42F7N4O6P [ No CAS ]
  • [ 6284-40-8 ]
  • Fosaprepitant dimeglumine [ No CAS ]
YieldReaction ConditionsOperation in experiment
97% With 10% palladium hydroxide on charcoal; hydrogen; In methanol; water; at 25℃; under 1034.32 Torr; for 1h; A mixture of 21.0 g of compound IV (22.2 mmol ) Was dissolved in 150 mL of methanol,8.7 g of N-methyl-D-glucosamine (44.4 mmol) and 3.0 g of 10% Pd (OH) 2 / C (water content 66%) were added and catalytically hydrogenated at 25 C, 20 psi hydrogen for 1 h,The reaction was complete by filtration, and the filter cake was rinsed with 10 mL of methanol. The filtrate was added dropwise to a stirred mixture of 1.1 L of acetone, filtered under nitrogen and the filter cake was washed with 100 mL of acetone and dried in vacuo at room temperature to give 21.6 g of the title compound as a white solid in 97% yield.
  • 14
  • [ CAS Unavailable ]
  • [ 172673-20-0 ]
  • [ 265121-04-8 ]
YieldReaction ConditionsOperation in experiment
8.1 kg In isopropyl alcohol for 2.5h; Large scale; 2 7.1 Kg of product (II) was dissolved in 70 L of methyl tert-butyl ether.Control the reaction temperature -5 ° C,2.6 L of 1 M BCl3 dichloromethane solution was slowly added dropwise under nitrogen protection.After the drop,TLC was used to monitor the endpoint of the reaction.The reaction is over,Concentrated under reduced pressureCrude,This crude product was dissolved in 60 L of methanol.Stir for 30min,Filter to remove insoluble matter,3.66 Kg was added to the obtained filtrate.N-methyl-D-glucosamine,Continue to stir the reaction for 1.5 h,Then 180 L of isopropanol was added dropwise thereto.After the addition is completed,Stirring and crystallization for 1 h,Filtered under nitrogen,Vacuum drying gave 8.53 Kg of a white solid.The yield was 95%.The white solid obtained above was dissolved in 10 L of anhydrous methanol.Under nitrogen protection,Slowly add it to 150 L of acetone,After the drop,Continue to stir for 2h,Filtered under nitrogen,Drying at 25 ° C in vacuo gave a white solid 8.1 Kg.
  • 15
  • [ 170729-80-3 ]
  • [ 265121-04-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium hexamethyldisilazane / tetrahydrofuran / 0 °C / Large scale 2: boron trichloride / tert-butyl methyl ether; dichloromethane / -5 °C / Inert atmosphere; Large scale 3: isopropyl alcohol / 2.5 h / Large scale
  • 16
  • [ 6284-40-8 ]
  • [ 172673-20-0 ]
  • [ 265121-04-8 ]
YieldReaction ConditionsOperation in experiment
96.3% In methanol at 20℃; for 1h; 1.3; 2.3; 3.3; 4.3 Step (3) Dissolve 30mmol of fosaprepitant obtained in step (2) in 50ml methanol, add 65mmol N-methyl-D-glucosamine, stir at room temperature for 1h, after the reaction is completed, add 150ml isopropanol dropwise to the system, stir and crystallize for 1h , Filter, dissolve the solid in 20ml methanol again, then add it to 200ml acetone, keep stirring for crystallization, and vacuum drying to obtain a white solid fosaprepitant dimethylmeglumine. The calculated yield is 96.3% and the purity is 99.8%.
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