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[ CAS No. 24280-93-1 ] {[proInfo.proName]}

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Chemical Structure| 24280-93-1
Chemical Structure| 24280-93-1
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Product Details of [ 24280-93-1 ]

CAS No. :24280-93-1 MDL No. :MFCD00036814
Formula : C17H20O6 Boiling Point : -
Linear Structure Formula :- InChI Key :HPNSFSBZBAHARI-RUDMXATFSA-N
M.W : 320.34 Pubchem ID :446541
Synonyms :
Mycophenolate;MPA;Mycophenolic acid, Mycophenolate mofetil, Cellcept, Myfortic, RS-61443;NSC 129185;RS-61443

Calculated chemistry of [ 24280-93-1 ]

Physicochemical Properties

Num. heavy atoms : 23
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.41
Num. rotatable bonds : 6
Num. H-bond acceptors : 6.0
Num. H-bond donors : 2.0
Molar Refractivity : 84.35
TPSA : 93.06 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.98 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.38
Log Po/w (XLOGP3) : 3.2
Log Po/w (WLOGP) : 2.58
Log Po/w (MLOGP) : 1.82
Log Po/w (SILICOS-IT) : 3.52
Consensus Log Po/w : 2.7

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.56

Water Solubility

Log S (ESOL) : -3.64
Solubility : 0.0735 mg/ml ; 0.00023 mol/l
Class : Soluble
Log S (Ali) : -4.83
Solubility : 0.00478 mg/ml ; 0.0000149 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -3.56
Solubility : 0.0878 mg/ml ; 0.000274 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 3.02

Safety of [ 24280-93-1 ]

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 [ 24280-93-1 ]

* 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 [ 24280-93-1 ]

[ 24280-93-1 ] Synthesis Path-Downstream   1~75

  • 1
  • [ 31858-66-9 ]
  • [ 24280-93-1 ]
YieldReaction ConditionsOperation in experiment
4.2 mg With sodium hydroxide; for 1h; Further purification and isolation of the Ulva extracts of the present invention have excellent resistance to influenzaThe toxicological active ingredient SAOF-K09 (compound of formula (I), 6 mg) was placed as a starting materialIn a 5-mL tube, add 1 ml 0.1 N NaOH_to shake for 1 hour and add 1.5 ml0. 1. HC1 iv acidified, extracted with ethyl acetate 5ml 3 times, the combined extracts,5 g of anhydrous sodium sulfate in addition to water, filtered, concentrated and crystallized to hydrolyze the compound(AnWen 2150, 4.2 mg), identified as Mycophenolic acid,
  • 2
  • [ 24280-93-1 ]
  • [ 75-31-0 ]
  • [ 1000853-03-1 ]
YieldReaction ConditionsOperation in experiment
75.1% In ethyl acetate; at 11 - 55℃; for 2h; Example 2 Crystallization of MPA-isopropylamine salt (MPA-IPA) from MPA extract From an MPA ethyl acetate extract (200 ml_, containing 8.12 mmol MPA) obtained analogous to Example 1 , 1 10 ml. were distilled off over a period of 1 h at 79C. The residue was cooled to 55C and a mixture of ethyl acetate (10 ml.) and isopropyl amine (6 ml.) were added. During cooling at ca 48C crystallization started, further cooled to 1 1 C and stirred for 1 h. The precipitate was filtered off and washed/replaced with ethyl acetate (15 ml_). The wet cake was dried under vacuum at room temperature to give 2.788 g of the title compound with a purity of 83%; yield: 75.1 %.
  • 3
  • [ 24280-93-1 ]
  • [ 108-24-7 ]
  • [ 31377-08-9 ]
YieldReaction ConditionsOperation in experiment
83% With pyridine; dmap; at 0℃; Acetic anhydride (0.2 mL, 1.9 mmol) was slowly added to a pyridine (5 mL) solution of MPA (0.2 g, 0.62 mmol) and 4-Dimethylaminopyridine (DMAP, 0.03 g, 0.25 mmol) at 0 C. The reaction mixture was stirred for 2 h and then poured onto crushed ice. The aqueous phase was acidified with 2 M aq. HC1 (pH ~ 2) and extracted with EtOAc (3 x 400 mL). The combined organic extracts were dried over Na2S04, filtered, and the solvent was removed under reduced pressure to afford acetylated MPA 2 (0.18 g, 83%) as a white powder mp 155-157 C. 1H NMR (500MHz, CDC13): delta 5.18-5.5 (m, 3H), 3.79 (s, 3H), 3.28 (d, J = 6.9 Hz, 2 H), 2.43-2.38 (m, 5H), 2.33-2.28 (m, 2H), 2.21 (s, 3H), 1.79 (s, 3H). Mass: 385.2 (M+Na).
  • 4
  • [ 38877-93-9 ]
  • [ 24280-93-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 189 mg / ethyl acetate 2: BCl3 / CH2Cl2 / 12 h / 20 °C 3: 92 mg / LiOH / methanol; H2O / 6 h / 20 °C
Multi-step reaction with 3 steps 1: ethyl acetate 2: 86 percent / BCl3 / CH2Cl2 / 192 h 3: LiOH / H2O
  • 5
  • [ 24280-93-1 ]
  • [ 402731-01-5 ]
YieldReaction ConditionsOperation in experiment
75% Stage #1: mycophenolic acid With osmium(VIII) oxide; 4-methylmorpholine N-oxide In tetrahydrofuran; water; acetic acid at 20℃; for 1.5h; Stage #2: With sodium periodate In water at 0℃; Stage #3: With sodium tetrahydroborate In ethanol at 20℃; for 3h; Inert atmosphere; 2-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)acetaldehyde (33) To a solution of MPA (1.92 g, 6 mmol) and NMO (1.41 g, 12 mmol) in a 3:1 (v/v) mixtureof THF/H2O (24 mL) was added a solution of OsO4 (50 mg, 0.2 mmol) in acetone (2 mL). Theresulting mixture was stirred at room temperature for 1.5 h, and then diluted with H2O (60 mL).The mixture was cooled to 0 oC, and a solution of NaIO4 (4.28 g, 3.33 mmol) in H2O (40 mL) wasadded in portions. The formed precipitate was filtered, washed with cold water (3 × 10 mL) anddried to give a white solid. This intermediate (50 mg, 0.2 mmol) in EtOH (2 mL) was added NaBH4(18.9 mg, 0.5 mmol) under argon. The resulting mixture was stirred at room temperature for 3 hand then quenched by the addition of 3N HCl until pH 7. The aqueous layer was extracted withEtOAc (2 × 50 mL), and the combined organic extracts were washed with brine, dried overanhydrous Na2SO4, filtered and concentrated. The residue was purified by column chromatographyon silica gel (EtOAc/DCM, 5:95 to 10:90) to afford 33 (36 mg, 75%) as a white solid.
Multi-step reaction with 2 steps 1.1: OsO4; aq. 4-methylmorpholine-N-oxide / tetrahydrofuran; acetone / 3.5 h 2.1: aq. NaIO4 / acetone; tetrahydrofuran / 0 °C 2.2: NaBH4 / ethanol / 2 h / 20 °C
  • 6
  • [ 3465-69-8 ]
  • [ 24280-93-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1: 87 percent / HCl / H2O / 13 h / 0 - 20 °C 2: 99 percent / H2; MgO / Pd/C / ethyl acetate / 16 h / 20 °C 3: 92 percent / I2; CF3CO2Ag / CH2Cl2 / 27 h / 20 °C 4: 22 percent / NaH; n-Bu4NCl / [Pd2(dba)3CHCl3] / dimethylsulfoxide / 4 h / 80 °C 5: 49 percent / NaCl; H2O / dimethylsulfoxide / 3 h / 150 °C 6: 88 percent / LiOH; H2O / methanol / 40 h / 20 °C 7: 70 percent / Mg; I2; pyridine / diethyl ether; benzene / 6 h / 90 °C
  • 7
  • [ 622-40-2 ]
  • [ 24280-93-1 ]
  • [ 115007-34-6 ]
YieldReaction ConditionsOperation in experiment
84% toluene-4-sulfonic acid; at 160℃; for 5h;Product distribution / selectivity; A mixture of <strong>[24280-93-1]mycophenolic acid</strong> (96.1 g, 0.3 mol), 4-(2-hydroxyethyl)morpholine (147 ml, 4 molar equivalents), toluene-4-sulfonic acid monohydrate (1.7 g, 20 mol %) was stirred at 160 C. for 6 hours. The cooled mixture was poured into a stirred mixture of sodium hydrogen carbonate (100 g), Celite 545 (100 g), seeding crystals in 2 L of water. Stirring was continued for 4 hours at room temperature, then the solid was filtered off, washed with water (0.5 L), and dried at room temperature. The crude product was 209.07 g (84%). Crude product: MMF 91 area %, MPA 2 area %, Compound 1: 0.4 area %.
84% (1S)-10-camphorsulfonic acid; at 150 - 155℃; for 8h;Product distribution / selectivity; A mixture of <strong>[24280-93-1]mycophenolic acid</strong> (9.60 g, 30 mmol), 4-(2-hydroxyethyl)morpholine (14.7 ml, 4 molar equivalents) and (+)-camphorsulfonic acid (0.21 g, 0.9 mmol, 3 mol %) was stirred at 150-155 C. for 8 hours. After cooling to room temperature, water (200 ml) was added to the reaction mixture, and the mixture was seeded and stirred for 2 hours. The solid material was filtered off, washed with water (100 ml) and dried at room temperature. The product was 10.93 g (84% yield). MPA level: 2.4 area %.
84% at 160℃; for 5h;Product distribution / selectivity; A mixture of <strong>[24280-93-1]mycophenolic acid</strong> (9.6 g, 30 mmol), 4-(2-hydroxyethyl)morpholine (147 ml, 4 molar equivalents) was stirred at 160 C. for 5 hours. After cooling to room temperature, water (200 ml) was added, followed by seeding. The solid was filtered off and washed with water. The dry product was 10.9 g (84%). Crude product: MPA 3 area %, Compound 1: 0.2 area %.
75% Under the protection of nitrogen, Ph3 P (18.4 g, 70 mmol, 1.40 eq), morpholine ethanol (6.6 g, 50 mmol, 1.0 eq) dissolved in 200 ml ethyl acetate after, cooled to 0 C, control temperature of not more than 10 C, in 15 - 20 min by adding DIAD (15.2 g, 75 mmol, 1.50 eq) of ethyl acetate (30 ml) solution, canada finishes, orange solution is continuously stirred for 15 min. Then 0 - 10 C adding <strong>[24280-93-1]mycophenolic acid</strong> (17.6 g, 55 mmol, 1.10 eq) of ethyl acetate (40 ml) solution, canada finishes, stirring at room temperature for 6 h. The reaction liquid is poured into 150 ml water, stirring 5 min, liquid, organic uses 60 ml of 1 N extraction a hydrochloric acid solution, then hydrochloric acid solution for 30 ml ethyl acetate washed, saturated sodium bicarbonate solution for adjusting the pH to 8, have more white turbid to separate out, for sequentially 50 ml ethyl acetate, 20 ml ethyl acetate extraction, the combined organic phase, dried with anhydrous sodium sulfate, filtered, concentrated, get the yellow oily liquid. To the yellow oily liquid adding 180 ml anhydrous ethanol, heating to reflux to dissolve, slightly cold, adding 1 g of active carbon, continue to reflux 10 min, the condiments filtering, the filtrate is 5 C left crystallization 4 h, filtered, 30 ml anhydrous ethanol washing, to obtain white powder, mycophenolate mofetil 16.2 g, yield 75%.
70% 1.09g of freshly prepared sodium methoxide (in methanol) was dissolved in 25 ml toluene. Then into it 2.62g of 4-(2-hydroxyethyl)morpholine was added and stirred for 30min. to lhr. at room temperature. Further reaction mixture was stirred for 30min- lhrs. at 70 0C to give a clear solution of 2-Morpholin-4-yl-sodium ethoxide. In a separate round bottom flask 5g of Mycophenolic acid and 10ml of toluene was taken, equipped with Dean Stark assembly and it was heated at 110 0C. Then into it a solution of 2-Morpholin-4-yl-sodium ethoxide in toluene was added drop wise with constant removal and addition of fresh toluene under Dean Stark trap for 30min. to 80 min., after that removal of toluene stopped and reaction mass left at this temperature for 4hr. TLC checked, for reaction completion. From reaction mass toluene was removed and water was added. Then reaction mass was extracted thrice with ethyl acetate. Combined organic layers were dried over sodium sulphate and distilled out under reduced pressure at 40 0C.Purification of Mycophenolate mofetil obtained as above is carried out in a similar way as disclosed in Example- 1, to obtained highly pure Mycophenolate mofetil. [Yield-70%, HPLC Purity- 99.8%]
68% zinc(II) sulfate; at 160 - 165℃; for 4h;Product distribution / selectivity; A mixture of <strong>[24280-93-1]mycophenolic acid</strong> (9.60 g, 30 mmol), 4-(2-hydroxyethyl)morpholine (22.0 ml, 6 molar equivalents) and zinc sulfate heptahydrate (0.04 g, 0.5 mol %) was stirred under nitrogen atmosphere at 160-165 C. for 4 hours. The cooled mixture was dissolved in toluene (100 ml) at room temperature, and the solution was washed saturated sodium bicarbonate solution (100 ml). The aqueous washing liquor was re-extracted with toluene (25 ml). The organic phases were combined, washed with saturated sodium bicarbonate solution (2×100 ml), dried on sodium sulfate, decolorized with charcoal (1 g) and evaporated to the 1/3 volume (ca. 38 g). To the solution isopropanol (150 ml) was added and the mixture was kept in the fridge overnight. The solid was filtered off, washed with heptane (15 ml) and dried at room temperature. The crude product was 8.80 g (68% yield). MPA level: 0.03 area %. Assay: 96.0%
65 - 75% tin(ll) chloride; at 150 - 180℃; for 1.5 - 4h;Product distribution / selectivity; A mixture of <strong>[24280-93-1]mycophenolic acid</strong> (192 g, 0.6 mol) and 4-(2-hydroxyethyl)morpholine (440 ml, 6 molar equivalents) was stirred at 150-155 C. for 4 hours in the presence of tin(II) chloride dihydrate (20.4 g, 0.15 molar equivalents) under nitrogen atmosphere. After the completion of the reaction, the reaction mixture was allowed to cool to room temperature. The obtained dark liquid was poured into isobutyl acetate (4.0 l). The solution was extracted with 2% of aqueous sodium bicarbonate solution (1.2 l, then 2×0.4 l). After the first addition of sodium bicarbonate solution, the formed two-phase system was treated with charcoal (40 g) and filtrated (an emulsion was filtered off). The solution was extracted with water (1 liter). After phase separation the organic phase was washed with water (1 liter) and evaporated to dryness at 40-50 C. under vacuum. To the solid material acetone (400 ml) and isopropanol (3.8 l) were added and the mixture was warmed to 40-45 C. The material was dissolved. The solution was cooled to -5 C. over 6 hours and stirred at this temperature for 10-12 hours. After filtration, the crystals were washed with a 2:19 acetone/isopropanol mixture (420 ml). The crude compound was dried under vacuum at 60 C. The yield was 169-195 g (65-75%). MPA level: 0.1 area %. Assay: 99.85%. A mixture of <strong>[24280-93-1]mycophenolic acid</strong> (9.60 g, 30 mmol), 4-(2-hydroxyethyl)morpholine (14.7 ml, 4 molar equivalents) and tin(II)chloride dihydrate (0.20 g, 3 mol %) was stirred under nitrogen atmosphere at 180 C. for 90 minutes. The cooled mixture was diluted in toluene (100 ml) at room temperature, and the solution was washed with saturated sodium bicarbonate solution (100 ml). The aqueous washing liquor was re-extracted with toluene (25 ml). The organic phases were combined, washed with saturated sodium bicarbonate solution (2×100 ml), dried on sodium sulfate, decolorized with charcoal (1 g) and evaporated to the 1/3 volume (ca. 44 g). Isopropanol (150 ml) was added to the solution and the mixture was kept in the fridge overnight. The solid was filtered off, washed with heptane (15 ml) and dried at room temperature. The crude product was 8.54 g (65% yield). MPA level: 0.06 area %. Assay: 97.1%
62% potassium dihydrogenphosphate; at 165℃; for 3h;Product distribution / selectivity; A mixture of <strong>[24280-93-1]mycophenolic acid</strong> (64.07 g, 0.2 mol), 4-(2-hydroxyethyl)morpholine (98 ml, 4 molar equivalents) and potassium dihydrogenphosphate (0.82 g, 3 mol %) was stirred under nitrogen atmosphere at 165 C. for 3 hours. The cooled mixture was dissolved in toluene (700 ml) at room temperature, and the solution was washed with 5% aqueous sodium bicarbonate solution (2×700 ml). The organic phase after drying on sodium sulfate was decolorized with charcoal (30 g). To the stirred solution, n-heptane (1000 ml) was added and the mixture was warmed to 60 C. The solution was cooled to -10 C., and after 1 hour the crystals were filtered off and dried at room temperature. The crude product was 54.0 g (62% yield). MPA level: 0.06 area %. Assay: 95.6%
57% sulfuric acid; In toluene; for 0.5h;Microwave irridation; ImM of MPA and 3mM of HEM TAKEN IN AN open 250 ml beaker and added 2g bentonite, mixed well with small amount of solvent Allowed the solvent to evaporate. The mixture was irradiated under microwave for 30 minutes. The yield OF MMF WAS 10 %
52% for 1.66667h;Microwave irridation; 1MM of MPA and 3mM of HEM taken in an open 250ML beaker and added 2g silica, mixed well with small amount of solvent. Allowed the solvent to evaporate. The mixture was irradiated under microwave for 100 minutes. The yield of MMF was 52%
37.3% sulfuric acid; In toluene; for 0.5h;Microwave irridation; 1MM of MPA and 3 mM of HEM taken in an open 250ML beaker and added 50 ML of Toluene and 0. 05ML of Sulfuric acid. The mixture was exposed to microwave radiation in AT 1000W for 30 minutes. The YIELD OF MMF WAS 37.3%
23% In toluene; xylene; for 0.5h;Microwave irridation; 1MM of MPA and 3mM of HEM taken in a 50 ML beaker and added 2ML of Toluene and Xylene (5: 1). The mixture was exposed to microwave radiation at 1000W for 30 minutes. The yield OF MMF was is 23%.
10% for 0.5h;Microwave irridation; ImM of MPA and 3mM of HEM TAKEN IN AN open 250 ml beaker and added 2g bentonite, mixed well with small amount of solvent Allowed the solvent to evaporate. The mixture was irradiated under microwave for 30 minutes. The yield OF MMF WAS 10 %
24%Chromat. In toluene; for 0.5h;Microwave irridation; 1MM of MPA and 3mM of HEM taken in a 50ML beaker and added to 0. 1G SILICA GEL in 2ML of Toluene and mixed well. The mixture was exposed to microwave radiation at 1000W for 30 minutes. The yield of MMF was calculated from HPLC assay to 24%.
In toluene; at 110 - 120℃; for 24h;Drying agent (sodium sulfate);Product distribution / selectivity; Example 1; Preparation of Mycophenolate Mofetil: Use of Sodium Sulfate as Drying AgentIn a 50 L of stainless reactor, 11.56 Kg of toluene, 10.0 Kg of <strong>[24280-93-1]mycophenolic acid</strong> (MPA), 6.14 Kg of 2-morpholinoethanol, and 1.0 Kg of sodium sulfate were added. The reaction mixture was heated until the pot temperature was between 110 C. and 120 C. The reaction temperature was kept at this range for performing the condensation reaction in a period of 24 hours.When mycphenolate mofetil was formed, the reaction mixture was cooled below 100 C. and added with 11.0 Kg of toluene and 10.0 Kg of water. The reaction mixture was maintained between 50 C. and 60 C., and further vigorously agitated for 1015 minutes. The layers were separated and organic layer was washed with 5% sodium bicarbonate aqueous solution. The organic layer was added with 10.0 Kg of water and further vigorously agitated for 1015 minutes. The aqueous layer was discarded from this reactor. The reaction mixture was cooled to 010 C. and kept stirred about 8 hours. 9.2 Kg of white crystalline powder was obtained by centrifuge. Loss on drying of this wet cake was about 12.8%. Purity by HPLC was 99.6%.9.2 Kg of wet cake were put in a 50 L of reactor with a reflux condenser together with 14.4 Kg of ethylacetate. The reaction mixture was heated to about 52 C. The resulting solution was passed through the filter into another 50 L of stainless reactor, and then was cooled to 2030 C. about 4 hours. The solution was further cooled to 010 C. and kept stirred not less than 8 hours. 8.0 Kg of white crystalline powder was obtained by centrifuge. 7.2 Kg of pure title compound was obtained by vacuum dried. (Purity by HPLC: 99.9%, M.P. by DSC: 95.7 C.)
In toluene; at 110 - 120℃; for 24h;Drying agent (magnesium sulfate);Product distribution / selectivity; Example 2; Preparation of Mycophenolate Mofetil: Use of Magnesium Sulfate as Drying AgentIn a 50 L of reactor, 13.0 Kg of toluene, 10.0 Kg of <strong>[24280-93-1]mycophenolic acid</strong> (MPA), 4.5 Kg of 2-morpholinoethanol, and 1.0 Kg of magnesium sulfate were added. The reaction mixture was heated until the pot temperature was between 110 C. and 120 C. The reaction temperature was kept at this range for performing the condensation reaction within 24 hours.When mycphenolate mofetil was formed, the reaction mixture was cooled below 100 C. and added with 9 Kg of toluene and 10 Kg of water. The reaction mixture was maintained between 50 C. and 60 C., and further vigorously agitated for 1015 minutes. The layers were separated and organic layer was washed with 5% sodium bicarbonate aqueous solution. The organic layer was added with 10 Kg of water and further vigorously agitated for 1015 minutes. The aqueous layer was discarded from this reactor. The reaction mixture was cooled to 010 C. and kept stirred about 8 hours. 9.0 Kg of white crystalline powder was obtained by centrifuge. Loss on drying of this wet cake was about 10.0%. Purity by HPLC was 99.6%.9.0 Kg of wet cake were put in a 50 L of stainless reactor with a reflux condenser together with 14.6 Kg of ethylacetate. The reaction mixture was heated to about 52 C. The resulting solution was passed through the filter into another 50 L of stainless reactor, and then was cooled to 2030 C. about 4 hours. The solution was further cooled to 010 C. and kept stirred not less than 8 hours. 8.1 Kg of white crystalline powder was obtained by centrifuge. 7.3 Kg of pure title compound was obtained by vacuum dried (Purity by HPLC: 99.7%, M.P. by DSC: 95.3 C.).
With 2,2'-dipyridyl carbonate;dmap; In toluene; at 20℃; for 10 - 24h;Product distribution / selectivity; EXAMPLE 1:To a solution of Mycophenolic acid (5 g) in toluene 100 mL added morpholino ethanol (2.2g) to obtain solution. Dipyridyl carbonate (3.4g) was added to this solution along with 0.1g of Dimethylaminopyridine. The reaction mixture was stirred at RT for about 24 hrs till the reaction is completed. Usual workup involves washing of toluene layer with 5% sodium bicarbonate solution and the organic layer separated was evaporated under vacuum at 30-500C to afford an oily residue. The oily residue was precipitated in Cyclohexane to yield off white solid as Mycophenolate mofetil (5.2g) Purity: >99%; EXAMPLE 3:To a solution of Mycophenolic acid (5g) in toluene (100 mL) added morpholino ethanol (2.2g) to obtain solution. Dipyridyl carbonate (3.4g) was added to this solution along with 0.1g of Dimethylaminopyridine. The reaction mixture was stirred at RT for about 10 hrs till the reaction completion. Usual workup involves washing of toluene layer with 5% sodium bicarbonate solution and the organic layer separated was evaporated under vacuum at 30-50 0C to afford an oily residue. The oily residue was precipitated in Cyclohexane to yield off white solid as Mycophenolate mofetil (5.1g). Purity. >99%.
With 2,2'-dipyridyl carbonate;dmap; In dichloromethane; at 20℃; for 24h;Product distribution / selectivity; To a solution of Mycophenolic acid (5g) in Dichloromethane 100 mL added morpholino ethanol (2.2g) to obtain solution. Dipyridyl carbonate (3.4g) was added to this solution along with 0.1g of Dimethylaminopyridine. The reaction mixture was stirred at RT for about 24 hrs till the reaction was completed. Usual workup involves washing of toluene layer with 5% sodium bicarbonate solution and the organic layer separated was evaporated under vacuum at 25-300C to afford an oily residue. The oily residue was precipitated in Cyclohexane to yield off white solid as Mycophenolate mofetil (5. 1g) Purity: > 99%
With 2,2'-dipyridyl carbonate;dmap; at 20℃; for 24h;Product distribution / selectivity; To a solution of Mycophenolic acid (5g), added morpholino ethanol (5.0g). Dipyridyl carbonate (3.4g) was added to this solution along with 0.1g of Dimethylaminopyridine. The reaction mixture was stirred at RT for about 24 hrs till reaction completion. Usual workup involves washing of organic layer with 5% sodium bicarbonate solution and the organic layer evaporated to afford an oily residue which was precipitated in Cyclohexane to yield off white solid as Mycophenolate mofetil. Purity: >99%
Example 661.4 gm of 2-(4-morpholinyl)ethanol and 2.3 gm DMF was added to 100 gm Mycophenolic acid and the resultant mixture was heated. 14 gm molecular sieve was added to reaction mixture and it was heated at 120-130 C. for 20-24 hrs. The reaction mixture was cooled and 800 ml toluene was added. Molecular sieve were separated by filtration and to the resultant solution 400 ml sodium carbonate aqueous solution was added. Layers were separated and to the organic layer 600 ml water was added, the pH was adjusted to 2-2.5 by adding HCl and layers were separated and the pH of aqueous layer was adjusted to 8-8.5 by sodium carbonate. The precipitated product was extracted by toluene. The toluene was distilled off to obtain mycophenolate mofetil 100 gm, purity 99% by HPLC.

  • 8
  • [ 24280-93-1 ]
  • sodium mycophenolate [ No CAS ]
YieldReaction ConditionsOperation in experiment
97% With sodium methylate; In methanol; ethyl acetate; at 20℃; for 1h;Charcoal;Product distribution / selectivity; Example 3; A mixture of MPA (128 g) and charcoal (2.56 g) in ethyl acetate (4750 ml) was stirred for 0.5 h, then the charcoal was filtered off and washed with ethyl acetate (250 ml). 30% sodium methoxide in methanol (75.9 ml) was then added dropwise to the stirred filtrate at room temperature. The mixture was stirred for an additional 30 minutes, then the precipitated product was filtered off and washed with ethyl acetate (250 ml). The solidmaterial was dried at 40-45 C in a vacuum oven. Form M2 of mycophenolate sodium wasobtained in 97% yield.
94 - 96% With sodium methylate; In methanol; ethyl acetate; at 20℃; for 0.5h;Product distribution / selectivity; Example 4; To a stirred solution of MPA (6.4 g) in ethyl acetate (250 ml), 30% sodium methoxide in methanol (3.8 ml) was added dropwise at room temperature. The reaction mixture was stirred for an additional 30 minutes, then the precipitated product was filtered off and washed with ethyl acetate. The solid material was dried at 40-45 C in a vacuum oven. Form M2 of mycophenolate sodium was obtained in 94% yield; Example 5; To a stirred solution of MPA (128 g) in ethyl acetate (5 L), 30% sodium methoxide in methanol (74 ml) was added dropwise at room temperature. The reaction mixture was stirred for an additional 30 minutes, then the precipitated product was filtered off and washed with ethyl acetate. The solid material was dried at 60-65C in a vacuum oven. Form M2 of mycophenolate sodium was obtained in 96% yield; Example 6; To a stirred solution of MPA (24 g) in ethyl acetate (0.93 L), 30% sodium methoxide in methanol (14 ml) was added dropwise at room temperature. The reaction mixture was stirred for an additional 30 minutes, then the precipitated product was filtered off and washed with ethyl acetate. A part of the solid material was divided into three parts and dried at 40-45 C, 60-65 C and 80-85 C in vacuum oven, respectively. Form M2 of mycophenolate sodium was obtained.
92% With sodium methylate; In methanol; ISOPROPYLAMIDE; at 20℃; for 0.166667h;Product distribution / selectivity; Example 420 ml of dimethylacetamide and 20 ml of methanol was added to 5 gm myophenolic acid and the resultant mixture was stirred for 10 minutes at ambient temperature. To the solution sodium methoxide Solution in methanol was added at ambient temperature. This reaction solution was added to 125 ml isopropyl alcohol to precipitate mycophenolate sodium salt in M2 form. The resultant mixture was filtered and precipitate washed with isopropyl alcohol to obtain sodium mycophenolate M2 form. Yield was 92% and purity was 99%.
90% With sodium acetate; In methanol; at 20℃; for 0.5h; lOg of sodium acetate is dissolved in 55 ml of methanol. To this 74g of MYCOPHENOLIC acid was added and stirred for half an hour at RT. The contents were chilled to 10C and filtered. The solid are washed with 50 ml acetone, dried under vacuum at 40 to 50C. A final yield 90% (70G) was observed.
90% With sodium 2-ethylhexanoic acid; In methanol; at 20℃; for 0.5h; 25g of sodium 2-ETHYLHEXANOATE is dissolved in 175 ml of ethyl acetate. To this 250g of MYCOPHENOLIC acid was added and stirred for half an hour at RT. The contents were chilled to 10C and filtered. The solid are washed with 50 ml acetone, dried under vacuum at 40 to 50C. A final yield 90% ( 22g) was observed.
90% With sodium 2-ethylcaprylate; In methanol; at 20℃; for 0.5h; 25g of sodium 2-ethylcaprylate is dissolved in 175 ml of methanol. To this 250g of <strong>[24280-93-1]mycophenolic acid</strong> was added and stirred for half an hour at RT. The contents were chilled to 10C and filtered. The solid are washed with 50 ml acetone, dried under vacuum at 40 to 50C. A final yield 90% ( 22g) was observed.
86% With sodium methylate; In methanol; dichloromethane; at 20℃;Product distribution / selectivity; Example 16; To a stirred solution of MPA (6.4 g) in dichloromethane (320 ml) and methanol (60 ml) 30%of sodium methoxide in methanol (3.8 ml) was added dropwise at room temperature.The product was precipitated by addition of n-hexane (960 ml) and filtered off. The solidmaterial was dried at 40 C in vacuum oven. The yield was 86%. Polymorphism wasdetermined by X-ray diffraction. The obtained material was form M2.
85% With sodium hydroxide; In water; acetone; at 20℃; for 0.5h;Product distribution / selectivity; Example 2; To a stirred solution of MPA (6.4 g) in acetone (130 ml), sodium hydroxide (0.8 g) in water (2 ml) was added dropwise at room temperature. The stirring was continued at this temperature for 0.5 hours. The precipitated product was filtered off and washed with cold acetone. The solid material was dried at 40-45 C in a vacuum oven. Form M2 of mycophenolate sodium was obtained in 85% yield.
66% With sodium methylate; In methanol; 2-methylpropyl acetate; at 20℃; for 0.5h;Product distribution / selectivity; Example 17; To a stirred solution of MPA (6.4 g) in isobutyl acetate (500 ml) 30% of sodium methoxide inmethanol (3.8 ml) was added dropwise at room temperature. The reaction mixture wasstirred for additional 30 minutes, then the precipitated product was filtered off and washedwith isobutyl acetate. The solid material was dried at 40 C in vacuum oven. The yield was66%. Polymorphism was determined by X-ray diffraction. The obtained material was formM2.
38% With sodium methylate; In methanol; at -15 - 20℃; for 24h;Heating / reflux;Product distribution / selectivity; Example 1;To a stirred solution of MPA (6.4 g) in methanol (32 ml), 30% sodium methoxide in methanol (3.8 ml) was added dropwise at room temperature. The reaction mixture was warmed to reflux temperature, then cooled to -15C with constant stirring. The reaction mixture was stirred at -15C for 24 hours. The precipitated product was then filtered off and washed with cold methanol. The solid material was dried at 40-45C in a vacuum oven. Form M2 of mycophenolate sodium was obtained in 38% yield.
With sodium ethanolate; In ethanol; at 20℃; for 1h;Product distribution / selectivity; Example 20; (J. Med. Chem., 39 (1996) 1236-1242)To a stirred solution of MPA (9.6 g) in absolute ethanol (360 ml), 21% sodium ethoxide in ethanol (8.6 ml) was added dropwise at room temperature. The reaction mixture was stirred for an additional 60 minutes, then the solvent was evaporated on a rotary evaporator at 40-45C under vacuum. The wet material was dried at 40-45C in a vacuum oven and proved to be Form M2.
Example 21; (ZA 68/4,959)To a stirred solution of MPA (13 g) in chloroform (650 ml), sodium methoxide solution (2.3 g NaOMe dissolved in 130 ml of methanol) was added dropwise at room temperature. The reaction mixture was stirred for an additional 30 minutes, then n-pentane (2.34 L) was added to the solution. After 30 minutes, the reaction mixture was filtered and a part of the wet material was dried at 40-45C in a vacuum oven. Both the wet sample and the dried material proved to be Form M2.
With sodium hydroxide; In water; toluene; at 105 - 111℃;Heating / reflux;Product distribution / selectivity; To a stirred suspension of <strong>[24280-93-1]mycophenolic acid</strong> (20 g) in water (50 mL), one molar equivalent of 50% aqueous NaOH (3.2 mL) was added. When all of the acid had been utilized and dissolved, toluene (360 mL) was added and the reaction mixture was heated to reflux and the water was azeotropically removed with the help of a Dean-Stark apparatus until the reaction mixture reached 110-111 C. The precipitation of the MPS started at 105 C. The mixture was cooled to room temperature and the crystalline material was recovered by filtration. The solid MPS Form CG1 was dried at 50+/-5 C. in a vacuum oven.

  • 10
  • [ 929-59-9 ]
  • [ 24280-93-1 ]
  • mono-mycophenolic acid 2,2'-(ethylenedioxy)diethyl amine salt [ No CAS ]
YieldReaction ConditionsOperation in experiment
98.8% In ethyl acetate at 60℃; 4 Commercially available mycophenolic acid (0.94 g, 2.93 mmol) was dissolved in ethyl acetate (25 mL) by heating the mixture to 60° C. 2,2'-(Ethylenedioxy)diethyl amine (EDEA, H2N-(CH2)2-O-(CH2)2-O-(CH2)2-NH2, 1.47 mmol, 0.5 equivalents) was dissolved in ethyl acetate and slowly (15-30 minutes) added to the solution of mycophenolic acid. During addition, a white precipitate was formed. After complete addition the suspension was allowed to slowly cool down to room temperature and further cooled to 4° C. The white solid precipitate was collected by filtration, washed with ethyl acetate and dried in vacuo to yield 0.68 g (1.45 mmol, 98.8% yield based on EDEA) of the mono-mycophenolate salt of 2,2'-(ethylenedioxy)diethyl amine. 1H-NMR (600 MHz) CD3OD: δ 1.81 (s, 3H, CH3-C), 2.14 (s, 3H, CH3-Ar), 2.23-2.35 (m, 4H, DOOC-CH2-CH2-C), 2.95 (t, 4H, D2N-CH2-CH2-), 3.38 (d, 2H, J3=6.8 Hz, Ar-CH2-CH), 3.62 (t, 4H, D2N-CH2-CH2-O-), 3.67 (s, 4H, -O-CH2-CH2-O-), 3.76 (s, 3H, O-CH3), 6.23 (s, 2H, -CH2-CO), 5.24 (t, 1H, Ar-CH2-CH).
  • 11
  • [ 24280-93-1 ]
  • [ 127828-22-2 ]
  • [ 1333040-60-0 ]
YieldReaction ConditionsOperation in experiment
83% With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; In acetonitrile; at 20℃; for 18h; Example 6; Preparation of (4Z,7Z,10Z,13Z,16Z,19Z)-N-(2-(2-((E)-6-(4-hydroxy-6-methoxy-7- methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4- enamido)ethoxy)ethyl)docosa-4,7,10,13,16,19-hexaenamide (I-2); In a typical run, sodium hydroxide (400 mg, 10 mmol) was dissolved in MeOH (70 mL) and 2-(2-aminoethoxy)ethanamine dihydrochloride (1.0 g, 5.65 mmol) was added. The resulting reaction mixture was stirred at room temperature for 30 min A solution containing Boc2O (740 mg, 3.40 mmol) in THF (15 mL) was then added dropwise, at room temperature, over a period of 15 min The resulting reaction mixture was stirred at room temperature for 18 h, and then concentrated under reduced pressure. The resulting residue was taken up in CH2Cl2 (200 mL) and stirred vigorously at room temperature for 4 h. The mixture was filtered and the filtrate was concentrated under reduced pressure to afford <strong>[127828-22-2]tert-butyl 2-(2-aminoethoxy)ethylcarbamate</strong> (850 mg, 74%).tert-Butyl 2-(2-aminoethoxy)ethylcarbamate (1.47 mmol) was then taken up in CH3CN (10 mL) along with mycophenolic acid (470 mg, 1.47 mmol) and EDCI (310 mg, 1.62 mmol). The resulting reaction mixture was stirred at room temperature for 18 h. It is then diluted with EtOAc (50 mL), washed with saturated aqueous NaHCO3, brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (9:1 CH2Cl2/MeOH) to afford 620 mg of (E)-tert-butyl 2-(2-(6- (4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4- enamido)ethoxy)ethylcarbamate (83% yield).(E)-tert-Butyl 2-(2-(6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3- dihydroisobenzofuran-5-yl)-4-methylhex-4-enamido)ethoxy)ethylcarbamate (620 mg, 1.22 mmol) was taken up in 10 mL of 4 M HC1 in dioxane and allowed to stir at room temperature for 2 h. The resulting reaction mixture was concentrated under reduced pressure to afford the HCl salt of (E)-N-(2-(2-aminoethoxy)ethyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3- dihydroisobenzofuran-5-yl)-4-methylhex-4-enamide This material was taken up in CH3CN (10 mL) along with (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid (400 mg, 1.22 mmol), HATU (510 mg, 1.34 mmol) and DIEA (640 muL, 3.66 mmol). The resulting reaction mixture was stirred at room temperature for 2 h. It was then diluted with EtOAc and washed successively with saturated aqueous NaHCO3 and brine. The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. Purification by silica gel chromatography (5% MeOH in CH2Cl2) afforded 600 mg of (4Z,7Z,10Z,13Z,16Z,19Z)-N-(2- (2-((E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4- methylhex-4-enamido)ethoxy)ethyl)docosa-4,7,10,13,16,19-hexaenamide (68% yield). MS (EI) calcd for C43H60N2O7: 716.44; found 717 (M+1).
  • 12
  • [ 24280-93-1 ]
  • [ 263162-13-6 ]
  • [ 1333040-76-8 ]
YieldReaction ConditionsOperation in experiment
84% With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; In acetonitrile; at 20℃; for 18h; Example 7; Preparation of (4Z,7Z,10Z,13Z,16Z,19Z)-N-(2-((2-((E)-6-(4-hydroxy-6-methoxy-7- methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4- enamido)ethyl)(methyl)amino)ethyl)docosa-4,7,10,13,16,19-hexaenamide (I-3); N1-(2-Aminoethyl)-N1-methylethane-1,2-diamine (5.0 g, 42.7 mmol) was dissolved in 100 mL of CH2Cl2 and cooled to 0 C. A solution of di-tert-butylcarbonate (0.93 g, 4.27 mmol) in CH2Cl2 (10 mL) was then added dropwise at 0 C. over a period of 15 min The resulting reaction mixture was stirred at 0 C. for 30 min and then warmed to room temperature. After stirring at room temperature for 2 h, the reaction mixture was diluted with CH2Cl2 (100 mL). The organic layer was washed with brine (3×25 mL), dried (Na2SO4) and concentrated under reduced pressure to afford 1.1 g of tert-butyl 2-((2-aminoethyl)(methyl)amino)ethylcarbamate.tert-butyl 2-((2-aminoethyl)(methyl)amino)ethylcarbamate (200 mg, 0.922 mmol) was taken up in 5 mL of CH3CN along with <strong>[24280-93-1]mycophenolic acid</strong> (295 mg, 0.922 mmol) and EDC (194 mg, 1.01 mmol). The resulting reaction mixture was stirred at room temperature for 18 h and diluted with EtOAc. The organic layer was washed with brine, dried (Na2SO4) and concentrated under reduced pressure. Purification by chromatography (95% CH2Cl2, 5% MeOH) afforded 400 mg of (E)-tert-butyl 2-((2-(6-(4-hydroxy-6-methoxy- 7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4- enamido)ethyl)(methyl)amino)ethylcarbamate (84% yield). This material was taken up in 10 mL of 4 M HCl in dioxane and allowed to stir at room temperature for 2 h. The mixture was diluted with EtOAc (30 mL) and concentrated under reduced pressure to afford the HC1 salt of (E)-N-(2-((2-aminoethyl)(methyl)amino)ethyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo- 1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enamide. This material was then taken up in 10 mL of CH3CN along with (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid (DHA, 252 mg, 0.77 mmol), HATU (322 mg, 0.85 mmol) and DIEA (540 3.1 mmol). The resulting reaction mixture was stirred at room temperature for 2 h and diluted with EtOAc (50 mL). The organic layer was washed with brine, dried (Na2SO4) and concentrated under reduced pressure. Purification by chromatography (95% CH2Cl2, 5% MeOH) afforded 300 mg of (4Z,7Z,10Z,13Z,16Z,19Z)-N-(2-((2-((E)-6-(4-hydroxy-6- methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4- enamido)ethyl)(methyl)amino)ethyl)docosa-4,7,10,13,16,19-hexaenamide (53% yield). MS (EI) calcd for C44H63N3O6: 729.47; found 730 (M+1).
  • 13
  • [ 24280-93-1 ]
  • [ 485800-26-8 ]
  • [ 1333040-54-2 ]
YieldReaction ConditionsOperation in experiment
With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In acetonitrile at 20℃; for 18h; 5 Preparation of (4Z,7Z,10Z,13Z,16Z,19Z)-N-(2-(2-(2-((E)-6-(4-hydroxy-6-methoxy-7- methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4- enamido)ethyl)disulfanyl)ethyl)docosa-4,7,10,13,16,19-hexaenamide (I-4) Example 5; Preparation of (4Z,7Z,10Z,13Z,16Z,19Z)-N-(2-(2-(2-((E)-6-(4-hydroxy-6-methoxy-7- methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4- enamido)ethyl)disulfanyl)ethyl)docosa-4,7,10,13,16,19-hexaenamide (I-4); Cystamine dihydrochloride (1.0 g, 4.44 mmol) was dissolved in MeOH (50 mL). Triethylamine (1.85 mL, 3 eq) was added at room temperature, followed by dropwise addition of Boc2O (0.97 g, 4.44 mmol) as a solution in MeOH (5 mL). The resulting reaction mixture was stirred at room temperature for 3 h. It was then concentrated under reduced pressure and the resulting residue was taken up in 1M aqueous NaH2PO4 (20 mL). The aqueous layer is washed with a 1:1 solution of pentane/EtOAc (10 mL), basified to pH 9 with 1M aqueous NaOH, and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to afford tert-butyl 2-(2-(2-aminoethyl)disulfanyl)ethylcarbamate (500 mg, 44%).tert-Butyl 2-(2-(2-aminoethyl)disulfanyl)ethylcarbamate (1 2 mmol) was taken up in CH3CN (5 mL) along with mycophenolic acid (1.2 mmol) and EDCI (1.3 mmol). The resulting reaction mixture was stirred at room temperature for 18 h and diluted with EtOAc. The organic layer was washed with saturated aqueous NaHCO3, brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (CH2Cl2) to afford (E)-tert-butyl 2-(2-(2-(6-(4-hydroxy-6-methoxy-7- methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4- enamido)ethyl)disulfanyl)ethylcarbamate.(E)-tert-butyl 2-(2-(2-(6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3- dihydroisobenzofuran-5-yl)-4-methylhex-4-enamido)ethyl)disulfanyl)ethylcarbamate (0.56 mmol) was taken up in 5 mL of 4 M HCl in dioxane and allowed to stand at room temperature for 2 h. The resulting reaction mixture is concentrated under reduced pressure to afford the HCl salt of (E)-N-(2-(2-(2-aminoethyl)disulfanyl)ethyl)-6-(4-hydroxy-6-methoxy- 7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enamide. This material is taken up in CH3CN (5 mL) along with (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19- hexaenoic acid (DHA, 183 mg, 0.56 mmol), HATU (234 mg, 0.62 mmol) and DIEA (290 1.7 mmol). The resulting reaction mixture was stirred at room temperature for 2 h. It was then diluted with EtOAc and washed successively with saturated aqueous NaHCO3 and brine. The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. Purification by silica gel chromatography (5% MeOH-CH2Cl2) afforded 200 mg of (4Z,7Z,10Z,13Z,16Z,19Z)-N-(2-(2-(2-9(E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3- dihydroisobenzofuran-5-yl)-4-methylhex-4-enamido)ethyl)disulfanyl)ethyl)docosa- 4,7,10,13,16,19-hexaenamide (47% yield). MS (EI) calcd for C43H60N2O6S2: 764.39; found 765 (M+1).
  • 14
  • [ 1393650-10-6 ]
  • [ 24280-93-1 ]
  • [ 1393650-27-5 ]
YieldReaction ConditionsOperation in experiment
72% With diphenyl phosphoryl azide; triethylamine; In N,N-dimethyl-formamide; at -15 - 20℃; To stirring at -15C solution of <strong>[24280-93-1]mycophenolic acid</strong> 1 (100 mg, 0.3125 mmol) and 2a (88.75 mg, 0.3125 mmol), cooled DPPA (0.067ml, 0.3125 mmol) in DMF and Et3N (0.056 ml, 0.625 mmol) were added. The reaction mixture was stirred for 2 hours at 0C and 24h at r.t. DMF was removed under reduced pressure. The residue was dissolved in chloroform and extracted by diluted NaHCO3. The organic layer was dried over anhydrous MgSO4 ,solvent was evaporated under reduced pressure and the residue was purified by column chromatography (chloroform: metanol) to yield 131 mg (0.225 mmol, 72%) Compound 4a 1H NMR (200 MHz, CDCl3): d 7.75 (m, 7H), 6.65 (s, 1H, NHCO), 5.3-5.2 (m, 1H), 5.05 (s, 2H); 4.0-3.9 (d, 2H), 3.75 (s, 3H), 2.4-2.2 (m, 4H), 2.15 (s, 3H), 1.7 (s, 3H)lambdamax (CHCl3)/nm 279, 385 (epsilon / dm3 mol-1 cm1 10434, 3165)MS (m/z): Calcl. for C32H32N4O7: 584,6; Found: 585,2 Anal. Calcd for: C32H32N4O7: C, 65.74; H, 5.52; N, 9.58; O, 19.16. Found: C, 65.87; H, 5.63; N, 9.32.
  • 15
  • [ 1393650-18-4 ]
  • [ 24280-93-1 ]
  • [ 1393650-31-1 ]
YieldReaction ConditionsOperation in experiment
50% With diphenyl phosphoryl azide; triethylamine; In N,N-dimethyl-formamide; at -15 - 20℃; General procedure: To stirring at -15C solution of <strong>[24280-93-1]mycophenolic acid</strong> 1 (100 mg, 0.3125 mmol) and 2a (88.75 mg, 0.3125 mmol), cooled DPPA (0.067ml, 0.3125 mmol) in DMF and Et3N (0.056 ml, 0.625 mmol) were added. The reaction mixture was stirred for 2 hours at 0C and 24h at r.t. DMF was removed under reduced pressure. The residue was dissolved in chloroform and extracted by diluted NaHCO3. The organic layer was dried over anhydrous MgSO4 ,solvent was evaporated under reduced pressure and the residue was purified by column chromatography (chloroform: metanol) to yield 131 mg (0.225 mmol, 72%)
  • 16
  • [ 24280-93-1 ]
  • [ 192136-39-3 ]
  • [ 1393650-29-7 ]
YieldReaction ConditionsOperation in experiment
55% With diphenyl phosphoryl azide; triethylamine; In N,N-dimethyl-formamide; at -15 - 20℃; General procedure: To stirring at -15C solution of <strong>[24280-93-1]mycophenolic acid</strong> 1 (100 mg, 0.3125 mmol) and 2a (88.75 mg, 0.3125 mmol), cooled DPPA (0.067ml, 0.3125 mmol) in DMF and Et3N (0.056 ml, 0.625 mmol) were added. The reaction mixture was stirred for 2 hours at 0C and 24h at r.t. DMF was removed under reduced pressure. The residue was dissolved in chloroform and extracted by diluted NaHCO3. The organic layer was dried over anhydrous MgSO4 ,solvent was evaporated under reduced pressure and the residue was purified by column chromatography (chloroform: metanol) to yield 131 mg (0.225 mmol, 72%)
  • 17
  • [ 24280-93-1 ]
  • [ 92751-08-1 ]
  • [ 1393650-28-6 ]
YieldReaction ConditionsOperation in experiment
59% With diphenyl phosphoryl azide; triethylamine; In N,N-dimethyl-formamide; at -15 - 20℃; General procedure: To stirring at -15C solution of <strong>[24280-93-1]mycophenolic acid</strong> 1 (100 mg, 0.3125 mmol) and 2a (88.75 mg, 0.3125 mmol), cooled DPPA (0.067ml, 0.3125 mmol) in DMF and Et3N (0.056 ml, 0.625 mmol) were added. The reaction mixture was stirred for 2 hours at 0C and 24h at r.t. DMF was removed under reduced pressure. The residue was dissolved in chloroform and extracted by diluted NaHCO3. The organic layer was dried over anhydrous MgSO4 ,solvent was evaporated under reduced pressure and the residue was purified by column chromatography (chloroform: metanol) to yield 131 mg (0.225 mmol, 72%)
  • 18
  • [ 24280-93-1 ]
  • [ 192136-40-6 ]
  • [ 1393650-30-0 ]
YieldReaction ConditionsOperation in experiment
52% With diphenyl phosphoryl azide; triethylamine; In N,N-dimethyl-formamide; at -15 - 20℃; General procedure: To stirring at -15C solution of <strong>[24280-93-1]mycophenolic acid</strong> 1 (100 mg, 0.3125 mmol) and 2a (88.75 mg, 0.3125 mmol), cooled DPPA (0.067ml, 0.3125 mmol) in DMF and Et3N (0.056 ml, 0.625 mmol) were added. The reaction mixture was stirred for 2 hours at 0C and 24h at r.t. DMF was removed under reduced pressure. The residue was dissolved in chloroform and extracted by diluted NaHCO3. The organic layer was dried over anhydrous MgSO4 ,solvent was evaporated under reduced pressure and the residue was purified by column chromatography (chloroform: metanol) to yield 131 mg (0.225 mmol, 72%)
  • 19
  • [ 24280-93-1 ]
  • [ 14316-06-4 ]
  • methyl ester N-mycophenoyl-D-alanine [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h; General procedure: Mycophenolic acid 1 (0.156 mmol), methyl ester amino acid hydrochloride 9 (0.178 mmol) and DMAP (0.178 mmol) was dissolved in dry DMF (3 mL). A reaction mixture was cooled to 0 C in an ice bath and with stirring was added EDCI (0.17053 mmol). The solution was stirred at 0 C for 2 h and after that time left at room temperature for 48 h. Progress of the reaction controlled by TLC plates. After completion of the reaction solution was poured into water (15 mL), extracted with ethyl acetate. The organic layer was separated, dried (MgSO4), filtered and concentrated. The crude products were purified by chromatography (SiO2). Structures of synthesized derivatives 10 were established by spectroscopic methods (1H NMR, 13C NMR, MS, HPLC-MS, optical rotation and melting point). Ester hydrolysis: the methyl ester 10 was dissolved in MeOH (30 mL/g), and a solution of LiOH*H2O (3 mol equiv - 2-fold more for 10d and 10e) in an equal volume of water was added. When hydrolysis was complete (48 h), the solution was added to water and washed with ether. The aqueous phase was acidified with 2 N HCl and extracted with EtOAC. The extract was dried with MgSO4 and evaporated, and the residue was recrystallized [17].
  • 20
  • [ 24280-93-1 ]
  • [ 2491-20-5 ]
  • methyl ester N-mycophenoyl-L-alanine [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h; General procedure: Mycophenolic acid 1 (0.156 mmol), methyl ester amino acid hydrochloride 9 (0.178 mmol) and DMAP (0.178 mmol) was dissolved in dry DMF (3 mL). A reaction mixture was cooled to 0 C in an ice bath and with stirring was added EDCI (0.17053 mmol). The solution was stirred at 0 C for 2 h and after that time left at room temperature for 48 h. Progress of the reaction controlled by TLC plates. After completion of the reaction solution was poured into water (15 mL), extracted with ethyl acetate. The organic layer was separated, dried (MgSO4), filtered and concentrated. The crude products were purified by chromatography (SiO2). Structures of synthesized derivatives 10 were established by spectroscopic methods (1H NMR, 13C NMR, MS, HPLC-MS, optical rotation and melting point). Ester hydrolysis: the methyl ester 10 was dissolved in MeOH (30 mL/g), and a solution of LiOH*H2O (3 mol equiv - 2-fold more for 10d and 10e) in an equal volume of water was added. When hydrolysis was complete (48 h), the solution was added to water and washed with ether. The aqueous phase was acidified with 2 N HCl and extracted with EtOAC. The extract was dried with MgSO4 and evaporated, and the residue was recrystallized [17].
  • 21
  • [ 24280-93-1 ]
  • [ 5680-79-5 ]
  • methyl ester N-mycophenoylglycine [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h; General procedure: Mycophenolic acid 1 (0.156 mmol), methyl ester amino acid hydrochloride 9 (0.178 mmol) and DMAP (0.178 mmol) was dissolved in dry DMF (3 mL). A reaction mixture was cooled to 0 C in an ice bath and with stirring was added EDCI (0.17053 mmol). The solution was stirred at 0 C for 2 h and after that time left at room temperature for 48 h. Progress of the reaction controlled by TLC plates. After completion of the reaction solution was poured into water (15 mL), extracted with ethyl acetate. The organic layer was separated, dried (MgSO4), filtered and concentrated. The crude products were purified by chromatography (SiO2). Structures of synthesized derivatives 10 were established by spectroscopic methods (1H NMR, 13C NMR, MS, HPLC-MS, optical rotation and melting point). Ester hydrolysis: the methyl ester 10 was dissolved in MeOH (30 mL/g), and a solution of LiOH*H2O (3 mol equiv - 2-fold more for 10d and 10e) in an equal volume of water was added. When hydrolysis was complete (48 h), the solution was added to water and washed with ether. The aqueous phase was acidified with 2 N HCl and extracted with EtOAC. The extract was dried with MgSO4 and evaporated, and the residue was recrystallized [17].
  • 22
  • [ 24280-93-1 ]
  • [ 23150-65-4 ]
  • dimethyl N-mycophenoyl-L-glutamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h; General procedure: Mycophenolic acid 1 (0.156 mmol), methyl ester amino acid hydrochloride 9 (0.178 mmol) and DMAP (0.178 mmol) was dissolved in dry DMF (3 mL). A reaction mixture was cooled to 0 C in an ice bath and with stirring was added EDCI (0.17053 mmol). The solution was stirred at 0 C for 2 h and after that time left at room temperature for 48 h. Progress of the reaction controlled by TLC plates. After completion of the reaction solution was poured into water (15 mL), extracted with ethyl acetate. The organic layer was separated, dried (MgSO4), filtered and concentrated. The crude products were purified by chromatography (SiO2). Structures of synthesized derivatives 10 were established by spectroscopic methods (1H NMR, 13C NMR, MS, HPLC-MS, optical rotation and melting point). Ester hydrolysis: the methyl ester 10 was dissolved in MeOH (30 mL/g), and a solution of LiOH*H2O (3 mol equiv - 2-fold more for 10d and 10e) in an equal volume of water was added. When hydrolysis was complete (48 h), the solution was added to water and washed with ether. The aqueous phase was acidified with 2 N HCl and extracted with EtOAC. The extract was dried with MgSO4 and evaporated, and the residue was recrystallized [17].
  • 23
  • [ 24280-93-1 ]
  • [ 13515-99-6 ]
  • dimethyl N-mycophenoyl-D-glutamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h; General procedure: Mycophenolic acid 1 (0.156 mmol), methyl ester amino acid hydrochloride 9 (0.178 mmol) and DMAP (0.178 mmol) was dissolved in dry DMF (3 mL). A reaction mixture was cooled to 0 C in an ice bath and with stirring was added EDCI (0.17053 mmol). The solution was stirred at 0 C for 2 h and after that time left at room temperature for 48 h. Progress of the reaction controlled by TLC plates. After completion of the reaction solution was poured into water (15 mL), extracted with ethyl acetate. The organic layer was separated, dried (MgSO4), filtered and concentrated. The crude products were purified by chromatography (SiO2). Structures of synthesized derivatives 10 were established by spectroscopic methods (1H NMR, 13C NMR, MS, HPLC-MS, optical rotation and melting point). Ester hydrolysis: the methyl ester 10 was dissolved in MeOH (30 mL/g), and a solution of LiOH*H2O (3 mol equiv - 2-fold more for 10d and 10e) in an equal volume of water was added. When hydrolysis was complete (48 h), the solution was added to water and washed with ether. The aqueous phase was acidified with 2 N HCl and extracted with EtOAC. The extract was dried with MgSO4 and evaporated, and the residue was recrystallized [17].
  • 24
  • [ 24280-93-1 ]
  • [ 13515-99-6 ]
  • N-mycophenoyl-D-glutamic acid [ No CAS ]
  • 25
  • [ 24280-93-1 ]
  • [ 6306-52-1 ]
  • methyl ester N-mycophenoyl-L-valine [ No CAS ]
YieldReaction ConditionsOperation in experiment
54% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h; General procedure: Mycophenolic acid 1 (0.156 mmol), methyl ester amino acid hydrochloride 9 (0.178 mmol) and DMAP (0.178 mmol) was dissolved in dry DMF (3 mL). A reaction mixture was cooled to 0 C in an ice bath and with stirring was added EDCI (0.17053 mmol). The solution was stirred at 0 C for 2 h and after that time left at room temperature for 48 h. Progress of the reaction controlled by TLC plates. After completion of the reaction solution was poured into water (15 mL), extracted with ethyl acetate. The organic layer was separated, dried (MgSO4), filtered and concentrated. The crude products were purified by chromatography (SiO2). Structures of synthesized derivatives 10 were established by spectroscopic methods (1H NMR, 13C NMR, MS, HPLC-MS, optical rotation and melting point). Ester hydrolysis: the methyl ester 10 was dissolved in MeOH (30 mL/g), and a solution of LiOH*H2O (3 mol equiv - 2-fold more for 10d and 10e) in an equal volume of water was added. When hydrolysis was complete (48 h), the solution was added to water and washed with ether. The aqueous phase was acidified with 2 N HCl and extracted with EtOAC. The extract was dried with MgSO4 and evaporated, and the residue was recrystallized [17].
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In chloroform; at 20℃;Inert atmosphere; Mycophenolic-L-Valine methyl ester (23).To the solution of MPA (1g, 3.13 mmol) in CHCl3 (35 mL) were addedEDC (660 mg, 3.44 mmol) and valine methyl ester hydrochloride (524.7 mg, 3.13mmol) followed by TEA (480 uL, 3.44 mmoL). Mixture was stirred overnight at rt.Evaluated by TLC: silica gel, CHCl3:MeOH, 9:1. Reaction mixture waswashed with water (3 x 15 mL), citric acid (0.5 M), and brine, organicphase was dried over MgSO4, filtered and evaporated leaving whitecrystalline product. 1H NMR (CDCl3)deltappm 5.93 (d, J = 8.22 Hz, 1H), 5.27 (t, J = 6.64 Hz, 1H), 5.20(s, 2H), 4.54 (dd, J = 8.76, 4.88 Hz, 1H), 3.76 (s, 3H), 3.72 (s, 3H),3.39 (d, J = 6.97 Hz, 2H), 2.37-2.29 (m, 4H), 2.15 (s, 3H), 2.13-2.06(m, 1H), 1.82 (s, 3H), 0.89 (d, J = 6.85 Hz, 3H), 0.86 (d, J = 6.90Hz, 3H). HRMS calcdfor C23H30NO7 432.2028 (M-H)-,found 432.2035.
  • 26
  • [ 24280-93-1 ]
  • [ 7146-15-8 ]
  • methyl ester N-mycophenoyl-D-valine [ No CAS ]
YieldReaction ConditionsOperation in experiment
55% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h; General procedure: Mycophenolic acid 1 (0.156 mmol), methyl ester amino acid hydrochloride 9 (0.178 mmol) and DMAP (0.178 mmol) was dissolved in dry DMF (3 mL). A reaction mixture was cooled to 0 C in an ice bath and with stirring was added EDCI (0.17053 mmol). The solution was stirred at 0 C for 2 h and after that time left at room temperature for 48 h. Progress of the reaction controlled by TLC plates. After completion of the reaction solution was poured into water (15 mL), extracted with ethyl acetate. The organic layer was separated, dried (MgSO4), filtered and concentrated. The crude products were purified by chromatography (SiO2). Structures of synthesized derivatives 10 were established by spectroscopic methods (1H NMR, 13C NMR, MS, HPLC-MS, optical rotation and melting point). Ester hydrolysis: the methyl ester 10 was dissolved in MeOH (30 mL/g), and a solution of LiOH*H2O (3 mol equiv - 2-fold more for 10d and 10e) in an equal volume of water was added. When hydrolysis was complete (48 h), the solution was added to water and washed with ether. The aqueous phase was acidified with 2 N HCl and extracted with EtOAC. The extract was dried with MgSO4 and evaporated, and the residue was recrystallized [17].
  • 27
  • [ 24280-93-1 ]
  • [ 7517-19-3 ]
  • methyl ester N-mycophenoyl-L-leucine [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h; General procedure: Mycophenolic acid 1 (0.156 mmol), methyl ester amino acid hydrochloride 9 (0.178 mmol) and DMAP (0.178 mmol) was dissolved in dry DMF (3 mL). A reaction mixture was cooled to 0 C in an ice bath and with stirring was added EDCI (0.17053 mmol). The solution was stirred at 0 C for 2 h and after that time left at room temperature for 48 h. Progress of the reaction controlled by TLC plates. After completion of the reaction solution was poured into water (15 mL), extracted with ethyl acetate. The organic layer was separated, dried (MgSO4), filtered and concentrated. The crude products were purified by chromatography (SiO2). Structures of synthesized derivatives 10 were established by spectroscopic methods (1H NMR, 13C NMR, MS, HPLC-MS, optical rotation and melting point). Ester hydrolysis: the methyl ester 10 was dissolved in MeOH (30 mL/g), and a solution of LiOH*H2O (3 mol equiv - 2-fold more for 10d and 10e) in an equal volume of water was added. When hydrolysis was complete (48 h), the solution was added to water and washed with ether. The aqueous phase was acidified with 2 N HCl and extracted with EtOAC. The extract was dried with MgSO4 and evaporated, and the residue was recrystallized [17].
  • 28
  • [ 24280-93-1 ]
  • [ 5845-53-4 ]
  • methyl ester N-mycophenoyl-D-leucine [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h; General procedure: Mycophenolic acid 1 (0.156 mmol), methyl ester amino acid hydrochloride 9 (0.178 mmol) and DMAP (0.178 mmol) was dissolved in dry DMF (3 mL). A reaction mixture was cooled to 0 C in an ice bath and with stirring was added EDCI (0.17053 mmol). The solution was stirred at 0 C for 2 h and after that time left at room temperature for 48 h. Progress of the reaction controlled by TLC plates. After completion of the reaction solution was poured into water (15 mL), extracted with ethyl acetate. The organic layer was separated, dried (MgSO4), filtered and concentrated. The crude products were purified by chromatography (SiO2). Structures of synthesized derivatives 10 were established by spectroscopic methods (1H NMR, 13C NMR, MS, HPLC-MS, optical rotation and melting point). Ester hydrolysis: the methyl ester 10 was dissolved in MeOH (30 mL/g), and a solution of LiOH*H2O (3 mol equiv - 2-fold more for 10d and 10e) in an equal volume of water was added. When hydrolysis was complete (48 h), the solution was added to water and washed with ether. The aqueous phase was acidified with 2 N HCl and extracted with EtOAC. The extract was dried with MgSO4 and evaporated, and the residue was recrystallized [17].
  • 29
  • [ 24280-93-1 ]
  • [ 7524-50-7 ]
  • methyl ester N-mycophenoyl-L-phenylalanine [ No CAS ]
YieldReaction ConditionsOperation in experiment
64% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h; General procedure: Mycophenolic acid 1 (0.156 mmol), methyl ester amino acid hydrochloride 9 (0.178 mmol) and DMAP (0.178 mmol) was dissolved in dry DMF (3 mL). A reaction mixture was cooled to 0 C in an ice bath and with stirring was added EDCI (0.17053 mmol). The solution was stirred at 0 C for 2 h and after that time left at room temperature for 48 h. Progress of the reaction controlled by TLC plates. After completion of the reaction solution was poured into water (15 mL), extracted with ethyl acetate. The organic layer was separated, dried (MgSO4), filtered and concentrated. The crude products were purified by chromatography (SiO2). Structures of synthesized derivatives 10 were established by spectroscopic methods (1H NMR, 13C NMR, MS, HPLC-MS, optical rotation and melting point). Ester hydrolysis: the methyl ester 10 was dissolved in MeOH (30 mL/g), and a solution of LiOH*H2O (3 mol equiv - 2-fold more for 10d and 10e) in an equal volume of water was added. When hydrolysis was complete (48 h), the solution was added to water and washed with ether. The aqueous phase was acidified with 2 N HCl and extracted with EtOAC. The extract was dried with MgSO4 and evaporated, and the residue was recrystallized [17].
  • 30
  • [ 24280-93-1 ]
  • [ 13033-84-6 ]
  • methyl ester N-mycophenoyl-D-phenylalanine [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h; General procedure: Mycophenolic acid 1 (0.156 mmol), methyl ester amino acid hydrochloride 9 (0.178 mmol) and DMAP (0.178 mmol) was dissolved in dry DMF (3 mL). A reaction mixture was cooled to 0 C in an ice bath and with stirring was added EDCI (0.17053 mmol). The solution was stirred at 0 C for 2 h and after that time left at room temperature for 48 h. Progress of the reaction controlled by TLC plates. After completion of the reaction solution was poured into water (15 mL), extracted with ethyl acetate. The organic layer was separated, dried (MgSO4), filtered and concentrated. The crude products were purified by chromatography (SiO2). Structures of synthesized derivatives 10 were established by spectroscopic methods (1H NMR, 13C NMR, MS, HPLC-MS, optical rotation and melting point). Ester hydrolysis: the methyl ester 10 was dissolved in MeOH (30 mL/g), and a solution of LiOH*H2O (3 mol equiv - 2-fold more for 10d and 10e) in an equal volume of water was added. When hydrolysis was complete (48 h), the solution was added to water and washed with ether. The aqueous phase was acidified with 2 N HCl and extracted with EtOAC. The extract was dried with MgSO4 and evaporated, and the residue was recrystallized [17].
  • 31
  • [ 24280-93-1 ]
  • [ 362-75-4 ]
  • [ 1532533-29-1 ]
YieldReaction ConditionsOperation in experiment
86% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine Inert atmosphere; Mycophenolic-Adenosine ester (20). Mycophenolic-Adenosine ester (20). Prepared as compound 25 starting from: MPA (0.115 g, 0.36 mmol), iPrAde(110 mg, 0.36 mmol), EDC (77 mg, 0.396 mmol) and HOBt (54 mg, 0.396 mmol) andTEA (0.11 mL, 0.792 mmol). The protected intermediate was crystallized from MeOH (188 mg, 86%), dissolved in a mixture of MeOH:water (10 mL, 1:1) and TFA(1.5 mL) was added. The resulting clear mixture was stirred at rt overnight, evaporated, and purified by flash chromatography in 0 - 15 gradient of MeOH in CH2Cl2. Fractions containing product were evaporated leaving white crystalline compound 20, yield 120 mg, 68%. %) Mycophenolic-L-Valine-N-Adenosine (25) MPA-(L)-Val 24(151 mg, 0.36 mmol) and HOBT (54 mg, 0.39 mmol) was dissolved in dry DMF (2mL).To this stirred solution was added EDC (76 mg, 0.39 mmol) followed by 5'-aminoadenosine hydrochloride (122 mg, 0.36 mmol). Mixture was cooled in ice and TEA (0.11 mL,0.79 mmol) was added dropwise. Mixture was stirred until reaction reach rt andstirring was continued until reaction was complete. Mixture was diluted with EtOAc, washed with water, andbrine. Organic phase separated, dried over MgSO4, filtered, and solventsevaporated. TLC indicates small amount of the second diastereoisomer. Majorproduct was separated by chromatography on silica gel with CH2Cl2:MeOH,9:1 as solvent, and finally crystallized from EtOH to give 25. Yield: 100 mg, 42%.
  • 32
  • [ 24280-93-1 ]
  • [ 106-95-6 ]
  • (E)-allyl 6-(4-(allyloxy)-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% With 1,8-diazabicyclo[5.4.0]undec-7-ene; In N,N-dimethyl-formamide; at 20℃; for 18h; l,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) (602 muL, 4.03 mmol) and allyl bromide (238 muL, 2.82 mmol) were added to a solution of <strong>[24280-93-1]mycophenolic acid</strong> (250 mg, 0.809 mmol) in DMF (15 mL) and the mixture stirred at rt for 18 hours. The reaction was diluted with ethyl acetate (20 mL) and water (20 mL)and the aqueous phase extracted with ethyl acetate(2 x 30 mL). The combined organic extracts were washed with water and brine (40 mL each), dried (MgS04) and concentrated under reduced pressure to give the crude product. Silica gel chromatography (30% ethyl acetate/hexanes) gave the allyl ester XLI (292 mg, 93%) as a colourless oil.1H NMR (400 MHz, CDC13) delta 6.09 (ddt, J = 17.1, 10.4, 5.9 Hz, 1H), 5.86 (ddt, J = 17.2, 10.4, 5.7 Hz, 1H), 5.37 (dq, J = 17.2, 1.5 Hz, 1H), 5.30 - 5.15 (m, 4H), 5.13 (s, 2H), 4.78 (dt, J = 5.9, 1.3 Hz, 2H), 4.52 (dt, J = 5.7, 1.4 Hz, 2H), 3.76 (s, 3H), 3.41 (d, J = 6.5 Hz, 2H), 2.44 - 2.39 (m, 2H), 2.35 - 2.27 (m, 2H), 2.17 (s, 3H), 1.79 (s, 3H).
  • 33
  • [ 24280-93-1 ]
  • [ 18162-48-6 ]
  • [ 2036104-86-4 ]
YieldReaction ConditionsOperation in experiment
66% With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 6h; Inert atmosphere; (E)-tert-Butyldimethylsilyl 6-(4-((tert-butyldimethylsilyl)oxy)-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enoate (39) To a solution of MPA (200 mg, 0.62 mmol) in DMF (3 mL) was added imidazole (380 mg,5.6 mmol) and TBSCl (470 mg, 3.1 mmol) under argon. The resulting mixture was stirred at roomtemperature for 6 h and then quenched by the addition of H2O (100 mL). The aqueous layer wasextracted with diethyl ether (2 × 50 mL), and the combined organic extracts were washed withbrine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by columnchromatography on silica gel (EtOAc/hexane, 10:90 to 30:70) to afford 39 (225 mg, 66%) as aclear oil;
With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 1h;
With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 2.5h;
  • 34
  • [ 3891-07-4 ]
  • [ 24280-93-1 ]
  • (E)-2-(1,3-dioxoisoindolin-2-yl)ethyl-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
57% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 0 - 20℃; for 19h; General procedure: A mixture of the corresponding phthalimide derivatives2a-d (1.56 mmol), <strong>[24280-93-1]mycophenolic acid</strong> (1) (1.56 mmol; 500mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (1.56mmol; 243 mg), 4-dimethylaminopyridine (0.156 mmol; 19mg), triethylamine (1.87 mmol; 261 L) and 10 mL of anhydrousdichloromethane was stirred at 0C for 4 h. Then, thereaction was stirred for an additional 15 h at room temperature and monitored by TLC. Afterwards, the solvent wasconcentrated at reduced pressure and the crude product waspurified by column chromatography (flash silica, eluent:70% ethyl acetate; 30% hexane).
  • 35
  • [ 92789-55-4 ]
  • [ 24280-93-1 ]
  • (E)-3-(1,3-dioxoisoindolin-2-yl)benzyl-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 0 - 20℃; for 19h; General procedure: A mixture of the corresponding phthalimide derivatives2a-d (1.56 mmol), <strong>[24280-93-1]mycophenolic acid</strong> (1) (1.56 mmol; 500mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (1.56mmol; 243 mg), 4-dimethylaminopyridine (0.156 mmol; 19mg), triethylamine (1.87 mmol; 261 L) and 10 mL of anhydrousdichloromethane was stirred at 0C for 4 h. Then, thereaction was stirred for an additional 15 h at room temperature and monitored by TLC. Afterwards, the solvent wasconcentrated at reduced pressure and the crude product waspurified by column chromatography (flash silica, eluent:70% ethyl acetate; 30% hexane).
  • 36
  • [ 118-29-6 ]
  • [ 24280-93-1 ]
  • (E)-(1,3-dioxoisoindolin-2-yl)methyl-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
40% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 0 - 20℃; for 19h; General procedure: A mixture of the corresponding phthalimide derivatives2a-d (1.56 mmol), mycophenolic acid (1) (1.56 mmol; 500mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (1.56mmol; 243 mg), 4-dimethylaminopyridine (0.156 mmol; 19mg), triethylamine (1.87 mmol; 261 L) and 10 mL of anhydrousdichloromethane was stirred at 0C for 4 h. Then, thereaction was stirred for an additional 15 h at room temperature and monitored by TLC. Afterwards, the solvent wasconcentrated at reduced pressure and the crude product waspurified by column chromatography (flash silica, eluent:70% ethyl acetate; 30% hexane).
  • 37
  • [ 24280-93-1 ]
  • [ 145945-21-7 ]
  • (E)-(3-(1,3-dioxoisoindolin-2-yl)-2,6-dioxopiperidin-1-yl)methyl-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
42% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 0 - 20℃; for 19h; General procedure: A mixture of the corresponding phthalimide derivatives2a-d (1.56 mmol), <strong>[24280-93-1]mycophenolic acid</strong> (1) (1.56 mmol; 500mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (1.56mmol; 243 mg), 4-dimethylaminopyridine (0.156 mmol; 19mg), triethylamine (1.87 mmol; 261 L) and 10 mL of anhydrousdichloromethane was stirred at 0C for 4 h. Then, thereaction was stirred for an additional 15 h at room temperature and monitored by TLC. Afterwards, the solvent wasconcentrated at reduced pressure and the crude product waspurified by column chromatography (flash silica, eluent:70% ethyl acetate; 30% hexane).
  • 38
  • [ 24280-93-1 ]
  • [ 16115-80-3 ]
  • N-mycophenoyl malonic acid dimethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
45% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In N,N-dimethyl-formamide; at 20℃;Cooling with ice; The reaction was performed in dry DMF (Sigma-Aldrich), purification on silica gel 60 (230-400 mesh, Merck). 1H NMR and 13C NMR spectra were recorded in CDCl3 on a Varian Unity 500 Plus spectrometer, while the mass spectrometry measurements were performed with an Agilent 6540 Accurate Mass Q-TOF LC/MS system using the electrospray ionisation technique. Mycophenolic acid 1 (100 mg, 0.31 mmol), dimethyl aminomalonate hydrochloride 2 (63 mg, 0.34 mmol), triethylamine (217 mul, 1.56 mmol) were dissolved in dry DMF and then cooled in an ice bath. Next, T3P solution (365 mul, 0.62 mmol, 50% in DMF, Sigma-Aldrich) was added dropwise, and the reaction mixture was stirred at room temperature overnight. Subsequently, the solvent was evaporated under vacuum, while the remaining solids were dissolved in CH2Cl2, washed with water, and dried over anhydrous MgSO4. The suspension was filtered, the solvent was evaporated, and the crude product was purified via column chromatography (CH2Cl2:MeOH 100:1 to 50:1 v/v) to obtain amide 3, with a yield of 45% (63 mg, 0.14 mmol).Single crystals were obtained by vapor diffusion of petroleumether into a solution of about 10 mg product 3 in 5 mL dichloromethaneover 3-4 days, mp 157.0-157.7 C.1H NMR (d ppm): 1H NMR (d ppm): 1.81 (s, 3H, CH3), 2.15 (s, 3H,CH3), 2.31-2.40 (m, 4H, CH2), 3.39-3.40 (d, 2H, J 6.8 Hz, CH2),3.77 (s, 3H, OCH3), 3.81 (s, 6H, OCH3), 5.20 (s, 2H, OCH2), 5.22-5.28(m, 1H, CHvinyl), 6.46-6.48 (d, 1H, J 6.8 Hz, CH), 7.67 (m, 1H, NH).13C NMR (d ppm): 173.1, 172.6, 167.0, 163.9, 153.9, 144.3, 134.4,123.2, 122.3, 117.0, 106.6, 70.3, 61.3, 56.2, 53.7, 35.0, 34.8, 22.8, 16.4,11.8.ESIdMS for C22H28NO9 m/z calculated: 450.1764, obtained:450.1801 [MH], for C22H27NO9Na m/z calculated: 472.1584, obtained:472.1638 [MNa].
  • 39
  • [ 24280-93-1 ]
  • [ 104-84-7 ]
  • [ 2232213-08-8 ]
YieldReaction ConditionsOperation in experiment
75% With N′-hydroxy-[1,1′-biphenyl]-4-carboximidamide; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃; General procedure for the reaction of mycophenolicacid with different intermediates containing-amino General procedure: Mycophenolic acid (64 mg, 0.2 mmol), different aminecompounds (0.24 mmol), carboxylic mixture 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDCI)(114.7 mg, 0.6 mmol) and catalyst Biphenyl-4-amidoxime(HOBt) (84.8 mg, 0.4 mmol) were taken in a 25 ml roundbottom flask, and 5 ml dichloromethane as solvent, stirred at 0 °C for 4-6 h, progress of reaction was confirmed by TLC,the final products were purified using silica gel chromatography,and all the target compounds were obtained, whichare white powder in appearance, and the yield is 48-79%.
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0℃; for 6h;
  • 40
  • [ 96-50-4 ]
  • [ 24280-93-1 ]
  • [ 1451181-27-3 ]
YieldReaction ConditionsOperation in experiment
62% General procedure: To a solution of <strong>[24280-93-1]mycophenolic acid</strong> (2 mmol) in absolute DMF (1.5 mL) carbonyldiimidazole(2.2 mmol) was added and stirred for 2 h at room temperature. Then appropriate amine (2.2 mmol) wasadded and the reaction mixture is stirred at 70 C for 10 h. The mixture was cooled to room temperatureand distilled water (10 mL) was added. The precipitate formed was filtered and crystallized fromaqueous methanol. (E)-6-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methyl-N-(thiazol-2-yl)hex-4-enamide (1) [75]. Yield 62%, m.p. 216-217 C. 1H-NMR (300 MHz, DMSO-d6) : 1.77 (s, 3H,CH3), 2.05(s, 3H, CH3(arom)), 2.26 (t, 2H, J = 7.0 Hz, CH2CH2), 2.48 (t, 2H, J = 7.0 Hz, CH2CH2), 3.29 (d,2H, J = 6.1 Hz, CH2CH), 3.64 (s, 3H, OCH3), 5.16 (t, 1H, J = 6.1 Hz, CH2CH), 5.23 (s, 2H, OCH2), 7.15 (s,1H(thiaz)), 7.42 (s, 1H(thiaz)), 9.32 (bs, 1H, OH), 11.97 (bs, 1H, NH). 13C-NMR (500 MHz, CHCl3-d6):11.50, 16.46, 23.42, 34.32, 34.76, 60.97, 68.31, 112.40, 113.39, 119.94, 123.89, 128.70, 133.54, 136.06, 146.69,156.66, 159.59, 162.63, 168.80, 170.59. EI MS (m/z): 402 (M+, 16), 261 (14), 207 (22), 195 (43), 159 (22),142 (100), 127 (21), 100 (69), 91 (11), 55 (13). HRMS (ESI), m/z found 403.1322 [M + H] C20H23N2O5S.Calculated: [M + H] 403.1328.
  • 41
  • [ 7305-71-7 ]
  • [ 24280-93-1 ]
  • (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methyl-N-(5-methylthiazol-2-yl)hex-4-enamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% General procedure: To a solution of mycophenolic acid (2 mmol) in absolute DMF (1.5 mL) carbonyldiimidazole(2.2 mmol) was added and stirred for 2 h at room temperature. Then appropriate amine (2.2 mmol) wasadded and the reaction mixture is stirred at 70 C for 10 h. The mixture was cooled to room temperatureand distilled water (10 mL) was added. The precipitate formed was filtered and crystallized fromaqueous methanol.
  • 42
  • [ 2289-75-0 ]
  • [ 24280-93-1 ]
  • (E)-N-(4,5-dimethylthiazol-2-yl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% General procedure: To a solution of mycophenolic acid (2 mmol) in absolute DMF (1.5 mL) carbonyldiimidazole(2.2 mmol) was added and stirred for 2 h at room temperature. Then appropriate amine (2.2 mmol) wasadded and the reaction mixture is stirred at 70 C for 10 h. The mixture was cooled to room temperatureand distilled water (10 mL) was added. The precipitate formed was filtered and crystallized fromaqueous methanol.
  • 43
  • [ 1603-91-4 ]
  • [ 24280-93-1 ]
  • (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methyl-N-(4-methylthiazol-2-yl)hex-4-enamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% General procedure: To a solution of <strong>[24280-93-1]mycophenolic acid</strong> (2 mmol) in absolute DMF (1.5 mL) carbonyldiimidazole(2.2 mmol) was added and stirred for 2 h at room temperature. Then appropriate amine (2.2 mmol) wasadded and the reaction mixture is stirred at 70 C for 10 h. The mixture was cooled to room temperatureand distilled water (10 mL) was added. The precipitate formed was filtered and crystallized fromaqueous methanol.
  • 44
  • [ 7210-76-6 ]
  • [ 24280-93-1 ]
  • (E)-ethyl 2-(6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enamido)-4-methylthiazole-5-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% General procedure: To a solution of <strong>[24280-93-1]mycophenolic acid</strong> (2 mmol) in absolute DMF (1.5 mL) carbonyldiimidazole(2.2 mmol) was added and stirred for 2 h at room temperature. Then appropriate amine (2.2 mmol) wasadded and the reaction mixture is stirred at 70 C for 10 h. The mixture was cooled to room temperatureand distilled water (10 mL) was added. The precipitate formed was filtered and crystallized fromaqueous methanol.
  • 45
  • [ 53266-94-7 ]
  • [ 24280-93-1 ]
  • (E)-ethyl 2-(2-(6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enamido)thiazol-4-yl)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
59% General procedure: To a solution of mycophenolic acid (2 mmol) in absolute DMF (1.5 mL) carbonyldiimidazole(2.2 mmol) was added and stirred for 2 h at room temperature. Then appropriate amine (2.2 mmol) wasadded and the reaction mixture is stirred at 70 C for 10 h. The mixture was cooled to room temperatureand distilled water (10 mL) was added. The precipitate formed was filtered and crystallized fromaqueous methanol.
  • 46
  • [ 30235-28-0 ]
  • [ 24280-93-1 ]
  • (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methyl-N-(4-(pyridin-4-yl)thiazol-2-yl)hex-4-enamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
56% General procedure: To a solution of mycophenolic acid (2 mmol) in absolute DMF (1.5 mL) carbonyldiimidazole(2.2 mmol) was added and stirred for 2 h at room temperature. Then appropriate amine (2.2 mmol) wasadded and the reaction mixture is stirred at 70 C for 10 h. The mixture was cooled to room temperatureand distilled water (10 mL) was added. The precipitate formed was filtered and crystallized fromaqueous methanol.
  • 47
  • [ 24280-93-1 ]
  • [ 30235-27-9 ]
  • (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methyl-N-(4-(pyridin-3-yl)thiazol-2-yl)hex-4-enamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% General procedure: To a solution of mycophenolic acid (2 mmol) in absolute DMF (1.5 mL) carbonyldiimidazole(2.2 mmol) was added and stirred for 2 h at room temperature. Then appropriate amine (2.2 mmol) wasadded and the reaction mixture is stirred at 70 C for 10 h. The mixture was cooled to room temperatureand distilled water (10 mL) was added. The precipitate formed was filtered and crystallized fromaqueous methanol.
  • 48
  • [ 30235-26-8 ]
  • [ 24280-93-1 ]
  • (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methyl-N-(4-(pyridin-2-yl)thiazol-2-yl)hex-4-enamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
58% General procedure: To a solution of <strong>[24280-93-1]mycophenolic acid</strong> (2 mmol) in absolute DMF (1.5 mL) carbonyldiimidazole(2.2 mmol) was added and stirred for 2 h at room temperature. Then appropriate amine (2.2 mmol) wasadded and the reaction mixture is stirred at 70 C for 10 h. The mixture was cooled to room temperatureand distilled water (10 mL) was added. The precipitate formed was filtered and crystallized fromaqueous methanol.
  • 49
  • [ 136-95-8 ]
  • [ 24280-93-1 ]
  • (E)-N-(benzo[d]thiazol-2-yl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% General procedure: To a solution of <strong>[24280-93-1]mycophenolic acid</strong> (2 mmol) in absolute DMF (1.5 mL) carbonyldiimidazole(2.2 mmol) was added and stirred for 2 h at room temperature. Then appropriate amine (2.2 mmol) wasadded and the reaction mixture is stirred at 70 C for 10 h. The mixture was cooled to room temperatureand distilled water (10 mL) was added. The precipitate formed was filtered and crystallized fromaqueous methanol.
  • 50
  • [ 1747-60-0 ]
  • [ 24280-93-1 ]
  • (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-N-(6-methoxybenzo[d]thiazol-2-yl)-4-methylhex-4-enamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
64% General procedure: To a solution of <strong>[24280-93-1]mycophenolic acid</strong> (2 mmol) in absolute DMF (1.5 mL) carbonyldiimidazole(2.2 mmol) was added and stirred for 2 h at room temperature. Then appropriate amine (2.2 mmol) wasadded and the reaction mixture is stirred at 70 C for 10 h. The mixture was cooled to room temperatureand distilled water (10 mL) was added. The precipitate formed was filtered and crystallized fromaqueous methanol.
  • 51
  • [ 2933-29-1 ]
  • [ 24280-93-1 ]
  • (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methyl-N-(4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)hex-4-enamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% General procedure: To a solution of mycophenolic acid (2 mmol) in absolute DMF (1.5 mL) carbonyldiimidazole(2.2 mmol) was added and stirred for 2 h at room temperature. Then appropriate amine (2.2 mmol) wasadded and the reaction mixture is stirred at 70 C for 10 h. The mixture was cooled to room temperatureand distilled water (10 mL) was added. The precipitate formed was filtered and crystallized fromaqueous methanol.
  • 52
  • [ 24280-93-1 ]
  • [ 14292-44-5 ]
  • (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methyl-N-(5,6,7,8-tetrahydro-4H-cyclohepta[d]thiazol-2-yl)hex-4-enamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
67% General procedure: To a solution of <strong>[24280-93-1]mycophenolic acid</strong> (2 mmol) in absolute DMF (1.5 mL) carbonyldiimidazole(2.2 mmol) was added and stirred for 2 h at room temperature. Then appropriate amine (2.2 mmol) wasadded and the reaction mixture is stirred at 70 C for 10 h. The mixture was cooled to room temperatureand distilled water (10 mL) was added. The precipitate formed was filtered and crystallized fromaqueous methanol.
  • 53
  • [ 53051-97-1 ]
  • [ 24280-93-1 ]
  • (E)-N-(5,6-dihydro-4H-cyclopenta[d]thiazol-2-yl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% General procedure: To a solution of mycophenolic acid (2 mmol) in absolute DMF (1.5 mL) carbonyldiimidazole(2.2 mmol) was added and stirred for 2 h at room temperature. Then appropriate amine (2.2 mmol) wasadded and the reaction mixture is stirred at 70 C for 10 h. The mixture was cooled to room temperatureand distilled water (10 mL) was added. The precipitate formed was filtered and crystallized fromaqueous methanol.
  • 54
  • [ 24280-93-1 ]
  • [ 18162-48-6 ]
  • [ 1451181-22-8 ]
YieldReaction ConditionsOperation in experiment
60% With 1H-imidazole; In N,N-dimethyl-formamide; at 20℃; for 88h; Imidazole (128 mg, 1.87 mmol) and tert-butyl(chloro)dimethylsilane (TBSC1, 141 mg,0.93 7 mmol) were added to a solution of <strong>[24280-93-1]mycophenolic acid</strong> (MPA, 200 mg, 0.624 mmol) in DMF(7 mL) and the mixture stirred at rt for 22 hours. Extra portions of imidazole (65.0 mg, 0.954mmol) and TBSC1 (80.0 mg, 0.531 mmol) were added and the mixture stirred at rt for an additionaltwo days and 18 hours. The reaction was diluted with ethyl acetate (20 mL) and water (30 mL)and the aqueous phase extracted with ethyl acetate (3 x 30 mL). The combined organic extracts were washed with water and brine (80 mL each), dried (MgSO4) and concentrated under reduced pressure to give the crude product. Purification by silica gel chromatography (10% to 35% ethyl acetate/hexanes) gave MPA(OTBS) Int-82 (164 mg, 60%) as a colorless solid. ?H NMR (400 IVIHz, CDC13) 5.19 (m, 1H), 5.06 (s, 2H), 3.73 (s, 3H), 3.38 (d, J= 6.3 Hz, 2H), 2.46-2.36 (m, 2H), 2.33 - 2.24 (m, 2H), 2.14 (s, 3H), 1.75 (s, 3H), 1.02 (s, 9H), 0.23 (s, 6H); ?3C NIVIR (101 IVIFIz, CDC13) 179.4 (C), 169.4 (C), 163.3 (C), 151.9 (C), 146.2 (C), 133.5 (C), 127.7 (C), 124.0 (CH), 118.1 (C), 111.8 (C), 67.8 (CH2), 60.8 (CH3), 34.2 (CH2), 32.9 (CH2), 26.2 (3C; CH3), 23.8 (CH2), 18.9 (C), 16.4 (CH3), 11.5 (CH3), -3.4 (2C; CH3).
  • 55
  • [ 85342-65-0 ]
  • [ 24280-93-1 ]
  • C25H19Cl4NO8 [ No CAS ]
  • 56
  • [ 24280-93-1 ]
  • (x)C2HF3O2*C37H51N9O10 [ No CAS ]
  • C54H69N9O15 [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h;Inert atmosphere; General procedure: Derivative TFA Thr-Lys (Fmoc)-Pro-Arg (NO2)-OCH3 5a 0.025 g (0.0289 mmol), MPA0.0068 g (0.0212 mmol), TEA 0.0014 mL (0.0112 mmol) were dissolvedin 1 mL anhydrous DMF, under nitrogen. Then, the reactionmixture was coolded to 0 C, followed by addition of T3P 0.030 mL(0.052 mmol, 50% solution in DMF) and stirred for 2 h. Subsequently,stirring was continued for 48 h at room temperature. Theprogress of the reaction was monitored with TLC (solvent systemA). When the reaction was complete, the solvent was distilled ofunder vacuum, and the product isolated with preparative thin layerchromatography (PTLC), solvent system A.
  • 57
  • [ 24280-93-1 ]
  • (x)C2HF3O2*C39H54N10O11 [ No CAS ]
  • C56H72N10O16 [ No CAS ]
YieldReaction ConditionsOperation in experiment
48% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h;Inert atmosphere; General procedure: Derivative TFA Thr-Lys (Fmoc)-Pro-Arg (NO2)-OCH3 5a 0.025 g (0.0289 mmol), MPA0.0068 g (0.0212 mmol), TEA 0.0014 mL (0.0112 mmol) were dissolvedin 1 mL anhydrous DMF, under nitrogen. Then, the reactionmixture was coolded to 0 C, followed by addition of T3P 0.030 mL(0.052 mmol, 50% solution in DMF) and stirred for 2 h. Subsequently,stirring was continued for 48 h at room temperature. Theprogress of the reaction was monitored with TLC (solvent systemA). When the reaction was complete, the solvent was distilled ofunder vacuum, and the product isolated with preparative thin layerchromatography (PTLC), solvent system A.
  • 58
  • [ 24280-93-1 ]
  • (x)C2HF3O2*C40H56N10O11 [ No CAS ]
  • C57H74N10O16 [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h;Inert atmosphere; General procedure: Derivative TFA Thr-Lys (Fmoc)-Pro-Arg (NO2)-OCH3 5a 0.025 g (0.0289 mmol), MPA0.0068 g (0.0212 mmol), TEA 0.0014 mL (0.0112 mmol) were dissolvedin 1 mL anhydrous DMF, under nitrogen. Then, the reactionmixture was coolded to 0 C, followed by addition of T3P 0.030 mL(0.052 mmol, 50% solution in DMF) and stirred for 2 h. Subsequently,stirring was continued for 48 h at room temperature. Theprogress of the reaction was monitored with TLC (solvent systemA). When the reaction was complete, the solvent was distilled ofunder vacuum, and the product isolated with preparative thin layerchromatography (PTLC), solvent system A.
  • 59
  • [ 24280-93-1 ]
  • (x)C2HF3O2*C40H56N10O11 [ No CAS ]
  • C57H74N10O16 [ No CAS ]
YieldReaction ConditionsOperation in experiment
51% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h;Inert atmosphere; General procedure: Derivative TFA Thr-Lys (Fmoc)-Pro-Arg (NO2)-OCH3 5a 0.025 g (0.0289 mmol), MPA0.0068 g (0.0212 mmol), TEA 0.0014 mL (0.0112 mmol) were dissolvedin 1 mL anhydrous DMF, under nitrogen. Then, the reactionmixture was coolded to 0 C, followed by addition of T3P 0.030 mL(0.052 mmol, 50% solution in DMF) and stirred for 2 h. Subsequently,stirring was continued for 48 h at room temperature. Theprogress of the reaction was monitored with TLC (solvent systemA). When the reaction was complete, the solvent was distilled ofunder vacuum, and the product isolated with preparative thin layerchromatography (PTLC), solvent system A.
  • 60
  • [ 24280-93-1 ]
  • (x)C2HF3O2*C42H60N10O11 [ No CAS ]
  • C59H78N10O16 [ No CAS ]
YieldReaction ConditionsOperation in experiment
49% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h;Inert atmosphere; General procedure: Derivative TFA Thr-Lys (Fmoc)-Pro-Arg (NO2)-OCH3 5a 0.025 g (0.0289 mmol), MPA0.0068 g (0.0212 mmol), TEA 0.0014 mL (0.0112 mmol) were dissolvedin 1 mL anhydrous DMF, under nitrogen. Then, the reactionmixture was coolded to 0 C, followed by addition of T3P 0.030 mL(0.052 mmol, 50% solution in DMF) and stirred for 2 h. Subsequently,stirring was continued for 48 h at room temperature. Theprogress of the reaction was monitored with TLC (solvent systemA). When the reaction was complete, the solvent was distilled ofunder vacuum, and the product isolated with preparative thin layerchromatography (PTLC), solvent system A.
  • 61
  • [ 24280-93-1 ]
  • (x)C2HF3O2*C43H62N10O11 [ No CAS ]
  • C60H80N10O16 [ No CAS ]
YieldReaction ConditionsOperation in experiment
42% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h;Inert atmosphere; General procedure: Derivative TFA Thr-Lys (Fmoc)-Pro-Arg (NO2)-OCH3 5a 0.025 g (0.0289 mmol), MPA0.0068 g (0.0212 mmol), TEA 0.0014 mL (0.0112 mmol) were dissolvedin 1 mL anhydrous DMF, under nitrogen. Then, the reactionmixture was coolded to 0 C, followed by addition of T3P 0.030 mL(0.052 mmol, 50% solution in DMF) and stirred for 2 h. Subsequently,stirring was continued for 48 h at room temperature. Theprogress of the reaction was monitored with TLC (solvent systemA). When the reaction was complete, the solvent was distilled ofunder vacuum, and the product isolated with preparative thin layerchromatography (PTLC), solvent system A.
  • 62
  • [ 24280-93-1 ]
  • (x)C2HF3O2*C43H62N10O11 [ No CAS ]
  • C60H80N10O16 [ No CAS ]
YieldReaction ConditionsOperation in experiment
45% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h;Inert atmosphere; General procedure: Derivative TFA Thr-Lys (Fmoc)-Pro-Arg (NO2)-OCH3 5a 0.025 g (0.0289 mmol), MPA0.0068 g (0.0212 mmol), TEA 0.0014 mL (0.0112 mmol) were dissolvedin 1 mL anhydrous DMF, under nitrogen. Then, the reactionmixture was coolded to 0 C, followed by addition of T3P 0.030 mL(0.052 mmol, 50% solution in DMF) and stirred for 2 h. Subsequently,stirring was continued for 48 h at room temperature. Theprogress of the reaction was monitored with TLC (solvent systemA). When the reaction was complete, the solvent was distilled ofunder vacuum, and the product isolated with preparative thin layerchromatography (PTLC), solvent system A.
  • 63
  • [ 24280-93-1 ]
  • (x)C2HF3O2*C37H51N9O10 [ No CAS ]
  • C54H69N9O15 [ No CAS ]
YieldReaction ConditionsOperation in experiment
64% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h;Inert atmosphere; General procedure: CompoundTFA Arg (NO2)-Pro-Lys (Fmoc)-Thr-OCH3 5h 0.01 g (0.011 mmol),MPA 0.0026 g (0,008 mmola), DMAP 0.015 g (0.011 mmola) weredissolved in 1 mL of anydrous DMF under nitrogen. Then, the reactionmixture was cooled to 0 C, followed by addition of EDCI0.0017 g (0.0107 mmol), and after 2 h stirred for 48 h at roomtemperature. The progress of the reactionwas monitorem with TLC(solvent system A). When the reaction was complete, solvent wasdistilled of under vacuum and the product isolated with preparativethin layer chromatography (PTLC), solvent system A.
  • 64
  • [ 24280-93-1 ]
  • (x)C2HF3O2*C39H54N10O11 [ No CAS ]
  • C56H72N10O16 [ No CAS ]
YieldReaction ConditionsOperation in experiment
28% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h;Inert atmosphere; General procedure: CompoundTFA Arg (NO2)-Pro-Lys (Fmoc)-Thr-OCH3 5h 0.01 g (0.011 mmol),MPA 0.0026 g (0,008 mmola), DMAP 0.015 g (0.011 mmola) weredissolved in 1 mL of anydrous DMF under nitrogen. Then, the reactionmixture was cooled to 0 C, followed by addition of EDCI0.0017 g (0.0107 mmol), and after 2 h stirred for 48 h at roomtemperature. The progress of the reactionwas monitorem with TLC(solvent system A). When the reaction was complete, solvent wasdistilled of under vacuum and the product isolated with preparativethin layer chromatography (PTLC), solvent system A.
  • 65
  • [ 24280-93-1 ]
  • (x)C2HF3O2*C40H56N10O11 [ No CAS ]
  • C57H74N10O16 [ No CAS ]
YieldReaction ConditionsOperation in experiment
28% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h;Inert atmosphere; General procedure: CompoundTFA Arg (NO2)-Pro-Lys (Fmoc)-Thr-OCH3 5h 0.01 g (0.011 mmol),MPA 0.0026 g (0,008 mmola), DMAP 0.015 g (0.011 mmola) weredissolved in 1 mL of anydrous DMF under nitrogen. Then, the reactionmixture was cooled to 0 C, followed by addition of EDCI0.0017 g (0.0107 mmol), and after 2 h stirred for 48 h at roomtemperature. The progress of the reactionwas monitorem with TLC(solvent system A). When the reaction was complete, solvent wasdistilled of under vacuum and the product isolated with preparativethin layer chromatography (PTLC), solvent system A.
  • 66
  • [ 24280-93-1 ]
  • (x)C2HF3O2*C40H56N10O11 [ No CAS ]
  • C57H74N10O16 [ No CAS ]
YieldReaction ConditionsOperation in experiment
28% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h;Inert atmosphere; General procedure: CompoundTFA Arg (NO2)-Pro-Lys (Fmoc)-Thr-OCH3 5h 0.01 g (0.011 mmol),MPA 0.0026 g (0,008 mmola), DMAP 0.015 g (0.011 mmola) weredissolved in 1 mL of anydrous DMF under nitrogen. Then, the reactionmixture was cooled to 0 C, followed by addition of EDCI0.0017 g (0.0107 mmol), and after 2 h stirred for 48 h at roomtemperature. The progress of the reactionwas monitorem with TLC(solvent system A). When the reaction was complete, solvent wasdistilled of under vacuum and the product isolated with preparativethin layer chromatography (PTLC), solvent system A.
  • 67
  • [ 24280-93-1 ]
  • (x)C2HF3O2*C42H60N10O11 [ No CAS ]
  • C59H78N10O16 [ No CAS ]
YieldReaction ConditionsOperation in experiment
28% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h;Inert atmosphere; General procedure: CompoundTFA Arg (NO2)-Pro-Lys (Fmoc)-Thr-OCH3 5h 0.01 g (0.011 mmol),MPA 0.0026 g (0,008 mmola), DMAP 0.015 g (0.011 mmola) weredissolved in 1 mL of anydrous DMF under nitrogen. Then, the reactionmixture was cooled to 0 C, followed by addition of EDCI0.0017 g (0.0107 mmol), and after 2 h stirred for 48 h at roomtemperature. The progress of the reactionwas monitorem with TLC(solvent system A). When the reaction was complete, solvent wasdistilled of under vacuum and the product isolated with preparativethin layer chromatography (PTLC), solvent system A.
  • 68
  • [ 24280-93-1 ]
  • (x)C2HF3O2*C43H62N10O11 [ No CAS ]
  • C60H80N10O16 [ No CAS ]
YieldReaction ConditionsOperation in experiment
28% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h;Inert atmosphere; General procedure: CompoundTFA Arg (NO2)-Pro-Lys (Fmoc)-Thr-OCH3 5h 0.01 g (0.011 mmol),MPA 0.0026 g (0,008 mmola), DMAP 0.015 g (0.011 mmola) weredissolved in 1 mL of anydrous DMF under nitrogen. Then, the reactionmixture was cooled to 0 C, followed by addition of EDCI0.0017 g (0.0107 mmol), and after 2 h stirred for 48 h at roomtemperature. The progress of the reactionwas monitorem with TLC(solvent system A). When the reaction was complete, solvent wasdistilled of under vacuum and the product isolated with preparativethin layer chromatography (PTLC), solvent system A.
  • 69
  • [ 24280-93-1 ]
  • (x)C2HF3O2*C43H62N10O11 [ No CAS ]
  • C60H80N10O16 [ No CAS ]
YieldReaction ConditionsOperation in experiment
28% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃; for 50h;Inert atmosphere; General procedure: CompoundTFA Arg (NO2)-Pro-Lys (Fmoc)-Thr-OCH3 5h 0.01 g (0.011 mmol),MPA 0.0026 g (0,008 mmola), DMAP 0.015 g (0.011 mmola) weredissolved in 1 mL of anydrous DMF under nitrogen. Then, the reactionmixture was cooled to 0 C, followed by addition of EDCI0.0017 g (0.0107 mmol), and after 2 h stirred for 48 h at roomtemperature. The progress of the reactionwas monitorem with TLC(solvent system A). When the reaction was complete, solvent wasdistilled of under vacuum and the product isolated with preparativethin layer chromatography (PTLC), solvent system A.
  • 70
  • [ 524-38-9 ]
  • [ 24280-93-1 ]
  • [ 2173129-29-6 ]
YieldReaction ConditionsOperation in experiment
With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃; Typical procedure for the preparation of NHPI esters General procedure: A 100 mL round-bottom flask was charged with 4-phenylbutanoic acid (1.64 g,10 mmol), N-hydroxyphthalimide (1.63 g, 10 mmol) and 4-dimethylaminopyridine(122 mg, 1.0 mmol). Dichloromethane (50 mL) was added and the mixture was stirred vigorously. N,N’-Diisopropylcarbodiimide (1.39 g, 11 mmol) was then added dropwise via syringe and the mixture was allowed to stir at room temperature until the carboxylic acid or the N-hydroxyphthalimide was fully consumed (monitored byTLC). The resulting mixture was filtered over Celite and rinsed with additional CH2Cl2 (10 mL × 3). The solvent was removed under reduced pressure, and the crude product was purified by column chromatography on silica gel with hexane/ethylacetate (20:1, v:v) as the eluent to give the pure product 1,3-dioxoisoindolin-2-yl 4-phenylbutanoate (1a) as a white solid. Yield: 2.72 g (88% yield).
With dmap; diisopropyl-carbodiimide In dichloromethane
With dicyclohexyl-carbodiimide
With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃;
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃;
With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃; General procedure for the preparation of NHPI esters General procedure: A 100 mL round-bottom flask was charged with alkyl carboxylic acid (10 mmol),N-hydroxyphthalimide (1.63 g, 10 mmol) and 4-dimethylaminopyridine (122 mg, 1.0mmol). Dichloromethane (50 mL) was added and the mixture was stirred vigorously.N, N’-Diisopropylcarbodiimide (1.39 g, 11 mmol) was then added dropwise via syringeand the mixture was allowed to stir at room temperature until the carboxylic acid or Nhydroxyphthalimidewas fully consumed (monitored by TLC). The resulting mixturewas filtered over Celite and rinsed with CH2Cl2 (10 mL × 3). The combined organic phase was concentrated under reduced pressure, and the crude product was purified bycolumn chromatography on silica gel with hexane/ethyl acetate (5:1, v/v) as the eluentto give the pure product.

  • 71
  • [ 24280-93-1 ]
  • [ 320-51-4 ]
  • [ 2660137-64-2 ]
YieldReaction ConditionsOperation in experiment
80% With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 20℃; for 16h; Inert atmosphere; (E)-N-(3,4-Dichlorophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enamide (9) General procedure: To a solution of MPA (160.2 mg, 0.5 mmol) in anhydrous DMF (3 mL) was addedEDC•HCl (143.8 mg, 0.75 mmol), HOAt (102.1 mg, 0.75 mmol), triethylamine (100 μL, 0.75mmol) and 3,4-dichloroaniline (97.2 mg, 0.6 mmol) under argon. The resulting mixture was stirredat room temperature for 16 h and then quenched by the addition of H2O (100 mL). The aqueouslayer was extracted with EtOAc (2 × 50 mL), and the combined organic extracts were washed withbrine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by columnchromatography on silica gel (EtOAc/hexane, 20:80 to 30:70) to afford 9 (79 mg, 34%) as a whitesolid;
  • 72
  • [ 24720-64-7 ]
  • [ 24280-93-1 ]
  • [ 24280-92-0 ]
YieldReaction ConditionsOperation in experiment
77% Stage #1: mycophenolic acid With osmium(VIII) oxide; 4-methylmorpholine N-oxide In tetrahydrofuran; water; acetone at 20℃; for 1.5h; Stage #2: 2-(triphenylphosphoranylidene)propionaldehyde In benzene at 90℃; for 24h; Inert atmosphere; (E)-4-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-2-methylbut-2-enal (19) To a solution of MPA (1.92 g, 6 mmol) and NMO (1.41 g, 12 mmol) in a 3:1 (v/v) mixtureof THF/H2O (24 mL) was added a solution of OsO4 (50 mg, 0.2 mmol) in acetone (2 mL). Theresulting mixture was stirred at room temperature for 1.5 h and then diluted with H2O (60 mL).The mixture was cooled to 0 oC, and a solution of NaIO4 (4.28 g, 40 mL) was added in portions.The formed precipitate was filtered, washed with cold water (3 × 10 mL) and dried to give crudeproduct (1.29 g) as a white solid. A suspension of this crude product and Ph3P=C(Me)CHO (2.1 g,6.6 mmol) in anhydrous benzene (25 mL) under argon was heated under reflux (90 oC) for 24 h.The reaction mixture was concentrated and purified by column chromatography on silica gel(EtOAc/hexane, 20:80 to 30:70) to afford 19 (1.27 g, 77%) as a white solid;
  • 73
  • [ 31246-66-9 ]
  • [ 24280-93-1 ]
  • [ 2568205-00-3 ]
YieldReaction ConditionsOperation in experiment
83.9% With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In N,N-dimethyl-formamide at 40℃; for 60h; Darkness; 1.2-1.3; 2.2-2.3; 3.2-3.3 (2) Preparation process of new Pt(IV) complex mother liquor According to themass volume ratio ofdihydroxycisplatin (W) toDMF1g: 8mL,pipetteDMF, and according to dihydroxycisplatin (W) andThemolar ratio ofTBTU, triethylamine and mycophenolic acid is 1:3 respectively. WeighTBTU, triethylamine and mycophenolic acid (TBTU, triethylamine and mycophenolic acid)The molar ratio is 1:1:1).Add dihydroxycisplatin (W) to 40CDMF,stir at40Cfor 30min, filter, and transfer the filtrateAt 40C, addTBTU, triethylamine and mycophenolic acid, stir for 60h in thedark, filter, and collect the filtrate. (3)Preparation process of novelPt(W) complex product Pipette methanol or ethanol according to the volume ratio ofDMFand methanol or ethanol 1:5, and concentrate the remaining liquid and reaction according to .The volume ratio of the solvent is 1:10, and the back solvent is removed. The back solvent is a mixture of any two solvents in methanol, acetone or ether.The volume ratio of any two solvents is 1:1.Add methanol or ethanol to the filtrate collected in , stir evenly, and mixUse a rotary evaporator to evaporate the liquid until no droplets fall (water bath temperature 70C, vacuum degree 200hPa/mbar), take out the remaining liquidAdd the reverse analysis solvent in a dark environment,stir at40Cfor 60min, filter,stir and wash the filter cake 3 times with anappropriate amount of 20Cwater, filter dry, 50CAfter vacuum drying for 8hours,262.38g of thenewPt(W) complex was obtained. The overall yield (calculated as cisplatin) was 83.9%.
  • 74
  • [ 24280-93-1 ]
  • [ 108-00-9 ]
  • [ 2854299-30-0 ]
YieldReaction ConditionsOperation in experiment
79% With N′-hydroxy-[1,1′-biphenyl]-4-carboximidamide; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃; General procedure for the reaction of mycophenolicacid with different intermediates containing-amino General procedure: Mycophenolic acid (64 mg, 0.2 mmol), different aminecompounds (0.24 mmol), carboxylic mixture 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDCI)(114.7 mg, 0.6 mmol) and catalyst Biphenyl-4-amidoxime(HOBt) (84.8 mg, 0.4 mmol) were taken in a 25 ml roundbottom flask, and 5 ml dichloromethane as solvent, stirred at 0 °C for 4-6 h, progress of reaction was confirmed by TLC,the final products were purified using silica gel chromatography,and all the target compounds were obtained, whichare white powder in appearance, and the yield is 48-79%.
  • 75
  • [ 5036-48-6 ]
  • [ 24280-93-1 ]
  • (E)-N-(3-(1H-imidazol-1-yl)propyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% With N′-hydroxy-[1,1′-biphenyl]-4-carboximidamide; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃; General procedure for the reaction of mycophenolicacid with different intermediates containing-amino General procedure: Mycophenolic acid (64 mg, 0.2 mmol), different aminecompounds (0.24 mmol), carboxylic mixture 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDCI)(114.7 mg, 0.6 mmol) and catalyst Biphenyl-4-amidoxime(HOBt) (84.8 mg, 0.4 mmol) were taken in a 25 ml roundbottom flask, and 5 ml dichloromethane as solvent, stirred at 0 °C for 4-6 h, progress of reaction was confirmed by TLC,the final products were purified using silica gel chromatography,and all the target compounds were obtained, whichare white powder in appearance, and the yield is 48-79%.
Same Skeleton Products
Historical Records

Similar Product of
[ 24280-93-1 ]

Chemical Structure| 37415-62-6

A1378826[ 37415-62-6 ]

Sodium (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enoate

Reason: Free-salt