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[ CAS No. 6066-82-6 ]

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CAS No. :6066-82-6 MDL No. :MFCD00005516
Formula : C4H5NO3 Boiling Point : 262.4°C at 760 mmHg
Linear Structure Formula :- InChI Key :N/A
M.W :115.09 g/mol Pubchem ID :80170
Synonyms :

Safety of [ 6066-82-6 ]

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

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  • Upstream synthesis route of [ 6066-82-6 ]
  • Downstream synthetic route of [ 6066-82-6 ]

[ 6066-82-6 ] Synthesis Path-Upstream   1~43

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  • [ 74402-54-3 ]
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YieldReaction ConditionsOperation in experiment
24% With triethylamine In acetonitrile EXAMPLE 12
This example illustrates the synthesis of sulpiride with using as the condensation reagent N-succinimidyl diphenylphosphate (SDPP) which is prepared from N-hydroxysuccinimide (HOSu) and diphenylphospholy chloride.
A solution of 462 mg (0.002 mol) of 2-methoxy-5-aminosulfonylbenzoic acid and 256 mg (0.002 mol) of N-ethyl-2-aminomethylpyrrole in 10 ml of acetonitrile was admixed with 694 mg (0.002 mol) of SDPP and 202 mg (0.002 mol) of triethylamine, and the admixture was stirred overnight at room temperature.
The crystalline material deposited was collected by filtration and washed with acetonitrile and then with ethanol to give sulpiride, that is, 5-(aminosulfonyl)-N-[(1-ethyl-2-pyrrolidinyl) methyl]-2-methoxybenzamide. mp. 182°~185° C. Yield 24percent.
Reference: [1] Patent: US4341707, 1982, A,
  • 2
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  • [ 15761-38-3 ]
  • [ 3392-05-0 ]
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[2] Chemical and pharmaceutical bulletin, 2002, vol. 50, # 2, p. 239 - 252
[3] Journal of the Chemical Society, Chemical Communications, 1985, # 8, p. 473
[4] Carbohydrate Research, 1984, vol. 132, p. 275 - 286
[5] Journal of the American Chemical Society, 1992, vol. 114, # 17, p. 6653 - 6661
[6] Journal of the American Chemical Society, 1996, vol. 118, # 29, p. 6975 - 6985
[7] Journal of Medicinal Chemistry, 1997, vol. 40, # 15, p. 2386 - 2397
[8] Chemistry of Natural Compounds, 1997, vol. 33, # 5, p. 568 - 570
[9] Chemistry of Natural Compounds, 1998, vol. 34, # 1, p. 78 - 79
[10] Journal of Medicinal Chemistry, 2003, vol. 46, # 21, p. 4543 - 4551
[11] Patent: EP2123283, 2009, A1, . Location in patent: Page/Page column 17-18
[12] Patent: US2009/325894, 2009, A1, . Location in patent: Page/Page column 11-12
[13] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 12, p. 3220 - 3224
[14] Biomacromolecules, 2010, vol. 11, # 2, p. 496 - 504
[15] Organic and Biomolecular Chemistry, 2011, vol. 9, # 11, p. 4182 - 4187
[16] Synlett, 2012, # 1, p. 142 - 144
[17] Chinese Chemical Letters, 2011, vol. 22, # 12, p. 1443 - 1446
[18] Biochimie, 2013, vol. 95, # 6, p. 1120 - 1126
[19] Chinese Chemical Letters, 2016, vol. 27, # 3, p. 357 - 360
[20] Patent: EP2612857, 2017, B1, . Location in patent: Paragraph 0137
[21] Journal of Molecular Biology, 2018, vol. 430, # 6, p. 842 - 852
  • 3
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  • [ 3392-05-0 ]
Reference: [1] Collection of Czechoslovak Chemical Communications, 2005, vol. 70, # 10, p. 1615 - 1641
  • 4
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  • [ 56-40-6 ]
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Reference: [1] Journal of Organic Chemistry, 1988, vol. 53, # 15, p. 3583 - 3586
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  • [ 501-53-1 ]
  • [ 13139-17-8 ]
Reference: [1] Bulletin des Societes Chimiques Belges, 1987, vol. 96, # 10, p. 775 - 782
[2] Bulletin of the Chemical Society of Japan, 1987, vol. 60, # 7, p. 2409 - 2418
[3] Chemical and Pharmaceutical Bulletin, 1999, vol. 47, # 10, p. 1489 - 1490
[4] Organic Preparations and Procedures International, 2002, vol. 34, # 5, p. 531 - 537
[5] Patent: US3974137, 1976, A,
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  • [ 3303-84-2 ]
  • [ 32703-87-0 ]
YieldReaction ConditionsOperation in experiment
62% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In 1,4-dioxane at 20℃; Inert atmosphere In a dry flask containing a magnetic stir bar, 0.50 g of 1 (2.64 mmol) and 0.31 g of N-hydroxysuccinimide (SuOH) (2.72 mmol, 1.03 equivalent) were dissolved in 3mL of distilled dioxane. Subsequently, 1.25 equivalent of 3-(ethyliminomethyleneamino)-N,N-dimethylpropan-l-amine in hydrogen chloride form (EDC) (0.63 g, 3.3 mmol) was added into the flask. The solution was cloudy, and 2mL of freshly distilled dioxane was added into the reaction mixture. The reaction mixture was stirred under nitrogen for 30 minutes and then left for stirring overnight at room temperature. Dioxane was removed under vacuum. The residue was dissolved in chloroform and washed with water (3x). The organic layer was dried of over Na2S04 and concentrated under vacuum. The desire product was precipitated in ethanol and dried in a desiccator, yielding 0.47g of product (62percent). The 1H NMR spectral data matched the previously reported values for the compound.
Reference: [1] ACS Medicinal Chemistry Letters, 2018, vol. 9, # 6, p. 557 - 561
[2] Patent: WO2017/53486, 2017, A1, . Location in patent: Page/Page column 11
[3] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1981, p. 529 - 537
[4] Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 24, p. 3603 - 3608
[5] Chemical Communications, 2010, vol. 46, # 20, p. 3553 - 3555
[6] Patent: WO2011/133875, 2011, A2, . Location in patent: Page/Page column 46-47
[7] Patent: WO2013/110002, 2013, A1, . Location in patent: Page/Page column 45-46
[8] Patent: WO2013/109998, 2013, A1, . Location in patent: Page/Page column 45
[9] Bioconjugate Chemistry, 2018, vol. 29, # 4, p. 1454 - 1465
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YieldReaction ConditionsOperation in experiment
86% With triethylamine In ethyl acetate at 0 - 20℃; for 24 h; A dried round-bottom flask was charged with N-hydroxysuccinimide (5.83 g, 50.7 mmol), ethyl acetate (20 mL) as a solvent and cooled at 0 °C. To the mixture were slowly added triethylamine (4.76 g) and methylisocyanate (6.39 g, 0.112 mmol) at the same temperature. The reaction temperature was slowly raised to rt, and the mixture was stirred for 24 h at rt. After the volatile materials were removed under reduced pressure the crude residue was re-crystallized from ethyl acetate/diethyl ether to give 51a (86 percent). Colorless needles, mp 148.0–149.0 °C (lit [19]. 148.0–152.0°C); 1H NMR (300 MHz, CDCl3): δ 8.15 (1H, br, NH), 2.76 (4H, s, CH2CH2), 2.67 (3H, s-like, CH3); 13C NMR (22.5 MHz, CDCl3): δ 170.66, 151.98, 27.98, 25.47; MS (FAB+) m/z 173 (M+H).
Reference: [1] European Journal of Medicinal Chemistry, 2014, vol. 82, p. 16 - 35
[2] Journal of Medicinal Chemistry, 1982, vol. 25, # 2, p. 178 - 182
[3] Journal of the American Chemical Society, 1995, vol. 117, # 4, p. 1240 - 1245
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YieldReaction ConditionsOperation in experiment
53% With triethylamine In chloroform at 0℃; for 0.416667 h; To a solution of N-hydroxysuccinimide (640.3 mg, 5.56 mmol) in chloroform (8.5 mL) was added triethylamine (861.6 μ, 6.18 mmol) 0 C. Then, a-chloroacetyl chloride was added dropwise over a 5 minute period and stirred for an additional 20 minutes at 0°C. The reaction mixture was washed with ice-cold water (15 mL) and brine (15 mL), concentrated to a volume of 1.7 mL in vacuo, then dried with sodium sulfate and filtered. To the resulting solution were added ethyl acetate (170 μ) and hexanes (1.2 mL), and the mixture was cooled down to 0 °C stirred for 2 h, and a white solid was precipitated. It was filtered and washed first with ice-cold 10 mL portion of hexanes/ethyl acetate (4: 1), then with 10 mL hexanes/ethyl acetate (9: 1), and finally with hexanes (10 mL, twice). The resulting white solid was dried under house vacuum to yield 2,5-dioxopyrrolidin-l-yl 2-chloroacetate (563.9 mg, 53percent). NMR 400 MHz (CDC13) δ 4.37 (s, 2H), 2.87 (s, 4H).
Reference: [1] Angewandte Chemie - International Edition, 2014, vol. 53, # 1, p. 199 - 204[2] Angew. Chem., 2013, vol. 126, # 1, p. 203 - 208,6
[3] Patent: WO2014/160200, 2014, A1, . Location in patent: Paragraph 000273
[4] Polish Journal of Chemistry, 1992, vol. 66, # 1, p. 111 - 118
[5] Journal of Medicinal Chemistry, 2014, vol. 57, # 6, p. 2380 - 2392
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[2] Helvetica Chimica Acta, 1996, vol. 79, p. 133 - 136
[3] Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 24, p. 3671 - 3676
[4] Patent: US6335437, 2002, B1, . Location in patent: Page column 22
[5] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 11, p. 6156 - 6166
[6] Organic and Biomolecular Chemistry, 2011, vol. 9, # 21, p. 7296 - 7299
[7] Journal of Medicinal Chemistry, 2015, vol. 58, # 16, p. 6516 - 6532
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  • [ 65-85-0 ]
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YieldReaction ConditionsOperation in experiment
93% With dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃; for 48 h; General procedure: benzoic acid (0.353 g, 2.89 mmol) was dissolved in 50 mL of dry THF, and N-hydroxysuccinimide (0.40 g, 3.47 mmol) and DCC (0.776 g, 3.76 mmol) were added. The mixture was stirred at room temperature for 2 days. The soluble portion was separated from the viscous residue and the solvent was removed under reduced pressure. The residue was dissolved in CHCl3separated and dried over anhydrous Na2SO4, the solvent was removed by evaporation to dryness. The crude product was purified by column chromatography with 40percent ethyl acetate in hexane to afford a white solid (0.586 g, 93percent). The white solid wasrecrystallized from 2-propanol.
78% With triethylamine; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 20℃; for 3 h; General procedure: Benzoic acid (ring d-5, heavy isotope, d-Bz) (127 mg, 1.00 mmol) or benzoic acid (ring d-0, light isotope, Bz) (122 mg, 1.00 mmol), N-hydroxysuccinimide (230 mg, 2.00 mmol) and triethylamine (167 μL, 1.20 mmol) were dissolved in anhydrous dimethylformamide (DMF) (1 mL). After addition of dicyclohexylcarbodiimide (DCC) (206 mg, 1.20 mmol), the solution was stirred at room temperature for 3 h. The reaction mixture was filtered to remove the precipitate, and concentrated in vacuo. The resulting syrup was crystallized from isopropanol (5 mL) to yield benzoic acid N-succinimidyl ester (d-Bz labeling reagent, 184 mg, 82percent) (Bz labeling reagent, 170 mg, 78percent). Rf = 0.42 (toluene-EtOAc = 10:1); 1H-NMR (600 MHz, CDCl3): δ 2.91 (s, 4H) for the heavy isotope, δ 2.91 (s, 4H), 7.52 (dd, 2H), 7.69 (dd, 1H), 8.14 (dd, 2H) for the light isotope; 13C-NMR (125 MHz, CDCl3): δ 25.63, 124.88, 128.31, 130.13, 134.38, 161.82, 169.24 for the heavy isotope, δ 25.65, 125.08, 128.83, 130.55, 134.91, 161.84, 169.23 for the light isotope.
61% With dicyclohexyl-carbodiimide In dichloromethane at 0℃; for 6 h; Benzoic acid (3 g, 24.6 mmol) and N-hydroxysuccinimide (4.24 g, 36.8 mmol, 1.5 eq) were dissolved in 50 mL CH2Cl2, and the mixture was cooled to 0 °C. To this solution was added 7.6 g of DCC (36.8 mmol, 1.5 eq) in 25 mL CH2Cl2. The reaction mixture was stirred vigorously for 6 h. After filtration, the solvent was evaporated, and the crude product was purified by column chromatography to afford 7 as a white solid with a yield 61percent. m.p.:134-136 °C.1H NMR (400 MHz, CDCl3): δ 8.14 (400 MHz, d, J = 7.8 Hz, 2H, Ar-H), 7.69 (t, J = 7.4 Hz, 1H, Ar-H), 7.52 (t, J = 7.7 Hz, 2H, Ar-H), 2.91 (s, 4H, CH2).
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[2] Chemistry Letters, 1980, p. 1161 - 1164
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[10] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 4, p. 949 - 954
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[14] Tetrahedron, 1991, vol. 47, # 39, p. 8407 - 8416
[15] Journal of Medicinal Chemistry, 1992, vol. 35, # 7, p. 1246 - 1259
[16] Tetrahedron Letters, 1998, vol. 39, # 11, p. 1321 - 1324
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[27] Patent: WO2018/71879, 2018, A1, . Location in patent: Sheet 5
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YieldReaction ConditionsOperation in experiment
80% With oxygen In acetonitrile at 80℃; for 10 h; Green chemistry General procedure: p-Fluorobenzaldehyde 1a (124.0 mg, 1.0 mmol, 1.0 equiv.) and NHSI (2b) (62.5 mg, 0.5 mmol, 0.5 equiv.) were dissolved in DEC/CH3CN (1:1 3 mL) and stirred under 80oC for 10 h. After the reaction was completed (monitored by TLC), the reaction mixture was concentrated under vacuum. The residue was purified by ethanol recrystallization to give the 4a as a white solid, m. p. 100-102 °C.
Reference: [1] Angewandte Chemie - International Edition, 2012, vol. 51, # 50, p. 12538 - 12541[2] Angew. Chem., 2012, vol. 124, # 50, p. 12706 - 12709,4
[3] New Journal of Chemistry, 2018, vol. 42, # 2, p. 807 - 811
[4] Tetrahedron Letters, 2017, vol. 58, # 18, p. 1742 - 1746
[5] RSC Advances, 2015, vol. 5, # 56, p. 44928 - 44932
[6] Tetrahedron Letters, 2012, vol. 53, # 38, p. 5094 - 5098
[7] Organic and Biomolecular Chemistry, 2013, vol. 11, # 47, p. 8241 - 8246
[8] Advanced Synthesis and Catalysis, 2014, vol. 356, # 11-12, p. 2709 - 2713
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YieldReaction ConditionsOperation in experiment
84% With 1,4-diaza-bicyclo[2.2.2]octane In acetonitrile at 20℃; for 1 h; General procedure: To a test tube charged with a stir bar, 0.20 mmol of1a and 0.20 mmol of BPO weresequentially added MeCN 1.0 mL and 0.20 mmol of DABCO. The resulting reactionmixture was stirred at room temperature for 3 h and diluted by addition of EtOAc,the organic layer was briefly washed by saturated aqueous sodium bicarbonatesolution, brine and dried over anhydrous sodium sulfate. The bulk solvent wasremoved in vacuo, and the residue waspurified by silica gel flash chromatography (hexane/EtOAc = 5:1) to affordproduct 2a 48.8 mg, 90percent yield.
Reference: [1] Tetrahedron Letters, 2014, vol. 55, # 31, p. 4404 - 4406
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Reference: [1] Tetrahedron Letters, 2003, vol. 44, # 12, p. 2477 - 2480
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[2] RSC Advances, 2013, vol. 3, # 44, p. 21306 - 21310
[3] Tetrahedron Letters, 2012, vol. 53, # 38, p. 5094 - 5098
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YieldReaction ConditionsOperation in experiment
95% With dicyclohexyl-carbodiimide In ethyl acetate at 20℃; for 12 h; Lauric acid (12.0 g, 60 mmol) dissolved in dry ethyl acetate (100 mL) was added to a solution of N-hydroxysuccinimide (NHS) (6.9 g, 60 mmol) and N,N’-dicyclohexylcarbodiimide (DCC) (12.4 g, 60 mmol) in dry ethyl acetate (300 mL). The reaction mixture was left overnight at room temperature. Dicyclohexylurea (DCU) was removed by filtration and the filtrate was evaporated under reduced pressure to yield white crystals (17.4 g, 95 percent yield). Recrystallization from ethanol yielded 16.6g of pure dodecanoic acid 2,5-dioxo-pyrrolidine-1-yl ester.
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Reference: [1] Bioconjugate Chemistry, 2017, vol. 28, # 11, p. 2772 - 2783
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YieldReaction ConditionsOperation in experiment
61.8% With dicyclohexyl-carbodiimide In dichloromethane at 15 - 20℃; Step2: 2,5-Dioxopyrrolidine-1-yl 2-(fert-butoxycarbonylamino)acetate. /V-Boc-glycine (7.31 g, 41 .7 mmol) was dissolved in 100 mL of DCM and to the cooled (15°C) solution /V-hydroxysuccinimide (5.28 g, 45.9 mmol) was added. Λ/,Λ/'-dicyclohexylcarbodiimide (9.47 g, 45.9 mmol) was added to the formed suspension under vigorous stirring. After a few seconds, a cloudy white suspension formed, the mixture was allowed to reach room temperature and stirred for 1 h. It was subsequently filtrated over celite, washed with 50m L saturated sodium - - bicarbonate, dried over sodium sulfate and concentrated in vacuo to yield a crystalline powder. Yield: 7.02 g, 61 .8percent 1 H NMR (400 MHz, DMSO -cfe) : δ 1 .38 (s, 9H), 2.80 (s, 4H), 4.07 (d, J = 6 Hz, 2H), 7.43 (br s, 1 H). MS (ESI) m/z 567.2 [2M + Na]+.
61.8% With dicyclohexyl-carbodiimide In dichloromethane at 15℃; N-Boc-glycine (7.31 g, 41.7 mmol) was dissolved in 100 mL of DCM and to the cooled (15° C.) solution N-hydroxysuccinimide (5.28 g, 45.9 mmol) was added. N,N'-dicyclohexylcarbodiimide (9.47 g, 45.9 mmol) was added to the formed suspension under vigorous stirring.
After a few seconds, a cloudy white suspension formed, the mixture was allowed to reach room temperature and stirred for 1 h.
It was subsequently filtrated over celite, washed with 50 mL saturated sodium bicarbonate, dried over sodium sulfate and concentrated in vacuo to yield a crystalline powder. Yield: 7.02 g, 61.8percent
1H NMR (400 MHz, DMSO-d6): δ 1.38 (s, 9H), 2.80 (s, 4H), 4.07 (d, J=6 Hz, 2H), 7.43 (br s, 1H). MS (ESI) m/z 567.2 [2M+Na]+.
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YieldReaction ConditionsOperation in experiment
65.4 mg
Stage #1: With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In dichloromethane at 20℃; for 0.333333 h;
Stage #2: for 48 h;
To a solution of Gly-Gly (1.00 g, 7.57 mmol) in dioxane:water (30:5 mL) at room temperature was added triethylamine (1.15 g,11.4 mmol) and di-tert-butyl-dicarbonate (1.84 g, 8.33 mmol) consecutively. The mixture was stirred at room temperature overnight, then diluted with water, acidified to approximately pH 2via the addition of solid KHSO4, extracted with EtOAc, dried(Na2SO4), and concentrated in vacuo to afford (tert-butoxycarbonyl)glycylglycine [8] as a white solid. To a solution of crude (tertbutoxycarbonyl)glycylglycine (0.106 g, 0.451 mmol) in anhydrous dichloromethane (5.00 mL) was added triethylamine (45.6 mg,0.451 mmol) and propylphosphonic anhydride solution (T3P®) [9] (0.344 g, 0.541 mmol) at room temperature. The mixture was stirred for 20 min, followed by the addition of N-hydroxy succinimide (51.9 mg, 0.451 mmol). The reaction was stirred for 48 h and upon completion, the organic layer was washed with brine (3),dried (Na2SO4), and concentrated in vacuo to afford the product as a white solid. The crude solid was triturated from diethyl ether toafford 65.4 mg (44percent) of the product as a white solid: 1H NMR(400 MHz, CDCl3) d 6.76 (brs, 1 H), 5.15 (brs, 1 H), 4.43 (d, 2 H,J 5.7 Hz), 3.87 (d, 2 H, J 5.3 Hz), 2.85 (s, 4 H), 1.45 (s, 9 H); ESIMSm/z 330 [MH]. Direct infusion ESI-MS on a high resolution accurate mass measurements (Exactive Plus, Thermo Fisher Scientific) in the negative ion mode yielded an elemental composition of the expected product within 5 ppm (see Fig. 1).
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[2] Journal of Pharmaceutical Sciences, 1984, vol. 73, # 2, p. 275 - 277
[3] Analytical Biochemistry, 2016, vol. 512, p. 114 - 119
  • 36
  • [ 6066-82-6 ]
  • [ 110-15-6 ]
  • [ 30364-60-4 ]
YieldReaction ConditionsOperation in experiment
27% With dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 20℃; To succinic acid (3 0 g, 25 42 mmol, 1 OO equiv) m THF (50 mL) was added a solution of 1- hydroxypyrrohdine-2,5-dione (64 g, 55 65 mmol, 2 20 eqmv) This was followed by the addition of a solution of DCC (11 5 g, 55 83 mmol, 2 20 equiv) in THF (50 mL) dropwise with stirring at O0C The resulting solution was stirred overnight at room temperature The reaction progress was monitored by LCMS The solids were collected by filtration and the filtrate was concentrated to give the crude product The resulting solids were washed with THF and ethanol This resulted in 2 4 g (27percent) of bis(2,5- dioxopyrrohdin-1-yl) succinate as a white solid.
Reference: [1] Patent: WO2010/78449, 2010, A2, . Location in patent: Page/Page column 291
[2] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1980, vol. 29, # 5, p. 785 - 789[3] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1980, # 5, p. 1078 - 1081
[4] Chemical Papers, 2016, vol. 70, # 4, p. 505 - 514
[5] Patent: WO2016/205488, 2016, A1, . Location in patent: Paragraph 0264
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[2] Patent: WO2015/155231, 2015, A1, . Location in patent: Page/Page column 67; 68
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[4] Patent: WO2015/21092, 2015, A1, . Location in patent: Page/Page column 36
  • 39
  • [ 6066-82-6 ]
  • [ 68858-20-8 ]
  • [ 130878-68-1 ]
YieldReaction ConditionsOperation in experiment
89% With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 3 h; Dicyclocarbodiimide (1 .55 g, 7.52 mmol) and N-hydroxysuccinimide (762 mg, 6.63 mmol) are added at room temperature to a stirrer solution of Fmoc-Val-OH [9] (1 .5 g, 4.42 mmol) in anhydrous dichloromethane (25 ml_). The mixture is kept at room temperature for 3 hours. The white solid formed in this reaction is filtrated with dichloromethane to remove the dicyclohexylurea, the organic phase is washed with HCI 0.1 N and water, then dried over anhydrous sodium sulfate and the solvent removed by rotatory evaporation. The residue is subjected to a flash column chromatography in 1 percent methanol in dichloromethane to afford product [10] as a white solid, 1 .7 g (89percent yield). MS: m/z 459 [M+Na]+.1H NMR (400 MHz, CDCIs) δ 7.80 (d, J = 7.5 Hz, 2H), 7.68 - 7.55 (m, 2H), 7.43 (t, J = 7.4 Hz, 2H), 7.34 (dd, J = 15.9, 8.5 Hz, 2H), 4.70 (d, J = 4.6 Hz, 1 H), 4.56 - 4.40 (m, 3H), 4.28 (t, J = 6.6 Hz, 1 H), 2.85 (s, 4H), 2.37 (dd, J = 12.3, 6.5 Hz, 1 H), 1 .08 (dd, J = 1 1 .0, 6.9 Hz, 6H).
65% With dicyclohexyl-carbodiimide In 1,2-dimethoxyethane at 20℃; for 23 h; Cooling with ice; Inert atmosphere Fmoc-Valine (1.02 g, 3 mmol) and N-hydroxysuccinimide (0.345 g, 3 mmol) were dissolved in dimethoxy ethane (35 ml) and cooled in an ice bath, then DCC (0.681 g, 3.3 mmol) was added. The resulting mixture was stirred in the ice bath for 3 hours, then at room temperature for 20 hours. The precipitate formed was filtered off and the filtrate concentrated under vacuo. The crude product was further purified by flash chromatography (ethyl acetate/hexane, v:v, 4:6) to afford SI20B as a white solid. Isolated yield: 65percent. TLC (EtOAc:Hexane 3:2). Rf=0.57, irradiated by a UV lamp. HPLC: 0.1percent TFA (v/v) in water (solvent A):acetonitrile (solvent B); gradient 45-85percent in 30 min, flow rate=0.5 mL/min. Retention time (Rt)=15.77 min. 1H NMR (FIG. 26A): (400 MHz, CDCl3) δ 7.76-7.78 (d, J=7.20 Hz, 2H), 7.59-7.60 (d, J=7.20 Hz, 2H), 7.38-7.42 (t, J=7.20 Hz, 2H), 7.30-7.34 (m, 2H), 5.26-5.28 (d, J=9.20 Hz, 1H), 4.67-4.71 (dd, J=4.8, 5.2 Hz, 1H), 4.42-4.46 (dd, J=6.8, 6.4 Hz, 2H), 4.23-4.26 (t, J=6.8 Hz, 1H), 2.84 (s, 4H), 2.04-2.36 (m, 1H), 0.83-088 (m, 6H). 13C NMR (FIG. 26B): (101 MHz, CDCl3) δ 168.7, 141.5, 127.9, 127.3, 127.3, 125.3, 120.2, 120.2, 67.5, 57.7, 47.4, 31.9, 25.8, 18.9, 17.5.
26.51 g With dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 20℃; for 6 h; Inert atmosphere [00125] This compound is prepared according to R. A. Firestone et al, US 6,214,345. Fmoc-Val-OH (20.24 g; 59.64 mmol) and N-hydroxysuccinimide (6.86 g =1 .0 eq.) in tetrahydrofuran (200 ml) at 000 were treated with N,N’dicyclohexylcarbodiimide (12.30 g; 1.0 eq.). The mixture was stirred at RT under argon atmosphere for 6 h and then the solid dicyclohexyl urea (DCU) by-product was filtered off and washed with THF and the solvent was removed by rotavap. The residue was dissolved in 300 ml dichloromethane, cooled in an ice bath for 1 h and filtered again to remove additional DCU. The dichloromethane was evaporated and the solid foam (26.51 g) was used in the next step without further purification.
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  • [ 253265-97-3 ]
YieldReaction ConditionsOperation in experiment
99.6% With triethylamine In tetrahydrofuran for 2 h; Reflux The compounds of formula 1 obtained in Example 3 (3.8g, 0.02mol) was dissolved in 30ml of tetrahydrofuran, was added dropwise to N- hydroxyalkylSuccinimide (2.3g, 0.02mol) in 45ml of tetrahydrofuran was added triethylamine (2.02g, 0.02mol), the addition was complete, reflux, 2 hours reaction, TLC detection material disappeared, water was added to brine and extracted , take the upper concentrated to give 5.4g compound of formula 6-1 in a yield of 99.6percent.
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  • [ 1172623-98-1 ]
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