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Product Details of [ 2295-31-0 ]

CAS No. :2295-31-0 MDL No. :MFCD00005478
Formula : C3H3NO2S Boiling Point : -
Linear Structure Formula :HNC(O)CH2SC(O) InChI Key :ZOBPZXTWZATXDG-UHFFFAOYSA-N
M.W : 117.13 Pubchem ID :5437
Synonyms :
Thiazolidinedione

Calculated chemistry of [ 2295-31-0 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 7
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.33
Num. rotatable bonds : 0
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 29.52
TPSA : 71.47 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.96 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.54
Log Po/w (XLOGP3) : 0.07
Log Po/w (WLOGP) : -0.41
Log Po/w (MLOGP) : -0.94
Log Po/w (SILICOS-IT) : 0.95
Consensus Log Po/w : 0.04

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -0.61
Solubility : 28.7 mg/ml ; 0.245 mol/l
Class : Very soluble
Log S (Ali) : -1.12
Solubility : 8.79 mg/ml ; 0.075 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -0.6
Solubility : 29.6 mg/ml ; 0.253 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.24

Safety of [ 2295-31-0 ]

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:

Application In Synthesis of [ 2295-31-0 ]

* 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.

  • Upstream synthesis route of [ 2295-31-0 ]
  • Downstream synthetic route of [ 2295-31-0 ]

[ 2295-31-0 ] Synthesis Path-Upstream   1~22

  • 1
  • [ 2295-31-0 ]
  • [ 74-88-4 ]
  • [ 16312-21-3 ]
YieldReaction ConditionsOperation in experiment
79% With potassium carbonate In N,N-dimethyl-formamide at 75℃; for 3 h; Step 1 : Preparation of intermediate 3-methyl-thiazolidine-2,4-dione (33a)A solution of thiazolidine-2,4-dione (2 g, 17.1 mmol), potassium carbonate (3.55 g, 27.7 mmol) and methyl iodide (1 .87 mL, 30 mmol) in Λ/,/V-dimethylformamide (16 mL) was stirred at 75 °C for 3 hours. The mixture was then filtered and concentrated. The residue was diluted with water (30 mL) and ethyl acetate (30 mL). The organic layer was washed with water (2x10 mL), brine (30 mL), dried over sodium sulfate, filtered and evaporated under reduced pressure to give, after purification by flash chromatography on silica gel (dichloromethane), the desired product (33a) as a white solid (1 .77 g, 13.5 mmol, 79percent).1H NMR (400 MHz, CDCI3) .pound.3.19 (s, 3H), 3.95 (s, 2H). MS m/z ([M+H]+) 132.
50% With potassium carbonate In N,N-dimethyl-formamide at 0 - 20℃; for 12 h; To a mixture of 233 (20 g, 171 mmol) and potassium carbonate (47.3 g, 342mmoi) in DMF (100 ml) is added Mel (32 mL, 513 mmoi) dropwise at 0 °C. After stirring at room temperature for 12 hours, the mixture is concentrated and the residue is partitioned between water (100 mL) and DCM (100 mL). The aqueous layer is extracted with DCM (60 niL, x 4). The combined organic layers are dried over anhvdrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography (DCM) to give Di as an off- white solid (10 g, 50percent yield). (MS: IM-f-HL 132.2)
Reference: [1] Journal of Chemical Research, 2005, # 8, p. 492 - 494
[2] Organic and Biomolecular Chemistry, 2011, vol. 9, # 10, p. 3801 - 3807
[3] Organic Letters, 2015, vol. 17, # 6, p. 1361 - 1364
[4] Patent: WO2012/137181, 2012, A1, . Location in patent: Page/Page column 136-137
[5] Patent: WO2017/176812, 2017, A1, . Location in patent: Paragraph 0503
[6] Justus Liebigs Annalen der Chemie, 1888, vol. 249, p. 30
[7] Gazzetta Chimica Italiana, 1966, vol. 96, p. 612 - 624
[8] Tetrahedron, 1996, vol. 52, # 9, p. 3189 - 3194
[9] European Journal of Medicinal Chemistry, 2013, vol. 59, p. 15 - 22
  • 2
  • [ 186581-53-3 ]
  • [ 2295-31-0 ]
  • [ 16312-21-3 ]
Reference: [1] Helvetica Chimica Acta, 1954, vol. 37, p. 2057,2064
[2] Yakugaku Zasshi, 1948, vol. 68, p. 245[3] Chem.Abstr., 1954, p. 3962
  • 3
  • [ 2295-31-0 ]
  • [ 124-41-4 ]
  • [ 74-88-4 ]
  • [ 16312-21-3 ]
Reference: [1] Justus Liebigs Annalen der Chemie, 1888, vol. 249, p. 30
  • 4
  • [ 2295-31-0 ]
  • [ 4175-76-2 ]
YieldReaction ConditionsOperation in experiment
76% at 5 - 125℃; for 4.25 h; 2,4-dichlorothiazoleCool to 5 0C a mixture of thiazolidine-2,4-dione (50 g, 0.43 mol) in phosphorus oxychloride (240 mL) and add pyridine (34 mL, 0.43 mol) over 15 min. Heat the mixture to 125 0C for 4 h and then cool to 22 0C. Remove the excess phosphorus oxychloride by vacuum distillation and add the residue to water (1 L) chilled to a temperature of 5 0C. Extract the mixture with methylene chloride (3 x 400 mL). Combine the organic portions and evaporate the solvent to afford the title compound (50 g, 76percent). EI/MS m/z : (35C135C1/35C137C1/37C137C1) 153/155/157 (M+l)+.
70% With trichlorophosphate In pyridine at 120℃; for 3 h; A mixture of thiazole-2,4-dione (25 g), POCl3 (130 mL) and freshly distilled pyridine (17 mL) were heated at 120° C. for 3 hours.
After cooling to room temperature, excess POCl3 was removed under reduced pressure.
The residue was poured into ice/water, and extracted with ether.
The combined ether solution was washed with aqueous 5percent NaOH, water, then dried.
Removal of solvent gave the desired intermediate in 70percent yield.
26% With pyridine; trichlorophosphate In methanol at 120℃; for 3 h; Step 1 : 2,4-Dichloro-thiazole To a stirred solution of thiazolidine-2,4-dione (4 g, 26 mmol) in anhydrous MeOH (100 mL) was added POCl3 (130 mL) and pyridine (17 mL). The mixture was heated at 120 °C for 3 hours and then cooled to room temperature. Excess POCl3 was removed under reduced pressure. The residue was poured into ice/water, and extracted with ethyl acetate (3 x 20 mL). The combined organic layer was washed with brine (50 mL), dried over Na2S04, filtered and concentrated in vacuo to give the crude product, which was purified by column chromatography to give the pure product 2,4-dichloro-thiazole (8.4 g, 26percent yield): lH NMR (400 MHz, CDC13) δ 5.90 (s, 1H); ES-LCMS m/z 153.9 (M+H).
14% With pyridine; trichlorophosphate In dichloromethane at 0℃; for 3 h; Reflux To a mixture of thiazolidine-2,4-dione (5.00 g, 42.69 mmol) in phosphorous oxychloride (25 mL) at 0 °C was added pyridine (3.80 mL, 46.96 mmol) dropwise. The mixture was then stirred at reflux for 3 hours, then cooled and poured onto ice-water. The aqueous layer was then extracted by DCM, and the combined organic layers dried and evaporated. Column (0508) chromatography with 19: 1 hexanes/EtOAc afforded the product 103. Yield = 0.94 g, 14percent. 1H MR (CDC13) δ 7.02 (1H, s). Found: [M+H]=133.3
34.8 g at 5 - 125℃; for 4.25 h; 50 g (427 mmol) thiazolidine-2,4-dione was dissolved in 240 ml POCI3 and 34 ml (422 mmol) pyridine were added at 5°C during 15 minutes. The reaction mixture was heated at 125°C for 4 hours and cooled down. Phosphoroxychloride was removed by evaporation and the residue was poured into a mixture of water and ice. 2,4-Dichlorothiazole crystallized and was filtered to give 34.8 g 2,4-dichlorothiazole in form of white crystals, Mp: 45-6°C.

Reference: [1] Patent: WO2008/36579, 2008, A1, . Location in patent: Page/Page column 36-37
[2] Patent: US2005/234046, 2005, A1, . Location in patent: Page/Page column 60
[3] Journal of the American Chemical Society, 2013, vol. 135, # 5, p. 1986 - 1996
[4] Patent: WO2013/149362, 2013, A1, . Location in patent: Page/Page column 55
[5] Patent: WO2017/155909, 2017, A1, . Location in patent: Paragraph 0159
[6] Patent: US2007/112011, 2007, A1,
[7] Patent: WO2008/83070, 2008, A1, . Location in patent: Page/Page column 62-63
[8] Patent: WO2005/28444, 2005, A1, . Location in patent: Page/Page column 73
[9] Patent: WO2006/2981, 2006, A1, . Location in patent: Page/Page column 106
[10] Patent: EP2532661, 2012, A1, . Location in patent: Page/Page column 23
[11] Patent: WO2012/168361, 2012, A1, . Location in patent: Page/Page column 49
[12] Patent: WO2013/156433, 2013, A1, . Location in patent: Page/Page column 19; 37
  • 5
  • [ 2295-31-0 ]
  • [ 4175-77-3 ]
YieldReaction ConditionsOperation in experiment
71%
Stage #1: at 130℃; for 0.5 h;
Stage #2: With sodium carbonate In water at 0℃;
EXAMPLE 41; Preparation of 2-Amino-3-methyl-5-(3-pyrimidin-5-ylphenyl)-5-(1,3-thiazol-4-yl)-3,5-dihydro-4H-imidazol-4-one; Step a); Preparation of Compound 2; A mixture of 2,4-thiazolidinedione 1 (2.28 g, 19.5 mmol) and phosphorous oxybromide (25.0 g, 87.0 mmol) was heated at 130° C. for 30 min, then cooled to room temperature. The reaction was diluted with ice water (300 mL) and carefully neutralized by the addition of solid sodium carbonate in small portions. Once neutral, the mixture was extracted with dichloromethane (3.x.150 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated. Purification of the residue by flash chromatography (silica, 0:100 to 5:95 ethyl acetate/hexanes) afforded 2 (3.34 g, 71percent) as light yellow crystals: 1H NMR (500 MHz, CDCl3) δ 7.21 (s, 1H).
50% at 80 - 125℃; for 2 h; 2-4-thiazolidinione (10 g, 0.085 mol) was added portionwise to stirred phosphorus oxybromide (160 g) at 80° C. The mixture was then warmed slowly to 125° C. with stirring (vigorous evolution of HBr occurred at approximately 118° C.) and held at 125° C. for 2 hrs. After cooling, the resultant solid was added portionwise to ice/sodium bicarbonate and the brown solid was collected by filtration. The reaction was repeated as above on 10 g and then on 20 g scale, and all three batches of the brown solids were combined. The crude combined material was purified via short path silica gel column chromatograph. The purified product was isolated as a pale yellow solid (41.23 g, 50percent).
47% at 110℃; for 3 h; A mixture of 21-1 (5.0 g, 38.42 mmol) and POBr3 (55.07 g, 192.09 mmol) was stirred at 110 °C for 3 h, then cooled to 55 °C and poured onto ice (300 g). Solid Na2CO3 (40g) was added portionwise and the mixture was extracted with EA (150 ml x 3). The combined organic layers were washed with brine (80 ml), dried over Na2SO4, filtered, concentrated and purified by silica gel column chromatography (pure PE to PE : EA = 50 : 1) to afford 21-2 as a white solid (4.86 g, yield 47percent).
47% at 110℃; for 3 h; Compound 22-2 (0434) A mixture of 22-1 (5.0 g, 38.42 mmol) and POBr3 (55.07 g, 192.09 mmol) was stirred at 110° C. for 3 h, then cooled to 55° C. and poured onto ice (300 g). Solid Na2CO3 (40 g) was added portionwise and the mixture was extracted with EA (150 mL×3). The combined organic layers were washed with brine (80 mL), dried over Na2SO4, filtered, concentrated and purified by silica gel column chromatography (pure PE to PE:EA=50:1) to afford 22-2 as a white solid (4.86 g, yield 47percent).

Reference: [1] Journal of Organic Chemistry, 2006, vol. 71, # 10, p. 3754 - 3761
[2] Synthesis, 2012, vol. 44, # 7, p. 1026 - 1029
[3] Journal of Materials Chemistry C, 2017, vol. 5, # 45, p. 11927 - 11936
[4] Patent: US2007/4786, 2007, A1, . Location in patent: Page/Page column 21
[5] Tetrahedron, 2006, vol. 62, # 38, p. 9017 - 9037
[6] Patent: US2004/254236, 2004, A1,
[7] Patent: US2008/234267, 2008, A1, . Location in patent: Page/Page column 17
[8] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 19, p. 5849 - 5853
[9] Patent: US9138427, 2015, B2, . Location in patent: Page/Page column 298-299
[10] Journal of Chemical Crystallography, 2015, vol. 45, # 10-12, p. 461 - 465
[11] Journal of Organic Chemistry, 2017, vol. 82, # 11, p. 5947 - 5951
[12] Journal of Organic Chemistry, 2018, vol. 83, # 2, p. 664 - 671
  • 6
  • [ 2295-31-0 ]
  • [ 21295-51-2 ]
  • [ 4175-77-3 ]
Reference: [1] Patent: US4990520, 1991, A,
  • 7
  • [ 2295-31-0 ]
  • [ 68-12-2 ]
  • [ 92972-48-0 ]
YieldReaction ConditionsOperation in experiment
52%
Stage #1: at 0 - 115℃; for 5.5 h;
Stage #2: With sodium hydrogencarbonate In dichloromethane
Step 1. 2,4-dichloro-1,3-thiazole-5-carbaldehydeTo a suspension of 2,4-thiazolidinedione (10.0 g, 85.4 mmol) in phosphoryl chloride (48.0 mL, 515 mmol) at 0° C. was added DMF (7.3 mL, 94 mmol) drop-wise. The reaction mixture was allowed to warm to ambient temperature and stirred for 1 h. The mixture was then heated at 85° C. for 1 h before stirring at 115° C. for 3.5 h. After cooling to ambient temperature, the mixture was carefully poured onto ice with slow stirring. The aqueous layer was extracted with DCM three times. The combined organic extracts were washed with saturated NaHCO3, water, dried over MgSO4, filtered, and concentrated. The residue was purified by silica gel column (0percent to 20percent ethyl acetate/hexanes) to give the desired product as off white solid (8.1 g, 52percent). 1H NMR (300 MHz, DMSO-d6): δ 9.92 (s, 1H); LCMS (M+H-CO)+: 153.9
48%
Stage #1: at 20 - 115℃; for 6 h;
To a cooled solution of 2,4-thiazolidinedione (5 g, 42.7 mmol) in POCl3 (24 ml) was added DMF (3.7 mL, 26.4 mmol).
The mixture was stirred at room temperature for 1 hour, and then heated at 90° C. for 1 h and 115° C. for 4 h.
The mixture was poured into a large amount of cold crashed ice.
The mixture was extracted with CH2Cl2, washed with water, purified by chromatography on a silica gel column using CHCl8 as an eluant to afford the title compound to afford compound II (3.6 g, 48percent) as a brown solid. 1H NMR (400 MHz, CDCl3) ppm 9.90 (s, 1H).
33% at 0 - 120℃; for 5.25 h; Inert atmosphere [000270] Synthesis of 2, 4-dichlorothiazole-5-carbaldehyde (330): A mixture of compound 329 (2.7 g, 23.07 mmol) in DMF (1.23 mL, 15.98 mmol) at 0 °C under argon atmosphere was added phosphorous oxychloride (8.15 mL, 87.17 mmol) dropwise for 15 mm at 0 °C; warmed to RT and stirred for 1 h; heated to 120 °C and stirred for 4 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was poured into ice cold water slowly and extracted with CH2C12 (3 x 100 mL). The combined organic extracts were washed with saturated NaHCO3 solution (100 mL), water (100 mL), dried over sodium sulfate, filtered and concentrated in vacuo to obtain the crude. The crude was purified through column chromatography using 5percent EtOAc/ hexanes to afford compound 330 (1.4 g, 33percent) as brown color oil. TLC: 30percent EtOAc/ hexanes (R 0.8); 1H NMR (500 MHz, DMSO-d6): ö 9.87 (s, 1H).
30% at 0 - 85℃; for 4 h; Reflux DMF (68.4 g, 940.2 mmol) was added dropwise to a suspension of XLVI-1 (100 g, 854.7 mmol) in POCl3 (476 mL, 780 g, 1.71 mol) at 0° C. Then the mixture was stirred for 1 h at rt, then for 1 h at 85° C., after which the mixture was refluxed for 2 h. POCl3 was removed in vacuum and the mixture was poured onto water, then extracted with DCM. The organic layer was washed with brine, dried over Na2SO4, concentrated in vacuum. The residue was purified by column on silica gel (PE/EA=50/1) to afford XLVI-2 (47 g, yield: 30percent).

Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1992, # 8, p. 973 - 978
[2] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 1, p. 235 - 238
[3] Phosphorus, Sulfur and Silicon and the Related Elements, 2006, vol. 181, # 10, p. 2435 - 2444
[4] Patent: US2010/298334, 2010, A1, . Location in patent: Page/Page column 78
[5] Chemistry of Heterocyclic Compounds, 2010, vol. 46, # 3, p. 334 - 341
[6] Patent: US2009/270456, 2009, A1, . Location in patent: Page/Page column 8
[7] Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 18, p. 6012 - 6017
[8] Patent: WO2015/138895, 2015, A1, . Location in patent: Paragraph 000270
[9] Patent: US2014/200215, 2014, A1, . Location in patent: Paragraph 1306; 1307
[10] Arzneimittel-Forschung/Drug Research, 2009, vol. 59, # 12, p. 659 - 665
[11] Journal of Enzyme Inhibition and Medicinal Chemistry, 2012, vol. 27, # 3, p. 419 - 427
[12] Patent: WO2016/132134, 2016, A1, . Location in patent: Page/Page column 92; 93
[13] Indian Journal of Heterocyclic Chemistry, 2018, vol. 28, # 3, p. 335 - 344
  • 8
  • [ 2295-31-0 ]
  • [ 92972-48-0 ]
Reference: [1] Patent: US5679683, 1997, A,
[2] Patent: US4555577, 1985, A,
  • 9
  • [ 2295-31-0 ]
  • [ 10025-87-3 ]
  • [ 92972-48-0 ]
Reference: [1] Patent: US2003/45546, 2003, A1,
  • 10
  • [ 7647-01-0 ]
  • [ 39130-96-6 ]
  • [ 2295-31-0 ]
  • [ 563-41-7 ]
Reference: [1] Journal of the Chemical Society, 1928, p. 1421
  • 11
  • [ 294886-88-7 ]
  • [ 2295-31-0 ]
  • [ 6142-15-0 ]
Reference: [1] Arzneimittel-Forschung/Drug Research, 2000, vol. 50, # 6, p. 569 - 575
  • 12
  • [ 2295-31-0 ]
  • [ 68-12-2 ]
  • [ 139669-95-7 ]
YieldReaction ConditionsOperation in experiment
37%
Stage #1: With phosphorus(V) oxybromide In N,N-dimethyl-formamide at 0 - 105℃; for 8 h;
Stage #2: With sodium hydrogencarbonate In dichloromethane; water
Preparation of Intermediates for Example 26 and Related Analogs 2,4-Dibromo-thiazole-5-carbaldehyde
To a mixture of 2,4-thiazolidinedione (technical grade, 90percent; 19.1 g, 147 mmol) and POBr3 (210 g, 734 mmol) at 0° C. was added dropwise dimethylformamide (12.5 ml, 161.5 mmol).
The resulting solid was heated to 105° C. for 8 hrs.
The dark oil solidified upon cooling.
A large amount of ice was added to quench the excess POBr3.
The precipitate was filtered and the filtrate was extracted with 3*200 ml CH2Cl2.
The combined organics were washed with 50 ml saturated NaHCO3 and 100 ml brine, dried with MgSO4 and concentrated in vacuo to afford a brown solid.
The crude was purified by flash chromatography with 0 to 5percent ethyl acetate/Hexanes to afford 2,4-dibromo-thiazole-5-carbaldehyde (14.8 g, 37percent) as a yellow solid. 1H NMR (300 MHz, CDCl3) 9.89 (s, 1H).
8 g at 75 - 100℃; for 6 h; A mixture of thiazolidine-2,4-dione (15.0 g, 128 mmol), POBr3 (183.6 g, 640 mmol) andDMF(i0.8 ml,140.9 mmol) was heated to 75 °C for 1 h and then at 100 °C for 5 h. Thereaction mixture was cooled to room temperature, diluted with CH2C12 and washed with saturated NaHCO3 solution, filtered and concentrated. Trituration of the evaporation residue with petroleum ether afforded 8.0 g of 2,4-dibromothiazole-5 -carbaldehyde 8.0 g as black solid.
Reference: [1] Synthetic Communications, 1995, vol. 25, # 17, p. 2639 - 2645
[2] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 1, p. 49 - 54
[3] Patent: US2007/203210, 2007, A1, . Location in patent: Page/Page column 42
[4] Patent: WO2016/193551, 2016, A1, . Location in patent: Page/Page column 31
  • 13
  • [ 2295-31-0 ]
  • [ 139669-95-7 ]
Reference: [1] Patent: US2006/166906, 2006, A1, . Location in patent: Page/Page column 26
  • 14
  • [ 2295-31-0 ]
  • [ 21295-51-2 ]
  • [ 68-12-2 ]
  • [ 139669-95-7 ]
Reference: [1] Patent: US2003/153752, 2003, A1,
  • 15
  • [ 2295-31-0 ]
  • [ 104146-17-0 ]
Reference: [1] Patent: US4839350, 1989, A,
  • 16
  • [ 2295-31-0 ]
  • [ 104146-17-0 ]
Reference: [1] Patent: US4839350, 1989, A,
  • 17
  • [ 2295-31-0 ]
  • [ 122321-03-3 ]
  • [ 122320-73-4 ]
YieldReaction ConditionsOperation in experiment
58%
Stage #1: With pyrrolidine; acetic acid In toluene at 110℃; for 2 h;
Stage #2: With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate In toluene for 13 h; Heating / reflux
A mixture of 20.0 g (78 mmol) of 4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy] benzaldehyde (IV), 9.6 g (82 mmol) of thiazolidine-2,4-dione (V), 0.3 mL (3.9 mmol) of pyrrolidine, 0.2 mL (3.9 mmol) of glacial acetic acid and 120 mL of toluene is stirred under nitrogen atmosphere at reflux temperature with azeotropic distillation of water for two hours. After cooling to room temperature, 39.5 g (156 mmol) of 3,5-dicarbethoxy-2,6-dimethyl-1,4- dihydropyridine (Hantzsch ethyl ester), 13.9 g of silica gel and 46 mL of toluene are added. The resulting suspension is heated to reflux temperature with azeotropic distillation of water for 13 hours. The reaction is cooled to room temperature, and the resulting solid is filtered. Silica gel is removed after digestion with tetrahydrofuran and filtration of the solid. The solvent is removed by distillation delivering a crude material that is purified by crystallization from n-butyl acetate, yielding 16.3 g (58percent) of Rosiglitazone (I).
Reference: [1] Patent: WO2005/108394, 2005, A1, . Location in patent: Page/Page column 10 - 11
  • 18
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  • [ 122320-73-4 ]
Reference: [1] Patent: WO2005/105794, 2005, A1, . Location in patent: Page/Page column 16
[2] Patent: WO2005/105794, 2005, A1, . Location in patent: Page/Page column 16
  • 19
  • [ 2295-31-0 ]
  • [ 372-48-5 ]
  • [ 123-08-0 ]
  • [ 147687-15-8 ]
  • [ 122320-73-4 ]
Reference: [1] Journal of Organic Chemistry, 1999, vol. 64, # 5, p. 1723 - 1726
  • 20
  • [ 2295-31-0 ]
  • [ 454-89-7 ]
  • [ 438190-29-5 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 4, p. 1077 - 1084
[2] Journal of Medicinal Chemistry, 2009, vol. 52, # 1, p. 74 - 86
  • 21
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  • [ 1265965-22-7 ]
Reference: [1] Patent: US2011/34460, 2011, A1, . Location in patent: Page/Page column 8
  • 22
  • [ 2295-31-0 ]
  • [ 1055361-66-4 ]
  • [ 1055361-35-7 ]
Reference: [1] Journal of Medicinal Chemistry, 2011, vol. 54, # 3, p. 788 - 808
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