* 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.
Reference：
[1] Chemical and Pharmaceutical Bulletin, 1998, vol. 46, # 4, p. 581 - 586
2
[ 104-01-8 ]
[ 531-95-3 ]
Reference：
[1] Organic Letters, 2006, vol. 8, # 24, p. 5441 - 5443
[2] Tetrahedron, 2012, vol. 68, # 26, p. 5172 - 5178
[3] Journal of the American Chemical Society, 2012, vol. 134, # 44, p. 18245 - 18248
[4] Tetrahedron, 2018, vol. 74, # 16, p. 2020 - 2029
3
[ 104-01-8 ]
[ 491-80-5 ]
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 2000, vol. 4, p. 567 - 570
[2] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 9, p. 2962 - 2970
4
[ 104-01-8 ]
[ 108-73-6 ]
[ 491-80-5 ]
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1991, # 12, p. 3005 - 3008
5
[ 104-01-8 ]
[ 13435-12-6 ]
[ 7087-68-5 ]
Reference：
[1] Patent: US2003/18193, 2003, A1,
6
[ 104-01-8 ]
[ 4693-91-8 ]
Yield
Reaction Conditions
Operation in experiment
100%
With thionyl chloride In benzene for 1 h; Heating / reflux
16.62g (0.1 mol) of 4-methoxyphenylacetic acid was dissolved in 10ml of benzene before 29ml (0. 2 mol) of thionylchloride was added thereto. Then, the solution was heated and refluxed, and was stirred for one hour. Thionylchloride remaining in the reaction solution and the solvent was condensed to be removed to obtain 4-methoxy-phenyl-acetyl chloride (compound I), a liquid phase product, at a quantitative yield. The product was used without purification.
100%
for 2 h; Reflux
General procedure: A mixture of various carboxylic acids (1.0mmol), an excess of thionyl chrolide (5mL) was refluxed for 2h and concentrated in vacuo to give corresponding acyl chloride (quant).
88%
With thionyl chloride In <i>N</i>-methyl-acetamide; water
(i) 4-Methoxyphenylacetyl chloride Thionyl chloride (200 ml) was added to 4-methoxyphenylacetic acid (78 g, 0.47 mole) followed by one drop of dimethylformamide. The reaction was heated at 65° C. for 4 hours and the solvent was removed under vacuum. The residue was distilled in vacuo (water aspirator) at 135° C. to give the product as a red oil (75.9 g, 88percent).
Reference：
[1] European Journal of Medicinal Chemistry, 2005, vol. 40, # 8, p. 764 - 771
[2] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 22, p. 6160 - 6163
[3] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 10, p. 2899 - 2903
[4] Patent: WO2005/92896, 2005, A1, . Location in patent: Page/Page column 27
[5] Chinese Chemical Letters, 2013, vol. 24, # 8, p. 673 - 676
[6] Synthetic Communications, 1991, vol. 21, # 6, p. 819 - 826
[7] Journal of Organic Chemistry, 1986, vol. 51, # 6, p. 902 - 921
[8] Journal of Organic Chemistry, 1992, vol. 57, # 12, p. 3278 - 3286
[9] Journal of Organic Chemistry, 1984, vol. 49, # 21, p. 3881 - 3887
[10] Patent: US4798843, 1989, A,
[11] Journal of Organic Chemistry, 1981, vol. 46, # 8, p. 1557 - 1564
[12] Monatshefte fuer Chemie, 1980, vol. 111, p. 81 - 92
[13] Organic Letters, 2009, vol. 11, # 12, p. 2659 - 2662
[14] Annales de Chimie (Cachan, France), 1940, vol. <11> 14, p. 5,54
[15] Journal of the American Chemical Society, 1946, vol. 68, p. 2592,2599
[16] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1982, # 10, p. 2407 - 2412
[17] Scientia Pharmaceutica, 2001, vol. 69, # 4, p. 329 - 350
[18] J. r., 1930, vol. <2> 126, p. 24,43
[19] Journal of the Chemical Society, 1913, vol. 103, p. 1038
[20] Journal of Medicinal Chemistry, 1990, vol. 33, # 5, p. 1496 - 1504
[21] Journal of Organic Chemistry, 1990, vol. 55, # 11, p. 3565 - 3568
[22] Journal of the American Chemical Society, 2003, vol. 125, # 23, p. 6856 - 6857
[23] Journal of Medicinal Chemistry, 2004, vol. 47, # 6, p. 1434 - 1447
[24] Archiv der Pharmazie, 1991, vol. 324, # 5, p. 283 - 286
[25] Tetrahedron, 1987, vol. 43, # 18, p. 4235 - 4239
[26] Tetrahedron Letters, 1989, vol. 30, # 13, p. 1605 - 1608
[27] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1980, p. 1176 - 1184
[28] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1985, vol. 24, p. 83 - 97
[29] Journal of Medicinal Chemistry, 1986, vol. 29, # 12, p. 2465 - 2472
[30] Journal of Medicinal Chemistry, 1985, vol. 28, # 8, p. 1106 - 1109
[31] Heterocycles, 2002, vol. 57, # 1, p. 39 - 46
[32] Journal of the American Chemical Society, 2006, vol. 128, # 21, p. 6938 - 6946
[33] Journal of Medicinal Chemistry, 1992, vol. 35, # 21, p. 3745 - 3754
[34] Indian Journal of Chemistry - Section B Organic Chemistry Including Medicinal Chemistry, 1990, vol. 29, # 11, p. 1034 - 1040
[35] Journal of Medicinal Chemistry, 1994, vol. 37, # 11, p. 1704 - 1711
[36] Journal of Medicinal Chemistry, 1995, vol. 38, # 10, p. 1600 - 1607
[37] Journal of Organic Chemistry, 1996, vol. 61, # 1, p. 55 - 62
[38] Organic and Biomolecular Chemistry, 2005, vol. 3, # 11, p. 2129 - 2139
[39] Journal of Heterocyclic Chemistry, 1995, vol. 32, # 6, p. 1767 - 1773
[40] Journal of Medicinal Chemistry, 1996, vol. 39, # 7, p. 1509 - 1513
[41] Journal of Mass Spectrometry, 1996, vol. 31, # 7, p. 761 - 766
[42] Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 8, p. 2779 - 2793
[43] Monatshefte fur Chemie, 2003, vol. 134, # 3, p. 403 - 409
[44] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 5, p. 821 - 823
[45] Synthesis, 2005, # 15, p. 2521 - 2526
[46] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2006, vol. 45, # 4, p. 1080 - 1085
[47] Journal of Medicinal Chemistry, 2006, vol. 49, # 12, p. 3563 - 3580
[48] Organic Letters, 2006, vol. 8, # 24, p. 5441 - 5443
[49] Journal of Medicinal Chemistry, 2000, vol. 43, # 4, p. 721 - 735
[50] Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 11, p. 3703 - 3710
[51] Patent: EP954520, 2002, B1,
[52] Patent: WO2008/92873, 2008, A1, . Location in patent: Page/Page column 30
[53] Patent: US6348468, 2002, B1, . Location in patent: Page column 16
[54] Bulletin of the Chemical Society of Japan, 2009, vol. 82, # 2, p. 254 - 260
[55] Patent: EP1221441, 2002, A2, . Location in patent: Page 54
[56] Organic and Biomolecular Chemistry, 2009, vol. 7, # 17, p. 3561 - 3571
[57] Journal of Medicinal Chemistry, 2009, vol. 52, # 10, p. 3366 - 3376
[58] Journal of Organic Chemistry, 2010, vol. 75, # 1, p. 16 - 29
[59] Tetrahedron Letters, 2010, vol. 51, # 21, p. 2888 - 2891
[60] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 2, p. 734 - 737
[61] Tetrahedron, 2010, vol. 66, # 26, p. 4882 - 4887
[62] Chemical Communications, 2010, vol. 46, # 21, p. 3666 - 3668
[63] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 23, p. 7089 - 7093
[64] European Journal of Pharmaceutical Sciences, 2011, vol. 42, # 1-2, p. 37 - 44
[65] Comptes Rendus Chimie, 2011, vol. 14, # 12, p. 1071 - 1079
[66] Organic and Biomolecular Chemistry, 2012, vol. 10, # 8, p. 1598 - 1601
[67] Organic Letters, 2012, vol. 14, # 8, p. 2154 - 2157
[68] Medicinal Chemistry Research, 2012, vol. 21, # 11, p. 3818 - 3825
[69] Journal of Medicinal Chemistry, 2013, vol. 56, # 1, p. 254 - 263
[70] Journal of the American Chemical Society, 2012, vol. 134, # 44, p. 18245 - 18248
[71] Chemical Communications, 2013, vol. 49, # 16, p. 1654 - 1656
[72] Journal of the American Chemical Society, 2013, vol. 135, # 19, p. 7304 - 7311
[73] European Journal of Organic Chemistry, 2013, # 16, p. 3271 - 3277
[74] Journal of Medicinal Chemistry, 2013, vol. 56, # 13, p. 5351 - 5381
[75] Chemistry - A European Journal, 2013, vol. 19, # 46, p. 15565 - 15571
[76] Organic and Biomolecular Chemistry, 2013, vol. 11, # 48, p. 8375 - 8386
[77] Journal of Medicinal Chemistry, 2014, vol. 57, # 6, p. 2755 - 2772
[78] Journal of Medicinal Chemistry, 2014, vol. 57, # 15, p. 6479 - 6494
[79] Tetrahedron Letters, 2015, vol. 56, # 12, p. 1575 - 1580
[80] Medicinal Chemistry, 2014, vol. 10, # 8, p. 810 - 823
[81] Letters in Drug Design and Discovery, 2015, vol. 12, # 3, p. 190 - 205
[82] Chemistry - An Asian Journal, 2015, vol. 10, # 4, p. 925 - 937
[83] RSC Advances, 2015, vol. 5, # 88, p. 72373 - 72386
[84] Patent: EP2949651, 2015, A1, . Location in patent: Paragraph 0087
[85] Angewandte Chemie - International Edition, 2015, vol. 54, # 50, p. 15051 - 15054[86] Angew. Chem., 2015, vol. 54-127, # 50, p. 15265 - 15268,4
[87] Molecules, 2016, vol. 21, # 3,
[88] Organic and Biomolecular Chemistry, 2016, vol. 14, # 24, p. 5477 - 5480
[89] MedChemComm, 2016, vol. 7, # 9, p. 1858 - 1869
[90] Journal of Molecular Structure, 2017, vol. 1138, p. 177 - 191
[91] European Journal of Organic Chemistry, 2017, vol. 2017, # 20, p. 2866 - 2870
[92] Tetrahedron Letters, 2017, vol. 58, # 29, p. 2835 - 2837
[93] Patent: CN106467499, 2017, A, . Location in patent: Paragraph 0022; 0025; 0026
[94] Patent: KR2017/4492, 2017, A, . Location in patent: Paragraph 0106; 0107
[95] Journal of Organic Chemistry, 2017, vol. 82, # 14, p. 7332 - 7345
[96] Molecules, 2017, vol. 22, # 5,
[97] Chemical Communications, 2017, vol. 53, # 78, p. 10812 - 10815
[98] Organic Letters, 2017, vol. 19, # 19, p. 5216 - 5219
[99] Journal of Medicinal Chemistry, 2017, vol. 60, # 23, p. 9769 - 9789
[100] Journal of the American Chemical Society, 2018, vol. 140, # 5, p. 1952 - 1955
[101] Advanced Synthesis and Catalysis, 2018, vol. 360, # 5, p. 965 - 971
[102] Tetrahedron, 2018, vol. 74, # 16, p. 2020 - 2029
[103] Angewandte Chemie - International Edition, 2018, vol. 57, # 30, p. 9425 - 9429[104] Angew. Chem., 2018, vol. 130, # 30, p. 9569 - 9573,5
[105] Tetrahedron Letters, 2018, vol. 59, # 30, p. 2913 - 2916
[106] Fitoterapia, 2018, vol. 129, p. 257 - 266
[107] Angewandte Chemie - International Edition, 2018, vol. 57, # 38, p. 12347 - 12351[108] Angew. Chem., 2018, vol. 130, # 38, p. 12527 - 12531,5
[109] Pharmaceutical Chemistry Journal, 2018, vol. 52, # 5, p. 424 - 437
[110] Patent: WO2007/102679, 2007, A1, . Location in patent: Page/Page column 68
Stage #1: With thionyl chloride In dichloromethane at 0 - 20℃; Stage #2: With ammonia In dichloromethane; water
Example 6N-(4-(4-Fluoro-2-methoxyphenyl)pyridin-2-yl)-2-(4-methoxyphenyl)-acetamidePreparation of the starting material 2-(4-Methoxyphenyl)acetamide. A solution of 2-(4-methoxyphenyl)acetic acid (500 mg, 3.00 mmol) in DCM (30 ml) was added thionyl chloride (0.4 ml, 4.5 mmol) at 0° C. The reaction mixture was allowed to warm up to room temperature and continued to stirred overnight. Then aqueous ammonia (2 ml) was added to the reaction mixture. The white solid forming was filtered and dried under vacuum to obtained 350 mg (70percent) of 2-(4-methoxyphenyl)acetamide as a white solid.
Reference：
[1] Patent: US2011/224225, 2011, A1, . Location in patent: Page/Page column 21
[2] Phytochemistry, 2008, vol. 69, # 17, p. 2937 - 2949
[3] Molecules, 2016, vol. 21, # 3,
[4] New Journal of Chemistry, 2016, vol. 40, # 7, p. 6109 - 6119
13
[ 104-01-8 ]
[ 77287-34-4 ]
[ 6343-93-7 ]
Reference：
[1] Yakugaku Zasshi, 1942, vol. 62, p. 532; engl. Ref. S. 169[2] Chem.Abstr., 1951, p. 2861
(5S,8R,13R,15aS)-8-[(S)-2-Amino-3-(4-methoxy-phenyl)-3-oxo-propionylamino]-5-hydroxymethyl-4,7,15-trioxo-tetradecahydro-10,11-dithia-3a,6,14-triaza-cyclopentacyclotetradecene-13-carboxylic acid[ No CAS ]
Example 6N-(4-(4-Fluoro-2-methoxyphenyl)pyridin-2-yl)-2-(4-methoxyphenyl)-acetamidePreparation of the starting material 2-(4-Methoxyphenyl)acetamide. A solution of 2-(4-methoxyphenyl)acetic acid (500 mg, 3.00 mmol) in DCM (30 ml) was added thionyl chloride (0.4 ml, 4.5 mmol) at 0° C. The reaction mixture was allowed to warm up to room temperature and continued to stirred overnight. Then aqueous ammonia (2 ml) was added to the reaction mixture. The white solid forming was filtered and dried under vacuum to obtained 350 mg (70percent) of 2-(4-methoxyphenyl)acetamide as a white solid.
With triethylamine; dicyclohexyl-carbodiimide; In acetonitrile; at 20℃;
To a solution of [4-(methyloxy)phenyl]acetic acid (2.156 g, 12.97 mmol), ethyl 3- amino-1 H-pyrrole-2-carboxylate (2 g, 12.97 mmol) and triethylamine (1.989 mL, 14.27 mmol) in acetonitrile (60 mL) at RT was added drop-wise a solution of DCC (4.28 g, 20.76 mmol) in acetonitrile (20 mL). The reaction mixture was stirred for 2h before being filtered. The filtrate was concentrated under reduced pressure and extracted with EtOAc/ water then washed successively with sat. NaHC03 and brine. The organic layer was dried over Na2S04 and evaporated. The crude solid was dissolved in DCM and precipitated with cyclohexane, filtered and dried to give the desired product ethyl 3-([4-(methyloxy)phenyl]acetyl}amino)-1 H-pyrrole-2- carboxylate (1.5 g, 4.96 mmol, 38.2 % yield) as a cream powder. LCMS: (M+H)+ : 303; Rt: 2.83 min.
With potassium carbonate; In acetonitrile; at 80℃;
General procedure: To the flame dried K2CO3 (14.5 g, 0.104 mol), were added 2-chloro-1-(2,4-difluorophenyl)ethanone (5.0 g, 0.026 mol) and 3,4-dichloro phenyl acetic acid (5.38 g, 0.026 mol) in acetonitrile (100 ml) at room temperature and the reaction mixture was refluxed for 4 h. It was then cooled to room temperature, diluted with water, extracted with ethyl acetate, dried over Na2SO4, concentrated and purified by column chromatography using pet ether-ethyl acetate (90:10) as eluent to give pure compound 3-(3,4-dichlorophenyl)-4-(2,4-difluorophenyl) furan-2(5H)-one (18b); Yield: 81%; Nature: Yellow solid; M. p. 127 0C; IR (Chloroform): nu max 1145, 1164, 1272, 1361, 1429, 1472, 1593, 1611, 1648, 1754, 2934, 3021, 3082, 3105 cm-1. 1H NMR (200 MHz, CDCl3): delta 5.18 (s, 2H), 6.84-6.98 (m, 2H), 7.15-7.26 (m, 2H), 7.41 (d, J=8 Hz, 1H), 7.55 (d, J=2 Hz, 1H). 13C NMR (200 MHz, CDCl3): delta 71.0 (d), 105.2 (t), 112.5 (d), 114.5(d), 125.7, 128.0, 129.5, 130.5 (2C), 130.9 (d), 132.7, 133.1, 152.3, 159.5 (dd), 164.6 (dd), 171.6. MS (ESI) m/z: 362.94 (M + Na).
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 12h;
General procedure: To a round-bottom flask (500 mL) that contained a solution of aryl sulfonamide (6 mmol), 4-dimethyaminopyridine (DMAP, 13 mmol), and 1-[3-(dimethyamino)-propyl]-3-ethylcarbodiimide hydrochloride (EDCI, 13 mmol) in CH2Cl2 (150 mL) was added the synthesized phenylacetic acid (6 mmol) at room temperature. The resulting mixture was stirred at room temperature for 12 h, then cooled to 5 C, and acidified to pH 1 with addition of HCl aqueous solution (10%), which was followed by extraction with CH2Cl2/MeOH (9:1, 3 × 100 mL). The combined organic layers were washed with H2O and brine, dried over Na2SO4, and concentrated in vacuo. The residue was subjected to silica gel chromatography or crystallization if necessary to afford the compounds (20-44) (Scheme 2).
With sodium sulfate; In methanol; at 50℃; for 24h;
General procedure: To a solution of substituted indole-3-carbaldehyde 1 (1.5 mmol) in methanol (5 mL) were addedsuccessively Na2SO4 (0.3 g), propargylamine 2 (1.1 equiv), acid 3 (1.1 equiv) and isonitrile 4(1.1 equiv) in a 25 mL RBF equipped with a magnetic stir bar. The reaction mixture was stirredat 50 C for 24 h. After completion of the reaction, the mixture was diluted with EtOAc (100 mL) and was extracted with water (50 mL). The organic layer was washed with brine(50 mL), dried over magnesium sulfate and evaporated under reduced pressure to obtain residuewhich was subjected to silica gel column chromatography (80% EtOAc in heptane) to afford thedesired product 5a-q as solid.
2-(4-methoxyphenyl)-3-(4-((E)-3-methoxy-3-oxoprop-1-en-1-yl)phenyl)acrylic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With N-ethyl-N,N-diisopropylamine; In acetic anhydride; at 30℃; for 2h;
General procedure: General procedure A Step-a: Synthesis of 2-(4-fluorophenyl)-3-(4-((E)-3-methoxy-3-oxoprop-1-en-1-yl) phenyl) acrylic acid (C). A mixture of 4-fluorophenylacetic acid (2.5 g, 13.2 mmol) and methyl (E)-3-(4-formylphenyl)acrylate (2.03 g, 13.2 mmol) were dissolved under stirring with acetic anhydride (8 ml). To this mixture diisopropylethylamine (DIPEA) (3.4 ml, 19.7 mmol) was added and stirred at 30 C for 2 h. Upon completion (as monitored by TLC using 100% ethyl acetate as eluent), the reaction mixture was poured into water and the pH was adjusted to 1 using dil. HClaq (1:1). The aqueous layer was extracted with ethyl acetate (2 * 150 ml). The combined ethyl acetate layer was washed with water till the washings were neutral and dried over anhydrous Na2SO4. The ethyl acetate layer was evaporated to dryness to obtain a sticky compound, which was triturated with cold dichloromethane (DCM) to furnish a white solid. It was filtered and dried under vacuum to afford the title compound (2 g, 47%).
N,4-Dimethoxy-N-methylbenzamide (12s, Q= OCH3). To a suspension of 4- methoxyphenylacetic acid (1.02 g, 6.6 mmol) in DCM (21 ml) oxalyl chloride (1,2 ml, 13.8 mmol, 2.1 eq.) was added at 0C. After 3.5 h at 0C a slightly yellow solution was formed. The solution was added dropwise during 1 h to a suspension of N,O-dimethylhydroxylamine hydrochloride (1.09 g, 11 mmol) and triethylamine (9.6 ml, 6.91 g, 68 mmol, 10 eq.) in DCM(17 ml) at 0C. After 4 h when the temperature had reached it water (25 ml) was added to the reaction mixture. The organic phase was separated, washed with aq. sat. NaHCO3 (2x25 ml), aq. sat. NaC1 (20 ml), dried over Na2SO4 and concentrated at reduced pressure to afford a slightly yellow oil (0.83 g, 64%). The crude product was purified by silica gel flash chromatography (hept/EtOAc 3:1 to 0:1) to afford a colourless oil 12s (0.71 g, 55%).
With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 0 - 23℃;Inert atmosphere;
General procedure: To a flame-dried round-bottom flask with a magnetic stir bar were added the aryl acetic acid (12.0 mmol, 1.00 equiv) and dry dichloromethane (13 mL). The solution was stirred under nitrogen while DMAP (approx. 50 mg) and the alcohol (12.0 mmol, 1.00 equiv) were added. The solution was cooled to 0 C using an ice water bath and DCC (2.72 g, 13.2 mmol, 1.10 equiv) was added. The mixture was allowed to stir for five minutes at 0 C, and then the ice water bath was removed and the mixture was allowed to warm to 23C. Upon completion (as determined by TLC analysis), the heterogeneous mixture was filtered through Celite, rinsing with dichloromethane (20 mL). The filtrate was concentrated, suspended in dichloromethane, and filtered through Celite, washing with dichloromethane (20 mL). The filtrate was washed with 0.5 M aqueous hydrochloric acid (2 x 50 mL) and saturated aqueous sodium bicarbonate (1 x 50 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by silica gel column chromatography using a mixture of hexanes and ethyl acetate as eluent. To a flame-dried round-bottom flask with a magnetic stir bar were added the aryl acetic acid ester (10.0 mmol, 1.00 equiv), p-ABSA (2.88 g, 12.0 mmol, 1.20 equiv), and dry acetonitrile (35 mL). The solution was stirred under nitrogen and cooled to 0 C using an ice water bath. DBU (1.65 mL, 11.0 mmol, 1.10 equiv) was added by syringe rapidly in one portion, and the reaction mixture was allowed to warm to 23 C and stir overnight. Upon completion (as determined by TLC analysis) or after 24 hours, whichever came first, the reaction mixture was quenched with saturated aqueous ammonium chloride (50 mL) and extracted with ether (3 x 50 mL). The combined organic layers were washed with brine (1 x 100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by silica gel column chromatography using a mixture of hexanes and ethyl acetate as eluent. The aryl diazoacetates were obtained in 12-50% yield over two steps.
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃;Inert atmosphere;
General procedure: An oven-dried 50 mL round-bottom flask containing a magnetic stirrer bar was sealed with a septum, charged with Ar and tared on a balance. KH (~0.5 g, 30% mineral oil dispersion) was then added to the flask and the mineral oil removed by trituration under Ar with pet. spirit (2 x 30 mL) using a syringe. The flask containing dry KH was purged with Ar and reweighed to obtain an accurate mass of KH. Dry THF (10 mL) was added to the flask containing KH (0.15 g, 3.7 mmol, under Ar) and the mixture cooled to 0 oC. 3,5-Dimethyl-1H-pyrrole-2-carbaldehyde 5 (0.23 g, 1.9 mmol) was dissolved in dry THF (5 mL) under Ar and added dropwise to the stirring KH solution (Caution - flask requires outlet needle to release evolving H2 gas). After complete addition the mixture was stirred for a further 5 minutes at 0 oC. The phenylacetic acid derivative (1.9 mmoles) was added to a separate dry 50 mL round-bottom flask under Ar along with HBTU (0.71 g, 1.9 mmoles) and dry CH2Cl2 (10 mL). DIPEA (0.65 mL, 3.7 mmoles) was added dropwise to the stirring solution and upon complete addition the mixture was stirred for a further 5 minutes or until the HBTU was completely dissolved. The HBTU solution was then cooled to 0 oC and added in a single portion to the K+ pyrrolate salt solution at 0 oC and the combined mixture allowed to warm slowly to room temperature. A dark red colour observed in each reaction indicated formation of the desired 5,7-dimethyl-2-aryl-3H-pyrrolizin-3-one. The reaction was quenched after ~ 2 h with ice-cold water (100 mL) and extracted with Et2O (2 x 50 mL). The combined organic phase was washed with 1 M HCl (2 x 50 mL), saturated NaHCO3 (2 x 50 mL) and brine (2 x 50 mL), dried over anhydrous MgSO4 and concentrated. The crude residue was purified by silica gel column chromatography using a gradient from 100% pet. spirit to 1:9 acetone:pet. spirit to afford the 5,7-dimethyl-2-aryl-3H-pyrrolizin-3-one as a deep red solid.
2-(4-methoxybenzyl)-1H-benzo[d]imidazol-4-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With hydrogenchloride; In water; for 16h;Reflux;
General procedure: To a solution of the corresponding substituted alkyloxybenzene-1,2-diamine 4 (2.26 mmol) in 6N HCl (10 mL), corresponding acid 5 (6.80 mmol) was added. The resulting solution was refluxed for 16 h. The reaction mixture was cooled to 0 °C, diluted with EtOAc, and then pH was adjusted to ~ 7 by using solid NaHCO3, extracted with EtOAc. The combined organic extracts were washed with brine solution, dried over anhydrous Na2SO4 and then concentrated under reduced pressure. The crude mixture was subjected to flash silica gel (230?400 mesh) column chromatography to afford the title compounds 6a?f and 6h?s.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
Life Science
For Research Only
88K+ Compounds
Competitive Price
1-2 Day Shipping
