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USD 15-60
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USD 80+
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Structure of 536-38-9 * Storage: {[proInfo.prStorage]}
* 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.
General procedure: A mixture of thiourea (1.2 mmol) and 2-bromoacetophenone (1 mmol) in EtOH (2 mL) was stirred at 70 oC for 1h. The reaction mixture was cooled to room temperature, poured into ice-cold water, and the resulting precipitate was filtered and dried to give the desired compounds: [6a ( 99percent) as a white solid, mp 150-152 oC (Lit.26 149-150 oC) ; 6b (100percent) as a white solid, mp 162-165 oC (Lit.26 163-164 oC); 6c (0.236 g, 93percent) as a white solid, mp 179-181 oC (Lit.26 180-181 oC); 6d (98percent) as a white solid, mp 203.6-204.2 oC (Lit.28/22 204.0-204.5 oC); 6e (94percent) as a bright yellow solid, mp 287-288 oC (Lit.26,27 285-286 oC); 6f (100percent) as a white solid, mp 172-174 oC (Lit.29-31 172 oC).
99%
With sodium fluoride In methanol; water at 20℃; for 0.0166667 h;
General procedure: The appropriate phenacylbromide or 3-(2-bromoacetyl)-2H-chromen-2-one (1mmol) and either thiourea, phenylthiourea or selenourea (1mmol) were dissolved in 2mL of methanol, water (2mL) containing 0.02g of NaF added and the mixture stirred at room temperature for the appropriate time. After completion of the reaction, 10mL of water was added and the solid that separated out was filtered off and washed with water, affording analytically pure substituted 1,3-thiazoles or 1,3-selenazole derivatives in excellent yields.
99%
at 25℃; for 0.00555556 h; Sonication; Green chemistry
General procedure: A 100-mL borosil test-tube was charged with phenacyl bromide (1a–h)/3(2-bromoacetyl)coumarin (1i–n) (1 mmol), thiourea (2a)/phenylthiourea (2b)/selenourea(2c) (1 mmol) and water (1 mL). The tube was kept in such a way that thesurface of the reactants is just lower than the water level of the ultrasonic bath inwhich they were sonicated with a frequency of 50 kHz at 25 C for about 10–60 s.The progress of the reaction was monitored by TLC. After completion of thereaction, the solid separated out was filtered and washed with water. Analyticallypure products were obtained without further recrystallization.
98%
for 12 h; Inert atmosphere; Reflux
A mixture of thiourea (1.0 eq.), the α-haloketone (1.2 eq.) and dry ethanol (1 mL per 100 mg ofthiourea) was heated at reflux until the disappearance of the thiourea (12 h, checked by TLC, SiO2,petroleum ether:EtOAc 70:30). After that, the mixture was cooled at room temperature, and theprecipitated was filtered off and washed with ethanol:water (80:20). The solid was recrystallizedfrom ethanol or ethanol:water. Yield: 98percent; white solid, m.p. 167–168 °C; 1H NMR (400 MHz, CDCl3)δ: 7.74–7.70 (m, 2H), 7.38–7.33 (m, 2H), 6.73 (s, 1H), 5.07 (bs, 2H); 13C NMR (100 MHz, CDCl3) δ:167.3, 150.2, 133.4, 133.1, 128.8, 127.3, 103.3. MS (EI) m/z (abundance, percent): 211.01 (M+, 100). Anal. calc.for C9H9ClN2S: C, 51.06percent; H, 3.81percent; Cl, 16.75percent; N, 13.23percent; S, 15.15percent; found: C, 51.0percent; H, 3.8percent; Cl,16.8percent; N, 13.2percent; S,
96%
at 45℃; for 0.366667 h; Sonication
General procedure: α-Bromoarylethanones (deliquescent) were prepared accordingto the reported method [18]. The ethanolic mixture of α-bromoarylethanone (1a, 1 mmol) and thiourea in the boiling tube was ultrasonicated at 45 °C in an ultrasonic bath. The reaction was monitored by TLC at every 5 min. It was found that the heterocyclization was completed within 20 min. The same procedure was followed for the synthesis of 2-amino-4-substituted phenyl-1,3-thiazoles listed in Table 1
91%
at 100℃; for 0.25 h; Sealed tube; Microwave irradiation; Inert atmosphere
General procedure: 4.5. Microwave-assisted synthesis of substituted 4-phenylthiazol-2-amines (15e18) via Hantzsch condensationIn a sealed tube, a stirred solution of thiourea (10.91 mmol) andthe appropriate a-bromoacetophenone (10.91 mmol) in ethanol(15 mL) was irradiated (800 W) at 100 C for 15 min. The solventwas evaporated to dryness. The solid residue was neutralized witha saturated solution of sodium bicarbonate and extracted threetimes with methylene chloride. The organic layer was dried overmagnesium sulfate and the solvent was evaporated to dryness. Thesolid residuewas agitated for 30 min in cyclohexane and filtered offto afford the 4-phenylthiazol-2-amine in analytically pure form.
90%
at 50℃; for 0.0833333 h; Microwave irradiation
Method xxi\-Step 1: A mixture of 2-bromo-l-(4-chlorophenyl)ethanone (1 g, 4.28 mmol) and thiourea (0.326 g, 4.28 mmol) were placed in a MW test tube containing a magnetic stirring bar, rubber cap, and EtOH (Volume: 15 ml). The test tube was placed in the microwave cavity and subjected to MW irradiation at 50 oC (100 W) for 5 min. After completion of the reaction, the tube was removed, cooled to room temperature, and the contents added to water (10 mL). The product was extracted into methylene chloride (15 mL), which was filtered though a short silica column to afford the 2-aminothiazole (90percent yield); LCMS: m/z (M+H)+= 211.0
78.7%
Microwave irradiation
General procedure: Substituted phenacylbromide (0.01 mol) and thiourea (0.76 g, 0.01 mol) were takenin a reaction vessel and added water (10 mL). The reactionmixture was irradiated under micro wave (40 W) for 10-15min. The solid separated was filtered, washed with water andrecrystallized from absolute alcohol [17,23].Compound 2a (R = Cl): White solid; Yield 78.70 percent; m.p.188 °C; R f 0.80; λ max 238 nm; IR (KBr, ν max , cm -1 ): 3360.20(1 NH 2 , str.), 3063.22 (Ar-CH, str), 1686.10 (Ar C=C), 1602.45(NH 2 bend), 1534.30 (CN str.), 770.60 (C-S), 687.10 (C-Cl).
77%
With iodine In N,N-dimethyl-formamide at 100℃;
General procedure: Different substituded acetophenone (10a–10c, 10e–10h) (10 mmol), iodine (1.0 equiv.) and thiourea(2.0 equiv.) were dissolved in DMF, then the mixture heated at 100 oC overnight with stirring. WhenTLC indicated that the reaction was complete, the mixture was cooled and diethyl ether added toremove un-reacted iodine and corresponding acetophenone. The solid residue was then put in distilledwater and treated with saturated sodium sulfite solution and the solid that separated was filtered,washed and dried under reduced pressure to afford product 12a–12g. 5
Reference：
[1] Arkivoc, 2018, vol. 2018, # 7, p. 110 - 118
[2] Chinese Chemical Letters, 2014, vol. 25, # 1, p. 172 - 175
[3] Research on Chemical Intermediates, 2015, vol. 41, # 11, p. 8099 - 8109
[4] Molecules, 2017, vol. 22, # 5,
[5] Synthetic Communications, 2009, vol. 39, # 16, p. 2895 - 2906
[6] Journal of Fluorescence, 2015, vol. 25, # 6, p. 1727 - 1738
[7] Tetrahedron, 2007, vol. 63, # 45, p. 11066 - 11069
[8] Heterocycles, 2010, vol. 81, # 12, p. 2849 - 2854
[9] Synthetic Communications, 2011, vol. 41, # 4, p. 579 - 582
[10] Tetrahedron Letters, 2005, vol. 46, # 35, p. 5953 - 5955
[11] Synthetic Communications, 2009, vol. 39, # 13, p. 2317 - 2320
[12] Tetrahedron, 2015, vol. 70, # 35, p. 5532 - 5540
[13] RSC Advances, 2016, vol. 6, # 54, p. 49164 - 49172
[14] Patent: WO2016/106331, 2016, A1, . Location in patent: Paragraph 0245
[15] Asian Journal of Chemistry, 2017, vol. 29, # 12, p. 2639 - 2642
[16] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 17, p. 2861 - 2864
[17] Journal of the Indian Chemical Society, 2008, vol. 85, # 6, p. 660 - 664
[18] Indian Journal of Chemistry - Section B Organic Chemistry Including Medicinal Chemistry, 1989, vol. 28, # 9, p. 786 - 789
[19] Journal of Agricultural and Food Chemistry, 2009, vol. 57, # 10, p. 4279 - 4286
[20] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2012, vol. 51, # 11, p. 1649 - 1654
[21] Helvetica Chimica Acta, 1950, vol. 33, p. 1353,1360
[22] Journal of Organic Chemistry, 1952, vol. 17, p. 1494
[23] Journal of Chemical Research, 2009, # 2, p. 84 - 86
[24] European Journal of Medicinal Chemistry, 2010, vol. 45, # 4, p. 1536 - 1543
[25] Chinese Chemical Letters, 2010, vol. 21, # 4, p. 412 - 416
[26] Medicinal Chemistry Research, 2011, vol. 20, # 2, p. 261 - 268
[27] European Journal of Medicinal Chemistry, 2012, vol. 52, p. 70 - 81
[28] Patent: WO2012/100734, 2012, A1, . Location in patent: Page/Page column 34
[29] Journal of Heterocyclic Chemistry, 2012, vol. 49, # 4, p. 959 - 964
[30] Current Medicinal Chemistry, 2012, vol. 19, # 35, p. 6072 - 6079
[31] European Journal of Medicinal Chemistry, 2013, vol. 69, p. 908 - 919
[32] European Journal of Medicinal Chemistry, 2014, vol. 80, p. 569 - 578
[33] Journal of Chemical Sciences, 2014, vol. 126, # 6, p. 1913 - 1921
[34] Medicinal Chemistry Research, 2015, vol. 24, # 8, p. 3194 - 3211
[35] RSC Advances, 2016, vol. 6, # 23, p. 19271 - 19279
[36] Drug Design, Development and Therapy, 2016, vol. 10, p. 1807 - 1815
[37] Journal of Heterocyclic Chemistry, 2017, vol. 54, # 1, p. 524 - 530
[38] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 5, p. 1199 - 1204
[39] Journal of the Chinese Chemical Society, 2017, vol. 64, # 12, p. 1408 - 1416
[40] Bioorganic Chemistry, 2018, vol. 78, p. 195 - 200
[41] Inorganic Chemistry, 2018, vol. 57, # 6, p. 3420 - 3433
[42] Tetrahedron, 2018, vol. 74, # 27, p. 3602 - 3607
[43] Journal of Heterocyclic Chemistry, 2018, vol. 55, # 6, p. 1410 - 1418
[44] European Journal of Medicinal Chemistry, 2018, vol. 157, p. 310 - 319
3
[ 333-20-0 ]
[ 536-38-9 ]
[ 2103-99-3 ]
Reference：
[1] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 3, p. 613 - 623
4
[ 536-38-9 ]
[ 2103-99-3 ]
Reference：
[1] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 19, p. 5354 - 5367
5
[ 622-98-0 ]
[ 141-78-6 ]
[ 34966-48-8 ]
[ 7099-88-9 ]
[ 536-38-9 ]
Reference：
[1] Synlett, 2011, # 10, p. 1381 - 1384
6
[ 64-17-5 ]
[ 13651-12-2 ]
[ 34966-48-8 ]
[ 536-38-9 ]
Reference：
[1] Synlett, 2011, # 10, p. 1381 - 1384
7
[ 536-38-9 ]
[ 4996-21-8 ]
Yield
Reaction Conditions
Operation in experiment
70%
With water; hydrogen bromide In dimethyl sulfoxide at 80℃; for 5 h;
A solution of 4'-chloro-2-bromoacetophenone (25. 0 g, 107 MMOL), water (1. 92 mL, 107 mmol) and 47percent HYDROBROMIC ACID (0. 20 ML) IN DIMETHYLSULFOXIDE (160 mL) was stirred at 80°C for 5 h. After the reaction mixture was poured into water, the precipitate was filtered, washed with diethylether and dried, affording 4 -CHLORO-2, 2-DIHYDROXYACETOPHENONE (14. 0 G, percent). 1H NMR (300MHZ, CDCL3), No. 5. 92 (1H, S), 7. 45-7. 52 (2H, M), 8. 05-8. 20 (2H, M).
Reference：
[1] Bulletin de la Societe Chimique de France, 1899, vol. <3> 21, p. 67
9
[ 622-98-0 ]
[ 141-78-6 ]
[ 34966-48-8 ]
[ 7099-88-9 ]
[ 536-38-9 ]
Reference：
[1] Synlett, 2011, # 10, p. 1381 - 1384
10
[ 536-38-9 ]
[ 5467-71-0 ]
Yield
Reaction Conditions
Operation in experiment
50%
Stage #1: With sodium diformamide In acetonitrile for 4 h; Reflux Stage #2: With hydrogenchloride In ethanol at 20℃; for 72 h;
A mixture of 2-bromo-1-(4-chlorophenyl)ethanone (1.0 eq.) and NaN(CHO)2 (1.1 eq.) in acetonitrile (1.5 mL per mmol) was heated to reflux for 4 h at 105° C. ext. temperature. The formed sodium bromide was removed by filtration and the filtrate concentrated in vacuo. The residue was dissolved in ethanol (2.5 mL per mmol) and conc. aq. hydrochloric acid (0.9 mL per mmol) added at ambient temperature. After stirring for 72 h at room temperature the solids were filtered off and washed with ethanol (1.x.0.5 mL per mmol). Drying of the solids afforded 2-amino-1-(4-chlorophenyl)ethanone hydrochloride in ca. 50percent yield that was used in the next step without purification.
Reference：
[1] Patent: US2010/210849, 2010, A1, . Location in patent: Page/Page column 34
[2] Journal of Medicinal Chemistry, 1982, vol. 25, # 9, p. 1045 - 1050
[3] Arzneimittel-Forschung/Drug Research, 1992, vol. 42, # 5, p. 592 - 594
[4] Tetrahedron Letters, 1989, vol. 30, # 39, p. 5285 - 5286
[5] Synthesis, 1990, # 7, p. 615 - 618
[6] Patent: US4968702, 1990, A,
[7] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 5, p. 2550 - 2557
11
[ 100-97-0 ]
[ 536-38-9 ]
[ 5467-71-0 ]
Reference：
[1] Journal of Organic Chemistry, 1939, vol. 4, p. 198,204
[2] Patent: WO2009/62118, 2009, A2, . Location in patent: Page/Page column 209-210
0.157 g of cyclopentanone thiosemicarbazone Schiff base and 0.234 g of p-chloroα-bromoacetophenone were weighed into a reaction flask, 15 ml of isopropanol was added, and the reaction was stirred at normal temperature, and the reaction was followed by TLC ( Ethyl acetate: petroleum ether = 1:2). After 4h, the system did not change, the reaction was stopped, filtered, and the filter cake was washed with ethanol to give 0.271 g of white solid.
Reference：
[1] Patent: CN108409683, 2018, A, . Location in patent: Paragraph 0010; 0011
[2] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 16, p. 4635 - 4640
[3] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 14, p. 5063 - 5070
In ethanol; at 150℃; for 0.333333h;Microwave irradiation;
(4,5,6,7-Tetrahydrobenzo [d] thiazol-2-amine, 46.2 mg, 0.3 mmol) and 2-bromo- 4'-fluoroacetophenone (70 mg, 0.3 mmol) was dissolved in ethanol (3 ml) and stirred in a microwave reactor at 150 C for 20 minutes. The residue was concentrated under reduced pressure and subjected to column chromatography (EtOAc: Hex = 1: 5) to obtain Compound 2b (18.9 mg, 22%).
General procedure: A mixture of equimolar quantities of <strong>[76074-47-0]5-m-tolyl-1,3,4-thiadiazol-2-amine</strong> 8 (0.01mol) and substituted phenacyl bromides (0.01mol) was refluxed in dry ethanol (50mL) for 24h. The excess of solvent was distilled off and the solid hydrobromide salt that separated out was collected by filtration, suspended in water and neutralized by sodium carbonate to get free base 9(a-i). The product was filtered, washed with water, dried and crystallized from carbon tetrachloride.
5-(4-chlorophenyl)-2-p-tolylimidazo[2,1-b][1,3,4]thiadiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
In ethanol; at 80 - 85℃; for 24h;
General procedure: 4.2.3.1. 6-(4-Chlorophenyl)-2-methyl imidazo[2,1-b][1,3,4]thiadiazole(3a). A mixture of 2a (2 g, 17.39 mmol) and 4-chloro phenacyl bromide (4.032 g, 17.39 mmol) was refluxed in dry ethanol (20 mL)for 24 h. The excess of solvent was removed under reduced pressureand the solid hydrobromide salt was suspended in water, and neutralized by the aqueous sodium carbonate solution to get free base. It was then filtered, washed with water, dried, and recrystallized from ethanol to get compound 3a as light yellow solid. Yield: 3.4 g, 80%
General procedure: A stirred mixture of <strong>[90008-50-7]3-amino-6-propoxypyridazine</strong> 3 (4.50g, 29.4mmol), 2-bromo-1-[4-(2-methoxyethoxy)phenyl]ethanone 11 (8.03g, 29.4mmol) and EtOH (280mL) was heated at reflux for 2.5 hours. The mixture was cooled and NaHCO3 (2.50g, 30mmol) was added. The mixture was stirred at room temperature for 15 hours, heated at reflux for 1 hour, then cooled and evaporated. The residue was extracted with CHCl3 (150mL) and the extract washed with saturated, aqueous NaCl solution (50mL), dried (MgSO4) and evaporated. The residue was purified by flash chromatography over silica gel. Elution with 1-2% MeOH in CH2Cl2 afforded a green/brown solid. Treatment with decolourising charcoal and recrystallization from cyclohexane gave 6f (3.95g, 41%) as pale green crystals, m.p. 82.5-84C. 1H NMR (CDCl3) ? 1.06 (3H, t, J=7.2Hz), 1.75-1.94 (2H, m), 3.47 (3H, s), 3.74-3.81 (2H, m), 4.14-4.21 (2H, m), 4.27 (2H, t, J=6.6Hz), 6.68 (1H, d, J=9.3Hz), 7.00 (2H, d, J=8.8Hz), 7.76-7.88 (3H, m), 7.94 (1H, s). MS (APCI+) m/z 328 (M+H, 100%).
6.1. 2-(4-Chlorophenyl)-6-methoxyimidazo[1,2-a]pyridine A mixture of 1.3 g (10.5 mmol) of 5-methoxy-2-pyridinamine, 2.44 g (1eq) of alpha-bromo-4-chloroacetophenone and 1.76 g (2eq) of sodium bicarbonate in 20 ml of 95percent strength alcohol is heated under reflux for 4 h 30 min. under argon. The mixture is evaporated to dryness and the residue taken up between CH2 Cl2 and H2 O, followed by washing, drying and evaporation. The product is purified by chromatography and then crystallized in ether. M.p. 148°-9° C. 5-Methoxy-2-pyridinamine was obtained according to a process described in the literature: G. J. Clark and L. W. Deady, Aust. J. Chem. 34, 927 (1981).
With triethylamine;silica gel; In water; N,N-dimethyl-formamide; toluene;
EXAMPLE 2 Preparation of 1-(4-chlorophenyl)-8,9-dihydro-7H-pyrrolo[3,2,1-ij]quinolin-7-one 5,6,7,8-Tetrahydroquinolin-5-one (35 g) was dissolved in 80 ml of toluene. To this solution was added 4-chlorophenacyl bromide (55.6 g) gradually and refluxed for 18 hours. The reaction mixture was cooled to room temperature, and depositing crystals were collected by filtration (78 g). These solids were dissolved in 700 ml of N,N-dimethylformamide. To this solution was added, molecular sieves 3A (30 g) and triethylamine (34 ml), then the reaction mixture was heated at 100 C. for 1 hour. The reaction mixture became dark brown. The dark brown solution that obtained after removing insoluble matter by filtration was concentrated under reduced pressure. To the residue was added 300 ml of water, and extracted with 200 ml of methylene chloride three times. This methylene chloride solution was washed with 100 ml of brine and dried over anhydrous sodium sulfate. The dark brown solution that obtained after removing drying agent by filtration was concentrated under reduced pressure, the resultant dark brown residue was purified by alumina column chromatography. The title compound was obtained as dark red crystals (29 g). m.p.: 153.4-157.2 C. IR: 2360, 1683, 1535, 1514, 1471, 1448, 1400, 1384, 1271 264, 1229, 1089, 8365
2-(4-chlorophenyl)-2-bromomethyl-4-hydroxyethyl-1,3-dioxolane[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With potassium carbonate; In toluene;
EXAMPLE 14 Preparation of 2-(4-chlorophenyl)-2-bromomethyl-4-hydroxyethyl-1,3-dioxolane. A mixture of 1,2,4-butanetriol (18 g), paratoluenesulphonic acid (2.5 g), n-butanol (50 ml), toluene (250 ml), 2-bromo-1-(4-chlorophenyl)-ethanone (33 g) is refluxed for 25 hours, water being distilled off azeotropically. After cooling, the reaction mixture is treated with a solution of potassium carbonate; the organic phase separated is then washed with water, dried over sodium sulphate, and evaporated to dryness. A reddish oil is obtained (42.2 g) which is used as such for the reaction according to Example 13.
With potassium carbonate; In toluene;
Example 14 Preparation of 2-(4-chlorophenyl)-2-bromomethyl-4-hydroxyethyl-1,3-dioxolane. A mixture of 1,2,4-butanetriol (18 g), paratoluenesulphonic acid (2.5 g), n-butanol (50 ml), toluene (250 ml), 2-bromo-1-(4-chlorophenyl)-ethanone (33 g) is refluxed for 25 hours, water being distilled off azeotropically. After cooling, the reaction mixture is treated with a solution of potassium carbonate; the organic phase separated is then washed with water, dried over sodium sulphate, and evaporated to dryness. A reddish oil is obtained (42.2 g) which is used as such for the reaction according to Example 13. I.R. (cmmin1): 3400, 1100, 1050, 1020. 1H-N.M.R. (60 MHz), TMS in CCl4, delta: 1.70 (m, 2H); 2.80 (s, 1H which swaps with D2O); 3.55 (s, 2H); 3.55-4.50 (m, 5H); 7.40 (m, 4H);
8-Bromo-6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]-pyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With sodium bicarbonate; In ethanol; ethyl acetate;
1.2. 8-Bromo-6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]-pyridine 17 g (82 mmol) of <strong>[26163-03-1]2-amino-3-bromo-5-chloropyridine</strong> dissolved in 150 ml of ethanol are reacted with 29 g of 2-bromo-1-(4-chlorophenyl)-1-ethanone and 14 g of sodium hydrogen carbonate. The mixture is brought to the refluxing temperature for 6 h and cooled. The precipitate is filtered off and rinsed with CH2 Cl2, and the filtrate is concentrated under reduced pressure. After recrystallization of the evaporation residue in ethyl acetate, the compound melts at 178 C.
Example 1A. 4-(4-(4-chlorophenyl)-2-oxo-2,5-dihydrofuran-3-yl)benzonitrile; To a stirred and cooled (-15° to -10°C) solution of <strong>[5462-71-5]2-<strong>[5462-71-5](4-cyanophenyl)acetic acid</strong></strong> (35 g, 217.18 mmol) in DMF (250 mL) was added potassium t-butoxide (95percent, 25.66 g, 217.22 mmol) under argon in small portions keeping the temperature below-10°C. After the addition was complete a solution of 2-bromo-l-(4-chlorophenyl)ethanone (50.71 g, 217.18 mmol) in DMF (75 mL) was added slowly over 30 min. The reaction mixture was stirred for 1 hr keeping the temperature between -10° to 0° C. Et3N (12.0 mL, 86.1mmol) was added at 0° C and the reaction mixture was allowed to warm to room temperature over 1.5 hr. Then EtOH (70 mL) was added at room temperature and the reaction mixture was stirred for 10 min. The reaction mixture was cooled in an ice bath and water (300 mL) was added slowly. The light green precipitate formed was collected by filtration, washed thoroughly with water followed by hexanes. The solid thus obtained was dried in a vacuum oven overnight at 50°C to obtain 4-(4-(4-chlorophenyl)-2-oxo-2,5-dihydrofuran-3-yl)benzonitrile (58.2 g, 91percent yield) as a light green solid.
EXAMPLE 71; 5 2-(4-Chlorophenyl)-3-(hydroxymethyl)imidazo[l,2-a]pyridine-6-carboxamide; 6-Aminonicotinamide (41 mg, 0.30 mmol) and 4-chlorophenacyl bromide (47 mg, 0.20 mmol) were mixed in ethanol (0.5 mL) and stirred at rt over the weekend. The mixture was then heated at 70 °C overnight. 0.5 M NaOH (1.2 mL) was added slowly with stirring. The0 precipitate that formed was collected by centrifugation and washed with water (1.5 mL) to give the intermediate compound 2-(4-chlorophenyl)imidazo[l,2-a]pyridine-6-carboxamide. MS (ESI+) m/z 272, 274 [M+H]+.
EXAMPLE 104; Methyl 6-(4-chlorophenyl)-5-(hydroxymethyl)imidazo[2,l-b][l,3]thiazole-2- carboxylate; A solution of methyl-2-aminothiazole-5-carboxylate (1.0 g, 7.8 mmol) and 2-bromo-4'- chloroacetophenone (1.8 g, 7.8 mmol) in acetone (200 mL) was heated at reflux for 72 h. The remaining intermediate was filtered off and the filtrate was collected. The solvent was removed under reduced pressure to afford the intermediate compound methyl 6-(4- chlorophenyl)imidazo[2,l-b][l,3]thiazole-2-carboxylate as a yellow solid (1.5 g).
INTERMEDIATE 4; 6-(4-Chlorophenyl)-5-(hydroxymethyl)imidazo [2, 1-b] [ 1 ,3] thiazoIe-2-carbaldehyde; A solution of <strong>[1003-61-8]2-aminothiazole-5-carboxaldehyde</strong> (1.0 g, 7.8 mmol) and 2-bromo-4'- chloroacetophenone (1.8 g, 7.8 mmol) in acetone (5 mL) was heated at reflux for 5 h. The solvent was evaporated and the crude material purified by preparative HPLC (Xterra Cl 8, 50 mM NH4HCO3 (pH 10) - CH3CN) to give the intermediate compound 6-(4- chlorophenyl)imidazo[2,l-b][l,3]thiazole-2-carbaldehyde as a yellow solid (176 mg).
With toluene-4-sulfonic acid; In toluene; at 130℃;Product distribution / selectivity;
Example 23; Synthesis of (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange between substrates A mixture of 2-bromo-4'-chloroacetophenone (4.94 g, 2-chloro-4'-chloroacetophenone content=0.09%), p-toluenesulfonic acid monohydrate (0.20 g, 0.05 equivalent) and toluene (100 mL) was refluxed at 130C using an azeotropic distillation device with a Dean-Stark tube, and (S)-monochlorohydrin (2.59 g, 1.1 equivalents, >99%ee) was added dropwise under reflux such that the amount of the (S)-monochlorohydrin present in the reaction solution would be not more than 0.1 equivalent (not more than 2.1 mmol) relative to the amount of 2-bromo-4'-chloroacetophenone to be used (21.2 mmol), while analyzing the progress of the reaction by GC. After confirmation of the completion of the azeotropic distillation, the reaction mixture was cooled and washed with 10% aqueous sodium hydrogen carbonate solution and 10% brine. The solvent was evaporated under reduced pressure to give (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane (6.56 g, >99%ee). Here, the content percentage of (4S)-trans-,cis-2-(4-chlorophenyl)-2-chloromethyl-4-chloromethyl-1,3-dioxolane halogen-exchanged with a chlorine atom was 0.09%.
A solution of 4-chlorophenacyl bromide (0.79 g, 3.38 mmol) and ethyl-3- amino-3-thioxopropanoate (0.50 g, 3.38 mmol) in EtOH (10 mL) was heated to 75C for 2 h under an atmosphere of N2. At the completion of the reaction the EtOH was evaporated, water was added and the mixture was washed with EtOAc (3 x 50 mL). The combined organic phases were washed with water and brine, dried over a2S04, filtered and concentrated. The crude residue was purified by silica chromatography (5% EtOAc/hexane) to afford ethyl 2-(4-(4-chlorophenyl)thiazol-2-yl)acetate (0.67 g, 70%).
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere;
General procedure: Activated (heated at 100 C in a hot-air oven for about 24 h) K2CO3 (896.1 mg,6.4 mmol) was added into a 100-ml, round-bottomed flask containing a stirred mixtureof 5-bromomethyl salicylate (500.0 mg, 2.1 mmol) and 4-chlrophenacyl bromide(601.7, 498.0 mg, 2.1 mmol) in 10 ml of dried DMF at room temperature under nitrogen.The stirring was continued, and the progress of the reaction was monitored byTLC. Most of the reactants had disappeared in about 30 min. However, the reactionmixture was stirred for a total period of 1 h. Then, about 50 g of crushed ice wereadded into the mixture and acidified with 1N HCl. The precipitated solid wascollected by filtration and chromatographed on a silica-gel column by using 1:9,2:8, and 3:7 mixtures of ethyl acetate and petroleum ether to get 700.0 mg of 4g(2.0 mmol, 91%).
[4-(4-chlorophenyl)thiazol-2-yl]methylamine hydrochloride[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
100%
To <strong>[89226-13-1]tert-butyl 2-amino-2-thioxoethylcarbamate</strong> (1.0 g, 5.3 mmol) and 4-chlorophenacylbromide (1.2 g, 5.3 mmol) was added ethanol (8 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, 4 mol/L hydrochloric acid/1,4-dioxane solution (10 ml) was added to the obtained residue, and the mixture was stirred at room temperature for 2 hr. The precipitate was collected by filtration, washed with a small amount of 1,4-dioxane, and dried under reduced pressure to give the title compound as a white powder (1.4 g, 5.3 mmol, 100%). 1H NMR (400 MHz, DMSO) delta 8.56 (s, 3H), 8.27 (s, 1H), 8.04 (d, J=8.6 Hz, 2H), 7.55 (d, J=8.6 Hz, 2H), 4.51 (s, 2H). MS (ESI) m/z 225 (M+H)+
2-(4-chlorophenyl)-7-methyl-imidazo[1,2-a]pyrimidin-5(8H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In N,N-dimethyl-formamide;
Step 1 To a solution of <strong>[3977-29-5]2-amino-4-hydroxy-6-methylpyrimidine</strong> (1, 250 mg, 2.00 mmol) in N,N-dimethylformamide (10 mL) was added 2-bromo-1-(4-chlorophenyl)ethanone (467 mg, 2.00 mmol), and the solution was heated to reflux for 4 hours under argon atmosphere. The reaction was cooled to room temperature, and the precipitate was collected by filtration to yield 2-(4-chlorophenyl)-7-methyl-imidazo[1,2-a]pyrimidin-5(8H)-one (2, 301 mg, yield: 58percent) as a pale yellow solid. 1H-NMR (delta ppm TMS/DMSO-d6) 8.13 (s, 1H), 7.94 (d, 2H, J=8.1 Hz), 7.48 (d, 2H, J=8.1 Hz), 5.65 (s, 1H), 2.30 (s, 3H).
6-(4-chlorophenyl)-2-(3,4-dimethoxybenzyl)imidazo[2,1-b][1,3,4]thiadiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
61%
In ethanol;Reflux;
General procedure: In a two-necked flask, 2-amino-1,3,4-thiadiazole derivatives2a-b (0.004 mol) were dissolved in absolute ethanol (30mL). Phenacyl bromide derivatives 3a-i (0.04 mol) werealso dissolved in absolute ethanol (20 mL) and then addeddrop by drop to this solution at room temperature with theassistance of a dropping funnel. The mixture was thenrefluxed and stirred for 12-16 h. The progress of reactionwas monitored by thin layer chromatographyat appropriatetime intervals. The excess solvent was removed underreduced pressure and neutralized by an aqueous sodiumcarbonate (Na2CO3) solution. The solution was filtered andwashed with deionized water. The solid matter wasrecrystallized from acetone. The synthesized compoundswere dried with P2O5 in a vacuum oven. The physicalproperties and spectral data derived from the obtainedproducts are listed below.
Step one, 3.7mmol <strong>[480-41-1]naringenin</strong> was dissolved in 50mL N, N-dimethylformamide, with stirring 4.5mmol freshly dried anhydrous sodium bicarbonate, heated to reflux at 75 C 10min, was slowly added dropwise 4.5mmolChloro bromoacetophenone,Continue to heat reflux at 75 4h vacuum distillation, dissolved in water diluted with dilute hydrochloric acid to adjust the pH to 6, with ethyl acetate extractant, each time The organic layer was combined, washed twice with water and saturated brine successively, dried over anhydrous sodium sulfate and then distilled under reduced pressure. The residue was purified by column chromatography on a silica gel column using petroleum ether: ethyl acetate in a volume ratio of 3: 1 As eluent, chromatography to give compound 2e;
Step one, 3.7mmol <strong>[480-41-1]naringenin</strong> was dissolved in 50mL N, N-dimethylformamide, added with stirring 7.5mmol freshly dried anhydrous sodium bicarbonate, heated to reflux at 75 C 10min, was slowly added dropwise 10mmol bromine Acetophenone, continue heating at 75 refluxed 10h after distillation under reduced pressure, dissolved in water after the resulting solute with dilute hydrochloric acid to adjust the pH to 4, with ethyl acetate as extractant, eachTake 20mL, extracted three times, the combined organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, vacuum distillation, the silica gel column to petroleum ether: ethyl acetate volume ratio of 5: 1 Eluant, chromatography to isolate compound 2f;
1-(2-(4-chlorophenyl)-2-oxoethyl)-1H-pyrrole-2-carbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With potassium carbonate; In acetonitrile; at 20℃; for 12h;
To a cold solution of hydroxylamine hydrochloride (0.38 g, 5.5 mmol, 1.1 equiv.) in anhydrous acetonitrile (50 mL), triethylamine (0.77 mL, 5.5 mmol, 1.1 equiv.) and 1H-pyrrole-2-carboxaldehyde (5.0 mmol, 1.0 equiv.) were added and stirred for around 30 mins. Then phthalic anhydride (0.75 g, 5.05 mmol, 1.01 equiv.) was slowly added under nitrogen protection. The resulting mixture was stirred at 80 C for about 8 h. After concentration, the resulting residue was added cold CH2Cl2 (30 ml × 3) and stirred. The combined filtrates were washed with 5% ammonia water to remove phthalic acid completely. The separated organic layer was dried over anhydrous Na2SO4, and then concentrated under reduced pressure. Finally the residue was purified by passing it through a short silica gel column using CHCl3 as eluent to give pure <strong>[4513-94-4]1H-<strong>[4513-94-4]pyrrole-2-carbonitrile</strong></strong> as yellow oil (80%).3 A mixture of <strong>[4513-94-4]1H-<strong>[4513-94-4]pyrrole-2-carbonitrile</strong></strong> (3.0 mmol, 1.0 equiv.), substituted methyl bromide (3.3 mmol, 1.1 equiv.) and K2CO3 (3.6 mmol, 1.2 equiv.) was stirred in CH3CN (20 mL) at room temperature. After being stirred for 12 h, the reaction mixture was concentrated under reduced pressure, diluted with EtOAc (30 mL), and washed with H2O (30 mL). The water layer was extracted with EtOAc (30 mL) one more time. The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane: EtOAc = 10:1) to afford 1b as white solid.
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