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CAS No. :2103-94-8 MDL No. :MFCD00051953
Formula : C9H7BrN2S Boiling Point : -
Linear Structure Formula :- InChI Key :ZBRNKOLWXWMLTA-UHFFFAOYSA-N
M.W : 255.13 Pubchem ID :620683
Synonyms :

Safety of [ 2103-94-8 ]

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

Application In Synthesis of [ 2103-94-8 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 2103-94-8 ]

[ 2103-94-8 ] Synthesis Path-Downstream   1~85

  • 1
  • [ 2103-94-8 ]
  • [ 1147550-11-5 ]
  • [ 98948-98-2 ]
YieldReaction ConditionsOperation in experiment
88% With air; alizarine red S-sensitized TiO2 In tetrahydrofuran at 25℃; for 24h; Irradiation; Green chemistry; regioselective reaction;
With bromine; acetic acid
With iodic acid In water at 20℃; for 0.166667h; Green chemistry; General procedure for synthesis of 3a-k General procedure: To a mixture of 2-aminothiazole1a-k(1 mmol), ammoniumthiocyanate(1mmol)dissolvedin(10mL)ofPEG400andwatermixture, iodic acid (1 mmol) dissolved in water (1 mL) wasadded with stirring and then the reaction mixture was stirredfor 10-15 min at room temperature. After completion of reaction (As indicated by TLC) the reaction mixture was dilutedwith ice cold water and neutralized with sodium bicarbonate.The solid product was filtered, washed with cold water. Thecrude products were further purified by column chromatography (Petroleum ehter/Ethyl acetate) 20%. All the remainingderivatives2a-kwere prepared according to the typical procedure given above with more than 90% yield.
  • 2
  • [ 99-90-1 ]
  • [ 17356-08-0 ]
  • [ 2103-94-8 ]
YieldReaction ConditionsOperation in experiment
99% With iodine at 130 - 150℃; for 0.166667h; Neat (no solvent); Microwave irradiation; General procedure for the synthesis of 2-amino-4-aryl-1,3-thiazoles (3a-h) General procedure: Method A: A mixture of p-substituted acetophenone 1 (8.6 mmol), thiourea 2 (17.2 mmol, 1.3 g) and iodine (8.6 mmol, 2.2 g) was placed in an open vessel containing a Teflon coated stir bar. The vessel was placed in the microwave cavity (CEM, Discover) and subjected to MW irradiation (50 W) at indicated temperature for 10 min. After the completion of the reaction, the crude mixture was cooled to 70 °C and then it was triturated, filtered and washed with Et2O. The crude product was dissolved in hot water and the pH was adjusted to 11-12 with NH4OH. The precipitated was filtered and crystallized from EtOH-H2O (1:4) to obtain the 2-amino-4-aryl-1,3-thiazole (3a-h).
98% With iodine at 100℃;
98% With N-iodo-succinimide In ethanol at 20℃; for 1h; 2.4. General procedure for the synthesis of 2-aminothiazoles General procedure: A mixture of methyl carbonyl (2 mmol), thiourea (3 mmol), NIS(2 mmol), and NH2-MMT (0.10 g) in EtOH (5 mL) at room temperature was stirred until completion of reaction. The progress of the reaction was monitored by TLC (petroleum ether-ethyl acetate 4:1). After completion of the reaction, the NH2-MMT was separated by filtration. After evaporation of EtOH under vacuum, the crude product was dissolved in boiling water and adjusted to pH 8 withthe amount of ammonia to give the solid products. The solid obtained was recrystallized from a mixture of ethanol-water.
97% With iodine In ethanol at 70℃; for 3.5h;
97% With N-Bromosuccinimide In ethanol for 2h; Reflux; Green chemistry;
97% With iodine In dimethyl sulfoxide at 85℃; for 3.5h; 2.2. General procedure for the catalytic synthesis of 2-aminothiazoles General procedure: A mixture of methylcarbonyl (5 mmol), thiourea (7.5 mmol), I2(5 mmol), and nano Asp-Al2O3 (0.2 g) in DMSO was stirred at 85 °C for desired time. After the completion of reaction (monitored by TLC), the heterogeneous organocatalyst was separated by simple filtration and the solvent was removed under reduced pressure. The crude product was dissolved in hot water, extracted with ether(3 x 30 mL), and adjusted to pH = 9-10 by ammonia to give the solid products. Finally, the pure product was recrystallized by ethanol in high yield. All corresponding products are known and were characterized by comparison of their physical (Mp) and spectral data (IR and 1H NMR) with those of authentic samples.
96% With iodine In ethanol for 2.5h; Reflux; 2.3. General procedure for the preparation of 2-aminothiazole derivatives General procedure: A mixture of the acetophenone (2 mmol), thiourea (3 mmol) and iodine (2 mmol), in the presence of 0.03 g nanochitosan was refluxed in EtOH. The progress of the reaction was monitored by TLC (petroleum ether-ethyl acetate 4:1). After completion of the reaction, the catalyst was separated by simple filtration. After evaporation of solvent, the crude product was dissolved in boiling water, extracted with ether (3 * 30 mL), and adjusted to pH = 8 with the amount of ammonia to give the solid products. The solid was recrystallized with ethanol-water to give pure 2-aminothiazole.
96% With N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide In neat (no solvent) at 80℃; for 1h;
92% Stage #1: para-bromoacetophenone; thiourea In methanol at 20℃; for 0.25h; Stage #2: With hydrogenchloride In methanol at 90℃; for 2h;
92% With iodine; triethylamine sulfate In neat (no solvent) at 40℃;
90% With iodine In ethanol for 4h; Microwave irradiation;
90% With sodium iodine dichloride In tetrahydrofuran; water for 12h; Reflux; General procedure for the synthesis of 2-aminothiazole General procedure: To a stirred solution of thiourea (2 equiv), and ketone (1 equiv) in THF (10 mL) at room temperaturewas slowly added aqueous NaICl2 (0.5 equiv, 30% W/W aqueous NaICl2). Theresultant reaction mixture was refluxed for 12 h. After completion of thereaction (TLC), the solvent was evaporated under vacuum. The resulted residuewas diluted with water (10 mL) and extracted with ethyl acetate (3 10 mL). The organic layer was separated and washed successively with 10% sodiumbisulfate solution (2 10 mL), 10% sodium bicarbonate (2 10 mL) and water(2 15 mL). The organic layer was finally dried over anhydrous sodiumsulphate and concentrated under reduced pressure to give the crude product.Pure product was obtained after silica gel column chromatography (30% EtOAc/hexane).
88% With iodine In ethanol for 14h; Heating;
80% With iodine at 100℃;
80% With carbon tetrabromide; triethylamine In acetonitrile at 20℃; for 4h; General procedure for the synthesis of 2-aminothiazoles 3 General procedure: To a mixture of ketone (0.5 mmol), thiourea (0.5 mmol), and triethylamine (0.5 mmol) in acetonitrile (3 mL) was added carbon tetrabromide (0.5 mmol) in a round bottom flask at room temperature and the reaction mixture was stirred for 2-6 h. After completion of the reaction (monitored by TLC), water (5 mL) was added and the mixture was extracted with EtOAc (3*5 mL). The combined organic phase was dried over MgSO4, filtered, and evaporated under reduced pressure to give the crude product. The resulting product was purified by silica gel column chromatography using a gradient mixture of hexane/ethyl acetate as eluent to afford an analytically pure sample of 3.
78% With iodine In ethanol for 14h; Reflux; 3 4.1.2.2 General procedure for the synthesis of 2-amino-4-phenylthiazoles (7a-c) General procedure: 2-Amino-4-phenyl thiazoles (7a-c) were synthesized by using substituted acetophenones (5a-c, 0.0025mol) and thiourea (6, 0.003mol). The reaction mixture was refluxed for 14h in the presence of iodine (0.0062mol) and ethanol as a solvent. The product 7a-c were basified with sodium hydroxide solution to get the white solid. The product was recrystallized from ethanol to get needle like crystals.
77% Stage #1: para-bromoacetophenone With bromine; urea In N,N-dimethyl-formamide at 20℃; for 24h; Stage #2: thiourea In N,N-dimethyl-formamide at 20 - 80℃; for 26h;
65% With iodine at 100℃; for 8h; 4.1.2. General procedure for synthesis of 2-amino-4-(substituted phenyl)-1,3-thiazoles (3a-k) General procedure: A mixture of thiourea (50 mmol), the corresponding acetophenone (25 mmol) and iodine (25 mmol) is stirred at 100 °C for 8 h.Then the reaction mixture is cooled, extracted with diethyl ether toremove excess of acetophenone, and then washed with aqueous sodium thiosulfate to remove excess iodine and later with cold water. The crude product is dissolved in hot water, filtered to remove sulphone, and the filtrate is basified with aqueous Na2CO3to yield the corresponding 2-amino-4-(substituted-phenyl)-1,3-thiazole. The crude product is purified by recrystallization from alcohol.
62% Stage #1: para-bromoacetophenone; thiourea In propan-1-ol for 2h; Reflux; Stage #2: With pyridine In propan-1-ol for 5h; Reflux;
55% With iodine at 150℃;
48% With iron(III) chloride hexahydrate; iodine at 110℃; for 24h; Sealed tube; Green chemistry;
42.3% With iodine In dimethyl sulfoxide at 80℃; for 12h; 7 Example 7 Add 0.796 g (4 mmol) of p-bromoacetophenone to the reaction tube containing the stirring magnet.Thiourea 0.152g (2mmol),0.051 g (0.4 mmol) of iodine and 4 ml of DMSO.Place the reaction tube in an oil bath at 80 ° C.The reaction was stirred for 12 h.After the reaction, the reaction solution was treated with a saturated NaHCO3 solution (20 mL).An additional 30 ml of water was added and extracted three times with 20 mL of ethyl acetate.The extract was washed with water and saturated NaCl solution, and dried over anhydrous Na2SO4.The solvent was removed under reduced pressure on a rotary evaporator, and the residue was separated by silica gel column chromatography.Eluted with petroleum ether / ethyl acetate (5: 1 by volume),2-amino-4-p-bromophenylthiazole (0.216 g) was obtained in a yield of 42.3%.
42% With iodine; dimethyl sulfoxide at 80℃; for 12h; Schlenk technique; I2-catalyzed coupling reaction of ketones and thiourea: general procedure General procedure: A Schlenk tube (20 mL) was charged with ketone 1 (4 mmol),thiourea (2) (2 mmol), I2 (0.4 mmol) and DMSO (4 mL). Thetube was sealed with a rubber septum and the reaction mixturewas stirred at 80 °C for 12 h. After completion of thereaction, the mixture was cooled to room temperature. Ethylacetate (20 mL) and a saturated solution of NaHCO3 (20 mL)were added and the organic layer was separated. The aqueousphase was extracted with ethyl acetate (3 × 10 mL). Thecombined organic layer was washed with a saturated solutionof NaCl (20 mL) and then dried over anhydrous Na2SO4.After filtration, the solvent was removed under reduced pressure.The crude mixture was purified by chromatography onsilica gel to yield the desired products.
With iodine
With iodine
With iodine
With iodine In ethanol for 24h; Reflux; General procedure for the preparation of 2-bromo-N-thiazolyl acetamide derivatives (Intermediate 7a, Scheme 2):Some of the (2-amino-4-aryl)thiazoles used for the synthesis of 2-bromo-N- thiazolyl acetamides of general formula (7a) were not commercially available and were prepared from appropriately substituted acetophenones and thiourea as described below. Step 1: A mixture of appropriate aryl alkyl ketone (1.0 equiv.), thiourea (2.0 eqiv.) and iodine (1.0 equiv.) in dry ethanol (5 volumes) was refluxed for 24h. The reaction mixture was diluted with ethyl acetate and washed with saturated solution of sodium thiosulphate.The organic layer was treated with IN HCl and the precipitated salt collected by filtration. The salt was then treated with saturated solution OfNaHCO3 and extracted with dichloromethane, washed with brine, dried over sodium sulfate and the solvent was evaporated to afford the 2-aminothiazole derivative.Step 2: To a stirred and cooled (O 0C) solution of appropriate amine (1.0 equiv.) and pyridine (1.2 equiv.) in dichloromethane (5 volume) was added bromoacetyl bromide (1.2 eq.) over 5 min and the resulting mixture was allowed to warm to room temperature and then further stirred at room temperature for 2 h. The reaction mixture was diluted with dichloromethane (50 ml) and water (50 ml). The layers were separated. The aqueous layer was extracted with dichloromethane (2 x 50 ml) and the combined organic layers were washed with water (2 x 50 ml) followed by brine (50 ml), dried (Na2SO4) and filtered. The filtrate was concentrated under reduced pressure. The residue obtained after the evaporation of the solvent was purified by silica gel column chromatography using 5-10% ethyl acetate in petroleum ether to obtain the desired product as an off-white solid.
With iodine
With halogen for 24h; Reflux;
With iodine at 100℃; for 8h; General procedure for synthesis of 2-amino-4-(substituted-phenyl)-1,3-thiazoles General procedure: A mixture of thiourea (7, 50 mmol), the corresponding acetophenone (6, 25 mmol) and iodine(25 mmol) is stirred at 100 °C for 8 h. Then the reaction mixture is cooled, extracted with diethylether to remove excess of acetophenone, and then washed with aqueous sodium thiosulfate to remove excess iodine and later with cold water. The crude product is dissolved in hot water, filtered to remove sulphone, and the filtrate is basified with aqueous Na2CO3 to yield the corresponding 2-amino-4-(substituted-phenyl)-1,3-thiazole (5). The crude product is purified by recrystallization from alcohol. The synthesis and spectral data of compounds 5a-i have been reported by us earlier [2]. The data in respect of compounds 5j-l is described here.
With iodine at 140℃; for 0.166667h; Microwave irradiation;
With iodine In ethanol for 72h; Reflux;
With iodine In ethanol for 72h; Reflux;
With iodine at 100℃; 4.1.2. General procedure for preparation of aminothiazoleintermediates 9a-r General procedure: A mixture of the appropriate aryl ketones, 1-cyclobutylethan-1-one or 1-(furan-2-yl)ethan-1-one (8a-r, 0.1 mol) and thiourea(0.20 mol), and iodine (0.1 mol) were heated for 5 h to thick mass at100 C. After the thick mass was cooled, methanol was added, thesolid was treated with water and filtered. The residue was dried invacuo yielding the hydriodide salt of the aminothiazole intermediates9a-r, which was suitable for use in the next reaction.
With iodine for 24h; Heating;
With iodine at 110℃; for 12h;
With iodine In ethanol Reflux;
With sodium iodide dichloride In tetrahydrofuran; water for 12h; Reflux; General procedure for the synthesis of 3a General procedure: To a stirred solution of thiourea (0.002 mol, 0.15 g), and ketone (0.001 mol, 0.12 g) in THF (10 mL) at room temperature was slowly added aq. NaICl2 (0.0005 mol, 0.11 ml, 30%w/w aqueous NaICl2).[61] The resultant reaction mixture was refluxed for 12 h. After completion of reaction (TLC), thesolvent was evaporated under the vacuum. Then the resulted residue was diluted with water and extracted with ethyl acetate.The organic layer was separated and washed successivelywith of 10% sodium bisulfate solution (5 mL), 10% sodium bicarbonate (3 mL) of water. The organic layer was driedover anhydrous sodium sulfate and concentrated under thereduced pressure to give the crude product. Pure product was obtained after silica gel column chromatography with 30% EtOAc-Hexane.

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  • 3
  • [ 17356-08-0 ]
  • [ 99-73-0 ]
  • [ 2103-94-8 ]
YieldReaction ConditionsOperation in experiment
99% With diammonium hydrogen orthophosphate In ethanol; water monomer at 20℃; for 0.5h;
98% In ethanol at 70℃; 4-(4-bromophenyl)thiazol-2-amine To a stirred suspension of 2-bromo- 1 -(4-bromophenyl)ethanone (4.66 g, 16.9 mmol) in EtOH (105 mL) was added thiourea (1.53 g, 20 mmol) and the mixture was heated at 70°C overnight. After cooling to room temperature, the solvent was evaporated to dryness. The resulting solid was stirred in a mixture of EtO Ac/saturated aqueous NaHCO3 solution (2: 1) until dissolution, and then extracted with EtOAc. The organic layer was dried over Na2SO4, filtrated and the solvent was removed under reduced pressure. The product was crystallized in PE and filtered to afford a yellow solid (4.21 g, 98%). NMR (300 MHz, MeOD) δ 7.66 (d, J = 8.6 Hz, 2H, Har), 7.49 (d, J = 8.6 Hz, 2H, Har), 6.85 (s, 1H, Har). 13C NMR (75 MHz, MeOD) δ 150.5 (C), 135.3 (C), 132.6 (2xCH), 128.7 (2xCH), 122.2 (C), 103.5 (CH). HRMS (ESI) [M+H]+ C9H8BrN2S: Calcd. 254.9586 found 254.9577.
97% at 20℃; 4.2 General procedure for the synthesis of 2-(3-pyridyl)/2-amino thiazole derivatives (3/5) General procedure: A mixture of phenacyl bromide (1a) (10.0mmol), pyridine-3-carbothioamide/thiourea (2/4) (10.0mmol) and 5.0wt% of silica-supported HClO4 was taken in a mortar and ground together with a pestle for 5-10min at RT. At this stage, the progress of the reaction was monitored by TLC. After completion of the reaction, the crude mass was washed with water (20mL) twice and extracted with ethyl acetate (10mL) twice. Then the catalyst was separated by filtration under vacuum. The organic layer was washed with water, dried with anhydrous Na2SO4 and the solvent was evaporated under reduced pressure. The obtained product (3a/5a) was purified by recrystallization using ethanol. The same procedure was applied for the preparation of all other compounds (3b-k & 5b-k). All the compounds gave satisfactory physical and spectroscopic data following their proposed procedure. Compounds 5a-d and 5f-5k were synthesized and reported in the literature [82,83].
96% With sodium flouride In methanol; water monomer at 20℃; General procedure for the synthesis of 1,3-thiazoles and selenazoles 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.
95% In ethanol at 20℃; for 18h;
95% In water monomer at 25℃; for 0.00694444h; Sonication; Green chemistry; General procedure for the synthesis of 2,4-disubstituted-1,3-thiazolesand selenazoles (3-16) 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.
93% In ethanol at 70℃; for 1h; The known 2-aminothiazoles (6) were obtained following reported methods.16-18 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 ( 99%) as a white solid, mp 150-152 oC (Lit.26 149-150 oC) ; 6b (100%) as a white solid, mp 162-165 oC (Lit.26 163-164 oC); 6c (0.236 g, 93%) as a white solid, mp 179-181 oC (Lit.26 180-181 oC); 6d (98%) as a white solid, mp 203.6-204.2 oC (Lit.28/22 204.0-204.5 oC); 6e (94%) as a bright yellow solid, mp 287-288 oC (Lit.26,27 285-286 oC); 6f (100%) as a white solid, mp 172-174 oC (Lit.29-31 172 oC).
93% In ethanol at 70℃; for 1h; 2.1.1. Preparation of the 2-aminothiazoles 6a-f. General procedure: Following reported methodology,9,10 mixtures of thiourea 4 (1.2 mmol) and the haloketones 5a-f (1 mmol) in EtOH (2 mL) were stirred at 70 °C for 1h. The reaction mixtures were cooled to room temperature, poured into ice-cold water and the resulting precipitates were filtered off and dried to give the known compounds:
92% With copper (II) acetate In ethanol at 20℃; for 0.0833333h;
90% In water monomer at 20℃; for 3h; 3.1.1. 4-(4-bromophenyl) thiazol-2-amine (2) A mixture of 2, 4’-dibromoacetophenone (1.0 mmol) and thiourea (1.0 mmol) in 3 mL of water was stirred at room temperature for 3 h. The progress of the reaction was monitoredby thin-layer chromatography. On completion of the reaction, the reaction mixture was diluted with cold waterand product was extracted to ethylacetate, the organic layer was dried over anhydrous Na2SO4 and evaporated under reduced pressure to give the desired product 4-(4-bromophenyl)-thiazol-2-amine (2) in crude form which was purified by column chromatography to get the pure form of 2 (90%) as awhite solid. mp 179-181°C (lit10 mp 178-180oC); 1H NMR(400 MHz, DMSO-d6): δ 7.68-7.66 (d, J = 8.2 Hz, 2H, ArH),7.44-7.42 (d, J = 8.2 Hz, 2H, ArH), 6.72 (s, 1H, thiazole C-5H), 6.34 (br s, 2H, NH2).
89% With sodium hydrogen sulphate In water monomer at 20℃; for 0.416667h; regioselective reaction;
89% With iodine In N,N-dimethyl-formamide at 100℃; 4.3 General procedure for the synthesis of 4-arylthiazol-2-amine 12a-12g 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
87% With β‐cyclodextrin In water monomer; acetone at 50℃; for 1.5h;
87% In ethanol; water monomer at 20℃; for 0.166667h; Irradiation;
80% In ethanol at 50℃; for 0.5h; Microwave irradiation;
80% In ethanol for 0.5h; Reflux; General procedure for the synthesis of 4-phenylthiazol-2-amine derivatives 2a, 2b General procedure: The mixture of compound 1a (20 mmol) or 1b and thiourea(22 mmol) in anhydrous EtOH (30 mL) was heated to reflux for 30 min. After that, the solvent was removed in vacuo and the saturated aqueous NaHCO3 was added to make the mixture basic (pH 8-9). Then the mixture was extracted with CH2Cl2 (3×30mL). The combined organic phases were dried with anhydrous Na2SO4. After removal of all the solvent, the residue was purified by recrystallization from anhydrous EtOH to afford product 2a or 2b.
80% In ethanol at 90℃; for 12h; 4.5. General process for the synthesis of the compounds (11a-c) General procedure: To a stirred solution of compound 9a-c (10 mmol) in EtOH (15 mL)was added compound 10 (10 mmol) at room temperature, then the mixture was stirred under reflux for 12 h. The solvent was removed under reduced pressure, and the precipitate was purified by column chromatography over silica gel to give the compound 11a-c with 80%yield.
68% With sodium hydrogen sulphate In water monomer for 12h; General procedure for the synthesis of 2-amino-4-aryl-1,3-thiazoles 3a-e General procedure: 1-aryl-2-bromoethanone (20 mmol) was added to a single-necked round-bottom flask under magnetic stirring at room temperature. Afterwards, thiourea (40 mmol) and sodium hydrogen sulfate (20 mmol) were added in water (50 mL) to the flask. The reaction mixture was stirred for 12 h. Upon finishing stirring, the medium was neutralized by saturated aqueous Na2CO3 until the product precipitation, subsequently being filtered and washed with ice-cold water. Finally, the product was dried under high vacuum; the crude product was purified by flash chromatography on silica gel, being eluted with hexane and with a mixture of hexane/ethyl acetate (80:20).
41%
With ethanol
In acetone
With acetic acid for 2h; Reflux;
In tetrahydrofuran Reflux; 1 General procedure for the preparation of 2-amino-4-aryl thiazoles:Method 1A solution of acetophenone derivative (1.0 eq) in glacial acetic acid (5 vol) was added liquid bromine (1.0 eq) at 0 °C and reaction mixture was stirred at room temperature for 2h. The reaction mixture was diluted with water and extracted with ethyl acetate, washed with brine and dried over Na2SO4. The crude product obtained upon concentration was dissolved in dry THF (10 vol) and thiourea (2.0 eq) was added and refluxed for overnight. The reaction mixture was diluted with ethyl acetate, washed with sodium thiosulfate solution and organic layer was treated with IN HCl to result salt formation of the amine. The precipitated salt was collected by filtration. The salt was then treated with saturated solution of NaHCO3 to re-generate the amine. The mixture was extracted with dichloromethane (2x 50 ml) and the combined organic extracts were washed with water and brine. The solvent was evaporated under reduced pressure to afford the 2-amino-4-aryl-thiazole derivative.
In PEG-400 at 20℃; for 1h;
In acetic acid for 2h; Reflux;
In ethanol at 20℃; Reflux; General procedure of 2-aminothiazole derivatives 2a-h General procedure: 2-Bromo-1-arylethanones (0.015 mol) were added to a solution of thiourea (1.5 g, 0.02 mol) in ethanol (50 mL).The mixture was reflux for 8 h and then cooled down to room temperature. The solvent was removed to half its volume in vacuum. The residue was brought to about pH 9 using ammonia. The mixture was extracted by EtOAc, and the extract was washed with saturated NaCl solution and dried over anhydrous Na2SO4. The solvent was removed in vacuum to give a precipitate which was crystallized from ethanol to afford the target compounds 2a-h.
In methanol
Reflux;
In ethanol Reflux; 1 4.1.4. General procedure B: synthesis of aminoarylthiazole analogues General procedure: Haloketones (1 eq) were conjugated with thioureas (1 eq) in anhydrous ethanol (EtOH) (1ml). Reaction was stirred at reflux from 2 to 24h until the reaction was judged complete (HPLC-MS). The mixture was then extracted with ethyl acetate (3×3ml). The organic phases were concentrated in vacuum and lyophilized. Products were verified by HPLC and MS and purified with preparative HPLC. Relevant fractions were collected and concentrated to afford the desired product in 40-95% yields, with purity of >95% as determined by HPLC-MS.
In ethanol Reflux;
In ethanol at 80℃; for 2h; General procedure for the synthesis of aminothiazoles 2a-2ah General procedure: To a mixture of olefin (0.5 mmol) and tween-80 (30 mL) in water (3 mL) was added DBH (214.5 mg, 0.75 mmol) at room temperature, and the mixture was stirred under the conditions as indicated in Table 1. After cooling to room temperature and removal of solvent under reduced pressure, EtOH (3 mL), thiourea (57.1 mg, 0.75 mmol) (or 0.75 mmol of N-methylthiourea/N-phenethylthiourea) were added to the mixture, and the obtained mixture was stirred for 2 h at 80 °C. The mixture was diluted with ethyl acetate (60 mL). The organic phase was washed with brine (10mL x 3) and dried over Na2SO4. After concentrated under reduced pressure, the residue was purified by preparative thin layer chromatography to afford the corresponding 2-aminothiazoles.
In methanol
In ethanol for 12h; Reflux; 1 2.3 General procedure B for the synthesis of 4′-substituted-4-aryl-2-aminothiazoles (3a-g) General procedure: A mixture of 4′-substituted-2-bromo acetophenones 2a-g (1 mmol) and thiourea (1.2 mmol, 0.0912 g) was refluxed in ethanol for 12h. Then, the reaction mixture was cooled and poured slowly into ice-cold water with constant stirring. The precipitate obtained was filtered, washed and dried. The crude product was recrystallized from ethanol to afford 4′-substituted 2-aminothiazoles 3a-g. The completion of reaction was monitored by TLC.
201.6 mg In ethyl acetate at 20℃; for 1h;
In ethanol for 5h; Reflux;
With triethylamine In ethanol Reflux;
With anhydrous Sodium acetate In ethanol at 20℃; for 4h;
In ethanol Reflux;
In ethanol at 25℃; Sonication; General procedure for the synthesis of aminothiazole Schiff base (Z1-Z16) General procedure: Appropriate substituted α-bromoacetophenone (10 mmol) was dissolved in anhydrous EtOH (30 mL), and the solution was added to a single neck flask and stirred at room temperature. Then thiourea (10 mmol) was added to the above mixture. The flask was placed in ultrasonic instrument. The reaction was performed by ultrasonic method for 10-15 min at 25 °C. Frequency and intensity were 40 Hz and 300 W respectively. The progress of reaction was tracked by thin layer chromatography (TLC). After the reaction was finished, the reaction solution was adjusted pH = 7 with ammonia water to afford precipitates. The precipitates were filtered, and then washed with 70% EtOH. The precipitates were recrystallized from EtOH. To a mixture of aminothiazole (1 mmol) and substituted benzaldehyde (1 mmol) in EtOH (15 mL), piperidine (0.2 mL) was added. The reaction mixture was refluxed for 1-12 h. The progress of reaction was tracked by TLC. When the reaction was finished, the reaction solution was cooled to room temperature. The precipitates were filtered and washed with EtOH to afford the corresponding aminothiazole Schiff base derivatives. Some compounds were further purified by column chromatography, and the petroleum ether/EtOAc (4:1-2:1) was used as eluent.
With triethylamine In ethanol at 20℃; for 3h; Reflux; General procedure of synthesis of 2-aminothiazolederivatives 3-6 General procedure: The mixture of phenacyl bromide derivatives 1 (0.1 mol) and thiourea 2 (0.11 mol) in anhydrous ethanol (100 ml) was heated at reflux for 3 h in presence of drops of trimethylamine (TEA). After that, the solvent was removed and a saturated aqueous NaHCO3 was added to adjust the pH to about 8-9. Then, the mixture was filtered to afford 3-6 as a white solids.
With triethylamine In ethanol at 20℃; for 3h; Reflux; General procedure of synthesis of 2-aminothiazolederivatives 3-6 General procedure: The mixture of phenacyl bromide derivatives 1 (0.1 mol) and thiourea 2 (0.11 mol) in anhydrous ethanol (100 ml) was heated at reflux for 3 h in presence of drops of trimethylamine (TEA). After that, the solvent was removed and a saturated aqueous NaHCO3 was added to adjust the pH to about 8-9. Then, the mixture was filtered to afford 3-6 as a white solids.

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[2]Current Patent Assignee: THE UNIVERSITY OF MILANO-BICOCCA; UNIVERSITY OF LYON; UNIVERSITY OF GENEVA - WO2015/1024, 2015, A1 Location in patent: Page/Page column 86
[3]Chellappa Subramanyam, Dwaraka Viswanath; Divi, Haranath; Godugu, Kumar; Gundala, Trivikram Reddy; Loka, Subramanyam Sarma; Mohinuddin Pinjari, Mohammad Khaja; Reddy Nallagondu, Chinna Gangi; Shaik, Sultana; Vemula, Venkatramu [Dyes and Pigments, 2021, vol. 187]
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[19]Ibatullin, U. G.; Petrushina, T. F.; Leitis, L. Ya; Minibaev, I. Z.; Logvin, B. O. [Chemistry of Heterocyclic Compounds, 1993, vol. 29, # 5, p. 612 - 616][Khimiya Geterotsiklicheskikh Soedinenii, 1993, # 5, p. 715 - 718]
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[23]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2010/109287, 2010, A1 Location in patent: Page/Page column 40-41
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[38]Nasli Esfahani, Anita; Iraji, Aida; Alamir, Amir; Moradi, Shahram; Asgari, Mohammad Sadegh; Hosseini, Samanesadat; Mojtabavi, Somayeh; Nasli-Esfahani, Ensieh; Faramarzi, Mohammad Ali; Bandarian, Fatemeh; Larijani, Bagher; Hamedifar, Haleh; Hajimiri, Mir Hamed; Mahdavi, Mohammad [Molecular Diversity, 2021]
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  • 4
  • [ 2103-94-8 ]
  • [ 79-04-9 ]
  • [ 6125-32-2 ]
YieldReaction ConditionsOperation in experiment
77% Stage #1: chloroacetyl chloride With triethylamine In tetrahydrofuran at 0℃; for 0.25h; Inert atmosphere; Stage #2: 4-(4-bromophenyl)-1,3-thiazol-2-amine In tetrahydrofuran at 0 - 20℃; for 13h; General procedure for the synthesis of N-(4-aryl-1,3-thiazol-2-yl)-2-chloro-acetamide 4a-e. General procedure: A solution of triethylamine (7.5 mmol in 5 mL of THF) was added to a twin-necked round-bottom flask under argon atmosphere, cooled to 0 °C, in a 2-chloroacetyl chloride solution (3 mmol in 3 mL of THF). The mixture was stirred for 15 min, followed by the addition of 2-amino-4-aryl-1,3-thiazole (1.5 mmol in 1 mL of THF). The reaction was kept under stirring for 1 h at 0 °C and for additionally 12 h at room temperature. Following the 12 h, the reaction content was diluted in dichloromethane (50 mL) and washed with aqueous 1M NaOH (2 x 10mL) and saturated aqueous NaCl (10 mL). The organic layer was dried over anhydrous MgSO4 and filtered. Finally, the solvent was removed under reduced pressure. When necessary, the crude product was purified by flash chromatography on silica gel, employing a mixture of hexane/ethyl acetate (70:30) as the eluent.
64% Stage #1: 4-(4-bromophenyl)-1,3-thiazol-2-amine With triethylamine In dichloromethane at 0 - 5℃; for 0.5h; Stage #2: chloroacetyl chloride In dichloromethane at 0 - 20℃; for 2h; The general procedure for the preparation of the known 2-(2-chloroacetamido)thiazoles (7) involved a modification of the procedure reported by Xu and collegues18. General procedure: A solution of 2-amino-4-phenylthiazole 6a (0.530 g, 3 mmol) and Et3N (560 μL, 4 mmol) in dichloromethane (15 mL) was cooled to 0-5 C in an ice-bath and stirred for 30 min. 2-Chloroacetyl chloride (578 μL, 6.6 mmol) in dry dichloromethane (1.5 mL) was then added slowly, and the reaction mixture was allowed to warm to room temperature and stirred until the amine was completely consumed (ca. 1 h, as monitored by TLC). The reaction mixture was diluted with dichloromethane and washed successively with water and saturated brine. The organic layer was dried over anhydrous Na2SO4, the solvent was removed under reduced pressure and the residue was recrystallised from ethanol to give compound 7a (0.413 g, 54%) as light-grey crystals, mp 170-171 oC (Lit.18,20,26 171-173 oC). The remaining analogues were obtained similarly [7b (100%) as a brown solid, mp 194-195 oC (Lit.27 mp not cited); 7c (64%) as a brown solid, mp 241-243 oC (Lit.27 mp not cited); 7d (64%) as a brown solid, mp 135-137 oC (Lit.28 135 oC); 7e (0.262 g, 88%) as a yellow solid, mp 174-176 C (Lit.29 175 oC); 7f (70%) as a light-brown solid, mp 213-216 oC (Lit.30 216 oC).
58% In benzene for 3h; Reflux;
51% With potassium carbonate In benzene for 4h;
In benzene
In acetone
With triethylamine In dichloromethane at 20℃; for 24h;
With triethylamine In dichloromethane at 20℃; for 4h;
With triethylamine In dichloromethane at 20℃; for 24h;

Reference: [1]Wolf, Lucas; Quoos, Natália; Mayer, João C.P.; De Souza, Diego; Sauer, André C.; Meichtry, Luana; Bortolotto, Vandreza; Prigol, Marina; Rodrigues, Oscar E.D.; Dornelles, Luciano [Tetrahedron Letters, 2016, vol. 57, # 9, p. 1031 - 1034]
[2]Olawode, Emmanuel O.; Tandlich, Roman; Prinsloo, Earl; Isaacs, Michelle; Hoppe, Heinrich; Seldon, Ronnett; Warner, Digby F.; Steenkamp, Vanessa; Kaye, Perry T. [Arkivoc, 2018, vol. 2018, # 7, p. 110 - 118]
[3]Alagarsamy; Senthilraja; Raja Solomon [Journal of Heterocyclic Chemistry, 2016, vol. 53, # 5, p. 1635 - 1639]
[4]Ibatullin, U. G.; Petrushina, T. F.; Leitis, L. Ya; Minibaev, I. Z.; Logvin, B. O. [Chemistry of Heterocyclic Compounds, 1993, vol. 29, # 5, p. 612 - 616][Khimiya Geterotsiklicheskikh Soedinenii, 1993, # 5, p. 715 - 718]
[5]Sharma,S.C. [Indian Journal of Chemistry, 1966, vol. 4, p. 33 - 36] Bhargava,P.N.; Ram,P. [Journal of the Indian Chemical Society, 1961, vol. 38, p. 167 - 168]
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[7]Wang, Guangcheng; Peng, Zhiyun; Gong, Zipeng; Li, Yongjun [Bioorganic Chemistry, 2018, vol. 78, p. 195 - 200]
[8]El-Dash, Yara; Elzayat, Emad; Abdou, Amr M.; Hassan, Rasha A. [Bioorganic Chemistry, 2021, vol. 114]
[9]Nasli Esfahani, Anita; Iraji, Aida; Alamir, Amir; Moradi, Shahram; Asgari, Mohammad Sadegh; Hosseini, Samanesadat; Mojtabavi, Somayeh; Nasli-Esfahani, Ensieh; Faramarzi, Mohammad Ali; Bandarian, Fatemeh; Larijani, Bagher; Hamedifar, Haleh; Hajimiri, Mir Hamed; Mahdavi, Mohammad [Molecular Diversity, 2021]
  • 5
  • [ 2103-94-8 ]
  • [ 614-23-3 ]
  • [ 113333-06-5 ]
YieldReaction ConditionsOperation in experiment
In acetone for 0.25h; Heating; Yield given;
  • 6
  • [ 2103-94-8 ]
  • [ 80-35-3 ]
  • [ 97855-03-3 ]
  • 7
  • [ 2103-94-8 ]
  • [ 526-08-9 ]
  • [ 97854-97-2 ]
  • 8
  • [ 2103-94-8 ]
  • [ 123-08-0 ]
  • [ 99756-62-4 ]
YieldReaction ConditionsOperation in experiment
40.8% With piperidine In ethanol Reflux; General procedure for the synthesis of aminothiazole Schiff base (Z1-Z16) General procedure: Appropriate substituted α-bromoacetophenone (10 mmol) was dissolved in anhydrous EtOH (30 mL), and the solution was added to a single neck flask and stirred at room temperature. Then thiourea (10 mmol) was added to the above mixture. The flask was placed in ultrasonic instrument. The reaction was performed by ultrasonic method for 10-15 min at 25 °C. Frequency and intensity were 40 Hz and 300 W respectively. The progress of reaction was tracked by thin layer chromatography (TLC). After the reaction was finished, the reaction solution was adjusted pH = 7 with ammonia water to afford precipitates. The precipitates were filtered, and then washed with 70% EtOH. The precipitates were recrystallized from EtOH. To a mixture of aminothiazole (1 mmol) and substituted benzaldehyde (1 mmol) in EtOH (15 mL), piperidine (0.2 mL) was added. The reaction mixture was refluxed for 1-12 h. The progress of reaction was tracked by TLC. When the reaction was finished, the reaction solution was cooled to room temperature. The precipitates were filtered and washed with EtOH to afford the corresponding aminothiazole Schiff base derivatives. Some compounds were further purified by column chromatography, and the petroleum ether/EtOAc (4:1-2:1) was used as eluent.
With piperidine In ethanol Heating; Yield given;
With acetic acid In ethanol
In ethanol Reflux;

  • 9
  • [ 2103-94-8 ]
  • [ 108-24-7 ]
  • [ 53173-91-4 ]
YieldReaction ConditionsOperation in experiment
72% With pyridine; aluminum oxide at 95 - 99℃; for 13h; microwave irradiation;
45.5% With sodium acetate Heating;
  • 10
  • [ 2103-94-8 ]
  • [ 98-88-4 ]
  • 2-(N-benzoylamino)-4-(4-bromophenyl)thiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
99% With pyridine; aluminum oxide at 81 - 83℃; for 0.0333333h; microwave irradiation;
With pyridine at 0 - 20℃; General procedure for the synthesis of 2-phenyl-N-(4-phenylthiazol-2-yl) acetamide derivatives 3a-3l and 4a-4l General procedure: For 3i,3l, 4i, 4l, the solution of amine 2a or 2b (1 mmol) in pyridine (2 mL) was added to a solution of acyl chloride (1 mmol) at 0 oC. The resultant mixture was warmed to room temperature and stirred for 3 h. Then oil was formed when the pyridine was removed at the vacuum. The oil washed with HCl to give a precipitate, which was collected and crystallized to get 3i, 3l, 4i, 4l.
With dmap In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere;
With triethylamine at 90℃; for 1h;

  • 11
  • [ 2103-94-8 ]
  • [ 1761-61-1 ]
  • 4-bromo-2-([4-(4-bromophenyl)thiazol-2-yl]imino}methyl)phenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
58.8% With piperidine In ethanol Reflux; General procedure for the synthesis of aminothiazole Schiff base (Z1-Z16) General procedure: Appropriate substituted α-bromoacetophenone (10 mmol) was dissolved in anhydrous EtOH (30 mL), and the solution was added to a single neck flask and stirred at room temperature. Then thiourea (10 mmol) was added to the above mixture. The flask was placed in ultrasonic instrument. The reaction was performed by ultrasonic method for 10-15 min at 25 °C. Frequency and intensity were 40 Hz and 300 W respectively. The progress of reaction was tracked by thin layer chromatography (TLC). After the reaction was finished, the reaction solution was adjusted pH = 7 with ammonia water to afford precipitates. The precipitates were filtered, and then washed with 70% EtOH. The precipitates were recrystallized from EtOH. To a mixture of aminothiazole (1 mmol) and substituted benzaldehyde (1 mmol) in EtOH (15 mL), piperidine (0.2 mL) was added. The reaction mixture was refluxed for 1-12 h. The progress of reaction was tracked by TLC. When the reaction was finished, the reaction solution was cooled to room temperature. The precipitates were filtered and washed with EtOH to afford the corresponding aminothiazole Schiff base derivatives. Some compounds were further purified by column chromatography, and the petroleum ether/EtOAc (4:1-2:1) was used as eluent.
In ethanol
  • 12
  • [ 2103-94-8 ]
  • [ 13089-11-7 ]
  • [ 1007583-24-5 ]
YieldReaction ConditionsOperation in experiment
44% Stage #1: 4-(4-bromophenyl)-1,3-thiazol-2-amine; methyl 3,3,3-trifluoropyruvate In dichloromethane for 0.25h; Stage #2: With sodium tris(acetoxy)borohydride In methanol; dichloromethane for 0.25h; 64.1 Step 1: Methyl N-[4-(4-bromophenyl)-1,3-thiazol-2-yl]-3,3,3-trifluoroalaninate 4-(4-Bromophenyl)-1,3-thiazol-2-ylamine (510 mg, 2.0 mmol) and methyl-3,3,3-trifluoropyruvate (0.10 mL, 1.0 mmol) were dissolved in 50 mL methylene chloride. Titanium (IV) chloride (1M in toluene, 1.6 mL, 1.6 mmol) was added dropwise to give an orange-brown suspension. The mixture was stirred for 15 min and then added by cannula to a solution of sodium cyanoborohydride (0.26 g, 3.0 mmol) in 50 mL of methanol. The mixture was stirred for 15 min and then quenched by the addition of H2O and saturated aqueous sodium bicarbonate. The mixture was extracted three times with methylene chloride. The organics were combined, washed with water, brine, dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. Flash chromatography (100% methylene chloride) afforded methyl N-[4-(4-bromophenyl)-1,3-thiazol-2-yl]-3,3,3-trifluoroalaninate (0.17 g, 44%) as a white solid. MS (ES) m/z 392.8.
  • 13
  • [ 2103-94-8 ]
  • [ 13831-31-7 ]
  • [ 901347-68-0 ]
YieldReaction ConditionsOperation in experiment
42% With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 2h; 77.1 Step 1: 2-[4-(4-Bromophenyl)-1,3-thiazol-2-yl]amino}-2-oxoethyl acetate4-(4-Bromophenyl)-1,3-thiazol-2-ylamine (2.00 g, 7.84 mmol) was dissolved in methylene chloride, diisopropylethylamine (1.50 mL, 8.62 mmol) was added and the mixture was cooled to 0° C. Acetoxy acetyl chloride (0.920 mL, 8.62 mmol) was added dropwise, the mixture was stirred for 2 h and then diluted with ethyl acetate. The mixture was washed with NaHCO3, water, brine, dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. Flash chromatography (20% acetone/hexane) followed by recrystallization from acetone/hexane afforded 1.16 g of 2-[4-(4-bromophenyl)-1,3-thiazol-2-yl]amino}-2-oxoethyl acetate (1.16 g, 42%) as a white solid. HRMS: calcd for C13H, BrN2O3S+H+, 354.97465; found (ESI, [M+H]+), 354.9738. Analytical HPLC: retention time 9.8 min, 210-370 nm the Xterra RP18 column, 3.5%, 150×4.6 mm 40° C. 85/15-5/95 (Ammon. Form. Buff. pH=3.5/ACN+MeOH) for 10 min, hold 4 min, 1.2 mL/min 5 μL injection.
  • 14
  • [ 2103-94-8 ]
  • [ 25015-63-8 ]
  • [ 269410-17-5 ]
YieldReaction ConditionsOperation in experiment
Stage #1: With triethylamine In 1,4-dioxane at 80℃; for 18h; Stage #2: 4-(4-bromophenyl)-1,3-thiazol-2-amine; 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane In 1,4-dioxane at 80℃; for 48h; 66 4-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1,3-thiazol-2-amine [00397] In a reaction tube under nitrogen, a mixture of PdCl2(dppf)CH2Cl2 (21 mg; 0.026 mmol) and triethylamine (0.34 ml; 2.44 mmol) in dioxane (2.5 ml; dried over 4 A sieves) was sealed and stirred at 80 C. overnight (18 h). After cooling to room temperature, HB(pin) (0.32 ml; 2.21 mmol) was added followed by 2-amino-4-(4-bromophenyl)thiazole (213 mg; 0.858 mmol) in dioxane (2.5 ml; dried over 4 A sieves) the reaction mixture was stirred at 80 C. GC analysis after 2 days showed the desired borate compound at 17.5 minutes.
  • 15
  • [ 4209-02-3 ]
  • [ 17356-08-0 ]
  • [ 2103-94-8 ]
YieldReaction ConditionsOperation in experiment
In ethanol;Heating / reflux; N-[4-(4-Bromophenyl)thiazol-2-yll-l-naphthamide (Compound 101)This compound was prepared as described in Scheme I. 1H NMR (500 MHz, CDCl3) 10.53 (s, IH), 8.42 (m, IH), 7.93 (m, IH), 7.87 (m, IH), 7.71 (dd, J = 7.1, 1.2 Hz, IH), 7.61 (ddd, J = 8.3, 6.8, 1.5 Hz, IH), 7.57 (ddd, J = 8.1, 6.8, 1.5 Hz, IH), 7.51 (d, J = 8.7 Hz, 2H), 7.40 (dd, J = 8.2, 7.1 Hz, IH), 7.33 (d, J = 8.7 Hz, 2H), 7.17 (s, IH).
  • 16
  • [ 2103-94-8 ]
  • [ 86-55-5 ]
  • [ 433708-65-7 ]
YieldReaction ConditionsOperation in experiment
64% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h; General procedure for the synthesis of acetamide derivatives 4i-4l and 5i-5l General procedure: The key intermediates 3a or 3b (1 mmol), corresponding acids (1 mmol) and carbodiimide hydrochloride (EDC*HCl,1.5 mmol) and N-hydroxybenzotriazole (HOBt, 0.05 mmol) were stirred in CH2Cl2 (20-30 mL) at room temperature for 24 h. After that, the solvent was evaporated under reduced pressure to afford a residue, which was extracted with EtOAc (3 x 20 mL). The combined organic phases were dried with anhydrous Na2SO4. Removal of all the solvent under reduced pressure distillation to get the residue, which was purified with recrystallization to give target products 4i-4l and 5i-5l.
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h; General procedure for the synthesis of 2-phenyl-N-(4-phenylthiazol-2-yl) acetamide derivatives 3a-3l and 4a-4l General procedure: For the synthesis of compounds 3a-3h, 3j, 3k, 4a-4h, 4j, 4k, a mixtureof corresponding acids (1 mmol), 4-phenylthiazol-2-ylamine derivatives (2a or 2b, 1 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl, 1.5 mmol), 1-hydroxybenzotrizole (HOBt, 0.05 mmol) in CH2Cl2 (20-30mL) was stirred at room temperature for 24 h. After that, the solvent was removed in vacuo to afford a residue, which was extracted with EtOAc (3 ×20mL). The combined organic phases were dried with anhydrous Na2SO4. Removal of all the solvent in vacuo resulted in a residue, which was purified with recrystallization to give target products.
With pyridine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide Heating / reflux; 1 N-[4-(4-Bromophenyl)thiazol-2-yll-l-naphthamide (Compound 101); This compound was prepared as described in Scheme I. 1H NMR (500 MHz, CDCl3) 10.53 (s, IH), 8.42 (m, IH), 7.93 (m, IH), 7.87 (m, IH), 7.71 (dd, J = 7.1, 1.2 Hz, IH), 7.61 (ddd, J = 8.3, 6.8, 1.5 Hz, IH), 7.57 (ddd, J = 8.1, 6.8, 1.5 Hz, IH), 7.51 (d, J = 8.7 Hz, 2H), 7.40 (dd, J = 8.2, 7.1 Hz, IH), 7.33 (d, J = 8.7 Hz, 2H), 7.17 (s, IH).
  • 17
  • [ 2103-94-8 ]
  • [ 598-21-0 ]
  • [ 37614-89-4 ]
YieldReaction ConditionsOperation in experiment
With pyridine In dichloromethane at 0 - 20℃; General procedure for the preparation of 2-bromo-N-thiazolyl acetamide derivatives (Intermediate 7a, Scheme 2):Some of the (2-amino-4-aryl)thiazoles used for the synthesis of 2-bromo-N- thiazolyl acetamides of general formula (7a) were not commercially available and were prepared from appropriately substituted acetophenones and thiourea as described below. Step 1: A mixture of appropriate aryl alkyl ketone (1.0 equiv.), thiourea (2.0 eqiv.) and iodine (1.0 equiv.) in dry ethanol (5 volumes) was refluxed for 24h. The reaction mixture was diluted with ethyl acetate and washed with saturated solution of sodium thiosulphate.The organic layer was treated with IN HCl and the precipitated salt collected by filtration. The salt was then treated with saturated solution OfNaHCO3 and extracted with dichloromethane, washed with brine, dried over sodium sulfate and the solvent was evaporated to afford the 2-aminothiazole derivative.Step 2: To a stirred and cooled (O 0C) solution of appropriate amine (1.0 equiv.) and pyridine (1.2 equiv.) in dichloromethane (5 volume) was added bromoacetyl bromide (1.2 eq.) over 5 min and the resulting mixture was allowed to warm to room temperature and then further stirred at room temperature for 2 h. The reaction mixture was diluted with dichloromethane (50 ml) and water (50 ml). The layers were separated. The aqueous layer was extracted with dichloromethane (2 x 50 ml) and the combined organic layers were washed with water (2 x 50 ml) followed by brine (50 ml), dried (Na2SO4) and filtered. The filtrate was concentrated under reduced pressure. The residue obtained after the evaporation of the solvent was purified by silica gel column chromatography using 5-10% ethyl acetate in petroleum ether to obtain the desired product as an off-white solid.
  • 18
  • [ 2103-94-8 ]
  • [ 1203712-34-8 ]
  • [ 1203712-50-8 ]
YieldReaction ConditionsOperation in experiment
With 1-hydroxy-pyrrolidine-2,5-dione; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 80℃; for 24h; Inert atmosphere; 10 To a stirred solution of Intermediate 2 (100 mg, 0.399 mmol) in dimethylfbrmamide (5 ml) was added 4-(4-bromophenyl)-l,3-thiazol-2-amine (122 mg, 0.679 mmol) followed by dicyclohexyl carbodimide (122 mg, 0.598 mmol) and iV-hydroxysuccinimide (67 mg, 0.598 mmol). The reaction mixture was heated to 80°C under nitrogen for 24 h. The reaction mixture was cooled to room temperature and the residue was filtered through a celite bed. The product was extracted with ethyl acetate (3 x 50 ml) and the combined organic layers were washed by water, brine and dried (Na2SO4). The crude product obtained after evaporation under reduced pressure was purified by silica gel column chromatography using 5% ethyl acetate in petroleum ether to give 79 mg of the product as an off-white solid; 1H NMR (300 MHz, CDCl3) δ 1.45-1.55 (m, 2H), 1.58-1.70 (m, 2H), 1.84-1.90 (m, IH), 1.98-2.10 (m, 2H), 2.16-2.22 (m, IH), 2.31-2.38 (m, IH), 2.77 (dd, J= 4.2, 10.8 Hz, IH), 3.40 (br s, IH), 6.56 (d, J= 8.7 Hz, IH), 6.72-6.79 (m, 2H), 7.13 (s, IH), 7.47 (d, J= 8.1 Hz, 2H), 7.60 (d, J= 8.4 Hz, 2H), 10.42 (br s, IH).
With 1-hydroxy-pyrrolidine-2,5-dione; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 80℃; for 24h; Inert atmosphere; 10 Example 10N-[4-(4-Bromophenyl)-1,3-thiazol-2-yl]-2-(6-fluoro-3,4-dihydrospiro[chromene-2,1'-cyclobutan]-4-yl)acetamideTo a stirred solution of Intermediate 2 (100 mg, 0.399 mmol) in dimethylformamide (5 ml) was added 4-(4-bromophenyl)-1,3-thiazol-2-amine (122 mg, 0.679 mmol) followed by dicyclohexyl carbodimide (122 mg, 0.598 mmol) and N-hydroxysuccinimide (67 mg, 0.598 mmol). The reaction mixture was heated to 80° C. under nitrogen for 24 h. The reaction mixture was cooled to room temperature and the residue was filtered through a celite bed. The product was extracted with ethyl acetate (3×50 ml) and the combined organic layers were washed by water, brine and dried (Na2SO4). The crude product obtained after evaporation under reduced pressure was purified by silica gel column chromatography using 5% ethyl acetate in petroleum ether to give 79 mg of the product as an off-white solid; 1H NMR (300 MHz, CDCl3) δ 1.45-1.55 (m, 2H), 1.58-1.70 (m, 2H), 1.84-1.90 (m, 1H), 1.98-2.10 (m, 2H), 2.16-2.22 (m, 1H), 2.31-2.38 (m, 1H), 2.77 (dd, J=4.2, 10.8 Hz, 1H), 3.40 (br s, 1H), 6.56 (d, J=8.7 Hz, 1H), 6.72-6.79 (m, 2H), 7.13 (s, 1H), 7.47 (d, J=8.1 Hz, 2H), 7.60 (d, J=8.4 Hz, 2H), 10.42 (br s, 1H).
  • 19
  • [ 2103-94-8 ]
  • [ 924624-36-2 ]
  • Butyric acid 4-{2-[4-(4-bromo-phenyl)-thiazol-2-ylcarbamoyl]-vinyl}-2-methoxy-phenyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
29% Stage #1: Butyric acid 4-(2-carboxy-vinyl)-2-methoxy-phenyl ester With oxalyl dichloride In dichloromethane at 20℃; for 0.5h; Stage #2: 4-(4-bromophenyl)-1,3-thiazol-2-amine With pyridine In 1,4-dioxane at 100℃; for 1h; 2.20 Compound 20. Butyric acid 4-{2-[4-(4-bromo-phenyl)-thiazol-2-ylcarbamoyl]-vinyl}-2-methoxy-phenyl ester (B240827) 4-Butanoyl3-methoxycinnamic acid (91 mg, 0.34 mmol) was suspended in dichloromethane (5 mL) DMF (50 μL) and 2 M oxalyl chloride in CH2Cl2 (0.6 mL) were added to it at RT. The suspension became a yellowish solution. After 0.5 hour stirring, the solvent was removed in vacuo. The residue was dissolved in dioxane (5 mL). 2-Amino-4-(4-bromophenyl)thiazole (133 mg, 0.52 mmol) was added to it, followed by addition of pyridine (100 uL). The mixture was heated at 100° C. for one hour. After cooling down to RT, the solvent was removed in vacuo. The residue was dissolved in EtOAc (50 mL) and washed with water (50 mL). The EtOAc solution was dried over sodium sulfate. After filtration and concentration, the residue was purified by chromatography eluted with CHCl3. The collected fractions were concentrated and purified again by chromatotron (silica) eluted with CHCl3 to afford the solid product (50 mg, Y=29%). NMR confirmed it was the compound
  • 20
  • [ 2103-94-8 ]
  • [ 1335010-92-8 ]
  • [ 1335010-33-7 ]
YieldReaction ConditionsOperation in experiment
Stage #1: (5,7-dimethyl-4,6-dioxo-4,5,6,7-tetrahydroisoxazolo[3,4-d]pyrimidin-3-yl)acetic acid With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In 1,2-dichloro-ethane at 20℃; for 0.25h; Stage #2: 4-(4-bromophenyl)-1,3-thiazol-2-amine In 1,2-dichloro-ethane Inert atmosphere; 78 General procedure for the preparation of Examples (78-109):Method A: To a stirred solution of isoxazole acetic acid (1.0 equiv.) in 1,2-dichloroethane was added EDCI (1.2 equiv.), HOBt (0.3 equiv.) and 4-dimethylaminopyridine (0.1 equiv.) and the mixture was stirred at room temperature for 10-15 min. An appropriate amine (1.0 equiv.) was then added and mixture was stirred under nitrogen atmosphere at the same temperature for 48 h or heated at reflux temperature for 24 h. The solvent was evaporated under reduced pressure and the residue obtained was diluted with methanol and stirred at room temperature for 30 min. The solid separated out was collected by filtration. The solid product was further purified by recrystalisation from isopropanol or methanol to give the desired products.Example 78N-[4-(4-Bromophenyl)-l,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-4,5,6,7- tetrahydro[l,2]oxazolo[3,4-i/|pyrimidin-3-yl)acetamideThe title compound was prepared according to the general procedure (Method A) by coupling Intermediate 10 (200 mg, 0.836 mmol) with 4-(4-bromophenyl)-l,3-thiazol-2- amine (214 mg, 0.836 mmol) in the presence of EDCI hydrochloride (192 mg, 1.003 mmol), HOBt (34 mg, 0.250 mmol) and DMAP (10 mg, 0.083 mmol) in 1,2- dichloroethane (8.3 ml) at room temperature to give 30 mg of the product as an off-white solid; NMR (300 MHz, DMSO-i 6): δ 3.17 (s, 3H), 3.34 (s, 3H), 4.47 (s, 2H), 7.64 (d, J = 8.1 Hz, 2H), 7.75 (s, 1H), 7.86 (d, J = 8.4 Hz, 2H), 12.80 (br s, 1H); ESI-MS (m/z) 476.01 (M+H)+.
  • 21
  • [ 81585-72-0 ]
  • [ 17356-08-0 ]
  • [ 2103-94-8 ]
YieldReaction ConditionsOperation in experiment
With iodine; copper(II) oxide In ethanol at 78℃; 4.2. General procedure for preparation of 3 and 5 (3a as an example) General procedure: A mixture of acetophenone 1a (120 mg, 1 mmol), iodine (279.2 mg, 1.1 mmol), and CuO (88 mg, 1.1 mmol) in anhydrous ethanol (30 mL) was heated at reflux, after disappearance of the reactant (1-12 h, monitored by TLC), thiourea 2 (76 mg, 1 mmol) was added and the mixture was refluxed for 1 h. After that, the solvent was removed under reduce pressure, and added 50 mL water to the residue, then extracted with EtOAc three times (3×50 mL). The extract was washed with 10% Na2S2O3 then a small amount 5% NaOH solution, dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel using petroleum ether/EtOAc as the eluent to give the expected products 3a in 90% yield.
  • 22
  • [ 2103-94-8 ]
  • [ 79-04-9 ]
  • C17H24N10O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
66% With potassium carbonate In toluene at 20℃; for 24h; N-[4-(4-bromophenyl)-1,3-thiazol-2-yl]-2-chloro-acetamide (9) and N-[4-(4-bromophenyl)-1,3-thiazol-2-yl]-3-chloro-propanamide(10) General procedure: A solution of 2-amino-4-(4-bromophenyl)-1,3-thiazole (6, 2.5 g, 0.01 mol) in dry toluene (50 ml), potassium carbonate (2.07 g, 0.015 mol) was stirred at room temperature, while 2-chloroacetyl chloride (7, 1.7 g, 1.2 ml, 0.015 mol) or 3-chloropropionyl chloride (8, 1.9 g, 1.4 ml. 0.015 mol), was added dropwise. Stirring continued for 24 h, solvent was then removed in vacuo and the residue obtained was triturated with water, filtered, dried and recrystallized (Table 1). 9:1H-NMR (DMSO-d6)δ3.34 (s, 1H, NH), 4.03 (s, 2H, CH2), 7.17(s, 1H, thiazole-H), 7.52 (d, 2H, J = 8.5 Hz, Ar-H), 7.82 (d, 2H, J = 8.5Hz, Ar-H).13C-NMR δ 38.9, 39.9, 47.6, 62.9, 105.8, 127.4, 128.0, 129.5, 131.1, 145.2, 170.2. MS m/z (%): 332 (25, M+). 10:1H-NMR (DMSO-d6) δ3.04 (t, 2H, J = 12 Hz,CH2CH2), 4.12 (t, 2H, J = 12 Hz,CH2CH2), 7.22 (s, 1H, thiazole-H), 7.52 (d, 2H, J = 7.5 Hz, Ar-H), 7.91 (d, 2H, J = 7.5 Hz, Ar-H), 9.32 (s, 1H, NH). 13C-NMR δ 38.5, 39.4, 40.0, 46.9, 63.0, 104.3, 128.0, 128.8, 129.4, 131.5, 145,6, 171.3. MS m/z (%): 345 (13.1, M+)
  • 23
  • [ 2103-94-8 ]
  • [ 625-36-5 ]
  • [ 545364-91-8 ]
YieldReaction ConditionsOperation in experiment
60% With potassium carbonate In toluene at 20℃; for 24h; N-[4-(4-bromophenyl)-1,3-thiazol-2-yl]-2-chloro-acetamide (9) and N-[4-(4-bromophenyl)-1,3-thiazol-2-yl]-3-chloro-propanamide(10) General procedure: A solution of 2-amino-4-(4-bromophenyl)-1,3-thiazole (6, 2.5 g, 0.01 mol) in dry toluene (50 ml), potassium carbonate (2.07 g, 0.015 mol) was stirred at room temperature, while 2-chloroacetyl chloride (7, 1.7 g, 1.2 ml, 0.015 mol) or 3-chloropropionyl chloride (8, 1.9 g, 1.4 ml. 0.015 mol), was added dropwise. Stirring continued for 24 h, solvent was then removed in vacuo and the residue obtained was triturated with water, filtered, dried and recrystallized (Table 1). 9:1H-NMR (DMSO-d6)δ3.34 (s, 1H, NH), 4.03 (s, 2H, CH2), 7.17(s, 1H, thiazole-H), 7.52 (d, 2H, J = 8.5 Hz, Ar-H), 7.82 (d, 2H, J = 8.5Hz, Ar-H).13C-NMR δ 38.9, 39.9, 47.6, 62.9, 105.8, 127.4, 128.0, 129.5, 131.1, 145.2, 170.2. MS m/z (%): 332 (25, M+). 10:1H-NMR (DMSO-d6) δ3.04 (t, 2H, J = 12 Hz,CH2CH2), 4.12 (t, 2H, J = 12 Hz,CH2CH2), 7.22 (s, 1H, thiazole-H), 7.52 (d, 2H, J = 7.5 Hz, Ar-H), 7.91 (d, 2H, J = 7.5 Hz, Ar-H), 9.32 (s, 1H, NH). 13C-NMR δ 38.5, 39.4, 40.0, 46.9, 63.0, 104.3, 128.0, 128.8, 129.4, 131.5, 145,6, 171.3. MS m/z (%): 345 (13.1, M+)
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0 - 20℃; 4.1.3. General procedure for preparation of intermediates 10a-s General procedure: To synthesize intermediates 10a-s, aminothiazoles 9a-r andDIPEA in THFwas cooled to 0 C, and added with 3-chloropropanoylchloride THF solution dropwise. After overnight reaction, the reactionmixture was evaporated to dryness, extracted with EtOAc,washed with saturated brine. The crude product was purified byflash silica chromatography.
  • 24
  • [ 2103-94-8 ]
  • [ 14559-87-6 ]
  • [ 1415695-77-0 ]
YieldReaction ConditionsOperation in experiment
13% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 140℃; for 0.5h; Microwave irradiation;
  • 25
  • [ 103-82-2 ]
  • [ 2103-94-8 ]
  • [ 299405-68-8 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h; General procedure for the synthesis of 2-phenyl-N-(4-phenylthiazol-2-yl) acetamide derivatives 3a-3l and 4a-4l General procedure: For the synthesis of compounds 3a-3h, 3j, 3k, 4a-4h, 4j, 4k, a mixtureof corresponding acids (1 mmol), 4-phenylthiazol-2-ylamine derivatives (2a or 2b, 1 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl, 1.5 mmol), 1-hydroxybenzotrizole (HOBt, 0.05 mmol) in CH2Cl2 (20-30mL) was stirred at room temperature for 24 h. After that, the solvent was removed in vacuo to afford a residue, which was extracted with EtOAc (3 ×20mL). The combined organic phases were dried with anhydrous Na2SO4. Removal of all the solvent in vacuo resulted in a residue, which was purified with recrystallization to give target products.
  • 26
  • [ 2103-94-8 ]
  • [ 405-50-5 ]
  • [ 922700-48-9 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h; General procedure for the synthesis of 2-phenyl-N-(4-phenylthiazol-2-yl) acetamide derivatives 3a-3l and 4a-4l General procedure: For the synthesis of compounds 3a-3h, 3j, 3k, 4a-4h, 4j, 4k, a mixtureof corresponding acids (1 mmol), 4-phenylthiazol-2-ylamine derivatives (2a or 2b, 1 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl, 1.5 mmol), 1-hydroxybenzotrizole (HOBt, 0.05 mmol) in CH2Cl2 (20-30mL) was stirred at room temperature for 24 h. After that, the solvent was removed in vacuo to afford a residue, which was extracted with EtOAc (3 ×20mL). The combined organic phases were dried with anhydrous Na2SO4. Removal of all the solvent in vacuo resulted in a residue, which was purified with recrystallization to give target products.
  • 27
  • [ 1878-66-6 ]
  • [ 2103-94-8 ]
  • [ 433967-00-1 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h; General procedure for the synthesis of 2-phenyl-N-(4-phenylthiazol-2-yl) acetamide derivatives 3a-3l and 4a-4l General procedure: For the synthesis of compounds 3a-3h, 3j, 3k, 4a-4h, 4j, 4k, a mixtureof corresponding acids (1 mmol), 4-phenylthiazol-2-ylamine derivatives (2a or 2b, 1 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl, 1.5 mmol), 1-hydroxybenzotrizole (HOBt, 0.05 mmol) in CH2Cl2 (20-30mL) was stirred at room temperature for 24 h. After that, the solvent was removed in vacuo to afford a residue, which was extracted with EtOAc (3 ×20mL). The combined organic phases were dried with anhydrous Na2SO4. Removal of all the solvent in vacuo resulted in a residue, which was purified with recrystallization to give target products.
  • 28
  • [ 2103-94-8 ]
  • [ 1878-68-8 ]
  • [ 926570-28-7 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h; General procedure for the synthesis of 2-phenyl-N-(4-phenylthiazol-2-yl) acetamide derivatives 3a-3l and 4a-4l General procedure: For the synthesis of compounds 3a-3h, 3j, 3k, 4a-4h, 4j, 4k, a mixtureof corresponding acids (1 mmol), 4-phenylthiazol-2-ylamine derivatives (2a or 2b, 1 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl, 1.5 mmol), 1-hydroxybenzotrizole (HOBt, 0.05 mmol) in CH2Cl2 (20-30mL) was stirred at room temperature for 24 h. After that, the solvent was removed in vacuo to afford a residue, which was extracted with EtOAc (3 ×20mL). The combined organic phases were dried with anhydrous Na2SO4. Removal of all the solvent in vacuo resulted in a residue, which was purified with recrystallization to give target products.
  • 29
  • [ 2103-94-8 ]
  • [ 1878-65-5 ]
  • [ 1446490-40-9 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h; General procedure for the synthesis of 2-phenyl-N-(4-phenylthiazol-2-yl) acetamide derivatives 3a-3l and 4a-4l General procedure: For the synthesis of compounds 3a-3h, 3j, 3k, 4a-4h, 4j, 4k, a mixtureof corresponding acids (1 mmol), 4-phenylthiazol-2-ylamine derivatives (2a or 2b, 1 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl, 1.5 mmol), 1-hydroxybenzotrizole (HOBt, 0.05 mmol) in CH2Cl2 (20-30mL) was stirred at room temperature for 24 h. After that, the solvent was removed in vacuo to afford a residue, which was extracted with EtOAc (3 ×20mL). The combined organic phases were dried with anhydrous Na2SO4. Removal of all the solvent in vacuo resulted in a residue, which was purified with recrystallization to give target products.
  • 30
  • [ 2103-94-8 ]
  • [ 1878-67-7 ]
  • [ 1446490-42-1 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h; General procedure for the synthesis of 2-phenyl-N-(4-phenylthiazol-2-yl) acetamide derivatives 3a-3l and 4a-4l General procedure: For the synthesis of compounds 3a-3h, 3j, 3k, 4a-4h, 4j, 4k, a mixtureof corresponding acids (1 mmol), 4-phenylthiazol-2-ylamine derivatives (2a or 2b, 1 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl, 1.5 mmol), 1-hydroxybenzotrizole (HOBt, 0.05 mmol) in CH2Cl2 (20-30mL) was stirred at room temperature for 24 h. After that, the solvent was removed in vacuo to afford a residue, which was extracted with EtOAc (3 ×20mL). The combined organic phases were dried with anhydrous Na2SO4. Removal of all the solvent in vacuo resulted in a residue, which was purified with recrystallization to give target products.
  • 31
  • [ 2103-94-8 ]
  • [ 1798-09-0 ]
  • [ 926458-30-2 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h; General procedure for the synthesis of 2-phenyl-N-(4-phenylthiazol-2-yl) acetamide derivatives 3a-3l and 4a-4l General procedure: For the synthesis of compounds 3a-3h, 3j, 3k, 4a-4h, 4j, 4k, a mixtureof corresponding acids (1 mmol), 4-phenylthiazol-2-ylamine derivatives (2a or 2b, 1 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl, 1.5 mmol), 1-hydroxybenzotrizole (HOBt, 0.05 mmol) in CH2Cl2 (20-30mL) was stirred at room temperature for 24 h. After that, the solvent was removed in vacuo to afford a residue, which was extracted with EtOAc (3 ×20mL). The combined organic phases were dried with anhydrous Na2SO4. Removal of all the solvent in vacuo resulted in a residue, which was purified with recrystallization to give target products.
  • 32
  • [ 2103-94-8 ]
  • [ 38464-04-9 ]
  • [ 1446490-45-4 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h; General procedure for the synthesis of 2-phenyl-N-(4-phenylthiazol-2-yl) acetamide derivatives 3a-3l and 4a-4l General procedure: For the synthesis of compounds 3a-3h, 3j, 3k, 4a-4h, 4j, 4k, a mixtureof corresponding acids (1 mmol), 4-phenylthiazol-2-ylamine derivatives (2a or 2b, 1 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl, 1.5 mmol), 1-hydroxybenzotrizole (HOBt, 0.05 mmol) in CH2Cl2 (20-30mL) was stirred at room temperature for 24 h. After that, the solvent was removed in vacuo to afford a residue, which was extracted with EtOAc (3 ×20mL). The combined organic phases were dried with anhydrous Na2SO4. Removal of all the solvent in vacuo resulted in a residue, which was purified with recrystallization to give target products.
  • 33
  • [ 2103-94-8 ]
  • [ 93-09-4 ]
  • [ 461410-43-5 ]
YieldReaction ConditionsOperation in experiment
67% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h; General procedure for the synthesis of acetamide derivatives 4i-4l and 5i-5l General procedure: The key intermediates 3a or 3b (1 mmol), corresponding acids (1 mmol) and carbodiimide hydrochloride (EDC*HCl,1.5 mmol) and N-hydroxybenzotriazole (HOBt, 0.05 mmol) were stirred in CH2Cl2 (20-30 mL) at room temperature for 24 h. After that, the solvent was evaporated under reduced pressure to afford a residue, which was extracted with EtOAc (3 x 20 mL). The combined organic phases were dried with anhydrous Na2SO4. Removal of all the solvent under reduced pressure distillation to get the residue, which was purified with recrystallization to give target products 4i-4l and 5i-5l.
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h; General procedure for the synthesis of 2-phenyl-N-(4-phenylthiazol-2-yl) acetamide derivatives 3a-3l and 4a-4l General procedure: For the synthesis of compounds 3a-3h, 3j, 3k, 4a-4h, 4j, 4k, a mixtureof corresponding acids (1 mmol), 4-phenylthiazol-2-ylamine derivatives (2a or 2b, 1 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl, 1.5 mmol), 1-hydroxybenzotrizole (HOBt, 0.05 mmol) in CH2Cl2 (20-30mL) was stirred at room temperature for 24 h. After that, the solvent was removed in vacuo to afford a residue, which was extracted with EtOAc (3 ×20mL). The combined organic phases were dried with anhydrous Na2SO4. Removal of all the solvent in vacuo resulted in a residue, which was purified with recrystallization to give target products.
  • 34
  • [ 2103-94-8 ]
  • [ 383-53-9 ]
  • [ 1449488-33-8 ]
YieldReaction ConditionsOperation in experiment
41% With sodium hydrogencarbonate In ethanol for 8h; Reflux; 4 General procedure: To a solution of 2-aminoheteroarene (10mmol) in ethanol (50mL), phenacyl bromide (10mmol) and NaHCO3 (30mmol) were added at rt and the reaction mixture was refluxed for 8h. On removal of solvent, the residue was dissolved with ethyl acetate (100mL) and washed with water (50mL), brine (50mL), and dried over sodium sulfate. The solvent was evaporated to give crude product, which was purified by combiflash chromatography (1-20% EtOAc/PE) to give the desired product 3-(4-bromophenyl)-6-(4-(trifluoromethyl)phenyl)imidazo[2,1-b]thiazole (4f) Isolated yield 41%; Rf (1:4 EtOAc/PE) 0.71; off white solid: mp 192-194 °C; 1H NMR (300 MHz, CDCl3) δ (ppm): 6.86 (s, 1H), 7.57 (d, J=8.4 Hz, 2H), 7.67 (d, J=8.4 Hz, 2H), 7.72 (d, J=8.4 Hz, 2H), 7.94 (s, 1H), 7.96 (d, J=8.1 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ (ppm): 108.1, 109.4, 122.5, 124.0, 125.3 (*2C), 125.8 (q), 128.4, 128.6, 129.0, 129.5, 131.5, 132.7, 137.4, 146.5, 150.5; HRMS (ESI): m/z [M+H]+ calcd for C18H11BrF3N2S: 422.9773, found 422.9768; HPLC: 99.2%.
  • 35
  • [ 2103-94-8 ]
  • [ 28081-52-9 ]
  • [ 1458056-16-0 ]
YieldReaction ConditionsOperation in experiment
44% With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 49h; Cooling with ice; S6. General procedure for synthesis of analogs 1a-1t and 11a-11i General procedure: To a 100 ml RBF, compound 6a (10 mmol), heterocyclic amine (2.18 g, 10 mmol) and TBTU (3.21 g, 10 mmol) and dry CH2Cl2 (15 ml) were taken and the contents of the flask were cooled in an ice-bath. DIPEA (8.9 ml, 50 mmol) was added drop wise to the flask over a 1-hr period. The reaction mixture became clear after complete addition. The ice-bath was removed and the reaction mixture was stirred at room temperature for 48 hrs. The white solid (precipitated out of the reaction mixture) was filtered and washed with water (20 ml). The crude products were directly recrystallised from boiling 1,4-dioxane.
  • 36
  • [ 875-97-8 ]
  • [ 2103-94-8 ]
  • [ 1449015-98-8 ]
YieldReaction ConditionsOperation in experiment
67% Stage #1: 2-(2,4-dioxothiazolidin-5-yl)acetic acid With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate In dichloromethane at 0℃; for 0.75h; Stage #2: 4-(4-bromophenyl)-1,3-thiazol-2-amine With N-ethyl-N,N-diisopropylamine In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃; for 11h; 4.1.3. General procedure for the synthesis of N-(4-aryl-1,3-thiazol-2-yl)-2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamides (4a-k) and N-(1,3-benzothiazol-2-yl)-2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamide derivatives (4l-o) General procedure: The general protocol followed by us in obtaining 2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamide compounds 4a-o is illustrated for the synthesis of N-(4-phenyl-1,3-thiazol-2-yl)-2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamide (4a) as an example. A solution of compound 1 (0.4 g, 2.55 mmol) in DCM (10 mL) is cooled to 0 °C and then charged with HOBT (0.36 g, 2.4 mmol), followed by HBTU (0.90 g, 2.4 mmol). The reaction mixture is stirred at 0 °C for 45 min. After that, a solution of 4-phenylthiazol-2-amine, 3a (0.29 g,1.70 mmol) and DIEA (0.8 mL, 5.1 mmol) in a mixture of DCM (5 mL) and DMF (2.5 mL) is added drop wise over 5 min. The reaction temperature is initially maintained at 0 °C for 1 h and later at RT for 10 h. Completion of reaction is evidenced by TLC analysis. After evaporating the DCM solvent on rotavapor, the reaction mixture is diluted with 40 mL of distilled water and extracted with (3 15 mL) of ethyl acetate. The combined organic layer is washed with saturated aqueous sodium bicarbonate solution (2 10 mL), followed by saturated aqueous sodium chloride solution (2 20 mL). After drying over anhydrous sodium sulfate, the organic layer is filtered and the filtrate is stripped off the solvent. The crude product thus obtained is purified by column chromatography over silica gel. The rest of the 2-(thiazolidinedion-5-yl)acetamide derivatives (4b-o) are prepared similarly by reacting 2,4-dioxo-1,3-thiazolidine-5-acetic acid (1) with the appropriate amine (3b-o).
  • 37
  • [ 2103-94-8 ]
  • [ 65-85-0 ]
  • 2-(N-benzoylamino)-4-(4-bromophenyl)thiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h; General procedure for the synthesis of acetamide derivatives 4i-4l and 5i-5l General procedure: The key intermediates 3a or 3b (1 mmol), corresponding acids (1 mmol) and carbodiimide hydrochloride (EDC*HCl,1.5 mmol) and N-hydroxybenzotriazole (HOBt, 0.05 mmol) were stirred in CH2Cl2 (20-30 mL) at room temperature for 24 h. After that, the solvent was evaporated under reduced pressure to afford a residue, which was extracted with EtOAc (3 x 20 mL). The combined organic phases were dried with anhydrous Na2SO4. Removal of all the solvent under reduced pressure distillation to get the residue, which was purified with recrystallization to give target products 4i-4l and 5i-5l.
64% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 24h; 25 4.1.5.22 2-((4-(4-bromophenyl) thiazol-2-yl)carbamoyl)phenyl acetate (16 a) General procedure: 2-acetoxybenzoic acid (14 mg, 0.078 mmol) was dissolved in anhydrous DMF (500 μl) at room temp, and HATU (29 mg, 0.078 mmoli) and DIPEA (14 μl, 0.078 mmol) were added. After few minutes, 2-amino-4(4Br-phenyl) thiazole (10 mg, 0.039 mmol) in anhydrous DMF (500 μl) was added, and the reaction was kept at room temperature for 24 h. The resulting solution was suspended in CH2Cl2 (1 ml) and washed with H2O (3 * 2 ml) and finally concentrated in vacuum. Crude product was purified by preparative HPLC and the peak of interest was concentrated to obtain the title compound. (8 mg,49%) 1H NMR (300 MHz, CDCl3): δ 9.08 (s, NH), 7.99 (dd, J = 7.7,1.5 Hz, 1H), 7.87 (dd, J = 7.5, 1.5 Hz, 1H), 7.73 (dd, J = 7.7, 1.5 Hz, 2H), 7.69 (ddd, J = 8.0, 7.5, 0.9 Hz, 1H), 7.66 (dd, J = 7.5, 1.5 Hz, 2H), 7.44 (ddd, J = 7.5, 7.1, 1.5 Hz, 1H), 6.87 (s, 1H), 2.27 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 169.2, 164.7, 161.4, 150.2, 148.7, 133.5, 132.1, 132.1, 130.5, 128.4, 128, 127.4, 125.6, 125.2, 123.5, 123.1, 105.1, 20.3. ESI -MS m/z = 418.9 [M+H]+.
  • 38
  • [ 50881-96-4 ]
  • [ 2103-94-8 ]
  • [ 347370-70-1 ]
YieldReaction ConditionsOperation in experiment
83% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h; General procedure for the synthesis of acetamide derivatives 4i-4l and 5i-5l General procedure: The key intermediates 3a or 3b (1 mmol), corresponding acids (1 mmol) and carbodiimide hydrochloride (EDC*HCl,1.5 mmol) and N-hydroxybenzotriazole (HOBt, 0.05 mmol) were stirred in CH2Cl2 (20-30 mL) at room temperature for 24 h. After that, the solvent was evaporated under reduced pressure to afford a residue, which was extracted with EtOAc (3 x 20 mL). The combined organic phases were dried with anhydrous Na2SO4. Removal of all the solvent under reduced pressure distillation to get the residue, which was purified with recrystallization to give target products 4i-4l and 5i-5l.
  • 39
  • [ 2103-94-8 ]
  • [ 6834-42-0 ]
  • [ 926458-30-2 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate In acetone for 5h; Cooling with ice; General procedure for the synthesis of acetamide derivatives 4a-4h and 5a-5h General procedure: For the synthesis of compounds 4a-4h and 5a-5h was depicted in Scheme 2. Firstly, 2-phenylacetic acid (1 mmol) and SOCl2 (4-6 mL) were refluxed at 80 °C for 3 h. The reaction liquid was cooled to room temperature and then evaporated to give reactive acyl chloride. The product was obtained as an oil matter, which would be dissolved in acetone (5-6 mL) in the next step. Treatment of 3a (5-phenylthiazol-2-amine) with 2-phenylacetyl chloride in acetone for 5 h at ice-bath afforded the aimed amine. Meanwhile, K2CO3 (0.8 g) was added to the mixture. Then the mixture was evaporated under reduced pressure and the resulting solid was washed with diluted NaOH liquid. The aimed amide was extracted from the NaOH liquid with ethyl acetate for column chromatography. Column chromatography was performed using silica gel (200-300 mesh) eluting with ethyl acetate and petroleum ether to give the aimed amine (4a). Compounds of 4b-4h and 5a-5h could begot with corresponding acids by the procedures above.
  • 40
  • [ 2103-94-8 ]
  • [ 17304-62-0 ]
  • C20H13BrN6OS2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% Stage #1: 4-(4-bromophenyl)-1,3-thiazol-2-amine With sulfuric acid; acetic acid; propionic acid; sodium nitrite at -5℃; for 2.5h; Stage #2: 2-(1,3-benzothiazol-2-yl)-5-methyl-2,4-dihydro-3H-pyrazol-3-one With potassium hydroxide at 0 - 5℃; for 2h; Stage #3: With sodium carbonate for 0.5h; 1 Synthesis of hetarylazopyrazolone dyes (II-a-f) General procedure: 2-Aminothiazole (0.002 mol, 0.200 g) was dissolved in icy acetic acid-propionic acid mixture (3 mL, 2 mL) and was cooled to -5 °C in ice-salt bath. Nitrosyl sulphuric acid, prepared with dissolving sodium nitrite (0.002 mol, 0.14 g) in sulphuric acid (4 mL) was added into the heterocyclic amine dropwise in 30 min at -5 °C. The mixture was stirred in cold for additional 2 h. Urea was added into the mixture in order to decompose the unreacted nitrous acid. 1-(2-benzothiazolyl)-3-methylpyrazol-5-one (0.002 mol, 0.46 g) was dissolved in KOH solution (10 mL, 0.2 M) and cooled. The prepared coupling compound solution was added into the diazonium solution in half an hour. The mixture was stirred for additional 2 h at 0-5 °C and Na2CO3 solution was added till the mixture had a value of pH 5-6. The mixture was stirred for 30 min. Water was added to precipitate the product. The product was filtered, washed with water and air dried. Recrystallization was performed in ethanol to obtain the pure orange compound.
  • 41
  • [ 2103-94-8 ]
  • [ 141-97-9 ]
  • ethyl 2-(2-(4-(4-bromophenyl)thiazol-2-yl)hydrazono)-3-oxobutanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% Stage #1: 4-(4-bromophenyl)-1,3-thiazol-2-amine With hydrogenchloride; sodium nitrate In water at 0℃; Stage #2: ethyl acetoacetate With sodium acetate In ethanol; water Cooling; General Procedure for the Synthesis of Various Ethyl3-oxo-2-(2-(substituted phenyl thiazol-2-yl) hydrazono)butanoate 6a-d General procedure: To a various substituted phenyl thiazole Amine 5a-d(0.01 mole) was dissolved in a mixture of HCl (8 ml) andwater (6 ml) and cooled to 0 °C in ice bath. To it a coldaqueous solution of sodium nitrate (0.03 mole) was added.The diazonium salt solution was filtered into a cooledsolution of ethyl acetoacetate (0.01 mole) and sodium acetate(0.12 mole) in ethanol (50 ml). The resulting solid waswashed with water and recrystallized from EtOH/MeOH.
  • 42
  • [ 148-24-3 ]
  • [ 2103-94-8 ]
  • 5-[4-(4-bromophenyl)thiazol-2-yldiazenyl]-8-hydroxyquinoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% Stage #1: 4-(4-bromophenyl)-1,3-thiazol-2-amine With nitrosylsulfuric acid; acetic acid; propionic acid at -5 - 0℃; for 2h; Stage #2: 8-quinolinol With potassium hydroxide In water at 0 - 5℃; for 2h; Stage #3: With sodium carbonate In water at 20℃; for 24h; 7 Preparation of 5-[4-(4-bromophenyl)thiazol-2-yldiazenyl]-8-hydroxyquinoline (II-7) General procedure: 2 mmol heterocyclic amines were dissolved in hot glacial aceticacid-propionic acid mixture (2:1, 6.0 mL) and was rapidly cooled inan ice-salt bath to-5 °C. The liquor was then added in portions during30 min to a cold solution of nitrosyl sulfuric acid (prepared fromsodiumnitrite (0.15 g) and concentrated sulfuric acid, 98% (3mL at 50 °C)). Themixturewas stirred for an additional 2 h at 0 °C. Excess nitrous acidwasdestroyed by the addition of urea. The resulting diazonium salt wascooled in ice-salt bath. After diazotization was complete the azo liquorwas slowly added to vigorously stirred solution of 8-hydroxyquinoline(2 mmol, 0.29 g) in potassium hydroxide (2.0 × 10-3 mol, 0.112 g)and water (2 mL). The solution was stirred at 0-5 °C for 2 h. After thatthe pH of the reaction mixture was maintained at 4-6 by the simultaneousaddition of saturated sodium carbonate solution. The mixturewas stirred for 1 day at room temperature. The resulting solid was filtered,washed with cold water and dried. The obtained compoundswere purified by crystallization using ethanol and then analyzed. Theyields of the dyes are in range of 54-78%. Characterization data areshown below. This dye was obtained from 2-amino-4-(4-bromophenyl)thiazole and 8-hydroxyquinoline as dark brown powder (yield: 0.64 g, 78%; m.p: 227-228 °C). IR (KBr): νmax: 3448-3095 (quinoline OH), 3056 (aromatic CH), 1592, 1510 (C=C), 1240 (C-O) cm- 1; 1H NMR(DMSO-d6/CDCl3): δ 9.20 (m,1H), 9.04 (d,1H), 8.15 (d,1H), 8.08 (s,1H), 7.95 (d,2H), 7.65 (d,2H), 7.85 (m,1H), 7.30 (d,1H).). Anal. calcd. for C18H11BrN4OS (411.28): C, 52.57; H, 2.70; N, 13.62; S, 7.80. Found C, 52.45; H, 2.65; N, 13.46; S, 7.76. MS: (m/z, 100 eV): 410 (M-1)+, 172, 144.
  • 43
  • [ 2103-94-8 ]
  • [ 70-11-1 ]
  • 3-(4-bromophenyl)-6-phenylimidazo[2,1-b]thiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
44% In ethanol at 100℃; Sealed tube; Microwave irradiation; General procedure for the synthesis of 3-aryl-6-phenylimidazo[2,1-b]thiazoles (4a-l) General procedure: A mixture of 2 mmol each of the respective 4-(aryl)-1,3-thiazol-2-amine (5a-l) and 2-bromo-1-phenylethanone (6) in ethanol are taken in a 20 mL sealed pressure tube and subjected to microwave irradiation (CEM Discover, 180 W, 250 psi, 100 °C) for 5-6 min. The reaction mixture is cooled to room temperature and ethanol is evaporated under reduced pressure. The residue is suspended in water (5 mL) and a saturated aqueous solution of Na2CO3 is added dropwise under stirring to bring the pH of the medium to 8-9, before extracting the organics with 3 x15 mL portions of ethyl acetate. The organic phase is dried (anhydrous Na2SO4) and the solvent evaporated in vacuo. The crude product is purified by column chromatography (ethyl acetate/petroleum ether = 1:8) to provide the corresponding 3-aryl-6-phenylimidazo[2,1-b]thiazole (4a-l) as solid.
  • 44
  • [ 2103-94-8 ]
  • [ 314268-40-1 ]
  • N-(4-(4-bromophenyl)thiazol-2-yl)-4-((4-methylpiperazin-1-yl)methyl)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
48% Stage #1: 4-(4-bromophenyl)-1,3-thiazol-2-amine With trimethylaluminum In toluene at 50℃; for 0.333333h; Inert atmosphere; Stage #2: 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester In toluene Reflux; N-(4-(4-bromophenyl)thiazol-2-yl)-4-((4-methylpiperazin-l- yl)methyl)benzamide 4-(4-bromophenyl)thiazol-2-amine (1 g, 3.9 mmol) was diluted with toluene (4 mL) in a two necked round bottom flask equipped with a reflux condenser under an argon atmosphere. The solution was stirred and trimethylaluminium in toluene (1.84 mL, 2M) was slowly added. The solution was heated at 50°C during 20 min and the ester (645 mg, 2.6 mmol) in toluene (2 mL) was added. The resulting solution was heated under reflux for one night, cooled to room temperature and slowly hydrolyzed with water to prevent foam formation. The aqueous layer was based with a 1M NaOH solution (pH9-10). The mixture was extracted three times with DCM, and the organic layers were combined and dried over Na2SO4.The solvent was evaporated under reduced pressure. Purification by silica gel flash chromatography (DCM/MeOH 9: 1) afforded the product (584 mg, 48%) as a yellow solid. NMR (300 MHz, CDCb) δ 10.35 (bs, 1H, NH), 7.81 (d, J = 7.8 Hz, 2H, Har), 7.62 (d, J = 8.2 Hz, 2H, Har), 7.45 (d, J = 8.2 Hz, 2H, Har), 7.39 (d, J = 7.7 Hz, 2H, Har), 7.18 (s, 1H, Har), 3.54 (s, 2H, CH2), 2.51 (bs, 8H, 2xCH2), 2.34 (s, 3H, CH3). 13C NMR (75 MHz, CDCb) δ 165.1 (C), 159.1 (C), 149.3 (C), 144.3 (C), 133.5 (C), 132.1 (2xCH), 130.9 (C), 129.6 (2xCH), 127.9 (2xCH), 127.8 (2xCH), 122.3 (C), 108.8 (CH), 62.7 (CH2), 55.3 (2xCH2), 53.2 (2xCH2), 46.1 (CH3). HRMS [M+H]+ C22H24BrN4OS: Calcd. 471.0849 found 471.0841.
  • 45
  • [ 2103-94-8 ]
  • [ 314268-40-1 ]
  • N-(4-(3-bromophenyl)thiazol-2-yl)-4-((4-methylpiperazin-1-yl)methyl)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% Stage #1: 4-(4-bromophenyl)-1,3-thiazol-2-amine With trimethylaluminum In n-heptane; toluene at 50℃; for 0.333333h; Inert atmosphere; Stage #2: 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester In n-heptane; toluene Reflux; N-(4-(3-bromophenyl)thiazol-2-yl)-4-((4-methylpiperazin-l- yl)methyl)benzamide 4-(4-bromophenyl)thiazol-2-amine (195 mg, 0.76 mmol) was diluted with toluene (2.5 mL) in a two necked round bottom flask equipped with a reflux condenser under an argon atmosphere. The solution was stirred and trimethylaluminium in heptane (360 2M) was slowly added. The solution was heated at 50°C during 20 min and the ester 2 (126 mg, 0.51 mmol) in toluene (500 L) was added. The resulting solution was heated under reflux for one night, cooled to room temperature and slowly hydrolyzed with water to prevent foam formation. The aqueous layer was based with a 1M NaOH solution (pH9-10). The mixture was extracted three times with DCM, and the organic layers were combined and dried over Na2SO4.The solvent was evaporated under reduced pressure. Purification by silica gel flash chromatography (DCM/MeOH 85: 15) afforded the product (206 mg, 86%) as a yellow viscous oil. NM (300 MHz, CDC13) δ 8.00 (dd, J = 1.7, 1.7 Hz, 1H, Har), 7.90 (d, J = 8.3 Hz, 2H, Har), 7.73 (ddd, J = 7.8, 2.6, 1.1 Hz, 1H, Har), 7.49 (d, J = 8.3 Hz, 2H, Har), 7.44 (ddd, J = 7.9, 1.9, 1.0 Hz, 1H, Har), 7.27 (dd, J = 7.9, 7.9 Hz, 1H, Har), 7.21 (s, 1H, Har), 3.59 (s, 2H, CH2), 2.55 (bs, 8H, 4xCH2), 2.35 (s, 3H, CH3). 13C NMR (75 MHz, CDC13) δ 165.33 (C), 159.4 (C), 148.7 (C), 144.2 (C), 136.5 (C), 131.1 (CH), 130.9 (C), 130.4 (CH), 129.6 (CH), 129.4 (C), 127.8 (C), 124.8 (CH), 123.1 (C), 109.3 (CH), 62.7 (CH2), 55.3 (2xCH2), 53.3 (2xCH2), 46.2 (CH3). HRMS (ESI) [M+H]+ C22H24BrN4OS: Calcd. 471.0844 found 471.0849.
  • 46
  • [ 2103-94-8 ]
  • [ 100-44-7 ]
  • N-benzyl-4-(4-bromophenyl)thiazol-2-amine [ No CAS ]
  • N,N-dibenzyl-4-(4-bromophenyl)thiazol-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 69% 2: 27% Stage #1: 4-(4-bromophenyl)-1,3-thiazol-2-amine With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; Stage #2: benzyl chloride In N,N-dimethyl-formamide; mineral oil for 12h; Reflux; 26 4.1.5.26. N-benzyl-4-(4-bromophenyl) thiazol-2-amine (17a) and N,N-dibenzyl-4-(4-bromophenyl) thiazol-2-amine (17b). 2-Amino-4-(4-bromophenyl)thiazole (26 mg, 0.1 mmol) was dissolved in of anhydrous DMF (1 ml) at room temp, and 60% dispersion in mineral oil of NaH (8.5 mg, 0.2 mmol) was added at T = 0 °C. When the bubbling stopped, a solution of benzyl chloride (28 μl, 0.25 mmol), in anhydrous DMF (500 μl) was added and the reaction was heated to reflux for 12 h. The mixture was then extracted with diethyl ether (3 * 2 ml) and washed with water (2 * 1 ml). The organic phase was dried under vacuum. The product was purified by preparative HPLC to afford 17a (24 mg, 69%) and 17b (11.5 mg, 27%). 17a1H NMR (300 MHz, CDCl3): δ 7.88 (dd, J = 7.5, 1.5 Hz, 2H), 7.64 (dd, J = 7.5, 1.5, Hz, 2H), 7.33 (td, J = 7.5, 7.5, 1.5 Hz, 2H), 7.26 (tt, J = 7.5, 7.5, 1.5, 1.5 Hz, 1H), 7.23 (dt, J = 7.5, 1.5,1.5 Hz, 2H), 6.88 (s,1H), 4.35 (s, 2H). 13C NMR (75 MHz, CDCl3): δ 164.1, 150.2, 139.4, 134, 132.1, 130.2, 128.9, 128.5, 128.2, 127, 126.9, 126.2, 125.6, 123.1, 105.2, 49.1. ESI -MS m/z = 345.0 [M+H]+. 17 b1H NMR (300 MHz, CDCl3): δ 7.79 (dd, J = 7.5, 1.5 Hz, 2H), 7.66 (dd, J = 7.5, 1.5, Hz, 2H), 7.33 (td, J = 7.5, 7.5, 1.5 Hz, 4H), 7.26 (tt, J = 7.5, 7.5, 1.5, 1.5 Hz, 2H), 7.23 (dt, J = 7.5, 1.5, 1.5 Hz, 4H), 6.88 (s, 1H), 4.71 (s, 4H). 13C NMR (75 MHz, CDCl3): δ 157.3, 150.2, 140, 138.7, 132.2, 132.1, 131.9, 128.7, 128.5, 128.2, 128.1, 128.1, 128, 127.9, 127.9, 127.8, 127.7, 127, 126.9, 123.3, 105.4, 55.1, 54.3. ESI-MS m/z = 435.0 [M+H]+.
  • 47
  • [ 2103-94-8 ]
  • [ 50-78-2 ]
  • 2-((4-(4-bromophenyl)thiazol-2-yl)carbamoyl)phenyl acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
49% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 24h; 22 4.1.5.22 2-((4-(4-bromophenyl) thiazol-2-yl)carbamoyl)phenyl acetate (16 a) 2-acetoxybenzoic acid (14 mg, 0.078 mmol) was dissolved in anhydrous DMF (500 μl) at room temp, and HATU (29 mg, 0.078 mmoli) and DIPEA (14 μl, 0.078 mmol) were added. After few minutes, 2-amino-4(4Br-phenyl) thiazole (10 mg, 0.039 mmol) in anhydrous DMF (500 μl) was added, and the reaction was kept at room temperature for 24 h. The resulting solution was suspended in CH2Cl2 (1 ml) and washed with H2O (3 * 2 ml) and finally concentrated in vacuum. Crude product was purified by preparative HPLC and the peak of interest was concentrated to obtain the title compound. (8 mg,49%) 1H NMR (300 MHz, CDCl3): δ 9.08 (s, NH), 7.99 (dd, J = 7.7,1.5 Hz, 1H), 7.87 (dd, J = 7.5, 1.5 Hz, 1H), 7.73 (dd, J = 7.7, 1.5 Hz, 2H), 7.69 (ddd, J = 8.0, 7.5, 0.9 Hz, 1H), 7.66 (dd, J = 7.5, 1.5 Hz, 2H), 7.44 (ddd, J = 7.5, 7.1, 1.5 Hz, 1H), 6.87 (s, 1H), 2.27 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 169.2, 164.7, 161.4, 150.2, 148.7, 133.5, 132.1, 132.1, 130.5, 128.4, 128, 127.4, 125.6, 125.2, 123.5, 123.1, 105.1, 20.3. ESI -MS m/z = 418.9 [M+H]+.
  • 48
  • [ 2103-94-8 ]
  • [ 69-72-7 ]
  • [ 50728-44-4 ]
YieldReaction ConditionsOperation in experiment
41% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 24h; 23 2-((4-(4-bromophenyl) thiazol-2-yl) carbamoyl) phenyl acetate (16 a) General procedure: 2-acetoxybenzoic acid (14 mg, 0.078 mmol) was dissolved in anhydrous DMF (500 μl) at room temp, and HATU (29 mg, 0.078 mmoli) and DIPEA (14 μl, 0.078 mmol) were added. After few minutes, 2-amino-4(4Br-phenyl) thiazole (10 mg, 0.039 mmol) in anhydrous DMF (500 μl) was added, and the reaction was kept at room temperature for 24 h. The resulting solution was suspended in CH2Cl2 (1 ml) and washed with H2O (3 * 2 ml) and finally concentrated in vacuum. Crude product was purified by preparative HPLC and the peak of interest was concentrated to obtain the title compound. (8 mg,49%) 1H NMR (300 MHz, CDCl3): δ 9.08 (s, NH), 7.99 (dd, J = 7.7,1.5 Hz, 1H), 7.87 (dd, J = 7.5, 1.5 Hz, 1H), 7.73 (dd, J = 7.7, 1.5 Hz, 2H), 7.69 (ddd, J = 8.0, 7.5, 0.9 Hz, 1H), 7.66 (dd, J = 7.5, 1.5 Hz, 2H), 7.44 (ddd, J = 7.5, 7.1, 1.5 Hz, 1H), 6.87 (s, 1H), 2.27 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 169.2, 164.7, 161.4, 150.2, 148.7, 133.5, 132.1, 132.1, 130.5, 128.4, 128, 127.4, 125.6, 125.2, 123.5, 123.1, 105.1, 20.3. ESI -MS m/z = 418.9 [M+H]+.
  • 49
  • [ 55-22-1 ]
  • [ 2103-94-8 ]
  • N-(4-(4-bromophenyl)thiazol-2-yl)isonicotinamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
41% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 24h; 24 2-((4-(4-bromophenyl) thiazol-2-yl) carbamoyl) phenyl acetate (16 a) General procedure: 2-acetoxybenzoic acid (14 mg, 0.078 mmol) was dissolved in anhydrous DMF (500 μl) at room temp, and HATU (29 mg, 0.078 mmoli) and DIPEA (14 μl, 0.078 mmol) were added. After few minutes, 2-amino-4(4Br-phenyl) thiazole (10 mg, 0.039 mmol) in anhydrous DMF (500 μl) was added, and the reaction was kept at room temperature for 24 h. The resulting solution was suspended in CH2Cl2 (1 ml) and washed with H2O (3 * 2 ml) and finally concentrated in vacuum. Crude product was purified by preparative HPLC and the peak of interest was concentrated to obtain the title compound. (8 mg,49%) 1H NMR (300 MHz, CDCl3): δ 9.08 (s, NH), 7.99 (dd, J = 7.7,1.5 Hz, 1H), 7.87 (dd, J = 7.5, 1.5 Hz, 1H), 7.73 (dd, J = 7.7, 1.5 Hz, 2H), 7.69 (ddd, J = 8.0, 7.5, 0.9 Hz, 1H), 7.66 (dd, J = 7.5, 1.5 Hz, 2H), 7.44 (ddd, J = 7.5, 7.1, 1.5 Hz, 1H), 6.87 (s, 1H), 2.27 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 169.2, 164.7, 161.4, 150.2, 148.7, 133.5, 132.1, 132.1, 130.5, 128.4, 128, 127.4, 125.6, 125.2, 123.5, 123.1, 105.1, 20.3. ESI -MS m/z = 418.9 [M+H]+.
  • 50
  • [ 2103-94-8 ]
  • [ 98592-19-9 ]
YieldReaction ConditionsOperation in experiment
67% With bromine; acetic acid at 20 - 80℃; for 13.5h; General procedure of 5-bromothiazol-2-amine derivatives 3a-f General procedure: 2-Aminothiazoles (0.1 mol) were dissolved in the least amount of glacial acetic acid, and then bromine (0.11 mol) was added drop-wise with continuous stirring at room temperature. The mixture was heated at 80 °C for 90 min then stirred at room temperature for 12 h. The mixture was filtered and washed with water. The precipitate was heated in water, and the aqueous solution was alkalized by ammonia, filtered, washed with water and then dried. Crystals were formed from ethanol/water to give the 5-bromothiazol-2-amine compounds 3a-f.
With sulfuric acid; bromine; acetic acid at 20℃; for 18h;
  • 51
  • [ 2103-94-8 ]
  • [ 4635-59-0 ]
  • N-(4-(4-bromophenyl)thiazol-2-yl)-4-chlorobutanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% With potassium carbonate In chloroform at 20℃; for 48h; General procedure of N-(thiazol-2-yl)-4-chlorobutanamide derivatives 4a-m General procedure: A mixture of 2-aminothiazole derivatives 2a-h and 3a-e (1.0 mmol) and K2CO3 (4.0 mmol) was stirred at room temperature with drop-wise addition of 4-chlorobutyryl chloride (4.0 mmol) in chloroform for 48 h. The reaction mixture was monitored by TLC (using chloroform/ethyl acetate 9:1). Ammoniated water was added, and the organic layer was separated and dried over anhydrous Na2SO4, and the solvent was removed in vacuum. The resulting precipitate was crystallized from ethanol to give crystals of pure N-(thiazole-2-yl)-4-chlorobutanamide derivatives.
  • 52
  • [ 85-44-9 ]
  • [ 2103-94-8 ]
  • 2-(4-(4-bromophenyl)thiazol-2-yl)isoindoline-1,3-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
94% With triethylamine In dichloromethane for 6h; Reflux; 3.1 Step 1: 4-(4-Bromophenyl)thiazol-2-amine (254 mg, 1 mmol) was dissolved in 10 ml of dichloromethane, to which were added phthalic anhydride (140 mg, 0.96 mmol) and triethylamine (202 mg, 2 mmo), and then the mixture was stirred under reflux for 6 h. The reaction solution was washed with 10 ml of 1 N hydrochloric acid, and extracted with 10 ml of ethyl acetate, then washed with 10 ml saturated sodium bicarbonate and 10 ml saturated brine, respectively. The organic layer was concentrated under reduced pressure, and then separated and purified by thin-layer chromatography to obtain 360 mg of compound 2-(4-(4-bromophenyl)thiazol-2-yl)isoindolin-1,3-dione, with a yield of 94%.
82% In neat (no solvent) for 2h; Heating; General procedure of 2-(thiazol-2-yl)isoindoline-1,3-dione derivatives 6a-g General procedure: 2-Aminothiazole derivatives 2a-g (0.01 mol) were triturated and mixed with phthalic anhydride (1.48 g, 0.01 mol). The mixture was heated on an oil bath with occasional stirring for 2 h. The crude product was dissolved in hot EtOAc and filtered to remove any undissolved particles, and the 2-(thiazole-2-yl)isoindoline-1,3-dione derivatives were precipitated by cooling.
  • 53
  • [ 2103-94-8 ]
  • [ 117-08-8 ]
  • 2-(4-(4-bromophenyl)thiazol-2-yl)-4,5,6,7-tetrachloroisoindoline-1,3-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With sodium acetate; acetic acid for 3h; Reflux; General procedure of 2-(thiazol-2-yl)4,5,6,7-tetrachloroisoindoline-1,3-dione derivatives 6h-n General procedure: A mixture of 2-aminothiazole derivatives 2a-g (0.01 mol), anhydrous sodium acetate (0.8 g, 0.01 mol) and 4,5,6,7-tetrachlorophthalic anhydride (2.8 g, 0.01 mol) was heated in glacial acetic acid (50 mL) under reflux for 3 h. On cooling, the separated solid was filtered, washed with water (20 mL), dried and crystallized from ethanol to yield the title compounds.
  • 54
  • [ 333-20-0 ]
  • [ 89108-50-9 ]
  • [ 2103-94-8 ]
YieldReaction ConditionsOperation in experiment
86% With palladium diacetate In propan-1-ol at 80℃; for 12h;
  • 55
  • [ 2103-94-8 ]
  • [ 1415683-28-1 ]
  • 3-(4-(4-(4-bromophenyl)thiazol-2-ylamino)butoxy)-4-methoxybenzaldehyde [ No CAS ]
YieldReaction ConditionsOperation in experiment
26.4% With potassium carbonate In N,N-dimethyl-formamide for 12h; Reflux; 3.1. Synthesis of compounds 3a - 3i. 3.1.6. 3-(4-(4-(2-Bromophenyl)thiazol-2-ylamino)butoxy)-4-methoxybenzaldehyde (3f) General procedure: To a solution of 4-(4-bromobutoxy)benzaldehyde (400.00 mg, 1.56 mmol) and 4-phenylthiazol-2-amine (275.00 mg, 1.56 mmol) in DMF (15 mL), potassium carbonate (331.80 mg, 2.34 mmol) was added. The reaction mixture was refluxed for 12 h. The reaction mixture was quenched with water, and extracted with toluene (20 mL*3). The combined organic layer was washed with brine, dried with anhydrous sodium sulphate, concentrated under vacuum, then purified by flash chromatography (petroleum ether:ethyl acetate = 3:1) to afford a yellow oil.
  • 57
  • [ 2103-94-8 ]
  • [ 98-80-6 ]
  • [ 2834-79-9 ]
YieldReaction ConditionsOperation in experiment
86% With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,4-dioxane; ethanol; water at 130℃; for 0.5h; Sealed tube; 3.2. General Procedure for the Synthesis of Compounds 3(a-n) General procedure: 4-(4-bromophenyl)thiazol-2-amine (1.0 mmol) was takenin water:Ethanol:1,4dioxane (6 mL) mixture in 1:1:5 ratio, potassium carbonate (3.0 mmol) and different boronic acids(1.1 mmol) were added to the reaction mixture and degassed with nitrogen gas for 15 min with stirring at RT. Bis(triphenylphosphine) palladium(II) dichloride (0.1 mmol) catalyst was added to the mixture and heated for 30 min at 130°C in seal tube. The reaction mixture was filtered through celite, washed with methanol and filtrate was concentrated under reduced pressure, the resulting residue was dilutedwith ethylacetate and washed with water and brine solution.The organic layer was dried over anhydrous Na2SO4 andconcentrated under vacuo to give the crude product which was purified by column chromatography using hexane: ethylacetate as an eluent to get the title compounds (3a-n). It is noteworthy to mention that, in the presence of free aminogroup, coupling reaction underwent smoothly with desired products in good yields.
85% With potassium phosphate; tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane at 90 - 100℃; for 8h; Inert atmosphere; 3.1. Synthesis of 4-(biphenyl-4-yl)-1,3-thiazol-2-amine (1) In a screw capped reaction tube, 4-phenyl-1,3-thiazol-2-amine(100 mg, 0.48 mmol), Pd(PPh3)4 (8 mg, 1.5 mol%), phenyl boronicacid (136 mg, 0.531 mmol) and K3PO4 (153 mg, 0.724 mmol) wereadded to 3 mL of dioxane solvent. The resulting reaction mixturewas flushed with dry nitrogen gas for few minutes. The reactionmixture was heated at 90e100 C for 8 h. After the completion ofthe reaction, 20 mL of water was added. After cooling at roomtemperature, organic and the aqueous layers were separated andthe latter was extracted with ethyl acetate three times (3 15 mL).The obtained residue was then purified through column chromatographyand compound (1) was isolated as dark yellow crystallinesolid (95 mg, 85%).
55% With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,4-dioxane; water at 80℃; for 16h; Inert atmosphere; 49 Preparative Example 49 (0398) 4-(G 1 , 1 '-biphenyll -4-yl)thiazol-2-amine A mixture of dioxane and water (2.0 + 0.5 mL) was added to a mixture of 4-(4-bromophenyl)thiazol-2- amine (0.127 g, 0.5 mmol), phenylboronic acid (0.076 g, 0.62 mmol), K2CO3 (0.275 g, 1.99 mmol) and PdCl2(PPh3)2 (0.035 g, 0.05 mmol). The reaction mixture was purged with N2 for 5 min, then it was stirred at 80 °C for 16 h. The mixture was cooled to 25 °C, diluted with EtOAc (5 mL), poured into a saturated aqueous solution of NH4CI (20 mL), and extracted with EtOAc (3 x 25 mL). The combined organic extracts were washed with water (30 mL) and brine (30 mL), dried over MgS04, filtered, and the solvent was evaporated in vacuo. The residue was purified by column chromatography (hexane: EtOAc; 1:0 to 2:1). The product was obtained as a white solid (0.087 g, 55 %). (0401) NMR (500 MHz, DMSO-de) d (ppm) 7.9 (d, J = 8.4 Hz, 2H), 7.7 - 7.6 (m, 4H), 7.5 - 7.4 (m, 2H), 7.4 - 7.3 (m, 1H), 7.1 (s, 1H), 7.0 (s, 2H); (0402) 13C NMR (126 MHz, DMSO-de) d (ppm) 168.2, 149.4, 139.7, 138.6, 128.9, 127.3, 126.6, 126.4, 126.0, 101.7; (0403) HRMS calcd for C15H13N2S [M+H]+ 253.0794, found 253.0796
  • 58
  • [ 2103-94-8 ]
  • [ 144025-03-6 ]
  • 4-(2',4'-difluorobiphenyl-4-yl)thiazol-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With potassium phosphate; tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane at 90 - 100℃; for 8h; 3.2. Synthesis of 4-(2,4-difluorobiphenyl-4-yl)-1,3-thiazol-2-amine(2) In a screw capped reaction tube 4-phenyl-1,3-thiazol-2-amine(100 mg, 0.48 mmol), 4-phenyl-1,3-thiazol-2-amine, Pd(PPh3)4 (8 mg, 1.5 mol%), 2,4-diflurophenyl boronic acid (153 mg,0.724 mmol) and K3PO4 (153 mg, 0.724 mmol) were added to 3 mLof dioxane solvent. The resulting reaction mixturewas flushed withdry nitrogen gas for few minutes. The reaction mixture was heatedat 90e100 C for 8 h. After the completion of the reaction, 20 mL ofwater was added. After cooling at room temperature, organic andthe aqueous layers were separated and the latter was extractedwith ethyl acetate three times (3 15 mL). The obtained residuewas then purified through column chromatography and compound(2) was isolated as light yellow crystalline solid (146 mg, 90%).
  • 59
  • [ 2103-94-8 ]
  • [ 26280-19-3 ]
  • 2-(5-benzoyl-1-methyl-1H-pyrrol-2-yl)-N-(4'-(4-bromophenyl)thiazol-2'-yl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% Stage #1: 5-benzoyl-1-methyl-pyrrole-2-acetic acid With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate In N,N-dimethyl-formamide for 0.5h; Inert atmosphere; Stage #2: 4-(4-bromophenyl)-1,3-thiazol-2-amine With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 50℃; for 6h; Inert atmosphere; General procedure for the synthesis of 2-(5-benzoyl-1-methyl-1H-pyrrol-2-yl)-N-(4′-aryloxazol-2′-yl)acetamide (10a-f)/ 2-(5-benzoyl-1-methyl-1H-pyrrol-2-yl)-N-(4′-arylthiazol-2′-yl)acetamide (11a-f)/ 2-(5-benzoyl-1-methyl-1H-pyrrol-2-yl)-N-(4′-aryl-1H-imidazol-2′-yl)acetamide (12a-f). General procedure: The (5-benzoyl-1-methyl-1H-pyrrol-2-yl)acetic acid (6)(1 mmol) was dissolved in dry DMF. To this TBTU (2mmol) was added and stirred for 30 min under nitrogenatmosphere. Then 4-aryloxazol-2-amine (7)/4-arylthiazol-2-amine (8)/4-aryl-1H-imidazol-2-amine (9) (1 mmol) followedby DIPEA (0.5 ml) were added and the reactionmixture was heated at 50 °C for 6 h. After completion ofreaction (progress of reaction was monitored by TLC) thecontents were allowed to cool and poured into ice water.The resultant solid was filtered, dried and recrystallizedfrom 2-propanol.
  • 60
  • bicyclo[2.2.2]oct-2-ene-2,3-dicarboxylic anhydride [ No CAS ]
  • [ 2103-94-8 ]
  • (4R,7S)-2-(4-(4-bromophenyl)thiazol-2-yl)-3a,4,7,7a-tetrahydro-1H-4,7-ethanoisoindole-1,3(2H)-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% Stage #1: 4-(4-bromophenyl)-1,3-thiazol-2-amine With triethylamine In toluene for 0.166667h; Stage #2: bicyclo[2.2.2]oct-2-ene-2,3-dicarboxylic anhydride In toluene for 48h; Reflux; General procedure for synthesis of (4R,7S)-2-(4-phenylthiazol-2-yl)-3a,4,7,7a-tetrahydro-1H-4,7-ethanoisoindole-1,3(2H)-dione derivatives (9a-j) General procedure: Thiazole derivative (3a-h and 5a,b) (1 mmol) was dissolved in toluene (7.5 mL) and NEt3 (1 mL) and stirred forabout 10 min. Then, dicarboxylicanhydride (8) (1 mmol)in toluene (7.5 mL) was added drop wise into the reaction mixture. The reaction mixture was reuxed for 48 h.Toluene was removed by a rotovap. The residue wasextracted with chloroform, the organic layer was driedover Na2SO4 and solvent was removed by rotovap. Thecrude product was crystallized in chloroform/hexane (3/7)mixture.
  • 61
  • [ 607-68-1 ]
  • [ 2103-94-8 ]
  • N2,N4-bis[4-(4-bromophenyl)thiazol-2-yl]quinazoline-2,4-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% With hydrogenchloride In isopropyl alcohol at 20℃; Sonication; General procedure for the synthesis of N2,N4-bis(4-aryloxazol-2-yl)quinazoline-2,4-diamines 5a-5f, N2,N4-bis(4-arylthiazol-2-yl)quinazoline-2,4-diamines 6a-6f, andN2,N4-bis(4-aryl-1H-imidazol-2-yl)quinazoline-2,4-diamines7a-7f General procedure: A solution of 2,4-dichloroquinazoline (1, 1.0 mmol),4-aryloxazol-2-amine 2/4-arylthiazol-2-amine 3/4-aryl-1H-imidazol-2-amine 4 (2.5 mmol) and conc. HCl(2.0 mmol) in 5 cm3 2-propanol was sonicated at roomtemperature for 30-45 min in an ultrasonic bath working at 46 kHz (constant frequency). After completion of there action (monitored by TLC), the separated solid was filtered, dried, and recrystallized from 2-propanol.
  • 62
  • [ 2103-94-8 ]
  • 2-(N-(4,6-bis(4-bromophenyl)pyrimidin-2-yl)sulfamoyl)acetic acid [ No CAS ]
  • 2-(N-(4,6-bis(4-bromophenyl)pyrimidin-2-yl)sulfamoyl)-N-(4-(4-bromophenyl)thiazol-2-yl)-acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 25℃; Inert atmosphere; Method B General procedure: A solution of EDCI (10 mmol) and HOBt (10 mmol) inDMF (8 mL) was added dropwise to a stirred suspension ofacid 4 (9.09 mmol) and 5/6/7 (10 mmol) in DMF (15 mL) at0 °C under nitrogen atmosphere. DIPEA (20 mmol) wasadded dropwise to the mixture and continued stirring at 25 °C for 12-16 h. EtOAc (80 mL) was added and the organiclayer was washed with brine (4 × 20 mL), dried (Na2SO4),and concentrated in vacuo. Purification of the residue bycolumn chromatography (silica gel, PE-EtOAc, 3:2) affordedthe compounds 8/9/10.
  • 63
  • [ 1878-91-7 ]
  • [ 2103-94-8 ]
  • 2-(4-bromophenoxy)-N-(4-(4-bromophenyl) thiazol-2-yl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: Phenoxyacetic acids (4a-j, 2mmol) in dry DCM (20ml) was stirred at 25-30C, and then lutidine (3mmol) was added, followed by the addition of substituted amino-4-phenyl-1,3-thiazoles (2mmol). The reaction mixture was stirred at the same temperature for 30min, then cooled to 0-5C and TBTU (2mmol) was added over a period of 30min maintaining the temperature below 5C. The reaction mass was stirred overnight and monitored by TLC using chloroform: methanol (9:1) as the mobile phase. The purity of the compounds was determined using high performance liquid chromatography (HPLC) by reversed phase agilent zorbax SB-C18 column method, with methanol (50%): acetonitrile (30%): water (20%) as mobile phase. The solvent was evaporated at reduced pressure, quenched by the addition of crushed ice and the obtained solid was filtered, dried and recrystallized from ethanol to afford compounds 8a-ab in good yield [supplementary files].
  • 64
  • [ 2103-94-8 ]
  • [ 122-59-8 ]
  • N-(4-(4-bromophenyl) thiazol-2-yl)-2-phenoxyacetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 4-(4-bromophenyl)-1,3-thiazol-2-amine; 2-phenoxyacetic acid With 2,6-dimethylpyridine In dichloromethane at 25 - 30℃; for 0.5h; Stage #2: With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate In dichloromethane at 0 - 5℃; 11 4.1.2.3 General synthetic procedure for 4-Phenyl-2-Phenoxyacetamide Thiazoles analogues (8a-ab) General procedure: Phenoxyacetic acids (4a-j, 2mmol) in dry DCM (20ml) was stirred at 25-30°C, and then lutidine (3mmol) was added, followed by the addition of substituted amino-4-phenyl-1,3-thiazoles (2mmol). The reaction mixture was stirred at the same temperature for 30min, then cooled to 0-5°C and TBTU (2mmol) was added over a period of 30min maintaining the temperature below 5°C. The reaction mass was stirred overnight and monitored by TLC using chloroform: methanol (9:1) as the mobile phase. The purity of the compounds was determined using high performance liquid chromatography (HPLC) by reversed phase agilent zorbax SB-C18 column method, with methanol (50%): acetonitrile (30%): water (20%) as mobile phase. The solvent was evaporated at reduced pressure, quenched by the addition of crushed ice and the obtained solid was filtered, dried and recrystallized from ethanol to afford compounds 8a-ab in good yield [supplementary files].
  • 65
  • [ 2103-94-8 ]
  • [ 1878-49-5 ]
  • N-(4-(4-bromophenyl) thiazol-2-yl)-2-(o-tolyloxy)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: Phenoxyacetic acids (4a-j, 2mmol) in dry DCM (20ml) was stirred at 25-30C, and then lutidine (3mmol) was added, followed by the addition of substituted amino-4-phenyl-1,3-thiazoles (2mmol). The reaction mixture was stirred at the same temperature for 30min, then cooled to 0-5C and TBTU (2mmol) was added over a period of 30min maintaining the temperature below 5C. The reaction mass was stirred overnight and monitored by TLC using chloroform: methanol (9:1) as the mobile phase. The purity of the compounds was determined using high performance liquid chromatography (HPLC) by reversed phase agilent zorbax SB-C18 column method, with methanol (50%): acetonitrile (30%): water (20%) as mobile phase. The solvent was evaporated at reduced pressure, quenched by the addition of crushed ice and the obtained solid was filtered, dried and recrystallized from ethanol to afford compounds 8a-ab in good yield [supplementary files].
  • 66
  • [ 2103-94-8 ]
  • [ 25141-58-6 ]
  • N-(4-(4-bromophenyl) thiazol-2-yl)-2-(2-isopropylphenoxy)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: Phenoxyacetic acids (4a-j, 2mmol) in dry DCM (20ml) was stirred at 25-30C, and then lutidine (3mmol) was added, followed by the addition of substituted amino-4-phenyl-1,3-thiazoles (2mmol). The reaction mixture was stirred at the same temperature for 30min, then cooled to 0-5C and TBTU (2mmol) was added over a period of 30min maintaining the temperature below 5C. The reaction mass was stirred overnight and monitored by TLC using chloroform: methanol (9:1) as the mobile phase. The purity of the compounds was determined using high performance liquid chromatography (HPLC) by reversed phase agilent zorbax SB-C18 column method, with methanol (50%): acetonitrile (30%): water (20%) as mobile phase. The solvent was evaporated at reduced pressure, quenched by the addition of crushed ice and the obtained solid was filtered, dried and recrystallized from ethanol to afford compounds 8a-ab in good yield [supplementary files].
  • 67
  • [ 2103-94-8 ]
  • [ 405-79-8 ]
  • N-(4-(4-bromophenyl) thiazol-2-yl)-2-(4-fluorophenoxy)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% General procedure: Phenoxyacetic acids (4a-j, 2mmol) in dry DCM (20ml) was stirred at 25-30C, and then lutidine (3mmol) was added, followed by the addition of substituted amino-4-phenyl-1,3-thiazoles (2mmol). The reaction mixture was stirred at the same temperature for 30min, then cooled to 0-5C and TBTU (2mmol) was added over a period of 30min maintaining the temperature below 5C. The reaction mass was stirred overnight and monitored by TLC using chloroform: methanol (9:1) as the mobile phase. The purity of the compounds was determined using high performance liquid chromatography (HPLC) by reversed phase agilent zorbax SB-C18 column method, with methanol (50%): acetonitrile (30%): water (20%) as mobile phase. The solvent was evaporated at reduced pressure, quenched by the addition of crushed ice and the obtained solid was filtered, dried and recrystallized from ethanol to afford compounds 8a-ab in good yield [supplementary files].
  • 68
  • [ 2103-94-8 ]
  • [ 940-64-7 ]
  • N-(4-(4-bromophenyl) thiazol-2-yl)-2-(4-methylphenoxy)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 4-(4-bromophenyl)-1,3-thiazol-2-amine; 2-(4-methylphenoxy)acetic acid With 2,6-dimethylpyridine In dichloromethane at 25 - 30℃; for 0.5h; Stage #2: With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate In dichloromethane at 0 - 5℃; 24 4.1.2.3 General synthetic procedure for 4-Phenyl-2-Phenoxyacetamide Thiazoles analogues (8a-ab) General procedure: Phenoxyacetic acids (4a-j, 2mmol) in dry DCM (20ml) was stirred at 25-30°C, and then lutidine (3mmol) was added, followed by the addition of substituted amino-4-phenyl-1,3-thiazoles (2mmol). The reaction mixture was stirred at the same temperature for 30min, then cooled to 0-5°C and TBTU (2mmol) was added over a period of 30min maintaining the temperature below 5°C. The reaction mass was stirred overnight and monitored by TLC using chloroform: methanol (9:1) as the mobile phase. The purity of the compounds was determined using high performance liquid chromatography (HPLC) by reversed phase agilent zorbax SB-C18 column method, with methanol (50%): acetonitrile (30%): water (20%) as mobile phase. The solvent was evaporated at reduced pressure, quenched by the addition of crushed ice and the obtained solid was filtered, dried and recrystallized from ethanol to afford compounds 8a-ab in good yield [supplementary files].
  • 69
  • [ 122-88-3 ]
  • [ 2103-94-8 ]
  • N-(4-(4-bromophenyl)thiazol-2-yl)-2-(4-chlorophenoxy)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: Phenoxyacetic acids (4a-j, 2mmol) in dry DCM (20ml) was stirred at 25-30C, and then lutidine (3mmol) was added, followed by the addition of substituted amino-4-phenyl-1,3-thiazoles (2mmol). The reaction mixture was stirred at the same temperature for 30min, then cooled to 0-5C and TBTU (2mmol) was added over a period of 30min maintaining the temperature below 5C. The reaction mass was stirred overnight and monitored by TLC using chloroform: methanol (9:1) as the mobile phase. The purity of the compounds was determined using high performance liquid chromatography (HPLC) by reversed phase agilent zorbax SB-C18 column method, with methanol (50%): acetonitrile (30%): water (20%) as mobile phase. The solvent was evaporated at reduced pressure, quenched by the addition of crushed ice and the obtained solid was filtered, dried and recrystallized from ethanol to afford compounds 8a-ab in good yield [supplementary files].
  • 70
  • [ 862574-89-8 ]
  • [ 2103-94-8 ]
  • 1-(benzo[d][1,3]dioxol-5-yl)-N-(4-(4-bromophenyl)thiazol-2-yl)cyclopropanecarboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
35% With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; for 22h; General procedure: The benzo [1, 3] dioxol-5-yl-cyclopropanecarboxylic acid (1 eq) was resuspended in anhydrous DMF (1ml), HBTU (1 eq) and DIPEA (1 eq) were added. The reaction was vigorously stirred for 5min and the appropriate thiazole or aminic derivative (1 eq) in anhydrous DMF (500muL) was added, and the reaction was kept at T=40C until completeness (from 14h to 24h) depending from reactants. The mixture was concentrated under vacuum and after extraction with organic solvent (3×3ml), washed with H2O (3×2ml). The organic phases were dried over Na2SO4 and concentrated under reduced pressure and concentrated under vacuum. The crude product was then purified by preparative HPLC; the peak of interest was concentrated in vacuum and finally lyophilized to obtain the final compound.
  • 71
  • [ 2039-82-9 ]
  • [ 17356-08-0 ]
  • [ 2103-94-8 ]
YieldReaction ConditionsOperation in experiment
85% Stage #1: 1-bromo-4-ethenyl-benzene With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione In water at 60℃; for 1h; Stage #2: thiourea In ethanol for 1h; Reflux; 2 Example 2Synthesis of 2-Amino-4-(p-bromophenyl)thiazole In a 25 mL reaction flask, add 3 mL of water and 30 μL of Tween,0.5mmolP-bromostyreneAnd 0.75mmol DBH reacted at 60°C for 1h.After the reaction is completed, dry the water, add 3 mL of ethanol, and add 0.5 mmol of thiourea.The reaction was refluxed for 1 h. After the reaction was completed, ethanol was spin-dried, and ethyl acetate was added to dissolve the mixture.The mixture was extracted with saturated brine, and the organic layer was concentrated. Column chromatography gave 108 mg of a white solid with a yield of 85%.
  • 72
  • [ 2103-94-8 ]
  • [ 3900-89-8 ]
  • 4-(2'-chlorobiphenyl-4-yl)thiazol-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,4-dioxane; ethanol; water at 130℃; for 0.5h; Sealed tube; 3.2. General Procedure for the Synthesis of Compounds 3(a-n) General procedure: 4-(4-bromophenyl)thiazol-2-amine (1.0 mmol) was takenin water:Ethanol:1,4dioxane (6 mL) mixture in 1:1:5 ratio, potassium carbonate (3.0 mmol) and different boronic acids(1.1 mmol) were added to the reaction mixture and degassed with nitrogen gas for 15 min with stirring at RT. Bis(triphenylphosphine) palladium(II) dichloride (0.1 mmol) catalyst was added to the mixture and heated for 30 min at 130°C in seal tube. The reaction mixture was filtered through celite, washed with methanol and filtrate was concentrated under reduced pressure, the resulting residue was dilutedwith ethylacetate and washed with water and brine solution.The organic layer was dried over anhydrous Na2SO4 andconcentrated under vacuo to give the crude product which was purified by column chromatography using hexane: ethylacetate as an eluent to get the title compounds (3a-n). It is noteworthy to mention that, in the presence of free aminogroup, coupling reaction underwent smoothly with desired products in good yields. 3.2.1. 4-(2'-Chlorobiphenyl-4-yl) thiazol-2-amine (3b)Yield: 84%; Pale yellow solid; mp: 120-122°C; IR γmax(KBr) 756, 866, 1028, 1231, 1571, 1622, 3059 cm-1; 1HNMR (400 MHz, DMSO-d6): δ 7.26 (s, 1H, thiazole-CH),7.40-7.43 (m, 3H, ArH), 7.50-7.53 (d, J = 8.4 Hz, 2H, ArH),7.55-7.57 (m, 1H, ArH), 7.82-7.84 (d, J = 8.8 Hz, 2H, ArH). 13C NMR (100 MHz, DMSO-d6): δ 103.3, 125.5, 126.0,128.0, 129.9, 130.2, 130.3, 131.6, 131.8, 139.4, 139.6, 170.5.HRMS (ESI) m/z Calcd for C15H11ClN2S [M + 1] + 287.7792,found 287.7799.
  • 73
  • [ 2103-94-8 ]
  • [ 872041-86-6 ]
  • 4-(4-(5-fluoropyridin-3-yl)phenyl)thiazol-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In 1,4-dioxane; ethanol; water; at 130℃; for 0.5h;Sealed tube; General procedure: 4-(4-bromophenyl)thiazol-2-amine (1.0 mmol) was takenin water:Ethanol:1,4dioxane (6 mL) mixture in 1:1:5 ratio, potassium carbonate (3.0 mmol) and different boronic acids(1.1 mmol) were added to the reaction mixture and degassed with nitrogen gas for 15 min with stirring at RT. Bis(triphenylphosphine) palladium(II) dichloride (0.1 mmol) catalyst was added to the mixture and heated for 30 min at 130C in seal tube. The reaction mixture was filtered through celite, washed with methanol and filtrate was concentrated under reduced pressure, the resulting residue was dilutedwith ethylacetate and washed with water and brine solution.The organic layer was dried over anhydrous Na2SO4 andconcentrated under vacuo to give the crude product which was purified by column chromatography using hexane: ethylacetate as an eluent to get the title compounds (3a-n). It is noteworthy to mention that, in the presence of free aminogroup, coupling reaction underwent smoothly with desired products in good yields.
  • 74
  • [ 2103-94-8 ]
  • [ 94839-07-3 ]
  • 4-(4-(benzo[d][1,3]dioxol-5-yl)phenyl)thiazol-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,4-dioxane; ethanol; water at 130℃; for 0.5h; Sealed tube; 3.2. General Procedure for the Synthesis of Compounds 3(a-n) General procedure: 4-(4-bromophenyl)thiazol-2-amine (1.0 mmol) was takenin water:Ethanol:1,4dioxane (6 mL) mixture in 1:1:5 ratio, potassium carbonate (3.0 mmol) and different boronic acids(1.1 mmol) were added to the reaction mixture and degassed with nitrogen gas for 15 min with stirring at RT. Bis(triphenylphosphine) palladium(II) dichloride (0.1 mmol) catalyst was added to the mixture and heated for 30 min at 130°C in seal tube. The reaction mixture was filtered through celite, washed with methanol and filtrate was concentrated under reduced pressure, the resulting residue was dilutedwith ethylacetate and washed with water and brine solution.The organic layer was dried over anhydrous Na2SO4 andconcentrated under vacuo to give the crude product which was purified by column chromatography using hexane: ethylacetate as an eluent to get the title compounds (3a-n). It is noteworthy to mention that, in the presence of free aminogroup, coupling reaction underwent smoothly with desired products in good yields.
  • 75
  • [ 2103-94-8 ]
  • 3-acetylphenylboronic acid [ No CAS ]
  • 1-(4'-(2-aminothiazol-4-yl)biphenyl-3-yl)ethanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,4-dioxane; ethanol; water at 130℃; for 0.5h; Sealed tube; 3.2. General Procedure for the Synthesis of Compounds 3(a-n) General procedure: 4-(4-bromophenyl)thiazol-2-amine (1.0 mmol) was takenin water:Ethanol:1,4dioxane (6 mL) mixture in 1:1:5 ratio, potassium carbonate (3.0 mmol) and different boronic acids(1.1 mmol) were added to the reaction mixture and degassed with nitrogen gas for 15 min with stirring at RT. Bis(triphenylphosphine) palladium(II) dichloride (0.1 mmol) catalyst was added to the mixture and heated for 30 min at 130°C in seal tube. The reaction mixture was filtered through celite, washed with methanol and filtrate was concentrated under reduced pressure, the resulting residue was dilutedwith ethylacetate and washed with water and brine solution.The organic layer was dried over anhydrous Na2SO4 andconcentrated under vacuo to give the crude product which was purified by column chromatography using hexane: ethylacetate as an eluent to get the title compounds (3a-n). It is noteworthy to mention that, in the presence of free aminogroup, coupling reaction underwent smoothly with desired products in good yields.
  • 76
  • [ 2103-94-8 ]
  • [ 1993-03-9 ]
  • 4-(2'-fluorobiphenyl-4-yl)thiazol-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,4-dioxane; ethanol; water at 130℃; for 0.5h; Sealed tube; 3.2. General Procedure for the Synthesis of Compounds 3(a-n) General procedure: 4-(4-bromophenyl)thiazol-2-amine (1.0 mmol) was takenin water:Ethanol:1,4dioxane (6 mL) mixture in 1:1:5 ratio, potassium carbonate (3.0 mmol) and different boronic acids(1.1 mmol) were added to the reaction mixture and degassed with nitrogen gas for 15 min with stirring at RT. Bis(triphenylphosphine) palladium(II) dichloride (0.1 mmol) catalyst was added to the mixture and heated for 30 min at 130°C in seal tube. The reaction mixture was filtered through celite, washed with methanol and filtrate was concentrated under reduced pressure, the resulting residue was dilutedwith ethylacetate and washed with water and brine solution.The organic layer was dried over anhydrous Na2SO4 andconcentrated under vacuo to give the crude product which was purified by column chromatography using hexane: ethylacetate as an eluent to get the title compounds (3a-n). It is noteworthy to mention that, in the presence of free aminogroup, coupling reaction underwent smoothly with desired products in good yields.
  • 77
  • [ 2103-94-8 ]
  • [ 128796-39-4 ]
  • 4-(4'-(trifluoromethyl)biphenyl-4-yl)thiazol-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,4-dioxane; ethanol; water at 130℃; for 0.5h; Sealed tube; 3.2. General Procedure for the Synthesis of Compounds 3(a-n) General procedure: 4-(4-bromophenyl)thiazol-2-amine (1.0 mmol) was takenin water:Ethanol:1,4dioxane (6 mL) mixture in 1:1:5 ratio, potassium carbonate (3.0 mmol) and different boronic acids(1.1 mmol) were added to the reaction mixture and degassed with nitrogen gas for 15 min with stirring at RT. Bis(triphenylphosphine) palladium(II) dichloride (0.1 mmol) catalyst was added to the mixture and heated for 30 min at 130°C in seal tube. The reaction mixture was filtered through celite, washed with methanol and filtrate was concentrated under reduced pressure, the resulting residue was dilutedwith ethylacetate and washed with water and brine solution.The organic layer was dried over anhydrous Na2SO4 andconcentrated under vacuo to give the crude product which was purified by column chromatography using hexane: ethylacetate as an eluent to get the title compounds (3a-n). It is noteworthy to mention that, in the presence of free aminogroup, coupling reaction underwent smoothly with desired products in good yields.
  • 78
  • [ 2103-94-8 ]
  • [ 1692-15-5 ]
  • 4-(4-(pyridin-4-yl)phenyl)thiazol-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,4-dioxane; ethanol; water at 130℃; for 0.5h; Sealed tube; 3.2. General Procedure for the Synthesis of Compounds 3(a-n) General procedure: 4-(4-bromophenyl)thiazol-2-amine (1.0 mmol) was takenin water:Ethanol:1,4dioxane (6 mL) mixture in 1:1:5 ratio, potassium carbonate (3.0 mmol) and different boronic acids(1.1 mmol) were added to the reaction mixture and degassed with nitrogen gas for 15 min with stirring at RT. Bis(triphenylphosphine) palladium(II) dichloride (0.1 mmol) catalyst was added to the mixture and heated for 30 min at 130°C in seal tube. The reaction mixture was filtered through celite, washed with methanol and filtrate was concentrated under reduced pressure, the resulting residue was dilutedwith ethylacetate and washed with water and brine solution.The organic layer was dried over anhydrous Na2SO4 andconcentrated under vacuo to give the crude product which was purified by column chromatography using hexane: ethylacetate as an eluent to get the title compounds (3a-n). It is noteworthy to mention that, in the presence of free aminogroup, coupling reaction underwent smoothly with desired products in good yields.
  • 79
  • [ 6165-69-1 ]
  • [ 2103-94-8 ]
  • 4-(4-(thiophen-3-yl)phenyl)thiazol-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,4-dioxane; ethanol; water at 130℃; for 0.5h; Sealed tube; 3.2. General Procedure for the Synthesis of Compounds 3(a-n) General procedure: 4-(4-bromophenyl)thiazol-2-amine (1.0 mmol) was takenin water:Ethanol:1,4dioxane (6 mL) mixture in 1:1:5 ratio, potassium carbonate (3.0 mmol) and different boronic acids(1.1 mmol) were added to the reaction mixture and degassed with nitrogen gas for 15 min with stirring at RT. Bis(triphenylphosphine) palladium(II) dichloride (0.1 mmol) catalyst was added to the mixture and heated for 30 min at 130°C in seal tube. The reaction mixture was filtered through celite, washed with methanol and filtrate was concentrated under reduced pressure, the resulting residue was dilutedwith ethylacetate and washed with water and brine solution.The organic layer was dried over anhydrous Na2SO4 andconcentrated under vacuo to give the crude product which was purified by column chromatography using hexane: ethylacetate as an eluent to get the title compounds (3a-n). It is noteworthy to mention that, in the presence of free aminogroup, coupling reaction underwent smoothly with desired products in good yields.
  • 80
  • [ 6165-68-0 ]
  • [ 2103-94-8 ]
  • 4-(4-(thiophen-2-yl)phenyl)thiazol-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,4-dioxane; ethanol; water at 130℃; for 0.5h; Sealed tube; 3.2. General Procedure for the Synthesis of Compounds 3(a-n) General procedure: 4-(4-bromophenyl)thiazol-2-amine (1.0 mmol) was takenin water:Ethanol:1,4dioxane (6 mL) mixture in 1:1:5 ratio, potassium carbonate (3.0 mmol) and different boronic acids(1.1 mmol) were added to the reaction mixture and degassed with nitrogen gas for 15 min with stirring at RT. Bis(triphenylphosphine) palladium(II) dichloride (0.1 mmol) catalyst was added to the mixture and heated for 30 min at 130°C in seal tube. The reaction mixture was filtered through celite, washed with methanol and filtrate was concentrated under reduced pressure, the resulting residue was dilutedwith ethylacetate and washed with water and brine solution.The organic layer was dried over anhydrous Na2SO4 andconcentrated under vacuo to give the crude product which was purified by column chromatography using hexane: ethylacetate as an eluent to get the title compounds (3a-n). It is noteworthy to mention that, in the presence of free aminogroup, coupling reaction underwent smoothly with desired products in good yields.
  • 81
  • [ 2103-94-8 ]
  • [ 55552-70-0 ]
  • 4-(4-(furan-3-yl)phenyl)thiazol-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,4-dioxane; ethanol; water at 130℃; for 0.5h; Sealed tube; 3.2. General Procedure for the Synthesis of Compounds 3(a-n) General procedure: 4-(4-bromophenyl)thiazol-2-amine (1.0 mmol) was takenin water:Ethanol:1,4dioxane (6 mL) mixture in 1:1:5 ratio, potassium carbonate (3.0 mmol) and different boronic acids(1.1 mmol) were added to the reaction mixture and degassed with nitrogen gas for 15 min with stirring at RT. Bis(triphenylphosphine) palladium(II) dichloride (0.1 mmol) catalyst was added to the mixture and heated for 30 min at 130°C in seal tube. The reaction mixture was filtered through celite, washed with methanol and filtrate was concentrated under reduced pressure, the resulting residue was dilutedwith ethylacetate and washed with water and brine solution.The organic layer was dried over anhydrous Na2SO4 andconcentrated under vacuo to give the crude product which was purified by column chromatography using hexane: ethylacetate as an eluent to get the title compounds (3a-n). It is noteworthy to mention that, in the presence of free aminogroup, coupling reaction underwent smoothly with desired products in good yields.
  • 82
  • [ 2103-94-8 ]
  • [ 135145-90-3 ]
  • 4-(2',5'-dichlorobiphenyl-4-yl)thiazol-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In 1,4-dioxane; ethanol; water; at 130℃; for 0.5h;Sealed tube; General procedure: 4-(4-bromophenyl)thiazol-2-amine (1.0 mmol) was takenin water:Ethanol:1,4dioxane (6 mL) mixture in 1:1:5 ratio, potassium carbonate (3.0 mmol) and different boronic acids(1.1 mmol) were added to the reaction mixture and degassed with nitrogen gas for 15 min with stirring at RT. Bis(triphenylphosphine) palladium(II) dichloride (0.1 mmol) catalyst was added to the mixture and heated for 30 min at 130C in seal tube. The reaction mixture was filtered through celite, washed with methanol and filtrate was concentrated under reduced pressure, the resulting residue was dilutedwith ethylacetate and washed with water and brine solution.The organic layer was dried over anhydrous Na2SO4 andconcentrated under vacuo to give the crude product which was purified by column chromatography using hexane: ethylacetate as an eluent to get the title compounds (3a-n). It is noteworthy to mention that, in the presence of free aminogroup, coupling reaction underwent smoothly with desired products in good yields.
  • 83
  • [ 2103-94-8 ]
  • [ 51067-38-0 ]
  • 4-(4'-phenoxybiphenyl-4-yl)thiazol-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,4-dioxane; ethanol; water at 130℃; for 0.5h; Sealed tube; 3.2. General Procedure for the Synthesis of Compounds 3(a-n) General procedure: 4-(4-bromophenyl)thiazol-2-amine (1.0 mmol) was takenin water:Ethanol:1,4dioxane (6 mL) mixture in 1:1:5 ratio, potassium carbonate (3.0 mmol) and different boronic acids(1.1 mmol) were added to the reaction mixture and degassed with nitrogen gas for 15 min with stirring at RT. Bis(triphenylphosphine) palladium(II) dichloride (0.1 mmol) catalyst was added to the mixture and heated for 30 min at 130°C in seal tube. The reaction mixture was filtered through celite, washed with methanol and filtrate was concentrated under reduced pressure, the resulting residue was dilutedwith ethylacetate and washed with water and brine solution.The organic layer was dried over anhydrous Na2SO4 andconcentrated under vacuo to give the crude product which was purified by column chromatography using hexane: ethylacetate as an eluent to get the title compounds (3a-n). It is noteworthy to mention that, in the presence of free aminogroup, coupling reaction underwent smoothly with desired products in good yields.
  • 84
  • [ 2103-94-8 ]
  • [ 942190-74-1 ]
  • 1-(4-(4-(2-aminothiazol-4-yl)phenyl)thiophen-2-yl)ethanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,4-dioxane; ethanol; water at 130℃; for 0.5h; Sealed tube; 3.2. General Procedure for the Synthesis of Compounds 3(a-n) General procedure: 4-(4-bromophenyl)thiazol-2-amine (1.0 mmol) was takenin water:Ethanol:1,4dioxane (6 mL) mixture in 1:1:5 ratio, potassium carbonate (3.0 mmol) and different boronic acids(1.1 mmol) were added to the reaction mixture and degassed with nitrogen gas for 15 min with stirring at RT. Bis(triphenylphosphine) palladium(II) dichloride (0.1 mmol) catalyst was added to the mixture and heated for 30 min at 130°C in seal tube. The reaction mixture was filtered through celite, washed with methanol and filtrate was concentrated under reduced pressure, the resulting residue was dilutedwith ethylacetate and washed with water and brine solution.The organic layer was dried over anhydrous Na2SO4 andconcentrated under vacuo to give the crude product which was purified by column chromatography using hexane: ethylacetate as an eluent to get the title compounds (3a-n). It is noteworthy to mention that, in the presence of free aminogroup, coupling reaction underwent smoothly with desired products in good yields.
  • 85
  • [ 50-00-0 ]
  • [ 2103-94-8 ]
  • [ 135-19-3 ]
  • 2-(4-(4-bromophenyl)thiazol-2-yl)-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% In methanol at 80 - 90℃; for 12h; 11 2-(4-(4-Chlorophenyl)thiazol-2-yl)-2,3-dihydro-8-methoxy-1H-naphtho[1,2-e][1,3]oxazine (4j) 2.4.11 2-(4-(4-Bromophenyl)thiazol-2-yl)-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazine (4k) Following general procedure C, compound 4k was purified by column chromatography, eluting with hexane-EtOAc (8:2). Pinkish white solid, yield 0.35 g, 82%, mp 219-222 °C. IR (cm-1): 2930.87, 1602.59, 1447.26, 1326.29, 1244.87, 1047.99, 829.07, 658.42, 551.27. 1H NMR(400 MHz, CDCl3) δ: 4.26 (1H; s; Thia-H), 5.15 (2H; s; O-CH2-), 5.55 (2H; s; O-CH2-N), 7.12 (1H; d; J = 9.2 Hz; Naph-H), 7.42-7.46 (3H; m; Naph-H & Ph-H), 7.49 (2H; d; J = 6.4 Hz; Ph-H), 7.54-7.58 (1H; m; Naph-H), 7.70-7.74 (2H; t; J = 9.2 Hz; Naph-H), 7.82 (1H; d; J = 8 Hz; Naph-H). 13C NMR δ: 46.45 (-N-CH2-), 76.55 (-N-CH2-O-), 111.23 (Thia C-5), 118.62, 121.02, 122.25, 124.11, 127.01, 128.61, 128.63, 128.72, 129.11, 129.50, 130.06, 132.79 (phenyl & naphthyl carbons), 133.23 (Ph C-4), 145.68 (Thia C-4), 150.55 (Naph C-2), 165.48 (Thia C-2). HRMS (ESI): m/z [M+H] calcd. For C21H16ON2SBr: 425.0141; found: 425.0150.
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