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[ CAS No. 2104-04-3 ] {[proInfo.proName]}

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Chemical Structure| 2104-04-3
Chemical Structure| 2104-04-3
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Product Details of [ 2104-04-3 ]

CAS No. :2104-04-3 MDL No. :MFCD00170663
Formula : C10H10N2OS Boiling Point : -
Linear Structure Formula :- InChI Key :YPVVEXKDPBRGIK-UHFFFAOYSA-N
M.W : 206.26 Pubchem ID :159644
Synonyms :

Calculated chemistry of [ 2104-04-3 ]

Physicochemical Properties

Num. heavy atoms : 14
Num. arom. heavy atoms : 11
Fraction Csp3 : 0.1
Num. rotatable bonds : 2
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 58.45
TPSA : 76.38 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.73 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.01
Log Po/w (XLOGP3) : 2.57
Log Po/w (WLOGP) : 2.41
Log Po/w (MLOGP) : 1.02
Log Po/w (SILICOS-IT) : 2.92
Consensus Log Po/w : 2.19

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.19
Solubility : 0.134 mg/ml ; 0.00065 mol/l
Class : Soluble
Log S (Ali) : -3.82
Solubility : 0.0311 mg/ml ; 0.000151 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.59
Solubility : 0.0535 mg/ml ; 0.000259 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.12

Safety of [ 2104-04-3 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 2104-04-3 ]

* 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 [ 2104-04-3 ]

[ 2104-04-3 ] Synthesis Path-Downstream   1~69

  • 1
  • [ 2104-04-3 ]
  • [ 79-04-9 ]
  • [ 6202-74-0 ]
YieldReaction ConditionsOperation in experiment
82% Stage #1: chloroacetyl chloride With triethylamine In tetrahydrofuran at 0℃; for 0.25h; Inert atmosphere; Stage #2: 4-(4-methoxyphenyl)-thiazol-2-yl-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.
77% With pyridine for 6.5h;
69% In benzene for 3h; Reflux;
67% With anhydrous Sodium acetate In glacial acetic acid for 6h; Heating; Synthesis of 2-chloro-N-(4-(4-substituted phenyl)thiazol-2-yl) acetamides (5a-f): General procedure General procedure: 4-(4-substituted phenyl) thiazol-2-amine (0.05 mole) wasdissolved in 25 mL glacial acetic acid containing saturated solution of sodium acetate. To this solution, chloroacetyl chloride (0.06 mole) was added with stirring. Then, the mixture was heated on water bath for 6 h, cool at room temperature, and then poured over crushed ice. The product precipitated out was then filtered, washed with water, dried,and recrystallized from ethanol to afford pure compound in satisfactory yield.
60% With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 1h; 6.1.17. 2-chloro-N-(4-phenylthiazol-2-yl)acetamide (8a) General procedure: To a vial was added 7a (1.76 g, 10 mmol) and DIPEA (2.3 ml,13 mmol). The mixture was stirred at 0 C in CH2Cl2 (50 ml), then asolution of chloroacetic chloride (0.83 ml, 11 mmol) in CH2Cl2(10 mL) was added to the mixture slowly. The mixture was thenwarm to room temperature and stirred for 1 h. After completion ofthe reaction, the mixture was diluted with CH2Cl2 and washedthrice with saturated NaCl. The organic layer was dried overanhydrous sodium sulfate, the solvent was removed under reducedpressure and the residual mass was purified by column chromatographyto obtain 8a as white solid (2.25 g, 89% yield).
60% With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 1h; Cooling with ice; 19 Example 19 Synthesis of 2-chloro-N-(4-p-methylphenylthiazol-2-yl)acetamide (Compound 6b) Compound 6a (206 mg, 1 mmol) was added to dry dichloromethane (5 ml) at room temperature, DIPEA (0.23 ml, 1.3 mmol) was added and chloroacetyl chloride (0.083 ml, 1.1 mmol) was added dropwise on ice bath. Stir for 1 hour at room temperature. TLC test. After the reaction was completed, it was diluted with dichloromethane (10 ml) and extracted three times with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, evaporated to dryness, and columned, petroleum ether:ethyl acetate=8:1, to give a white solid, yield: 60%.
35% With triethylamine In tetrahydrofuran; dichloromethane at 0 - 20℃; 4.3 Compound 5a-5f were obtained according to the following general procedure General procedure: To a solution of 1 molar equiv of 2-aminothiazole derivatives and 1.5 molar equiv of triethylamine in THF, 1.2 molar equiv of chloroacetyl chloride or 3-bromopropionyl chloride in THF/CH2Cl2 was added dropwise at 0 °C. The reaction mixture was stirred at room temperature, and monitored by TLC (petroleum ether/ethyl acetate = 2/1). After reaction complete, the solvent was removed and the residue was purified by flash chromatography (petroleum ether/ethyl acetate = 10/1) to yield the product.
In benzene
In propan-2-one
In benzene for 3h; Heating;
In benzene at 80℃; for 3h;
In N,N-dimethyl-formamide at 20℃; for 2h;
With triethylamine In tetrahydrofuran at 20℃;
In benzene at 80℃; for 3h; General procedure for the synthesis of 2-chloro-N-[1,3-(benzo)thiazol-2-yl]ethanamides (3a-e) and 3-chloro-N-[1,3-(benzo)thiazol-2-yl]propanamides (4a-c) General procedure: To a solution of 2-aminothiazole or 2-aminobenzothiazole, 4-substituted 2-aminothiazole or 2-aminobenzothiazole (0.025mol) in dry benzene a cooled solution of chloroacetyl or 3-chloropropionyl chloride (0.041mol) in dry benzene (9ml) was added dropwise. The reaction mixture was stirred for 3h at reflux temperature, and then solvent and surplus of chloroacetyl or 3-chloropropionyl chloride were removed in vacuum. The residue was washed with 5% aqueous sodium bicarbonate solution followed by cold water. The crude product was dried and crystallized from ethanol.
Stage #1: 4-(4-methoxyphenyl)-thiazol-2-yl-amine With potassium carbonate In dichloromethane at 20℃; for 0.5h; Stage #2: chloroacetyl chloride In dichloromethane at 20℃; Cooling with ice; Reflux; 2.2 General procedure: A suspension of 4-phenylthiazol-2-amine (2 g, 11.4 mM) and anhydrous potassium carbonate (1.89 g, 13.6 mM) in dichloromethane (20 mL) was stirred for 30 min at room temperature. The reaction mixture was then cooled on an ice bath followed by addition of ice-cooled solution of chloroacetyl chloride (1.5 g, 13.6 mM) in dichloromethane (25 mL) in drop wise manner over a period of 30 min. The reaction mixture was then stirred at room temperature overnight followed by reflux for additional 30 min. The excess solvent was distilled off and the residue obtained was neutralized with aqueous sodium bicarbonate solution (5% w/v).
With potassium carbonate In toluene for 3h; Reflux;
With triethylamine In dichloromethane at 20℃; for 24h;
With potassium carbonate In toluene for 8h; Reflux; 3.2. General procedure for the preparation of 2-chloro-acetamido-4-sbstituted arylthiazoles (2a-c) General procedure: A mixture of 2-amino 4-substitutedarylthiazoles (10 mmol) andchloroacetylchloride (15 mmol) was refluxed in dry toluene (20 ml) inthe presence of anhydrous K2CO3 (10 mmol) for 8 h. The reactionmixture was then filtered while hot and the filtrate was evaporated to dryness under vacuum. The residual mass was washed with water, driedand crystallized from ehanol to obtain white crystals with better yield.2-chloro-N-(4-(4-methoxyphenyl) thiazol-2-yl) acetamide (2a):White solid, M.P. (158 °C):IR (cm-1): 3414, 3043, 2928, 2844, 2042, 1692, 1615, 1567, 1493,1452, 1408, 1325, 1254, 1171, 1100, 1027, 970, 911, 533, 495. 1HNMR (300 MHz, CDCl3): δ 3.85 (s, 3H), 4.23 (s, 2H), 6.96 (d, 2H), 7.05(s, 1H), 7.73-7.76 (d, 2H), 10.01 (s, 1H, NH);13C NMR (75 MHz,CDCl3): δ 42.83, 56.00, 102.00, 113.76, 125.46, 129.15, 148.20,161.74, 165.00, 166.43
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; General procedure for the synthesis of (2-amino-4-phenylthiazole) amide derivatives (4a-4e) General procedure: Compounds 1, 2, and 3 (Ma et al. 2014) were obtainedaccording to the previously described method. Chloroacetylchloride (1.45 mmol) in CH2Cl2 (15 mL) wasadded dropwise to a cooled solution (0 °C) of 4-(4-methoxyphenyl)thiazol-2-amine 3 (1.21 mmol) and diisopropylethylamine(DIEA) (1.24 mmol) in CH2Cl2(25 mL). The completion of the reaction was assessed bythin-layer chromatography (TLC). The organic layer wasseparated, washed with saturated NaHCO3 solution(100 mL), water, and brine, the aqueous phase wasextracted with CH2Cl2 (60 mL), and the organic phaseswere collected, dried over anhydrous MgSO4, and evaporatedin vacuo. The product was separated and purifiedby column chromatography on silica gel using an ethylacetate/petroleum ether mixture (1/4) as the eluent toafford pure compound 4a (Scheme 1).
With triethylamine In dichloromethane at 20℃; for 24h;
With triethylamine In acetonitrile for 1h; Reflux;

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  • 2
  • [ 2104-04-3 ]
  • [ 6295-57-4 ]
  • [ 79420-11-4 ]
YieldReaction ConditionsOperation in experiment
With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline In N,N-dimethyl-formamide for 24h; Ambient temperature;
  • 3
  • [ 2104-04-3 ]
  • [ 691-64-5 ]
  • [ 136810-98-5 ]
YieldReaction ConditionsOperation in experiment
83% With sodium t-butanolate In tetrahydrofuran for 3.5h; Ambient temperature;
  • 4
  • [ 2104-04-3 ]
  • [ 614-23-3 ]
  • [ 89402-64-2 ]
YieldReaction ConditionsOperation in experiment
In acetone for 1h; Heating; Yield given;
  • 5
  • [ 2104-04-3 ]
  • [ 80-35-3 ]
  • [ 97855-01-1 ]
  • 6
  • [ 2104-04-3 ]
  • [ 526-08-9 ]
  • [ 97854-95-0 ]
  • 7
  • [ 17356-08-0 ]
  • [ 100-06-1 ]
  • [ 2104-04-3 ]
YieldReaction ConditionsOperation in experiment
97% With iodine In ethanol at 70℃; for 0.25h;
97% With iodine In ethanol at 70℃; for 0.25h;
94% With carbon tetrabromide; triethylamine In acetonitrile at 20℃; for 2h; 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.
93% Stage #1: 1-(4-methoxyphenyl)ethanone With polymer-supported [(hydroxy(sulfonyloxy)iodo]benzene In acetonitrile for 16h; Heating; Stage #2: thiourea With potassium carbonate In acetonitrile for 6h; Heating;
91% With iodine; N-triethylammonium hydrogen sulfate In neat (no solvent) at 40℃;
90% With iodine In dimethyl sulfoxide at 85℃; for 4.5h; 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.
85% With iodine In ethanol for 14h; Heating;
85% With iodine In ethanol for 16h; Reflux; 4.1.5. General procedure for the synthesis of 2-amino-4-phenylthiazoles (9a-b) General procedure: 2-Amino-4-phenyl thiazoles (9aeb) were synthesized by using substituted acetophenones (7a-b) (0.0037 mol) and thiourea (8) (0.004 mol). The reaction mixture was refluxed for 16 h in the presence of iodine (0.0074 mol) and ethanol as a solvent. The product was basified with sodium hydroxide solution to get the white solid. The product was recrystallized from ethanol to get needle like crystals [31].
85% With iodine In ethanol for 16h; Reflux;
84% With iodine for 16h; Heating;
83% With sodium iodine dichloride In tetrahydrofuran; lithium hydroxide monohydrate 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).
81% With bromine In ethanol for 11h; Reflux;
80% 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).
79% With N,N',N,N'-tetrabromo-benzene-1,3-disulfonylamide In neat (no solvent) at 80℃; for 1.5h;
73% Stage #1: thiourea; 1-(4-methoxyphenyl)ethanone In propyl alcohol for 2h; Reflux; Stage #2: With pyridine In propyl alcohol for 5h; Reflux; 2.1.7. Synthesis of 4-(4-methoxyphenyl)thiazol-2-amine (TA) In 100 ml RBF, a solution of 0.01 mol thiourea and 0.01mol p-methoxy acetophenone in 35 ml N-propanol (35 ml)were taken and refluxed for 2 hours. Drop by drop with vigorousstirring 5 ml of pyridine was added to the above solutionand refluxed for 5 hours further. Evaporated the solutionto dryness and mixed with sodium bicarbonate solution (5%). The obtained product [4-(4-methoxyphenyl)thiazol-2-amine (TA)] was filtered, washed with water and dried. Theproduct was recrystallized using methanol. Yield (in %): 73. Melting point (in °C): 205-207. IR(KBr) cm-1: 3349 (N-H stretching), 3035 (Aromatic C-Hstretching), 2921 (Aliphatic C-H stretching), 1632 (C=Nstretching), 1608 (C=C stretching), 1376 (CH3 bending),1024 (C-O-C stretching). 1H-NMR (CDCl3, 300 MHz) δppm: 6.84-7.78 (m, 4H, Aromatic C-H), 6.46 (s, 1H, =CH ofthiazole), 4.75 (s, 2H, NH2), 3.91 (s, 3H, OCH3). 13C-NMR(CDCl3, 125 MHz) δ ppm: 173.9 (C=N of thiazole), 168.0(C-4), 153.6 (C-4 of thiazole), 130.3 (C-2 & C-6), 127.3 (C-1), 119.7 (C-3 & C-5), 107.1 (C-5 of thiazole), 56.5 (OCH3).EI-MS (m/z): 206 (M+). Anal. Calcd for C10H10N2OS: C,58.23; H, 4.89; N, 13.58. Found: C, 58.44; H, 4.87; N, 13.54.
73% Stage #1: thiourea; 1-(4-methoxyphenyl)ethanone In propyl alcohol for 2h; Reflux; Stage #2: With pyridine In propyl alcohol for 5h; Reflux; 2.1.7. Synthesis of 4-(4-methoxyphenyl)thiazol-2-amine (TA) In 100 ml RBF, a solution of 0.01 mol thiourea and 0.01mol p-methoxy acetophenone in 35 ml N-propanol (35 ml)were taken and refluxed for 2 hours. Drop by drop with vigorousstirring 5 ml of pyridine was added to the above solutionand refluxed for 5 hours further. Evaporated the solutionto dryness and mixed with sodium bicarbonate solution (5%). The obtained product [4-(4-methoxyphenyl)thiazol-2-amine (TA)] was filtered, washed with water and dried. Theproduct was recrystallized using methanol. Yield (in %): 73. Melting point (in °C): 205-207. IR(KBr) cm-1: 3349 (N-H stretching), 3035 (Aromatic C-Hstretching), 2921 (Aliphatic C-H stretching), 1632 (C=Nstretching), 1608 (C=C stretching), 1376 (CH3 bending),1024 (C-O-C stretching). 1H-NMR (CDCl3, 300 MHz) δppm: 6.84-7.78 (m, 4H, Aromatic C-H), 6.46 (s, 1H, =CH ofthiazole), 4.75 (s, 2H, NH2), 3.91 (s, 3H, OCH3). 13C-NMR(CDCl3, 125 MHz) δ ppm: 173.9 (C=N of thiazole), 168.0(C-4), 153.6 (C-4 of thiazole), 130.3 (C-2 & C-6), 127.3 (C-1), 119.7 (C-3 & C-5), 107.1 (C-5 of thiazole), 56.5 (OCH3).EI-MS (m/z): 206 (M+). Anal. Calcd for C10H10N2OS: C,58.23; H, 4.89; N, 13.58. Found: C, 58.44; H, 4.87; N, 13.54.
63% With iodine at 100℃; for 2h;
62% Stage #1: thiourea; 1-(4-methoxyphenyl)ethanone In propyl alcohol for 2h; Reflux; Stage #2: With pyridine In propyl alcohol for 5h; Reflux;
60% Stage #1: 1-(4-methoxyphenyl)ethanone With NBS; toluene-4-sulfonic acid In dichloromethane for 12h; Reflux; Stage #2: thiourea In ethanol for 2h; Reflux; 47 Example 47 4- ((3,5-dimethylisoxazole-4-yl)methoxy) -N- (4-(4-methoxyphenyl)thiazole-2-yl)-3-methylbenzamide synthesis (ZAC1) Commercially available p-methoxyacetophenone and p-toluenesulfonic acid (TsOH, 0.1 eq) were dissolved in dry dichloromethane,Stir at room temperature,N-Bromosuccinimide (NBS, 1.0 eq) was added in batches,Heating to reflux, after 12h, TLC detected that the reaction was complete,The reaction solution changed from pale yellow to reddish brown.After cooling to room temperature, add an appropriate amount of saturated brine to wash, extract with dichloromethane,It was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was separated by column chromatography to obtain a brown-red oil.Thiourea (1.2eq) was dissolved in ethanol, stirred at room temperature,An ethanol solution of brown-red oil was added and heated to reflux.After 2h, TLC detected that the reaction was complete, and the reaction solution changed from light yellow to dark yellow.After cooling, the solvent was evaporated under reduced pressure, washed with an appropriate amount of saturated sodium bicarbonate solution, and extracted with ethyl acetate.Dry over anhydrous sodium sulfate, evaporate the solvent under reduced pressure,The residue was separated by column chromatography to obtain 4-(4-methoxyphenyl)thiazol-2-amine as a pale yellow solid in a yield of 60%.
46% With bromine at 80℃; for 16h;
36.1% With iodine at 150℃;
With bromine 1.) dioxane, dichloroethane, 60-70 deg C, 2 h, reflux, 4 h; 2.) 60-70 deg C, 2 h, reflux, 4 h; Yield given. Multistep reaction;
1.42 g With iodine for 4h; Heating;
With iodine
With iodine
With iodine
With halogen for 24h; Reflux;
With iodine at 140℃; for 0.166667h; Microwave irradiation;
With iodine In ethanol for 72h; Reflux;
With iodine In ethanol for 72h; Reflux;
With bromine 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 bromine Synthesis of 4-(4-substituted phenyl)thiazol-2-amines(4a-f): General procedure: General procedureVarious 4-(4-substituted phenyl)thiazol-2-amines were synthesized form acetophenone, thiourea, and bromine.
With iodine for 24h; Heating;
With iodine In ethanol Reflux;
With sodium dichloroiodate In tetrahydrofuran; lithium hydroxide monohydrate 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.
With bromine 2-Amino-4-substituted phenyl-1,3-thiazoles(4A1-4K11) General procedure: The thiazoles 4A1-4K11 were synthesized accordingto literature procedure[17] involving reaction of aromaticketones with thiourea in the presence of bromine.
With iodine at 100℃; Procedure for 2-amino-4-(4-methoxyphenyl)thiazole2a49 The title compound was set up by the expansionof resublimed iodine (0.01 moles) to 1-(4-methoxyacetophenone (0.01 mol) and thiourea(0.02 mol), trailed by warming of the blend on a waterbath at 100°C. The cooled reaction mixture wastriturated with diethyl ether to evacuate any unreactediodine and acetophenone. The solid residue wasplaced in cold water (250 mL) and treated withaqueous ammonium hydroxide. The precipitatedthiazole was gathered and cleansed by crystallizationfrom ethanol. The yield was 88%.
With iodine at 80℃;

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  • [ 17356-08-0 ]
  • [ 2632-13-5 ]
  • [ 2104-04-3 ]
YieldReaction ConditionsOperation in experiment
100% In ethanol at 45℃; for 0.333333h; Sonication; Synthesis of 2-amino-4-substituted phenyl-1,3-thiazoles(1b-7b) General procedure: α-Bromoarylethanones (deliquescent) were prepared accordingto the reported method [18]. The ethanolic mixture of α-bromoarylethanone (1a, 1 mmol) and thiourea in the boiling tube was ultrasonicated at 45 °C in an ultrasonic bath. The reaction was monitored by TLC at every 5 min. It was found that the heterocyclization was completed within 20 min. The same procedure was followed for the synthesis of 2-amino-4-substituted phenyl-1,3-thiazoles listed in Table 1
100% In ethanol for 2h; Reflux;
99% In ethanol for 1h; Reflux; 4-(4-Methoxyphenyl)thiazol-2-amine. A mixture of 2-bromo-1-(4-methoxyphenyl)ethanone (5.00 g, 21.8 mmol) and thiourea (1.72 g, 22.6 mmol) in 95% EtOH (40 mL) was heated at reflux for 60 min. The solution was concentrated and mixed with water (100 mL) and saturated aqueous Na2CO3 (5.0 mL). The resultant precipitate was filtered and recrystallized in toluene. The solids were filtered and dried under vacuum to give 4-(4-methoxyphenyl)thiazol-2-amine (5.24 g) as yellow solids in >99% yield: 1H NMR (500 MHz, DMSO-d6) δ 7.72 (d, 2H), 6.99 (s, 2H), 6.92-6.91 (m, 2H), 6.82 (s, 1H), 3.76 (s, 3H).
99% In ethanol for 1h; Reflux; 4-(4-Methoxyphenyl)thiazol-2-amine A mixture of 2-bromo-1-(4-methoxyphenyl)ethanone (5.00 g, 21.8 mmol) and thiourea (1.72 g, 22.6 mmol) in 95% EtOH (40 mL) was heated at reflux for 60 min. The solution was concentrated and mixed with water (100 mL) and saturated aqueous Na2CO3 (5.0 mL). The resultant precipitate was filtered and recrystallized in toluene. The solids were filtered and dried under vacuum to give 4-(4-methoxyphenyl)thiazol-2-amine (5.24 g) as yellow solids in >99% yield: 1H NMR (500 MHz, DMSO-d6) δ 7.72 (d, 2 H), 6.99 (s, 2 H), 6.92-6.91 (m, 2 H), 6.82 (s, 1 H), 3.76 (s, 3 H).
98% In ethylene glycol at 20℃; for 0.166667h;
98% In lithium hydroxide monohydrate at 25℃; for 0.00277778h; 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.
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].
94% at 20℃; for 0.25h; Neat (no solvent); Grinding;
94% Stage #1: thiourea; 2-bromo-1-(4-methoxyphenyl)ethan-1-one In propan-2-one at 20℃; Stage #2: With ammonia In lithium hydroxide monohydrate 2 4-(4-methoxyphenyl)thiazol-2-amine 2.2 4-(4-methoxyphenyl)thiazol-2-amine (2) A mixture of thiourea (0.53 g, 7 mmol) and 1 (1.6 g, 7 mmol) in 70 ml acetone was stirred overnight at room temperature and filtered to afford the corresponding hydrobromide salt quantitatively. Then, the salt was treated with 5% ammonia solution with stirring and filtered to give the desired thiazole product 2 as a white powder. Yield: 94%. Mp 205-206 °C [28] . 1H NMR (600 MHz, DMSO-d6) δ 3.77 (s, 3H, OCH3), 6.84 (s, 1H, 5-H), 6.93 (d, 2H, J = 4.8 Hz, Ar-H), 7.04 (s, 2H, NH2), 7.3 (d, 2H, J = 4.8 Hz, Ar-H). 13C NMR (125 MHz, DMSO-d6) δ 55.02, 99.28, 113.76, 126.78, 127.77, 149.59, 158.45, 168. MS m/z (%) 206 (M+, 100), 191 (45.8), 149 (43.4), 121 (33.8), 77 (25). IR ν/cm-1 3438, 3267, 3118, 2965, 1623, 1535, 1492, 1177, 1033, 834, 737, 698. Calcd for C10H10N2OS: C, 58.23%; H, 4.89%; N, 13.58%; S, 15.54. Found: C, 58.45%; H, 4.93%; N, 13.74%; S, 15.04.
93% With sodium flouride In methanol; lithium hydroxide monohydrate 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.
93% 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. 2.3.1 4-(4-methoxyphenyl)thiazol-2-amine(3a) Following general procedure B, compound 3a was purified by recrystallization in absolute 17 ethanol. Crystalline white solid, yield 0.19 g, 93% 1H NMR(400 MHz, CDCl3) δ: 3.81 (3H; s; OCH3), 6.36 (1H; s; Thia-H), 6.94 (2H, d; J=8.8 Hz; Ph-H), 7.66 (2H; d; J=8.8 Hz, Ph-H), 8.87 (2H; bs; NH2).
91% In ethanol at 100℃; for 0.25h; Sealed tube; Microwave irradiation; Inert atmosphere; 4.5. Microwave-assisted synthesis of substituted 4-phenylthiazol-2-amines (15e18) via Hantzsch condensation General procedure: 4.5. Microwave-assisted synthesis of substituted 4-phenylthiazol-2-amines (15e18) via Hantzsch condensationIn a sealed tube, a stirred solution of thiourea (10.91 mmol) andthe appropriate a-bromoacetophenone (10.91 mmol) in ethanol(15 mL) was irradiated (800 W) at 100 C for 15 min. The solventwas evaporated to dryness. The solid residue was neutralized witha saturated solution of sodium bicarbonate and extracted threetimes with methylene chloride. The organic layer was dried overmagnesium sulfate and the solvent was evaporated to dryness. Thesolid residuewas agitated for 30 min in cyclohexane and filtered offto afford the 4-phenylthiazol-2-amine in analytically pure form.
91.6% In ethanol at 80℃; for 3h; 1.1. Chemistry experimental procedure A of intermediates 3a-j General procedure: Some of the intermediates 3a-j were commercially unavailable or expensive, so the compounds were obtained by the following chemistry experimental procedure A. To a solution of bromoacetophenone analogue (1 mmol) in anhydrous ethanol (30 mL), thiourea (1 mmol) was added, and the mixture solution was stirred at 80 °C for 3 h. The completion of the reaction was monitored by TLC. The mixed solution was concentrated under reduced pressure to remove the solvent, and the saturated NaHCO3 solution was added to adjust the pH to 8~9. Large amounts of solids were observed to precipitate out of the solution. The solid was collected by suction filtration, washed with anhydrous ethanol and dried in vacuo to obtain the crude product. The crude product was purified by silica gel column chromatography eluting with a gradient of ethyl acetate/petroleum ether mixture to afford pure intermediates 3a-j
91.6% In ethanol at 80℃; for 3h; 1.1. Chemistry experimental procedure A of intermediates 3a-j General procedure: Some of the intermediates 3a-j were commercially unavailable or expensive, so the compounds were obtained by the following chemistry experimental procedure A. To a solution of bromoacetophenone analogue (1 mmol) in anhydrous ethanol (30 mL), thiourea (1 mmol) was added, and the mixture solution was stirred at 80 °C for 3 h. The completion of the reaction was monitored by TLC. The mixed solution was concentrated under reduced pressure to remove the solvent, and the saturated NaHCO3 solution was added to adjust the pH to 8~9. Large amounts of solids were observed to precipitate out of the solution. The solid was collected by suction filtration, washed with anhydrous ethanol and dried in vacuo to obtain the crude product. The crude product was purified by silica gel column chromatography eluting with a gradient of ethyl acetate/petroleum ether mixture to afford pure intermediates 3a-j
89% In lithium hydroxide monohydrate at 20℃; for 1h;
89% With tetra-n-butylammonium hexafluoridophosphate In methanol at 20℃; for 0.233333h;
89% In ethanol for 2h; Reflux;
88% With 1,3-di-n-butylimidazolium tetrafluoroborate at 20℃; for 0.25h;
87% In ethanol at 80℃; for 0.333333h; Microwave irradiation;
85% In ethanol; lithium hydroxide monohydrate at 20℃; for 0.15h; Irradiation;
85% 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
84.4% In lithium hydroxide monohydrate Microwave irradiation; General procedure for the synthesis of 2-amino-4-(4-substituted phenyl)thiazoles (2a-c): General procedure: Substituted phenacylbromide (0.01 mol) and thiourea (0.76 g, 0.01 mol) were takenin a reaction vessel and added water (10 mL). The reactionmixture was irradiated under micro wave (40 W) for 10-15min. The solid separated was filtered, washed with water andrecrystallized from absolute alcohol [17,23].
81% With sodium hydrogen sulphate In lithium hydroxide monohydrate at 20℃; for 0.5h; regioselective reaction;
81% In methanol at 20℃; for 3h;
73% In acetonitrile for 3h; Reflux;
70% In ethanol; lithium hydroxide monohydrate Reflux; 2.2. Synthesis of 2-amino-4-(4-substituted-phenyl) thiazoles (1a-b) General procedure: The 2-amino-4-(4-substituted-phenyl)thiazole derivatives (1a-b) were synthesized by the reaction of 4-methoxy/nitro substituted phenacyl bromide (1 mmol) with thiourea (1 mmol). 15 mL aqueous ethanol was refluxed with constant stirring for about 2-3 h according to the procedure of Ramamurthy et al., [22] then recrystallized using methanol and dried to afford pure solid products ( Scheme 1 ). The reported m.p. of compounds 1a and 1b are 208 °C and 238 °C, respectively. 2.2.1. 4-(4-methoxyphenyl)-1,3-thiazol-2-amine (1a) White solid, yield-70%, m.p. 206-208 °C; 1 H NMR (400 MHz, DMSO-d 6 , δppm): 3.78 (s, 3H, OCH 3 ), 7.21 (s, 2H, NH 2 ), 7.40 (s, 1H, CH), 8.11-8.13 (d, J = 8 Hz, 2H, Ar-H), 8.20-8.22 (d, J = 8 Hz, 2H, Ar-H); 13 C NMR (100 MHz, DMSO-d 6 , δppm): 56.18 (OCH 3 ), 107.12, 125.10, 127.51, 142.01, 147.12, 148.26 and 169.03 (C -NH 2 ); HRMS: m/z 206.0120 [M + H] + .
67.6% In ethanol for 24h; Reflux;
65% With sodium hydrogen sulphate In lithium hydroxide monohydrate 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).
64% In lithium hydroxide monohydrate at 20℃; for 2h; 6.1.8. 4-phenylthiazol-2-amine (7a) General procedure: To a solution of thiourea (1.67 g, 22 mmol) inwater (100 ml) wasadded 2-bromo-1-phenylethanone (3.98 g, 20 mmol). The mixturewas stirred at room temperature for 2 h. After the completion of thereaction, the mixture was filtered to obtain the crude solid product.The crude product was further purified by recrystalization usingEtOH/H2O to afford the pure product 7a as white acicular crystal(3.20 g, 91% yield).
64% In lithium hydroxide monohydrate at 20℃; for 2h; 7 Example 7 Synthesis of 4-(4-methoxyphenyl)thiazol-2-amine (Compound 6a) 2-bromo-4'-methoxyacetophenone (416 mg, 2 mmol) and thiourea (167 mg, 2.2 mmol) were added to 5 ml of water at room temperature and stirred for 2 h at room temperature. TLC tests the reaction of the raw materials completely. Filtration, the filtrate was extracted with ethyl acetate 3 times, spin-drying to give a white solid, the residue was combined, recrystallization with EtOH / H2O to give white needles, yield 64%.
57% In ethanol at 50℃; for 0.5h; Microwave irradiation;
In ethanol for 3h; Heating; Yield given;
With 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene on polystyrene.HL In tetrahydrofuran for 0.5h; Heating;
at 20℃; for 0.0833333h; grinding; neat (no solvent);
In PEG-400 at 20℃; for 1h;
In ethanol for 2h; Reflux; 5.1.2. General procedure for the synthesis of 4-(2-chlorophenyl)thiazol-2-amine General procedure: The crude 2-bromo-1-(2-chlorophenyl)ethanone (0.64 mL, 4.28 mmol) was dissolved in anhydrous ethanol (10 mL) and treated with thiourea (344 mg, 4.51 mmol). After heating at reflux for 2 h, the reaction mixture was cooled to room temperature, with a yellow precipitation. The solid obtained was filtered, washed with water and ethanol and vacuum dried to afford 4b as a yellow solid (884 mg, 98.0%).
With potassium carbonate In ethyl acetate for 5h; Reflux;
at 20℃; for 4h; Ionic liquid;
In isopropanol for 1.5h; Reflux;
In ethanol for 1.5h; Reflux;
In ethanol for 1.5h; Reflux;
In ethanol for 3h; Reflux;
In ethanol at 20℃; 2.1 General procedure: Phenacylbromide (5.0 g, 25 mM) and thiourea (1.9 g, 25 mM) were taken in a 50 mL round bottom flask equipped with a condenser, calcium chloride guard tube and magnetic stirrer. The mixture was dissolved in dry ethanol (30 mL) and stirred at room temperature for overnight. Excess solvent was distilled off and the concentrated reaction mixture was slowly poured into a beaker containing ice-cooled saturated sodium bicarbonate solution. The yellow colored precipitate obtained was filtered off, washed thoroughly with chilled water and dried under vacuum (4.2 g, yield: 95%). TLC (ethyl acetate/hexane (1:3), Rf = 0.14). The product obtained was used in the next step without further purification.
In ethanol for 3h; Reflux; General procedure: (iii) A mixture of the above synthetic 9a-10n(calculate to yield 100% for last step, 4 mmol, 1.0 equiv.) and thiourea (4.4 mmol,1.1 equiv.) in anhydrous ethanol (50 mL) was refluxed for 3 h. After that, thesolvent was removed in vacuo andwashed with cold ether. Then the mixture was extracted dichloromethane (3*15mL) and washed with saturated aqueous NaHCO3. The combined organicphases were dried with anhydrous Na2SO4. Then removingthe solvent, the residue was purified by silica gel column (hexane/EtOAc=8:1 to4:1) and dried under vacuum to give 4-arylthiazol-2-amine 10a-10n, yieldwas 50~90%.
With triethylamine In ethanol Reflux;
Reflux;
In ethanol Reflux;
In methanol
In ethanol for 8h; Reflux;
In ethanol for 5h; Reflux;
In ethanol at 85℃; for 12h; 2.1.3. General Procedure for the Synthesis of 4-Arylthiazol-2-Amines (4l-4o) General procedure: To a solution of α-bromoacetophenone (3a-3d, 50 mmol)in ethanol (110 mL), thiourea (60 mmol) was added. Themixture was stirred at 85°C. After 12 h, the mixture waspoured into water, the precipitate was collected through filtration. The precipitate was recrystallized from ethanol toafford compound 4l-4o.
In ethanol Reflux;
In ethanol at 20℃; for 1h; General synthesis of 4-(substituted aryl)thiazol-2-amine (1, 2, 3) General procedure: 2-bromo-1-(naphthalen-2-yl)ethan-1-one (3.0 g, 12.043mmol)was reacted with thiourea (0.917 g, 12.043mmol) in ethanol(20mL) for 1 h at room temperature to obtain 4-(naphthalen-2-yl)-1,3-thiazol-2-amine (1). Likewise, with the same reactionconditions, 2-bromo-1-(4-chlorophenyl)ethan-1-one (3.0 g,13.096mmol) was reacted with thiourea (0.997 g, 13.096mmol)to obtain 4-(4-chlorophenyl)-1,3-thiazol-2-amine (2); and 2-bromo-1-(4-methoxyphenyl)ethan-1-one (3 g, 13.096mmol)with thiourea (0.997 g, 13.096mmol) to obtain 4-(4-methoxyphenyl)-1,3-thiazol-2-amine (3). The reaction was monitoredusing TLC. The mixture was filtered after the reaction was finished,and the residue was recrystallized using ethanol.
In ethanol at 80℃; for 1h; 1.1 Step 1: Synthesis of Compound 1-1 Compound 2-bromo-1-(4-methoxyphenyl)ethan-1-one (5 g) and thiourea (1.71 g) were dissolved in ethanol (20 mL) at room temperature, and reacted at 80° C. for 1 hour. The ethanol was evaporated to obtain a white solid residue, to which was added water, saturated sodium bicarbonate solution, suction filtration, and the filter cake was washed with water and dried. The crude 1-1 (4.6 g) was obtained as a white solid.

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[54]Current Patent Assignee: BETTA PHARMACEUTICALS CO LTD - WO2022/95989, 2022, A1 Location in patent: Page/Page column 17
  • 9
  • [ 2104-04-3 ]
  • [ 22312-81-8 ]
  • 3-(2-methoxy-phenyl)-2-[4-(4-methoxy-phenyl)-thiazol-2-ylamino]-methyl}-3<i>H</i>-quinazolin-4-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
51.7% In pyridine for 4h; Heating;
  • 10
  • [ 2104-04-3 ]
  • [ 625-36-5 ]
  • [ 516451-70-0 ]
YieldReaction ConditionsOperation in experiment
In benzene for 3h; Heating;
In benzene at 80℃; for 3h;
In benzene at 80℃; for 3h; General procedure for the synthesis of 2-chloro-N-[1,3-(benzo)thiazol-2-yl]ethanamides (3a-e) and 3-chloro-N-[1,3-(benzo)thiazol-2-yl]propanamides (4a-c) General procedure: To a solution of 2-aminothiazole or 2-aminobenzothiazole, 4-substituted 2-aminothiazole or 2-aminobenzothiazole (0.025mol) in dry benzene a cooled solution of chloroacetyl or 3-chloropropionyl chloride (0.041mol) in dry benzene (9ml) was added dropwise. The reaction mixture was stirred for 3h at reflux temperature, and then solvent and surplus of chloroacetyl or 3-chloropropionyl chloride were removed in vacuum. The residue was washed with 5% aqueous sodium bicarbonate solution followed by cold water. The crude product was dried and crystallized from ethanol.
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.
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; General procedure for the synthesis of (2-amino-4-phenylthiazole) amide derivatives (4a-4e) General procedure: Compounds 1, 2, and 3 (Ma et al. 2014) were obtainedaccording to the previously described method. Chloroacetylchloride (1.45 mmol) in CH2Cl2 (15 mL) wasadded dropwise to a cooled solution (0 °C) of 4-(4-methoxyphenyl)thiazol-2-amine 3 (1.21 mmol) and diisopropylethylamine(DIEA) (1.24 mmol) in CH2Cl2(25 mL). The completion of the reaction was assessed bythin-layer chromatography (TLC). The organic layer wasseparated, washed with saturated NaHCO3 solution(100 mL), water, and brine, the aqueous phase wasextracted with CH2Cl2 (60 mL), and the organic phaseswere collected, dried over anhydrous MgSO4, and evaporatedin vacuo. The product was separated and purifiedby column chromatography on silica gel using an ethylacetate/petroleum ether mixture (1/4) as the eluent toafford pure compound 4a (Scheme 1).

  • 11
  • [ 2104-04-3 ]
  • [ 108-24-7 ]
  • [ 60867-76-7 ]
YieldReaction ConditionsOperation in experiment
85.7% With sulfuric acid; acetic acid for 1h; Reflux; 3 N-(4-(4-methoxyphenyl)thiazol-2-yl)acetamide 2.3 N-(4-(4-methoxyphenyl)thiazol-2-yl)acetamide (3) A mixture of 2 (4.12 g, 20 mmol), acetic anhydride (20 ml) and glacial acetic acid (100 ml) with few drops of conc. H2SO4 was refluxed for 1 h. The reaction mixture was allowed to cool at room temperature and then recrystallized from ethanol to afford compound 3. Yield: 85.7%. Mp 189-190 °C. 1H NMR (600 MHz, DMSO-d6) δ 2.16 (S, 3H, COCH3), 3.79 (S, 3H, OCH3), 6.99 (d, 2H, J = 7.14 Hz, Ar-H), 7.42 (S, 1H, 5-H), 7.82 (d, 2H, J = 7.08 Hz, Ar-H), 12.2 (S, 1H, NH). 13C NMR (125 MHz, DMSO-d6) δ 22.63, 55.27, 105.96, 114.22, 127.12, 127.27, 148.72, 157.94, 159.08, 168.8.
78.8% With sodium acetate Heating;
  • 12
  • [ 51527-73-2 ]
  • [ 2104-04-3 ]
  • [ 376349-13-2 ]
YieldReaction ConditionsOperation in experiment
262A 2,4,6-Trichloro-N-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]benzenesulfonamide The title compound was prepared from 4-(4-methoxy-phenyl)-thiazol-2-ylamine and <strong>[51527-73-2]2,4,6-trichlorobenzenesulfonyl chloride</strong> as described in the synthetic METHOD B to give a white-yellow solid (58.2 mg) with purity >90%. MS (pos) m/z 449.1, 451.1, 453.1.
  • 13
  • [ 2104-04-3 ]
  • [ 5462-71-5 ]
  • [ 934276-27-4 ]
YieldReaction ConditionsOperation in experiment
With N-[([(1E)-1-cyano-2-ethoxy-2-oxoethylidene]amino}oxy)(dimethylamino)-methylidene]-N-methylmethanaminium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; 1.41 g 4-(4-Methoxyphenyl)-1 ,3-thiazol-2-amine was dissoveld in 2 ml dimethylformamide. 3.0 ml N,N-Diisopropylethylamine, 1.O g commercially available (4- Cyano-phenyl)-acetic acid and 2.25 g O-((Ethoxycarbonyl)cyanomethyleneamino)- N,N,N',N'-tetramethyluronium tetrafluoroborat were added. The reaction mixture was stirred at room temperature overnight. Then 200 ml ethylacetate were added and the mixture was washed three times with portions of 50 ml saturated NaHCO3 solution and then dried over MgSO4. The solvents were removed in vacuo and the residue purified by RP-HPLC to obtain 610 mg 2-(4-Cyano-phenyl)-N-[4-(4-methoxy-phenyl)-thiazol-2- yl]-acetamide as yellow solid. C19H15N3O2S (349.41), MS (ESI): 350.1 (M+H+).
  • 14
  • [ 93435-57-5 ]
  • [ 17356-08-0 ]
  • [ 2104-04-3 ]
YieldReaction ConditionsOperation in experiment
90% With sodium carbonate In poly(ethylene glycol-400) at 20℃;
80% In water at 60℃; for 4h; General experimental procedure General procedure: To a stirred solution of aryl thioamide or amidine (1 mmol) in 5 mL distilled water was added α-tosyloxyketone (1 mmol) and the reaction mixture stirred at 60 °C or 80 °C till completion. Progress of the reaction was monitored by thin layer chromatography. After completion of the reaction, product was readily filtered and recrystallized from ethanol (3a-k, 3p-o and 4a-e). In some cases (3l-m and 4f-i) product was extracted with dichloromethane (25 mL), washed with brine (25 mL), the organic layers were combined, dried over anhydrous Na2SO4 and distilled off in vacuum. The residue so obtained was purified by column chromatography on silica gel (100-200 mesh) (EtOAc/Hexane) to give pure product.
  • 15
  • [ 2104-04-3 ]
  • [ 423-39-2 ]
  • [ 1257330-00-9 ]
YieldReaction ConditionsOperation in experiment
63% With sodium dithionite; sodium hydrogencarbonate In water; N,N-dimethyl-formamide at 5 - 10℃; Inert atmosphere; 4.2. Typical procedure for the polyfluoroalkylation of 2-aminothiazoles under sulfinato-dehalogenation conditions General procedure: Sodium dithionite (1.0 mmol) was added in one portion to a mixture of 2-aminothiazole (1.0 mmol), NaHCO3 (1.0 mmol) and polyfluoroalkyl iodide (1.5 mmol) in acetonitrile/water (4:1/v:v) at 5-10 °C under Ar atmosphere. The mixture was stirred until complete conversion of starting material as indicated by TLC analysis. Acetonitrile was removed under reduced pressure and water (5 mL) was added. The mixture was extracted with ethyl acetate (4.0 mL × 3) and the combined organic layers were dried over Na2SO4. The solvent was removed under vacuum and the residue was purified by column chromatography on silica gel (petroleum/ethyl acetate) to give the product.
  • 16
  • [ 2104-04-3 ]
  • [ 2752-65-0 ]
  • 4-(4-methoxyphenyl)thiazol-2-gambogamide [ No CAS ]
  • 17
  • [ 2104-04-3 ]
  • [ 159749-28-7 ]
  • [ 1400283-99-9 ]
  • 18
  • [ 212650-43-6 ]
  • [ 2104-04-3 ]
  • [ 1400284-00-5 ]
  • 19
  • [ 128453-98-5 ]
  • [ 2104-04-3 ]
  • [ 1400284-01-6 ]
  • 20
  • [ 2104-04-3 ]
  • [ 1214196-85-6 ]
  • [ 1400284-02-7 ]
  • 21
  • [ 2104-04-3 ]
  • [ 1401242-74-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C 2: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 3: triethylamine / dichloromethane / 20 °C
  • 22
  • [ 2104-04-3 ]
  • [ 15486-96-1 ]
  • [ 1359984-16-9 ]
YieldReaction ConditionsOperation in experiment
26% With triethylamine In tetrahydrofuran; dichloromethane at 0 - 20℃; 4.3 Compound 5a-5f were obtained according to the following general procedure General procedure: To a solution of 1 molar equiv of 2-aminothiazole derivatives and 1.5 molar equiv of triethylamine in THF, 1.2 molar equiv of chloroacetyl chloride or 3-bromopropionyl chloride in THF/CH2Cl2 was added dropwise at 0 °C. The reaction mixture was stirred at room temperature, and monitored by TLC (petroleum ether/ethyl acetate = 2/1). After reaction complete, the solvent was removed and the residue was purified by flash chromatography (petroleum ether/ethyl acetate = 10/1) to yield the product.
  • 23
  • [ 2104-04-3 ]
  • [ 31541-36-3 ]
  • [ 1450832-73-1 ]
YieldReaction ConditionsOperation in experiment
80% With aluminum oxide In ethyl acetate for 0.316667h; Microwave irradiation; Alkaline conditions; Green chemistry; Using inorganic solid supports in dry media. General procedure: Equimolar quantities of 4 and 5a were adsorbed separately on montmorillonite KSF and basic alumina (20% by weight of the reactants) via a solution in ethyl acetate, mixed thoroughly, and irradiated for 15 min at 640W until the completion of the reaction (monitored by TLC). The recyclable inorganic solid support was separated by filtration after eluting the product with ethanol. The solvent was evaporated to give the crystalline product 7a of reasonable purity (Table 3). Comparison of the results obtained by the conventional methods and MW-assisted synthesis prove basic alumina to be the most effective support. Likewise, the same procedure was followed for the synthesis of compounds 7b-g and their structural characterization was done on the basis of IR, 1H NMR, mass spectra, and elemental analysis (Tables 3 and 4 and supporting information).
  • 24
  • [ 2104-04-3 ]
  • [ 141-97-9 ]
  • [ 863107-04-4 ]
YieldReaction ConditionsOperation in experiment
75% Stage #1: 4-(4-methoxyphenyl)-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.
  • 25
  • [ 2104-04-3 ]
  • [ 2602-85-9 ]
  • N-[4-(4-methoxyphenyl)thiazol-2-yl]benzo[d]thiazole-2-carboximidamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
44% In N,N-dimethyl-formamide; at 180℃; for 3h;Sealed tube; Microwave irradiation; Inert atmosphere; General procedure: 4.6. Microwave-assisted synthesis of N-(4-phenylthiazol-2-yl)-benzo[d]thiazole-, thiazolo[4,5-b]pyridine-, thiazolo[5,4-b]pyridine-, benzo[d]oxazole-2-carboximidamides (19e45)In a sealed tube, a stirred solution of carbonitrile (2 mmol) andthe appropriate 4-phenylthiazol-2-amine (2.4 mmol) in dry DMF(4 mL) was heated under microwave irradiation (800 W) at 180 Cfor 3 h. Evaporation of the solvent gave a crude product, which waspurified by flash chromatography using petroleum ether/methylenechloride (100:0 to 0:100, v/v) as eluent. 4.6.1. N-(4-Phenylthiazol-2-yl)benzo[d]thiazole-2-carboximidamide(19). Yield 80% (0.536 g), yellow solid, mp228e230 C; IR (cm1)ymax 3364, 3107, 2914, 1619, 1592, 1537, 1509, 1476, 1318, 1234, 1117,1044, 818, 766, 754, 726, 619; 1H NMR (300 MHz, DMSO-d6) d 9.54(br s, bs, 1H, NH), 9.26 (br s, 1H, NH), 8.25e8.19 (m, 1H, Har), 8.16 (d,J7.5 Hz, 1H, Har), 7.95 (d, J7.2 Hz, 2H, H-Ph), 7.84 (s, 1H, Hthiazole),7.68e7.55 (m, 2H, Har), 7.48 (t, J7.5 Hz, 2H, H-Ph), 7.37 (t, J7.3 Hz,1H, H-Ph); 13C NMR (75 MHz, DMSO-d6) d 173.2, 165.6, 153.7, 151.8,151.7, 136.9, 134.6, 129.4 (2C), 128.7, 127.6, 127.5, 126.3 (2C), 124.2,123.4, 110.6; HRMS calcd for C17H13N4S2 [MH] 337.0582, found337.0596.
  • 26
  • [ 2104-04-3 ]
  • (4-benzoyl-2-methyl-phenoxy)-acetic acid [ No CAS ]
  • 2-(4-benzoyl-2-methyl-phenoxy)-N-[4-(4-methoxyphenyl)-thiazol-2-yl]-acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% Stage #1: 4-(4-methoxyphenyl)-1,3-thiazol-2-amine; (4-benzoyl-2-methyl-phenoxy)-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℃; 4.1.6. General procedure for the synthesis of 2-(4-benzoylphenoxy)-N-(4-phenyl-thiazol-2-yl)-acetamides (10a-n) General procedure: To the compounds 6a-h (0.0037 mol) in dry dichloromethane (15 mL), lutidine (1.2 vol.) was added at 25-30 °C, followed by the addition of 9a-b (0.0037 mol) and the mixture was stirred at 25-30 C for 30 min. The reaction was cooled to 0-5 °C and TBTU (0.0037 mol) was added over a period of 30 min while maintaining the temperature below 5 C. The reactionwas stirred overnight and monitored by TLC using chloroform:methanol (9:1) as an eluent. The reaction mixture was diluted with 20 mL of dichloromethane and washed with 1.5 N hydrochloric acid (20 mL). The organic layer was washed with water (25 mL x 3), dried over anhydrous sodium sulphate, concentrated to a syrupy liquid and recrystallized twice from diethyl ether to afford compounds 10a-n in good yield.
  • 27
  • [ 2104-04-3 ]
  • [2-methyl-4-(4-methyl-benzoyl)-phenoxy]-acetic acid [ No CAS ]
  • N-[4-(4-methoxyphenyl)-thiazol-2-yl]-2-[2-methyl-4-(4-methylbenzoyl)phenoxy]acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% Stage #1: 4-(4-methoxyphenyl)-1,3-thiazol-2-amine; [2-methyl-4-(4-methyl-benzoyl)-phenoxy]-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℃; 4.1.6. General procedure for the synthesis of 2-(4-benzoylphenoxy)-N-(4-phenyl-thiazol-2-yl)-acetamides (10a-n) General procedure: To the compounds 6a-h (0.0037 mol) in dry dichloromethane (15 mL), lutidine (1.2 vol.) was added at 25-30 °C, followed by the addition of 9a-b (0.0037 mol) and the mixture was stirred at 25-30 C for 30 min. The reaction was cooled to 0-5 °C and TBTU (0.0037 mol) was added over a period of 30 min while maintaining the temperature below 5 C. The reactionwas stirred overnight and monitored by TLC using chloroform:methanol (9:1) as an eluent. The reaction mixture was diluted with 20 mL of dichloromethane and washed with 1.5 N hydrochloric acid (20 mL). The organic layer was washed with water (25 mL x 3), dried over anhydrous sodium sulphate, concentrated to a syrupy liquid and recrystallized twice from diethyl ether to afford compounds 10a-n in good yield.
  • 28
  • [ 2104-04-3 ]
  • C16H13FO4 [ No CAS ]
  • 2-[4-(4-fluoro-benzoyl)-2-methyl-phenoxy]-N-[4-(4-methoxy-phenyl)-thiazol-2-yl]-acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% Stage #1: 4-(4-methoxyphenyl)-1,3-thiazol-2-amine; C16H13FO4 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℃; 4.1.6. General procedure for the synthesis of 2-(4-benzoylphenoxy)-N-(4-phenyl-thiazol-2-yl)-acetamides (10a-n) General procedure: To the compounds 6a-h (0.0037 mol) in dry dichloromethane (15 mL), lutidine (1.2 vol.) was added at 25-30 °C, followed by the addition of 9a-b (0.0037 mol) and the mixture was stirred at 25-30 C for 30 min. The reaction was cooled to 0-5 °C and TBTU (0.0037 mol) was added over a period of 30 min while maintaining the temperature below 5 C. The reactionwas stirred overnight and monitored by TLC using chloroform:methanol (9:1) as an eluent. The reaction mixture was diluted with 20 mL of dichloromethane and washed with 1.5 N hydrochloric acid (20 mL). The organic layer was washed with water (25 mL x 3), dried over anhydrous sodium sulphate, concentrated to a syrupy liquid and recrystallized twice from diethyl ether to afford compounds 10a-n in good yield.
  • 29
  • [ 2104-04-3 ]
  • [4-(benzoyl-2,6-dimethylphenoxy)]acetic acid [ No CAS ]
  • 2-(4-benzoyl-2,6-dimethyl-phenoxy)-N-[4-(4-methoxyphenyl)-thiazol-2-yl]-acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% Stage #1: 4-(4-methoxyphenyl)-1,3-thiazol-2-amine; [4-(benzoyl-2,6-dimethylphenoxy)]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℃; 4.1.6. General procedure for the synthesis of 2-(4-benzoylphenoxy)-N-(4-phenyl-thiazol-2-yl)-acetamides (10a-n) General procedure: To the compounds 6a-h (0.0037 mol) in dry dichloromethane (15 mL), lutidine (1.2 vol.) was added at 25-30 °C, followed by the addition of 9a-b (0.0037 mol) and the mixture was stirred at 25-30 C for 30 min. The reaction was cooled to 0-5 °C and TBTU (0.0037 mol) was added over a period of 30 min while maintaining the temperature below 5 C. The reactionwas stirred overnight and monitored by TLC using chloroform:methanol (9:1) as an eluent. The reaction mixture was diluted with 20 mL of dichloromethane and washed with 1.5 N hydrochloric acid (20 mL). The organic layer was washed with water (25 mL x 3), dried over anhydrous sodium sulphate, concentrated to a syrupy liquid and recrystallized twice from diethyl ether to afford compounds 10a-n in good yield.
  • 30
  • [ 2104-04-3 ]
  • C16H13BrO4 [ No CAS ]
  • 2-[4-(3-bromo-benzoyl)-2-methyl-phenoxy]-N-[4-(4-methoxy-phenyl)-thiazol-2-yl]-acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% Stage #1: 4-(4-methoxyphenyl)-1,3-thiazol-2-amine; C16H13BrO4 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℃; 4.1.6. General procedure for the synthesis of 2-(4-benzoylphenoxy)-N-(4-phenyl-thiazol-2-yl)-acetamides (10a-n) General procedure: To the compounds 6a-h (0.0037 mol) in dry dichloromethane (15 mL), lutidine (1.2 vol.) was added at 25-30 °C, followed by the addition of 9a-b (0.0037 mol) and the mixture was stirred at 25-30 C for 30 min. The reaction was cooled to 0-5 °C and TBTU (0.0037 mol) was added over a period of 30 min while maintaining the temperature below 5 C. The reactionwas stirred overnight and monitored by TLC using chloroform:methanol (9:1) as an eluent. The reaction mixture was diluted with 20 mL of dichloromethane and washed with 1.5 N hydrochloric acid (20 mL). The organic layer was washed with water (25 mL x 3), dried over anhydrous sodium sulphate, concentrated to a syrupy liquid and recrystallized twice from diethyl ether to afford compounds 10a-n in good yield.
  • 31
  • [ 2104-04-3 ]
  • C16H13FO4 [ No CAS ]
  • 2-[4-(3-fluoro-benzoyl)-2-methyl-phenoxy]-N-[4-(4-methoxy-phenyl)thiazol-2-yl]acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% Stage #1: 4-(4-methoxyphenyl)-1,3-thiazol-2-amine; C16H13FO4 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℃; 4.1.6. General procedure for the synthesis of 2-(4-benzoylphenoxy)-N-(4-phenyl-thiazol-2-yl)-acetamides (10a-n) General procedure: To the compounds 6a-h (0.0037 mol) in dry dichloromethane (15 mL), lutidine (1.2 vol.) was added at 25-30 °C, followed by the addition of 9a-b (0.0037 mol) and the mixture was stirred at 25-30 C for 30 min. The reaction was cooled to 0-5 °C and TBTU (0.0037 mol) was added over a period of 30 min while maintaining the temperature below 5 C. The reactionwas stirred overnight and monitored by TLC using chloroform:methanol (9:1) as an eluent. The reaction mixture was diluted with 20 mL of dichloromethane and washed with 1.5 N hydrochloric acid (20 mL). The organic layer was washed with water (25 mL x 3), dried over anhydrous sodium sulphate, concentrated to a syrupy liquid and recrystallized twice from diethyl ether to afford compounds 10a-n in good yield.
  • 32
  • [ 2104-04-3 ]
  • [ 108-94-1 ]
  • [ 123-11-5 ]
  • 2-[(4-methoxyphenyl)[4-(4-methoxyphenyl)thiazol-2-yl]amino}methyl]cyclohexanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% With triethylamine sulfate at 100℃; for 6h; General procedure for preparation of rac-(2S)-2-[(R)-[(4-substituted phenyl)[4-(4-substituted phenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanone (4a-u) [35] The selectivity of ionic liquids was optimized by investigating the preparation of rac-(2S)-2-[(R)-[(4-chloro phenyl)[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanones in sulfated ionic liquids derived from triethylamine, n-tripropylamine, di-isopropyl amine and tri-n-butyl amine. These reactions were carried out in four separate 100mL round bottomed flasks set in a water bath. Quaternary ammonium sulfated ionic liquids (0.05mmol) were added, drop wise at room temperature, to a well stirred solution of cyclohexanone (0.05mmol), 4-(4-methoxyphenyl) thiazole-2-amine (0.05mmol), and 2-chlorobenzaldehyde (0.05mmol) in each 100mL round bottom flask. All ionic liquids were intended to serve dual functions of solvent as well as catalysts. The mixtures were stirred for about 2h at room temperature and then refluxed for 6h at 100°C. The progress of the each reaction was monitored by TLC to ascertain the conversion levels. At the end of the reaction, the mixtures were treated with water. The products were separated by filtration as the ionic liquids could be dissolved in water, while the products could not. 100% conversion level with 90% isolated yield was observed in quaternary triethylammonium sulfated ionic liquid. The isolated product was purified by recrystallization from alcohol to give rac-(2S)-2-[(R)-(4-chloro phenyl)[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanone 4a. All ionic liquids were recovered by removing water under vacuum and oven drying. The quaternary triethylammonium sulfate [Et3NH][HSO4] was the choice of ionic liquid used in all further syntheses (4b-u).
  • 33
  • [ 2104-04-3 ]
  • [ 108-94-1 ]
  • [ 100-10-7 ]
  • 2-[((4-dimethylamino)phenyl)[4-(4-methoxyphenyl)thiazol-2-yl]amino}methyl]cyclohexanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With triethylamine sulfate at 100℃; for 6h; General procedure for preparation of rac-(2S)-2-[(R)-[(4-substituted phenyl)[4-(4-substituted phenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanone (4a-u) [35] The selectivity of ionic liquids was optimized by investigating the preparation of rac-(2S)-2-[(R)-[(4-chloro phenyl)[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanones in sulfated ionic liquids derived from triethylamine, n-tripropylamine, di-isopropyl amine and tri-n-butyl amine. These reactions were carried out in four separate 100mL round bottomed flasks set in a water bath. Quaternary ammonium sulfated ionic liquids (0.05mmol) were added, drop wise at room temperature, to a well stirred solution of cyclohexanone (0.05mmol), 4-(4-methoxyphenyl) thiazole-2-amine (0.05mmol), and 2-chlorobenzaldehyde (0.05mmol) in each 100mL round bottom flask. All ionic liquids were intended to serve dual functions of solvent as well as catalysts. The mixtures were stirred for about 2h at room temperature and then refluxed for 6h at 100°C. The progress of the each reaction was monitored by TLC to ascertain the conversion levels. At the end of the reaction, the mixtures were treated with water. The products were separated by filtration as the ionic liquids could be dissolved in water, while the products could not. 100% conversion level with 90% isolated yield was observed in quaternary triethylammonium sulfated ionic liquid. The isolated product was purified by recrystallization from alcohol to give rac-(2S)-2-[(R)-(4-chloro phenyl)[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanone 4a. All ionic liquids were recovered by removing water under vacuum and oven drying. The quaternary triethylammonium sulfate [Et3NH][HSO4] was the choice of ionic liquid used in all further syntheses (4b-u).
  • 34
  • [ 2104-04-3 ]
  • [ 108-94-1 ]
  • [ 459-57-4 ]
  • 2-[(4-fluorophenyl)[4-(4-methoxyphenyl)thiazol-2-yl]amino}methyl]cyclohexanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With triethylamine sulfate at 100℃; for 6h; General procedure for preparation of rac-(2S)-2-[(R)-[(4-substituted phenyl)[4-(4-substituted phenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanone (4a-u) [35] The selectivity of ionic liquids was optimized by investigating the preparation of rac-(2S)-2-[(R)-[(4-chloro phenyl)[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanones in sulfated ionic liquids derived from triethylamine, n-tripropylamine, di-isopropyl amine and tri-n-butyl amine. These reactions were carried out in four separate 100mL round bottomed flasks set in a water bath. Quaternary ammonium sulfated ionic liquids (0.05mmol) were added, drop wise at room temperature, to a well stirred solution of cyclohexanone (0.05mmol), 4-(4-methoxyphenyl) thiazole-2-amine (0.05mmol), and 2-chlorobenzaldehyde (0.05mmol) in each 100mL round bottom flask. All ionic liquids were intended to serve dual functions of solvent as well as catalysts. The mixtures were stirred for about 2h at room temperature and then refluxed for 6h at 100°C. The progress of the each reaction was monitored by TLC to ascertain the conversion levels. At the end of the reaction, the mixtures were treated with water. The products were separated by filtration as the ionic liquids could be dissolved in water, while the products could not. 100% conversion level with 90% isolated yield was observed in quaternary triethylammonium sulfated ionic liquid. The isolated product was purified by recrystallization from alcohol to give rac-(2S)-2-[(R)-(4-chloro phenyl)[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanone 4a. All ionic liquids were recovered by removing water under vacuum and oven drying. The quaternary triethylammonium sulfate [Et3NH][HSO4] was the choice of ionic liquid used in all further syntheses (4b-u).
  • 35
  • [ 2104-04-3 ]
  • [ 108-94-1 ]
  • [ 104-88-1 ]
  • rac-(2S)-2-[(R)-(4-chlorophenyl)[4-(4-methoxyphenyl)thiazol-2-yl]amino}methyl]cyclohexanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% With triethylamine sulfate at 100℃; for 6h; General procedure for preparation of rac-(2S)-2-[(R)-[(4-substituted phenyl)[4-(4-substituted phenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanone (4a-u) [35] The selectivity of ionic liquids was optimized by investigating the preparation of rac-(2S)-2-[(R)-[(4-chloro phenyl)[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanones in sulfated ionic liquids derived from triethylamine, n-tripropylamine, di-isopropyl amine and tri-n-butyl amine. These reactions were carried out in four separate 100mL round bottomed flasks set in a water bath. Quaternary ammonium sulfated ionic liquids (0.05mmol) were added, drop wise at room temperature, to a well stirred solution of cyclohexanone (0.05mmol), 4-(4-methoxyphenyl) thiazole-2-amine (0.05mmol), and 2-chlorobenzaldehyde (0.05mmol) in each 100mL round bottom flask. All ionic liquids were intended to serve dual functions of solvent as well as catalysts. The mixtures were stirred for about 2h at room temperature and then refluxed for 6h at 100°C. The progress of the each reaction was monitored by TLC to ascertain the conversion levels. At the end of the reaction, the mixtures were treated with water. The products were separated by filtration as the ionic liquids could be dissolved in water, while the products could not. 100% conversion level with 90% isolated yield was observed in quaternary triethylammonium sulfated ionic liquid. The isolated product was purified by recrystallization from alcohol to give rac-(2S)-2-[(R)-(4-chloro phenyl)[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanone 4a. All ionic liquids were recovered by removing water under vacuum and oven drying. The quaternary triethylammonium sulfate [Et3NH][HSO4] was the choice of ionic liquid used in all further syntheses (4b-u).
  • 36
  • [ 2104-04-3 ]
  • [ 108-94-1 ]
  • [ 587-04-2 ]
  • 2-[(3-chlorophenyl)[4-(4-methoxyphenyl)thiazol-2-yl]amino}methyl]cyclohexanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% With triethylamine sulfate at 100℃; for 6h; General procedure for preparation of rac-(2S)-2-[(R)-[(4-substituted phenyl)[4-(4-substituted phenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanone (4a-u) [35] The selectivity of ionic liquids was optimized by investigating the preparation of rac-(2S)-2-[(R)-[(4-chloro phenyl)[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanones in sulfated ionic liquids derived from triethylamine, n-tripropylamine, di-isopropyl amine and tri-n-butyl amine. These reactions were carried out in four separate 100mL round bottomed flasks set in a water bath. Quaternary ammonium sulfated ionic liquids (0.05mmol) were added, drop wise at room temperature, to a well stirred solution of cyclohexanone (0.05mmol), 4-(4-methoxyphenyl) thiazole-2-amine (0.05mmol), and 2-chlorobenzaldehyde (0.05mmol) in each 100mL round bottom flask. All ionic liquids were intended to serve dual functions of solvent as well as catalysts. The mixtures were stirred for about 2h at room temperature and then refluxed for 6h at 100°C. The progress of the each reaction was monitored by TLC to ascertain the conversion levels. At the end of the reaction, the mixtures were treated with water. The products were separated by filtration as the ionic liquids could be dissolved in water, while the products could not. 100% conversion level with 90% isolated yield was observed in quaternary triethylammonium sulfated ionic liquid. The isolated product was purified by recrystallization from alcohol to give rac-(2S)-2-[(R)-(4-chloro phenyl)[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanone 4a. All ionic liquids were recovered by removing water under vacuum and oven drying. The quaternary triethylammonium sulfate [Et3NH][HSO4] was the choice of ionic liquid used in all further syntheses (4b-u).
  • 37
  • [ 2104-04-3 ]
  • [ 108-94-1 ]
  • [ 99-61-6 ]
  • 2-[(3-nitrophenyl)[4-(4-methoxyphenyl)thiazol-2-yl]amino}methyl]cyclohexanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% With triethylamine sulfate at 100℃; for 6h; General procedure for preparation of rac-(2S)-2-[(R)-[(4-substituted phenyl)[4-(4-substituted phenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanone (4a-u) [35] The selectivity of ionic liquids was optimized by investigating the preparation of rac-(2S)-2-[(R)-[(4-chloro phenyl)[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanones in sulfated ionic liquids derived from triethylamine, n-tripropylamine, di-isopropyl amine and tri-n-butyl amine. These reactions were carried out in four separate 100mL round bottomed flasks set in a water bath. Quaternary ammonium sulfated ionic liquids (0.05mmol) were added, drop wise at room temperature, to a well stirred solution of cyclohexanone (0.05mmol), 4-(4-methoxyphenyl) thiazole-2-amine (0.05mmol), and 2-chlorobenzaldehyde (0.05mmol) in each 100mL round bottom flask. All ionic liquids were intended to serve dual functions of solvent as well as catalysts. The mixtures were stirred for about 2h at room temperature and then refluxed for 6h at 100°C. The progress of the each reaction was monitored by TLC to ascertain the conversion levels. At the end of the reaction, the mixtures were treated with water. The products were separated by filtration as the ionic liquids could be dissolved in water, while the products could not. 100% conversion level with 90% isolated yield was observed in quaternary triethylammonium sulfated ionic liquid. The isolated product was purified by recrystallization from alcohol to give rac-(2S)-2-[(R)-(4-chloro phenyl)[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanone 4a. All ionic liquids were recovered by removing water under vacuum and oven drying. The quaternary triethylammonium sulfate [Et3NH][HSO4] was the choice of ionic liquid used in all further syntheses (4b-u).
  • 38
  • [ 2104-04-3 ]
  • [ 108-94-1 ]
  • [ 100-52-7 ]
  • 2-[(phenyl)[4-(4-methoxyphenyl)thiazol-2-yl]amino}methyl]cyclohexanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With triethylamine sulfate at 100℃; for 6h; General procedure for preparation of rac-(2S)-2-[(R)-[(4-substituted phenyl)[4-(4-substituted phenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanone (4a-u) [35] The selectivity of ionic liquids was optimized by investigating the preparation of rac-(2S)-2-[(R)-[(4-chloro phenyl)[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanones in sulfated ionic liquids derived from triethylamine, n-tripropylamine, di-isopropyl amine and tri-n-butyl amine. These reactions were carried out in four separate 100mL round bottomed flasks set in a water bath. Quaternary ammonium sulfated ionic liquids (0.05mmol) were added, drop wise at room temperature, to a well stirred solution of cyclohexanone (0.05mmol), 4-(4-methoxyphenyl) thiazole-2-amine (0.05mmol), and 2-chlorobenzaldehyde (0.05mmol) in each 100mL round bottom flask. All ionic liquids were intended to serve dual functions of solvent as well as catalysts. The mixtures were stirred for about 2h at room temperature and then refluxed for 6h at 100°C. The progress of the each reaction was monitored by TLC to ascertain the conversion levels. At the end of the reaction, the mixtures were treated with water. The products were separated by filtration as the ionic liquids could be dissolved in water, while the products could not. 100% conversion level with 90% isolated yield was observed in quaternary triethylammonium sulfated ionic liquid. The isolated product was purified by recrystallization from alcohol to give rac-(2S)-2-[(R)-(4-chloro phenyl)[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanone 4a. All ionic liquids were recovered by removing water under vacuum and oven drying. The quaternary triethylammonium sulfate [Et3NH][HSO4] was the choice of ionic liquid used in all further syntheses (4b-u).
  • 39
  • [ 2104-04-3 ]
  • [ 108-94-1 ]
  • [ 89-98-5 ]
  • 2-[(2-chlorophenyl)[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
99% With triethylamine sulfate at 100℃; for 6h; General procedure for preparation of rac-(2S)-2-[(R)-[(4-substituted phenyl)[4-(4-substituted phenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanone (4a-u) [35] The selectivity of ionic liquids was optimized by investigating the preparation of rac-(2S)-2-[(R)-[(4-chloro phenyl)[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanones in sulfated ionic liquids derived from triethylamine, n-tripropylamine, di-isopropyl amine and tri-n-butyl amine. These reactions were carried out in four separate 100mL round bottomed flasks set in a water bath. Quaternary ammonium sulfated ionic liquids (0.05mmol) were added, drop wise at room temperature, to a well stirred solution of cyclohexanone (0.05mmol), 4-(4-methoxyphenyl) thiazole-2-amine (0.05mmol), and 2-chlorobenzaldehyde (0.05mmol) in each 100mL round bottom flask. All ionic liquids were intended to serve dual functions of solvent as well as catalysts. The mixtures were stirred for about 2h at room temperature and then refluxed for 6h at 100°C. The progress of the each reaction was monitored by TLC to ascertain the conversion levels. At the end of the reaction, the mixtures were treated with water. The products were separated by filtration as the ionic liquids could be dissolved in water, while the products could not. 100% conversion level with 90% isolated yield was observed in quaternary triethylammonium sulfated ionic liquid. The isolated product was purified by recrystallization from alcohol to give rac-(2S)-2-[(R)-(4-chloro phenyl)[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanone 4a. All ionic liquids were recovered by removing water under vacuum and oven drying. The quaternary triethylammonium sulfate [Et3NH][HSO4] was the choice of ionic liquid used in all further syntheses (4b-u).
  • 41
  • [ 645-12-5 ]
  • [ 2104-04-3 ]
  • N-(4-(4-methoxyphenyl)thiazol-2-yl)-5-nitrofuran-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
46% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h; General procedure: (iv) 10a-10n (2 mmol, 1.0 equiv.) wasdissolved in dry dichloromethane (10 mL), and the reaction was followed to add 5-nitro-2-furoicacid (2.4 mmol, 1.2 equiv.), DMAP (2.4 mmol, 1.2 equiv.), EDCI (4 mmol, 2.0 equiv.),then stirred under room temperature for 1 day. The reaction mixture wasquenched with H2O (10 mL) and extracted with dichloromethane (2*30 mL).The combined organic layers were washed in turn with 2N HCl (20 mL), H2O(20 mL) and brine (20 mL). The organic layer was collected, dried overanhydrous Na2SO4 and concentrated in vacuo. The residue waspurified by column chromatography on silica gel (hexane/EtOAc=8:1 to 4:1) toprovide 12a-12n. 11a and 11b were prepared by thesame way, just starting from 10b and replacing 5-nitro- furic with2-furoic acid and 4-nitrobenzoic acid. The yield was 29~80%.
  • 42
  • [ 2104-04-3 ]
  • [ 5081-36-7 ]
  • 3-methoxy-N-(4-(4-methoxyphenyl)thiazol-2-yl)-4-nitrobenzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In acetonitrile at 65℃; The commercially available 3-methoxy-4-nitrobenzoic acid (1.0 eq) was dissolved in acetonitrile (0.25 M) and treated with triethylamine (2.0 eq) and HATU (1.0 eq). To this mixture was then added 4-(4-methoxyphenyl)thiazol-2-amine (1.0 eq). The resulting solution was warmed to 65°C and stirred until the reaction was complete. At this time the solution was cooled to room temperature and diluted with water. The resulting precipitate was collected via filtration, washed with additional water, and dried in vacuo to give 3-methoxy-N-(4-(4-methoxyphenyl)thiazol-2-yl)-4-nitrobenzamide as a pale yellow solid (82% yield). A dry round bottom flask was charged with 10% palladium on carbon (0.05 eq) under an atmosphere of nitrogen. EtOAc (-0.2 M) was then added, followed by 3-methoxy-N-(4-(4-methoxyphenyl)thiazol-2-yl)-4- nitrobenzamide (1.0 eq). A hydrogen-filled balloon was then affixed to the flask and the airspace was evacuated and back-filled with hydrogen. The mixture was vigorously stirred until the reaction was complete, adding additional catalyst as needed and some methanol to ensure solubility. The mixture was then filtered through celite, washing with methanol to give 3-methoxy-N-(4-(4-methoxyphenyl)thiazol-2-yl)-4-nitrobenzamide as a yellow solid. This solid (1.0 eq) was then dissolved in acetonitrile (0.1 M) and treated with excess glyoxylic acid (-15 eq of a 50% aqueous solution). Sodium cyanoborohydride (5.0 eq) was then added and stirred at room temperature until the reaction was complete. The solution was then quenched with acetic acid, and partitioned between EtOAc and IN HC1. The organic portion was then concentrated to a yellow solid that was used without further purification. The crude (2-methoxy-4-((4-(4- methoxyphenyl)thiazol-2-yl)carbamoyl) phenyl)glycine (1.0 eq) was dissolved in DMF and treated with morpholine (10.0 eq). To this room temperature solution was added HATU (3.0 eq) and stirring was continued until the reaction was complete. The solution was then quenched with water which initiated the formation of a white precipitate. This impure solid was collected via filtration and then purified on silica gel (hexane/EtOAc gradient 35%-100%) to give 3-methoxy-N-(4-(4-methoxyphenyl)thiazol-2-yl)-4-((2- mo holino-2-oxoethyl)amino)benzamide as a white solid. ^-NMR (DMSO-d6, 500 MHz): δ 12.33 (s, 1H), 7.88 (d, J = 8.8 Hz, 2H), 7.75 (dd, J = 8.3, 1.9 Hz, 1H), 7.67 (d, J = 2.0 Hz, 1H), 7.44 (s, 1H), 7.00 (d, J = 8.9 Hz, 2H), 6.67 (d, J = 8.5 Hz, 1H), 5.84 (t, J = 4.6 Hz, 1H), 4.05 (d, J = 4.6 Hz, 2H), 3.94 (s, 3H), 3.79 (s, 3H), 3.63 (br, 2H), 3.58 (br, 2H), 3.51 (br, 4H). 1 C-NMR (DMSO-d6, 125 MHz): δ 167.19, 164.61 , 158.90, 158.87, 148.82, 145.38, 141.20, 127.36, 127.05, 123.02, 1 18.38, 1 14.02, 108.83, 108.75, 106.03, 65.98, 65.90, 55.72, 55.12, 44.28, 43.82, 41.87. MS [M+H] : 483.22.
  • 43
  • [ 2104-04-3 ]
  • [ 874-61-3 ]
  • N-(4-(4-methoxyphenyl)thiazol-2-yl)-4-oxocyclohexane-1-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In acetonitrile; at 70℃; for 4h; A vial was charged with 4-oxocyclohexane-l-carboxylic acid (1.0 eq) and MeCN (0.15 M) at room temperature. To this solution was then added triethylamine (3.0 eq) and HATU (1.0 eq). 4-(4-methoxyphenyl)thiazol-2-amine (1.0 eq) was lastly added and the solution was warmed to 70C for 4 h. The solution was then cooled to room temperature and diluted with water which initiated the precipitation of N-(4-(4- methoxyphenyl)thiazol-2-yl)-4-oxocyclohexane-l-carboxamide. ^-NMR (500 MHz, CDC13) delta 7.77 (d, J = 8.8 Hz, 2H), 7.06 (s, 1H), 6.97 (d, J = 8.8 Hz, 2H), 3.85 (s, 3H), 2.59 (m, 1H), 2.47 (m, 2H), 2.25 - 2.08 (m, 4H), 2.03 (m, 2H). This ketone (1.0 eq) was then dissolved in dichloromethane/methanol (4: 1) and treated with sodium borohydride (2.0 eq) at room temperature. After 10 min the reaction was completed and the solution was quenched with HC1 (1 N). Dichloromethane was used to extract the solution two times, the combined organic portions were dried over sodium sulfate and concentrated in vacuo to give 4-hydroxy-N-(4-(4-methoxyphenyl)thiazol-2-yl)cyclohexane-l- carboxamide. This material (1.0 eq) was then dissolved in THF (0.1 M) and treated with potassium t-butoxide (1.1 eq) at room temperature. 2-chloro-l-morpholinoethan-l-one (1.1 eq) was then added and the solution was warmed to 60C until alkylation was complete. The solution was then poured into aqueous NH4C1 and extracted with EtOAc. The organic portion was washed with brine and dried over sodium sulfate. Concentration in vacuo gave N-(4-(4-methoxyphenyl)thiazol-2-yl)-4-(2-morpholino-2- oxoethoxy)cyclohexane-l-carboxamide as a white solid that was washed twice with hexane and thrice with Et20 to give the clean product. ^-NMR (500 MHz, DMSO-d6) delta 7.82 (d, J = 8.3 Hz, 2H), 7.44 (d, J = 30.6 Hz, 1H), 6.98 (d, J = 8.3 Hz, 2H), 5.27 (s, 1H), 3.79 (d, J = 2.0 Hz, 3H), 3.73 (s, 2H), 3.61 - 3.43 (m, 8H), 2.78 - 2.57 (m, 1H), 1.93 - 1.77 (m, 4H), 1.56 - 1.40 (m, 2H), 1.31 - 1.03 (m, 2H). MS [M+H]: 460.22
  • 44
  • [ 2104-04-3 ]
  • [ 26280-19-3 ]
  • 2-(5-benzoyl-1-methyl-1H-pyrrol-2-yl)-N-(4'-(4-methoxyphenyl)thiazol-2'-yl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% 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-methoxyphenyl)-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.
  • 45
  • [ 2104-04-3 ]
  • 2-(N-(4,6-bis(4-methoxyphenyl)pyrimidin-2-yl)sulfamoyl)acetic acid [ No CAS ]
  • 2-(N-(4,6-bis(4-methoxyphenyl)pyrimidin-2-yl)sulfamoyl)-N-(4-(4-methoxyphenyl)-thiazol-2-yl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% 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.
  • 46
  • [ 34910-42-4 ]
  • [ 1147550-11-5 ]
  • [ 2104-04-3 ]
YieldReaction ConditionsOperation in experiment
72% With copper diacetate In acetonitrile at 20℃; for 20h; Irradiation; Inert atmosphere;
72% With copper diacetate In acetonitrile at 25℃; for 36h; Irradiation; 5 Example 5 A method of driving visible light to synthesize 4-alkyl or aryl-2-aminothiazoles. This method refers to the olefin azide compound, ammonium thiocyanate and copper acetate were added to the solvent acetonitrile, at a temperature of 25 ° C under the conditions of a wavelength of 460nm visible light drive reaction, 36h after the reaction solution. The reaction solution was spin-dried at a temperature of 25° C. and a pressure of 1.3 kPa to obtain a concentrate; the concentrate was subjected to silica gel column chromatography (200 to 300 mesh silica gel, eluent: petroleum ether: ethyl acetate=4 mL: 1 mL) gives 4-(4-methoxyphenyl)-2-aminothiazole (2e) as a pale yellow solid (14.8 mg, 72%).
  • 47
  • [ 2104-04-3 ]
  • [ 58734-32-0 ]
  • 8-methyl-2-oxo-2H-chromene-3-carboxylic acid [4-(4-methoxyphenyl)thiazol-2-yl]amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% Stage #1: 4-(4-methoxyphenyl)-1,3-thiazol-2-amine; 8-methyl-2-oxo-2H-chromene-3-carboxylic acid 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℃;
  • 48
  • [ 2104-04-3 ]
  • [ 20300-59-8 ]
  • 7-methoxy-2-oxo-2H-chromene-3-carboxylic acid [4-(4-methoxyphenyl)thiazol-2-yl]amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% Stage #1: 4-(4-methoxyphenyl)-1,3-thiazol-2-amine; 7-methoxycoumarin-3-carboxylic acid 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℃;
  • 49
  • [ 2104-04-3 ]
  • 4-((5-oxo-5,6-dihydropyrido[2,3-d]pyridazin-8-yl)methyl)benzoyl chloride [ No CAS ]
  • N-(4-(4-methoxyphenyl)thiazol-2-yl)-4-((5-oxo-5,6-dihydropyrido[2,3-d]pyridazin-8-yl)methyl)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
52% With triethylamine In N,N-dimethyl-formamide at 100℃; for 6h; 12 5.1.5. General procedure for the synthesis of compounds 8a-g, 9a and b,10a-d and 11a-g General procedure: The crude acid chloride 7 obtained in the previous step was cooledto 0 °C and dissolved in dry DMF (2 mL). To this solution, the appropriateamine (1.65 mmol) and triethylamine (1 mL, 10 mmol) wereadded. The reaction mixture was stirred at 100 °C for 6 h. The solutionwas poured over crushed ice and the precipitated solid was filtered off,washed with water, dried and recrystallized from the suitable solvent. Yield: 52%, m.p.: 145-147 °C, I.R (KBr, cm-1): υmax 3444 (2NH), 3116 (CH aromatic), 2999 (CH aliphatic), 1670 (2C=O), 1620 (C=N), 1485 (C=C), 1H NMR: δ 3.78 (s, 3H, OCH3), 4.43 (s, 2H, CH2), 6.90 (d, 2H, J = 8.8 Hz, methoxyphenyl-H), 7.00 (d, 2H, J = 8.4 Hz, methoxyphenyl-H), 7.25 (s, 1H, thiazolyl-H), 7.81 (d, 2H, J = 8.4 Hz, phenyl-H), 7.88 (d, 2H, J = 8.3 Hz, phenyl-H), 8.07 (d, 1H, J = 8.0 Hz, pyridyl-H), 8.39 (d, 1H, J = 4.0 Hz, pyridyl-H), 9.05 (d, 1H, J = 4.1 Hz, pyridyl-H), 12.86 (s, 2H, NH exchanged by D2O). Anal. Calcd. for C25H19N5O3S (469.52): C, 63.95; H, 4.08; N, 14.92. Found: C, 64.23; H, 4.21; N, 15.13.
  • 50
  • [ 2104-04-3 ]
  • [ 927-58-2 ]
  • 4-bromo-N-(4-(4-methoxyphenyl)thiazol-2-yl)butanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; General procedure for the synthesis of (2-amino-4-phenylthiazole) amide derivatives (4a-4e) General procedure: Compounds 1, 2, and 3 (Ma et al. 2014) were obtainedaccording to the previously described method. Chloroacetylchloride (1.45 mmol) in CH2Cl2 (15 mL) wasadded dropwise to a cooled solution (0 °C) of 4-(4-methoxyphenyl)thiazol-2-amine 3 (1.21 mmol) and diisopropylethylamine(DIEA) (1.24 mmol) in CH2Cl2(25 mL). The completion of the reaction was assessed bythin-layer chromatography (TLC). The organic layer wasseparated, washed with saturated NaHCO3 solution(100 mL), water, and brine, the aqueous phase wasextracted with CH2Cl2 (60 mL), and the organic phaseswere collected, dried over anhydrous MgSO4, and evaporatedin vacuo. The product was separated and purifiedby column chromatography on silica gel using an ethylacetate/petroleum ether mixture (1/4) as the eluent toafford pure compound 4a (Scheme 1).
  • 51
  • [ 2104-04-3 ]
  • [ 4509-90-4 ]
  • 5-bromo-N-(4-(4-methoxyphenyl)thiazol-2-yl)pentanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; General procedure for the synthesis of (2-amino-4-phenylthiazole) amide derivatives (4a-4e) General procedure: Compounds 1, 2, and 3 (Ma et al. 2014) were obtainedaccording to the previously described method. Chloroacetylchloride (1.45 mmol) in CH2Cl2 (15 mL) wasadded dropwise to a cooled solution (0 °C) of 4-(4-methoxyphenyl)thiazol-2-amine 3 (1.21 mmol) and diisopropylethylamine(DIEA) (1.24 mmol) in CH2Cl2(25 mL). The completion of the reaction was assessed bythin-layer chromatography (TLC). The organic layer wasseparated, washed with saturated NaHCO3 solution(100 mL), water, and brine, the aqueous phase wasextracted with CH2Cl2 (60 mL), and the organic phaseswere collected, dried over anhydrous MgSO4, and evaporatedin vacuo. The product was separated and purifiedby column chromatography on silica gel using an ethylacetate/petroleum ether mixture (1/4) as the eluent toafford pure compound 4a (Scheme 1).
  • 52
  • [ 2104-04-3 ]
  • [ 22809-37-6 ]
  • 6-bromo-N-(4-(4-methoxyphenyl)thiazol-2-yl)hexanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; General procedure for the synthesis of (2-amino-4-phenylthiazole) amide derivatives (4a-4e) General procedure: Compounds 1, 2, and 3 (Ma et al. 2014) were obtainedaccording to the previously described method. Chloroacetylchloride (1.45 mmol) in CH2Cl2 (15 mL) wasadded dropwise to a cooled solution (0 °C) of 4-(4-methoxyphenyl)thiazol-2-amine 3 (1.21 mmol) and diisopropylethylamine(DIEA) (1.24 mmol) in CH2Cl2(25 mL). The completion of the reaction was assessed bythin-layer chromatography (TLC). The organic layer wasseparated, washed with saturated NaHCO3 solution(100 mL), water, and brine, the aqueous phase wasextracted with CH2Cl2 (60 mL), and the organic phaseswere collected, dried over anhydrous MgSO4, and evaporatedin vacuo. The product was separated and purifiedby column chromatography on silica gel using an ethylacetate/petroleum ether mixture (1/4) as the eluent toafford pure compound 4a (Scheme 1).
  • 53
  • [ 22106-33-8 ]
  • [ 2104-04-3 ]
  • N-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-4-(1H-pyrrol-1-yl)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; General procedure for the synthesis of N-4-(4-substituted phenyl)thiazole-2-yl-4-(1H-pyrrol-1yl)bezamides (3a-e)/N-4-(4-substituted phenyl)thiazol-2-yl-4-(2,5-dimethyl-1H-pyrrol-1-yl)benzamides(4a-f) General procedure: The 2-amino-4-(4-substituted phenyl)thiazoles (2a-f) (Pattanet al. 2009) (0.0018 mol) and 4-(1H-pyrrolyl-1-yl)benzoicacid (9a) (Joshi et al. 2018)/4-(2,5-dimethyl-1Hpyrrolyl-1-yl)benzoic acid (9b) (Joshi et al. 2008)(0.0019 mol) were dissolved, respectively in 50 mL of dry dimethyl formamide. HBTU (0.87 g, 0.0023 mol) and DIEA(0.93 mL, 0.0053 mol) were then added to the above mixturesand stirred for 24-30 h at ambient temperature. Thereaction was quenched by adding NaCl solution and themixture was extracted with ethyl acetate (3 × 50 mL). Thecombined ethyl acetate layer was washed with 1 N HCl andwith a saturated sodium bicarbonate solution followed byNaCl. The organic layer was dried over anhydrous sodiumsulfate and concentrated using a rotary flash evaporator.Thus obtained residue was dried and purified by column chromatography using petroleum ether:ethyl acetate (6:4)mixture as the eluent to afford the compounds (3a-e) and(4-f) (Scheme 1).
  • 54
  • [ 2104-04-3 ]
  • [ 15898-26-7 ]
  • N-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-4-(2,5-dimethyl-1H-pyrrol-1-yl)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; General procedure for the synthesis of N-4-(4-substituted phenyl)thiazole-2-yl-4-(1H-pyrrol-1yl)bezamides (3a-e)/N-4-(4-substituted phenyl)thiazol-2-yl-4-(2,5-dimethyl-1H-pyrrol-1-yl)benzamides(4a-f) General procedure: The 2-amino-4-(4-substituted phenyl)thiazoles (2a-f) (Pattanet al. 2009) (0.0018 mol) and 4-(1H-pyrrolyl-1-yl)benzoicacid (9a) (Joshi et al. 2018)/4-(2,5-dimethyl-1Hpyrrolyl-1-yl)benzoic acid (9b) (Joshi et al. 2008)(0.0019 mol) were dissolved, respectively in 50 mL of dry dimethyl formamide. HBTU (0.87 g, 0.0023 mol) and DIEA(0.93 mL, 0.0053 mol) were then added to the above mixturesand stirred for 24-30 h at ambient temperature. Thereaction was quenched by adding NaCl solution and themixture was extracted with ethyl acetate (3 × 50 mL). Thecombined ethyl acetate layer was washed with 1 N HCl andwith a saturated sodium bicarbonate solution followed byNaCl. The organic layer was dried over anhydrous sodiumsulfate and concentrated using a rotary flash evaporator.Thus obtained residue was dried and purified by column chromatography using petroleum ether:ethyl acetate (6:4)mixture as the eluent to afford the compounds (3a-e) and(4-f) (Scheme 1).
  • 55
  • [ 2104-04-3 ]
  • [ 122-51-0 ]
  • [ 868-85-9 ]
  • tetramethyl (((4-(4-methoxyphenyl)thiazol-2-yl)amino)methylene)bis(phosphonate) [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% With silver In neat (no solvent) at 60℃; for 0.416667h; Conventional heating method for the synthesis ofaminomethylene bisphosphonates from (5 a-l) General procedure: Ag NPs (7.5 mol%, 0.80 g) was added to a mixture of 4-methoxy phenyl thiazol amine (0.002 mol, 0.35 g) (3a),dimethyl phosphite (0.0045 mol, 0.41 mL) (4a), and triethylorthoformate (0.0025 mol, 0.38 mL) taken in a 50mL roundbottomed flask. The mixture was stirred for about20-30 min at 60 °C. After completion of the reaction which was monitored by TLC, the reaction mixture was cooledand extracted with dichloromethane to separate the catalyst for reuse. The catalyst residue was dried under vacuum at 100 °C and reused. Then the organic extract was washed with water, dried over anhydrous Na2SO4, and concentrated under reduced pressure to obtain the crude product which was purified by column chromatography using silica gel(100-200 mesh) as the adsorbent and ethyl acetate-hexane in 7:3 ratio as the eluent and obtained pure α-aminobisphosphonate 5a in 94% yield. The same procedure was adopted for the preparation of other compounds from 5b-l.
  • 56
  • [ 2104-04-3 ]
  • [ 122-51-0 ]
  • [ 762-04-9 ]
  • tetraethyl (((4-(4-methoxyphenyl)thiazol-2-yl)amino)methylene)bis(phosphonate) [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With silver In neat (no solvent) at 60℃; for 0.333333h; Conventional heating method for the synthesis ofaminomethylene bisphosphonates from (5 a-l) General procedure: Ag NPs (7.5 mol%, 0.80 g) was added to a mixture of 4-methoxy phenyl thiazol amine (0.002 mol, 0.35 g) (3a),dimethyl phosphite (0.0045 mol, 0.41 mL) (4a), and triethylorthoformate (0.0025 mol, 0.38 mL) taken in a 50mL roundbottomed flask. The mixture was stirred for about20-30 min at 60 °C. After completion of the reaction which was monitored by TLC, the reaction mixture was cooledand extracted with dichloromethane to separate the catalyst for reuse. The catalyst residue was dried under vacuum at 100 °C and reused. Then the organic extract was washed with water, dried over anhydrous Na2SO4, and concentrated under reduced pressure to obtain the crude product which was purified by column chromatography using silica gel(100-200 mesh) as the adsorbent and ethyl acetate-hexane in 7:3 ratio as the eluent and obtained pure α-aminobisphosphonate 5a in 94% yield. The same procedure was adopted for the preparation of other compounds from 5b-l.
  • 57
  • [ 1809-19-4 ]
  • [ 2104-04-3 ]
  • [ 122-51-0 ]
  • tetrabutyl (((4-(4-methoxyphenyl)thiazol-2-yl)amino)methylene)bis(phosphonate) [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With silver In neat (no solvent) at 60℃; for 0.333333h; Conventional heating method for the synthesis ofaminomethylene bisphosphonates from (5 a-l) General procedure: Ag NPs (7.5 mol%, 0.80 g) was added to a mixture of 4-methoxy phenyl thiazol amine (0.002 mol, 0.35 g) (3a),dimethyl phosphite (0.0045 mol, 0.41 mL) (4a), and triethylorthoformate (0.0025 mol, 0.38 mL) taken in a 50mL roundbottomed flask. The mixture was stirred for about20-30 min at 60 °C. After completion of the reaction which was monitored by TLC, the reaction mixture was cooledand extracted with dichloromethane to separate the catalyst for reuse. The catalyst residue was dried under vacuum at 100 °C and reused. Then the organic extract was washed with water, dried over anhydrous Na2SO4, and concentrated under reduced pressure to obtain the crude product which was purified by column chromatography using silica gel(100-200 mesh) as the adsorbent and ethyl acetate-hexane in 7:3 ratio as the eluent and obtained pure α-aminobisphosphonate 5a in 94% yield. The same procedure was adopted for the preparation of other compounds from 5b-l.
  • 58
  • [ 2104-04-3 ]
  • [ 4712-55-4 ]
  • [ 122-51-0 ]
  • tetraphenyl (((4-(4-methoxyphenyl)thiazol-2-yl)amino)methylene)bis(phosphonate) [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With silver In neat (no solvent) at 60℃; for 0.416667h; Conventional heating method for the synthesis ofaminomethylene bisphosphonates from (5 a-l) General procedure: Ag NPs (7.5 mol%, 0.80 g) was added to a mixture of 4-methoxy phenyl thiazol amine (0.002 mol, 0.35 g) (3a),dimethyl phosphite (0.0045 mol, 0.41 mL) (4a), and triethylorthoformate (0.0025 mol, 0.38 mL) taken in a 50mL roundbottomed flask. The mixture was stirred for about20-30 min at 60 °C. After completion of the reaction which was monitored by TLC, the reaction mixture was cooledand extracted with dichloromethane to separate the catalyst for reuse. The catalyst residue was dried under vacuum at 100 °C and reused. Then the organic extract was washed with water, dried over anhydrous Na2SO4, and concentrated under reduced pressure to obtain the crude product which was purified by column chromatography using silica gel(100-200 mesh) as the adsorbent and ethyl acetate-hexane in 7:3 ratio as the eluent and obtained pure α-aminobisphosphonate 5a in 94% yield. The same procedure was adopted for the preparation of other compounds from 5b-l.
  • 59
  • [ 2104-04-3 ]
  • [ 5533-02-8 ]
  • 4-hydroxy-3-methoxy-N-(4-(4-methoxyphenyl)thiazol-2-yl)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% Stage #1: 4-(4-methoxyphenyl)-1,3-thiazol-2-amine; 3-methoxy-4-(methoxymethoxy)benzoic acid With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In acetonitrile at 75℃; Stage #2: With hydrogenchloride In tetrahydrofuran; water at 65℃; SBI-477-step-3 A vial was charged with 4-(4-methoxyphenyl)thiazol-2-amine (412 mg, 1.0 eq), triethylamine (558 μ, 2.0 eq), and acetonitrile (-0.4 M). To this solution was then added 3-methoxy-4-(methoxymethoxy)benzoic acid (509 mg, 1.2 eq). Finally, HATU (912 mg, 1.0 eq) was added and the vial was warmed to 75°C. Stirring at 75°C was continued until full consumption of the carboxylic acid by LCMS. The solution was then cooled to room temperature, diluted with EtOAc, and then sequentially washed with water and brine. Concentration in vacuo gave an oil that was used without further purification. This oil was directly dissolved in THF (16 mL) and treated with IN HC1 (4 mL). The solution was then warmed to 65°C and stirred until the acetal deprotection was complete by LCMS (45 min). Upon completion, the solution was cooled to room temperature, diluted with EtOAc and sequentially washed with saturated NaHC03, water, and brine. After drying over sodium sulfate, the material was concentrated and purified on silica gel (10- 50% hex/EtOAc gradient) to give 4-hydroxy-3-methoxy-N-(4-(4-ethoxyphenyl)thiazol- 2-yl)benzamide as a white solid (441 mg,62% yield). 1H NMR (500 MHz, Chloroform- d) δ 7.76 (d, J = 8.8 Hz, 2H), 7.57 (d, J = 2.0 Ηζ, ΙΗ), 7.45 (dd, J = 8.3, 2.1 Hz, 1H), 7.04 (s, 1H), 7.01 (d, J = 8.3 Hz, 1H), 6.95 (d, J = 8.8 Hz,2H), 3.99 (s, 3H), 3.85 (s, 3H).
  • 60
  • [ 2104-04-3 ]
  • [ 2927-71-1 ]
  • 4-(4-methoxyphenyl)-N-(5-fluoro-2-chloropyrimidin-4-yl)thiazol-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
48.9% With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 8h; 5 4-(4-methoxyphenyl)-N-(5-fluoro-2-chloropyrimidin-4-yl)thiazol-2-amine (II-5) Add 5-fluoro-2,4-dichloropyrimidine (0.166g, 1mmol), 4-(4-methoxyphenyl)-2-aminothiazole (0.206g, 1mmol), K2CO3 (0.207) to the test tube reactor g, 1.5mmol) and DMF (2ml), placed in an oil bath at 100 for 8h. To the reaction solution was added 30 ml of ethyl acetate, washed with 30 ml of water three times, the organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and eluted with petroleum ether/ethyl acetate (V/V=10/1) as the elution The agent was subjected to silica gel column chromatography to obtain the compound of formula (II-5) (0.164 g, yield 48.9%).
  • 61
  • [ 2104-04-3 ]
  • α-phthalimido-o-toluoyl chloride [ No CAS ]
  • 2-((1,3-dioxoisoindolin-2-yl)methyl)-N-(4-(4-methoxyphenyl)thiazol-2-yl)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With triethylamine In dichloromethane at 20℃; 8.2.2 Synthesis of 2-((1,3-dioxoisoindolin-2-yl)methyl)-N-(4-arylthiazol-2-yl)benzamides 7a-h 8.2.2.1 General procedure General procedure: A mixture of compound 5 (0.16g, 0.534mmol), amino-thiazoles 6 (0.534mmol) and triethyl amine (TEA) (0.534mmol) in 15mL abs. Methylene chloride was stirred 4-8h at rt. The reaction was monitored by tlc. The reaction mixture was extracted with ethyl acetate, washed with brine, 1N HCl, NaHCO3 and finally with H2O. The solvent was evaporated and the residue was recrystallized from ethanol-chloroform to give the title compounds.
  • 62
  • 2-[dimethyl(oxo)-λ6-sulfaneylidene]-1-(4-methoxyphenyl)ethan-1-one [ No CAS ]
  • [ 17356-08-0 ]
  • [ 2104-04-3 ]
YieldReaction ConditionsOperation in experiment
70% With chloro(1,5-cyclooctadiene)rhodium(I) dimer In 1,2-dichloro-ethane at 80℃; for 24h; Green chemistry; 3 Example 3: Synthesis of Compound 3 (1) Add (4-methoxy) phenylsulfur ylide in a clean reactor one by one (45.2 mg, 0.2 mmol), thiourea (30.4 mg, 0.4 mmol), Bis(1,5-cyclooctadiene) rhodium chloride (I) dimer (3.0 mg, 0.006 mmol) And 1,2-dichloroethane (2 mL), put them in a 80°C oil bath and stir for 24 h. (2) After the reaction, collect the reaction solution and remove the solvent under reduced pressure. The residue was separated and purified by silica gel column chromatography to obtain a white solid with a yield of 70%.
70% With dirhodium tetraacetate In 1,2-dichloro-ethane at 80℃; for 24h; Schlenk technique; chemoselective reaction; 3. General Procedures for Annulation of Sulfoxonium Ylides and Thiourea General procedure: A mixture of substituted sulfoxonium ylides (1, 0.2 mmol, 1.0 equiv), thiourea (2,0.4 mmol, 2.0 equiv), Rh2(OAc)4 (5 mol%) were weighted in a Schlenk tube equipped with a stir bar. 1,2-Dichloroethane (1.5 mL) was added and the mixture was stirred at 80 °C for 24 h under air. After completion, the solvent of the reaction is distilled under reduced pressure. The purification was performed by flash column chromatography on silica gel with EtOAc/petroleum ether.
  • 63
  • [ 17356-08-0 ]
  • [ 768-60-5 ]
  • [ 2104-04-3 ]
YieldReaction ConditionsOperation in experiment
80% With N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide; sodium alginate In water at 70℃; for 2h; Green chemistry; 2.3 General procedure for the synthesis of 2-amino-4-arylthiazoles In a round bottom flask (25mL), a mixture of phenyl acetylene (1mmol), TBBDA (0.25mmol), thiourea (2mmol) and sodium alginate (10mol%) in H2O (10mL) was stirred at 70°C. The progress of the reaction was monitored by TLC (eluent: n-hexane-EtOAc, 6:1). Solvent was evaporated and, then, the crude product was dissolved in boiling water, extracted with ether (3×30ml), and, finally adjusted to pH=10 with the amount of ammonia to gain the pure product. The products were characterized using physical and spectroscopic (IR, NMR, MS) data.
  • 64
  • [ 67-52-7 ]
  • [ 2104-04-3 ]
  • [ 99-61-6 ]
  • 7-(4-methoxyphenyl)-5-(3-nitrophenyl)-1,5-dihydro-2H-pyrimido[4,5-d][1,3]thiazolo[3,2-a]pyrimidine-2,4(3H)-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% With <i>L</i>-proline In ethanol; water for 5h; Reflux; Green chemistry; 2.3. General procedure for the synthesis of (4-substituted-phenyl)-1,5- dihydro-2H-pyrimido[4,5-d][1,3]thiazolo[3,2a]-pyrimidine-2,4(3H)- dione derivatives (4a-g) General procedure: An equimolar quantity of 2-amino-4-(4-substituted-phenyl) thiazoles (1a/b, 1 mmol), substituted benzaldehyde (2, 1 mmol), and barbituric/thiobarbituric acid (3, 1 mmol) in the presence of aqueous ethanol using 10 mol% of L -Proline was refluxed with con- stant stirring for about 4-5 h. Simultaneously, the reaction was monitored by TLC (Ethyl acetate & petroleum ether). After completion of the reaction, the reaction mixture was cooled to room temperature and poured into the 100 mL flake ice with vigorous stirring to get solid precipitate. Then, it was filtered, washed, re- crystallized from absolute ethanol, and dried to afford pure solid products (4a-g).
  • 65
  • [ 67-52-7 ]
  • [ 2104-04-3 ]
  • [ 123-08-0 ]
  • 5-(4-hydroxyphenyl)-7-(4-methoxyphenyl)-1,5-dihydro-2H-pyrimido[4,5-d][1,3]thiazolo[3,2-a]pyrimidine-2,4(3H)-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With <i>L</i>-proline In ethanol; water for 5h; Reflux; Green chemistry; 2.3. General procedure for the synthesis of (4-substituted-phenyl)-1,5- dihydro-2H-pyrimido[4,5-d][1,3]thiazolo[3,2a]-pyrimidine-2,4(3H)- dione derivatives (4a-g) General procedure: An equimolar quantity of 2-amino-4-(4-substituted-phenyl) thiazoles (1a/b, 1 mmol), substituted benzaldehyde (2, 1 mmol), and barbituric/thiobarbituric acid (3, 1 mmol) in the presence of aqueous ethanol using 10 mol% of L -Proline was refluxed with con- stant stirring for about 4-5 h. Simultaneously, the reaction was monitored by TLC (Ethyl acetate & petroleum ether). After completion of the reaction, the reaction mixture was cooled to room temperature and poured into the 100 mL flake ice with vigorous stirring to get solid precipitate. Then, it was filtered, washed, re- crystallized from absolute ethanol, and dried to afford pure solid products (4a-g).
  • 66
  • [ 67-52-7 ]
  • [ 2104-04-3 ]
  • [ 121-33-5 ]
  • 5-(4-hydroxy-3-methoxyphenyl)-7-(4-methoxyphenyl)-1,5-dihydro-2H-pyrimido[4,5-d][1,3]thiazolo[3,2-a]pyrimidine-2,4(3H)-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With <i>L</i>-proline In ethanol; water for 5h; Reflux; Green chemistry; 2.3. General procedure for the synthesis of (4-substituted-phenyl)-1,5- dihydro-2H-pyrimido[4,5-d][1,3]thiazolo[3,2a]-pyrimidine-2,4(3H)- dione derivatives (4a-g) General procedure: An equimolar quantity of 2-amino-4-(4-substituted-phenyl) thiazoles (1a/b, 1 mmol), substituted benzaldehyde (2, 1 mmol), and barbituric/thiobarbituric acid (3, 1 mmol) in the presence of aqueous ethanol using 10 mol% of L -Proline was refluxed with con- stant stirring for about 4-5 h. Simultaneously, the reaction was monitored by TLC (Ethyl acetate & petroleum ether). After completion of the reaction, the reaction mixture was cooled to room temperature and poured into the 100 mL flake ice with vigorous stirring to get solid precipitate. Then, it was filtered, washed, re- crystallized from absolute ethanol, and dried to afford pure solid products (4a-g).
  • 67
  • [ 67-52-7 ]
  • [ 2104-04-3 ]
  • [ 100-10-7 ]
  • 5-(4-N-dimethylphenyl)-7-(4-methoxyphenyl)-1,5-dihydro-2H-pyrimido[4,5-d][1,3]thiazolo[3,2-a]pyrimidine-2,4(3H)-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% With <i>L</i>-proline In ethanol; water for 5h; Reflux; Green chemistry; 2.3. General procedure for the synthesis of (4-substituted-phenyl)-1,5- dihydro-2H-pyrimido[4,5-d][1,3]thiazolo[3,2a]-pyrimidine-2,4(3H)- dione derivatives (4a-g) General procedure: An equimolar quantity of 2-amino-4-(4-substituted-phenyl) thiazoles (1a/b, 1 mmol), substituted benzaldehyde (2, 1 mmol), and barbituric/thiobarbituric acid (3, 1 mmol) in the presence of aqueous ethanol using 10 mol% of L -Proline was refluxed with con- stant stirring for about 4-5 h. Simultaneously, the reaction was monitored by TLC (Ethyl acetate & petroleum ether). After completion of the reaction, the reaction mixture was cooled to room temperature and poured into the 100 mL flake ice with vigorous stirring to get solid precipitate. Then, it was filtered, washed, re- crystallized from absolute ethanol, and dried to afford pure solid products (4a-g).
  • 68
  • [ 5703-26-4 ]
  • [ 17356-08-0 ]
  • [ 2104-04-3 ]
YieldReaction ConditionsOperation in experiment
90% With iodine In dimethyl sulfoxide at 80℃; for 0.025h; Green chemistry; General procedure for the catalytic synthesis of 2-aminothiazoles General procedure: A mixture of methylcarbonyl (1 mmol), thiourea (1.5 mmol), I2(1 mmol) and Nizeolite-Im-IL (15 mg) in DMSO (2 mL) was stirred at 80 °C for desired time. Afterthe satisfactory completion of the reaction (monitored by TLC), the nanocatalystwas separated through centrifugation. The reaction media (DMSO) was quenchedby adding ammonia to pH = 9-10 to give the solid products. Finally, the pure productwas recrystallized from ethanol at a high yield. All 2-aminothiazole products areknown and were identified by comparing their melting point, FT-IR and 1H NMRwith authentic samples.
  • 69
  • [ 4940-39-0 ]
  • [ 2104-04-3 ]
  • N-(4-(4-methoxyphenyl)thiazol-2-yl)-4-oxo-4H-chromene-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
61.5% Stage #1: acide chromone carboxylique-2 With N-ethyl-N,N-diisopropylamine In dichloromethane; N,N-dimethyl-formamide for 0.5h; Stage #2: 4-(4-methoxyphenyl)-thiazol-2-yl-amine In dichloromethane; N,N-dimethyl-formamide at 20℃; 1.3. Chemistry experimental procedure B of reported compounds General procedure: To a solution of the chromone-2-carboxylic acid (1 mmol) in DMF (10 mL) was added N,N-diisopropylethylamine (1 mmol) and a solution of PyBOP or HATU (1 mmol) in CH2Cl2 (5 mL). The mixture was stirred for half an hour in an ice bath environment. After this period 2-aminothiazole analogues was added and the mixed solution was allowed to warm up to room temperature. The reaction was kept under stirring for 2-8 hours. Then the reaction solution was diluted with water and large amounts of solids were observed to precipitate out of the solution. The solid was collected by suction filtration, which was washed with water and MeOH, dried in vacuo to obtain the crude product. The crude product was purified by silica gel column chromatography eluting with a gradient of MeOH/CH2Cl2 mixture to afford pure compound
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