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Chemical Structure| 30748-47-1

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Product Details of [ 30748-47-1 ]

CAS No. :30748-47-1
Formula : C6H8N2OS
M.W : 156.21
SMILES Code : CC(C1=C(C)N=C(N)S1)=O
MDL No. :MFCD00051952
InChI Key :PKUKCASRNJIQNU-UHFFFAOYSA-N
Pubchem ID :720882

Safety of [ 30748-47-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of [ 30748-47-1 ]

* 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 [ 30748-47-1 ]

[ 30748-47-1 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 30748-47-1 ]
  • [ 99-81-0 ]
  • [ 106735-84-6 ]
YieldReaction ConditionsOperation in experiment
92% With polyethylene glycol (PEG-400); In water; for 0.133333h;Microwave irradiation; Green chemistry; To stirred solution of polyethylene glycol (PEG-400) (2 mL) in water (2 mL) were added 1-(2-amino-4-methylthiazol-5-yl)ethanone (2 mmol)/ethyl 2-amino-4-methylthiazole-5-carboxylate (2 mmol) and α-bromo aralkyl ketones (phenacyl bromides) (2 mmol), and the mixture was heated at 90 C or subject to microwave irradiation at 300 W, until reaction completion as indicated by TLC. After reaction completion, the reaction mixture was cooled at room temperature, and the solid product formed was collected by filtration, washed with water, and recrystallized from ethanol to give pure product. The recovered PEG with water was reused for five further cycles.
  • 2
  • [ 3043-28-5 ]
  • [ 17356-08-0 ]
  • [ 30748-47-1 ]
YieldReaction ConditionsOperation in experiment
In ethanol; at 20℃; for 8.5h;Reflux; 5.0g (50. 0mmol) acetylacetone was dissolved in 40mL of acetone solution and added in batches under ice bath conditions.8.9 g (50. Ommol) of NBS was continued at 0 C for 3 h. The reaction was poured into 50 mL of water.Extracted by 3 X 90 mL of dichloromethane, washed with water, dried over anhydrous sodium sulfate and evaporated to dissolve.A yellow oily liquid was obtained which was used directly in the next reaction. 3.8 g (50.0 mmol) of thiourea was dissolved in 40 mL of ethanol solution, and was dropwise added next to crude obtained above, stirred at room temperature for 30 min, and refluxed for 8 h. The mixture was allowed to stand for cooling, suction filtration, and the filter cake was dissolved in 100 mL of water, and the ammonia water was adjusted to pΗ = 10 to precipitate a large amount of solid, which was filtered off and dried to give 4-methyl-5-acetyl-2-aminothiazole as a white solid.Yield 80.3% (based on acetylacetone), m.p. 247~249C.
  • 3
  • [ 17356-08-0 ]
  • [ 1694-29-7 ]
  • [ 30748-47-1 ]
YieldReaction ConditionsOperation in experiment
94% With pyridine; In methanol; at 20℃;Cooling with ice; Thiourea (5.18 g, 68.1 mmol) and pyridine (5.5 g, 70 mmol)Add to 60 ml of methanol, then add the compound shown in formula I-105-a under ice bath3-Chloropentane-2,4-dione (as in Formula 1) (9.3 g, 69 mmol) was stirred at rt overnight.The solid precipitated in the solution was filtered and the filter cake was washed with 50 ml of methanol.10 g of white solid target product was obtained, yield: 94%
86% In methanol; for 12h;Reflux; 3-chloropentane-2,4-dione (1) (3g, 0.02 moles) in drydistilled methanol was refluxed with thiourea. The reactionmixture was heated for 12 hrs and progress of reaction wasmonitored by TLC. Upon completion of reaction, the reactionmixture was poured into ice cold water and precipitateswere filtered by suction filtration and recrystallized by aqueousethanol. Yield: 86%; M.P.: 70-73C.
73% With pyridine; In methanol; To a solution of thiourea (14.0 g, 18.4 mol) in MeOH (130 mL) and pyridine (10 mL) cooled on an ice bath was added dropwise 3-chloropentane-2,4-dione1(21.8 mL, 18.4 mol). The reaction mixture was warmed up to room temperature and stirred for 8 h. The resulting precipitate was filtered and washed with EtOAc (50 mL) to give2as a white solid (21.0 g, 73%).1H-NMR(DMSO-d6):δ2.36 (s, 3H, CH3), 2.43 (s, 3H, CH3), 8.33 (s, 2H, NH2).MS(ESI)m/z[M+H]+calcd. for C6H9N2OS+, 157.04; found 157.05.
In methanol;Acidic conditions; Reflux; 3-chloropentane-2,4-dione (1.0 equiv., 0.013 mmol)was refluxed with thiourea for 6-7 h (MeOH/H) whichyielded 1-(2-amino-4-methylthiazol-5-yl)ethenone andthen the yielded product was further refluxed with(Benzoyl chloride(R)) for 23 h (Et 3N CH2Cl2) whichlead to the formation of a parent compound that was(N-(5-acetyl-4-methylthiazol-2-yl)-4-(substituted)benzamide)(Table 1).

  • 4
  • [ 30748-47-1 ]
  • [ 100-07-2 ]
  • [ 39884-16-7 ]
YieldReaction ConditionsOperation in experiment
78% With triethylamine; In dichloromethane;Reflux; General procedure: 3-chloropentane-2,4-dione (1.0 equiv., 0.013 mmol)was refluxed with thiourea for 6-7 h (MeOH/H) whichyielded 1-(2-amino-4-methylthiazol-5-yl)ethenone andthen the yielded product was further refluxed with(Benzoyl chloride(R)) for 23 h (Et 3N CH2Cl2) whichlead to the formation of a parent compound that was(N-(5-acetyl-4-methylthiazol-2-yl)-4-(substituted)benzamide)(Table 1).
72% With pyridine; at 0 - 5℃; for 0.166667h; General procedure: Substitutedcarbonyl chlorides (3a-d) were prepared by the reactionof substituted carboxylic acid (50 mmol) and thionyl chloride(5.5 mL, 75 mmol) at about 50 C. 3a-d was added tocooled mixture of 50.0 mmol of 1 or 2 in pyridine (10 mL)respectively with continuous stirring for about 10 min at0-5 C to give dark yellow precipitate of correspondingcarboxamides 4a-d and 5a-d respectively (Scheme 2). Theproduct obtained was filtered and washed with dilute solutionof sodium bicarbonate to remove unreacted carboxylicacid if any. It was then washed with water and dried. Thecompounds obtained were recrystallized using hot ethylacetate [28].
  • 5
  • [ 30748-47-1 ]
  • [ 122-04-3 ]
  • [ 39884-15-6 ]
YieldReaction ConditionsOperation in experiment
68% With triethylamine; In dichloromethane;Reflux; General procedure: 3-chloropentane-2,4-dione (1.0 equiv., 0.013 mmol)was refluxed with thiourea for 6-7 h (MeOH/H) whichyielded 1-(2-amino-4-methylthiazol-5-yl)ethenone andthen the yielded product was further refluxed with(Benzoyl chloride(R)) for 23 h (Et 3N CH2Cl2) whichlead to the formation of a parent compound that was(N-(5-acetyl-4-methylthiazol-2-yl)-4-(substituted)benzamide)(Table 1).
  • 6
  • [ 30748-47-1 ]
  • (Z)-ethyl 2-chloro-2-(2-(4-nitrophenyl)hydrazono)-acetate [ No CAS ]
  • 2-acetyl-3-methyl-5-oxo-6-(4'-nitrophenyl)hydrazinoimidazo<2,1-b>thiazole [ No CAS ]
  • 7
  • [ 17356-08-0 ]
  • [ 123-54-6 ]
  • [ 30748-47-1 ]
YieldReaction ConditionsOperation in experiment
96% With N-Bromosuccinimide; for 0.1h;Microwave irradiation; Green chemistry;Mechanism; To solution of acetyl acetone (2 mmol) in polyethylene glycol PEG-400 (2 mL) were added N-bromosuccinimide (NBS) (2.2 mmol) and thiourea (2 mmol), and the mixture was heated under microwave irradiation at 180 W until reaction completion as indicated by TLC (approximately 5 min). After consumption of starting materials as indicated by TLC, the reaction mixture was cooled at room temperature, poured into water, and basified with aqueous ammonia with continuous stirring. The resulting precipitate was filtered and washed with water, and recrystallized from ethanol to give pure product. Off-white solid M.p. = 215-217 C. IR mmax (KBr) cm-1: 3334, 3268, 3052, 2993, 2379, 1709, 1663, 1511, 1309, 1297, 1102, 972, 761. 1H NMR (400 MHz, DMSO-d6): δH (ppm) 2.33 (s, 3H, CH3), 2.41 (s, 3H, COCH3), 7.85 (s, 2H, thiazole-2-NH2). 13C NMR (100 MHz, DMSO): δC (ppm) 188.20, 170.45, 157.66, 121.23, 29.45, 18.27. MS (ESI) m/z for (156.21): 157.1 (M + 1)+, 258.1 (M + 2)+. Elemental analysis: Calculated for C6H8N2OS (156.04): C 46.13%, H 5.16%, N 17.93%, S 20.53%; Found: C 46.11%., H 5.19%, N 17.92%, S 20.51%.
92% With N-iodo-succinimide; In ethanol; at 20℃; for 2h; General procedure: A mixture of methyl carbonyl (2 mmol), thiourea (3 mmol), NIS(2 mmol), and NH2-MMT (0.10 g) in EtOH (5 mL) at room temperature was stirred until completion of reaction. The progress of the reaction was monitored by TLC (petroleum ether-ethyl acetate 4:1). After completion of the reaction, the NH2-MMT was separated by filtration. After evaporation of EtOH under vacuum, the crude product was dissolved in boiling water and adjusted to pH 8 withthe amount of ammonia to give the solid products. The solid obtained was recrystallized from a mixture of ethanol-water.
80% With iodine; In ethanol; for 4.5h;Reflux; General procedure: A mixture of the acetophenone (2 mmol), thiourea (3 mmol) and iodine (2 mmol), in the presence of 0.03 g nanochitosan was refluxed in EtOH. The progress of the reaction was monitored by TLC (petroleum ether-ethyl acetate 4:1). After completion of the reaction, the catalyst was separated by simple filtration. After evaporation of solvent, the crude product was dissolved in boiling water, extracted with ether (3 * 30 mL), and adjusted to pH = 8 with the amount of ammonia to give the solid products. The solid was recrystallized with ethanol-water to give pure 2-aminothiazole.
52% With tert.-butylhydroperoxide; 2,2'-azobis(isobutyronitrile); In methanol; at 20 - 65℃; for 24h; General procedure: General procedure: The substrate 1 (1.0 mmol) and thiourea 2(2.0 mmol) were added to solvent (5 mL methanol) at room tem-perature. To the reaction mixture, TBHP (3.0 mmol) and AIBN(0.2 mmol) were added respectively. The reaction mixture wasstirred at room temperature (for substrates 1a-f) or reux tem-perature (for substrates 1g-r) until TLC indicated the total consumption of 1 (for substrates 1p-q, the reaction time is 24 h).The residue was treated with saturated aqueous NaHCO3 (50 mL)and then extracted with EA (30 mL 3). The organic phase waswashed with brine (50 mL 1), dried over anhydrous Na2SO4. Thesolvent was removed and the residue was puried by ash columnchromatography on silica gel (EA/PE) to afford the desired compound 3.

  • 8
  • [ 30748-47-1 ]
  • [ 81-16-3 ]
  • 1-[2-(2-amino-naphthalen-1-ylazo)-4-methyl-thiazol-5-yl]-ethanone [ No CAS ]
  • 9
  • [ 30748-47-1 ]
  • [ 70-11-1 ]
  • [ 107922-02-1 ]
YieldReaction ConditionsOperation in experiment
93% With polyethylene glycol (PEG-400); In water; for 0.116667h;Microwave irradiation; Green chemistry; General procedure: To stirred solution of polyethylene glycol (PEG-400) (2 mL) in water (2 mL) were added 1-(2-amino-4-methylthiazol-5-yl)ethanone (2 mmol)/ethyl 2-amino-4-methylthiazole-5-carboxylate (2 mmol) and α-bromo aralkyl ketones (phenacyl bromides) (2 mmol), and the mixture was heated at 90 C or subject to microwave irradiation at 300 W, until reaction completion as indicated by TLC. After reaction completion, the reaction mixture was cooled at room temperature, and the solid product formed was collected by filtration, washed with water, and recrystallized from ethanol to give pure product. The recovered PEG with water was reused for five further cycles. 1-(3-Methyl-6-phenylimidazo[2,1-b]thiazol-2-yl)ethanone (3) Off-white solid IR mmax (KBr) cm-1: 3130.89, 1642.48, 1571.57, 1145.37, 1171.78, 1017.64. 1H NMR (400 MHz, DMSO-d6): δH (ppm) 2.55 (s, 3H, CH3), 2.80 (s, 3H, COCH3), 7.28-7.31 (t, 1H, J = 7.2 Hz, ArH), 7.43-7.40 (t, J = 7.4 Hz, 2H, ArH), 7.86-7.88 (d, J = 7.2 Hz, 2H, ArH), 8.45 (s, 1H, ArH). 13C NMR (100 MHz, DMSO): δC (ppm) 13.81, 29.36, 108.94, 125.47, 127.59, 128.69, 133.43, 135.60, 146.95, 147.44, 191.18. MS (ESI) m/z for (256.32): 257.2 (M + 1)+, 258.2 (M + 2)+. Elemental analysis: Calculated for C11H9NO2 (256.07): C 65.60%, H 4.72%, N 10.93%, S 12.51%; Found: C 65.63%, H 4.70%, N 10.92%, S 12.54%.
  • 10
  • [ 30748-47-1 ]
  • [ 614-16-4 ]
  • 2-amino-4-methyl-5-(3-cyano-2-phenylthiophene-4-yl)thiazole [ No CAS ]
  • 11
  • [ 30748-47-1 ]
  • [ 105-56-6 ]
  • 2-amino-4-methyl-5-(3-cyano-2-hydroxythiophene-4-yl)thiazole [ No CAS ]
  • 12
  • [ 30748-47-1 ]
  • [ 109-77-3 ]
  • 2-amino-4-methyl-5-(2-amino-3-cyanothiophene-4-yl)thiazole [ No CAS ]
  • 13
  • 1-(2-amino-4-methyl-thiazol-5-yl)-ethanone oxime [ No CAS ]
  • [ 30748-47-1 ]
  • 14
  • [ 30748-47-1 ]
  • [ 4637-24-5 ]
  • N'-[5-(3-dimethylaminoacryloyl)-4-methylthiazol-2-yl]-N,N-dimethylformamidine [ No CAS ]
  • 15
  • [ 30748-47-1 ]
  • [ 121-51-7 ]
  • [ 804482-40-4 ]
  • 16
  • [ 102-09-0 ]
  • [ 30748-47-1 ]
  • [ 382637-99-2 ]
YieldReaction ConditionsOperation in experiment
85% Part F: Preparation of (5-Acetyl-4-methyl-thiazol-2-yl)-carbamic Acid Phenyl Ester Sodium hydride (60% dispersion in mineral oil, 3.07 g, 77 mmol) was washed twice with hexane and suspended in N,N-dimethylformamide. 2-Amino-5-acetyl-4-methylthiazole (10.0 g, 64 mmol) was added with stirring and cooling on an ice bath. Stirring was continued until the sodium hydride was consumed. Diphenyl carbonate (34 g, 160 mmol) was added and the mixture was stirred for 30 minutes at room temperature. The solvent was removed under vacuum to yield a brown residue, which was dissolved in chloroform and washed successively with 0.5N aqueous hydrochloric acid, twice with water and finally with saturated aqueous sodium chloride. The aqueous phases were back extracted twice with chloroform. The combined organic fractions were dried over sodium sulfate and concentrated under vacuum to give a white solid. This was chromatographed on silica gel, eluding with 15%-70% ethyl acetate in hexane, to give a white solid (15.0 g, 85%). 1H NMR (300 MHz, CDCl3) δ 11.42 (bs, 1H), 7.47-7.40 (m, 2H), 7.33-7.27 (m, 1H), 7.22-7.18 (m, 2H), 2.72 (s, 3H), 2.50 (s, 3H). Mass spec (ES+) m/z 277.1 (M+H+).
With hydrogenchloride; NaH; In chloroform; water; N,N-dimethyl-formamide; mineral oil; Example 6 (5-Acetyl-4-methyl-thiazol-2-yl)-carbamic Acid Phenyl Ester In a round-bottom flask, NaH 60% dispersion in mineral oil (3.07 g, 77 mmol) was washed 2*with hexane and suspended in DMF. Then 2-amino-5-acetyl-4-methyl-thiazole (10.0 g, 64 mmol) was added and stirred while cooling in an ice bath. Stirring continued until the NaH was consumed. Diphenyl carbonate (34 g, 160 mmol) was added while cooling and after the addition was complete the reaction mixture was stirred for an additional 30 minutes at room temperature. The DMF was removed on a rotary evaporator (high vacuum, 40 C.) to yield a brown residue. This residue was dissolved in 1 L of CHCl3 and washed successively with 2 L of 0.5N HCl, 2*1 L of water, and finally by 1 L of brine. The aqueous portions were back extracted twice with ~300 mL of CHCl3. The combined organic fractions were dried over anhydrous sodium sulfate, filtered and concentrated on a rotary evaporator to give a white solid. This was chromatographed on silica (15%-70% EtOAc/hexane) to give 15 g of the desired carbamate as a white solid. 1H NMR (300 MHz, CDCl3) δ 11.42 (bs, 1H), 7.47-7.40 (m, 2H), 7.33-7.27 (m, 1H), 7.22-7.18 (m, 2H), 2.72 (s, 3H), 2.50 (s, 3H). ESI MS: (M+H)+=277.1.
With hydrogenchloride; NaH; In chloroform; water; N,N-dimethyl-formamide; mineral oil; Part A Preparation of (5-acetyl-4-methyl-thiazol-2-yl)-carbamic acid phenyl ester In a round-bottom flask, NaH 60% dispersion in mineral oil (3.07 g, 77 mmol) was washed 2* with hexane and suspended in DMF. Then 2-amino-5-acetyl-4-methyl-thiazole (10.0 g, 64 mmol) was added and stirred while cooling in an ice bath. Stirring continued until the NaH was consumed. Diphenyl carbonate (34 g, 160 mmol) was added while cooling and after the addition was complete the reaction mixture was stirred for an additional ~30 minutes at room temperature. The dimethylformamide was removed on a rotary evaporator (high vacuum, 40 C.) to yield a brown residue. This residue was dissolved in 1 L of chloroform and washed successively with 2 L of 0.5N aqueous hydrochloric acid, twice with 1 L of water, and finally by 1 L of brine. The aqueous portions were back extracted twice with 300 mL of chloroform. The combined organic fractions were dried over anhydrous sodium sulfate, filtered and concentrated on a rotary evaporator to give a white solid. This was chromatographed on silica (15%-70% EtOAc/hexane) to give 15 g of the desired carbamate as a white solid. 1H NMR (300 MHz, CDCl3) δ: 11.42 (bs, 1 H), 7.47-7.40 (m, 2 H), 7.33-7.27 (m, 1 H), 7.22-7.18 (m, 2 H), 2.72 (s, 3 H), 2.50 (s, 3 H). ESI MS: (M+H)+=277.1.
  • 17
  • [ 681143-31-7 ]
  • [ 30748-47-1 ]
  • [ 681139-36-6 ]
  • 18
  • [ 123-54-6 ]
  • [ 30748-47-1 ]
YieldReaction ConditionsOperation in experiment
With sulfuryl dichloride; thiourea; In tetrachloromethane; ethanol; water; EXAMPLE 29 To a solution of acetylacetone (30 g) in carbon tetrachloride (80 m) was dropwise added sulfuryl chloride (40.5 g) under ice-cooling with stirring and the mixture was stirred at ambient temperature for one hour. The reaction mixture was evaporated in vacuo and the residue was added to a solution of thiourea (45.6 g) in ethanol (200 ml). The resulting mixture was stirred at ambient temperature for 3 hours. The precipitate was collected by filtration. The filtrate was concentrated in vacuo and the second crop of precipitate was collected by filtration. The combined precipitate was added to water (400 ml) and the mixture was acidified to pH 1.0 with 10% hydrochloric acid. The resulting precipitate was collected by filtration, washed successively with water and ethyl acetate, and dried over phosphorus pentoxide to give 5-acetyl-2-amino-4-methylthiazole (35.0 g). mp 272 C. (dec.) IR (Nujol): 3250, 1660, 1600 cm-1 NMR (DMSO-d6, δ): 2.50 (3H, s), 2.58 (3H, s), 5.87 (2H, br. s)
  • 19
  • [ 30748-47-1 ]
  • [ 75-36-5 ]
  • [ 39884-12-3 ]
YieldReaction ConditionsOperation in experiment
83.6% With pyridine; In tetrahydrofuran; dichloromethane; at 0℃; for 2h; 5-Acetyl-2-amino-4-methylthiazole (P5) (12.35 g, 79 mmol) is suspended in THF/DCM 3: 2 mixture (150 mL). The mixture was cooled down to 0'0-and pyridine (16 mL) is added, followed by the dropwise addition of acetyl chloride (8.43 mL, 119 mmol, 1.5 eq). The mixture was stirred 2 hours at 0 C. As the acetylation is complete, the reaction is quenched with addition of water (70 mL) and diluted with EtOAc (100 mL). The two phases are separated and the organic phase is washed with one portion of 10% citric acid solution. Organic layer is dried over MgS04, filtrated and evaporated. The resulting crude mass is purified by crystallization in EtOAc/Cyclohexane mixture, to obtain N- (5-acetyl-4-methyl- 1, 3-thiazol-2-yl) acetamide (P6) as a colorless powder (13.13 g, 83. 6% yield). 1H NMR (DMSO-d6) # : 2.17 (s, 3H), 2.47 (s, 3H), 2.56 (s, 3H), 12.44 (br s, 1H). Nf (ESI) : 197.3 ; MF (ESI) : 199.3. HPLC, Rt: 1.7 min (purity: 99.7%).
83.6% With pyridine; In tetrahydrofuran; dichloromethane; at 0℃; for 2h; 5-Acetyl-2-amino-4-methylthiazole (P5) (Flrochem) (12.4 g, 79 mmol) is suspended in THF/DCM 3:2 mixture (150 ml). The mixture is cooled down to 00C and pyridine (16 ml) is added, followed by the dropwise addition of acetyl chloride (8.43 ml, 119 mmol, 1.5 eq.). The mixture is stirred 2 hours at 00C. As the acetylation is complete, the reaction is quenched with addition of water (70 ml) and diluted with EtOAc (100 ml). The two phases are separated and the organic phase is washed with one portion of 10% citric acid solution. Organic layer is dried over MgSO4, filtrated and evaporated. The resulting crude mass is purified by crystallization in EtOAc/Cyclohexane mixture, to obtain N-(5-acetyM-methyl- l,3-thiazol-2-yl)acetamide (P6) as a colorless powder (13.1 g, 83.6% yield).1HNMR (DMSO-d6) δ: 2.17 (s, 3H), 2.47 (s, 3H), 2.56 (s, 3H), 12.44 (br s, 1H). M (ESI): 197.3; M+(ESI): 199.3. HPLC (method A), Rt: 1.7 min (purity: 99.7%).
  • 20
  • [ 30748-47-1 ]
  • [ 94284-80-7 ]
YieldReaction ConditionsOperation in experiment
74% With hydrogen bromide; bromine; In 1,4-dioxane; water; at 60℃; for 3h; 5-Acetyl-2-amino-4-methylthiazole (P5) (1.0 g, 6.4 mmol) is suspended in 48% HBr solution in water (20 mL, 6.4 mmol). The mixture is warmed to 60 C and a solution of Br2 (0.262 mL, 5.12 mmol, 0.8 eq) in dioxane (20 mL) is added dropwise. The mixture is stirred at 60 C for 3 hours. The progression of the reaction is followed by LC/MS. When it is complete, the solvents are evaporated, and the water is removed by azeotropic distillation with toluene. The resulting solid is recrystallized in isopropanol/Et20 mixture, affording Intermediate 2 as colorless solid (890 mg, 74% yield).'H NMR (DMSO-d6) 8 : 2.46 (s, 3H), 4.50 (s, 3H), 6.90 (br s, 1H), 9.18 (br s, 2H). M- (ESI) : 234.1 ; M+ (ESI) : 236. 1.
74% With hydrogen bromide; bromine; In 1,4-dioxane; water; at 60℃; for 3h; 5-Acetyl-2-amino-4-methylthiazole (P5) (Flrochem) (1.0 g, 6.4 mmol) is suspended in 48% HBr solution in water (20 ml, 6.4 mmol). The mixture is warmed to 600C and a solution of Br2 (0.262 ml, 5.12 mmol, 0.8 eq.) in dioxane (20 ml) is added dropwise. The mixture is stirred at 600C for 3 hours. The progression of the reaction is followed by LC/MS. When it is complete, the solvents are evaporated, and the water is removed by azeotropic distillation with toluene. The resulting solid is recrystallized in isopropanol/Et2O mixture, affording Intermediate 2 as colorless solid (890 mg, 74% yield). It is used in bis-thiazol synthesis as HBr salt or as parent, after 5 min treatment with Amberlyst A21 in DCM/MeOH mixture. 1K NMR (DMSO-d6) δ: 2.46 (s, 3H), 4.50 (s, 3H), 6.90 (br s, IH), 9.18 (br s, 2H). M (ESI): 234.1; M+(ESI): 236.1.
47% With hydrogen bromide; phenyltrimethylammonium tribromide; acetic acid; at 20℃; A solution of <strong>[30748-47-1]5-acetyl-2-amino-4-methylthiazole</strong> (0.101 g, 0.599 mmol) and phenyltrimethylammonium tribromide (0.246 g, 0.658 mmol) in 33% of HBr in acetic acid was stirred at room temperature for overnight. The solution was poured into ice water and CH2Cl2. The undissolved solid was collected from the organic layer and washed with diethyl ether to give 1-(2-amino-4-methyl-1,3-thiazol-5-yl)-2-bromoethanone hydrobromide (0.680 g, 47%) as a white solid. 1H NMR (DMSO-d6, 300 MHz) δ 8.90-8.40 (br, 2H), 4.53 (s, 2H), 2.46 (s, 3H).
With hydrogen bromide; pyridinium hydrobromide perbromide; In acetic acid; EXAMPLE 44 To a suspension of 2-amino-4-methyl-5-acetylthiazole (15.6 g) in 30% solution of hydrogen bromide in acetic acid (120 ml) was added pyridinium hydrobromide perbromide (36 g) at ambient temperature and the mixture was stirred at the same temperature for 5 hours. The precipitate was collected by filtration, washed with diisopropyl ether, and dried over calcium chloride to give 2-amino-4-methyl-5-(2-bromoacetyl)thiazole hydrobromide (26.8 g). IR (Nujol): 1660, 1620, 1600, 1540 cm-1

  • 21
  • [ 30748-47-1 ]
  • [ 530-62-1 ]
  • [ 860620-63-9 ]
YieldReaction ConditionsOperation in experiment
39% With ammonia; In 1,4-dioxane; DMF (N,N-dimethyl-formamide); for 48h; 2-Amino-4-methyl-5-acetylthiazole (3 g, 19.2 mmol) is dissolved in DMF (30 mL). CDI (3.5 g, 21.1 mmol) is added and the mixture is stirred at RT for 3h. Ammonia 0.5 N in dioxane is added (60 mL, 30 mmol) is added and the mixture is stirred for 2 days in a closed system. The resulting precipitate is recovered by filtration, washed with petroleum ether and dried under vacuo, affording N- (5-acetyl-4-methyl-1, 3-thiazol-2-yl) urea as colorless solid (1.5 g, 39%).
  • 22
  • [ 30748-47-1 ]
  • [ 32315-10-9 ]
  • [ 228559-74-8 ]
  • [ 475108-51-1 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In chloroform; water; acetone; Example 36 N-(5-Acetyl-4-methyl-1,3-thiazol-2-yl)-N'-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}urea 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (30 mg) was dissolved in chloroform (3 ml) to prepare a solution. Triethylamine (0.3 ml) and a solution of triphosgene (27 mg) in chloroform (0.2 ml) were then added thereto, and the mixture was stirred at room temperature for 30 min. Next, a solution of <strong>[30748-47-1]5-acetyl-2-amino-4-methylthiazole</strong> (64 mg) in chloroform (0.6 ml) was added thereto, and the mixture was further stirred at room temperature overnight. Water was added to the reaction solution, and the mixture was subjected to separatory extraction with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The organic layer was concentrated under the reduced pressure, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give 6 mg of the title compound. 1H-NMR (CDCl3, 400 MHz): δ 2.47 (s, 3H), 2.56 (s, 3H), 3.93 (s, 3H), 3.95 (s, 3H), 6.57 (d, 1H, J=4.9 Hz), 7.14 (d, 1H, J=8.3 Hz), 7.38-7.41 (m, 1H), 7.49 (s, 1H), 7.80 (s, 1H), 8.17 (t, 1H, J=9.0 Hz), 8.51 (d, 1H, J=5.4 Hz), 9.17 (s, 1H), 11.23 (br, 1H) Mass spectrometry value (ESI-MS, m/z): 495 (M+-1)
  • 23
  • [ 30748-47-1 ]
  • [ 110-46-3 ]
  • [ 38205-55-9 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; N-methyl-acetamide; di-isopropyl ether; water; ethyl acetate; EXAMPLE 119 To a solution of <strong>[30748-47-1]5-acetyl-2-amino-4-methylthiazole</strong> (15.6 g) in a mixture of tetrahydrofuran (200 ml) and dimethylformamide (50 ml) was dropwise added isoamylnitrite (14.6 g) at 50 C. to 55 C. with stirring and the mixture was stirred at 55 C. to 60 C. for 4 hours. The reaction mixture was poured into a mixture of ethyl acetate and water with stirring. The separated organic layer was washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was subjected to column chromatography on silica gel and eluted with a mixture of diisopropyl ether and ethyl acetate (1:1). The fractions containing the desired compound were combined and evaporated in vacuo to give 5-acetyl-4-methylthiazole (7.7 g) as an oil. IR (Film): 1660 cm-1 NMR (DMSO-d6, δ): 2.56 (3H, s), 2.68 (3H, s), 9.16 (1H, s)
  • 24
  • [ 504-29-0 ]
  • [ 30748-47-1 ]
  • 2-(2-amino-4-methyl-5-thiazolyl)imidazo[1,2-a]pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With hydrogen bromide; pyridinium hydrobromide perbromide; triethylamine; In ethanol; di-isopropyl ether; water; acetic acid; ethyl acetate; EXAMPLE 80 To a suspension of 2-amino-4-methyl-5-acetylthiazole (4.7 g) in 30% solution of hydrogen bromide in acetic acid (50 ml) was added pyridinium hydrobromide perbromide (10.8 g) at ambient temperature and the mixture was stirred at the same temperature for 3 hours. To the reaction mixture was added diisopropyl ether and the solvent was decanted. The residue was added to a solution of 2-aminopyridine (8.5 g) and triethylamine (10 ml) in ethanol (100 ml) and the resulting mixture was refluxed for 5 hours. The reaction mixture was evaporated in vacuo. The residue was suspended in a mixture of water and ethyl acetate and the suspension was acidified to pH 1.0 with 10% hydrochloric acid. The separated aqueous layer was adjusted to pH 7.0 with 20% aqueous potassium carbonate with stirring. The precipitate was collected by filtration, washed successively with water and ethyl acetate. The crude product was recrystallized from a mixture of tetrahydrofuran and water to give 2-(2-amino-4-methyl-5-thiazolyl)imidazo[1,2-a]pyridine (1.4 g). mp 275
  • 25
  • [ 30748-47-1 ]
  • [ 1885-14-9 ]
  • [ 382637-99-2 ]
YieldReaction ConditionsOperation in experiment
To an ice-cold solution of 1.00 g of <strong>[30748-47-1]5-acetyl-2-amino-4-methylthiazole</strong> and 1.5 ml. of pyridine, 1.2 ml of phenyl chloroformate are added. After stirring for 10 minutes at ambient temperature, the mixture obtained is quenched with saturated aq. sodium hydrogen carbonate solution. After exhaustive extraction with CH2CI2, the combined organic extracts are dried and concentrated. (5-Acetyl-4-methyl-thiazol-2-yl)-carbamic acid phenyl ester is obtained.
  • 26
  • [ 30748-47-1 ]
  • [ 29568-33-0 ]
  • [ 1065640-14-3 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In tetrahydrofuran; at 50℃; for 18h; Example 40A N-(5-acetyl-4-methylthiazol-2-yl)-5-chloro-2-methoxybenzamide To a solution of <strong>[30748-47-1]5-acetyl-2-amino-4-methylthiazole</strong> (5.0 g, 32 mmol) in 50 mL of tetrahydrofuran was added triethylamine (13.4 mL, 96 mmol) followed by Example 18B (32 mmol) in 10 mL of tetrahydrofuran via cannula. The mixture was warmed to 50 C. and was allowed to stir for 18 hours. The mixture was cooled to ambient temperature quenched with 15 mL of NH4Cl and diluted with 15 mL of ethyl acetate. The layers were separated and the aqueous layer was extracted with three 10 mL portions of ethyl acetate. The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was washed with ethyl acetate and the remaining solids were pure title compound. MS (DCI/NH3) m/z 325 (M+H)+.
With triethylamine; In tetrahydrofuran; at 50℃; for 18h; To a solution of <strong>[30748-47-1]5-acetyl-2-amino-4-methylthiazole</strong> (5.0 g, 32 mmol) in 50 mL of tetrahydrofuran was added triethylamine (13.4 mL, 96 mmol) followed by Example 205B (32 mmol) in 10 mL of tetrahydrofuran via cannula. The mixture was warmed to 50 0C and was allowed to stir for 18 hours. The mixture was cooled to ambient temperature quenched with 15 mL OfNH4Cl and diluted with 15 mL of ethyl acetate. The layers were separated and the aqueous layer was extracted with three 10 mL of portions of ethyl acetate. The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was washed with ethyl acetate and the remaining solids were pure title compound. MS (DCI/NH3) m/z 325 (M+H)+
  • 27
  • [ 1943-83-5 ]
  • [ 30748-47-1 ]
  • [ 1072805-54-9 ]
YieldReaction ConditionsOperation in experiment
99% With triethylamine; In tetrahydrofuran; at 20℃; for 45h;Heating / reflux; EXAMPLE 35; Synthesis of l-(5-acetyl-4-methylthiazol-2-yl)imidazolidin-2-one; To a solution of <strong>[30748-47-1]5-acetyl-2-amino-4-methylthiazole</strong> (5.50 g, 35.20 mrnol) in tetrahydrofuran (200 mL) was added triethylamine ( 1 5.0 mL, 107.6 mrnol) and 2- chloroethyl isocyanate (3.90 mL, 45.70 mrnol). The reaction mixture was stirred at ambient temperature for 18 hours, and then heated to reflux for 27 hours. The solvent was removed in vacuo, and the residue was washed with water (200 mL) and ethyl acetate/hexanes ( 1 /1 , 50 mL) to afford the title compound in 99% yield (7.9 g): MS (ES+) m/z 226.1 (M + 1 ).
99% With triethylamine; In tetrahydrofuran; at 20℃; for 45h;Reflux; To a solution of <strong>[30748-47-1]5-acetyl-2-amino-4-methylthiazole</strong> (5.50 g, 35.20 mmol) in tetrahydrofuran (200 mL) was added triethylamine (15.0 mL, 107.6 mmol) and 2-chloroethyl isocyanate (3.90 mL, 45.70 mmol). The reaction mixture was stirred at ambient temperature for 18 hours, and then heated to reflux for 27 hours. The solvent was removed in vacuo, and the residue was washed with water (200 mL) and ethyl acetate/hexanes (1/1, 50 mL) to afford the title compound in 99% yield (7.9 g): MS (ES+) m/z 226.1 (M + 1).
  • 29
  • [ 30748-47-1 ]
  • [ 4637-24-5 ]
  • [ 507487-90-3 ]
YieldReaction ConditionsOperation in experiment
at 100℃; for 15h; A mixture of <strong>[30748-47-1]5-acetyl-2-amino-4-methylthiazole</strong> (12.5 g) and N,N-dimethylformamide-dimethylacetal (35.4 ml) is heated for 15 hours at 100 C. After cooling to room temperature the reaction mixture is evaporated, triturated with ethyl acetate, and filtered to give the title compound as an orange solid. MS (Method D) M+H 267.
  • 30
  • [ 10531-41-6 ]
  • [ 30748-47-1 ]
  • [ 1170673-57-0 ]
YieldReaction ConditionsOperation in experiment
Intermediate 17: (+/-V1-r3-Methyl-6-(2-thienvnimidazor2.1-biϖ .3lthiazol-2-yllethanolA solution of 2-bromo-1-(2-thienyl)ethanone (commercially available from Acros Organics) (0.820 g, 4 mmol) in ethanol (12 ml) was added to 1-(2-amino-4-methyl- 1 ,3-thiazol-5-yl)ethanone (commercially available from Aldrich) (0.625 g, 4.00 mmol). The reaction mixture was heated at reflux over night. 1-Butanol (5 ml) was added and the reaction mixture was stirred at reflux for 2 days. The mixture was evaporated under vacuum. Ethanol (25ml) followed by NaBH4 (197 mg, 5.20 mmol) were added and the reaction mixture was stirred at room temperature over night. Water (2ml) was added and the solvent removed under vacuum to obtain a solid which was dissolved <n="41"/>in 50% MeOH/DCM. The MeOH/DCM solution was loaded onto a SCX-2 cartridge. The cartridge was washed with MeOH (40ml) then eluted with a solution of NI-13/MeOH (0.5M) (60ml). The eluant was evaporated to dryness and the residue was purified by MDAP to give the title compound (1 1 mg); MS: ES+ m/z: 265 [MH+] at RT 2.6 min. Ci2H12N2OS2 requires 264 (analysed by LCMS A).
  • 31
  • [ 30748-47-1 ]
  • [ 843643-01-6 ]
  • [ 681138-84-1 ]
YieldReaction ConditionsOperation in experiment
To a solution of [5-ACETYL-2-AMINO-4-METHYL] thiazole (2.19 g, 14.02 [MMOL)] in a mixture of THF (10 [ML)] and toluene (20 ml) was added 2 M AlMe3 in toluene (7 [ML,] 14 [MMOL)] at room temperature and stirred for 1 hr. [2- [2- (3, 5-DIFLUORO-PHENYL)-ACETYLAMINO]-PENTANOIC] acid methyl ester (2.000 g, 7.01 [MMOL)] was added and the resulting mixture was heated at reflux overnight. The mixture was quenched with Rocelle salt and extracted with ethyl acetate. The organic layer was washed with water, diluted HCI, brine, separated, dried and concentrated to give 2.48 g of the title compound as an orange solid. The solid was purified by silica gel column chromatography using [1% METHANOL] in methylene chloride as eluent to give the title compound as a yellow solid. LC-MS RT 2.3 min, M+1=410. 3,'H NMR [(CDCI3)] d 6.86 (m, 2H), 6.75 (m, 1H), 6.10 (d, [1H,] NH), 4.68 (m, 1H), 3.65 (Abq, 2H), 2.64 (s, 3H), 2.50 (s, 3H), 1.89 (m, [1H),] 1.68 (m, [1H),] 1.34 (m, 2H), 0.92 (t, 3H) ppm.
  • 32
  • [ 30748-47-1 ]
  • [ 4637-24-5 ]
  • [ 507487-90-3 ]
YieldReaction ConditionsOperation in experiment
82% at 20 - 103℃; for 21h; 5-Acetyl-2-amino-4-methylthiazole(30 g, 192 mmol) was added portion wise to N,N-dimethylformamide dimethyl acetal (90ml, ex Aldrich), over 1 hour, at room temperature. The resulting pale-yellowsuspension was then heated at reflux for 20 hours, cooled to room temperatureand EtOAc (150 ml) added. After stirring the suspension for 30 minutes at roomtemperature the first crop of crystals of compound 7 were collected by filtration, washing with EtOAc (2x 50 ml). Thefiltrate was evaporated and the residue suspended in EtOAc (50 ml), triturated,stirred, and then filtered to give a second crop of crystals. The two cropswere combined and dried under high vacuum to give compound 7 as an orange crystalline solid, 44.4 g (95% purity, 82% yield).mp: 157-159 C. 1H NMRin CDCl3 (400 MHz): 8.23 (s, 1H), 7.68 (d, J = 12.1 Hz, 1H), 5.35 (d, J= 12.1 Hz, 1H), 3.11 (s, 3H), 3.08 (s, 3H), 2.63 (s, 3H), 1.56 (s, 6H).
at 100℃; Step 42.2: 4-Methyl-5-[2-(1 -methyl-cvclopropyD-pyrimidin^-yli-thiazol^-ylamine; Powdered sodium hydroxide (5.86 g) is added to a solution of N'-[5-(3-dimethylamino- acryloyl)-4-methyl-thiazol-2-yl]-N,N-dimethyl-formamidine (13 g, prepared as described byS. Wang et al J. Med. Chem. 2004, 47, 1662-1675.) and 1-methyl- cyclopropanecarboxamidine hydrochloride (7.2 g, prepared as described in EP0227415) in2-methoxyethanol (98 ml) and the mixture heated at 125 0C for 1 hour with stirring. The reaction mixture is cooled, water is added, and the title compound isolated by filtration. ESI- MS: M+H 247 and M-H 245.
  • 33
  • [ 30748-47-1 ]
  • [ 79-04-9 ]
  • [ 32519-70-3 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In tetrahydrofuran; at 0 - 20℃; General procedure: A solution of 2-amino-5-substituted-4-methylthiazole (1) (0.01 mol) (1a:1.2 g, 1b:1.3 g, 1c:1.6 g, 1d:1.9 g, 1e:1.9 g)[29, 30] and triethylamine (0.01 mol) (1.5 mL) was prepared by stirring in THF (50 mL) at room temperature. After cooling the mixture in an ice bath, chloroacetyl chloride (0.01mol) (0.8 mL) was added drop wise with constant stirring. Before evaporation of the solvent under reduced pressure,the reaction mixture was further stirred for 1 hour at room temperature. The precipitate formed was crystallised from ethanol [31, 12].
With potassium carbonate; In dichloromethane; General procedure: Aminothiazole (A1-A18, 50 mmol) and 100 mmol of potassiumcarbonate were dissolved in dichloromethane (100 mL), chloroacetylchloride (8.0 mL) was added dropwise under ice bath, andreacted at room temperature monitored by TLC. When the reactionis completed, the reaction solution is poured into water, andwashed with sodium bicarbonate solution, saturated saline andwater successively, dry the organic phase with anhydrous sodiumsulfate, remove the solvent under reduced pressure, and recrystallizewith ethanol to obtain raw product B1-B18. Then intermediate(30 mmol) and KSCN (45 mmol) were dissolved in 100 mLof ethanol, and reflux for 6 h. The reaction mixture were cooleddown, filtered, and washed with ethanol and water, the crudeproduct was recrystallized from ethanol/water to afford the pure 4-thiazolinone intermediate C1-C18.
 

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Thiazoles

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