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[ CAS No. 2285-12-3 ] {[proInfo.proName]}

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Chemical Structure| 2285-12-3
Chemical Structure| 2285-12-3
Structure of 2285-12-3 * Storage: {[proInfo.prStorage]}
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Product Details of [ 2285-12-3 ]

CAS No. :2285-12-3 MDL No. :MFCD00002008
Formula : C8H4F3NO Boiling Point : -
Linear Structure Formula :- InChI Key :GZWGTVZRRFPVAS-UHFFFAOYSA-N
M.W : 187.12 Pubchem ID :16794
Synonyms :

Safety of [ 2285-12-3 ]

Signal Word:Danger Class:6.1,3
Precautionary Statements:P210-P233-P240-P241-P242-P243-P260-P261-P264-P270-P271-P280-P284-P285-P301+P310-P302+P352-P303+P361+P353-P304-P304+P340-P304+P341-P305+P351+P338-P310-P312-P320-P321-P330-P332+P313-P337+P313-P340-P342+P311-P362-P370+P378-P403-P403+P233-P403+P235-P405-P501 UN#:3080
Hazard Statements:H225-H301-H315-H319-H330-H334-H335 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 2285-12-3 ]

* 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 [ 2285-12-3 ]

[ 2285-12-3 ] Synthesis Path-Downstream   1~87

  • 1
  • [ 57368-82-8 ]
  • [ 2285-12-3 ]
  • [ 72030-57-0 ]
YieldReaction ConditionsOperation in experiment
In benzene; EXAMPLE 5 1-(2-Trifluoromethylphenyl)-3-[1-(4-phenyl-4-oxobutyl)piperid-4-yl]urea. 4-Amino-1-(4-phenyl-4-oxobutyl)piperidine (1.23 g) and 2-trifluoromethylphenyl isocyanate (1.03 g) were condensed together in benzene (125 ml) in the manner of Example 1 to give the title compound (1.01 g). Crystallization from EtOH/HCl afforded the hydrochloride (0.67 g), m.p. 193.7 C C23 H26 F3 N3 O2 HCl requires C 58.73; H 5.75; N 8.94%; Found C 58.88; H 5.93; N 8.79%.
  • 2
  • [ 2008-58-4 ]
  • [ 2285-12-3 ]
  • [ 50822-24-7 ]
YieldReaction ConditionsOperation in experiment
With sodium hydride In N,N-dimethyl-formamide 1.) 30 min., -10 to 0 deg C, 2.) 4h, room temperature;
  • 3
  • [ 40835-96-9 ]
  • [ 2285-12-3 ]
  • 1-(1H-Perimidin-2-yl)-3-(2-trifluoromethyl-phenyl)-urea [ No CAS ]
  • 4
  • [ 2285-12-3 ]
  • [ 68614-93-7 ]
  • [ 86866-74-2 ]
  • 5
  • [ 161708-60-7 ]
  • [ 2285-12-3 ]
  • [ 161708-81-2 ]
  • 6
  • (S)-Pyrrolidine-2-carboxylic acid [(S)-1-(benzyl-methyl-carbamoyl)-2-naphthalen-2-yl-ethyl]-amide [ No CAS ]
  • [ 2285-12-3 ]
  • (S)-Pyrrolidine-1,2-dicarboxylic acid 2-[(S)-1-(benzyl-methyl-carbamoyl)-2-naphthalen-2-yl-ethyl]-amide} 1-[(2-trifluoromethyl-phenyl)-amide] [ No CAS ]
  • 7
  • [ 684-16-2 ]
  • [ 2285-12-3 ]
  • [ 246875-94-5 ]
  • 8
  • [ 220597-65-9 ]
  • [ 2285-12-3 ]
  • (2-trifluoromethyl-phenyl)-carbamic acid 2,2-dimethyl-4-(2-oxo-2<i>H</i>-pyridin-1-yl)-2<i>H</i>-chromen-6-yl ester [ No CAS ]
  • 9
  • [ 89-77-0 ]
  • [ 2285-12-3 ]
  • 4-chloro-2-[3-(2-trifluoromethyl-phenyl)-ureido]-benzoic acid [ No CAS ]
  • 10
  • [ 613-94-5 ]
  • [ 2285-12-3 ]
  • 1-(phenyl)carbonyl-4-(2-trifluoromethylphenyl)semicarbazide [ No CAS ]
  • 11
  • [ 860464-47-7 ]
  • [ 2285-12-3 ]
  • ethyl 3-(2-(trifluoromethyl)phenyl)-3,4-dihydro-7-(methylsulfonyl)-4-oxopyrazolo[5,1-d][1,2,3,5]tetrazine-8-carboxylate [ No CAS ]
  • 12
  • [ 2285-12-3 ]
  • tetrapropylzirconacyclopentadiene [ No CAS ]
  • 1-(2'-trifluoromethyl)-3,4,5,6-tetrapropylpyridin-2-one [ No CAS ]
  • 13
  • [ 915158-00-8 ]
  • [ 2285-12-3 ]
  • ethyl 7-(trifluoromethyl)-3-(2-(trifluoromethyl)phenyl)-3,4-dihydro-4-oxopyrazolo[5,1-d][1,2,3,5]tetrazine-8-carboxylate [ No CAS ]
  • 14
  • [ 1021392-48-2 ]
  • [ 2285-12-3 ]
  • [ 1021392-49-3 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; at 0 - 60℃; for 12h; Step B] 1-Cyclopropyl-1-(1-hydroxymethyl-2-methyl-propyl)-3-(2-trifluoromethyl-phenyl)-urea; To a solution of crude 2-cyclopropylamino-3-methyl-butan-1-ol (195 mg) in THF (10 mL) was slowly added a solution of 2-trifluoromethylphenylisocyanate (225 mg) in THF (3 mL) at 0 C. The mixture was then heated to 60 C. for 12 hours. After cooling, the solution was concentrated in vacuo and the residue was purified by flash chromatography using ethyl acetate/heptane 1:1 as an eluent to give the desired material as a colorless solid (245 mg). MS (ESI): 331.3 (MH+).
  • 15
  • [ 181519-16-4 ]
  • [ 2285-12-3 ]
  • [ 317356-47-1 ]
YieldReaction ConditionsOperation in experiment
56% With triethylamine; In tetrahydrofuran; Example 70 4-[(4S)-fluoro-1-[3-methoxy-4-[N'-(2-trifluoromethylphenyl)ureido]phenylacetyl]-(2S)-pyrrolidinyl methoxy]benzoic Acid To a stirred solution of tert-butyl 4-amino-3-methoxyphenylacetate (1.11 g, 4.68 mmol) and Et3N (720 ml 5.17 mmol) in THF (10 ml) was added 2-trifluoromethylphenyl isocyanate (707 ml, 4.68 mmol) and the reaction mixture was stirred at room temperature for 2 days. The reaction mixture was concentrated to a small volume and diluted with n-hexane. Resulting precipitate was collected under a reduced pressure and washed with n-hexane to give tert-butyl 3-methoxy-4-[N'-(2-trifluoromethylphenyl)ureido]phenylacetate (1.11 g, 56%) as a white crystalline powder. up 131-133 C.; 1H-NM (CDCl3) δ 1.44 (s, 9H), 3.49 (s, 2H), 3.85 (s, 3H), 6.83-6.88 (m, 3H), 6.98 (br s, 1H), 7.17-7.21 (m, 1H), 7.52-7.59 (m, 2H), 7.89-7.91 (m, 1H), 8.04-8.06 (m, 1H).
  • 16
  • 5-[4-[6-(3-aminophenoxy)-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione di-hydrochloride [ No CAS ]
  • [ 2285-12-3 ]
  • 1-(3-[2-[4-(2,4-dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl)-3-[2-(trifluoromethyl)phenyl]urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In N,N-dimethyl-formamide; EXAMPLE 24 1-(3-[2-[4-(2,4-Dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl)-3-[2-(trifluoromethyl)phenyl]urea (exemplification compound number 2-24) The title compound (452 mg, mp 160.7-164.4 C.) was obtained by a similar procedure to that described in Example 1 using 5-[4-[6-(3-aminophenoxy)-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione dihydrochloride (400 mg), α,α,α-trifluoro-o-tolyl isocyanate (210 mg), triethylamine (153 mg) and anhydrous N,N-dimethylformamide (8 ml).
  • 17
  • C36H67N5O10 [ No CAS ]
  • [ 2285-12-3 ]
  • 5-O-desosaminyl-9-deoxo-9-dihydro-9a-N-[N'-(2-(trifluoromethyl)phenylcarbamoyl)-γ-aminopropyl]-9a-aza-9a-homoerithronolide A [ No CAS ]
YieldReaction ConditionsOperation in experiment
In toluene; at 20℃; for 0.5h; A mixture of 1.0 g (1.57 mmol) 5-O-DESOSAMINYL-9-DEOXO-9-DIHYDRO-9A-N- (Y- -AMINOPROPYL)-9A-AZA-HOMOERITHRONOLIDE A and 0.30 g (1.57 mmol) of 2- - (trifluoromethyl) phenylisocyanate in 10 ml dry toluene was stirred for 30 minutes at room temperature to complete the reaction. The crystalls of the crude product were filtered, wherefrom by chromatography on sillica gel column using the solvent system methylene-chloride : methanol: ammonia= 90: 20: 1.5, pure 5-O- - DESOSAMINYL-9-DEOXO-9-DIHYDRO-9A-N- [N'- (2- (TRIFLUOROMETHYL) PHENYLCARBAMOYL-Y- - AMINOPROPYL]-9A-AZA-9A-HOMOERITHRONOLIDE A was obtained. MS (ES+) M/Z = 821
  • 18
  • C36H67N5O10 [ No CAS ]
  • [ 2285-12-3 ]
  • 5-O-desosaminyl-9-deoxo-9-dihydro-9a-N-[N'-(β-cyanoethyl)-N'-(2-(trifluoromethyl)phenyl)carbamoyl-γ-aminopropyl]-9a-aza-9a-homoerithronolide A [ No CAS ]
YieldReaction ConditionsOperation in experiment
In toluene; at 20℃; for 0.5h; A mixture of 0.5 g (0.728 mmol) 5-O-DESOSAMINYL-9-DEOXO-9-DIHYDRO-9A-N- (Y- -aminopropyl)-9a-aza-homoerithronolide A and 0.14 g (0.728 mmol) of 2- - (TRIFLUOROMETHYL) phenylisocyanate in 10 ml dry toluene was stirred for 30 minutes at room temperature to complete the reaction. The crystalls of the crude product were filtered, wherefrom by chromatography on sillica gel column using the solvent system methylene-chloride: methanol: ammonia= 90: 20: 1.5, pure 5-O- -DESOSAMINYL-9-DEOXO-9-DIHYDRO-9A-N-[N'-(ß-CYANOETHYL)-N'-(2-(TRIFLUOROMETHYL)- phenylcarbamoyl-Y-aminopropyl]-9a-aza-9a-homoerithronolide A was obtained. MS (ES+) m/z = 873
  • 19
  • 9-deoxo-9-dihydro-9a-N-[N'-(β-cyanoethyl)-γ-aminopropyl]-9a-aza-9a-homoerithromycin A [ No CAS ]
  • [ 2285-12-3 ]
  • 9-deoxo-9-dihydro-9a-N-[N'-(β-cyanoethyl)-N'-(2-(trifluoromethyl)phenyl)carbamoyl-γ-aminopropyl]-9a-aza-9a-homoerithromycin A [ No CAS ]
YieldReaction ConditionsOperation in experiment
In toluene; at 20℃; for 0.5h; A mixture of 0.5 g (0.591 mmol) 9-DEOXO-9-DIHYDRO-9A-N- [N'- (P-CYANOETHYL)-Y- - AMINOPROPYL]-9A-AZA-9A-HOMOERITHROMYCIN A and 0.08 g (0.591 mmol) of 2- - (trifluoromethyl) phenylisocyanate in 10 ml dry toluene was stirred for 30 minutes at room temperature to complete the reaction. The crystalls of the crude product were filtered, wherefrom by chromatography on sillica gel column using the solvent system methylene-chloride: methanol: ammonia= 90 : 9: 1.5, pure 9-deoxo-9- -DIHYDRO-9A-N- [N'- (P-CYANOETHYL)-N,- (2- (TRIFLUOROMETHYL) phenyl) carbamoyl-y- - AMINOPROPYL]-9A-AZA-9A-HOMOERITHROMYCIN A was obtained. MS (ES+) m/z = 1033
  • 20
  • 9-deoxo-9-dihydro-9a-aza-9a-(γ-aminopropyl)-9a-homoerithromycin A [ No CAS ]
  • [ 2285-12-3 ]
  • 9-deoxo-9-dihydro-9a-N-[N'-(2-trifluoromethyl)phenylcarbamoyl-γ-aminopropyl]-9a-aza-9a-homoerithromycin A [ No CAS ]
YieldReaction ConditionsOperation in experiment
In toluene; at 20℃; for 0.5h; A mixture of 1.0 g (1.26 mmol) 9-DEOXO-9-DIHYDRO-9A-AZA-9A- (Y-AMINOPROPYL)-9A- -HOMOERITHROMYCIN A and 0.24 g (1.3 mmol) of 2- (trifluoromethyl) phenylisocyanate in 10 ml dry toluene was stirred for 30 minutes at room temperature to complete the reaction. The crystalls of the crude product were filtered, wherefrom by chromatography on sillica gel column using the solvent system methylene-chloride: methanol: ammonia= 90 : 9 : 1.5, pure 9-DEOXO-9-DIHYDRO-9A-N- [N'- (2- trifluoromethylphenyl) CARBAMOYL-Y-AMINOPROPYL]-9A-AZA-9A-HOMOERITHROMYCIN A was obtained. MS (ES+) M/Z = 979
  • 21
  • [ 720708-51-0 ]
  • [ 2285-12-3 ]
  • [ 720708-52-1 ]
YieldReaction ConditionsOperation in experiment
73% In dichloromethane; at 20℃; for 5h; Example 38 1-(Toluene-4-sulfonyl)-4-{3-[3-(2-trifluoromethyl-phenyl)-ureido]-phenyl}-1H-pyrrole-2-carboxylic Acid Benzyl Ester A mixture of 4-(3-amino-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrole-2-carboxylic acid benzyl ester (150 mg, 0.336 mmol; from Example 37) and trifluoro-o-tolyl isocyanate (1.5 eq.) in DCM (4 ML) was stirred at room temperature for 5 hours.The reaction was concentrated to give 155 mg (73%) of the titled compound as an off-white solid.
  • 22
  • [ 95-85-2 ]
  • [ 2285-12-3 ]
  • 1-(5-chloro-2-hydroxy-phenyl)-3-(2-trifluoromethyl-phenyl)-urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
In toluene; 5-Chloro-2-hydroxyaniline (1 g) was suspended in toluene (50 ML) and treated with 2-trifluoromethylphenylisocyanate (1.2 ML). The reaction was stirred overnight and then filtered. The filter-cake was slurried and filtered twice with 15 ml toluene and washed once more with petrol. Drying at 55C gave 1- (5-CHLORO-2- hydroxy-phenyl)-3- (2-trifluoromethyl-phenyl)-urea (2.06 g). Mp. = 183-184C.
In toluene; 5-Chloro-2-hydroxyaniline (1 g) was suspended in toluene (50 ml) and treated with 2-trifluoromethylphenylisocyanate (1.2 ml). The reaction was stirred overnight and then filtered. The filter-cake was slurried and filtered twice with 15 ML toluene and washed once more with petrol. Drying at 55C gave 1- (5-CHLORO-2- HYDROXY-PHENYL)-3-(2-TRIFLUOROMETHYL-PHENYL)-UREA (2.06 G). Mp. = 183-184C.
  • 23
  • [ 109-12-6 ]
  • [ 2285-12-3 ]
  • [ 501685-46-7 ]
YieldReaction ConditionsOperation in experiment
In toluene; Aminopyrimidine (1 g) was suspended in toluene (50 ML) and treated with 3-trifluoromethylphenylisocyanate (1.5 ML). The reaction was stirred overnight and then concentrated in vacuo to provide a white solid, which was taken up in 700 mi of boiling methanol and filtered. The filtrate was refluxed to provide a clear solution, which was slowly cooled to 3C overnight. Filtration, washing with methanol and air drying gave 1-Pyrimidin-2-yl-3- (2-trifluoromethyl-phenyl)-urea (2.24 g). Mp. = 224- 225C.
With tetrabutylammomium bromide; at 80 - 100℃; General procedure: The synthetic route for N-fluorinated phenyl-N′-pyrimidyl urea derivatives is depicted in Scheme 1. At first, 40 mL toluene solution which contained 5 mmol fluorine-containing aniline was slowly dropped into another toluene solution which contained 2 mmol BTC (triphosgene) and a few drops Et3N while mixing at 0C for about 1h. The mixture was stirred at room temperature for 1 h and then heated to 80C until the white solid completely dissolved. The intermediate 1 was isolated and obtained by concentration under reduced pressure and flushing by nitrogen [16,17]. To obtain the final target compounds, the unpurified intermediate 1 was added into a series of substituted pyrimidinamine (5 mmol, as shown in Table 1) solutions which contained a little tetrabutylammonium bromide that was used as phase transfer catalyst. Then, the mixture was agitated at 80-100C for 6-9h. The reaction was detected according to TLC. When the reaction was complete, the product was cooled to room temperature, filtered, and washed with 10% Na2CO3, water, and acetone. The final target compounds were purified by recrystallization (DMF/acetone).
  • 24
  • 3-decladinosyl-9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A [ No CAS ]
  • [ 2285-12-3 ]
  • 3-decladinosyl-9-deoxo-9-dihydro-9a-N-[N'-(2-trifluoromethylphenyl)carbamoyl]-9a-aza-9a-homoerythromycin A [ No CAS ]
YieldReaction ConditionsOperation in experiment
In toluene; at 20℃; for 0.5h; To a solution of 3-decladinosyl-9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A (1,00 g) in toluene (20 ML) 2-TRIFLUORMETILPHENYLISOCYANATE (0,35 g) was added. Reaction mixture was stirred for 30 min at room temperature. The solvent was evaporated and 1,29 g of crude product is obtained. Crystallization from mixture ethyl ether-petrol ether yielding 0,84 g of chromatographically homogenous title product with following physical-chemical constants: TLC RF = 0,69 (CH2C12 : MEOH = 8 : 2) IR (KBR) [v/cm-1] : 3458, 2975,2940, 2879,2786, 1727, 1658, 1591,1536, 1457, 1384,1322, 1282, 1244,1171, 1112,1035, 979,956, 934,901, 864,834, 762,702. MS M/Z : (FAB): MH = 764,3 H NMR (300 MHZ, CDC13) [8/PPM] 8. 01 (6"H), 7.55 (3"H), 7.26 (4"-H), 7.16 (5"-H), 4.98 (13-H), 4.62 (9A-NCON H), 4. 38 (1 -H), 3.90 (3-H), 3.65 (5 -H), 3.64 (5-H), 3.61 (11-H), 3.31 (2 -H), 2.64 (2-H), 2.52 (3 -H), 2.27 (3'-N (CH3) 2), 1.91 (14-Ha), 1.72 (4 -HA), 1.57 (14-Hb), 1.56 (4-H), 1.35 (10-CH3), 1.32 (2-CH3), 1.28 (6-CH3), 1.31 (4'-Hb), 1.24 (5'-CH3), 1.15 (12-CH3), 1.10 (8-CH3), 0.96 (4-CH3), 0.91 (15-CH3). 13C NMR (75 MHz, CDCl3) [S/PPM] 177.3 (1-C), 157.0 (9A-NCONH), 136.4 (1"-C), 132.5 (3"-C), 125.7 (5"-C), 125.1 (4"-C), 123.4 (6 =C), 105.9 (1 -C), 82.9 (5-C), 77.9 (13-C), 74.4 (12-C), 75.2 (3-C), 74.4 (6-C), 73.8 (11-C), 70.4 (5'-C), 69.2 (2 -C), 64.9 (3 -C), 44.7 (2-C), 39. 9 (3'N-(CH3) 2), 38. 6 (4-C), 27.6 (4 -C), 21.3 (14-C), 20.7 (5 -CH3), 19.1 (8-CH3), 16.6 (12-CH3), 15.9 (2- CH3), 12.5 (10-CH3), 10.5 (15-CH3), 7.7 (4-CH3).
  • 25
  • 8,9,10,11-tetrahydropyrazino[1',2':1,2]imidazo[4,5-c]quinolin-6-amine hydrochloride [ No CAS ]
  • [ 2285-12-3 ]
  • C2HF3O2*C21H17F3N6O [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In DMF (N,N-dimethyl-formamide); Examples 74-113 The reagent (0.11 mmol) indicated in the table below was added to a solution of 8,9, 10, 11-tetrahydropyrazino [l', 2' : 1, 2] imidazo [4,5-c] quinolin-6-amine hydrochloride (24 mg, 0.077 mmol) and N, N diisopropylethylamine (0.070 mL, 0.40 mmol) in anhydrous DMF (2 mL) in a test tube. The test tube was capped and shaken overnight. One drop of deionized water was added to each test tube, and the solvent was removed by vacuum centrifugation. The compounds were purified by prep HPLC using the method described above. The table below shows the acid chloride, sulfonyl chloride, isocyanate, or carbamoyl chloride used for each example, the structure of the resulting compound, and the observed accurate mass for the isolated trifluoroacetate salt.
  • 26
  • [ 869733-91-5 ]
  • [ 2285-12-3 ]
  • 6-chloro-3,4-dihydro-2-(4-fluorobenzyl)-3-oxo-2H-1,2-benzothiazine-4-(2-trifluoromethyl)carboxanilide 1,1-dioxide [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% At room temperature 77 mg (0.76 mmol) triethylamin were added to a mixture of 250 mg (0.74 mmol) 6-chloro-3,4-dihydro-2-(4-fluorobenzyl)-3-oxo-2H-1,2-benzothiazine 1,1-dioxide and 142 mg (0.76 mmol) o-trifuoromethyl-phenylisocyanate dissolved in 3 mL DMSO. After stirring for 2.5 hrs the resulting mixture was quenched with dilute HCI in an ice bath and then extracted with methylenechloride (2 times). The combined extracts were washed, dried and concentrated to give 380 mg crude product. This material was recrystallized from methylenechloride/hexane to give 263 mg 6-chloro- 3,4-dihydro-2-(4-fluorobenzyl)-3-oxo-2H-1,2-benzothiazine-4-(2- trifluoromethyl) carboxanilide 1,1-dioxide. Yield: 68 % Melting point: 198 - 199 C Structure was confirmed by elementary analysis (C23H15F4CIN2O4S: C, H,N) and mass- spectroscopy.
  • 27
  • [ 869733-91-5 ]
  • [ 2285-12-3 ]
  • 6-chloro-3,4-dihydro-2-(4-fluorobenzyl)-3-oxo-2H-1,2-benzothiazine-4-(3-trifluoromethyl)carboxanilide 1,1-dioxide [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% At room temperature 70 mg (0.7 mmol) triethylamin were added to a mixture of 250 mg (0.74 mmol) 6-chloro-3,4-dihydro-2-(4-fluorobenzyl)-3-oxo-2H-1,2-benzothiazine 1,1- dioxide and 130 mg (0.7 mmol) o-trifuoromethyl-phenylisocyanate dissolved in 3 mL DMSO. After stirring for 2.5 hrs the resulting mixture was quenched with dilute HCI in an ice bath and then extracted with methylenechloride (2 times). The combined extracts were washed, dried and concentrated to give 380 mg crude product. This material was recrystallized from methylenechloride/hexane to give 240 mg 6-chloro- 3,4-dihydro-2-(4-fluorobenzyl)-3-oxo-2H-1,2-benzothiazine-4-(3- trifluoromethyl) carboxanilide 1,1-dioxide. Yield: 62 % Melting point: 183 - 184 C Structure was confirmed by elementary analysis (C23H15F4CIN2O4S: C, H,N) and mass- spectroscopy.
  • 28
  • [ 865-47-4 ]
  • [ 2285-12-3 ]
  • [ 141940-36-5 ]
YieldReaction ConditionsOperation in experiment
52% In tetrahydrofuran; at 0 - 20℃; for 3h; Part A. tert-Butyl 2-(trifluoromethyl)phenylcarbamate To a solution of 1-isocyanato-2-(trifluoromethyl)benzene (4.0 g, 21.4 mmol) in 50 mL of THF at 0 C. was added potassium tert-butoxide (32.0 mL of a 1M solution in THF, 32 mmol) dropwise. The reaction was allowed to stir for 3 h with warming to ambient temperature and then was quenched with 10 mL of water. The mixture was diluted with ethyl acetate and the organics were washed sequentially with 1N HCl, sat'd. aq. NaHCO3 and brine, dried (MgSO4) and concentrated. The residue was taken up in chloroform, filtered through a pad of silica gel and concentrated to afford 2.9 g (52%) of the title compound which was sufficiently pure to be used without further purification. 1H NMR (CDCl3): δ 8.13 (d, 1H, J=8.2 Hz), 7.56 (d, 1H, J=7.7 Hz), 7.52 (t, 1H, J=8.0 Hz), 7.14 (t, 1H, J=7.7 Hz), 6.80 (broad s, 1H), 1.53 (s, 9H).
  • 29
  • [ 114800-58-7 ]
  • [ 2285-12-3 ]
  • [ 252754-64-6 ]
YieldReaction ConditionsOperation in experiment
69% In 1,2-dichloro-ethane; at 20℃; for 2h; Example 35 6-(2-chlorophenyl)-7,10-dihydro-1-methyl-N-(2-trifluoromethylphenyl)-4H-pyrido[4',3';4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-9(8H)-carboxamide A mixture containing 2-trifluoromethylphenyl isocyanate (1.5 g, 0.008 mol) and 6-(2-chlorophenyl)-7,8,9,10-tetrahydro-1-methyl-4H-pyrido[4',3';4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine (2.1 g, 0.0057 mol) in 50 ml of 1,2-dichloromethane is agitated at ambient temperature for 2 hours. The reaction mixture is evaporated to dryness. The residual oil is precipitated by adding diisopropyl acetate. After filtration on frit, washing is carried out with ether and the solid is dried at 65 C. overnight (2.2 g, 69%). A beige powder is obtained. Melting point: 196-198 C. NMR 1H (400 MHz, DMSO d6, δ): 1.63 (m, 1H); 2.12 (m,1H); 2.61(s, 3H); 3.20 (m, 1H); 3.90 (m, 1H); 4.27 (d, 1H); 4.38 (d, 1H); 4.98 (d, 1H); 5.34 (d, 1H); 7.32-7.68 (m, 8H); 8.39 (s, 1H) IR: νNH(urea): 3333 cm-1; νC=O (carbonyl urea): 1670 cm-1; 1520 cm-1; 1318 cm-1
  • 30
  • 1-benzyl-6-(2-chlorophenyl)-7,8,9,10-tetrahydro-4H-pyrido[4',3';4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine [ No CAS ]
  • [ 2285-12-3 ]
  • 1-benzyl-6-(2-chlorophenyl)-7,10-dihydro-N-(2-trifluoromethylphenyl)-4H-pyrido[4',3';4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-9(8H)-carbothioamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
24% In 1,2-dichloro-ethane; at 20℃; for 12h; Example 40 1-benzyl-6-(2-chlorophenyl)-7,10-dihydro-N-(2-trifluoromethylphenyl)-4H-pyrido[4',3';4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-9(8H)-carbothioamide Trifluoromethylphenylisothiocyanate (0.56 g, 0.0027 mol) is added to a mixture containing 1-benzyl-6-(2-chlorophenyl)-7,8,9,10-tetrahydro-4H-pyrido[4',3';4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine (0.8 g, 0.0018 mol) in anhydrous 1,2-dichloroethane (13 ml). The reaction medium is agitated at ambient temperature for 12 hours. The precipitate is filtered on frit then washed with isopropyl ether, with ethyl acetate then with isopentane and finally dried under vacuum. 0.28 g (24%) of final productproduct is obtained in the form of a pale yellow coloured solid. Melting point: 239-240 C. NMR1H (400 MHz, CDCl3, δ): 1.72 (m,1H); 2.15 (m,1H); 3.50 (m, 1H); 4.12 (m, 1H); 4.19 (d, 1H); 4.46 (q, 2H); 4.74 (d, 1H); 5.33 (d, 1H); 5.62 (d, 1H); 7.16-7.67 (m, 14H). IR (cm-1): 3349, 1527, 1318, 1128, 756. HPLC (UV): 95.8%
  • 31
  • [ 316121-73-0 ]
  • [ 2285-12-3 ]
  • 4-[(4S)-fluoro-1-[3-methyl-4-[N'-(2-trifluoromethylphenyl)ureido]phenylacetyl]-(2S)-pyrrolidinylmethoxy]benzoic Acid [ No CAS ]
  • [ 317356-50-6 ]
YieldReaction ConditionsOperation in experiment
62% With triethylamine; In tetrahydrofuran; Example 71 4-[(4S)-fluoro-1-[3-methyl-4-[N'-(2-trifluoromethylphenyl)ureido]phenylacetyl]-(2S)-pyrrolidinylmethoxy]benzoic Acid To a stirred solution of tert-butyl 4-amino-3-methylphenylacetate (927 mg, 4.19 mmol) and Et3N (645 μl, 4.63 mmol) in THF (10 ml) was added 2-trifluoromethylphenyl isocyanate (633 μl, 4.19 mmol) and the reaction mixture was stirred at room temperature for 2 days. The reaction mixture was concentrated to a small volume and diluted with n-hexane. Resulting precipitate was collected under a reduced pressure and the filtrate was washed with n-hexane to give tert-butyl 3-methyl-4-[N'-(2-trifluoromethylphenyl)ureido]phenylacetate (1.06 g, 62%) as a white crystalline powder. mp 178-180 C.; 1H-NMR (CDCl3) δ 1.44 (s, 9H), 2.25 (s, 3H), 3.51 (s, 2H), 6.38 (or s, 1H), 7.12-7.18 (m, 3H), 7.36-7.37 (m, 1H), 7.49-7.53 (m, 2H), 8.13-8.16 (m, 1H).
  • 32
  • [ 5438-70-0 ]
  • [ 2285-12-3 ]
  • 4-[(4S)-fluoro-1-[4-[N'-(2-trifluoromethylphenyl)ureido]phenylacetyl]-(2S)-pyrrolidinylmethoxy]benzoic Acid [ No CAS ]
  • [ 317356-44-8 ]
YieldReaction ConditionsOperation in experiment
84% With triethylamine; In tetrahydrofuran; Example 69 4-[(4S)-fluoro-1-[4-[N'-(2-trifluoromethylphenyl)ureido]phenylacetyl]-(2S)-pyrrolidinylmethoxy]benzoic Acid To a stirred solution of ethyl 4-aminophenylacetate (1.13 g, 6.31 mmol) and Et3N (965 ml, 6.92 mmol) in THF (10 ml) was added 2-trifluoromethylphenyl isocyanate (953 ml, 6.31 mmol) and the reaction mixture was stirred at room temperature for 2 days. Resulting precipitate was collected under a reduced pressure and the filtrate was washed with n-hexane to give ethyl 4-[N'-(2-trifluoromethylphenyl)ureido]phenylacetate (1.93 g, 84%) as white needles. mp 137-1390C; 1H-NMR (CDCl3) delta 1.25-1.29 (m, 3H), 3.59 (s, 2H), 4.15-4.20 (m, 2H), 7.05 (br s, 1H), 7.13-7.23 (m, 6H), 7.47-7.51 (m, 1H), 7.54-7.56 (m, 1H), 8.01-8.03 (m, 1H).
  • 33
  • [ 197240-27-0 ]
  • [ 2285-12-3 ]
  • 2-(4-methanesulfonylphenyl)-2-oxoethyl (2-trifluoromethylphenyl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine; In acetonitrile; EXAMPLE 5 2-(4-methanesulfonylphenyl)-2-oxoethyl (2-trifluoromethylphenyl)carbamate Formula (II): A=phenyl, X1 =2-CF3, X2 =H, R'=CH3 5 g of the product of Example 2 and 3.3 ml of 2-trifluoromethylphenylisocyanate are dissolved in 100 ml of anhydrous acetonitrile. 5 drops of pyridine are added and the reaction mixture is heated under reflux for 4 hours. The acetonitrile is evaporated and 9 g of an oil are obtained which are used as such in the next step.
  • 34
  • [ 64987-08-2 ]
  • [ 2285-12-3 ]
  • ethyl 2-(3-o-trifluoromethylphenylureido)thiazol-4-ylglyoxylate [ No CAS ]
  • [ 126533-25-3 ]
YieldReaction ConditionsOperation in experiment
In N-methyl-acetamide; PREPARATION 32 Ethyl 2-(3-o-trifluoromethylphenylureido)thiazol-4-ylglyoxylate Following a procedure similar to that described in Preparation 1, the desired compound was prepared from 4.28 g of ethyl 2-aminothiazol-4-ylglyoxylate. 5 g of o-trifluoromethylphenyl isocyanate and 40 ml of dimethylformamide. The resulting product was a white powder having the following physical properties. Melting Point: circa 260 C. (with decomposition). Nuclear Maqnetic Resonance Spectrum (hexadeuterated dimethyl sulfoxide) delta ppm: 1.33 (3H. triplet, J=7 Hz). 4.37 (2H, quartet, J=7 Hz), 7.38 (1H. broad triplet, J=8 Hz), 7.69-7.75 (2H, not defined), 7.94 (1H, broad doublet, J=8 Hz), 8.41 (1H, broad singlet), 8.42 (1H, singlet), 11.65 (1H, broad singlet).
  • 35
  • [ 67467-27-0 ]
  • [ 2285-12-3 ]
  • 6-ethoxycarbonyl-5,7-dimethyl-3-[2-(trifluoromethyl)phenyl]-2,4-(1H,3H)-quinazolinedione [ No CAS ]
YieldReaction ConditionsOperation in experiment
67% With hydrogenchloride; In diethyl ether; ethanol; EXAMPLE 2 α,α,α-Trifluoro-o-tolyl isocyanate (434 mg) was added to a solution of 2-amino-5-ethoxycarbonyl-4,6-dimethylbenzoic acid (500 mg) in diethyl ether (22 ml), and the mixture was stirred overnight. The resulting precipitate was filtered off and dissolved in ethanol (15 ml). Then, hydrogen chloride (1 g) was introduced into the solution. The reaction mixture was refluxed for 3 hours and the solvent was evaporated off. The residue was recrystallized from diethyl ether to give 6-ethoxycarbonyl-5,7-dimethyl-3-[2-(trifluoromethyl)phenyl]-2,4-(1H,3H)-quinazolinedione (575 mg, 67%) melting at 175-176 C. MS: m/e, 406(M+), 377, 361, 357, 337, 332, 314, 309. NMR: δ(ppm, CDCl3) 1.40 (3H, t), 2.30 (3H, s), 2.68 (3H, s), 4.44 (2H, q), 6.70 (1H, b), 7.2-8.0 (4H, m), 10.25 (1H, s).
  • 36
  • [ 29107-30-0 ]
  • [ 2285-12-3 ]
  • 3,3-bis-(2-trifluoromethyl-phenylcarbamoyl-oxymethyl)-thiochroman-4-one [ No CAS ]
  • 37
  • [ 306935-14-8 ]
  • [ 2285-12-3 ]
  • 4-(3-phenyl-[1,2,4]thiadiazol-5-yl)-piperazine-1-carboxylic acid (2-trifluoromethyl-phenyl)-amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
42.1% With triethylamine; In tetrahydrofuran; at 20℃; for 1h; Example 45; 4-(3-Phenyl-1,2,4-thiadiazol-5-yl)-N-[2-(trifluoromethyl)phenyl]piperazine-1-carboxamide; To a solution of 1-(3-phenyl-1,2,4-thiadiazol-5-yl)piperazine (200 mg, 0.812 mmol) and triethylamine (0.113 ml, 0.812 mmol) in tetrahydrofuran (2 ml) was added 2-trifluoromethylphenyl isocyanate (0.169 ml, 1.22 mmol) at room temperature, and the mixture was stirred at room temperature for 1 hour. The solvent was distilled off under reduced pressure, and the residue was recrystallized from a mixed solvent of hexane and tetrahydrofuran to give 148 mg (42.1%) of the desired product as a solid. 1H-NMR (CDCl3) δ; 3.73 (8H, s), 6.81 (1H, br s), 7.16 - 7.21 (1H, m), 7.41 - 7.45 (3H, m), 7.53 - 7.61 (2H, m), 8.05 - 8.08 (1H, m), 8.16 - 8.22 (2H, m).
  • 38
  • [ 675850-45-0 ]
  • [ 2285-12-3 ]
  • [ 675850-44-9 ]
YieldReaction ConditionsOperation in experiment
31% Example 18 : 1-[3-Chloro-5-(3-cyclohexyl-ureido)-2-hydroxy-phenyl]-3-(2-trifluoromethyl-phenyl)-urea According to method J 1-(3-amino-5-chloro-4-hydroxy-phenyl)-3-cyclohexyl-urea (30 mg, 0.11 mmol) and 1-isocyanato-2-trifluoromethyl-benzene (21 mg, 0.11 mmol) gave 1-[3-chloro-5-(3-cyclohexyl-ureido)-2-hydroxy-phenyl]-3-(2-trifluoromethyl-phenyl)-urea (16 mg, 31%). NMR-1H (DMSO-d6) δ 0.98-1.28 (m, 5 H), 1.39-1.76 (m, 5 H), 3.30-3.42 (m, 1 H), 5.84 (d, J = 7.8 Hz, 1 H), 7.24 (d, J= 7.8 Hz, 1 H), 7.31 (d, J= 2.4 Hz, 1 H), 7.52-7.67 (m, 2 H), 7.71-7.75 (m, 2 H), 8.20 (br. s, 1 H), 8.80-8.82 (m, 1 H), 8.97-9.04 (m, 1 H), 9.11 (s, 1 H); MS:m/z: 471.1 [M+H+].
31% Example 18 1-[3-Chloro-5-(3-cyclohexyl-ureido)-2-hydroxy-phenyl]-3-(2-trifluoromethylphenyl)-urea According to method J 1-(3-amino-5-chloro-4-hydroxy-phenyl)-3-cyclohexyl-urea (30 mg, 0.11 mmol) and 1-isocyanato-2-trifluoromethyl-benzene (21 mg, 0.11 mmol) gave 1-[3-chloro-5-(3-cyclohexyl-ureido)-2-hydroxy-phenyl]-3-(2-trifluoromethyl-phenyl)-urea (16 mg, 31%). NMR-1H (DMSO-d6) δ 0.98-1.28 (m, 5 H), 1.39-1.76 (m, 5 H), 3.30-3.42 (m, 1 H), 5.84 (d, J = 7.8 Hz, 1 H), 7.24 (d, J = 7.8 Hz, 1 H), 7.31 (d, J = 2.4 Hz, 1 H), 7.52-7.67 (m, 2 H), 7.71-7.75 (m, 2 H), 8.20 (br. s, 1 H), 8.80-8.82 (m, 1 H), 8.97-9.04 (m, 1 H), 9.11 (s, 1H); MS:m/z: 471.1 [M+H+].
  • 39
  • C34H40N3O9PolS [ No CAS ]
  • [ 2285-12-3 ]
  • C42H44F3N4O10PolS [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; In dichloromethane; The following compounds are obtained:[TABLE-US-00014] R2 R7 R6 R1 Yield (%) 38-1Pro-NO2Pho-CF3PhMe20a) 38-2p-BrBnc-PrCH2 o-NO2PhEt1538-3Hepp-CN-Bno-CF3Phi-Pr 639-1p-tBuBnCH2COOtBup-ClPhMe14
  • 40
  • [ 1197-55-3 ]
  • [ 2285-12-3 ]
  • [ 317356-45-9 ]
  • 41
  • [ 16848-19-4 ]
  • [ 2285-12-3 ]
  • [ 1118980-24-7 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; at 20℃; for 6 - 7h; Example 2 Synthesis of 1,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(2-trifluoromethylphenyl)-urido]-α-D-glucofuranoside (Compound No. 41) To a solution of the compound 1,2;5,6-Di-O-isopropylidene-3-deoxy-3-amino-α-D-glucofuranoside (0.500 g, 1.1930 mmol) in dichloromethane (5 ml) was added triethyl amine (0.645 ml, 4.633 mmol) and 2-trifluoromethylphenyl isocyanate (0.433 g, 2.316 mmol) and stirred the reaction mixture at room temperature for 6-7 hours. The solvent was evaporated under reduced pressure and the residue thus obtained was treated with dichloromethane and water. The organic layer was separated, washed with water and brine, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The residue thus obtained was purified by column chromatography using 20% ethyl acetate in hexane as eluent to furnish the title compound. Yield: 0.838 g. 1H NMR (CDCl3+MeOD, 400 MHz): δ 7.95-7.93 (d 1H, J= 8.00 Hz, Ar-H), 7.53-7.51 (m, 2H, Ar-H), 7.59-7.51 (m, 2H, Ar-H), 7.20-7.09 (m, 1H, Ar-H), 5.87-5.86 (d, 1H, J = 4.00 Hz, -CH), 4.60-4.59 (m, 1H, J = 4.00 Hz, -CH), 4.43-4.41 (m, 1H, -CH), 4.26-4.23 (m, 1H, -CH), 4.12-4.08 (m, 1H, -CH), 4.01-3.98 (m, 1H, -CH), 1.59 (s, 3H, -CH3), 1.50 (s, 3H, -CH3) and 1.34-1.33 (m, 6H, 2x-CH3). Mass (m/z, +ve ion mode): 446 [M++1].
With triethylamine; In dichloromethane; at 20℃; for 6 - 7h; Example 2; Synthesis of 1,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(2-trifluoromethylphenyl)-urido]-α-D-glucofuranoside (Compound No. 41); To a solution of the compound 1,2;5,6-Di-O-isopropylidene-3-deoxy-3-amino-α-D-glucofuranoside (0.500 g, 1.1930 mmol) in dichloromethane (5 ml) was added triethyl amine (0.645 ml, 4.633 mmol) and 2-trifluoromethylphenyl isocyanate (0.433 g, 2.316 mmol) and stirred the reaction mixture at room temperature for 6-7 hours. The solvent was evaporated under reduced pressure and the residue thus obtained was treated with dichloromethane and water. The organic layer was separated, washed with water and brine, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The residue thus obtained was purified by column chromatography using 20% ethyl acetate in hexane as eluent to finish the title compound. Yield: 0.838 g.1H NMR (CDCl3+MeOD, 400 MHz): δ 7.95-7.93 (d iH, J=8.00 Hz, Ar-H), 7.53-7.51 (m, 2H, Ar-H), 7.59-7.51 (m, 2H, Ar-H), 7.20-7.09 (min, H Ar-H), 5.87-5.86 (d, 1H, J=4.00 Hz, -CH), 4.60-4.59 (m, 1H, J=4.00 Hz, -CH), 4.43-4.41 (m, in, -CH), 4.26-4.23 (m, 1H, -CH), 4.12-4.08 (m, 1H, -CH), 4.01-3.98 (m, 1H, -CH), 1.59 (s, 3H, -CH3), 1.50 (s, 3H, -CH3) and 1.34-1.33 (m, 6H, 2×-CH3).Mass (m/z, +ve ion mode): 446 [M++1].
  • 42
  • [ 1159997-92-8 ]
  • [ 2285-12-3 ]
  • [ 1159997-32-6 ]
YieldReaction ConditionsOperation in experiment
In dichloromethane; at 20℃; General procedure of examples (104-108)To a solution of (R)-I -(4-(trifluoromethyl)phenyl)-l,2,3,4-tetrahydroisoquinoline (252 μmol, example 87, Step 3) in DCM (1.7 mL) was added isocynate (278 μmol). The resulting mixture was then stirred at RT for overnight. Then, the solvent (DCM) was removed and the residue was dissolved in a solution of MeOH and DMSO (1 :1, 1.0 mL). The solution mixture was then purified by preparative HPLC (0%-100% MeCN 0.1% TFA/H2O 0.1% TFA) to give a desired product, which was then dissolved in MeOH (1.0 mL). The solution was then washed through PL-HCO3 MP resin (polymerlabs, 200 mg/6 mL tube). The resin was then washed with MeOH (2 x 0.5 mL). The combined washings were then concentrated and dried under vacuum to give the title compound.
  • 43
  • [ 32315-10-9 ]
  • [ 88-17-5 ]
  • [ 2285-12-3 ]
YieldReaction ConditionsOperation in experiment
With dmap; triethylamine; In toluene; at 0 - 80℃; for 3h; General procedure: The synthetic route for N-fluorinated phenyl-N′-pyrimidyl urea derivatives is depicted in Scheme 1. At first, 40 mL toluene solution which contained 5 mmol fluorine-containing aniline was slowly dropped into another toluene solution which contained 2 mmol BTC (triphosgene) and a few drops Et3N while mixing at 0C for about 1h. The mixture was stirred at room temperature for 1h and then heated to 80C until the white solid completely dissolved. The intermediate 1 was isolated and obtained by concentration under reduced pressure and flushing by nitrogen [16,17].
In toluene; at 0℃;Reflux; General procedure: To a stirred and cooled to 0C solution of triphosgene (0.1mol) in toluene, appropriate anilines (0.3mol) was added slowly. The mixture was stirred for 0.5hat room temperature, and for another 7-10h under reflux until TLC showed the completion of the reaction. The solvent was evaporated, the mixture was distilled under reduced pressure to afford intermediates 1a-f.
  • 44
  • 4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzoic acid hydrazide [ No CAS ]
  • [ 2285-12-3 ]
  • [ 1186619-75-9 ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide; at 20℃; for 3h; To a solution of 4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzoic acid hydrazide (O.lg, 0.3mmol) in dimethylformamide (10ml) was added 2-(trifluoromethyl)phenylisocyanate (0.1ml, O.mmol) and the mixture stirred at ambient temperature for 3hrs. The mixture was concentrated under vacuo, and 2-propanol (20ml) was added to the residue and reconcentrated to half of the volume. Diisopropylether (10ml) was then added, stirred and the solid obtained was filtered and dried to obtain a pale yellow solid.
  • 45
  • [ 1206687-12-8 ]
  • [ 2285-12-3 ]
  • [ 1206687-05-9 ]
YieldReaction ConditionsOperation in experiment
67% With triethylamine; In tetrahydrofuran; at 20℃; for 10h; [(4-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1 ,2,4-triazol-3-yl}bicyclo[2.2.2]oct-1- yl)methyl]amine (40 mg, 0.13 mmol) was dissolved in tetrahydrofuran (3 mL).Triethylamine (0.095 mL, 0.68 mmol) and i-isocyanato-2-trifluoromethyl benzene (38 mg,0.2 mmol) were added and the reaction was stirred for 10 hours at room temperature.The reaction was diluted with water and extracted with dichloromethane (3 x 5 mL). The combined organic layers were dried with magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by HPLC (Sepax 21.2 mm x250 mm column, 10-80% MeCN/H2O (with 0.07% TFA) over 21 min) to give the title compound as a white solid. (51 mg, 0.09 mmol, 67% yield) LCMS - RT = 1.94 min, M/Z (M+H) = 5521H NMR (400 MHz. DMSOd6) δ ppm 7.99 (m, 1 H), 7.87 (m, 2 H), 7.82 (d, 1 H), 7.67 (m, 1 H), 7.62 (d, 1 H), 7.56 (t, 1 H), 7.23 (t, 1 H), 3.60 (s, 3 H), 3.06 (s, 2 H), 2.15 (m, 6 H), 1.68 (m, 6 H).
  • 46
  • [ 1322089-67-7 ]
  • [ 2285-12-3 ]
  • [ 1322089-70-2 ]
YieldReaction ConditionsOperation in experiment
71% In tetrahydrofuran; at 20℃; General procedure: ethyl 4-(4-aminophenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (2) (0.34 mmol) and 2-fluorophenylisocynate (0.41 mmol) were taken THF The resultant reaction mixture was stirred at room temperature for a period of 10-12h, After completion of reaction. The reaction mixture was diluted with hexane and resultant solid was filtered to obtain the crude. This was purified by precipitation using dichloromethane and hexane to obtain a title compound as white solid. Yield 82%; 1HNMR (DMSO, 300MHz): δ 10.30 (s, 1H), 9.61 (s, 1H), 9.11 (s, 2H), 8.54 (d, 1H), 8.19 (d, 2H), 7.42 (d, 2H), 7.27 (d, 1H), 7.15 (m, 1H), 7.00 (m, 1H), 5.11 (d, 1H), 4.02 (q, 2H), 2.29 (s, 3H), 1.19 (t, 3H),; MS (APCI); m/z 429.1 [M+1]+: HPLC: 96.04%.
  • 47
  • [ 1125632-05-4 ]
  • [ 2285-12-3 ]
  • [ 1228465-78-8 ]
YieldReaction ConditionsOperation in experiment
61% With pyridine; at 20℃; for 0.5h; Example 25Production of N-{5-[4-fluoro-3-([2-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy][1,3]thiazolo[5,4-b]pyridin-2-yl}cyclopropanecarboxamide To a solution of N-[5-(3-amino-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide (100 mg, 0.290 mmol) produced in Example 16(vi) in pyridine (3 mL) was added 1-isocyanato-2-(trifluoromethyl)benzene (53 μL, 0.348 mmol), and the mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with ethyl acetate (15 mL)/tetrahydrofuran (5 mL), and washed successively with aqueous sodium hydrogen carbonate solution (15 mL) and saturated brine (5 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=50/50→90/10), and the obtained solution was concentrated under reduced pressure. The obtained residue was washed with ethyl acetate (10 mL) to give the title compound (95 mg, 61%) as a white solid.1H-NMR (DMSO-d6, 300 MHz) δ 0.82-1.00 (4H, m), 1.92-2.04 (1H, m), 6.83 (1H, ddd, J=8.9, 4.0, 2.9 Hz), 7.11 (1H, d, J=8.7 Hz), 7.25-7.38 (2H, m), 7.61 (1H, t, J=7.8 Hz), 7.68 (1H, dd, J=7.8, 1.2 Hz), 7.82 (1H, d, J=8.3 Hz), 8.00 (1H, dd, J=6.9, 2.9 Hz), 8.14 (1H, d, J=8.7 Hz), 8.65 (1H, br s), 9.44 (1H, d, J=2.3 Hz), 12.68 (1H, br s).
  • 48
  • [ 1375453-72-7 ]
  • [ 2285-12-3 ]
  • [ 1375454-16-2 ]
YieldReaction ConditionsOperation in experiment
20% General procedure: A solution of 10% of NaOH (5.00 mmol) was added to a solution of the corresponding 4-(aminealkoxy)benzenesulfonamide 10-19 (5.00 mmol) in acetone (25 ml). After 10 min of stirring, the solvent was removed under reduced pressure. The solid was redissolved in acetone (30 ml) and the reaction mixture was stirred under reflux. The appropriate isocyanate derivative (10.00 mmol) was added dropwise and the mixture was stirred at reflux for 4 h. The solvent was concentrated to dryness in vacuo and the obtained residue was purified by flash column chromatography (CH2Cl2/MeOH 95:5) in order to afford 20-64 derivatives.
  • 49
  • [ 1210758-62-5 ]
  • [ 2285-12-3 ]
  • [ 1210758-81-8 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; at 20℃; for 16h; General procedure: To a solution of compound 17 (0.5 mmol, 1 equiv) in THF (3 ml) was added the appropriately substituted phenyl isocyanate (1.1 equiv) and the mixture was stirred for 16 h at rt. The reaction mixture was then concentrated and purified using flash column chromatography (2:8 EtOAc/petroleum ether) to afford the desired methyl ester. To a solution of the methyl ester (1 equiv) in THF was added 1.0 M solution of LiOH in water (5 equiv) and stirred for 16 h at rt. The solvent was removed and the obtained residue was diluted with water and acidified to pH 2 using 2.0 M HCl. The material thus obtained was extracted with ethyl acetate, washed with water, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to obtain a solid that was crystallized in ethyl acetate to yield the desired acid.
  • 50
  • [ 5734-64-5 ]
  • [ 2285-12-3 ]
  • [ 1620783-97-2 ]
YieldReaction ConditionsOperation in experiment
With tetrabutylammomium bromide; at 80 - 100℃; General procedure: The synthetic route for N-fluorinated phenyl-N?-pyrimidyl urea derivatives is depicted in Scheme 1. At first, 40 mL toluene solution which contained 5 mmol fluorine-containing aniline was slowly dropped into another toluene solution which contained 2 mmol BTC (triphosgene) and a few drops Et3N while mixing at 0C for about 1h. The mixture was stirred at room temperature for 1 h and then heated to 80C until the white solid completely dissolved. The intermediate 1 was isolated and obtained by concentration under reduced pressure and flushing by nitrogen [16,17]. To obtain the final target compounds, the unpurified intermediate 1 was added into a series of substituted pyrimidinamine (5 mmol, as shown in Table 1) solutions which contained a little tetrabutylammonium bromide that was used as phase transfer catalyst. Then, the mixture was agitated at 80-100C for 6-9h. The reaction was detected according to TLC. When the reaction was complete, the product was cooled to room temperature, filtered, and washed with 10% Na2CO3, water, and acetone. The final target compounds were purified by recrystallization (DMF/acetone).
  • 51
  • [ 5600-21-5 ]
  • [ 2285-12-3 ]
  • [ 1620784-39-5 ]
YieldReaction ConditionsOperation in experiment
With tetrabutylammomium bromide; at 80 - 100℃; General procedure: The synthetic route for N-fluorinated phenyl-N′-pyrimidyl urea derivatives is depicted in Scheme 1. At first, 40 mL toluene solution which contained 5 mmol fluorine-containing aniline was slowly dropped into another toluene solution which contained 2 mmol BTC (triphosgene) and a few drops Et3N while mixing at 0C for about 1h. The mixture was stirred at room temperature for 1 h and then heated to 80C until the white solid completely dissolved. The intermediate 1 was isolated and obtained by concentration under reduced pressure and flushing by nitrogen [16,17]. To obtain the final target compounds, the unpurified intermediate 1 was added into a series of substituted pyrimidinamine (5 mmol, as shown in Table 1) solutions which contained a little tetrabutylammonium bromide that was used as phase transfer catalyst. Then, the mixture was agitated at 80-100C for 6-9h. The reaction was detected according to TLC. When the reaction was complete, the product was cooled to room temperature, filtered, and washed with 10% Na2CO3, water, and acetone. The final target compounds were purified by recrystallization (DMF/acetone).
  • 52
  • [ 36315-01-2 ]
  • [ 2285-12-3 ]
  • [ 1620784-57-7 ]
YieldReaction ConditionsOperation in experiment
With tetrabutylammomium bromide; at 80 - 100℃; General procedure: The synthetic route for N-fluorinated phenyl-N′-pyrimidyl urea derivatives is depicted in Scheme 1. At first, 40 mL toluene solution which contained 5 mmol fluorine-containing aniline was slowly dropped into another toluene solution which contained 2 mmol BTC (triphosgene) and a few drops Et3N while mixing at 0C for about 1h. The mixture was stirred at room temperature for 1 h and then heated to 80C until the white solid completely dissolved. The intermediate 1 was isolated and obtained by concentration under reduced pressure and flushing by nitrogen [16,17]. To obtain the final target compounds, the unpurified intermediate 1 was added into a series of substituted pyrimidinamine (5 mmol, as shown in Table 1) solutions which contained a little tetrabutylammonium bromide that was used as phase transfer catalyst. Then, the mixture was agitated at 80-100C for 6-9h. The reaction was detected according to TLC. When the reaction was complete, the product was cooled to room temperature, filtered, and washed with 10% Na2CO3, water, and acetone. The final target compounds were purified by recrystallization (DMF/acetone).
  • 53
  • [ 3977-29-5 ]
  • [ 2285-12-3 ]
  • [ 1620784-77-1 ]
YieldReaction ConditionsOperation in experiment
With tetrabutylammomium bromide; at 80 - 100℃; General procedure: The synthetic route for N-fluorinated phenyl-N?-pyrimidyl urea derivatives is depicted in Scheme 1. At first, 40 mL toluene solution which contained 5 mmol fluorine-containing aniline was slowly dropped into another toluene solution which contained 2 mmol BTC (triphosgene) and a few drops Et3N while mixing at 0°C for about 1h. The mixture was stirred at room temperature for 1 h and then heated to 80°C until the white solid completely dissolved. The intermediate 1 was isolated and obtained by concentration under reduced pressure and flushing by nitrogen [16,17]. To obtain the final target compounds, the unpurified intermediate 1 was added into a series of substituted pyrimidinamine (5 mmol, as shown in Table 1) solutions which contained a little tetrabutylammonium bromide that was used as phase transfer catalyst. Then, the mixture was agitated at 80?100°C for 6?9h. The reaction was detected according to TLC. When the reaction was complete, the product was cooled to room temperature, filtered, and washed with 10percent Na2CO3, water, and acetone. The final target compounds were purified by recrystallization (DMF/acetone).
  • 54
  • [ 63746-12-3 ]
  • [ 2285-12-3 ]
  • C17H11F3N2O4 [ No CAS ]
  • 55
  • [ 1345444-50-9 ]
  • [ 2285-12-3 ]
  • 6-iodine-5-methyl-3-(2-(trifluoromethyl)phenyl)quinazoline-2,4(1H,3H)-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With pyridine; at 100℃; Add 5 g of 6-amino-3-iodine-2-dimethylbenzoic acid to a 100 mL double-neck flask, add 36 mL of pyridine, and slowly add 4.22 g of o-trifluoromethylphenylisocyanate to the system under agitation. Heat the reaction solution to 100 C., react overnight, remove pyridine through reduced pressure distillation after the reaction, dissolve the obtained solid in acetone, and pass the column (the eluent is petroleum:acetone=6:1) to obtain 6 g of white solid, with a yield of 75%; melting point: 195-197 C. 1H NMR (600 MHz, DMSO-D6): δ 11.72 (s, 1H), 8.14 (d, J=9.0 Hz, 1H), 7.88 (d, J=7.8 Hz, 1H), 7.84 (t, J=7.8 Hz, 1H), 7.70 (t, J=7.8 Hz, 1H), 7.62 (d, J=7.8 Hz, 1H), 6.94 (d, J=8.4 Hz, 1H), 2.80 (s, 3H).
  • 56
  • 4-bromo-N1-phenethyl-N1-(3,3,3-trifluoropropyl)benzene-1,2-diamine [ No CAS ]
  • [ 2285-12-3 ]
  • 1-(5-bromo-2-(phenethyl(3,3,3-trifluoropropyl)amino)phenyl)-3-(2-(trifluoromethyl)phenyl)urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
35 mg In dichloromethane; at 20℃; 295A. 1 -(5-Bromo-2-(phenethyl(3 ,3 ,3 -trifluoropropyl)amino)phenyl)-3 -(2- (trifluoromethyl)phenyl)urea To a stirred solution of 4-bromo-N 1 -phenethyl-N 1 -(3,3,3 -trifluoropropyl)benzene-1,2-diamine (30 mg, 0.077 mmol) in DCM was added 1- isocyanato-2-(trifluoromethyl)benzene (17 mg, 0.093 mmol). The reaction mixture was stirred overnight. The reaction mixture was concentrated to give 1-(5-bromo-2- (phenethyl(3 ,3 ,3 -trifluoropropyl)amino)phenyl)-3 -(2-(trifluoromethyl)phenyl)urea (35 mg). MS(ES): m/z = 576.1 [M+H].
  • 57
  • 5-(3-aminophenyl)-3-isopropylbenzo[d] oxazol-2(3H)-one [ No CAS ]
  • [ 2285-12-3 ]
  • 1-(3-(3-isopropyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)phenyl)-3-(2-(trifluoromethyl)phenyl)urea [ No CAS ]
  • 58
  • [ 582-33-2 ]
  • [ 2285-12-3 ]
  • C17H15F3N2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
In toluene; for 7h;Cooling with ice; Reflux; General procedure: 3-Aminobenzoic acid ethyl ester (50 mmol) was dissolved in toluene (30 mL). With ice-water bath cooling, a substituted phenyl isocyanate (Ar-NCO) (50 mmol) dissolved in toluene (30 mL), was added dropwise. With the water bath, the mixture was reacted at a temperature of 25 C, for 5 h, and then heated to reflux for 2 h. After cooling to room temperature, the reaction mixture was filtered under vacuum and dried to produce ethyl 3-(3-substituted phenylureido)benzoates 1a-1m, in yields ranging from 85% to 95%.
  • 59
  • [ 35161-71-8 ]
  • [ 2285-12-3 ]
  • N-((E)-5-(iodomethylene)-3-methyloxazolidin-2-ylidene)-2-(trifluoromethyl)aniline [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With iodine; In ethyl acetate; for 12h;Heating; General procedure: A mixture of isocyanate (0.3 mmol) and propargylamine (0.3 mmol) was treated with iodine (0.3 mmol) in ethyl acetate (3 mL). The reaction tube was stirred for 12 h at 50 C (oil bath temperature) with the gradual formation of white precipitation. Subsequently, the reaction was quenched with K2CO3 aqueous solution to make the pH beyond 9. The mixture was extracted with EA (310 mL) and the combined organic layers were dried over Na2SO4, filtered and concentrated. Pure products 3 were obtained by column chromatography (silica gel, with a mixture of hexane/ethyl acetate (4:1) as eluent). N-((E)-5-(Iodomethylene)-3-methyloxazolidin-2-ylidene)-2-(trifluoromethyl)aniline (3ak). Dark brown oil. 1H NMR (400 MHz, CDCl3): δ7.56 (d, J=8.0 Hz, 1H), 7.40 (t, J=8.0 Hz, 1H), 7.10-7.04 (m, 2H), 5.65 (t, J=2.8 Hz, 1H), 4.15 (d, J=2.8 Hz, 2H), 3.06 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 150.62, 150.02, 145.39, 132.12, 126.29, 126.24, 125.76, 124.69, 123.04, 122.16, 55.58, 49.60, 31.66. 19F NMR (376 MHz, CDCl3): δ 62.24. HRMS (EI) (m/z): [M+H]+ Calcd for C12H11F3N2OI 382.9868, found 382.9862.
  • 60
  • [ 1372625-07-4 ]
  • [ 2285-12-3 ]
  • 2-(Z)-triisopropylsilylmethylidene-4-(o-trifluoromethylphenyl)-6-methoxy-2H-1,4-benzoxazin-3(4H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
58% With zinc diacetate; palladium diacetate; tricyclohexylphosphine; In toluene; at 120℃; for 24h;Inert atmosphere; General procedure: An alkynyl aryl ether (0.50mmol), an isocyanate (0.75-1.0mmol), and decane (an internal standard, 7.0mg, 0.049mmol) were added sequentially to a solution of Pd(OAc)2 (5.6mg, 25μmol), Zn(OAc)2 (1.6mg, 25μmol) and PCy3 (7.0mg, 25μmol) in toluene (1.0mL) prepared in a 3mL-vial in a dry box. The vial was closed with a screw cap, taken outside the dry box, and heated at 120C. The resultant mixture was filtered through Celite, and the filtrate was evaporated and dried in vacuo. The desired products were obtained in yields listed in this paper by preparative thin-layer chromatography.
  • 61
  • (S)-tert-butyl (1-(3-(3-aminophenyl)-5-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)carbamate [ No CAS ]
  • [ 2285-12-3 ]
  • (S)-tert-butyl (1-(5-chloro-4-oxo-3-(3-(3-(2-(trifluoromethyl)phenyl)ureido)phenyl)-3,4-dihydroquinazolin-2-yl)ethyl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dichloromethane; at 20℃; for 1h; E. Preparation of a compound of formula (2b) where W2 is CH, n is 1, R1 is chloro, m is 0, R3 is methyl, R6 is 2-trifluoromethylphenyl, and R5 is hydrogen A solution of (S)-tert-butyl(1-(3-(3-aminophenyl)-5-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)carbamate (0.43 g, 1.0 mmol) in dichloromethane (4 mL) was treated with 2-trifluoromethylphenylisocyanate (0.22 g, 0.17 mL, 1.2 mmol). After 1 hour of standing at room temperature, the mixture was treated with MeOH (˜1 mL) and then concentrated under reduced pressure to provide (S)-tert-butyl(1-(5-chloro-4-oxo-3-(3-(3-(2-(trifluoromethyl)phenyl)ureido)phenyl)-3,4-dihydroquinazolin-2-yl)ethyl)carbamate. ES/MS m/z=602.1 (M+H+).
  • 62
  • C11H16N2O [ No CAS ]
  • [ 2285-12-3 ]
  • C19H20F3N3O2 [ No CAS ]
  • 63
  • [ 864350-77-6 ]
  • [ 2285-12-3 ]
  • methyl 4-(2-fluoro-4-(3-(2-(trifluoromethyl)phenyl)ureido)phenoxy)picolinate [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% In dichloromethane; at 20℃; General procedure: A mixture of intermediate 9 (2mmol) and appropriate isocyanate (1a-e, 2mmol) in CH2Cl2 was stirred at room temperature for 4-7h until TLC showed the completion of reaction. The precipitate was filtered off and washed to give the solids 10a-f.
  • 64
  • [ 72080-83-2 ]
  • [ 2285-12-3 ]
  • C18H18F3N3O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% In tetrahydrofuran; at 20℃; for 2h; General procedure: A solutionof compound 10 (0.15 g, 0.772 mmol) and phenylisocyanate (0.17 g, 0.926 mmol) in THF (5 mL) was stirredat room temperature for 2 h. The solvent was evaporatedunder reduced pressure, and the residue was purifiedby flash column chromatography. The desired product wasobtained as white solid (0.2 g, 51 %).
  • 65
  • 4-(4-(fluoromethyl)-1H-1,2,3-triazol-1-yl)aniline [ No CAS ]
  • [ 2285-12-3 ]
  • 1-(4-(4-(fluoromethyl)-1H-1,2,3-triazol-1-yl)phenyl)-3-(2-(trifluoromethyl)phenyl)urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% In dichloromethane; at 20℃; for 4h;Inert atmosphere; General procedure: General procedure for the preparation of compounds 42a 42b and 42cThe opportune aniline compound 41a-c (100 mg, 0.46 mmol) was added to a solution of the 0-(Trifluoromethyl)phenyl isocyanate 24 (85 jiL, 0.65 mmol) in anhydrous CH2C12 (10 mL) inone portion. The solution was stirred for 4 hours at r.t. under a nitrogen atmosphere. Thesolvent was removed, at reduced pressure and the residue purified by flash chromatographyusing the opportune eluent. 1-(4-(4-(fluoromethyl)- 1H- 1 ,2,3-triazol- 1-yl)phenyl)-3-(2-(trifluoromethyl)phenyl)urea (42a). (Purification Eluent: DCM/EA 95:5).Yield 79% H NMR (400 MHz, ACETONE-d6): ö9.09 (s, 1H), 8.64-8.63 (d, J= 2.8 Hz, 1H), 8.15-8.13 (d, J= 8.0 Hz, 1H), 7.82-7.64 (m, 5H),7.31-7.27 (t, J 7.2 Hz, 1H), 5.60 (s, 1H), 5.44 (s, 1H) ppm 13C-NMR (100 MHz, ACETONEd 6): ö 152.2, 140.56, 140.57, 132.95, 131.72, 125.90, 125.48, 123.78, 122.80, 121.13, 119.28, 76.16-74.53 (JCF=163.0 Hz) ppm MS (ESI) m/z 378 [M-H]-, 414 [M+Cl]
79% In dichloromethane; at 20℃;Inert atmosphere; General procedure: The opportune aniline compound 41a-c (100 mg, 0.46 mmol) was added to a solution of the 0- (Trifluoromethyl)phenyl isocyanate 24 (85 jiL, 0.65 mmol) in anhydrous CH2C12 (10 mL) in one portion. The solution was stirred for 4 hours at r.t. under a nitrogen atmosphere. The solvent was removed, at reduced pressure and the residue purified by flash chromatographyusing the opportune eluent. 1-(4-(4-(fluoromethyl)- 1H- 1 ,2,3-triazol- 1-yl)phenyl)-3-(2-(trifluoromethyl)phenyl)urea(42a). (Purification Eluent: DCM/EA 95:5).Yield 79% H NMR (400 MHz, ACETONE-d6): ö9.09 (s, 1H), 8.64-8.63 (d, J= 2.8 Hz, 1H), 8.15-8.13 (d, J= 8.0 Hz, 1H), 7.82-7.64 (m, 5H),7.31-7.27 (t, J= 7.2 Hz, 1H), 5.60 (s, 1H), 5.44 (s, 1H) ppm 13C-NMR (100 MHz, ACETONEö 152.2, 140.56, 140.57, 132.95, 131.72, 125.90, 125.48, 123.78, 122.80, 121.13, 119.28,76.16-74.53 (JcF163.0 Hz) ppm MS (ESI) m/z 378 [M-H]-, 414 [M+Cl].
  • 66
  • 4-(2-butyl-2H-tetrazol-5-yl)aniline [ No CAS ]
  • [ 2285-12-3 ]
  • 1-(4-(2-butyl-2H-tetrazol-5-yl)phenyl)-3-(2-(trifluoromethyl)phenyl)urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% In methanol; at 20℃; for 9h;Inert atmosphere; Compound47 (0.10 mmol) was added to a solution of o-tolyl isocyanate (0.15 mmol) in anhydrous MeOH(10 mL) in one portion. The solution was stirred for 9 hours at r.t. under a nitrogen atmosphere. The solvent was removed at reduced pressureand the residue purified on silica to furnish the final product as white solid. (DCM-MeOH 98:2). Yield 70%, white solid. 1H NMR ( 400 MHz CDC13-d): ö 7.93-7.91 (d, J= 8 Hz,2H), 7.82-7.80 (d, J= 8.0 Hz, 1H), 7.48-7.39 (m, 2H), 7.36-7.34 (d, J 7.2 Hz, 2H), 7.09-7.05 (t, J 7.2 Hz, 1H), 4.60-4.57 (t, J= 6.8 Hz, 2H), 2.01-1.97 (m, 2H),1.39-1.33 (m, 2H), 0.95-0.91 (t, J= 7.2 Hz, 3H) ppm. 13C NMR (100 MHz, CDC13-d): ö 153.54,140.20, 135.38, 132.54, 127.60, 126.29, 126.11, 125.23, 124.54, 122.43, 122.01, 120.07, 52.96,31.27, 19.60, 13.34 ppm MS (ESI) m/z 405 [M+H], 428 [M+Na]t
  • 67
  • 4-(4-isopentyl-1H-1,2,3-triazol-1-yl)-3-methoxyaniline [ No CAS ]
  • [ 2285-12-3 ]
  • 1-(4-(4-isopentyl-1H-1,2,3-triazol-1-yl)-3-methoxyphenyl)-3-(2-(trifluoromethyl) phenyl)urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% In dichloromethane; at 20℃; for 9h;Inert atmosphere; General procedure: General procedure for the preparation of compounds 80 and 81.The opportune aniline 78 or 79 (0.10 mmol) was added to a solution of 2-(Trifluoromethyl)phenyl isocyanate (0.15 mmo 1) in anhydrous DCM (15 mL) in one portion.The solution was stirred for 9 hours at r.t. under a nitrogen atmosphere. The solvent wasremoved at reduced pressure and the residue purified on silica to afford the final product 80 or81.1-(4-(4-isopentyl- 1H- 1 ,2,3-triazol- 1-yl)-3-methoxyphenyl)-3-(2-(trifluoromethyl) phenyl)urea (80): (Purification eluent: DCM/MeOH 98:2).Yield 78%, white solid. 1H NMR(400 MHz, CDC13-d): ö 8.12-8.06 (m, 2H), 7.92 (s, 1H), 7.6 1-7.54 (m, 3H), 7.26-7.21 (m, 2H),7.18 (s, 1H), 3.97 (s, 3H), 2.83-2.80 (t, J=7.8 Hz, 2H), 1.71-1.63 (m, 3H), 0.98-0.97 (d,J=7.8Hz, 6H)ppm. 13C NMR (100 MHz, CDC13): ö 153.05, 152.05, 148.40, 136.61, 134.63,132.90, 127.92, 126.70, 126.17, 124.85, 124.78, 122.62, 122.53, 121.46, 121.08, 114.12, 56.43,38.52,27.77, 23.66, 22.52 ppm. MS (ESI) mlz 448.3 [M+H]
78% In dichloromethane; at 20℃;Inert atmosphere; General procedure: The opportune aniline 78 or 79 (0.10 mmol) was added to a solution of 2-(Trifluoromethyl)phenyl isocyanate (0.15 mmol) in anhydrous DCM (15 mL) in one portion.The solution was stirred for 9 hours at r.t. under a nitrogen atmosphere. The solvent wasremoved at reduced pressure and the residue purified on silica to afford the final product 80 or81.1-(4-(4-isopentyl- 1H- 1 ,2,3-triazol- 1-yl)-3-methoxyphenyl)-3-(2-(trifluoromethyl)phenyl)urea (80): (Purification eluent: DCM/MeOH 98:2).Yield 78%, white solid. 1H NMR(400 MHz, CDC13-d): ö 8.12-8.06 (m, 2H), 7.92 (s, 1H), 7.6 1-7.54 (m, 3H), 7.26-7.21 (m, 2H),7.18 (s, 1H), 3.97 (s, 3H), 2.83-2.80 (t, J=7.8 Hz, 2H), 1.71-1.63 (m, 3H), 0.98-0.97 (d,J7.8Hz, 6H)ppm. 13C NMR (100 MHz, CDC13): ö 153.05, 152.05, 148.40, 136.61, 134.63,132.90, 127.92, 126.70, 126.17, 124.85, 124.78, 122.62, 122.53, 121.46, 121.08, 114.12, 56.43,38.52,27.77, 23.66, 22.52 ppm. MS (ESI) mlz 448.3 [M+H]
  • 68
  • 6-(4-isopentyl-1H-1,2,3-triazol-1-yl)pyridin-3-amine [ No CAS ]
  • [ 2285-12-3 ]
  • 1-(6-(4-isopentyl-1H-1,2,3-triazol-1-yl)pyridin-3-yl)-3-(2-(trifluoromethyl) phenyl)urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% In dichloromethane; at 20℃; for 9h;Inert atmosphere; Aniline 85 (0.10 mmol) was added to a solution of 2-(Trifluoromethyl)phenyl isocyanate (0.15 mmol) in anhydrous CH2C12 (15 mL) in one portion. The solution was stirred for 9 hours at r.t. under a nitrogen atmosphere. The solvent was removed at reduced pressure and the residue purified on silica to furnish the final product as white solid. (Purification eluent: DCMMeOH 98:2). Yield 61%, white solid. 1H NMR (400 MHz, Acetone-d6): ö 9.14 (s, 1H), 8.66(s, 1H), 8.37 (s, 1H), 8.28-8.24 (d, J=8.0 Hz, 1H), 8.14-8.12 (d, J8.OHz, 1H), 8.06-8.04 (d, J8.0 Hz, 1H), 7.81 (s, 1H), 7.70-7.64 (m, 2H), 7.33-7.30 (t, J=8.0 Hz, 1H), 2.80-2.75 (t, J=7.7 Hz, 2H), 1.64-1.61 (m, 3H), 0.96-0.94 (d, J=8.0 Hz, 6H) ppm. 13C NMR (100 MHz, Acetoned 6): ö 152.31, 148.41, 144.17, 138.61, 138.26, 136.46, 132.84, 128.80, 125.95, 125.65, 123.96, 117.98, 117.71, 113.35, 38.34, 27.33, 23.23, 21.91, 21.64 ppm. MS (ESI) mlz 419.3 [M+H].
61% In dichloromethane; at 20℃;Inert atmosphere; Aniline 85 (0.10 mmol) was added to a solution of 2-(Trifluoromethyl)phenyl isocyanate(0.15 mmol) in anhydrous CH2C12 (15 mL) in one portion. The solution was stirred for 9 hoursat r.t. under a nitrogen atmosphere. The solvent was removed at reduced pressure and the residue purified on silica to furnish the final product as white solid. (Purification eluent: DCMMeOH 98:2). Yield 61%, white solid. 1H NMR (400 MHz, Acetone-d6): ö 9.14 (s, 1H), 8.66 (s, 1H), 8.37 (s, 1H), 8.28-8.24 (d, J=8.0 Hz, 1H), 8.14-8.12 (d, J8.OHz, 1H), 8.06-8.04 (d,J8.0 Hz, 1H), 7.81 (s, 1H), 7.70-7.64 (m, 2H), 7.33-7.30 (t, J8.0 Hz, 1H), 2.80-2.75 (t, J=7.7 Hz, 2H), 1.64-1.61 (m, 3H), 0.96-0.94 (d, J=8.0 Hz, 6H) ppm. 13C NMR (100 MHz, Acetoned 6): ö 152.31, 148.41, 144.17, 138.61, 138.26, 136.46, 132.84, 128.80, 125.95, 125.65, 123.96, 117.98, 117.71, 113.35, 38.34, 27.33, 23.23, 21.91, 21.64 ppm. MS (ESI) mlz 419.3 [M+H].
  • 69
  • 4-(5-butylisoxazol-3-yl)aniline [ No CAS ]
  • [ 2285-12-3 ]
  • 1-(4-(5-butylisoxazol-3-yl)phenyl)-3-(2-(trifluoromethyl)phenyl)urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% In dichloromethane; at 20℃; for 4h;Inert atmosphere; 100 (100 mg,0.46 mmol) was added to a solution of the 1-(Trifluoromethyl)phenyl isocyanate 24 (85 jiL,0.65 mmol) in anhydrous CH2C12 (10 mL) in one portion. The solution was stirred for 4 hoursat r.t. under a nitrogen atmosphere. The solvent was removed, at reduced pressure and theresidue purified by flah chromatography (PE/EtOAc 95:5) Yield 73% 1HNMR (400 MHz,CDC13-d): ö 7.99-7.97 (d, J=7.6 Hz, 2H), 7.7 1-7.69 (d, J=7.6 Hz, 2H), 7.5 8-7.56 (d, J 7.2 Hz,2H), 7.5 1-7.18 (m, 2H), 7.03 (s, 2H), 2.78-2.77 (d, J=6.8 Hz, 2H), 1.71-1.61 (m, 2H) , 1.42-1.40 (d, J=6.4 Hz, 2H), 0.96-0.87 (t, J=6.8 Hz, 3H) ppm 13C-NMR (100 MHz, CDC13-d): ö174.66, 163.30, 152.83, 139.94, 136.25, 134.15, 133.10, 128.10, 126.20, 125.37, 124.86,124.63, 124.22, 120.74, 98.30, 29.99, 26.83, 22.62, 13.94 ppm. MS (ESI) mlz 402.2 [M-H]
73% In dichloromethane; at 20℃;Inert atmosphere; 100 (100 mg,0.46 mmol) was added to a solution of the 1-(Trifluoromethyl)phenyl isocyanate 24 (85 jiL,0.65 mmol) in anhydrous CH2C12 (10 mL) in one portion. The solution was stirred for 4 hours at r.t. under a nitrogen atmosphere. The solvent was removed, at reduced pressure and the residue purified by flah chromatography (PE/EtOAc 95:5) Yield 73% 1HNMR (400 MHz, CDC13-d): ö 7.99-7.97 (d, J=7.6 Hz, 2H), 7.71-7.69 (d, J=7.6 Hz, 2H), 7.58-7.56 (d, J 7.2 Hz, 2H), 7.5 1-7.18 (m, 2H), 7.03 (s, 2H), 2.78-2.77 (d, J=6.8 Hz, 2H), 1.71-1.61 (m, 2H) , 1.42-1.40 (d, J6.4 Hz, 2H), 0.96-0.87 (t, J6.8 Hz, 3H) ppm 13C-NMR (100 MHz, CDC13-d): ö174.66, 163.30, 152.83, 139.94, 136.25, 134.15, 133.10, 128.10, 126.20, 125.37, 124.86,124.63, 124.22, 120.74, 98.30, 29.99, 26.83, 22.62, 13.94 ppm. MS (ESI) mlz 402.2 [M-H]
  • 70
  • [ 10364-73-5 ]
  • [ 2285-12-3 ]
  • 1-(4-(5-butyl-1,2,4-oxadiazol-3-yl)phenyl)-3-(2-(trifluoromethyl)phenyl)urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% In dichloromethane; at 20℃; for 4h;Inert atmosphere; (0.46 mmol) was added to a solution of the 1-(Trifluoromethyl)phenyl isocyanate 24 (85 jiL,0.65 mmol) in anhydrous CH2C12 (10 mL) in one portion. The solution was stirred for 4 hoursat r.t. under a nitrogen atmosphere. The solvent was removed, at reduced pressure and the residue purified by flah chromatography (PE/EtOAc 9:1) Yield 76% 1HNMR (400 MHz, CDC13-d): ö 7.58-7.56 (d, J= 7.6 Hz, 2H), 7.44-7.41 (m, 3H), 7.25 (s, 1H), 7.18 (s, 1H), 7.08 (s, 1H), 1.86-1.82 (t, J=7.2 Hz, 2H), 1.48-1.42 (m, 2H), 0.96-0.94 (t, J=7.6 Hz, 3H) ppm 13C-NMR (100 MHz, ACETONE-d6): ö 180.10, 152.51, 142.51, 136.56, 132.78, 127.87, 125.98, 125.32,123.81, 120.98, 118.33, 25.69, 21.82, 13.03 ppm.
In dichloromethane; at 20℃; for 4h;Inert atmosphere; 105(0.46 mmol) was added to a solution of the 1-(Trifluoromethyl)phenyl isocyanate 24 (85 jiL,0.65 mmol) in anhydrous CH2C12 (10 mL) in one portion. The solution was stirred for 4 hoursat r.t. under a nitrogen atmosphere. The solvent was removed, at reduced pressure and the residue purified by flah chromatography (PE/EtOAc 9:1) Yield 76% 1HNMR (400 MHz, CDC13-d): ö 7.58-7.56 (d, J= 7.6 Hz, 2H), 7.44-7.41 (m, 3H), 7.25 (s, 1H), 7.18 (s, 1H), 7.08 (s, 1H), 1.86-1.82 (t, J=7.2 Hz, 2H), 1.48-1.42 (m, 2H), 0.96-0.94 (t, J=7.6 Hz, 3H) ppm 13C-NMR(100 MHz, ACETONE-d6): ö 180.10, 152.51, 142.51, 136.56, 132.78, 127.87, 125.98, 125.32,123.81, 120.98, 118.33, 25.69, 21.82, 13.03 ppm.
  • 71
  • [ 100933-82-2 ]
  • [ 2285-12-3 ]
  • 1-(4-(5-butyl-1,3,4-oxadiazol-2-yl)phenyl)-3-(2-(trifluoromethyl)phenyl)urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% In dichloromethane; at 20℃; for 9h;Inert atmosphere; Aniline 111 (31 mg, 0.14 mmol) was added to a solution of 2-(Trifluoromethyl)phenyl isocyanate (22 jiL, 0.15 mmol) in anhydrous CH2C12 (15 mL) in one portion. The solution was stirred for 9 hours at r.t. under a nitrogen atmosphere. The solvent was removed at reduced pressure and the residue purified on silica to furnish the final product as white solid.(Purification eluent: PE/EtOAc 7:3). Yield 71%, white solid. 1HNMR (400 MHz, MeOD-d): ö7.95-7.93 (d, J= 8.4, 2H), 7.67-7.65 (d, J=8.8, 2H), 7.63-7.59 (m, 2H), 7.31-7.27 (m, 2H),2.96-2.92 (d, J= 7.6, 2H), 1.86-1.78 (m, 2H), 1.51-1.42 (m, 2H), 1.00-0.97 (t, J= 7.2, 3H) ppm.13C.NMR (100 MHz, ACETONE-d6 ): ö 166.35, 164.11, 152.03, 142.81, 136.48, 132.79,127.35, 125.90, 125.55, 123.65, 118.51, 29.30, 29.11, 28.92, 28.73, 28.54, 24.56, 21.82, 12.95ppm
71% In dichloromethane; at 20℃;Inert atmosphere; 1-(4-(5-butyl- 1 ,3,4-oxadiazol-2-yl)phenyl)-3-(2-(trifluoromethyl)phenyl)urea (112):Aniline 111 (31 mg, 0.14 mmol) was added to a solution of 2-(Trifluoromethyl)phenylisocyanate (22 jiL, 0.15 mmol) in anhydrous CH2C12 (15 mL) in one portion. The solution wasstirred for 9 hours at r.t. under a nitrogen atmosphere. The solvent was removed at reducedpressure and the residue purified on silica to furnish the final product as white solid.(Purification eluent: PE/EtOAc 7:3). Yield 71%, white solid. 1HNMR (400 MHz, MeOD-d): ö7.95-7.93 (d, J= 8.4, 2H), 7.67-7.65 (d, J=8.8, 2H), 7.63-7.59 (m, 2H), 7.31-7.27 (m, 2H),2.96-2.92 (d, J= 7.6, 2H), 1.86-1.78 (m, 2H), 1.5 1-1.42 (m, 2H), 1.00-0.97 (t, J= 7.2, 3H) ppm.13C.NMR (100 MHz, ACETONE-d6 ): ö 166.35, 164.11, 152.03, 142.81, 136.48, 132.79,127.35, 125.90, 125.55, 123.65, 118.51, 29.30, 29.11, 28.92, 28.73, 28.54, 24.56, 21.82, 12.95 ppm.
  • 72
  • 4-(5-butyl-4H-1,2,4-triazol-3-yl)aniline [ No CAS ]
  • [ 2285-12-3 ]
  • 1-(4-(5-butyl-4H-1,2,4-triazol-3-yl)phenyl)-3-(2-(trifluoromethyl)phenyl)urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% In dichloromethane; at 20℃; for 12h;Inert atmosphere; Aniline 118 (25 mg, 0.11 mmol) was added to a solution of 2-(Trifluoromethyl)phenyl isocyanate (18 jiL, 0.11 mmol) in anhydrous CH2C12 (15 mL) in one portion. The solution was stirred for 12 hours at r.t. under a nitrogen atmosphere. The solvent was removed at reducedpressure and the residue purified on silica to furnish the final product as white solid. (Purification eluent: PE/EtOAc 7:3). Yield 70%, white solid. 1HNMR (400 MHz, MeOD-d): ö 7.95-7.89 (m, 4H), 7.66-7.56 (m, 4H), 7.29-7.25 (m), 2.8 1-2.77 (d, J=7.6 Hz, 2H), 1.79-1.72 (m, 2H), 1.45-1.36 (m, 2H), 0.98-0.94 (t, J=7.6 Hz, 3H)ppm. 13C-NMR (100 MHz, MeOD-d6):ö153.58, 146.64, 140.81, 135.86, 132.40, 126.77, 126.01, 125.67, 124.01, 121.78, 121.44,118.53, 30.00, 29.31, 25.76, 21.88, 12.61 ppm
70% In dichloromethane; at 20℃; for 12h;Inert atmosphere; Aniline 118 (25 mg, 0.11 mmol) was added to a solution of 2-(Trifluoromethyl)phenylisocyanate (18 jiL, 0.11 mmol) in anhydrous CH2C12 (15 mL) in one portion. The solution wasstirred for 12 hours at r.t. under a nitrogen atmosphere. The solvent was removed at reduced pressure and the residue purified on silica to furnish the final product as white solid. (Purification eluent: PE/EtOAc 7:3). Yield 70%, white solid. 1HNMR (400 MHz, MeOD-d): ö 7.95-7.89 (m, 4H), 7.66-7.56 (m, 4H), 7.29-7.25 (m), 2.81-2.77 (d, J=7.6 Hz, 2H), 1.79-1.72(m, 2H), 1.45-1.36 (m, 2H), 0.98-0.94 (t, J=7.6 Hz, 3H)ppm. 13C-NMR (100 MHz, MeOD-d6):ö153.58, 146.64, 140.81, 135.86, 132.40, 126.77, 126.01, 125.67, 124.01, 121.78, 121.44, 118.53, 30.00, 29.31, 25.76, 21.88, 12.61 ppm.
  • 73
  • 4-(5-butyl-1,3,4-thiadiazol-2-yl)aniline [ No CAS ]
  • [ 2285-12-3 ]
  • 1-(4-(5-butyl-1,3,4-thiadiazol-2-yl)phenyl)-3-(2-(trifluoromethyl)phenyl)urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% In dichloromethane; at 20℃; for 12h;Inert atmosphere; Aniline 123 (25 mg, 0.11 mmol) was added to a solution of 2-(Trifluoromethyl)phenyl isocyanate (17 jiL, 0.11 mmol) in anhydrous CH2C12 (15 mL) in one portion. The solution was stirred for 12 hours at r.t. under a nitrogen atmosphere. The solvent was removed at reduced pressure and the residue purified on silica to furnish the final product as white solid.(Purification eluent: PE/EtOAc 7:3). Yield 68%, white solid. 1H NMR (400 MHz, CDC13-d) ö7.57 (m,, 5H), 7.31 -7.22 (m, 2H), 7.18 (dd, J 7.5, 1.6 Hz, 1H), 6.97 (td, J= 7.5, 1.6 Hz, 1H),4.18 (s, 1H), 2.75 (t, J 5.5 Hz, 2H), 1.65 (dq, J 7.7, 5.6 Hz, 2H), 1.46 - 1.32 (m, 2H), 1.32 --1.07 (m, 3H)ppm.
68% In dichloromethane; at 20℃; for 12h;Inert atmosphere; Aniline 123 (25 mg, 0.11 mmol) was added to a solution of 2-(Trifluoromethyl)phenyl isocyanate (17 jiL, 0.11 mmol) in anhydrous CH2C12 (15 mL) in one portion. The solution was stirred for 12 hours at r.t. under a nitrogen atmosphere. The solvent was removed at reduced pressure and the residue purified on silica to furnish the final product as white solid.(Purification eluent: PE/EtOAc 7:3). Yield 68%, white solid. 1H NMR (400 MHz, CDC13-d) ö7.57 (m,, 5H), 7.31 -7.22 (m, 2H), 7.18 (dd, J 7.5, 1.6 Hz, 1H), 6.97 (td, J= 7.5, 1.6 Hz, 1H),4.18 (s, 1H), 2.75 (t, J 5.5 Hz, 2H), 1.65 (dq, J 7.7, 5.6 Hz, 2H), 1.46 - 1.32 (m, 2H), 1.32 --1.07 (m, 3H)ppm.
  • 74
  • 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid hydrazide [ No CAS ]
  • [ 2285-12-3 ]
  • 2-(1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carbonyl)-N-(2-(trifluoromethyl)phenyl)hydrazine-1-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% In tetrahydrofuran; at 50℃; for 3h; General procedure: A solution of substituted phenyl isocyanates (0.25 g,0.0021 mol) was added to a solution of 19 (1.0 g, 0.0019 mol) inTHF (10.0 mL). The resulting reaction mixture was heated to 50 C for 3 h. After cooling to rt, the precipitate was collectedby filtration, washed with diethyl ether and dried to afford 22a-22c.
  • 75
  • [ 10328-92-4 ]
  • [ 2285-12-3 ]
  • [ 966-08-5 ]
  • 76
  • [ 39093-93-1 ]
  • [ 2285-12-3 ]
  • N-(2-(trifluoromethyl)phenyl)thiomorpholine-4-carboxamide 1,1-dioxide [ No CAS ]
YieldReaction ConditionsOperation in experiment
97.2% In diethyl ether; at 20℃; for 16h; [ 1771 ] A solution of l-isocyanato-2-(trifluoromethyl)benzene ( 1.000 g, 5.344 mmol) and thiomorpholine 1 , 1 -dioxide (0.722 g, 5.344 mmol) in diethylether (20 mL) was stirred at the room temperature for 16 hr. The precipitates were collected by filtration, washed by diethylether, and dried to give the title compound N- (2-(trifluoromethyl)phenyl)thiomoipholine-4-carboxamide 1 , 1 -dioxide as white solid ( 1.674 g, 97.2 %).
  • 77
  • [ 72784-43-1 ]
  • [ 2285-12-3 ]
  • C13H13F3N2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dichloromethane; at 20℃; <strong>[72784-43-1]1-amino-1-cyclopropylcarboxylic acid methyl ester</strong> was dissolved in 150 ml of DCM,The equimolar isocyanate solution was slowly added and the mixture was stirred at room temperature overnight. The solvent DCM was removed under reduced pressure,Add 4M hydrochloric acid 150ml (make the pH below 1), add ethyl acetate extraction, combined organic phase,Saturated sodium chloride was washed and the solvent was removed under reduced pressure to give a white solid.
  • 78
  • [ 2577-48-2 ]
  • [ 2285-12-3 ]
  • C14H15F3N2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dichloromethane; at 20℃; 4 g of L-proline methyl ester was dissolved in 100 ml of DCM,Adding equal equivalents of isocyanate,Stir overnight at room temperature. Add DCM dilution reaction solution, add 2M hydrochloric acid 100ml, the organic layer, 2MHCl washing, saturated sodium bicarbonate washing, saturated sodium chloride washing, anhydrous sodium sulfate drying, solvent removal under vacuum, vacuum drying to obtain crude,Directly into the next step.
  • 80
  • [ 57260-71-6 ]
  • [ 2285-12-3 ]
  • C17H22F3N3O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dichloromethane; at 20℃; for 2h; General procedure: Aniline (1 g, 10 mmol) was dissolved in DMSO (10 ml), addingCDI (2g, 12 mmol) into stirred solution. The reaction mixture wasstirred at room temperature for 2 h. The reaction mixture wasmonitored by TLC and concentrated in vacuo. The resulting oilwas dissolved in methylene chloride (20 ml), adding 1-Boc-piperazine(1.67 g, 9 mmol), The reaction mixture was stirred at roomtemperature for 2 h. The residue was purified by flash columnchromatography on silica gel using ethyl petroleum/ethyl acetate(1:1) as eluent to obtain 8. Compound 4 (1.2 g) was obtained andthe yield was 62.69%.
  • 81
  • [ 530-62-1 ]
  • [ 88-17-5 ]
  • [ 2285-12-3 ]
YieldReaction ConditionsOperation in experiment
In dimethyl sulfoxide; at 20℃; for 2h; General procedure: Aniline (1 g, 10 mmol) was dissolved in DMSO (10 ml), addingCDI (2g, 12 mmol) into stirred solution. The reaction mixture wasstirred at room temperature for 2 h. The reaction mixture wasmonitored by TLC and concentrated in vacuo.
  • 82
  • ethyl 2-(6-(4-aminophenyl)-2-ethyl-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)acetate [ No CAS ]
  • [ 2285-12-3 ]
  • ethyl 2-(2-ethyl-1-oxo-6-(4-(3-(2-(trifluoromethyl)phenyl)ureido)phenyl)-1,2,3,4-tetrahydronaphthalen-2-yl)acetate [ No CAS ]
  • 83
  • [ 623-47-2 ]
  • [ 2285-12-3 ]
  • ethyl 4-oxo-4-((2-(trifluoromethyl)phenyl)amino)but-2-ynoate [ No CAS ]
  • 84
  • [ 5713-61-1 ]
  • [ 2285-12-3 ]
  • [ 137272-70-9 ]
YieldReaction ConditionsOperation in experiment
38.7% In tetrahydrofuran; at -78℃; for 0.5h; Thiophen-2-yl magnesium bromide (28.6 mL, 28.6 mmol) was injected dropwise into a solution of 2-(trifluoromethyl)phenyl isocyanate (4.86 g, 26.0 mmol) in THF (100 mL) at -78 C. The reaction was stirred at -78C for 30 min. The reaction mixture was then quenched with a saturated solution of NH4Cl (100 mL) and extracted with EtOAc (3 x 100 mL). The organic layers were combined, dried over MgSO4, filtered and concentrated in vacuo. The product was purified on a silica gel column (0 % - 20 % EtOAc in DCM) to provide Example 356.01 (2.73g, 10.1 mmol, 38.7 % yield).1H NMR (400 MHz, DMSO-d6) δ 10.14 (s, 1 H) 7.96 (dd, J=3.72, 1.17 Hz, 1 H) 7.86 (dd, J=4.99, 1.08 Hz, 1 H) 7.80 (d, J=8.02 Hz, 1 H) 7.71 - 7.77 (m, 1 H) 7.52 - 7.58 (m, 2 H) 7.23 (dd, J=4.99, 3.81 Hz, 1 H). LCMS-ESI (pos.) m/z: 272.0 (M+H)+.
  • 85
  • [ 100-58-3 ]
  • [ 2285-12-3 ]
  • [ 2946-71-6 ]
YieldReaction ConditionsOperation in experiment
53% In tetrahydrofuran; diethyl ether; at -78 - 0℃; for 2h; To a 500- mL round-bottomed flask was added 3-(trifluoro-o-tolyl) isocyanate (Sigma-Aldrich Chemical Company, Inc., 5.06 g, 26.2 mmol) in THF (100 mL). The solution was cooled to -78 C and phenylmagnesium bromide (3.0 M solution in diethyl ether, Sigma-Aldrich Chemical Company, Inc., 9.62 mL, 28.9 mmol) was added dropwise via syringe with stirring. The reaction mixture was then stirred at -78 to 0 C for 2 h. LCMS analysis indicated the reaction was complete. The reaction mixture was then diluted with saturated NH4Cl at 0 C and extracted with DCM. The combined organic layers were washed with 10% Na2CO3 and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the material as a light-yellow oil. The material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (120 g), eluting with a gradient of 10% to 40% EtOAc in hexanes, to provide the title compound Example 51.1 (3.68 g, 13.9 mmol, 53 % yield) as a white solid. LCMS-ESI (pos.), m/z: 266.0 (M+H)+.
  • 86
  • ethyl 5-(chlorocarbonyl)-6,6-dimethyl-3-[1-(trimethylsilyl)cyclobutanecarbox amido]-5,6-dihydropyrrolo[3,4-c]pyrazole-2(4H)-carboxylate [ No CAS ]
  • [ 2285-12-3 ]
  • 6,6-dimethyl-N-[2-(trifluoromethyl)phenyl]-3-[1-(trimethylsilyl)cyclobutanecarboxamido]-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
51% To a solution of 108 mg (0.284 mmol) of ethyl6,6-dimethyl-3-[1 -(trimethylsilyl)cyclobutanecarboxamido]-5,6-dihydropyrrolo[3,4-c]pyrazole-2(4H)-carboxy- late synthesized in the same way as in Reference Example 3 in 3 ml of 1,4-dioxane, 0.076 ml (0.55 mmol) of 1-iso- cyanato-2-(trifluoromethyl)benzene was added at room temperature in an argon atmosphere and reacted at room temperature for 1 hour with stirring. Subsequently, 0.150 ml (1.38 mmol) of N,N-dimethylethane- 1 ,2-diamine was added to the reaction solution at room temperature and reacted at room temperature for 1 hour with stirring.10664] After completion of the reaction, a 5% aqueous potassium bisulfate solution was added to the reaction solution, followed by extraction with ethyl acetate. The whole organic layer thus obtained was washed with saturated saline, dried over anhydrous magnesium sulfate, then filtered, and concentrated under reduced pressure. The obtained concentration residue was subjected to preparative column chromatography (apparatus 2, DIOL silica gel, elution solvent: n-hexane:ethyl acetate=90:10-50:50 (V/V)), and a fraction containing the compound of interest was concentrated under reduced pressure. The obtained concentration residue was subjected to preparative colunm chromatography (apparatus 3, ODS silica gel, elution solvent:acetonitrile: 1 mM aqueous dipotassium biphosphate solution=60:40- 80:20 (V/V)), and a fraction containing the compound of interest was separated into an organic layer and an aqueous layer by the addition of ethyl acetate and a saturated aqueous solution of sodium bicarbonate. The obtained organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate, then filtered, and concentrated under reduced pressure. The obtained concentration residue was dissolved by the addition of ethyl acetate, then n-hexane was added thereto, and the deposited solid was collected by filtration and dried under reduced pressure to obtain 71.9 mg of the title compound (yield: 51%) as a white solid.10665] Mass spectrum (CI, mlz): 494 [M+1].10666] ‘H-NMR spectrum (400 MHz, DMSO-d5) ö: 12.28 & 11.80 (s, total 1H), 9.69-9.55 (m, 1H), 7.88-7.51 (m, 4H), 7.40-7.33 (m, 1H), 4.66-4.49 (m, 2H), 2.56-2.40 (m, 2H),2.27-2.13 (m, 2H), 1.91-1.73 (m, 2H), 1.71-1.55 (m, 6H),0.09 (s, 9H).
  • 87
  • [ 84807-09-0 ]
  • [ 2285-12-3 ]
  • 4-(1H-indol-4-yl)-N-(2-(trifluoromethyl)phenyl)piperazine-1-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dichloromethane; for 0.5h; General procedure: The synthesis of 1-(aryl)piperazine urea derivatives 1a, 1g-1i, 1l-1w, 2a-2j, 2l, 2n-2p, 2t-2as, 2aw, 2ba, 4c and 4f was accomplished by dropwise addition, with stirring, of 0.1 mmol aryl isocyanate solution in 0.5 mL dichloromethane to a 0.5 mL dichloromethane solution of 0.1 mmol 1-(aryl)piperazine and 0.11 mmol trimethylamine (Scheme 1). After 30 minutes, reaction mixtures were diluted as necessary with dichloromethane for complete solution and purified by normal phase chromatography utilizing gradients of hexanes and ethyl acetate.
Same Skeleton Products
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