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CAS No. : | 15996-84-6 |
Formula : | C9H10F3N |
M.W : | 189.18 |
SMILES Code : | CC(N)C1=CC=C(C=C1)C(F)(F)F |
MDL No. : | MFCD04038878 |
GHS Pictogram: | ![]() |
Signal Word: | Danger |
Hazard Statements: | H301-H319 |
Precautionary Statements: | P301+P310-P305+P351+P338 |
Class: | 6.1 |
UN#: | 2811 |
Packing Group: | Ⅲ |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonia; hydrogen;palladium 10% on activated carbon; In methanol; water; under 3102.97 Torr; for 2h; | EXAMPLE 136B 1-[4-(trifluoromethyl)phenyl]ethanamine The product from Example 136A (21.0 g, 100 mmol) in MeOH (220 mL) and ammonia (30 mL) was treated with 10% Pd/C under 60 psi of hydrogen gas for 2 hours. The mixture was filtered and the filtrate was concentrated to provide the title compound. 1H NMR (300 MHz, d6-DMSO) 7.60 (q, 4H), 4.07 (q, 1H), 3.28 (broad s, 2H), 1.24 (d, 3H); MS (DCI/NH3) m/e 190 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | Ti(OiPr)4 (31.5 mL, 106 mmol) was added to (p-trifluoromethyl)acetophenone 108 (10.0 g, 53.1 mmol) in NH3 (2.0 M in EtOH, 133 mL) and the resultant mixture was stirred at rt for 6 h. NaBH4 (3.01 g, 79.7 mmol) was added at 0 C, and the resultant suspension was stirred at rt for 3 h, then poured into 2.0 M aq NH4OH (200 mL). The resultant suspension was filtered (eluent EtOAc) and the aqueous layer was extracted with EtOAc (2*80 mL). The combined organic extracts were extracted with 1.0 M aq HCl (3*50 mL) and the combined aqueous extracts were washed with EtOAc (3*30 mL), treated with 2.0 M aq NaOH until pH>8 was observed, then extracted with EtOAc (4*50 mL). The combined organic extracts were washed with brine (200 mL), then dried and concentrated in vacuo to give (RS)-117 as a pale yellow oil (6.84 g, 68%);43 δH (400 MHz, CDCl3) 1.40 (3H, d, J 6.6, C(α)Me), 1.59 (2H, br s, NH2), 4.20 (1H, q, J 6.6, C(α)H), 7.48 (2H, d, J 7.8, C(2)H, C(6)H), 7.59 (2H, d, J 7.8, C(3)H, C(5)H). | |
52% | A mixture of 1-(4-(trifluoromethyl)phenyl)ethanone (400 mg, 2.13 mmol), Ti(O-i-Pr)4 (1.25 mL, ∼4.25 mmol) and ammonia in EtOH (2 M, 5.30 mL, ∼10.6 mmol) was stirred under argon at room temperature for 24 h NaBH4 (120 mg, 3.19 mmol) was then added, and the resulting mixture was stirred for another 24 h. The pH of the reaction mixture was adjusted to pH 2 using HCl (6 M), and washed with tert-butyl methyl ether (TBME) (3 × 20 mL). Using NaOH (pellets) the pH was adjusted to ca 10, and the mixture was extracted with TBME (6 × 30 mL). The combined organic phase was dried over MgSO4, and the solvent was removed under reduced pressure to give 210 mg (1.11 mmol, 52%) of a yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.58 (m, 2H), 7.46 (m, 2H), 4.19 (q, J = 6.7, 1H), 1.38 (d, J = 6.7, 3H), 1.51 (s, 2H, NH2). 13C NMR (100 MHz, CDCl3) δ: 152.1 (q, J = 1.1), 129.4 (q, J = 31.5), 126.5 (2C), 125.8 (q, J = 3.8, 2C), 124.6 (q, J = 270.9), 51.4, 25.1. | |
With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; ammonium formate; In methanol; at 70℃; for 7h;Inert atmosphere; | General procedure: The corresponding ketone (20 mmol, 1.0 eq) and CH3OH (20 mL) were added to a 250 mL Schlenk tube containing [RhCp*Cl2]2 (61.8 mg, 100 μmol, 0.005 equiv) and HCOONH4 (6.36 g, 100 mmol, 5.0eq). The brown mixture was frozen, and the whole system was evacuated. The system was closed and then stirred at 70 C for 7 h. After the dark green resulting solution was cooled to room temperature, 1M aqueous HCl solution (38.4 mL) was added, and the mixture was washed twice with CH2Cl2 (5 mL) to remove the neutral compounds. After addition of a cold 12 M aqueous NaOH solution (3.6 mL) to the aqueous layer, the mixture was extracted six times with CH2Cl2 (12 mL). The combined organic layers were dried over anhydrous Na2SO4. Filtration and evaporation under reduced pressure gave crude amine,which was used without purification. All the crude corresponding amine was dissolved in dichloromethane (50 mL), and TCCA (trichloroisocyanuric acid) (3.2 g, 14 mmol) was added in a250 ml round-bottom flask at 0 C. Then, the mixture was stirred at ambient temperature during 1 h. Triethylamine (6.0 g, 6 mol) dissolved in dichloromethane (50 mL) was added, and the resulting mixture was washed with water (200 mL) and hydrochloric acid (1 M, 200 mL)successively. The organic layer was dried over anhydrous sodium sulfate. After concentration under reduced pressure, purification by column chromatography on silica gel (n-hexane/EtOAc:40/1) afforded pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; dicyclohexyl-carbodiimide; at 20℃; | EXAMPLE 138A (1R)-2-oxo-1-phenyl-2-({1-[4-(trifluoromethyl)phenyl]ethyl}amino)ethyl Acetate 1-[4-(Trifluoromethyl)phenyl]ethanamine (37.5 g, 198.4 mmol) and (R)-acetylmandelic acid (40.4 g, 208.3 mmol, 1.05 eq.) were combined in DMAP (0.7 g, 5.7 mmol) and treated with DCC (45.0 g, 218 mmol). After stirring overnight at ambient temperature, the mixture was filtered through a plug of silica. The filtrate was concentrated and the residue was purified by chromatography on Biotage Flash 75 column (ethyl acetate:hexanes, 25:75) to provide a faster running diastereomer and a slower running diastereomer. (fast diastereomer) 1H NMR (300 MHz, CDCl3) 7.58 (d, 2H), 7.39 (m, 7H), 6.30 broad (d, 1H), 6.08 (s, 1H), 5.18 (m, 1H), 2.20 (s, 3H), 1.29 (d, 3H); MS (DCI/NH3) m/e 366 (M+H)+. (slow diastereomer) 1H NMR (300 MHz, CDCl3) 7.58 (d, 2H), 7.40 (m, 5H), 7.31 (d, 2H), 6.21 (broad d, 1H), 6.06 (s, 1H), 5.18 (m, 1H), 2.20 (s, 3H), 1.50 (d, 3H); MS (DCI/NH3) m/e 366 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | In methanol; at 0 - 20℃; for 96 - 120h; | To a stirred solution of compound 2b.4 (2.0 g, 7.8 mmol) in methanol (60 mL) was added 4-trifruorornethyl-α-methyl benzyl amine 2b.5 (1.6 g, 9.4 mmol) under nitrogen atmosphere. The reaction mixture stirred at room temperature for 4 to 5 days. Once the reaction was completed then solvent was removed under reduced pressure. The residue was purified by flash column chromatography eluting with 15 % ethyl acetate in n-hexane to provide compound 2b.6 (2.6 g, 92%). 1H-NMR (DMSO-^)δ 10.98 (1/2H, m, Ar-H), 9.94 (1/2H, m, Ar-H), 8.24-7.98 (IH, m, Ar-H), 7.80-7.56 (6H, m, Ar-H), 5.02 (IH, m, -CH), 1.72-1.47 (3H, 2 x d,-CH3). EIMS (m/z): 399.4 (M + H) + |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In iso-butanol; at 110℃; for 16h; | The diethyl [3-methoxypro-2-enylidene]malonate (1.0 g, 4.4 mmol), Compound 7.1, was added to a 2-dram vial in 2 ml of s-BuOH. To the mixture was added l-(4- trifluoromethyl-phenyl)-ethylamine (mixture of enantiomers) (0.74 g, 4.6 mmole). The reaction mixture was heated to 1100C for 16 hours. When the reaction was completed, the solvent was removed using GeneVac HT-12 to give Compound 51.1. ES (+) MS m/e = 340 (M+l). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33%; 36% | With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 0 - 20℃; for 16h; | DCC (2.35 g, 12.1 mmol) and DMAP (50 mg) were added to a stirred solution of (RS)-117 (2.29 g, 12.1 mmol) and (R)-O-acetylmandelic acid (2.35 g, 12.1 mmol, >99:1 er) in CH2Cl2 (60 mL) at 0 C and the resultant mixture was stirred at rt for 16 h. The reaction mixture was filtered and the filtrate was washed sequentially with 1.0 M aq HCl (40 mL), satd aq NaHCO3 (40 mL) and brine (40 mL), then dried and concentrated in vacuo. Purification via flash column chromatography (eluent 30-40 C petrol/EtOAc, 2:1, 1% Et3N) gave 119 as a white solid (1.58 g, 36%, >99:1 dr); mp 132.5-133.5 C; νmax (ATR) 3292 (N-H), 1742, 1662 (C=O), 1327 (C-F); [α]D20 -153.0 (c 1.0 in MeOH); δH (500 MHz, CDCl3) 1.40 (3H, d, J 7.0, C(α)Me), 2.13 (3H, s, COMe), 4.87 (1H, br s, NH), 5.00 (1H, q, J 7.0, C(α)H), 5.94 (1H, s, C(2)H), 7.33-7.39 (3H, m, C(2')H, C(6')H, Ph), 7.48-7.53 (4H, m, Ph), 7.58 (2H, d, J 8.2, C(3')H, C(5')H); δC (125 MHz, CDCl3) 20.8 (COMe), 22.1 (C(α)Me), 50.0 (C(α)), 77.2 (C(2)), 125.9 (q, J 269.9, CF3), 126.4 (q, J 3.8, C(3'), C(5')), 127.9 (C(2'), C(6')), 128.7 (o-Ph), 129.8 (m-Ph), 130.2 (p-Ph), 130.3 (q, J 31.5, C(4')), 136.8 (i-Ph), 149.5 (C(1')), 171.0 (C(1)), 172.1 (COMe); δF (377 MHz, CDCl3) -63.9 (CF3); m/z (ESI+) 388 ([M+Na]+, 100%); HRMS (ESI+) ([M+Na]+) requires 388.1131; found 388.1122. Further elution gave 118 as a white solid (1.46 g, 33%, >99:1 dr); mp 118-120 C; νmax (ATR) 3291 (N-H), 1744, 1663 (C=O), 1327 (C-F); [α]D20 -17.0 (c 1.0 in MeOH); δH (500 MHz, CDCl3) 1.47 (3H, d, J 7.0, C(α)Me), 2.15 (3H, s, COMe), 4.87 (1H, br s, NH), 5.06 (1H, q, J 7.0, C(α)H), 5.94 (1H, s, C(2)H), 7.24 (2H, d, J 8.4, C(2')H, C(6')H), 7.34-7.38 (3H, m, Ph), 7.44-7.49 (4H, m, C(3')H, C(5')H, Ph); δC (125 MHz, CDCl3) 20.8 (COMe), 22.0 (C(α)Me), 50.0 (C(α)), 77.1 (C(2)), 125.7 (q, J 270.8, CF3), 126.4 (q, J 3.8, C(3'), C(5')), 127.6 (C(2'), C(6')), 128.8 (o-Ph), 129.8 (m-Ph), 130.2 (p-Ph), 130.3 (q, J 32.4, C(4')), 136.7 (i-Ph), 149.5 (C(1')), 170.9 (C(1)), 172.1 (COMe); δF (377 MHz, CDCl3) -63.7 (CF3); m/z (ESI+) 388 ([M+Na]+, 100%); HRMS (ESI+) ([M+Na]+) requires 388.1131; found 388.1120. A 57:43 mixture of 118 and 119, respectively, was also recovered as a white solid (812 mg, 18%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium cyanoborohydride; In dichloromethane; at 20℃; for 16h; | A mixture of 4-methyl-3-oxo-3, 4-dihydro-quinoxaline-2-carbaldehyde (100 mg), sodium cyanoborohydride (0.050 g, 1.5 eq), and 1- (4-TRIFLUOROMETHYL-PHENYL)-ETHYLAMINE (100 mg) in dry CH2C12 (1.5 mL) was stirred at rt under nitrogen for 16h. The reaction mixture was basified with a sat. NAHCO3 solution, extracted CH2C12. The combined organic extracts were dried (MGS04), filtered and concentrated in vacuo to give a crude oil. FC (CH2C12/MEOH : 95/5) gave the title compound as a brown oil. LC-MS: RT = 0.77 min. m/z = 362 (M + 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonia; hydrogen;palladium-carbon; In methanol; | EXAMPLE 136B 1-[4-(trifluoromethyl)phenyl]ethanamine The product from Example 136A (21.0 g, 100 mmol) in MeOH (220 mL) and ammonia (30 mL) was treated with 10% Pd/C under 60 psi of hydrogen gas for 2 hours. The mixture was filtered and the filtrate was concentrated to provide the title compound. 1H NMR (300 MHz, d6-DMSO) 7.60 (q, 4H), 4.07 (q, 1H), 3.28 (broad s, 2H), 1.24 (d, 3H); MS (DCI/NH3) m/e 190 (M+H)+. | |
With ammonia; hydrogen;palladium-carbon; In methanol; | Example 136B 1-[4-(trifluoromethyl)phenyl]ethanamine The product from Example 136A (21.0 g, 100 mmol) in MeOH (220 mL) and ammonia (30 mL) was treated with 10% Pd/C under 60 psi of hydrogen gas for 2 hours. The mixture was filtered and the filtrate was concentrated to provide the title compound. 1H NMR (300 MHz, d6-DMSO) 7.60 (q, 4H), 4.07 (q, 1H), 3.28 (broad s, 2H), 1.24 (d, 3H); MS (DCI/NH3) m/e 190 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With aqueous HBr; In water; | EXAMPLE 138B (-) 1-[4-(trifluoromethyl)phenyl]ethanamine The faster running diastereomer from Example 138A (29.2 g, 80 mmol) was treated with 48% aqueous HBr (350 mL) and water (50 mL) and was refluxed for 16 hours. The mixture was cooled and extracted with diethyl ether. The aqueous phase was basified with 2N NaOH (pH 12-13) and extracted with diethyl ether. The organic phase was concentrated to provide the title compound. 94% ee (by Mosher amide NMR). [α]D -19.1 (c 1.15; MeOH); 1H NMR (300 MHz, CDCl3) 7.60 (d, 2H), 7.47 (d, 2H), 4.20 (m, 1H), 1.65 (br s, 2H), 1.40 (s, 3H); MS (DCI/NH3) m/e 190 (M+H)+. | |
With aqueous HBr; In water; | EXAMPLE 138C (+) 1-[4-(trifluoromethyl)phenyl]ethanamine The slower running diastereomer from Example 138A (29.2 g, 80 mmol) was treated with 48% aqueous HBr (350 mL) and water (50 mL) and was refluxed for 16 hours. The mixture was cooled and extracted with diethyl ether. The aqueous phase was basified with 2N NaOH (pH 12-13) and extracted with diethyl ether. The organic phase was concentrated to provide the title compound. [α]D +20.5 (c 1.47; MeOH). 94% ee (Mosher amide NMR); 1H NMR (300 MHz, CDCl3) 7.60 (d, 2H), 7.47 (d, 2H), 4.20 (m, 1H), 1.60 (br s, 2H), 1.40 (s, 3H); MS (DCI/NH3) m/e 190 (M+H)+. | |
With aqueous HBr; In water; | Example 138B (-) 1-[4-(trifluoromethyl)phenyl]ethanamine The faster running diastereomer from Example 138A (29.2 g, 80 mmol) was treated with 48% aqueous HBr (350 mL) and water (50 mL) and was refluxed for 16 hours. The mixture was cooled and extracted with diethyl ether. The aqueous phase was basified with 2N NaOH (pH 12-13) and extracted with diethyl ether. The organic phase was concentrated to provide the title compound. 94% ee (by Mosher amide NMR). [α]D -19.1 (c 1.15; MeOH); 1H NMR (300 MHz, CDCl3) 7.60 (d, 2H), 7.47 (d, 2H), 4.20 (m, 1H), 1.65 (br s, 2H), 1.40 (s, 3H); MS (DCI/NH3) m/e 190 (M+H)+. |
With aqueous HBr; In water; | Example 138C (+) 1-[4-(trifluoromethyl)phenyl]ethanamine The slower running diastereomer from Example 138A (29.2 g, 80 mmol) was treated with 48% aqueous HBr (350 mL) and water (50 mL) and was refluxed for 16 hours. The mixture was cooled and extracted with diethyl ether. The aqueous phase was basified with 2N NaOH (pH 12-13) and extracted with diethyl ether. The organic phase was concentrated to provide the title compound. [α]D +20.5 (c 1.47; MeOH). 94% ee (Mosher amide NMR); 1H NMR (300 MHz, CDCl3) 7.60 (d, 2H), 7.47 (d, 2H), 4.20 (m, 1H), 1.60 (br s, 2H), 1.40 (s, 3H); MS (DCI/NH3) m/e 190 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | To a solution of l-[4-(trifluoromethyl)phenyl]ethylamine (1.Og, 5.2 mmol) in dichloromethane (20 ml) at 3O0C was added a suspension of 1,1 '-carbonyl diimidazole (0.86g, 5.2mmol) in dichloromethane (7 ml) and the reaction was stirred at 3O0C for 1 hour. A suspension of azetidine-3-yl-carbamic acid terf-butyl ester (0.89g, 5.2mmol) in dichloromethane (5ml) was added and the reaction stirred at 30 for 5 hours. The reaction was cooled to room temperature (r.t.) and the product obtained by filtration as a white solid. Yield 1.35 g (67%): HPLC retention time, 3.56min (Solvent: CH3CN/H2O/0.05% NH3, 5-95% gradient H2O-6min. Column: Xterra 50 x 4.60 i.d., Cl 8 reverse phase. Flow rate: 1.5mL/min.). Mass spectrum (ES+) m/z 388 (M + H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | In butan-1-ol; at 145℃; for 24h;Inert atmosphere; | General procedure: The following is representative: 4-chloro-6-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine (7a) (275 mg, 1.06 mmol) and (R)-1-phenylethanamine (0.44 mL, ∼3.5 mmol) were added to a dry round bottle flask containing 1-butanol (3.5 mL) under argon atmosphere. The mixture was heated at 145 C for 24 h. The precipitate formed upon cooling to rt. was isolated by filtration, washed with diethyl ether (25 mL) and dried resulting in a solid. |
In butan-1-ol; at 145℃; | General procedure: Compound 1a-d or 54 (1 mmol) was mixed with the selected amine, 2-25, (3 mmol) and n-butanol (5 ml) and agitated at145 C for 14-24 h. Then the mixture was cooled to 22 C, dilutedwith water (15 ml) and ethyl acetate (40 ml). After phase separation,the water phase was back extracted with more ethyl acetate(2 10 ml). The combined organic phases were washed with brine(10 ml), dried over anhydrous Na2SO4, filtered and concentrated invacuo, before the crude mixture was purified as specified for eachindividual compound | |
In butan-1-ol; at 145℃; for 24h;Inert atmosphere; | General procedure: The following is representative: 4-chloro-6-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine (14) (275 mg, 1.06 mmol) and (S)-1-phenylethanamine ((S)-19i) (0.44 mL, ∼3.5 mmol) were added to a dry round bottle flask containing 1-butanol (3.5 mL) under argon atmosphere. The mixture was heated at 145 C for 24 h. The precipitate formed upon cooling to rt. was isolated by filtration, washed with diethyl ether (25 mL) and dried resulting in a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | General procedure: Example 3 - General procedure for the transfer hydroqenative reductive amination using ammonium formate Ketone (0.5 mmol) and HCOONH4 (5 mmol) were dissolved in MeOH (2ml) in a carousel reaction tube. The mixture was than degassed and stirred for 10 minutes at 80 C under nitrogen. HCOOH/NEt3 azeotrope (0.5 ml) and catalyst solution (1 ml) (prepared by dissolving catalyst (0.5 μηιοΙ) in MeOH (1 ml)) were then introduced. The resulting mixture was stirred at 80 C for the time indicated. The reaction was quenched with water, basified with aqueous KOH solution and extracted with DCM. The solvent was then removed under vacuum. The crude product was dissolved in ethanol (10 ml) and 6 N HCI solution (5 ml) was than added. The mixture was refluxed for 6 hrs. Ethanol was then removed under vacuum and the resultant aqueous layer was washed with ethyl acetate to remove impurities. The aqueous layer was basified with a KOH solution and extracted with DCM. The organic layers were combined and dried over sodium sulphate. The final product was obtained after the evaporation of solvent under vacuum. | |
85% | General procedure: Ketone (0.5 mmol) and HCOONH4 (5 mmol) were dissolved in MeOH (2 ml) in a carousel reaction tube. The mixture was than degassed and stirred for 10 minutes at 80 C. under nitrogen. HCOOH/NEt3 azeotrope (0.5 ml) and catalyst solution (1 ml) (prepared by dissolving catalyst (0.5 μmol) in MeOH (1 ml)) were then introduced. The resulting mixture was stirred at 80 C. for the time indicated. The reaction was quenched with water, basified with aqueous KOH solution and extracted with DCM. The solvent was then removed under vacuum. The crude product was dissolved in ethanol (10 ml) and 6 N HCl solution (5 ml) was than added. The mixture was refluxed for 6 hrs. Ethanol was then removed under vacuum and the resultant aqueous layer was washed with ethyl acetate to remove impurities. The aqueous layer was basified with a KOH solution and extracted with DCM. The organic layers were combined and dried over sodium sulphate. The final product was obtained after the evaporation of solvent under vacuum.This general reaction procedure was then applied to the following reductive amination reactions using catalyst 2c in methanol, the results for which are presented in Table 4A below | |
56% | With aluminium(III) triflate; (carbonyl)(chloro)(hydrido)tris(triphenylphosphine)ruthenium(II); ammonia; hydrogen; 1,2-bis-(diphenylphosphino)ethane; at 120℃; for 16h;Autoclave; | General procedure: Isolated yields (isolated from the reaction mixture by column chromatography). Examples 17-29 show that various carbonyl compounds can be converted to the corresponding primary amines in good yields using the inventive method. |
General procedure: Example 4 - General procedure for transfer hvdrogenative reductive ami nation using ammonium formate [00141 ] Ketone (0.5 mmol) and HCOONH4 (5 mmol) were dissolved in MeOH (2ml) in a carousel reaction tube. The mixture was than degassed and stirred for 10 minutes at 80 C under nitrogen. HCOOH/NEt3 azeotrope (0.5 ml) and catalyst solution (1 ml) (prepared by dissolving catalyst (0.5 μηιοΙ) in MeOH (1 ml)) were then introduced. The resulting mixture was stirred at 80 C for the time indicated. The reaction was quenched with water, basified with aqueous KOH solution and extracted with DCM. The solvent was then removed under vacuum. The crude product was dissolved in ethanol (10 ml) and 6 N HCI solution (5 ml) was than added. The mixture was refluxed for 6 hrs. Ethanol was then removed under vacuum and the resultant aqueous layer was washed with ethyl acetate to remove impurities. The aqueous layer was basified with a KOH solution and extracted with DCM. The organic layers were combined and dried over sodium sulphate. The final product was obtained after the evaporation of solvent under vacuum. | ||
With formic acid; C25H28ClIrN2O3; ammonium acetate; triethylamine; In 2,2,2-trifluoroethanol; at 80℃; | General procedure: Ketone (0.5 mmol) and HCOONH4 (5 mmol) were dissolved in MeOH (2 ml) in a carousel reaction tube. The mixture was than degassed and stirred for 10 minutes at 80 C. under nitrogen. HCOOH/NEt3 azeotrope (0.5 ml) and catalyst solution (1 ml) (prepared by dissolving catalyst (0.5 μamp in MeOH (1 ml)) were then introduced. The resulting mixture was stirred at 80 C. for the time indicated. The reaction was quenched with water, basified with aqueous KOH solution and extracted with DCM. The solvent was then removed under vacuum. The crude product was dissolved in ethanol (10 ml) and 6 N HCl solution (5 ml) was than added. The mixture was refluxed for 6 hrs. Ethanol was then removed under vacuum and the resultant aqueous layer was washed with ethyl acetate to remove impurities. The aqueous layer was basified with a KOH solution and extracted with DCM. The organic layers were combined and dried over sodium sulphate. The final product was obtained after the evaporation of solvent under vacuum. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; | General procedure: The racemic mixture of the title compound obtained using procedure described in scheme A and Example 8 was resolved by chiral separation on OJ column with 15% ]4eOH/C02 to afford isomerA (faster eluting), (R)2-.(inethylthio).-6oxo-.N.( I (4-(trif1uoromethyl)phenyl)ethy1)- I ,6-.dihydro pyrimidine.-4-carboxamide and isomer B (slower eluting), (S)-2-methyithio)..6.-oxoN-(l (4.. (trifluoromethyi)phenyl)ethyl)-i ,6dihydro pyrimidine.-4carboxamide. MS: 358.1 (M+H). |
Tags: 15996-84-6 synthesis path| 15996-84-6 SDS| 15996-84-6 COA| 15996-84-6 purity| 15996-84-6 application| 15996-84-6 NMR| 15996-84-6 COA| 15996-84-6 structure
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Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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