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[ CAS No. 936841-70-2 ]

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Chemical Structure| 936841-70-2
Chemical Structure| 936841-70-2
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Product Details of [ 936841-70-2 ]

CAS No. :936841-70-2 MDL No. :MFCD08061310
Formula : C6H3BrF3N Boiling Point : -
Linear Structure Formula :- InChI Key :N/A
M.W :225.99 g/mol Pubchem ID :-
Synonyms :

Safety of [ 936841-70-2 ]

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

Application In Synthesis of [ 936841-70-2 ]

  • Downstream synthetic route of [ 936841-70-2 ]

[ 936841-70-2 ] Synthesis Path-Downstream   1~17

  • 1
  • [ 214045-84-8 ]
  • [ 936841-70-2 ]
  • [ 1365763-32-1 ]
YieldReaction ConditionsOperation in experiment
64.5% With trans-N,N'-dimethyl-1,2-cyclohexyldiamine; potassium phosphate; copper(l) iodide; In 1,4-dioxane; at 120℃; for 36h; Preparation of 6-fluoro-2-(4-(trifluoromethyl)pyridin-3-yl)-3,4-dihydroisoquinolin-1(2H)-one (78A) 6-Fluoro-3,4-dihydroisoquinolin-1(2H)-one (I-78d: 500 mg, 3.029 mmol) was reacted with 3-bromo-4-(trifluoromethyl)-pyridine (890 mg, 3.93 mmol), 1,4-dioxane (15 mL), copper iodide (57.5 mg, 0.30 mmol), trans-N,N'-dimethyl-cyclohexyl-1,2-diamine (43 mg, 0.302 mmol) and potassium phosphate (1.92 g, 9.08 mmol) for 36 hours at 120 C. to afford the crude product. Purification by column chromatography on silica gel (2% methanol in CHCl3), afforded 600 mg of the product (64.5% yield). 1H NMR (CDCl3, 300 MHz): delta 8.86-8.80 (d, 1H), 8.7 (s, 1H), 8.2-8.1 (m, 1H), 7.7-7.64 (d, 1H), 7.19-7.0 (m, 1H), 6.99-6.96 (d, 1H), 4.03-3.9 (m, 1H), 3.83-3.73 (m, 1H), 3.3-3.3 (m, 1H), 3.09-3.02 (m, 1H). LCMS: 87.32%, m/z=311.1 (M+1).
With trans-N,N'-dimethyl-1,2-cyclohexyldiamine; potassium phosphate; copper(l) iodide; In 1,4-dioxane; at 120℃; for 36h; 6-Fluoro-3,4-dihydroisoquinolin-l(2H)-one fl-78d: 500mg, 3.029mmol) was reacted with 3-bromo-4-(trifluoromethyl)-pyridine (890mg, 3.93mmol), 1,4-dioxane (15mL), copper iodide (57.5mg, OJOmmol), /ra/M,-N,N'-dimethyl-cyclohexyl-l,2- diamine (43mg, 0.302mmol) and potassium phosphate (1.92g, 9.08mmol) for 36 hours at 120 C to afford the crude product. Purification by column chromatography on silica gel (2% methanol in CHCI3), afforded 600 mg of the product (64.5% yield).'H NMR (CDC13, 300MHZ): delta 8.86-8.80 (d, IH), 8.7 (s, IH), 8.2-8.1 (m, IH),7.7-7.64 (d, IH), 7.19-7.0 (m, IH), 6.99-6.96 (d, IH), 4.03-3.9 (m, IH), 3.83-3.73 (m, IH), 3.3-3.3 (m, IH), 3.09-3.02 (m, IH). LCMS: 87.32%, m/z = 311.1 (M+l).
  • 2
  • 3,4-dihydro-2H-benzo[4,5]thieno[3,2-c]pyridin-1-one [ No CAS ]
  • [ 936841-70-2 ]
  • [ 1365762-23-7 ]
YieldReaction ConditionsOperation in experiment
8.18% With potassium phosphate; XPhos In 1,4-dioxane at 120℃; for 48h; sealed tube; 58 X-Phos (35mg, 0.0739mmol) and Pd2(dba)3 (45mg, 0.0492mmol) were added to a previously degassed solution of 3,4-dihydro-2H-benzo[4,5]thieno[3,2-c]pyridin- 1-one q-9d: lOOmg, 0.4919mmol), 3P04 (313mg, 1.4759mmol) and 1,4-dioxane (5mL) in a sealed tube. This was followed by the addition of 3-bromo-4- (trifluoromethyl)pyridine (134mg, 0.5903mmol) and the resulting reaction mass was heated at 120°C for 48 hours. The reaction was monitored by TLC (50% ethyl acetate in hexane). The reaction mass was partitioned between water and ethylacetate. The organic layer was washed with water, brine solution, dried over Na2S04 and concentrated to afford the crude product. Purification by column chromatography on silica gel (30% ethyl acetate in hexane), followed by preparative HPLC afforded 14mg of the product (8.18% yield).1H NMR (400 MHz, CDC13): δ 8.85 (d, 1H), 8.78 (s, 1H), 8.6 (d, 1H), 7.85 (d, 1H), 7.7 (d, 1H), 7.50-7.38 (m, 2H), 4.2-4.1 (m, 1H), 3.92-3.86 (m, 1H), 3.58-3.45 (m, 1H), 3.3-3.2 (m, 1H). LCMS: 98.93%, m/z = 348.7 (M+l). HPLC: 95.59%
8.18% Stage #1: 3,4-dihydro-2H-benzo[4,5]thieno[3,2-c]pyridin-1-one With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos In 1,4-dioxane Sealed tube; Stage #2: 3-bromo-4-(trifluoromethyl)pyridine In 1,4-dioxane at 120℃; for 48h; 58 Preparation of 2-(4-trifluoromethylpyridine-3-yl)-3,4-dihydro-2H-benzo[4,5]thieno[3,2-c]pyridin-1-one (58A) Example 58 Preparation of 2-(4-trifluoromethylpyridine-3-yl)-3,4-dihydro-2H-benzo[4,5]thieno[3,2-c]pyridin-1-one (58A) X-Phos (35 mg, 0.0739 mmol) and Pd2(dba)3 (45 mg, 0.0492 mmol) were added to a previously degassed solution of 3,4-dihydro-2H-benzo[4,5]thieno[3,2-c]pyridin-1-one (I-9d: 100 mg, 0.4919 mmol), K3PO4 (313 mg, 1.4759 mmol) and 1,4-dioxane (5 mL) in a sealed tube. This was followed by the addition of 3-bromo-4-(trifluoromethyl)pyridine (134 mg, 0.5903 mmol) and the resulting reaction mass was heated at 120° C. for 48 hours. The reaction was monitored by TLC (50% ethyl acetate in hexane). The reaction mass was partitioned between water and ethylacetate. The organic layer was washed with water, brine solution, dried over Na2SO4 and concentrated to afford the crude product. Purification by column chromatography on silica gel (30% ethyl acetate in hexane), followed by preparative HPLC afforded 14 mg of the product (8.18% yield). 1H NMR (400 MHz, CDCl3): δ 8.85 (d, 1H), 8.78 (s, 1H), 8.6 (d, 1H), 7.85 (d, 1H), 7.7 (d, 1H), 7.50-7.38 (m, 2H), 4.2-4.1 (m, 1H), 3.92-3.86 (m, 1H), 3.58-3.45 (m, 1H), 3.3-3.2 (m, 1H). LCMS: 98.93%, m/z=348.7 (M+1). HPLC: 95.59%
  • 3
  • [ 936841-70-2 ]
  • [ 1082041-78-8 ]
  • [ 1365763-02-5 ]
YieldReaction ConditionsOperation in experiment
15.7% With trans-N,N'-dimethyl-1,2-cyclohexyldiamine; potassium phosphate; copper(l) iodide; In 1,4-dioxane; at 120℃; for 48.0h; 6-MethyI-3 -dihydroisoquinoliB~l(2H)~one (I-69d: SOOmg, 3.1 mmol) was reacted with 3~bromo-4-(trifluoromethyl)^yrid:ine (842rng, 3.72mmol), 1 ,4-dioxane (20mL), copper iodide (S9mg, OJ lm oi), . r^m'-N^N'-dimethyl-cyclbhexyl- 1 ,2- diaraine (44mg, 0.31mmo ) and potassium phosphate (1 ,64g5 7.76inmoi) 2 days ai 120C to afford the crude product. Purification by column chromatography on silica gel (2% methanol in CHCI3) afforded 150 mg of the product (15.7% yield),
15.7% With trans-N,N'-dimethyl-1,2-cyclohexyldiamine; potassium phosphate; copper(l) iodide; In 1,4-dioxane; at 120℃; for 48.0h; Example 71 Preparation of 6-methyl-2-(4-(trifluoromethyl)pyridin-3-yl)-3,4-dihydroisoquinolin-1(2H)-one (71A) 6-Methyl-3,4-dihydroisoquinolin-1(2H)-one (I-69d: 500 mg, 3.1 mmol) was reacted with 3-bromo-4-trifluoromethyl)-pyridine (842 mg, 3.72 mmol), 1,4-dioxane (20 mL), copper iodide (59 mg, 0.31 mmol), trans-N,N'-dimethyl-cyclohexyl-1,2-diamine (44 mg, 0.31 mmol and potassium phosphate (1.64 g, 7.76 mmol) 2 days at 120 C. to afford the crude product. Purification by column chromatography on silica gel (2% methanol in CHCl3) afforded 150 mg of the product (15.7% yield).
  • 4
  • [ 936841-70-2 ]
  • [ 1383618-53-8 ]
  • [ 1383618-56-1 ]
YieldReaction ConditionsOperation in experiment
25% With sodium carbonate In water; isopropyl alcohol at 80℃; for 16h; 76 Example 762,2-dimethyl-/V-[2-methyl-5-[6-[4-(trifluoromyllphenyllpropanamideAn 8 mL vial is charged with A/-[5-(6-chloroimidazo[2, 1- ]pyridazin-2-yl)-2-methyl-phenyl]-2,2- dimethyl-propanamide (0.034 g, 0.1 mmol), [4-(trifluoromethyl)-3-pyridyl]boronic acid (0.038 g), bis(triphenylphosphine)palladium(ll) dichloride (7 mg), Na2C03 (0.032 g), andisopropanol-water (1 mL, 3:1 ). The mixture is heated at 80 °C for 16 hr, cooled, concentrated, taken up in 1 :1 EtOAc and CH2CI2, filtered, concentrated onto celite and purified by silica gel chromatography (10-100% EtOAc in Hexanes) to give the title compound (0.01 1 g, 25% yield). LCMS m/z = 454.5 [M+H]+, tR = 2.47 min. (compound same as Example 364)
  • 5
  • [ 936841-70-2 ]
  • [ 68-12-2 ]
  • [ 1083197-78-7 ]
YieldReaction ConditionsOperation in experiment
n-Butyl lithium (1.65 mL, 0.00265 mol, 1.6 M) was added to a solution of 3- bromo-4-(trifluoromethyl)pyridine (E; 0.5 g, 0.022 mol) in anhydrous tetrahydrofuran (15 mL), at -78 C. The reaction mixture was stirred for 10 min followed by the addition of dimethlformamide (0.2 mL, 0.00265). It was stirred for 30 min at same temperature. The reaction mixture was quenched with a saturated aqueous ammonium chloride solution (25 mL) and the aqueous layer was extracted with ethyl acetate (2 x 50 mL). The organic extracts were combined and then washed with a saturated aqueous sodium chloride solution (1 x 50 mL), dried over sodiumsulphate and concentrated to afford 4- (trifluoromethyl)nicotinaldehyde. 1H NMR (400 MHz, DMSO- ¾) delta 10.39 (s, 1 H), 9.25 (s, 1 H), 9.10-9.09 (d, J= 4 Hz, 1 H), 7.95-7.94 (d, J= 4 Hz, 1 H).
  • 6
  • [ 936841-70-2 ]
  • tert-butyl 2-methyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate [ No CAS ]
  • tert-butyl 2-methyl-3-oxo-4-(4-(trifluoromethyl)pyridin-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
41% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 110℃; Inert atmosphere; 3S Intermediate 3S: tert-butyl 2-methyl-3-oxo-4-(4-(trifluoromethyl)pyridi n-3-yI)-1 - oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate Intermediate 3S: tert-butyl 2-methyl-3-oxo-4-(4-(trifluoromethyl)pyridi n-3-yI)-1 - oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate A mixture of intermediate 3H (1.00 g, 3.52 mmol), Cs2CO3 (1.49 g, 7.74 mmol),tris(dibenzylideneacetone)dipalladium(0) (161 mg, 0.176 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (173 mg, 0.299 mmol) and 3-bromo-4-(trifluoromethyl)pyridine (0.954 g, 4.22 mmol) in dry 1,4-dioxane (28 mL) was heated under an argon atmosphere at 110 00 overnight. After cooling the solids were filtered off and the reaction mixture was concentrated to dryness. Additional Cs2003 (1.49 g,7.74 mmol), tris(dibenzylideneacetone)dipalladium(0) (161 mg, 0.176 mmol), 4,5- bis(diphenylphosphino)-9,9-dimethylxanthene (173 mg, 0.299 mmol), 3-bromo-4-(trifluoromethyl)pyridine (0.397 g, 1.76 mmol) and dry 1,4-dioxane (28 mL) were added. After stirring an additional day at 110 00 under an argon atmosphere, the solids were filtered off and the solvent evaporated to dryness. Again, additional Cs2003 (1.49 g, 7.74 mmol), tris(dibenzylideneacetone)dipalladium(0) (161 mg, 0.176 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (173 mg, 0.299 mmol), 3-bromo-4-(trifluoromethyl)pyridine (0.410 g, 1.81 mmol) and dry 1,4-dioxane (28 mL) were added. The mixture was stirred at 110 00 overnight. The solids were filtered off, and the reaction mixture concentrated under vacuum. The residue was purified by flash chromatography, silica gel, gradient dichloromethane to methanol:dichloromethane (1:4) to give the title compound (627 mg, 41% yield).HPLC retention time: 4.25 mm; MS: 374 (M+H-56).
627 mg With caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; bis(dibenzylideneacetone)-palladium(0) In 1,4-dioxane at 110℃; for 72h; Schlenk technique; Inert atmosphere;
  • 7
  • [ 936841-70-2 ]
  • [ 536-74-3 ]
  • 3-(phenylethynyl)-4-(trifluoromethyl)pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 20℃; 8 4.2 General procedure I (for the preparation of 9a-c) General procedure: To a stirred solution of compound 8 (1.0 eq.) in deoxygenated DMF (1M) was added CuI (0.05 eq.), Et3N (4.0 eq.), alkyne (1.2 eq.) and Pd(PPh3)2Cl2 (0.05 eq.), the resulting mixture was stirred at r. t. overnight. After filtration through Celite, the organic layer was diluted with H2O and extracted with DCM. The combined organic phase was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to afford the crude product, which was purified by flash column chromatography using PE/EA (50:1-10:1) as eluent.
  • 8
  • [ 936841-70-2 ]
  • (2R,3R,4R,5S)-3,4,5-tris(benzyloxy)-2-methyl-1-((S)-pyrrolidin-3-ylmethyl)piperidine [ No CAS ]
  • 4-(trifluoromethyl)-3-((R)-3-(((2R,3R,4R,5S)-3,4,5-tris(benzyloxy)-2-methylpiperidin-1-yl)methyl)pyrrolidin-1-yl)pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
48% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; ruphos In toluene at 100℃; for 18h; Inert atmosphere; 124 (2R,3R,4R,5S)-2-methyl-1-(((R)-1-(4-(trifluoromethyl)pyridin-3-yl)pyrrolidin-3- yl)methyl)piperidine-3,4,5-triol To a solution of (2R,3R,4R,5S)-3,4,5-tris(benzyloxy)-2-methyl-1-((S)-pyrrolidin-3- ylmethyl)piperidine (120 mg, 0.24 mmol) and 3-bromo-4-(trifluoromethyl)pyridine (108 mg, 0.48 mmol) in toluene (5 mL) was added Pd2(dba)3 (46 mg, 0.050 mmol) and RuPhos (46 mg, 0.10 mmol), followed with Cs2CO3 (326 mg, 1.0 mmol) under Ar. The mixture was stirred at 100 °C for 18 h, and then H2O was added at 0 °C. The mixture was extracted with EtOAc (2 × 20 mL). The combined organic layer was washed with H2O (2 × 10 mL), separated, and dried over Na2SO4. After filtration the solvent was evaporated under reduced pressure, and the residue was purified on silica gel by flash chromatography affording 4- (trifluoromethyl)-3-((R)-3-(((2R,3R,4R,5S)-3,4,5-tris(benzyloxy)-2-methylpiperidin-1- yl)methyl)pyrrolidin-1-yl)pyridine as an oil (75 mg, 48%). ESI MS m/z 646.31 [M + H]+.
  • 9
  • [ 936841-70-2 ]
  • (2R,3R,4R,5S)-3,4,5-tris(benzyloxy)-2-methyl-1-((S)-piperidin-3-ylmethyl)piperidine [ No CAS ]
  • 4-(trifluoromethyl)-3-((R)-3-(((2R,3R,4R,5S)-3,4,5-tris(benzyloxy)-2-methylpiperidin-1-yl)methyl)piperidin-1-yl)pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
52% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; ruphos In toluene at 85℃; for 18h; Inert atmosphere; Sealed tube; 140 (2R,3R,4R,5S)-2-methyl-1-(((R)-1-(4-(trifluoromethyl)pyridin-3-yl)piperidin-3- yl)methyl)piperidine-3,4,5-triol Under Ar, to a mixture of (2R,3R,4R,5S)-3,4,5-tris(benzyloxy)-2-methyl-1-((S)- piperidin-3-ylmethyl)piperidine (120 mg, 0.23 mmol), 3-bromo-4-(trifluoromethyl)pyridine (108.7 mg, 0.48 mmol), Cs2CO3 (303 mg, 0.93 mmol) and RuPhos (22 mg, 0.05 mmol) in anhydrous and degassed toluene (5 mL) was added Pd2dba3 (21 mg, 0.023 mmol). The mixture was stirred at 85 °C in a sealed tube for 18 h, then cooled to RT. Et2O (50 mL) was added, and the resulting precipitate was filtered off. The filtrate was concentrated under reduced pressure, and the residue was purified on silica gel by flash chromatography using 15% EtOAc in hexanes, affording 4-(trifluoromethyl)-3-((R)-3-(((2R,3R,4R,5S)-3,4,5- tris(benzyloxy)-2-methylpiperidin-1-yl)methyl)piperidin-1-yl)pyridine as a oil (80 mg, 52%).
  • 10
  • [ 936841-70-2 ]
  • (2R,3R,4R,5S)-3,4,5-tris(benzyloxy)-2-methyl-1-((R)-piperidin-3-ylmethyl)piperidine [ No CAS ]
  • 4-(trifluoromethyl)-3-((S)-3-(((2R,3R,4R,5S)-3,4,5-tris(benzyloxy)-2-methylpiperidin-1-yl)methyl)piperidin-1-yl)pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
41% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; ruphos In toluene at 100℃; for 18h; Inert atmosphere; 142 (2R,3R,4R,5S)-2-methyl-1-(((S)-1-(4-(trifluoromethyl)pyridin-3-yl)piperidin-3- yl)methyl)piperidine-3,4,5-triol To a stirred solution of (2R,3R,4R,5S)-3,4,5-tris(benzyloxy)-2-methyl-1-((R)- piperidin-3-ylmethyl)piperidine (0.15 g, 0.29 mmol) and 3-bromo-4- (trifluoromethyl)pyridine (0.13 g, 0.6 mmol) in toluene (5 mL) was added Pd2(dba)3 (28 mg, 0.03 mmol) and RuPhos (28 mg, 0.06 mmol), followed by Cs2CO3 (0.3 g, 0.9 mmol) under Ar. The mixture was stirred at 100 °C for 18 h, and then water was added at 0 °C. The mixture was extracted with EtOAc (2 × 20 mL). The combined organic layer was washed with water (2 × 20 mL), separated, then dried over Na2SO4. After filtration the solvent was evaporated under reduced pressure, and the residue was purified on silica gel by flash chromatography (EtOAc/hexanes, 1:1) affording 4-(trifluoromethyl)-3-((S)-3- (((2R,3R,4R,5S)-3,4,5-tris(benzyloxy)-2-methylpiperidin-1-yl)methyl)piperidin-1-yl)pyridine as an oil (0.08 g, 41%). 1H NMR (500 MHz, CDCl3) d 8.62 (s, 1H), 8.48 (d, J = 5.0 Hz, 1H), 7.47 (d, J = 5.1 Hz, 1H), 7.37-7.26 (m, 15H), 4.98 (d, J = 11.0 Hz, 1H), 4.95 (d, J = 10.8 Hz, 1H), 4.84 (d, J = 11.0 Hz, 1H), 4.73 (d, J = 11.6 Hz, 1H), 4.66-4.60 (m, 2H), 3.57 (td, J = 9.8, 4.6 Hz, 1H), 3.50 (t, J = 9.0 Hz, 1H), 3.17 (dd, J = 11.1, 3.4 Hz, 1H), 3.12-3.04 (m, 2H), 2.98 (dd, J = 11.5, 4.7 Hz, 1H), 2.87 (t, J = 9.8 Hz, 1H), 2.70 (dd, J = 13.0, 8.3 Hz, 1H), 2.57-2.47 (m, 1H), 2.27 (dq, J = 11.9, 6.2 Hz, 1H), 2.10-1.98 (m, 2H), 1.84 (dt, J = 8.8, 4.6 Hz, 1H), 1.80-1.73 (m, 2H), 1.66 (qd, J = 11.7, 10.4, 4.8 Hz, 1H), 1.20 (d, J = 6.1 Hz, 3H), 1.16-1.07 (m, 1H); ESI MS m/z 660.338 [M + H]+.
  • 11
  • [ 936841-70-2 ]
  • 8-(N,N-dimethylamino)-3,4-dihydrobenzo[f][1,4]oxazepine-5(2H)-one [ No CAS ]
  • 8-(N,N-dimethylamino)-4-(4-trifluoromethyl-3-pyridyl)-3,4-dihydrobenzo[f][1,4]oxazepine-5(2H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
23.6% With copper(l) iodide; N,N,N,N,-tetramethylethylenediamine; potassium carbonate In 1,4-dioxane at 120℃; for 16h; General Method A General procedure: A mixture of the corresponding substituted 3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one (22 mmol), corresponding bromopyridine (22 mmol), K2CO3 (18.2 g, 132 mmol), CuI (2.08 g, 11 mmol), and N,N-dimethyl-1,2-ethanediamine (1.37 g, 15.4 mmol) in dioxane (60 mL) was stirred at 120 °C for 16 h. After the reaction mixture was cooled down to room temperature, it was filtrated and concentrated to give the crude product, which was subsequently purified by column chromatography (petroleum ether/ethyl acetate) to yield the desired product.
  • 12
  • [ 936841-70-2 ]
  • (2R,3R,4R,5S)-3,4,5-tris(benzyloxy)-2-methyl-1-((S)-pyrrolidin-3-ylmethyl)piperidine [ No CAS ]
  • 4-(trifluoromethyl)-3-((R)-3-(((3S,4R,5R)-3,4,5-tris(benzyloxy)piperidin-1-yl)methyl)pyrrolidin-1-yl)pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
59% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; ruphos In toluene at 90℃; for 18h; Inert atmosphere; 20 [00154] To a stirred solution of (2R,3R,4R,5S)-3,4,5-tris(benzyloxy)-2-methyl-1-((S)-pyrrolidin-3-ylmethyl)piperidine (150 mg, 0.31 mmol) and 3-bromo-4-(trifluoromethyl)pyridine (139 mg, 0.62 mmol) in toluene (5 mL) was added Pd2(dba)3 (28 mg, 0.031 mmol) and RuPhos (29 mg, 0.062 mmol), followed by Cs2CO3 (304 mg, 1.24 mmol) under Ar. The mixture was stirred at 90 °C for 18 h, and then water was added at 0 °C. The mixture was extracted with EtOAc (2 × 20 mL). The combined organic layer was washed with water (2 × 10 mL), separated, and dried over Na2SO4. After filtration the solvent was evaporated under reduced pressure, and the residue was purified on silica gel by flash chromatography affording 4-(trifluoromethyl)-3-((R)-3-(((3S,4R,5R)-3,4,5-tris(benzyloxy)piperidin-1-yl)methyl)pyrrolidin-1-yl)pyridine as an oil (115 mg, 59%). ESI MS m/z [M + H]+ 632.31.
59% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; ruphos In toluene at 90℃; for 18h; Inert atmosphere; 20 [00154] To a stirred solution of (2R,3R,4R,5S)-3,4,5-tris(benzyloxy)-2-methyl-1-((S)-pyrrolidin-3-ylmethyl)piperidine (150 mg, 0.31 mmol) and 3-bromo-4-(trifluoromethyl)pyridine (139 mg, 0.62 mmol) in toluene (5 mL) was added Pd2(dba)3 (28 mg, 0.031 mmol) and RuPhos (29 mg, 0.062 mmol), followed by Cs2CO3 (304 mg, 1.24 mmol) under Ar. The mixture was stirred at 90 °C for 18 h, and then water was added at 0 °C. The mixture was extracted with EtOAc (2 × 20 mL). The combined organic layer was washed with water (2 × 10 mL), separated, and dried over Na2SO4. After filtration the solvent was evaporated under reduced pressure, and the residue was purified on silica gel by flash chromatography affording 4-(trifluoromethyl)-3-((R)-3-(((3S,4R,5R)-3,4,5-tris(benzyloxy)piperidin-1-yl)methyl)pyrrolidin-1-yl)pyridine as an oil (115 mg, 59%). ESI MS m/z [M + H]+ 632.31.
59% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; ruphos In toluene at 90℃; for 18h; Inert atmosphere; 20 [00154] To a stirred solution of (2R,3R,4R,5S)-3,4,5-tris(benzyloxy)-2-methyl-1-((S)-pyrrolidin-3-ylmethyl)piperidine (150 mg, 0.31 mmol) and 3-bromo-4-(trifluoromethyl)pyridine (139 mg, 0.62 mmol) in toluene (5 mL) was added Pd2(dba)3 (28 mg, 0.031 mmol) and RuPhos (29 mg, 0.062 mmol), followed by Cs2CO3 (304 mg, 1.24 mmol) under Ar. The mixture was stirred at 90 °C for 18 h, and then water was added at 0 °C. The mixture was extracted with EtOAc (2 × 20 mL). The combined organic layer was washed with water (2 × 10 mL), separated, and dried over Na2SO4. After filtration the solvent was evaporated under reduced pressure, and the residue was purified on silica gel by flash chromatography affording 4-(trifluoromethyl)-3-((R)-3-(((3S,4R,5R)-3,4,5-tris(benzyloxy)piperidin-1-yl)methyl)pyrrolidin-1-yl)pyridine as an oil (115 mg, 59%). ESI MS m/z [M + H]+ 632.31.
  • 13
  • [ 936841-70-2 ]
  • (3S,4R,5R)-3,4,5-tris(benzyloxy)-1-((R)-pyrrolidin-3-ylmethyl)piperidine [ No CAS ]
  • 4-(trifluoromethyl)-3-((S)-3-(((3S,4S,5R)-3,4,5-tris(benzyloxy)piperidin-1-yl)methyl)pyrrolidin-1-yl)pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; ruphos In toluene at 100℃; for 16h; Inert atmosphere; Sealed tube; 25 [00166] A mixture of (3S,4R,5R)-3,4,5-tris(benzyloxy)-1-((R)-pyrrolidin-3-ylmethyl)piperidine (0.14 g, 0.28 mmol), 3-bromo-4-(trifluoromethyl)pyridine (0.11 g, 0.50 mmol), Cs2CO3 (0.26 g, 0.80 mmol), RuPhos (0.026 g, 0.056 mmol) and Pd2(dba)3 (0.026 g, 0.028 mmol) in anhydrous toluene (6 mL) was bubbled with Ar for 10 min, and then stirred in a sealed tube at 100 °C for 16 h. After cooling the reaction mixture was filtered through a celite cake. The filtrate was concentrated under reduced pressure, and the residue was purified on silica gel by flash chromatography (EtOAc/hexanes, 1:2 to 1:1), affording 4-(trifluoromethyl)-3-((S)-3-(((3S,4S,5R)-3,4,5-tris(benzyloxy)piperidin-1-yl)methyl)pyrrolidin-1-yl)pyridine as a pale-yellow oil (0.15 g, 85%). ESI MS m/z 632.315 [M + H]+.
85% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; ruphos In toluene at 100℃; for 16h; Inert atmosphere; Sealed tube; 25 [00166] A mixture of (3S,4R,5R)-3,4,5-tris(benzyloxy)-1-((R)-pyrrolidin-3-ylmethyl)piperidine (0.14 g, 0.28 mmol), 3-bromo-4-(trifluoromethyl)pyridine (0.11 g, 0.50 mmol), Cs2CO3 (0.26 g, 0.80 mmol), RuPhos (0.026 g, 0.056 mmol) and Pd2(dba)3 (0.026 g, 0.028 mmol) in anhydrous toluene (6 mL) was bubbled with Ar for 10 min, and then stirred in a sealed tube at 100 °C for 16 h. After cooling the reaction mixture was filtered through a celite cake. The filtrate was concentrated under reduced pressure, and the residue was purified on silica gel by flash chromatography (EtOAc/hexanes, 1:2 to 1:1), affording 4-(trifluoromethyl)-3-((S)-3-(((3S,4S,5R)-3,4,5-tris(benzyloxy)piperidin-1-yl)methyl)pyrrolidin-1-yl)pyridine as a pale-yellow oil (0.15 g, 85%). ESI MS m/z 632.315 [M + H]+.
85% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; ruphos In toluene at 100℃; for 16h; Inert atmosphere; Sealed tube; 25 [00166] A mixture of (3S,4R,5R)-3,4,5-tris(benzyloxy)-1-((R)-pyrrolidin-3-ylmethyl)piperidine (0.14 g, 0.28 mmol), 3-bromo-4-(trifluoromethyl)pyridine (0.11 g, 0.50 mmol), Cs2CO3 (0.26 g, 0.80 mmol), RuPhos (0.026 g, 0.056 mmol) and Pd2(dba)3 (0.026 g, 0.028 mmol) in anhydrous toluene (6 mL) was bubbled with Ar for 10 min, and then stirred in a sealed tube at 100 °C for 16 h. After cooling the reaction mixture was filtered through a celite cake. The filtrate was concentrated under reduced pressure, and the residue was purified on silica gel by flash chromatography (EtOAc/hexanes, 1:2 to 1:1), affording 4-(trifluoromethyl)-3-((S)-3-(((3S,4S,5R)-3,4,5-tris(benzyloxy)piperidin-1-yl)methyl)pyrrolidin-1-yl)pyridine as a pale-yellow oil (0.15 g, 85%). ESI MS m/z 632.315 [M + H]+.
  • 14
  • [ 936841-70-2 ]
  • (3S,4S,5R)-3,4,5-tris(benzyloxy)-1-((S)-piperidin-3-ylmethyl)piperidine [ No CAS ]
  • 4-(trifluoromethyl)-3-((R)-3-(((3S,4R,5R)-3,4,5-tris(benzyloxy)piperidin-1-yl)methyl)piperidin-1-yl)pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
41% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; ruphos In toluene at 100℃; for 16h; Sealed tube; Inert atmosphere; 167 [00217] A mixture of the above material (0.200 g, 0.400 mmol), 3-bromo-4-(trifluoromethyl)pyridine (0.12 g, 0.53 mmol), RuPhos (0.035 g, 0.075 mmol), Cs2CO3 (0.30 g, 0.92 mmol) and Pd2(dba)3 (0.035 g, 0.038 mmol) in anhydrous toluene (8 mL) in a sealed tube was bubbled with Ar for 10 min, and then stirred at 100 °C for 16 h. The reaction mixture was cooled to RT and filtered through a Celite cake. The filtrate was concentrated, and the residue was purified on silica gel by flash chromatography (EtOAc/hexanes, 1:3 to 1:2), affording 4-(trifluoromethyl)-3-((R)-3-(((3S,4R,5R)-3,4,5-tris(benzyloxy)piperidin-1-yl)methyl)piperidin-1-yl)pyridine as a pale-yellow oil (0.105 g, 41%); ESI MS m/z 646.325 [M + H]+.
41% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; ruphos In toluene at 100℃; for 16h; Sealed tube; Inert atmosphere; 167 [00217] A mixture of the above material (0.200 g, 0.400 mmol), 3-bromo-4-(trifluoromethyl)pyridine (0.12 g, 0.53 mmol), RuPhos (0.035 g, 0.075 mmol), Cs2CO3 (0.30 g, 0.92 mmol) and Pd2(dba)3 (0.035 g, 0.038 mmol) in anhydrous toluene (8 mL) in a sealed tube was bubbled with Ar for 10 min, and then stirred at 100 °C for 16 h. The reaction mixture was cooled to RT and filtered through a Celite cake. The filtrate was concentrated, and the residue was purified on silica gel by flash chromatography (EtOAc/hexanes, 1:3 to 1:2), affording 4-(trifluoromethyl)-3-((R)-3-(((3S,4R,5R)-3,4,5-tris(benzyloxy)piperidin-1-yl)methyl)piperidin-1-yl)pyridine as a pale-yellow oil (0.105 g, 41%); ESI MS m/z 646.325 [M + H]+.
41% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; ruphos In toluene at 100℃; for 16h; Sealed tube; Inert atmosphere; 167 [00217] A mixture of the above material (0.200 g, 0.400 mmol), 3-bromo-4-(trifluoromethyl)pyridine (0.12 g, 0.53 mmol), RuPhos (0.035 g, 0.075 mmol), Cs2CO3 (0.30 g, 0.92 mmol) and Pd2(dba)3 (0.035 g, 0.038 mmol) in anhydrous toluene (8 mL) in a sealed tube was bubbled with Ar for 10 min, and then stirred at 100 °C for 16 h. The reaction mixture was cooled to RT and filtered through a Celite cake. The filtrate was concentrated, and the residue was purified on silica gel by flash chromatography (EtOAc/hexanes, 1:3 to 1:2), affording 4-(trifluoromethyl)-3-((R)-3-(((3S,4R,5R)-3,4,5-tris(benzyloxy)piperidin-1-yl)methyl)piperidin-1-yl)pyridine as a pale-yellow oil (0.105 g, 41%); ESI MS m/z 646.325 [M + H]+.
  • 15
  • [ 936841-70-2 ]
  • (3S,4R,5R)-3,4,5-tris(benzyloxy)-1-((R)-piperidin-3-ylmethyl)piperidine [ No CAS ]
  • 4-(trifluoromethyl)-3-((S)-3-(((3S,4S,5R)-3,4,5-tris(benzyloxy)piperidin-1-yl)methyl)piperidin-1-yl)pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
35% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; ruphos In toluene at 100℃; for 16h; Inert atmosphere; Sealed tube; 38 [00195] A mixture of (3S,4R,5R)-3,4,5-tris(benzyloxy)-1-((R)-piperidin-3-ylmethyl)piperidine (0.22 g, 0.44 mmol), 3-bromo-4-(trifluoromethyl)pyridine (0.12 g, 0.53 mmol), Cs2CO3 (0.30 g, 0.92 mmol), RuPhos (0.035 g, 0.075 mmol) and Pd2(dba)3 (0.035 g, 0.038 mmol) in anhydrous toluene (8 mL) was bubbled with Ar for 10 min, and then stirred in a sealed tube at 100 °C for 16 h. After cooling the reaction mixture was filtered through a celite cake. The filtrate was concentrated under reduced pressure, and the residue was purified on silica gel by flash chromatography (EtOAc/hexanes, 1:2 to 1:1), affording 4-(trifluoromethyl)-3-((S)-3-(((3S,4S,5R)-3,4,5-tris(benzyloxy)piperidin-1-yl)methyl)piperidin-1-yl)pyridine as a pale-yellow oil (0.10 g, 35%).
35% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; ruphos In toluene at 100℃; for 16h; Inert atmosphere; Sealed tube; 38 [00195] A mixture of (3S,4R,5R)-3,4,5-tris(benzyloxy)-1-((R)-piperidin-3-ylmethyl)piperidine (0.22 g, 0.44 mmol), 3-bromo-4-(trifluoromethyl)pyridine (0.12 g, 0.53 mmol), Cs2CO3 (0.30 g, 0.92 mmol), RuPhos (0.035 g, 0.075 mmol) and Pd2(dba)3 (0.035 g, 0.038 mmol) in anhydrous toluene (8 mL) was bubbled with Ar for 10 min, and then stirred in a sealed tube at 100 °C for 16 h. After cooling the reaction mixture was filtered through a celite cake. The filtrate was concentrated under reduced pressure, and the residue was purified on silica gel by flash chromatography (EtOAc/hexanes, 1:2 to 1:1), affording 4-(trifluoromethyl)-3-((S)-3-(((3S,4S,5R)-3,4,5-tris(benzyloxy)piperidin-1-yl)methyl)piperidin-1-yl)pyridine as a pale-yellow oil (0.10 g, 35%).
35% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; ruphos In toluene at 100℃; for 16h; Inert atmosphere; Sealed tube; 38 [00195] A mixture of (3S,4R,5R)-3,4,5-tris(benzyloxy)-1-((R)-piperidin-3-ylmethyl)piperidine (0.22 g, 0.44 mmol), 3-bromo-4-(trifluoromethyl)pyridine (0.12 g, 0.53 mmol), Cs2CO3 (0.30 g, 0.92 mmol), RuPhos (0.035 g, 0.075 mmol) and Pd2(dba)3 (0.035 g, 0.038 mmol) in anhydrous toluene (8 mL) was bubbled with Ar for 10 min, and then stirred in a sealed tube at 100 °C for 16 h. After cooling the reaction mixture was filtered through a celite cake. The filtrate was concentrated under reduced pressure, and the residue was purified on silica gel by flash chromatography (EtOAc/hexanes, 1:2 to 1:1), affording 4-(trifluoromethyl)-3-((S)-3-(((3S,4S,5R)-3,4,5-tris(benzyloxy)piperidin-1-yl)methyl)piperidin-1-yl)pyridine as a pale-yellow oil (0.10 g, 35%).
  • 16
  • [ 936841-70-2 ]
  • rac-(1S)-1-[1-(2,2-dimethylpropyl)-5-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indol-3-yl]-2,2,2-trifluoroethanamine [ No CAS ]
  • 2,2,2-trifluoro-1-(5-fluoro-1-neopentyl-6-(4-(trifluoromethyl)pyridin-3-yl)-1H-indol-3-yl)ethan-1-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
94.97% With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; potassium carbonate In 1,4-dioxane; water monomer at 85℃; for 5h; Inert atmosphere; 530.1 Step 1: (S)-2,2,2-trifluoro-1-(5-fluoro-1-neopentyl-6-(4- (trifluoromethyl)pyridin-3-yl)-1H-indol-3-yl)ethan-1-amine A mixture of rac-(1S)-1-[1-(2,2-dimethylpropyl)-5-fluoro-6-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)indol-3-yl]-2,2,2-trifluoro-ethanamine (360 mg, 588.41 μmol) and 3-bromo-4-(trifluoromethyl)pyridine (172.87 mg, 764.94 μmol) in dioxane (10 mL) and H2O (2 mL) was added Pd(dppf)Cl2 (43.07 mg, 58.84 μmol) and K2CO3 (162.40 mg, 1.18 mmol) . The mixture was purged by N2 for 10 seconds. The mixture was stirred at 85 °C for 5 hours. The mixture was combined with crude material from a previous test reaction using the same condition. The product was purified by chromatograph silica on gel (EA:PE, 0%~60%, UV=254 nm). rac-(1S)-1-[1-(2,2-Dimethylpropyl)-5-fluoro-6-[4- (trifluoromethyl)-3-pyridyl]indol-3-yl]-2,2,2-trifluoro-ethanamine (250 mg, 558.79 μmol, 94.97% yield) as a yellow gum was obtained.
  • 17
  • [ 936841-70-2 ]
  • [ 6783-05-7 ]
  • (E)-3-styryl-4-(trifluoromethyl)pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
96% With dicyclohexyl({2’,6’-dimethoxy-[1,1‘-biphenyl]-2-yl})phosphane; tripotassium phosphate tribasic; palladium diacetate In toluene at 90℃; Schlenk technique; Sealed tube; Glovebox;
Historical Records

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