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Chemical Structure| 33016-47-6 Chemical Structure| 33016-47-6
Chemical Structure| 33016-47-6

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1-Trityl-1H-imidazole-4-carbaldehyde is a compound containing an imidazole ring, used as an intermediate in the synthesis of other drug molecules.

Synonyms: 4-Formyl-1-tritylimidazole

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Product Details of 1-Trityl-1H-imidazole-4-carbaldehyde

CAS No. :33016-47-6
Formula : C23H18N2O
M.W : 338.40
SMILES Code : C1=C(N=C[N]1C(C2=CC=CC=C2)(C3=CC=CC=C3)C4=CC=CC=C4)C=O
Synonyms :
4-Formyl-1-tritylimidazole
MDL No. :MFCD02179554
InChI Key :YQYLLBSWWRWWAY-UHFFFAOYSA-N
Pubchem ID :618233

Safety of 1-Trityl-1H-imidazole-4-carbaldehyde

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

Application In Synthesis of 1-Trityl-1H-imidazole-4-carbaldehyde

* 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 [ 33016-47-6 ]

[ 33016-47-6 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 96797-15-8 ]
  • [ 68-12-2 ]
  • [ 15469-97-3 ]
  • 4-iodo-2-formyl-1-tritylimidazole [ No CAS ]
  • [ 67478-50-6 ]
  • [ 33016-47-6 ]
  • 2
  • [ 146293-11-0 ]
  • [ 33016-47-6 ]
  • tert-butyl 4-[(Z)-2-(1-trityl-1H-imidazol-4-yl)vinyl]piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
51% With potassium tert-butylate; In tetrahydrofuran; for 12.0h; Potassium tert-butoxide (0.21 g) was added to a solution of 1-trityl-1H-imidazole-4-carbaldehyde (Kelly, J. L. et al., J. Med. Chem., 20, 721 (1977)) (0.63 g) and <strong>[146293-11-0](1-tert-butoxycarbonyl-4-piperidinyl)methyl(triphenyl)phosphonium iodide</strong> (WO 99/24421)(1.0 g) in THF (35 mL). After stirred for 12 hours, the reaction solution was poured into a mixture of ethyl acetate and an aqueous saturated ammonium chloride solution to separate an organic layer. The ethyl acetate solution was dried over anhydrous sodium sulfate and the solvent was distilled off. The residue was purified with a silica gel column to obtain the title compound (0.45 g, 51%). NMR (200 MHz, CDCl3) delta: 1.20-1.36 (2H, m), 1.45 (9H, s), 1.64-1.69 (2H, m), 2.67 (2H, t, J = 12.2), 3.05 (1H, m), 4.01 (2H, d, J = 12.8), 5.32 (1H, dd, J = 9.0, 11.6), 6.16 (1H, d, J = 11.6), 6.69 (1H, s), 7.10-7.20 (6H, m), 7.30-7.36 (9H, m), 7.43 (1H, s).
  • 3
  • [ 426219-35-4 ]
  • [ 33016-47-6 ]
  • [ 566200-96-2 ]
YieldReaction ConditionsOperation in experiment
74% Example 1Under a nitrogen atmosphere, 6-bromo-N-methyl-2- naphthamide (7.0 g, 26.5 mmol) was added to tetrahydrofuran (175 mL) , and then 2.0 mol/L isopropylmagnesium chloridetetrahydrofuran solution (13.7 mL) was added dropwise thereto at room temperature. The reaction mixture was cooled to -30C, 1.6 mol/L n-butyllithium hexane solution (26.6 mL) was added dropwise thereto, and the mixture, was stirred at the same temperature for 2 hr. To the reaction mixture was addeddropwise a solution of l-trityl-4-formyl-lH-imidazole (13.5 g, 39.9 mmol) in tetrahydrofuran (140 mL) at -20C, and themixture was stirred at the same temperature for 2 hr. The reaction mixture was allowed to warm to 0C, and stirred for 1 hr, and 20w/v% aqueous ammonium chloride solution (105 mL) was added dropwise thereto. The organic layer was separated, and concentrated to the volume of about 90 mL under reducedpressure. To the residue was added tetrahydrofuran (140 mL) , and the mixture was concentrated to the volume of about 90 mL under reduced pressure. To the residue was added acetone (140 mL) , and the mixture was concentrated to the volume of about 140 mL under reduced pressure. These operations were repeated three times. To the residue was added acetone to adjust the volume to about 180 mL, and the mixture was stirred at room temperature. The crystals were collected by filtration, and washed with acetone (70 mL) . The obtained wet crystals were dried under reduced pressure to give 6- [hydroxy ( 1-trityl-lH- imidazol-4-yl) methyl] -N-methyl-2-naphthamide (10.3 g, 19.7 mmol) . yield 74%.½ NMR (500 MHz , DMSO-d6) delta 2.84 (d, J = 4.7 Hz, 3H) , 5.76 (d, J = 5.0 Hz, 1H), 5.82 (d, J = 4.7 Hz, 1H) , 6.80 (s, 1H) , 6.98- 7.13 (m, 6H) , 7.28 (d, J = 1.6 Hz, 1H) , 7.32-7.50 (m, 9H) , 7.55 (dd, J = 8.5, 1.6. Hz, 1H) , 7.83-7.99 (m,. 4H) 8.37 (s, 1H) 8.58 (d, J = 4.4 Hz, 1H) ; HRMS (ESI) m/z Calcd for aC35H30 3O2 [M+H] +: 524.2338, Found: 524.2325; Anal. Calcd for a C35H29 3O2: C, 80.28; H, 5.58; N, 8.02. Found: C, 80.17; H, 5.80; N, 7.81.[0097]
71% Example 2Under a nitrogen atmosphere, 6-bromo-N-methyl-2- naphthamide (1.0 g, 3.79 mmol) was added to tetrahydrofuran (25 mL) , and then 1.0 mol/L dibutylmagnesium heptane solution (2.0 mL) was added dropwise thereto at room temperature. The obtained solution was cooled to -13C, 1.6 mol/L n-butyllithium hexane solution (2.6 mL) was added dropwise thereto, and the mixture was. stirred at the same temperature for 1.5 hr. A solution of l-trityl-4-formyl-lH-imidazole (1.4 g, 4.2 mmol) in tetrahydrofuran (15 mL) was added dropwise to the reaction mixture at -11C, and the mixture was stirred at the same temperature for 5 hr. The reaction mixture was allowed to warm to 6C over 2.5 hr, and 20w/v% aqueous ammonium chloride solution (30 mL) was added dropwise thereto. The organic layer was separated, and quantified to give 6- [hydroxy (1-trityl-lH- imidazol-4-yl) methyl] -N-methyl-2-naphthamide (1.2 g, 2.24 mmol). yield 71%.
58% Reference Example 8Under a nitrogen atmosphere, o- bromotrifluoromethylbenzene (1.35 kg, 6.00 mol) was added to tetrahydrofuran (7.9 L) . The reaction mixture was cooled to - 70C, 1.6 mol/L n-butyllithium hexane solution (3.75 L, 6.00 mol) was. added dropwise thereto, and the mixture was stirred at the same temperature for about 30 min. The reaction mixture was added dropwise at the same temperature to a solution prepared by adding <strong>[426219-35-4]6-bromo-N-methyl-2-naphthamide</strong> (1.13 kg, 4.28 mol) to THF (62.2 L) at -70C under a nitrogen atmosphere, and the mixture was stirred for 1.5 hr. To the reactionmixture were added dropwise successively 1.6 mol/L n- butyllithium hexane solution (2.67 L, 4.27 mol) and a solution of l-trityl-4-formyl-lH-imidazole (1.21 kg, 3.58 mol) in THF (7.9 L) at the same temperature, and the mixture was stirred for 2 hr. The reaction mixture was allowed to warm to -10C, and 20w/v% aqueous ammonium chloride solution (17.0 L) was added dropwise thereto at -10 to 0C. The separated organic layer was concentrated under reduced pressure. To the residue was added ethyl acetate . (11.3 L) , and the mixture was stirred at room temperature. The crystals were collected by filtration, and washed with ethyl acetate (11.3 L) . The obtained wet crystals were dried under reduced pressure to give 6- [hydroxy ( l-trityl-lH-imidazol-4-yl) methyl] -N-methyl-2- naphthamide (1.31 kg, 2.50 mol). yield 58%.
50% Under nitrogen atmosphere, 5.8 liters of THF was added to 105.6 g (0.40 mol, 1.2eq) of 6-bromo-N-methyl-2-naphtamide, the mixture was warmed to 50C to dissolve it. 500 ML (0.50 mol, 2.4eq) of a 1.6 M solution of n-butyllithium in hexane was added dropwise at -65C or lower over 35 minutes.. The mixture was stirred at -65C for 1 hour.. A solution of 112.7 g (0.33 mol) of 1-trityl-4-formyl-1H-imidazole in 810 ML of THF was added dropwise at -65C or lower over 40 minutes.. The mixture was stirred at -65C for 2 hours. 1.5 Liters of an aqueous saturated ammonium chloride solution was added dropwise at -20C or lower, and the mixture was warmed to 30C. After separation of the layers, the organic layer was washed with 1.5 liters of an aqueous saturated sodium chloride solution two times.. After concentration under reduced pressure, 1 liter of ethyl acetate was added to the residue, and the mixture was stirred at 25C for 3 hours.. Crystals were filtered, and washed with ethyl acetate.. Vacuum drying (50C) to a constant weight afforded 87.9 g of 6-[hydroxy(1-trityl-1H-imidazol-4-yl)methyl]-N-methyl-2-naphthamide (yield 50%).1H NMR (DMSO-d6): delta 2.82 (3H, d, J=4.4 Hz), 5.76 (2H, q,J=6.6 Hz), 6.78 (1H, s), 7.06-7.09 (6H, m), 7.26 (1H, s), 7.33-7.42 (9H, m), 7.53 (1H, d, J=8.5 Hz) 7.88-7.93 (4H, m) 8.36 (1H, s), 8.55 (1H, d, J=4.5 Hz).

  • 4
  • [ 14704-31-5 ]
  • [ 33016-47-6 ]
  • [ 1166974-39-5 ]
 

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