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Chemical Structure| 33626-98-1 Chemical Structure| 33626-98-1
Chemical Structure| 33626-98-1

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Product Details of Adapalene Related Compound A

CAS No. :33626-98-1
Formula : C12H9BrO2
M.W : 265.10
SMILES Code : O=C(OC)C1=CC=C2C=C(Br)C=CC2=C1
MDL No. :MFCD00100408
InChI Key :JEUBRLPXJZOGPX-UHFFFAOYSA-N
Pubchem ID :854134

Safety of Adapalene Related Compound A

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of Adapalene Related Compound A

* 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 [ 33626-98-1 ]

[ 33626-98-1 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 33626-98-1 ]
  • [ 52562-19-3 ]
  • C21H19NO2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% With tri-tert-butyl phosphine; palladium diacetate; caesium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene; for 5h;Inert atmosphere; Reflux; (Synthesis of Exemplary Compound (A-7)) (0457) Compound (A-7) in which D1 in Formula (I) is a compound represented by Formula (III) may be prepared by the following reaction scheme. 2-iso-propynylaniline (4.20 g, 31.5 mmol), palladium acetate (210 mg, 0.95 mmol), tri(t-butyl)phosphine (570 mg, 2.80 mmol), cesium carbonate (20.5 g, 62.9 mmol) and methyl 6-bromo-2-naphthoate (8.35 g, 31.5 mmol) were dissolved in 50 ml of xylene, and reacted by boiling under reflux for 5 hours under a nitrogen atmosphere to obtain Compound 17 in 78% yield. Compound 17 (7.80 g, 24.6 mmol) was added to a mixed solvent of 40 ml of acetic acid and 8 ml of hydrochloric acid, and followed by stirring at 60 C. for 30 minutes to obtain Compound 18 in 82% yield. Compound 18 (1.00 g, 3.15 mmol), palladium acetate (70.7 mg, 0.315 mmol), tri(t-butyl)phosphine (191 mg, 0.945 mmol), cesium carbonate (2.05 g, 6.30 mmol) and 1-bromo-4-tert-butylbenzene (671 mg, 3.15 mmol) were dissolved in 15 ml of xylene, and reacted by boiling under reflux for 7 hours under a nitrogen atmosphere to obtain Compound 19 in 95% yield. A 70% solution of sodium bis(2-methoxyethoxy)aluminum dihydride in toluene (5.37 ml, 18.6 mmol) was added to 13 ml of THF under a nitrogen atmosphere, and cooled to 0 C. N-methylpiperazine (2.01 g, 20.1 mmol) was added dropwise, and stirred for 30 minutes to adjust a reducing agent solution. The reducing agent solution was added dropwise to 20 ml of a solution of Compound 19 (1.35 g, 3.00 mmol) in THF at -40 C. under a nitrogen atmosphere. The reaction solution was stirred at -20 C. for 4 hours, and the reaction was then stopped with diluted hydrochloric acid to obtain Compound 20 in 81% yield. Compound 20 (700 mg, 1.67 mmol) and benzindandione (361 mg, 1.84 mmol) were added to 9 ml of an acetic acid solvent under a nitrogen atmosphere, and refluxed for 3 hours. After allowing to cool, suction filtration was performed, and recrystallization was performed with N,N-dimethylacetamide. Suction filtration was performed to obtain Compound (A-7) in 51% yield. The compound was identified by 1H-NMR. (0460) 1H-NMR (400 M Hz, in CDCl3): δ (ppm)=1.45 (s, 9H), 2.31 (s, 6H), 6.09 (d, J=8.6 Hz, 1H), 6.53 (d, J=8.7 Hz, 1H), 6.89-6.98 (m, 2H), 7.22 (d, J=8.7 Hz, 2H), 7.48-7.56 (m, 2H), 7.63-7.72 (m, 4H), 8.04-8.12 (m, 3H), 8.47-8.57 (m, 3H), 8.69-8.73 (m, 1H), 8.79 (s, 1H). m.p.=335 C., λmax=568 nm (in CHCl3) (ε=53000 mol-1·l·cm-1)
With caesium carbonate;palladium diacetate; triphenylphosphine; In xylene; for 4h;Reflux; (Example 12) <Synthesis of Compound (12)> [Show Image]<Synthesis of Compound 12a"> To 50 ml of dehydrated xylene, 4.2 g of <strong>[52562-19-3]2-isopropenylaniline</strong> (produced by Aldrich Chemical Co. Inc.), 8.4 g of methyl 6-bromo-2-naphthoate (produced by Wako Pure Chemical Industries, Ltd.), 210 mg of palladium acetate, 740 mg of triphenylphosphine and 20.5 g of cesium carbonate were added, followed by refluxing for 4 hours. The reaction mixture was suction-filtered and after distilling off the solvent by an evaporator, the residue was purified on a silica gel column (developing solvent: toluene). The solvent was distilled off to obtain 7.8 g of Compound (12a").
  • 2
  • [ 33626-98-1 ]
  • [ 105365-51-3 ]
  • methyl 6-(4-butoxyphenyl)-2-naphthoate [ No CAS ]
  • 3
  • [ 33626-98-1 ]
  • [ 52562-19-3 ]
  • methyl ortho-iodobenzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% With tri-tert-butyl phosphine; palladium diacetate; caesium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene; for 5h;Inert atmosphere; Reflux; (Synthesis of Exemplary Compound (A-19)) (0491) Compound (A-19) in which D1 in Formula (I) is a compound represented by Formula (III) may be prepared by the following reaction scheme. Isopropenylaniline, methyl ortho-iodobenzoate, palladium acetate, tri(t-butyl)phosphine and cesium carbonate were dissolved in 50 ml of xylene, and reacted under reflux for 5 hours under a nitrogen atmosphere to obtain Compound 41 in 78% yield. Compound 41 was added to a mixed solvent of acetic acid and concentrated hydrochloric acid, and followed by stirring at 60 C. for 1 hour to obtain Compound 42 in 82% yield. Compound 42, para-dibromobenzene, copper powder, copper iodide and calcium carbonate were added to diphenyl ether, and refluxed for 5 hours to obtain Compound 43 in 76% yield. Compound 43 was dissolved in dehydrated tetrahydrofuran, and a 3 M methyl Grignard reagent (ethyl ether solution) was added dripwise. After that, the reaction solution was heated to a reflux temperature, and followed by stirring for 1 hour to obtain Compound 44 in 95% yield. Compound 44 was added to phosphoric acid, and followed by stirring at 90 C. for 2 hours to obtain Compound 45 in 45% yield. Compound 45 was dissolved in dehydrated tetrahydrofuran, cooled to -40 C. by using a dry ice bath, and then, n-butyllithium (1.6 M in hexane) was added dropwise, and followed by stirring for 15 minutes. Dehydrated N,N-dimethylformamide was added dropwise thereto, and the dry ice bath was removed. 1 M diluted hydrochloric acid was added to obtain Compound 46 in 68% yield. Compound 46 and benzindandione were added to a 2-propanol solvent under a nitrogen atmosphere, and refluxed for 3 hours. After allowing to cool, suction filtration was performed, and recrystallization was performed with tetrahydrofuran. Suction filtration was performed to obtain Compound (A-19). The compound was identified by 1H-NMR. (0494) 1H-NMR (400 M Hz, in CDCl3): δ (ppm)=1.25 (s, 3H), 1.33 (s, 3H), 1.95 (s, 3H), 2.15 (s, 3H), 7.20-7.30 (m, 2H), 7.38-7.46 (m, 2H), 7.56-7.72 (m, 6H), 8.02 (s, 1H), 8.10-8.15 (m, 2H), 8.37 (d, J=15.0 Hz, 1H), 8.52 (d, J=15.0 Hz, 2H), 9.17 (s, 1H).
  • 4
  • [ 525362-07-6 ]
  • [ 33626-98-1 ]
  • C21H18O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
1.51g With potassium carbonate; palladium; In ethanol;Inert atmosphere; Heating; In a reaction vessel Compound 2.00g of the formula (I-4-1), the compound represented by formula (the I-4-2) 2.08g with potassium carbonate 1.56g, the ethanol 40mL were added. After nitrogen substitution, it was added a palladium catalyst. After heating was stirred and washed diluted with toluene hydrochloric acid, water, brine. This was purified by column chromatography and recrystallization to give the compound 1.51g of formula (I-4-3).
  • 5
  • [ 25415-67-2 ]
  • [ 33626-98-1 ]
  • 1-(6-bromonaphthalen-2-yl)-4-methylpentan-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% To a stirring solution of <strong>[25415-67-2]ethyl 4-methylvalerate</strong> (6.64mL, 40.0mmol) in anhydrous THF (20mL) at-78C was added LiHMDS (1.0M in THF, 40.0mL, 40.0mmol). The resultant mixture was stirred at-78C for 30min before a solution of 10 (5.30g, 20.0mmol) in anhydrous THF (100mL) was added. After complete addition, the reaction was stirred at room temperature for 3h. The THF was then removed in vacuo and hexane (50mL) added to the remaining residue. The solid which precipitated from solution was filtered off, re-dissolved in aqueous 1M NaOH (40mL) and stirred at 50C overnight. After cooling to room temperature, the pH was adjusted to 1 using conc aqueous HCl and the mixture heated at 60C for 1h. After cooling to room temperature, the reaction was extracted with diethyl ether (3×30mL). The organic extracts were combined, washed with water (25mL), brine (25mL), dried over MgSO4 and concentrated in vacuo. The resultant residue was purified by flash chromatography (10% EtOAc in hexane) to afford 36 as a light brown oil (4.57g, 75%); 1H NMR (400 Mz, CDCl3) delta 8.39 (s, 1H, ArH), 8.03-8.00 (m, 2H, ArH), 7.79 (d, J=8.8Hz, 1H, ArH), 7.76 (d, J=8.8Hz, 1H, ArH), 7.58 (dd, J=8.4 & 2.0Hz, 1H, ArH), 2.36 (t, J=7.6Hz, 2H, ArCOCH2-), 1.54-1.39 (m, 3H, -CH2CH(CH3)2), 0.85 (d, J=6.4Hz, 6H, -CH2CH(CH3)2); 13C NMR (100 Mz, CDCl3) delta 211.7, 136.3, 134.7, 131.0, 131.0, 130.2, 129.9, 129.3, 127.4, 125.1, 122.6, 40.7, 32.7, 27.7, 22.3.
 

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