Home Cart 0 Sign in  

[ CAS No. 399-51-9 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 399-51-9
Chemical Structure| 399-51-9
Structure of 399-51-9 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 399-51-9 ]

Related Doc. of [ 399-51-9 ]

Alternatived Products of [ 399-51-9 ]

Product Details of [ 399-51-9 ]

CAS No. :399-51-9 MDL No. :MFCD00056933
Formula : C8H6FN Boiling Point : -
Linear Structure Formula :- InChI Key :YYFFEPUCAKVRJX-UHFFFAOYSA-N
M.W :135.14 Pubchem ID :351278
Synonyms :

Calculated chemistry of [ 399-51-9 ]

Physicochemical Properties

Num. heavy atoms : 10
Num. arom. heavy atoms : 9
Fraction Csp3 : 0.0
Num. rotatable bonds : 0
Num. H-bond acceptors : 1.0
Num. H-bond donors : 1.0
Molar Refractivity : 38.26
TPSA : 15.79 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.6 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.58
Log Po/w (XLOGP3) : 2.15
Log Po/w (WLOGP) : 2.73
Log Po/w (MLOGP) : 2.0
Log Po/w (SILICOS-IT) : 3.0
Consensus Log Po/w : 2.29

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.7
Solubility : 0.271 mg/ml ; 0.002 mol/l
Class : Soluble
Log S (Ali) : -2.11
Solubility : 1.04 mg/ml ; 0.00769 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.53
Solubility : 0.0399 mg/ml ; 0.000295 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.56

Safety of [ 399-51-9 ]

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

Application In Synthesis of [ 399-51-9 ]

* 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.

  • Upstream synthesis route of [ 399-51-9 ]
  • Downstream synthetic route of [ 399-51-9 ]

[ 399-51-9 ] Synthesis Path-Upstream   1~30

  • 1
  • [ 1065183-63-2 ]
  • [ 399-51-9 ]
YieldReaction ConditionsOperation in experiment
87% With hydrogen; iron(II) acetate In tetrahydrofuran; toluene at 20℃; for 48 h; Inert atmosphere Intermediate 110: 6-Fluoro-1H-indole. To a stirred suspension of (1.pound.)-(4-fluoro-2-nitrophenyl)ethanal semicarbazone (27.0 g, 0.1 10 mol) in THF (750 ml.) in a 1 L bomb was added Rh/C (5 percent; 3.5 g, 0.002 mol Rh) slurried in toluene and Fe(OAc)2 (2.9 g, 0.017 mol). The bomb was charged with H2 to 50 atm and stirred at room temperature for 2 days. The reaction mixture was filtered through celite, washing with MeOH (150 ml_). The filtrate was concentrated to give a black oil that was partitioned between DCM (500 ml.) and water (300 ml_). The layers were separated and the aqueous fraction was extracted with DCM (2 x 200 ml_). The combined organic extracts were washed with brine (200 ml_), dried (Na2SO4), and concentrated under reduced pressure. The residue was dissolved in DCM (100 ml.) and treated with flash silica to decolourise the solution. The mixture was filtered concentrated under reduced pressure, giving 12.9 g (87 percent) of the title compound. 1H NMR: (300 MHz; DMSO-d6) δ 11.1 1 (1 H, s), 7.49 (1 H, dd, J=8.6 5.5), 7.30 (1 H, t, J=2.4), 7.13 (1 H, dd, J=10.3 2.4), 6.81 (1 H, ddd, J=1 1.0, 7.6 2.4) and 6.40-6.38 (1 H, m).
Reference: [1] Patent: WO2008/118724, 2008, A1, . Location in patent: Page/Page column 126
  • 2
  • [ 96631-90-2 ]
  • [ 399-51-9 ]
Reference: [1] Patent: EP971717, 2001, B1,
[2] Bioorganic and Medicinal Chemistry Letters, 1996, vol. 6, # 7, p. 857 - 860
[3] Patent: US2001/53783, 2001, A1,
[4] Patent: US5929072, 1999, A,
[5] Patent: EP897921, 1999, A1,
  • 3
  • [ 446-10-6 ]
  • [ 4637-24-5 ]
  • [ 399-51-9 ]
YieldReaction ConditionsOperation in experiment
5.7%
Stage #1: With pyrrolidine In DMF (N,N-dimethyl-formamide) at 20 - 115℃;
Stage #2: With hydrogen In methanol at 50℃;
Example S40; Preparation of 6-fluoro-1H-indole-7-carboxylic acid; A solution of 70.3 g of 4-fluoro-1-methyl-2-nitro-benzene (453 mmol) in 330 ml DMF was treated at rt with 87.5 ml of N,N-dimethylformamide dimethylacetal (DMFDMA, 589 mmol) and 50 ml of pyrrolidine (544 mmol) and then heated in an oil bath at 115° C. under argon. The dark red solution was then cooled down to rt, and poured into 1500 ml brine, extracted twice with diethylether. The combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo, leading to 106 g residue. About half of this residue (51.5 g) were dissolved in 800 ml methanol, treated with 12.5 g 10percent Pd/C and hydrogenated at 50° C. After removal of the catalyst by filtration, the residue was purified by silicagel chromatography (800 g silicagel, heptane/EtOAc 9:1) leading to 3.5 g of 6-fluoro-1H-indole as a light green solid (5.7percent).
Reference: [1] European Journal of Organic Chemistry, 2006, # 13, p. 2956 - 2969
[2] Patent: US2006/30613, 2006, A1, . Location in patent: Page/Page column 28
  • 4
  • [ 120192-70-3 ]
  • [ 399-51-9 ]
Reference: [1] Patent: US2003/225068, 2003, A1, . Location in patent: Page 6
  • 5
  • [ 3093-97-8 ]
  • [ 399-51-9 ]
YieldReaction ConditionsOperation in experiment
50% for 3 h; Neat (no solvent); Reflux General procedure: A mixture of compound 4a (23.5 g, 0.12 mol), copper powder (5.4 g, 0.084 mol) and quinoline (235 mL) was heated to reflux for 3 h. Upon cooling to room temperature, the filtrate was collected by filtration, diluted with ice-water and adjusted to pH 4 with concentrated hydrochloric acid, extracted with CH2Cl2 (3 .x. 100 mL), washed with 2 N hydrochloric acid (3 .x. 50 mL), saturated NaHCO3 solution (3 .x. 50 mL) and brine (2 .x. 50 mL), and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography. 5a was obtained as a white solid (9.6 g, 53percent).
Reference: [1] Journal of Organic Chemistry, 1993, vol. 58, # 20, p. 5558 - 5559
[2] Journal of Medicinal Chemistry, 2000, vol. 43, # 24, p. 4701 - 4710
[3] Canadian Journal of Chemistry, 2007, vol. 85, # 4, p. 283 - 292
[4] Nucleosides, Nucleotides and Nucleic Acids, 2007, vol. 26, # 8-9, p. 869 - 871
[5] European Journal of Medicinal Chemistry, 2011, vol. 46, # 7, p. 3149 - 3157
[6] Journal of the Chemical Society, 1955, p. 1283,1284
[7] Journal of the Chemical Society, 1959, p. 1913
  • 6
  • [ 169674-57-1 ]
  • [ 399-51-9 ]
YieldReaction ConditionsOperation in experiment
81% at 20℃; General procedure: The aryl halide was dissolved in 5mL of methanol per mmol of (hetero)arylhalide, magnesium (5 equiv.) added and the mixture was stirred at room temperature. After completion of the reaction (between 6-12h), the reaction mixture was poured into water, acidified with dilute HCl, and extracted with ethyl acetate. The organic phase was dried over MgSO4 and concentrated under reduced pressure. The product was purified if necessary by column chromatography on silica gel.
Reference: [1] Tetrahedron Letters, 2018, vol. 59, # 32, p. 3108 - 3111
  • 7
  • [ 255724-68-6 ]
  • [ 399-51-9 ]
Reference: [1] Journal of Medicinal Chemistry, 2001, vol. 44, # 10, p. 1603 - 1614
  • 8
  • [ 446-10-6 ]
  • [ 399-51-9 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 1996, vol. 6, # 7, p. 857 - 860
[2] Patent: US2016/168089, 2016, A1,
[3] Patent: WO2008/118724, 2008, A1,
[4] Patent: US2003/225068, 2003, A1,
  • 9
  • [ 96631-90-2 ]
  • [ 399-51-9 ]
  • [ 96631-93-5 ]
Reference: [1] Journal of Heterocyclic Chemistry, 1985, vol. 22, p. 121 - 125
  • 10
  • [ 348-37-8 ]
  • [ 399-51-9 ]
Reference: [1] Journal of the Chemical Society, 1955, p. 1283,1284
[2] European Journal of Medicinal Chemistry, 2011, vol. 46, # 7, p. 3149 - 3157
[3] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 18, p. 4403 - 4407
  • 11
  • [ 136818-43-4 ]
  • [ 399-51-9 ]
Reference: [1] Canadian Journal of Chemistry, 2007, vol. 85, # 4, p. 283 - 292
[2] Journal of Medicinal Chemistry, 2000, vol. 43, # 24, p. 4701 - 4710
  • 12
  • [ 658-27-5 ]
  • [ 399-51-9 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 18, p. 4403 - 4407
  • 13
  • [ 2343-23-9 ]
  • [ 399-51-9 ]
Reference: [1] Chemistry - A European Journal, 2018, vol. 24, # 9, p. 2065 - 2069
  • 14
  • [ 399-51-9 ]
  • [ 324-03-8 ]
Reference: [1] Chemistry - A European Journal, 2012, vol. 18, # 22, p. 6885 - 6894
[2] European Journal of Medicinal Chemistry, 2018, vol. 155, p. 516 - 530
  • 15
  • [ 399-51-9 ]
  • [ 50-00-0 ]
  • [ 124-40-3 ]
  • [ 343-93-1 ]
YieldReaction ConditionsOperation in experiment
85%
Stage #1: With acetic acid In water at 4.5 - 15℃; for 2.66667 h; Inert atmosphere
Stage #2: at 0 - 10℃; for 0.333333 h; Inert atmosphere
Procedure Using Formaldehyde in Place of Diethoxymethane:To a 250 L reactor, under N2 atmosphere, was charged with about 40percent aqueous dimethylamine (35.68 kg, 1.0 eqv.) at about 17° C. The mixture was cooled to about 4.5° C. and glacial acetic acid (43.4 kg, 2.5 eq.) was added dropwise over 140 min while maintaining the temperature using below about 15° C. After stirring for 20 min at about 3° C., 37percent aqueous formaldehyde (25.9 kg, 1.1 eq.) was slowly added over about 20 min while keeping the temperature between about 0° C. to about 10° C. 6-Fluoroindole (39.2 kg) was added. The reaction was exothermic and reached a final temperature of about 40° C., which was then cooled down to about 20° C. The reaction solution was slowly added in a 650 L reactor charged with aqueous 3M NaOH over a period of about 40 min. The suspension was stirred for about 40 min while keeping the temperature between about 5 and 20° C. The product was filtered, rinsed with DI water (120 kg) and dried at about 50° C. to afford the compound of Formula II (45.4 kg). Yield: 85percent.
81%
Stage #1: With acetic acid In water at 3 - 17℃; for 2.66667 h; Inert atmosphere; Large scale
Stage #2: at 0 - 40℃; Inert atmosphere; Large scale
Stage #3: With sodium hydroxide In water at 5 - 20℃; for 1.33333 h; Inert atmosphere; Large scale
A 250 L reactor was charged with approx. 40percent aq. dimethylamine (35.7 kg, 317 mol) at approx. 17°C. under an inert atmosphere. The mixture was cooled to approx. 4.5° C. and glacial acetic acid (43.4kg, 723 mol) was added dropwise over 140 mm while maintaining the temperature at approx. 15° C. Afier stirring for 20 mm at about 3° C., 37percent aqueous formaldehyde (25.9 kg, 319 mol) was slowly added over about 20 mm while keeping the temperature between approx. 0°C. to approx. 10°C. 6-Fluoroindole (39.2kg, 290 mol) was added. The reaction was exothermic and reached a final temperature of approx. 40° C., and it was then cooled down to approx. 20° C. The reaction solution was slowly added to a 650 L reactor previously charged with aq. NaOH (3 M) over a period of approx. 40 mm. The formed suspension was stirred for approx. 40 mm while keeping the temperature between 5 to 20°C. The precipitate was filtered from solution, washed with water on the filter, and dried at approx. 50° C. to afford Compound (II) (45.4 kg, 8 1percent).
Reference: [1] Patent: US2011/152539, 2011, A1, . Location in patent: Page/Page column 4
[2] Patent: US2016/168089, 2016, A1, . Location in patent: Page/Page column 0081; 0082
[3] Chemical Communications, 2016, vol. 52, # 34, p. 5868 - 5871
[4] Journal of Organic Chemistry, 2018, vol. 83, # 17, p. 9902 - 9913
[5] Patent: WO2010/36362, 2010, A1, . Location in patent: Page/Page column 44
  • 16
  • [ 399-51-9 ]
  • [ 462-95-3 ]
  • [ 124-40-3 ]
  • [ 343-93-1 ]
YieldReaction ConditionsOperation in experiment
95%
Stage #1: With formic acid In water at 80℃; for 2 h; Reflux
Stage #2: With acetic acid In water at 2 - 40℃;
Stage #3: With sodium hydroxide In water at 5 - 20℃;
Synthesis of the Compound of Formula IIDetailed syntheses of the compound of Formula II from commercially available 6-fluoroindole are provided below. Scheme II uses diethoxymethane and dimethylamine to generate the "iminium ion species". An alternative procedure using formaldehyde in place of diethoxymethane is also provided below. Synthetic Procedure:Preparation of formaldehyde was carried out in reactor A. The synthesis of the compound of Formula II was carried out in reactor B. Precipitation of the final product was carried out in reactor C.Procedure:To reactor A were charged diethoxymethane (65 ml/54 g), water (50 ml) and formic acid (39 ml/47 g). The mixture was heated to about 80° C./reflux for about 2 hours and then cooled to about 20° C. To reactor B were charged 6-fluoroindole (50 g) and 80percent acetic acid (66 ml/70 g, 2.5 eq. to 6-fluoroindole). The suspension was cooled to 2-5° C. 40percent Dimethylamine (aq) (103 ml/92 g, 2.2 eq. to 6-fluoroindole) was added drop-wise to reactor B keeping the temperature below about 15° C. The reaction mixture was stirred for about 20 minutes and at the same time the temperature was adjusted to 2-4° C.The mixture from reactor A (DEM, water, formic acid, formaldehyde and ethanol at about 20° C.) was added drop-wise to reactor B while keeping the temperature at 2-8° C. The reaction mixture was stirred for additional 10 minutes at 2-8° C. The reaction mixture was slowly warmed to about 40° C. over a 1 hour period. The reaction mixture was stirred at about 40° C. for an additional 1 hour. The reaction mixture was cooled to about 20° C.To reactor C was charged 3M NaOH (800 ml, 1.24 eq. to the acetic acid+the formic acid) and the solution was cooled to about 10° C. The reaction mixture from reactor B was added drop-wise to the NaOH solution in reactor C while keeping the temperature at 10-15° C. (pH>14). The suspension was stirred for 40 minutes at 5-20° C. (pH>14). The product was collected by filtration and the filter-cake was washed twice with water (2.x.250 ml). The product was dried at about 60° C. under vacuum for 16 hours. Yield: 95percent. Purity by HPLC (280 nm): 98 area percent.
95%
Stage #1: With acetic acid In water at 2 - 15℃; for 0.333333 h; Inert atmosphere
Stage #2: With formaldehyd; formic acid In ethanol; water at 2 - 40℃; for 2.16667 h; Inert atmosphere
Stage #3: With sodium hydroxide In ethanol; water at 5 - 20℃; for 0.666667 h; Inert atmosphere
To reactor A were charged diethoxymethane (DEM)(65 mE, 0.52 mol), water (50 mE) and formic acid (39 mE, 1.02 mol)). The mixture was heated at approx. 80° C. (reflux) for approx. 2 h and then cooled to approx. 20° C. To reactor B were charged 6-fluoroindole (50 g, 0.37 mol) and 80percent acetic acid (66 mE, 1.17 mol). The suspension was cooled to 2-5° C. 40percent Aq. dimethylamine (103 mE, 2.04 mol) was added drop- wise to reactor B keeping the temperature below approx. 15° C. The reaction mixture was stirred for approx. 20 mm and at the same time the temperature was adjusted to 2-4° C. The mixture from reactor A (DEM, water, formic acid, formaldehyde and ethanol at about 20° C.) was added drop-wise to reactor B while keeping the temperature at 2-8° C. The reaction mixture was stirred for additional 10 mm at 2-8° C. The reaction mixture was slowly warmed to approx.40° C. over a 1 h period. The reaction mixture was stirred at approx. 40°C. for an additional 1 h. The reaction mixture was cooled to about 20° C. To reactor C was charged aq. NaOH (800 mE, 2.40 mol, 3 M) and the solution was cooled to about 10° C. The reaction mixture from reactor B was added dropwise to the NaOH solution in reactor C while keeping the temperature at 10-15°C. (pH>14). The suspension was stirred for 40 mm at 5-20°C. (pH>1 4). The product was collected by filtration and the filter-cake was washed twice with water (2x250 mE). The product was dried at approx. 60° C. under vacuum for 16 h to yield Compound (II) (67.6 g, 95percent) with 98percent UV purity in HPLC analysis.
Reference: [1] Patent: US2011/152539, 2011, A1, . Location in patent: Page/Page column 4
[2] Patent: US2016/168089, 2016, A1, . Location in patent: Paragraph 0076-0080
  • 17
  • [ 399-51-9 ]
  • [ 321-50-6 ]
Reference: [1] Organic and Biomolecular Chemistry, 2013, vol. 11, # 43, p. 7455 - 7457
  • 18
  • [ 399-51-9 ]
  • [ 407-25-0 ]
  • [ 23077-44-3 ]
YieldReaction ConditionsOperation in experiment
66%
Stage #1: at 0℃; for 3 h;
Stage #2: With sodium hydroxide In N,N-dimethyl-formamide for 4 h; Reflux
Trifluoroacetic anhydride (9.009 ml, 64.8 mmol, 2.2 equiv.) was added drop wise to a stirring solution of 6-fluoroindole (4.000 g, 29.6 mmol, 1.0 equiv.) in DMF (25 mL) at 0°C (external ice bath temperature). After 3 hours in the ice bath the mixture was quenched with 40 mL of 2N sodium carbonate. The precipitate was collected by filtration and washed with water. The solid was taken up in 4M NaOH (50 mL) and refluxed for 4 hours. The reaction mixture was cooled to room temperature and poured into 50 mL of water. The mixture was cooled in an ice bath and slowly brought to pH 3 with 6N HCl. The precipitate which formed was collected by filtration, washed with water and dried under vacuum to give an off -white solid (3.5 g, 66percent). 1H NMR (DMSO-d6, 300 MHz): 12.03 (bs, 1H), 11.87 (s, 1H), 7.99-7.92(m, 2H), 7.23 (dd, J=9.9 & 2.4 Hz, 1Η),7.03-6.97 (m, 1H).
Reference: [1] Patent: WO2017/197177, 2017, A1, . Location in patent: Paragraph 0219-0221
[2] ChemMedChem, 2012, vol. 7, # 11, p. 1915 - 1920
  • 19
  • [ 399-51-9 ]
  • [ 23077-44-3 ]
Reference: [1] CrystEngComm, 2013, vol. 15, # 37, p. 7490 - 7497
  • 20
  • [ 399-51-9 ]
  • [ 68-12-2 ]
  • [ 2795-41-7 ]
YieldReaction ConditionsOperation in experiment
89%
Stage #1: at 0℃; for 1 h;
Stage #2: at 20℃; for 5 h;
Stage #3: With sodium hydroxide In N,N-dimethyl-formamide at 100℃; for 0.166667 h;
General procedure: Oxalyl chloride (0.3 mL) was added in a drop-wise manner to cooled (ice-bath) DMF (3 mL) under stirring. The mixture was then stirred at 0 °C for 1 h. A solution of the substituted indole (4 mmol) in DMF (1.5 mL) was then added to the reaction mixture in a dropwise manner. The resulting mixture was stirred at room temperature for 5 h. A 2 N solution of sodium hydroxide (2 mL) was then added, and the mixture was heated at 100 °C for 10 min. The mixture was then cooled and extracted with ethyl acetate (3 X 50 mL). The organic layers were combined and washed with sequentially water and brine. The organics were dried (Na2SO4) and distilled to dryness to give the crude residue, which was purified by flash column chromatography using ethyl acetate/petroleum ether (3:1, v/v) as the eluent to give pure indole-3-carbaldehyde (4a-k).
75%
Stage #1: for 0.583333 h; Cooling with ice
Stage #2: at 35℃; for 0.666667 h;
Place 40 ml DMF in a round bottom flaskSlowly add 6.89 ml of POCl3 (phosphorus oxychloride) under ice bath.After dropping,After stirring in an ice bath for 35 minutes,At a constant pressure dropping funnel was slowly added 5g6- fluoro indole in DMF,Stir at 35 °C for 40 min.The reaction solution gradually changed from colorless to red.TLC shows that after the reaction is completed,Add 100ml of 19.3mmol/L aqueous NaOH,Stir vigorously for 30 minutes at 80°C.Cool the reaction solutionAdd ethyl acetate extraction,30ml each time,A total of three extractions.Organic layers merge,After drying over anhydrous sodium sulfate,Evaporated to drynessSilica gel column chromatography 4.5g Intermediate I-1 (white solid, yield75percent).
Reference: [1] Journal of the American Chemical Society, 2009, vol. 131, # 31, p. 10796 - 10797
[2] European Journal of Medicinal Chemistry, 2013, vol. 65, p. 158 - 167
[3] Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 10, p. 3307 - 3312
[4] Journal of Enzyme Inhibition and Medicinal Chemistry, 2011, vol. 26, # 2, p. 261 - 269
[5] Patent: CN103664895, 2018, B, . Location in patent: Paragraph 0124-0126
[6] Organic and Biomolecular Chemistry, 2014, vol. 12, # 48, p. 9764 - 9768
[7] Bioorganic and Medicinal Chemistry Letters, 1996, vol. 6, # 7, p. 857 - 860
[8] Biochemical Pharmacology, 1995, vol. 49, # 10, p. 1435 - 1442
[9] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 13, p. 4783 - 4792
[10] Journal of Medicinal Chemistry, 2011, vol. 54, # 15, p. 5320 - 5334
[11] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 212 - 215
[12] ChemMedChem, 2012, vol. 7, # 11, p. 1915 - 1920
[13] MedChemComm, 2013, vol. 4, # 1, p. 228 - 232
[14] Angewandte Chemie - International Edition, 2013, vol. 52, # 11, p. 3250 - 3254[15] Angew. Chem., 2013, vol. 125, # 11, p. 3332 - 3336,5
[16] CrystEngComm, 2013, vol. 15, # 37, p. 7490 - 7497
[17] Angewandte Chemie - International Edition, 2014, vol. 53, # 44, p. 11881 - 11885[18] Angew. Chem., 2014, vol. 126, # 44, p. 12075 - 12079,5
[19] European Journal of Medicinal Chemistry, 2017, vol. 136, p. 184 - 194
[20] Organic and Biomolecular Chemistry, 2018, vol. 16, # 36, p. 6647 - 6651
  • 21
  • [ 399-51-9 ]
  • [ 50-00-0 ]
  • [ 2795-41-7 ]
YieldReaction ConditionsOperation in experiment
66% With iron(III) chloride; ammonia In water; N,N-dimethyl-formamide at 130℃; for 4.5 h; General procedure: A 50 mL round-bottomed flask equipped with a magnetic stirringbar was charged with the appropriate indole 1 (0.5 mmol,1.0 equiv), 37percent aq HCHO (0.5 mmol, 0.0406 g, 1.0 equiv), 25percent aqNH3 (1.0 mmol, 0.0681 g, 2.0 equiv), FeCl3 (0.01 mmol, 0.0016 g,2 molpercent), and DMF (2 mL). The flask was fitted with a reflux condenser,and the mixture was stirred at 130 °C under open air.When the reaction was complete (TLC), the mixture was cooledto r.t., diluted with sat. aq NaCl (10 mL) and 0.5 M aq HCl (2 mL),and extracted with EtOAc (3 x 7 mL). The organic layers werecombined, washed with sat. aq NaHCO3 (10 mL) and sat. aq NaCl(10 mL), dried (Na2SO4), and concentrated under reduced pressure.The residue was purified by flash column chromatography(silica gel, hexane–EtOAc).
Reference: [1] Synlett, 2017, vol. 28, # 19, p. 2670 - 2674
  • 22
  • [ 399-51-9 ]
  • [ 100-97-0 ]
  • [ 2795-41-7 ]
YieldReaction ConditionsOperation in experiment
65% With aluminum (III) chloride In N,N-dimethyl-formamide at 120℃; for 4.5 h; General procedure: A method for synthesizing compound III-1 wherein R1, R2 and R3 are simultaneously hydrogen in the formula III, the method comprising the steps of:(1) Add to a 50 mL round bottom flask1.0mmol indole(In the formula I, R1, R2, and R3 are both hydrogen) and1.0 mmol (0.140 g) of hexamethylenetetramine, then 2 mL of N,N-dimethylformamide (DMF), stirred in a magnetic stirrer to dissolve the solid, followed by the addition of 0.05 mmol (0.012 g) of crystalline trichloride Aluminum, connected to a reflux condenser, heated at 120 ° C, the reaction progress was monitored by TLC, and the reaction was cooled to room temperature after 1 h to prepare a suspension;(2) The suspension prepared in the step (1) is suction filtered with a funnel padded with diatomaceous earth.The filter cake was washed well with ethyl acetate, suction filtered, and the above operation was repeated until the filtrate had no product, and all the filtrates were combined.Dilute with 15 mL of saturated saline solution, disperse and separate the layers, and the aqueous layer was further extracted with ethyl acetate three times.Each time 10 mL, the ethyl acetate layer was combined and washed with 10 mL of 2 mol/L diluted hydrochloric acid.Wash with 10 mL of saturated sodium bicarbonate solution, and finally wash with 10 mL of saturated brine.The washed ethyl acetate layer was dried over anhydrous sodium sulfate, and after drying, the desiccant was filtered off.Then use a rotary evaporator to recover the solvent to concentrate the product, and finally,The residue is subjected to silica gel column chromatography using a mixture of n-hexane-ethyl acetate (V/V = 2:1) as an eluent to obtain a purified product.The mass of the compound III-indole-3-carbaldehyde is 0.137g,The product yield was 94percent.
Reference: [1] Patent: CN108329249, 2018, A, . Location in patent: Paragraph 0041-0044; 0096-0099
  • 23
  • [ 399-51-9 ]
  • [ 56341-39-0 ]
Reference: [1] European Journal of Organic Chemistry, 2018, vol. 2018, # 12, p. 1437 - 1442
  • 24
  • [ 399-51-9 ]
  • [ 25015-63-8 ]
  • [ 642494-36-8 ]
Reference: [1] Organic Letters, 2018,
  • 25
  • [ 399-51-9 ]
  • [ 283173-50-2 ]
Reference: [1] ACS Chemical Neuroscience, 2018, vol. 9, # 6, p. 1259 - 1263
  • 26
  • [ 399-51-9 ]
  • [ 283173-80-8 ]
Reference: [1] ACS Chemical Neuroscience, 2018, vol. 9, # 6, p. 1259 - 1263
  • 27
  • [ 399-51-9 ]
  • [ 467458-02-2 ]
Reference: [1] Patent: US2011/152539, 2011, A1,
[2] Patent: US2011/152539, 2011, A1,
[3] Patent: US2016/168089, 2016, A1,
[4] Patent: US2016/168089, 2016, A1,
[5] Patent: US2016/168089, 2016, A1,
[6] Patent: US2016/168089, 2016, A1,
[7] Patent: US2016/168089, 2016, A1,
[8] Patent: US2016/168089, 2016, A1,
  • 28
  • [ 399-51-9 ]
  • [ 1350543-67-7 ]
Reference: [1] Journal of Medicinal Chemistry, 2011, vol. 54, # 15, p. 5320 - 5334
  • 29
  • [ 399-51-9 ]
  • [ 1316695-35-8 ]
Reference: [1] Journal of Medicinal Chemistry, 2011, vol. 54, # 15, p. 5320 - 5334
  • 30
  • [ 399-51-9 ]
  • [ 1408282-26-7 ]
Reference: [1] ACS Chemical Neuroscience, 2018, vol. 9, # 6, p. 1259 - 1263
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 399-51-9 ]

Fluorinated Building Blocks

Chemical Structure| 40311-13-5

[ 40311-13-5 ]

6-Fluoro-2-methyl-1H-indole

Similarity: 0.98

Chemical Structure| 399-52-0

[ 399-52-0 ]

5-Fluoro-1H-indole

Similarity: 0.96

Chemical Structure| 162100-95-0

[ 162100-95-0 ]

6-Fluoro-5-methyl-1H-indole

Similarity: 0.94

Chemical Structure| 101125-32-0

[ 101125-32-0 ]

3-(4-Fluorophenyl)-1H-indole

Similarity: 0.91

Chemical Structure| 387-44-0

[ 387-44-0 ]

7-Fluoroindole

Similarity: 0.91

Related Parent Nucleus of
[ 399-51-9 ]

Indoles

Chemical Structure| 40311-13-5

[ 40311-13-5 ]

6-Fluoro-2-methyl-1H-indole

Similarity: 0.98

Chemical Structure| 399-52-0

[ 399-52-0 ]

5-Fluoro-1H-indole

Similarity: 0.96

Chemical Structure| 162100-95-0

[ 162100-95-0 ]

6-Fluoro-5-methyl-1H-indole

Similarity: 0.94

Chemical Structure| 101125-32-0

[ 101125-32-0 ]

3-(4-Fluorophenyl)-1H-indole

Similarity: 0.91

Chemical Structure| 387-44-0

[ 387-44-0 ]

7-Fluoroindole

Similarity: 0.91