Home Cart 0 Sign in  
X

[ CAS No. 1006-94-6 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 1006-94-6
Chemical Structure| 1006-94-6
Chemical Structure| 1006-94-6
Structure of 1006-94-6 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 1006-94-6 ]

Related Doc. of [ 1006-94-6 ]

Alternatived Products of [ 1006-94-6 ]

Product Citations

Shriver, James A. ; Kaller, Kaylie S. ; Kinsey, Ally L. , et al. DOI: PubMed ID:

Abstract: The spontaneous conversion of 3-indoxyl to indigo was a well-established process used to produce indigo dyes. It was recently shown that some indoles, when reacted with molybdenum hexacarbonyl and cumyl peroxide, proceed through an indoxyl intermediate to produce significant amounts of indirubin through a competing mechanism. Modulation of this system to lower temperatures allows for careful tuning, leading to selective production of indirubins in a general process. A systematic assay of indoles show that electron deficient indoles work well when substituted at the 5 and 7 positions. In contrast, 6-substituted electron rich indoles give the best results whereas halogeno indoles work well in all cases. This process shows broad functional group tolerance for generally reactive carbonyl-containing compounds such as aldehydes and carboxylic acids.

Purchased from AmBeed: ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;

Product Details of [ 1006-94-6 ]

CAS No. :1006-94-6 MDL No. :MFCD00005674
Formula : C9H9NO Boiling Point : -
Linear Structure Formula :- InChI Key :DWAQDRSOVMLGRQ-UHFFFAOYSA-N
M.W : 147.17 Pubchem ID :13872
Synonyms :

Calculated chemistry of [ 1006-94-6 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 9
Fraction Csp3 : 0.11
Num. rotatable bonds : 1
Num. H-bond acceptors : 1.0
Num. H-bond donors : 1.0
Molar Refractivity : 44.79
TPSA : 25.02 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) : -6.24 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.72
Log Po/w (XLOGP3) : 1.35
Log Po/w (WLOGP) : 2.18
Log Po/w (MLOGP) : 1.23
Log Po/w (SILICOS-IT) : 2.53
Consensus Log Po/w : 1.8

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.14
Solubility : 1.06 mg/ml ; 0.0072 mol/l
Class : Soluble
Log S (Ali) : -1.48
Solubility : 4.9 mg/ml ; 0.0333 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -3.39
Solubility : 0.06 mg/ml ; 0.000407 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.18

Safety of [ 1006-94-6 ]

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 [ 1006-94-6 ]

* 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 [ 1006-94-6 ]
  • Downstream synthetic route of [ 1006-94-6 ]

[ 1006-94-6 ] Synthesis Path-Upstream   1~31

  • 1
  • [ 94493-20-6 ]
  • [ 603-76-9 ]
  • [ 1006-94-6 ]
  • [ 61-70-1 ]
  • [ 2521-13-3 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1984, # 8, p. 1331 - 1340
  • 2
  • [ 1006-94-6 ]
  • [ 68-12-2 ]
  • [ 10601-19-1 ]
YieldReaction ConditionsOperation in experiment
94%
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).
92% at 0 - 55℃; for 2 h; General procedure: To a solution of compounds 17a, 17b (10 mmol) in 20 mL of DMF, phosphorus oxychloride (1.4 mL, 15 mmol) was added dropwise at 0°C. In 2 h of the reaction at 55°C, the mixture was poured into 150 mL of ice water. 20 percent NaOH solution was added to adjust pH at 8.0. The crude product was filtered off and recrystallized from anhydrous ethanol to give the corresponding product.
89.4% at 35℃; General procedure: To a stirring solution of POCl3 (18.36 g, 0.120 mol) in DMF (25 mL), indole (11.7 g, 0.100 mol) in DMF (15 mL) was added dropwise. The mixture was stirred at 35°C for 1 h, and then be poured into ice water and neutralized with 20 percent NaOH aq. The solution was filtered and the residue was washed with water and dried under IR to give the compound 4a as yellow needle (13.86 g, 95.48 percent). Mp = 192–194°C, lit.31 Mp = 196–197°C.
85%
Stage #1: at 0℃;
Stage #2: at 0℃; for 0.5 h;
Stage #3: With sodium hydroxide In waterCooling with ice; Reflux
Synthesis of 5-methoxy-indole-3-carbaldehydes; Preparation of S-methoxy-indole-3-carbaldehyde, 5-methoxy-2-methyl-indole-3- carbaldehyde, and 3-formyl-5-methoxy-indole-2-carboxylic acid POCI3 (1.6 ml_, 17 mmol, 1.1 eq.) was added to DMF (6 mL) at 00C and the solution was stirred for 30 minutes. This mixture was added to a stirring solution of the selected 5-methoxy- indole (15.5 mmol, 1 eq.) in DMF (11.5 mL) at 00C. The resulting mixture was stirred at 00C for 30 minutes, then allowed to warm to room temperature. The reaction was poured into ice, basified to pH 10 with 5 N NaOH, warmed to room temperature, refluxed for 5 minutes and allowed to cool to rt. Finally, it was acidified to pH 4 with 2 N HCI and the resulting precipitate was filtered and washed with water until pH 7. The solid product was dried under vacuum.5-Methoxy-indole-3-carbaldehydeYield: 85percent. MS (m/z): 176.2 (MH+).
83% at 0 - 40℃; for 1.5 h; General procedure: Phosphorus oxychloride (0.42 g, 2.74 mmol) was added dropwise to a solution of the indole 5b, 5e–5g (0.30 g, 2.29 mmol) in DMF (0.84 g, 11.4 mmol) at 0 °C for 30 min. The solution was then heated at 40 °C for 1 h. Ice was added to the reaction vessel, followed by a solution of sodium hydroxide (2 M). The solution was refluxed for 40 min. The mixture was cooled and extracted using ethyl acetate, and the organic phase was washed with brine. The organic extracts were combined, dried over Na2SO4, and concentrated. The crude residue was purified by chromatography on a silica gel column using hexane-ethyl acetate as an eluent to obtain the desired product [19].
79% at 20℃; for 1 h; A 5-methoxy-1H-indole (14.7 g, 0.1 mol) was dissolved in N, N -dimethylformamide (73.5 g, 1 mol) in a 500ml of reaction flask at 0 ° C with mechanical agitation, then phosphorus pentachloride / N, N -dimethylformamide mixed formylation reagent (15 g, 0.12 mol) was added in portions. The reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction, 100 mL of water was added and stirred at room temperature for 1 hour. The reaction was neutralized with 2N sodium hydroxide solution and the resulting suspension was filtered. The filter cake was dissolved in methanol / tetrahydrofuran and the pH was adjusted to 1 with concentrated hydrochloric acid. The solution was stirred at room temperature for 45 minutes and neutralized with 4N sodium hydroxide solution to neutral. The solvent was partially evaporated to give the product, filtered and washed with water. Finally, 5-methoxy-1-hydrogen-indole-3- carboxaldehyde was obtained (14 g, 79percent). This product can be used in the production of Tegaserod Hydrogen Maleate.
69%
Stage #1: at 20℃; for 0.75 h; Cooling with ice
Stage #2: at 40℃; for 1.25 h;
The Vilsmeier-Haack reagent was generated by the addition of 2 ml of POCI3 over the course of15 minutes to 8 ml of DMF cooled in an ice-salt bath. After the addition was complete, the icebath was removed and the contents of the flask allowed to warm to room temperature overapprox. 30 minutes. The substituted indole (21.9 mmol) was dissolved in 10 ml of DMF andadded over a period of 15 minutes to the formylating mixture. The stirring was continued for an10 hour during which the flask contents were heated to 40°C in a hot water bath. A total of 50 mlice cold H20 and 20 ml of 5 M NaOH were added, the mixture quickly brought to a boil and leftto cool slowly. The crystals were removed by filtration, washed with cold water and vacuumdried. The products thus obtained were in most cases sufficiently pure for the subsequentreactions, and the impure aldehydes were recrystallized from ethanol-water mixtures. Yields15 varied from 48 to 90percent.; The compound was synthesized from 5-methoxy-1H-indole (170 mmol) according to the25 general procedure 2, with the exception that it was scaled up proportionally to the 5-methoxyindole (69percent yield).LC-MS: m/z = 176.11; tR = 2.20 min.
63% at 20℃; for 1 h; (a) 5-methoxyindole (200 mg, 1.36 mmol) dissolved in anhydrous DMF,Drip the newly prepared Vilsmeier reagent,Allow to react at room temperature for one hour, then pour into ice water and filter by suction.Dryed to a yellow solid 150 mg, yield 63percent.

Reference: [1] Organic Letters, 2013, vol. 15, # 11, p. 2636 - 2639
[2] Chinese Chemical Letters, 2010, vol. 21, # 11, p. 1307 - 1309
[3] Synthetic Communications, 1988, vol. 18, # 7, p. 671 - 674
[4] European Journal of Medicinal Chemistry, 2013, vol. 65, p. 158 - 167
[5] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1993, # 21, p. 2561 - 2566
[6] Tetrahedron, 2013, vol. 69, # 50, p. 10733 - 10738
[7] Russian Journal of General Chemistry, 2017, vol. 87, # 12, p. 3006 - 3016
[8] Journal of Medicinal Chemistry, 2004, vol. 47, # 25, p. 6270 - 6282
[9] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6466 - 6476
[10] Patent: WO2010/30727, 2010, A1, . Location in patent: Page/Page column 99
[11] Marine Drugs, 2014, vol. 12, # 4, p. 1757 - 1772
[12] Chemical Biology and Drug Design, 2015, vol. 86, # 4, p. 731 - 745
[13] Angewandte Chemie - International Edition, 2014, vol. 53, # 22, p. 5600 - 5603[14] Angew. Chem., 2014, vol. 126, # 22, p. 5706 - 5709,4
[15] Patent: CN106554345, 2017, A, . Location in patent: Paragraph 0036-0037
[16] Patent: WO2018/15558, 2018, A1, . Location in patent: Page/Page column 15; 29
[17] Patent: CN108191719, 2018, A, . Location in patent: Paragraph 0252
[18] Chimia, 2004, vol. 58, # 9, p. 613 - 620
[19] Organic and Biomolecular Chemistry, 2014, vol. 12, # 48, p. 9764 - 9768
[20] Journal of the Chemical Society, 1958, p. 3493,3494
[21] European Journal of Medicinal Chemistry, 1989, vol. 24, p. 145 - 154
[22] Journal of medicinal chemistry, 1995, vol. 38, # 13, p. 2331 - 2338
[23] Archiv der Pharmazie, 2005, vol. 338, # 2-3, p. 67 - 73
[24] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 6, p. 1793 - 1798
[25] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 8, p. 2342 - 2346
[26] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 8, p. 2586 - 2590
[27] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 212 - 215
[28] Tetrahedron Letters, 2012, vol. 53, # 17, p. 2222 - 2225
[29] European Journal of Medicinal Chemistry, 2012, vol. 52, p. 70 - 81
[30] ChemMedChem, 2012, vol. 7, # 11, p. 1915 - 1920
[31] European Journal of Medicinal Chemistry, 2012, vol. 58, p. 346 - 354
[32] Angewandte Chemie - International Edition, 2013, vol. 52, # 11, p. 3250 - 3254[33] Angew. Chem., 2013, vol. 125, # 11, p. 3332 - 3336,5
[34] Journal of Organic Chemistry, 2013, vol. 78, # 6, p. 2362 - 2372
[35] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 9, p. 2571 - 2574
[36] Organic Letters, 2013, vol. 15, # 24, p. 6262 - 6265
[37] Journal of Asian Natural Products Research, 2013, vol. 15, # 9, p. 985 - 992
[38] European Journal of Medicinal Chemistry, 2014, vol. 81, p. 499 - 509
[39] European Journal of Medicinal Chemistry, 2015, vol. 99, p. 125 - 137
[40] RSC Advances, 2015, vol. 5, # 83, p. 68128 - 68135
[41] Chemistry - A European Journal, 2015, vol. 21, # 43, p. 15104 - 15107
[42] Journal of Medicinal Chemistry, 2016, vol. 59, # 11, p. 5264 - 5283
[43] Biochemistry, 2016, vol. 55, # 21, p. 3020 - 3035
[44] ChemMedChem, 2016, vol. 11, # 13, p. 1446 - 1458
[45] Tetrahedron, 2016, vol. 72, # 49, p. 8042 - 8049
[46] Synthesis (Germany), 2017, vol. 49, # 11, p. 2562 - 2562
[47] European Journal of Medicinal Chemistry, 2017, vol. 132, p. 310 - 321
[48] European Journal of Medicinal Chemistry, 2017, vol. 136, p. 184 - 194
[49] Green Chemistry, 2017, vol. 19, # 13, p. 2952 - 2956
[50] Organic and Biomolecular Chemistry, 2017, vol. 15, # 35, p. 7404 - 7410
[51] RSC Advances, 2016, vol. 6, # 36, p. 30412 - 30424
[52] European Journal of Medicinal Chemistry, 2018, vol. 156, p. 722 - 737
[53] Organic and Biomolecular Chemistry, 2018, vol. 16, # 36, p. 6647 - 6651
  • 3
  • [ 1006-94-6 ]
  • [ 100-97-0 ]
  • [ 10601-19-1 ]
YieldReaction ConditionsOperation in experiment
91% With iodine; oxygen; pyrographite In N,N-dimethyl-formamide at 120℃; for 0.8 h; General procedure: A 50 mL round bottom flask equipped with a magnetic stirring bar was charged with substituted indole 1 (1.0 mmol, 1.0 equiv), HMTA (2.0 mmol, 0.2803 g, 2.0 equiv), activated carbon (0.1 g) and DMF (2 mL). Then I2 (0.2 mmol, 0.0507g, 20 molpercent) was added and the flask was equipped with a reflux condenser. The reaction mixture was stirred at 120 oC under open air and monitored by TLC. Upon completion of the reaction, the reaction mixture was cooled to room temperature. The resultant mixture was filtered through a pad of celite and the filter cake was washed thoroughly with EtOAc (4 × 6 mL). The filtrate was washed with 0.5 M aqueous HCl (10 mL), saturated NaHCO3 solution (10 mL) and saturated NaCl solution ( 10 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel eluted with hexane and ethyl acetate to give the product.
60% With silica supported ceric ammonium nitrate In acetonitrile for 15 h; Reflux General procedure: a mixture of indole (1 mmol), HMTA (2.5 mmol), and 10percent CAN–SiO2 was refluxed in CH3CN (5.0 mL). After the reaction was complete, the mixture was evaporated to give a crude residue of CAN–SiO2 and product. The crude residue was washed with EtOAc (10 mL 5) and dried to leave a crude product that was purified by short flash column chromatography (EtOAc/hexane = 1:3).
Reference: [1] Tetrahedron Letters, 2017, vol. 58, # 30, p. 2877 - 2880
[2] Tetrahedron Letters, 2014, vol. 55, # 29, p. 3909 - 3912
[3] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 18, p. 5909 - 5914
  • 4
  • [ 1006-94-6 ]
  • [ 110-18-9 ]
  • [ 10601-19-1 ]
YieldReaction ConditionsOperation in experiment
72% With water; iodine; oxygen; sodium carbonate In 1,4-dioxane at 100℃; for 36 h; Schlenk technique; Sealed tube General procedure: Under air, a 20 mL of Schlenk tube equipped with a stir bar was charged with indole 1 (0.2 mmol, 1 equiv),TMEDA (75 µL, 0.5 mmol, 2.5 equiv), Na2CO3 (42.4 mg, 0.4mmol, 2.0 equiv), 1,4-dioxane (0.5 mL) and H2O (100 µL). Then I2 (101.5 mg, 0.4 mmol, 2.0 equiv) was added and the tube was sealed with a rubber plug and charged with O2. The reaction mixture was stirred at 100 °C for 36 h in oil bath. After cooling to room temperature, the resultant mixture was evaporated with EtOAc (20 mL) under reduced pressure and the residue was purified by flash column chromatography on a silica gel to give the products.
Reference: [1] Tetrahedron Letters, 2014, vol. 55, # 41, p. 5618 - 5621
  • 5
  • [ 1006-94-6 ]
  • [ 50-00-0 ]
  • [ 10601-19-1 ]
YieldReaction ConditionsOperation in experiment
92% With iron(III) chloride; ammonia In water; N,N-dimethyl-formamide at 130℃; for 1 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
[2] Journal of Medicinal Chemistry, 2006, vol. 49, # 12, p. 3509 - 3519
  • 6
  • [ 1006-94-6 ]
  • [ 10601-19-1 ]
Reference: [1] Synthesis, 2001, # 2, p. 267 - 275
[2] Tetrahedron, 1980, vol. 36, p. 2505 - 2512
[3] Patent: US6433175, 2002, B1,
[4] Patent: US6433175, 2002, B1,
[5] Patent: US6433175, 2002, B1,
  • 7
  • [ 1006-94-6 ]
  • [ 100-61-8 ]
  • [ 10601-19-1 ]
Reference: [1] Journal of the American Chemical Society, 2011, vol. 133, # 31, p. 11924 - 11927
[2] Chemical Communications, 2012, vol. 48, # 42, p. 5187 - 5189
  • 8
  • [ 1006-94-6 ]
  • [ 79-37-8 ]
  • [ 10601-19-1 ]
Reference: [1] Organic Letters, 2015, vol. 17, # 11, p. 2652 - 2655
  • 9
  • [ 1006-94-6 ]
  • [ 67-66-3 ]
  • [ 10601-19-1 ]
Reference: [1] Journal of the Chemical Society, 1924, vol. 125, p. 313
  • 10
  • [ 1006-94-6 ]
  • [ 712-09-4 ]
Reference: [1] Synthesis, 2001, # 2, p. 267 - 275
[2] Patent: WO2012/110986, 2012, A1,
[3] Tetrahedron, 2014, vol. 70, # 33, p. 4910 - 4920
  • 11
  • [ 1006-94-6 ]
  • [ 79-10-7 ]
  • [ 39547-16-5 ]
Reference: [1] Advanced Synthesis and Catalysis, 2016, vol. 358, # 18, p. 2873 - 2877
[2] Organic Letters, 2017, vol. 19, # 23, p. 6336 - 6339
  • 12
  • [ 1006-94-6 ]
  • [ 39547-16-5 ]
Reference: [1] Angewandte Chemie - International Edition, 2016, vol. 55, # 33, p. 9671 - 9675[2] Angew. Chem., 2016, vol. 128, p. 9823 - 9827,5
  • 13
  • [ 1006-94-6 ]
  • [ 60523-82-2 ]
Reference: [1] Synthetic Communications, 1988, vol. 18, # 7, p. 671 - 674
  • 14
  • [ 1006-94-6 ]
  • [ 37795-77-0 ]
Reference: [1] Organic and Biomolecular Chemistry, 2013, vol. 11, # 43, p. 7455 - 7457
  • 15
  • [ 1006-94-6 ]
  • [ 124-38-9 ]
  • [ 10242-01-0 ]
YieldReaction ConditionsOperation in experiment
92% With lithium tert-butoxide In N,N-dimethyl-formamide at 100℃; for 24 h; General procedure: In a dried two-necked test tube was charged with LiOtBu (160 mg, 2.00 mmol) and indole 1a (23.4 mg, 0.4 mmol). The reaction vessel was evacuated under high vacuum and the atmosphere was replace with a balloon of CO2. Then DMF (2 mL) was added and the mixture was stirred for 24 h at 100°C. Then the result mixture was cooled and carefully quenched with a solution of HCl (2 N) and extracted with EtOAc (5x). The combined organic layers were washed with water (2x), brine (1x) and dry over MgSO4. The dried organics were concentrated under reduce pressure and the residue was purified by preparative TLC (hexane:acetone = 1:1) to afford the desired product 2a (153.0 mg, 95percent) as a white solid.
Reference: [1] Organic Letters, 2012, vol. 14, # 20, p. 5326 - 5329,4
[2] Heterocycles, 2015, vol. 90, # 2, p. 1196 - 1204
  • 16
  • [ 1006-94-6 ]
  • [ 10242-01-0 ]
Reference: [1] Patent: US4940703, 1990, A,
[2] Journal of Medicinal Chemistry, 2014, vol. 57, # 17, p. 7293 - 7316
[3] Russian Journal of General Chemistry, 2017, vol. 87, # 12, p. 3006 - 3016
[4] Patent: WO2009/125923, 2009, A2,
  • 17
  • [ 1006-94-6 ]
  • [ 52157-82-1 ]
Reference: [1] Journal of Medicinal Chemistry, 2004, vol. 47, # 25, p. 6326 - 6337
[2] European Journal of Medicinal Chemistry, 2013, vol. 63, p. 484 - 500
[3] Patent: WO2004/43949, 2004, A1,
  • 18
  • [ 1006-94-6 ]
  • [ 40064-34-4 ]
  • [ 52157-82-1 ]
Reference: [1] Patent: US2002/147344, 2002, A1,
  • 19
  • [ 41661-47-6 ]
  • [ 1006-94-6 ]
  • [ 52157-82-1 ]
Reference: [1] Patent: US2004/116471, 2004, A1,
  • 20
  • [ 1006-94-6 ]
  • [ 6705-03-9 ]
Reference: [1] Synthetic Communications, 2010, vol. 40, # 23, p. 3480 - 3487
[2] Applied Organometallic Chemistry, 2011, vol. 25, # 1, p. 34 - 46
  • 21
  • [ 1006-94-6 ]
  • [ 21857-45-4 ]
YieldReaction ConditionsOperation in experiment
95.9% at 25℃; for 1 h; At 25 , 5-methoxy-indole (1.5g, 10.2mmol) was added to acetic acid (20 mL), and then added portionwise sodium cyanoborohydride (0.77g, 12.2mmol), 1 hour reaction, was added sodium hydroxide solution (20percent) neutralized to pH = 9 ~ 10, then ethyl acetate (50 mL) and extracted, the organic phase after separation was dried over anhydrous sodium sulfate. Filtered, the filtrate was spin dry, purified by column chromatography (petroleum ether / ethyl acetate (v / v) = 10/1) to give the title compound as a brown solid (1.46g, 95.9percent).
94% With sodium cyanoborohydride In acetic acid; ethyl acetate Reference Example 8-1
5-methoxy-2,3-dihydro-1H-indole
To a solution of 5-methoxyindole (528 mg, 3.6 mmol) in acetic acid (5 mL) was added sodium cyanoborohydride (452 mg, 7.2 mmol) by small portions at room temperature and the mixture was stirred for 18 h in situ.
The solvent was evaporated under reduced pressure and the obtained residue was dissolved in ethyl acetate.
The organic layer was washed with saturated aqueous sodium hydrogencarbonate solution (*3) and saturated brine, and dried over anhydrous sodium sulfate.
The solvent was evaporated under reduced pressure to give almost pure title compound (503 mg, 94percent).
86.3% at 20℃; for 2.5 h; 5-methoxy-1H-indole (0.4 g, 2.72 mmol) was weighed into a three-necked flask,Add acetic acid (25mL), add in batchesSodium cyanoborohydride (0.51 g, 8.16 mmol),After it is added, continue to react at room temperature.Check the progress of the reaction through the TLC point plate,About 2.5 hours after the reaction is completed,After processing,Add water (3mL) to quench,With saturated sodium bicarbonate solution adjusted pH = 5 ~ 6, DCM (10mL × 4) extraction,Combine organic layers,Dry with anhydrous magnesium sulfateconcentrate,The title compound (0.35 g, yield 86.3percent) was obtained.
Reference: [1] Organic Letters, 2011, vol. 13, # 19, p. 5124 - 5127
[2] Chemical Communications, 2013, vol. 49, # 63, p. 7052 - 7054
[3] Patent: CN105367474, 2016, A, . Location in patent: Paragraph 0194; 0195; 0196; 0197
[4] Journal of Medicinal Chemistry, 1997, vol. 40, # 4, p. 479 - 485
[5] Patent: EP1223170, 2002, A1,
[6] Chemistry - A European Journal, 2015, vol. 21, # 14, p. 5370 - 5379
[7] Journal of Medicinal Chemistry, 2000, vol. 43, # 25, p. 4850 - 4867
[8] Journal of the American Chemical Society, 2017, vol. 139, # 44, p. 15596 - 15599
[9] Patent: CN107793413, 2018, A, . Location in patent: Paragraph 0223-0226
[10] Heterocycles, 1992, vol. 34, # 5, p. 1031 - 1038
[11] Angewandte Chemie - International Edition, 2016, vol. 55, # 40, p. 12219 - 12223[12] Angew. Chem., 2016, vol. 128, p. 12407 - 12411,5
[13] Journal of Organic Chemistry, 1992, vol. 57, # 8, p. 2508 - 2511
[14] Organic Letters, 2013, vol. 15, # 11, p. 2798 - 2801
[15] Liebigs Annalen der Chemie, 1982, vol. No. 5, p. 830 - 844
[16] Heterocycles, 1980, vol. 14, # 10, p. 1441 - 1444
[17] Journal of the American Chemical Society, 2015, vol. 137, # 36, p. 11718 - 11724
[18] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 6, p. 845 - 848
[19] Patent: US6245769, 2001, B1,
[20] Journal of Medicinal Chemistry, 2008, vol. 51, # 14, p. 4351 - 4355
[21] Patent: US2009/176794, 2009, A1, . Location in patent: Page/Page column 3
[22] Patent: US2009/233910, 2009, A1, . Location in patent: Page/Page column 88
[23] Patent: WO2012/110986, 2012, A1, . Location in patent: Page/Page column 50
[24] Organic and Biomolecular Chemistry, 2013, vol. 11, # 7, p. 1209 - 1215
[25] Organic Letters, 2013, vol. 15, # 22, p. 5662 - 5665
[26] Chemistry - A European Journal, 2014, vol. 20, # 1, p. 58 - 63
[27] RSC Advances, 2015, vol. 5, # 30, p. 23727 - 23736
[28] Journal of Organic Chemistry, 2016, vol. 81, # 2, p. 396 - 403
[29] Journal of Organic Chemistry, 2018, vol. 83, # 4, p. 2425 - 2437
[30] Organic and Biomolecular Chemistry, 2018, vol. 16, # 32, p. 5889 - 5898
[31] Chemical Communications, 2018, vol. 54, # 20, p. 2494 - 2497
  • 22
  • [ 1006-94-6 ]
  • [ 497-19-8 ]
  • [ 21857-45-4 ]
YieldReaction ConditionsOperation in experiment
96% With hydrogenchloride; sodium hydroxide; borane In tetrahydrofuran; BH3 Preparation 13
5-Methoxy-indoline
To 5-methoxy-indole (4.55 g, 31 mmol) suspended in THF (10 mL) at 0°-5° C. was added borane/pyridine complex (15.5 ml of 8M in BH3) followed by dropwise aqueous 6N HCl (50 mL) over 15 min.
During the addition THF was added dropwise as required to control foaming.
The mixture was stirred 45 min at 20° C., the pH was raised to ~10 by the addition of aqueous NaOH and Na2 CO3, and the mixture was extracted with CHCl3.
The organic extracts were washed with brine at pH 9-10 dried over MgSO4(s), filtered, and concentrated in vacuo to afford 5-methoxy-indoline (96percent; GC-MS: RT=min, M+ =149) which was >97percent purity by 1 H NMR.
Reference: [1] Patent: US5736534, 1998, A,
  • 23
  • [ 1006-94-6 ]
  • [ 18334-96-8 ]
Reference: [1] Patent: WO2012/110986, 2012, A1,
  • 24
  • [ 1006-94-6 ]
  • [ 39974-94-2 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 6, p. 1793 - 1798
[2] Organic Letters, 2013, vol. 15, # 11, p. 2636 - 2639
[3] Angewandte Chemie - International Edition, 2014, vol. 53, # 41, p. 11051 - 11055[4] Angew. Chem., 2014, vol. 126, # 41, p. 11231 - 11235,5
[5] European Journal of Medicinal Chemistry, 2015, vol. 99, p. 125 - 137
[6] RSC Advances, 2015, vol. 5, # 83, p. 68128 - 68135
[7] Chemical Biology and Drug Design, 2015, vol. 86, # 4, p. 731 - 745
[8] Journal of Medicinal Chemistry, 2016, vol. 59, # 11, p. 5264 - 5283
[9] ChemMedChem, 2016, vol. 11, # 13, p. 1446 - 1458
[10] European Journal of Medicinal Chemistry, 2017, vol. 132, p. 310 - 321
[11] Organic and Biomolecular Chemistry, 2017, vol. 15, # 35, p. 7404 - 7410
[12] RSC Advances, 2016, vol. 6, # 36, p. 30412 - 30424
[13] European Journal of Medicinal Chemistry, 2018, vol. 156, p. 722 - 737
  • 25
  • [ 1006-94-6 ]
  • [ 85092-83-7 ]
YieldReaction ConditionsOperation in experiment
90% With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione In 1,4-dioxane at 10℃; General procedure: DBDMH (157 mg, 0.55 mmol) was added in five potion to a solution ofindoles (1.0 mmol) in dioxane at 10 °C over two minutes with stir, and the resulting solution was stirred for 5to 10 minutes. TLC indicate that the reaction is completed. The reactionsolution was poured into the saturated NaHCO3 solution (10 mL), themixtures was extracted by ethyl acetate (15 mL*2). The organic phase was dried over Na2SO4,filtered, concentrated under reduced pressure. The residue was then purified byflash chromatography on 200~300 mesh silica gel to provide the correspondingproduct 2.
74% With bromine In N,N-dimethyl-formamide for 24 h; A solution of Br2 (0.70 mL, 13.73 mmol, 1.01 eq.) in DMF (80 mL) has been added dropwise, during few minutes, to a solution of 5-methoxy indole 1 (2 g, 13.59 mmol, 1 eq) in DMF (80 mL) at room temperature under vigorous stirring. The mixture turned orange. The reaction has been monitored by TLC (eluents: n-Hexane/EtOAc 8:2). After 19 hours, additional 0.1 equivalents of bromine (0.07 mL, 0.01 mmol) have been added. After 5 hours the reaction is complete, and the mixture is poured into an aqueous solution (~1.6 L) containing ammonia (0.5percent) and Na2S203-5H20 (0.1percent) [1.6 L H20, 28.53 mL NH3, 2.48 g Na2S203, 5H20). The formed brownish precipitate has been filtered on a Buchner funnel and washed with cold water (4 x 100 mL). The solid has been dried overnight in the crystallization vessel. Pure 3- bromo-5-methoxyindole 2 has been obtained as brownish amorphous solid. 2. Yield: 74percent (2.28 g, MW 226.07, 10.08 mmol). Analytical characterization: - NMR (400 MHz, acetone-d6): δ: 10.41 (bs, 1H), 7.40 (d, 1H), 7.35 (d, J = 8.8 Hz, 1H), 6.93 (d, J = 2.4 Hz, 1H), 6.84 (dd, J = 8.8, 2.4 Hz, 1H), 3.84, (s, 3H).
Reference: [1] Synthesis, 1982, # 12, p. 1096 - 1097
[2] Gazzetta Chimica Italiana, 1982, vol. 112, # 11/12, p. 535 - 536
[3] Tetrahedron Letters, 2015, vol. 56, # 9, p. 1096 - 1098
[4] Tetrahedron, 2006, vol. 62, # 12, p. 2820 - 2830
[5] New Journal of Chemistry, 2018, vol. 42, # 23, p. 18889 - 18893
[6] Patent: WO2017/216732, 2017, A1, . Location in patent: Page/Page column 63; 64
[7] Journal of Medicinal Chemistry, 2018, vol. 61, # 4, p. 1483 - 1498
[8] Tetrahedron Letters, 2010, vol. 51, # 43, p. 5640 - 5642
[9] European Journal of Medicinal Chemistry, 2012, vol. 54, p. 626 - 636
  • 26
  • [ 1006-94-6 ]
  • [ 56-45-1 ]
  • [ 25197-96-0 ]
Reference: [1] Angewandte Chemie - International Edition, 2016, vol. 55, # 38, p. 11577 - 11581[2] Angew. Chem., 2016, vol. 128, p. 11749 - 11753,5
  • 27
  • [ 1006-94-6 ]
  • [ 25197-96-0 ]
Reference: [1] Patent: WO2016/115188, 2016, A1,
  • 28
  • [ 1006-94-6 ]
  • [ 192189-10-9 ]
Reference: [1] Tetrahedron, 2000, vol. 56, # 43, p. 8473 - 8480
[2] Journal of Medicinal Chemistry, 1997, vol. 40, # 15, p. 2430 - 2433
[3] European Journal of Organic Chemistry, 2011, # 24, p. 4532 - 4535
[4] European Journal of Organic Chemistry, 2013, # 21, p. 4564 - 4569
  • 29
  • [ 1006-94-6 ]
  • [ 24424-99-5 ]
  • [ 192189-10-9 ]
Reference: [1] Chemical Biology and Drug Design, 2010, vol. 76, # 2, p. 100 - 106
  • 30
  • [ 67-56-1 ]
  • [ 1006-94-6 ]
  • [ 76-02-8 ]
  • [ 172595-68-5 ]
Reference: [1] Journal of the American Chemical Society, 2008, vol. 130, # 48, p. 16162 - 16163
  • 31
  • [ 1006-94-6 ]
  • [ 24424-99-5 ]
  • [ 348640-11-9 ]
Reference: [1] Patent: US2004/9983, 2004, A1, . Location in patent: Page/Page column 108
Recommend Products
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 1006-94-6 ]

Ethers

Chemical Structure| 1076-74-0

[ 1076-74-0 ]

5-Methoxy-2-methyl-1H-indole

Similarity: 0.98

Chemical Structure| 10501-17-4

[ 10501-17-4 ]

5-Ethoxy-1H-indole

Similarity: 0.96

Chemical Structure| 14430-23-0

[ 14430-23-0 ]

5,6-Dimethoxyindole

Similarity: 0.94

Chemical Structure| 13838-47-6

[ 13838-47-6 ]

5-Methoxy-1H-indol-7-amine

Similarity: 0.94

Chemical Structure| 885522-46-3

[ 885522-46-3 ]

4-Methoxy-6-methyl-1H-indole

Similarity: 0.92

Related Parent Nucleus of
[ 1006-94-6 ]

Indoles

Chemical Structure| 1076-74-0

[ 1076-74-0 ]

5-Methoxy-2-methyl-1H-indole

Similarity: 0.98

Chemical Structure| 10501-17-4

[ 10501-17-4 ]

5-Ethoxy-1H-indole

Similarity: 0.96

Chemical Structure| 14430-23-0

[ 14430-23-0 ]

5,6-Dimethoxyindole

Similarity: 0.94

Chemical Structure| 13838-47-6

[ 13838-47-6 ]

5-Methoxy-1H-indol-7-amine

Similarity: 0.94

Chemical Structure| 885522-46-3

[ 885522-46-3 ]

4-Methoxy-6-methyl-1H-indole

Similarity: 0.92