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Product Citations

Product Citations

Shriver, James A. ; Kaller, Kaylie S. ; Kinsey, Ally L. ; Wang, Katelyn R. ; Sterrenberg, Summer R. ; Van Vors, Madison K. , et al.

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.

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Product Details of 5-Nitroindole

CAS No. :6146-52-7
Formula : C8H6N2O2
M.W : 162.15
SMILES Code : O=N(=O)C1=CC2=C(NC=C2)C=C1
MDL No. :MFCD00005673
InChI Key :OZFPSOBLQZPIAV-UHFFFAOYSA-N
Pubchem ID :22523

Safety of 5-Nitroindole

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H341
Precautionary Statements:P501-P202-P201-P280-P308+P313-P405

Application In Synthesis of 5-Nitroindole

* 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 [ 6146-52-7 ]
  • Downstream synthetic route of [ 6146-52-7 ]

[ 6146-52-7 ] Synthesis Path-Upstream   1~2

  • 1
  • [ 24424-99-5 ]
  • [ 6146-52-7 ]
  • [ 166104-19-4 ]
YieldReaction ConditionsOperation in experiment
100% at 0℃; for 0.0833333 h; Nitro-lH-indole (325 mg, 2.0 mmol)In dichloromethane (6 mL) was added di-tert-butyl dicarbonateEster (524 mg, 2.4 mmol),Stirred at 0 ° C for 5 minutes,A further catalytic amount of 4-dimethylaminopyridine (3 mg, 0.025 mmol) was added,Stirring is then continued for 30 minutes at room temperature.Quenched by adding water (2 mL)Extract with dichloromethane (15 mL x 3).The combined organic phase was washed with water (20 mL)Saturated brine (15 mL × 2)Dried over anhydrous sodium sulfate,The solvent was distilled off under reduced pressure,Obtained as a gray solid (526 mg, 100percent),Directly used for the next reaction.
99% With dmap In tetrahydrofuran at 0 - 20℃; for 3 h; Di-tert-butyl dicarbonate (8.07 g, 37.0 mmol)was siowly added to a stirred solution of 5-nitroindole (6.00 g, 37.0 mmol) and 4-dimethyianiinopyridine (226 Ing, 185 mmol) in THF (60 niL) at 0 °C. The mixture was then stirred for 3h at 20 °C. The reaction solution was concentrated in vacuo and the residue was dissolved in DCM (150 rnL). The organic layer was washed with water, brine, dried (MgSO4), filtered, and the solvent evaporated in vaeuo to yield the title compound (9.60 g, 99percent).
98% With triethylamine In dichloromethane at 0 - 20℃; Triethylamine (3.1 mL, 22.2 mmol) and 4-dimethylaminopyridine (226 mg, 1.85 mmol) were added to a solution of 5-nitro-1H-indole (3 g, 18.5 mmol) in DCM (30 mL) at 0° C., di-tert-butyl dicarbonate (4.3 g, 19.7 mmol) was then added.
The resulting mixture was warmed to room temperature and it was stirred overnight, it was then quenched by addition of water and extracted with DCM.
The organic extracts were dried over MgSO4, filtered and evaporated under reduced pressure; the crude residue was filtered through a silica pad and the filtrate was evaporated under reduced pressure to give 4.77 g (98percent yield) of 5-nitro-indole-1-carboxylic acid tert-butyl ester.
89% With dmap In dichloromethane at 20℃; for 1 h; 4-DMAP (414.4 mg, 3.4 mmol) and di-tert-butyl dicarbonate (740.3 mg, 3.4 mmol) were added to 5-nitro- l //-indole (500.0 mg, 3.1 mmol) in DCM (5 mL), stirred for 1 h at ambient temperature, 2 M HCL was added followed by extraction with DCM, organic phase was collected and the solvent was removed un- der reduced pressure. Yield 724.0 mg (89percent). HPLC 100percent. LC-MS 263 (M+H)+.
78% With dmap In tetrahydrofuran; ethyl acetate Part F.
5-Nitro-1H-indole (2.5 g, 15 mmol), di-tert-butyl dicarbonate (3.6 g, 17 mmol), and DMAP (190 mg, 1.5 mmol) were dissolved in 150 mL of THF.
The solution was stirred for 12 h at rt under N2 and was then concentrated.
The residue was taken up in EtOAc and the mixture was filtered.
The filtered solid was washed with 100 mL of hexanes and dried to give tert-butyl-5-nitro-1H-indole-1-carboxylate as an off-white solid (3.1 g, 78percent). LRMS (AP+): 304.2 (M+H+ACN)+. 1H NMR (CDCl3) δ8.51 (d, 1H), 8.23-8.29 (m, 2H), 7.75 (d, 1H), 6.73 (d, 1H), 1.71 (s, 9H).
78% With dmap In tetrahydrofuran at 20℃; for 12 h; Inert atmosphere Part F.
5-Nitro-1H-indole (2.5 g, 15 mmol), di-tert-butyl dicarbonate (3.6 g, 17 mmol), and DMAP (190 mg, 1.5 mmol) were dissolved in 150 mL of THF.
The solution was stirred for 12 h at rt under N2 and was then concentrated.
The residue was taken up in EtOAc and the mixture was filtered.
The filtered solid was washed with 100 mL of hexanes and dried to give tert-butyl-5-nitro-1H-indole-1-carboxylate as an off-white solid (3.1 g, 78percent). LRMS (AP+): 304.2 (M+H+ACN)+. 1H NMR (CDCl3) δ 8.51 (d, 1H), 8.23-8.29 (m, 2H), 7.75 (d, 1H), 6.73 (d, 1H), 1.71 (s, 9H).
1 g With dmap; triethylamine In dichloromethane at 20℃; for 16 h; 1(1.0 g, 6.17 mmol), DCM (30 mL). DMAP (cat.), TEA (3 eq), (Boc)20 (1.2 eq) reacted at RT. After 16 h anon-polar product was observed by TLC. The reaction was quenched with ice cold water and extracted with DCM (2X10 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford crude material which was purified by silica gel column chromatography [using 100-200 mesh, eluting with 10percent EtOAc-hexanej to afford 1 g of 2.

References: [1] Journal of Medicinal Chemistry, 2013, vol. 56, # 15, p. 6273 - 6277.
[2] Patent: CN104311541, 2017, B, . Location in patent: Paragraph 0162; 0163.
[3] Synthesis, 2009, # 21, p. 3617 - 3632.
[4] Patent: WO2016/176460, 2016, A1, . Location in patent: Page/Page column 96.
[5] Patent: US2009/247568, 2009, A1, . Location in patent: Page/Page column 35-36.
[6] Patent: WO2007/147874, 2007, A1, . Location in patent: Page/Page column 158-159.
[7] Synlett, 2008, # 2, p. 294 - 296.
[8] Patent: US2003/191115, 2003, A1, .
[9] Patent: US2017/50964, 2017, A1, . Location in patent: Paragraph 0733.
[10] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 23, p. 6481 - 6488.
[11] Journal of Medicinal Chemistry, 2011, vol. 54, # 4, p. 1106 - 1110.
[12] Patent: WO2016/73652, 2016, A1, . Location in patent: Page/Page column 121.
  • 2
  • [ 6146-52-7 ]
  • [ 686747-51-3 ]
References: [1] Collection of Czechoslovak Chemical Communications, 2006, vol. 71, # 6, p. 899 - 911.
[2] Journal of Medicinal Chemistry, 2012, vol. 55, # 22, p. 9875 - 9890.
[3] Organic Letters, 2016, vol. 18, # 24, p. 6504 - 6507.
[4] Patent: WO2007/135380, 2007, A2, .
 

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