CN102977000A - Synthetic method of 3-methoxy-7-nitroindoline - Google Patents
Synthetic method of 3-methoxy-7-nitroindoline Download PDFInfo
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- CN102977000A CN102977000A CN2012105001232A CN201210500123A CN102977000A CN 102977000 A CN102977000 A CN 102977000A CN 2012105001232 A CN2012105001232 A CN 2012105001232A CN 201210500123 A CN201210500123 A CN 201210500123A CN 102977000 A CN102977000 A CN 102977000A
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Abstract
The invention discloses a synthetic method of 3-methoxy-7-nitroindoline, belonging to the technical field of medicine and chemistry. 3-methoxy-7-nitroindoline is an important medical intermediate. Through exploration and practice, a method for synthesizing 3-methoxy-7-nitroindoline is obtained. The yield of the reaction is increased and the cost is reduced.
Description
Technical field
The present invention relates to the synthetic process of a kind of 3-methoxyl group-7-nitro indoline, belong to medicine, chemical technology field.
Background technology
3-methoxyl group-7-nitro indoline is a kind of white solid, is a kind of important medicine intermediate, and this patent provides a kind of method of synthetic 3-methoxyl group-7-nitro indoline.
Summary of the invention
The synthetic method of 3-methoxyl group of the present invention-7-nitro indoline; that employing 3-methoxy-Indole is raw material; at ambient temperature; after the acetic acid mixing; add boron hydrogen nitrilation sodium in batches; after reacting completely; after Rotary Evaporators evaporates most of acetic acid; after the ethyl acetate dilution; saturated sodium bicarbonate is transferred about pH to 8; separate organic layer, Rotary Evaporators is spin-dried for solvent behind the anhydrous sodium sulfate drying, gets intermediate; after intermediate is dissolved in pyridine; add aceticanhydride reaction one hour, obtain 15g1-ethyl ketone base-3-melonia indoles, stir at-10 degree with SODIUMNITRATE in the lower trifluoroacetic acid of nitrogen chlorine protection; add 1-ethyl ketone base-3-melonia indole reaction in batches; obtain 1-ethyl ketone base-3-methoxyl group-7-nitro indoline, 1-ethyl ketone base-3-methoxyl group-7-nitro indoline reacts in dilute hydrochloric acid, obtains 3-methoxyl group-7-nitro indoline.
The synthetic method of above-mentioned 3-methoxyl group-7-nitro indoline is characterized in that: after described intermediate is dissolved in pyridine, add aceticanhydride reaction one hour, wherein react and referred in one hour, long reaction time can make reaction product be difficult to purifying, and reaction time range is 0.5 ~ 2 hour.
The synthetic method of above-mentioned 3-methoxyl group-7-nitro indoline; it is characterized in that: stir at-10 degree with SODIUMNITRATE in the lower trifluoroacetic acid of described nitrogen chlorine protection; add 1-ethyl ketone base-3-melonia indole reaction in batches; wherein add 1-ethyl ketone base-3-melonia indoles, be in order to improve reaction yield in batches.
The synthetic method of above-mentioned 3-methoxyl group-7-nitro indoline, it is characterized in that: be after adopting the 20g3-methoxy-Indole to be raw material and the mixing of 250mL acetic acid, slowly add 17.5g boron hydrogen nitrilation sodium in batches, after adding, continue to stir 20 minutes, after chromatoplate is followed the tracks of and is reacted completely, after evaporating most of acetic acid, after the ethyl acetate dilution, saturated sodium bicarbonate solution is transferred pH to 8, separate organic layer, anhydrous sodium sulfate drying is spin-dried for, get the 29g intermediate, after the 29g intermediate is dissolved in the 400mL pyridine, add the 150mL aceticanhydride, back flow reaction one hour, after chromatoplate is followed the tracks of and is reacted completely, be cooled to room temperature, add the ethyl acetate dilution, 1mol/LHCl (2*600mL), after water (1*600mL) and saturated aqueous common salt (1*600mL) washing, Rotary Evaporators is spin-dried for, after sherwood oil and the washing of ethyl acetate mixed solvent (PE:EA=50:1), filter, obtain 15g 1-ethyl ketone base-3-melonia indoles, under-10 degree conditions, slowly add 1-ethyl ketone base-3-melonia indoles in the mixture of 7.4g SODIUMNITRATE and 250mL trifluoroacetic acid, continued again stirring reaction 30 minutes, chromatoplate is poured reaction solution in the 1200mL frozen water into ethyl acetate extraction after following the tracks of and reacting completely, organic layer is water respectively, the saturated common salt water washing, behind the anhydrous sodium sulfate drying, Rotary Evaporators is spin-dried for mixes sample, the chromatography column purifying, obtain 10g1-ethyl ketone base-3-methoxyl group-7-nitro indoline, 1-ethyl ketone base-3-methoxyl group-7-nitro indoline is dissolved in the 1mol/L dilute hydrochloric acid back flow reaction 3 hours, after chromatoplate is followed the tracks of and is reacted completely, the cooling room temperature has solid to separate out, and filters, recrystallization gets 5g3-methoxyl group-7-nitro indoline.
Above-mentioned with the 3-methoxy-Indole, boron hydrogen nitrilation sodium, aceticanhydride and SODIUMNITRATE etc. are as follows for chemical reaction and the reaction formula of the synthetic 3-methoxyl group of raw material-7-nitro indoline:
(1) the synthetic 1-ethyl ketone base of 3-methoxy-Indole-3-melonia indole reaction equation is:
(2) reaction equation of 1-ethyl ketone base-3-melonia indoles and SODIUMNITRATE is:
(3) reaction equation of 1-ethyl ketone base-3-methoxyl group-7-nitro indoline and dilute hydrochloric acid is:
Behind the solid filtering of (4) separating out, recrystallization gets 3-methoxyl group-7-nitro indoline.
Embodiment
Embodiment:
The synthetic method of described 3-methoxyl group-7-nitro indoline, after adopting the 20g3-methoxy-Indole to be raw material and the mixing of 250mL acetic acid, slowly add 17.5g boron hydrogen nitrilation sodium in batches, after adding, continue to stir 20 minutes, after chromatoplate is followed the tracks of and is reacted completely, after evaporating most of acetic acid, after the ethyl acetate dilution, saturated sodium bicarbonate solution is transferred pH to 8, separate organic layer, anhydrous sodium sulfate drying is spin-dried for, get the 29g intermediate, after the 29g intermediate is dissolved in the 400mL pyridine, add the 150mL aceticanhydride, back flow reaction one hour, after chromatoplate is followed the tracks of and is reacted completely, be cooled to room temperature, add the ethyl acetate dilution, 1mol/LHCl (2*600mL), after water (1*600mL) and saturated aqueous common salt (1*600mL) washing, Rotary Evaporators is spin-dried for, after sherwood oil and the washing of ethyl acetate mixed solvent (PE:EA=50:1), filter, obtain 15g 1-ethyl ketone base-3-melonia indoles, under-10 degree conditions, slowly add 1-ethyl ketone base-3-melonia indoles in the mixture of 7.4g SODIUMNITRATE and 250mL trifluoroacetic acid, continued again stirring reaction 30 minutes, chromatoplate is poured reaction solution in the 1200mL frozen water into ethyl acetate extraction after following the tracks of and reacting completely, organic layer is water respectively, the saturated common salt water washing, behind the anhydrous sodium sulfate drying, Rotary Evaporators is spin-dried for mixes sample, the chromatography column purifying, obtain 10g1-ethyl ketone base-3-methoxyl group-7-nitro indoline, 1-ethyl ketone base-3-methoxyl group-7-nitro indoline is dissolved in the 1mol/L dilute hydrochloric acid back flow reaction 3 hours, after chromatoplate is followed the tracks of and is reacted completely, the cooling room temperature has solid to separate out, and filters, recrystallization gets 5g3-methoxyl group-7-nitro indoline.
Claims (4)
1.3-the synthetic method of methoxyl group-7-nitro indoline; that employing 3-methoxy-Indole is raw material; at ambient temperature; after the acetic acid mixing; add boron hydrogen nitrilation sodium in batches; after reacting completely; after Rotary Evaporators evaporates most of acetic acid; after the ethyl acetate dilution; saturated sodium bicarbonate is transferred about pH to 8; separate organic layer, Rotary Evaporators is spin-dried for solvent behind the anhydrous sodium sulfate drying, gets intermediate; after intermediate is dissolved in pyridine; add aceticanhydride reaction one hour, obtain 15g1-ethyl ketone base-3-melonia indoles, stir at-10 degree with SODIUMNITRATE in the lower trifluoroacetic acid of nitrogen chlorine protection; add 1-ethyl ketone base-3-melonia indole reaction in batches; obtain 1-ethyl ketone base-3-methoxyl group-7-nitro indoline, 1-ethyl ketone base-3-methoxyl group-7-nitro indoline reacts in dilute hydrochloric acid, obtains 3-methoxyl group-7-nitro indoline.
2. the synthetic method of 3-methoxyl group-7-nitro indoline as claimed in claim, it is characterized in that: after described intermediate is dissolved in pyridine, add aceticanhydride reaction one hour, wherein react and referred in one hour, long reaction time, can make reaction product be difficult to purifying, reaction time range is 0.5 ~ 2 hour.
3. the synthetic method of 3-methoxyl group-7-nitro indoline as claimed in claim; it is characterized in that: stir at-10 degree with SODIUMNITRATE in the lower trifluoroacetic acid of described nitrogen chlorine protection; add 1-ethyl ketone base-3-melonia indole reaction in batches; wherein add 1-ethyl ketone base-3-melonia indoles, be in order to improve reaction yield in batches.
4. the synthetic method of 3-methoxyl group-7-nitro indoline as claimed in claim, it is characterized in that: be after adopting the 20g3-methoxy-Indole to be raw material and the mixing of 250mL acetic acid, slowly add 17.5g boron hydrogen nitrilation sodium in batches, after adding, continue to stir 20 minutes, after chromatoplate is followed the tracks of and is reacted completely, after evaporating most of acetic acid, after the ethyl acetate dilution, saturated sodium bicarbonate solution is transferred pH to 8, separate organic layer, anhydrous sodium sulfate drying is spin-dried for, get the 29g intermediate, after the 29g intermediate is dissolved in the 400mL pyridine, add the 150mL aceticanhydride, back flow reaction one hour, after chromatoplate is followed the tracks of and is reacted completely, be cooled to room temperature, add the ethyl acetate dilution, 1mol/LHCl (2*600mL), after water (1*600mL) and saturated aqueous common salt (1*600mL) washing, Rotary Evaporators is spin-dried for, after sherwood oil and the washing of ethyl acetate mixed solvent (PE:EA=50:1), filter, obtain 15g 1-ethyl ketone base-3-melonia indoles, under-10 degree conditions, slowly add 1-ethyl ketone base-3-melonia indoles in the mixture of 7.4g SODIUMNITRATE and 250mL trifluoroacetic acid, continued again stirring reaction 30 minutes, chromatoplate is poured reaction solution in the 1200mL frozen water into ethyl acetate extraction after following the tracks of and reacting completely, organic layer is water respectively, the saturated common salt water washing, behind the anhydrous sodium sulfate drying, Rotary Evaporators is spin-dried for mixes sample, the chromatography column purifying, obtain 10g1-ethyl ketone base-3-methoxyl group-7-nitro indoline, 1-ethyl ketone base-3-methoxyl group-7-nitro indoline is dissolved in the 1mol/L dilute hydrochloric acid back flow reaction 3 hours, after chromatoplate is followed the tracks of and is reacted completely, the cooling room temperature has solid to separate out, and filters, recrystallization gets 5g3-methoxyl group-7-nitro indoline.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2012105001232A CN102977000A (en) | 2012-11-30 | 2012-11-30 | Synthetic method of 3-methoxy-7-nitroindoline |
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| CN2012105001232A CN102977000A (en) | 2012-11-30 | 2012-11-30 | Synthetic method of 3-methoxy-7-nitroindoline |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002083639A1 (en) * | 2001-04-11 | 2002-10-24 | Medical Research Council | Process for nitrating photocleavable compounds |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002083639A1 (en) * | 2001-04-11 | 2002-10-24 | Medical Research Council | Process for nitrating photocleavable compounds |
Non-Patent Citations (3)
| Title |
|---|
| ALEEM GANGJEE, ET AL.: "Synthesis and Biological Evaluation of Nonclassical 2,4-Diamino-5-methylpyrido[2,3-d]pyrimidines with Novel Side Chain Substituents as Potential Inhibitors of Dihydrofolate Reductases", 《J. MED. CHEM.》, vol. 40, no. 4, 31 December 1997 (1997-12-31), pages 479 - 485 * |
| GEORGE PAPAGEORGIOU, ET AL.: "Effects of Aromatic Substituents on the Photocleavage of 1-Acyl-7-nitroindolines", 《TETRAHEDRON》, vol. 56, 31 December 2000 (2000-12-31), pages 8197 - 8205 * |
| GEORGE PAPAGEORGIOU, ET AL.: "Synthetic and photochemical studies of substituted 1-acyl-7-nitroindolines", 《PHOTOCHEM. PHOTOBIOL. SCI.》, vol. 4, 14 September 2005 (2005-09-14), pages 887 - 896 * |
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Application publication date: 20130320 |