CN108727157B - Process for preparing glucagon receptor antagonist intermediates - Google Patents
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- CN108727157B CN108727157B CN201810738529.1A CN201810738529A CN108727157B CN 108727157 B CN108727157 B CN 108727157B CN 201810738529 A CN201810738529 A CN 201810738529A CN 108727157 B CN108727157 B CN 108727157B
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- 229940122904 Glucagon receptor antagonist Drugs 0.000 title claims abstract description 13
- 239000000543 intermediate Substances 0.000 title description 8
- 238000004519 manufacturing process Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 10
- 238000006243 chemical reaction Methods 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 7
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 7
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims abstract description 5
- 239000000126 substance Substances 0.000 claims description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 8
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N benzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 claims description 8
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 claims description 6
- RIYABMKGORLKGD-UHFFFAOYSA-N 4-(4-tert-butylphenyl)-3,5-dimethylphenol Chemical compound CC1=CC(O)=CC(C)=C1C1=CC=C(C(C)(C)C)C=C1 RIYABMKGORLKGD-UHFFFAOYSA-N 0.000 claims description 5
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims description 4
- 239000000243 solution Substances 0.000 claims description 4
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 229910000085 borane Inorganic materials 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- VSTXCZGEEVFJES-UHFFFAOYSA-N 1-cycloundecyl-1,5-diazacycloundec-5-ene Chemical compound C1CCCCCC(CCCC1)N1CCCCCC=NCCC1 VSTXCZGEEVFJES-UHFFFAOYSA-N 0.000 claims 1
- ZFXWSWNLLZINFL-VWLOTQADSA-N 4-[(1S)-1-[4-(4-tert-butylphenyl)-3,5-dimethylphenoxy]-4,4,4-trifluorobutyl]benzoic acid Chemical compound CC=1C=C(O[C@@H](CCC(F)(F)F)C2=CC=C(C(=O)O)C=C2)C=C(C=1C1=CC=C(C=C1)C(C)(C)C)C ZFXWSWNLLZINFL-VWLOTQADSA-N 0.000 abstract description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 239000000945 filler Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000012036 alkyl zinc reagent Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- -1 compound 1(1mmol) Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- CVXXHXPNTZBZEL-UHFFFAOYSA-N methyl 4-carbonochloridoylbenzoate Chemical compound COC(=O)C1=CC=C(C(Cl)=O)C=C1 CVXXHXPNTZBZEL-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/31—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/313—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a preparation method of a glucagon receptor antagonist intermediate, belonging to the field of compound preparation. The main technical scheme is as follows: synthesizing an intermediate (S) -4- (1 ' - (3, 5-dimethyl-4- (4-tert-butylphenyl) phenoxy) -4 ', 4 ', 4 ' -trifluorobutyl) benzoic acid of a glucagon receptor antagonist adomeglitivant by taking ethyl 4- ((4 ', 4 ', 4 ' -trifluoro-3 ' -trifluoromethanesulfonyloxy) but-2 ' -alkenyl) benzoate as a raw material, wherein the reaction process is as follows:
Description
Technical Field
The invention relates to a preparation method of a glucagon receptor antagonist intermediate, belonging to the field of compound preparation.
Background
(S) -4- (1 '- (3, 5-dimethyl-4- (4-tert-butylphenyl) phenoxy) -4', 4 ', 4' -trifluorobutyl) benzoic acid is an intermediate for synthesizing a glucagon receptor antagonist adomegivant, and in the existing synthetic route, 4,4, 4-trifluoroiodopropane is used as a raw material to prepare an alkyl zinc reagent, the alkyl zinc reagent reacts with p-methoxycarbonyl benzoyl chloride, and the alkyl zinc reagent is prepared by sulfonic acid esterification, etherification and hydrolysis (J.Label.Compd.radiopharmarm.2017, 60,110.).
Disclosure of Invention
The invention aims to provide a method for synthesizing an intermediate (S) -4- (1 ' - (3, 5-dimethyl-4- (4-tert-butylphenyl) phenoxy) -4 ', 4 ', 4 ' -trifluorobutyl) benzoic acid of a glucagon receptor antagonist adomegivant by taking ethyl 4- ((4 ', 4 ', 4 ' -trifluoro-3 ' -trifluoromethanesulfonyloxy) but-2 ' -alkenyl) benzoate as a raw material.
The technical scheme of the invention is as follows: the preparation process of the glucagon receptor antagonist intermediate is shown as the following reaction formula:
the method specifically comprises the following steps:
(1) synthesizing a compound ethyl 4- (4 ', 4', 4 '-trifluorobutyryl) benzoate shown in a chemical formula 2 by taking ethyl 4- ((4', 4 ', 4' -trifluoro-3 '-trifluoromethanesulfonyloxy) but-2' -alkenyl) benzoate shown in a chemical formula 1 as a raw material and N, N-Dimethylformamide (DMF) as a solvent under the action of 1, 8-diazabicycloundecen-7-ene (DBU) and water;
(2) adding ethyl 4- (4 ', 4 ', 4 ' -trifluorobutyryl) benzoate shown in chemical formula 2 into a tetrahydrofuran solvent, adding a borane tetrahydrofuran solution at 0 ℃, and then adding (S) -3, 3-diphenyl-1-methylpyrrolidine [1,2-c ] [1,3,2] borazaoxazolidine ((S) -Me-CBS) to react for 20h to obtain ethyl (R) -4- (1 ' -hydroxy-4 ', 4 ', 4 ' -trifluorobutyl) benzoate shown in chemical formula 3; the mass ratio of the ethyl 4- (4 ', 4 ', 4 ' -trifluorobutyryl) benzoate to the borane to the (S) -Me-CBS is 1:1.5: 0.3;
(3) dissolving a compound (R) -ethyl 4- (1 ' -hydroxy-4 ', 4 ', 4 ' -trifluorobutyl) benzoate shown in chemical formula 3 in a tetrahydrofuran solvent, sequentially adding 3, 5-dimethyl-4- (4 ' -tert-butylphenyl) -phenol, diisopropyl azodicarboxylate (DIAD) and triphenylphosphine at 0 ℃, and then transferring to 25 ℃ for reaction for 24h to obtain a compound (S) -ethyl 4- (1 ' - (3, 5-dimethyl-4- (4-tert-butylphenyl) phenoxy) -4 ', 4 ', 4 ' -trifluorobutyl) benzoate shown in chemical formula 4; the mass ratio of the compound (R) -4- (1 ' -hydroxy-4 ', 4 ', 4 ' -trifluorobutyl) ethyl benzoate, 3, 5-dimethyl-4- (4 ' -tert-butylphenyl) -phenol, diisopropyl azodicarboxylate and triphenylphosphine shown in chemical formula 3 is 1:1.5:1.5: 1.5;
(4) adding a compound (S) -4- (1 '- (3, 5-dimethyl-4- (4-tert-butylphenyl) phenoxy) -4', 4 ', 4' -trifluorobutyl) ethyl benzoate shown in a chemical formula 4 into a tetrahydrofuran solvent, dropwise adding a 1mol/L sodium hydroxide aqueous solution, and stirring at 25-28 ℃ for 12h to obtain a glucagon receptor antagonist intermediate: the ratio of the amount of the ethyl (S) -4- (1 '- (3, 5-dimethyl-4- (4-tert-butylphenyl) phenoxy) -4', 4 ', 4' -trifluorobutyl) benzoate of the compound shown in the chemical formula 4 to the amount of the sodium hydroxide substance is 1: 5.
The invention has the following beneficial effects: the method has the advantages of cheap and easily obtained raw materials and mild conditions, and provides a convenient and effective way for synthesizing the intermediate (S) -4- (1 '- (3, 5-dimethyl-4- (4-tert-butylphenyl) phenoxy) -4', 4 ', 4' -trifluorobutyl) benzoic acid of the glucagon receptor antagonist adomegivant.
Detailed Description
The following non-limiting examples are presented to enable those of ordinary skill in the art to more fully understand the present invention and are not intended to limit the invention in any way.
The test methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials are commercially available, unless otherwise specified.
Example 1
(1) Under the protection of argon, compound 1(1mmol), water (1mmol) and a solvent DMF (5mL) are sequentially added into a 25mL Schlenk bottle, the temperature is reduced to-40 ℃ in a low-temperature reactor, DBU (4mmol) is added, the reaction is carried out for 5h, the mixture is transferred to 80 ℃ and is reacted for 3h, ethyl acetate is extracted for three times (3X 10mL), the combined organic phases are washed by saturated saline (2X 10mL) and dried by anhydrous sodium sulfate, and the compound 2 is obtained by column chromatography, the filler is silica gel, the eluent is petroleum ether/ethyl acetate, and the separation yield is 75%.
White solid, melting point: the temperature of 86.8 to 87.0 ℃,1H NMR(400MHz,CDCl3)δ8.14(d,J＝8.2Hz,2H),8.02(d,J＝8.2Hz,2H),4.41(q,J＝7.1Hz,2H),3.38–3.18(m,2H),2.75–2.47(m,2H),1.42(t,J＝7.1Hz,3H)。
(2) in a 25mL Schlenk flask, under the protection of argon, compound 2(108mg, 0.394mmol) is added to tetrahydrofuran (1mL) at 0 ℃, borane tetrahydrofuran solution is 0.6mL (1mol/mL), then (S) -Me-CBS 34mg (0.123mmol) is slowly added, after 20h reaction, ethyl acetate is extracted three times (3X 10mL), the combined organic phases are washed with saturated brine (2X 10mL), dried with anhydrous sodium sulfate, and compound 3 is obtained by column chromatography, the filler is silica gel, the eluent is petroleum ether/ethyl acetate, the separation yield is 86%, and the ee value is 90.2%.
A colorless liquid, and a non-coloring liquid,1H NMR(400MHz,CDCl3)δ7.99(dd,J＝10.9,8.4Hz,2H),7.39(d,J＝7.7Hz,2H),4.80(t,J＝7.3Hz,1H),4.38–4.31(m,2H),2.26–2.14(m,2H),2.05(q,J＝8.0Hz),1.39(t,J＝7.1Hz,3H)。
(3) in a 25mL Schlenk flask, under argon protection and at 0 deg.C, compound 3(70mg, 0.253mmol), 97mg (0.382mmol) of 3, 5-dimethyl-4- (4' -tert-butylphenyl) -phenol, 77mg (0.381mmol) of diisopropyl azodicarboxylate, 100mg (0.381mmol) of triphenylphosphine in tetrahydrofuran (1mL) were added in that order, and the mixture was transferred to 25 deg.C for reaction for 24 hours. After-treatment, extraction was carried out with ethyl acetate three times (3X 10mL), the combined organic phases were washed with saturated brine (2X 10mL), dried over anhydrous sodium sulfate, and subjected to column chromatography to obtain compound 4 in a 67% isolated yield using silica gel as the filler and petroleum ether/ethyl acetate as the eluent.
White solid, melting point: the temperature of the mixture is between 109.4 and 109.9 ℃,1H NMR(400MHz,CDCl3)δ7.96–7.88(m,2H),7.41–7.35(m,2H),7.32–7.25(m,2H),7.05–6.97(m,2H),6.56(s,2H),5.16(d,J＝7.3Hz,1H),2.47–2.24(m,2H),2.22–2.02(m,2H),2.05(q,J＝8.0Hz,2H),1.95(s,6H),1.39(t,J＝7.1Hz,3H),1.36(s,9H)。
(4) in a 25mL Schlenk flask, under argon protection, compound 4(70mg, 0.145mmol) was added to tetrahydrofuran (1mL) and 0.7mL of sodium hydroxide solution (1mol/L) was added dropwise at room temperature and stirred for 12 h. The combined organic phases were washed with brine (2 × 10mL), dried over anhydrous sodium sulfate and subjected to column chromatography to give (S) -4- (1 '- (3, 5-dimethyl-4- (4-tert-butylphenyl) phenoxy) -4', 4 ', 4' -trifluorobutyl) benzoic acid in 91% isolated yield using silica gel as the filler and petroleum ether/ethyl acetate as the eluent.
White solid, melting point: the temperature of the mixture is between 89.9 and 90.6 ℃,1H NMR(400MHz,CDCl3)δ7.96(d,J＝8.3,2H),7.45(d,J＝8.3,2H),7.36–7.25(m,2H),6.98–6.92(m,2H),6.55(s,2H),5.25(d,J＝7.3Hz,1H),2.47–2.24(m,2H),2.22–2.02(m,2H),1.95(s,6H),1.36(s,9H)。
Claims (1)
1. the preparation method of the glucagon receptor antagonist intermediate is characterized in that the preparation process is shown as the following reaction formula:
the method specifically comprises the following steps:
(1) synthesizing a compound ethyl 4- (4 ', 4', 4 '-trifluorobutylidene) benzoate shown in a chemical formula 2 by using ethyl 4- ((4', 4 ', 4' -trifluoro-3 '-trifluoromethanesulfonyloxy) but-2' -alkenyl) benzoate shown in a chemical formula 1 as a raw material and N, N-dimethylformamide as a solvent under the action of 1, 8-diazabicycloundec-7-ene and water;
(2) adding 4- (4 ', 4 ', 4 ' -trifluorobutyryl) ethyl benzoate shown in chemical formula 2 into a tetrahydrofuran solvent, adding a borane tetrahydrofuran solution at 0 ℃, and then adding (S) -Me-CBS for reaction for 20h to obtain (R) -4- (1 ' -hydroxy-4 ', 4 ', 4 ' -trifluorobutyl) ethyl benzoate shown in chemical formula 3; the mass ratio of the ethyl 4- (4 ', 4 ', 4 ' -trifluorobutyryl) benzoate to the borane to the (S) -Me-CBS is 1:1.5: 0.3;
(3) dissolving a compound (R) -4- (1 ' -hydroxy-4 ', 4 ', 4 ' -trifluorobutyl) ethyl benzoate shown in a chemical formula 3 in a tetrahydrofuran solvent, sequentially adding 3, 5-dimethyl-4- (4 ' -tert-butylphenyl) -phenol, diisopropyl azodicarboxylate and triphenylphosphine at 0 ℃, and then moving to 25 ℃ to react for 24h to obtain a compound (S) -4- (1 ' - (3, 5-dimethyl-4- (4-tert-butylphenyl) phenoxy) -4 ', 4 ', 4 ' -trifluorobutyl) ethyl benzoate shown in the chemical formula 4; the mass ratio of the compound (R) -4- (1 ' -hydroxy-4 ', 4 ', 4 ' -trifluorobutyl) ethyl benzoate, 3, 5-dimethyl-4- (4 ' -tert-butylphenyl) -phenol, diisopropyl azodicarboxylate and triphenylphosphine shown in chemical formula 3 is 1:1.5:1.5: 1.5;
(4) adding a compound (S) -4- (1 '- (3, 5-dimethyl-4- (4-tert-butylphenyl) phenoxy) -4', 4 ', 4' -trifluorobutyl) ethyl benzoate shown in a chemical formula 4 into a tetrahydrofuran solvent, dropwise adding a 1mol/L sodium hydroxide aqueous solution, and stirring at 25-28 ℃ for 12h to obtain a glucagon receptor antagonist intermediate: the ratio of the amount of the ethyl (S) -4- (1 '- (3, 5-dimethyl-4- (4-tert-butylphenyl) phenoxy) -4', 4 ', 4' -trifluorobutyl) benzoate of the compound shown in the chemical formula 4 to the amount of the sodium hydroxide substance is 1: 5.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101312723A (en) * | 2005-11-22 | 2008-11-26 | 伊莱利利公司 | Glucagon receptor antagonists, preparation and therapeutic uses |
| CN107501153A (en) * | 2017-08-17 | 2017-12-22 | 大连理工大学 | A kind of preparation method of 2 (2,2,2 trifluoroethyl) 3 aryl 2H azapropylene acridine compounds |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101312723A (en) * | 2005-11-22 | 2008-11-26 | 伊莱利利公司 | Glucagon receptor antagonists, preparation and therapeutic uses |
| CN107501153A (en) * | 2017-08-17 | 2017-12-22 | 大连理工大学 | A kind of preparation method of 2 (2,2,2 trifluoroethyl) 3 aryl 2H azapropylene acridine compounds |
Non-Patent Citations (5)
| Title |
|---|
| Base-Controlled Regiodivergent Azidation of Trifluoromethyl Alkenyl Triflates: Transition-Metal-Free Access to CF3-Containing Allyl Azides and Alkenyl Azides;Zhao,YL;Zhou,YH;《JOURNAL OF ORGANIC CHEMISTRY》;20180302;第83卷(第5期);2858-2868 * |
| Copper-catalysed ring-opening trifluoromethylation of cyclopropanols;He,XP;Shu,YJ;《ORGANIC & BIOMOLECULAR CHEMISTRY》;20150602;第13卷(第26期);7159-7163 * |
| Efficient Synthesis of β-CF3/SCF3 Substituted Carbonyls via;Yong Li,Zhishi Ye;《Org Lett.》;20150501;第17卷(第9期);2186-2189 * |
| Synthesis of C-14 radiolabeled glucagon receptor antagonist and its use in a human mass balance study;Boris A.Czeskis；Darlene K.Satonin;《JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS》;20170228;第60卷(第2期);110-115 * |
| 强有机碱试剂DBU和DBN在有机合成中的应用;倪志刚;《中国医药工业杂志》;19910430;第22卷(第4期);180-186 * |
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