CN105503920A - Method for preparing borate compound - Google Patents
Method for preparing borate compound Download PDFInfo
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- CN105503920A CN105503920A CN201510964696.4A CN201510964696A CN105503920A CN 105503920 A CN105503920 A CN 105503920A CN 201510964696 A CN201510964696 A CN 201510964696A CN 105503920 A CN105503920 A CN 105503920A
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- -1 borate compound Chemical class 0.000 title claims abstract description 7
- 238000000034 method Methods 0.000 title claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 80
- 238000006243 chemical reaction Methods 0.000 claims abstract description 37
- 229940125773 compound 10 Drugs 0.000 claims abstract description 21
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 claims abstract description 21
- 229940125898 compound 5 Drugs 0.000 claims abstract description 18
- 229940125904 compound 1 Drugs 0.000 claims abstract description 10
- 229940126214 compound 3 Drugs 0.000 claims abstract description 9
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 8
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 claims abstract description 7
- 150000001720 carbohydrates Chemical class 0.000 claims abstract description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 39
- 239000000243 solution Substances 0.000 claims description 37
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 23
- 238000002360 preparation method Methods 0.000 claims description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- 229940125782 compound 2 Drugs 0.000 claims description 11
- 239000012071 phase Substances 0.000 claims description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 8
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 8
- XPDWGBQVDMORPB-UHFFFAOYSA-N trifluoromethane acid Natural products FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 claims description 8
- 239000012074 organic phase Substances 0.000 claims description 6
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 239000012043 crude product Substances 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 4
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- DYHSDKLCOJIUFX-UHFFFAOYSA-N Di-tert-butyl dicarbonate Substances CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 claims description 3
- 238000009833 condensation Methods 0.000 claims description 3
- 230000005494 condensation Effects 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 3
- 235000015320 potassium carbonate Nutrition 0.000 claims description 3
- 238000005406 washing Methods 0.000 abstract description 3
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 abstract 2
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 6
- 238000000746 purification Methods 0.000 description 5
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 4
- 239000004327 boric acid Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- XZJBGQPXSSPRBY-UHFFFAOYSA-N [C].B(F)(F)F Chemical compound [C].B(F)(F)F XZJBGQPXSSPRBY-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- IKHKJYWPWWBSFZ-UHFFFAOYSA-N 4-[[4-(diethylamino)phenyl]-(4-diethylazaniumylidenecyclohexa-2,5-dien-1-ylidene)methyl]benzene-1,3-disulfonate;hydron Chemical compound C1=CC(N(CC)CC)=CC=C1C(C=1C(=CC(=CC=1)S([O-])(=O)=O)S(O)(=O)=O)=C1C=CC(=[N+](CC)CC)C=C1 IKHKJYWPWWBSFZ-UHFFFAOYSA-N 0.000 description 1
- SIAVMDKGVRXFAX-UHFFFAOYSA-N 4-carboxyphenylboronic acid Chemical compound OB(O)C1=CC=C(C(O)=O)C=C1 SIAVMDKGVRXFAX-UHFFFAOYSA-N 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000006068 polycondensation reaction Methods 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- NLIVDORGVGAOOJ-MAHBNPEESA-M xylene cyanol Chemical compound [Na+].C1=C(C)C(NCC)=CC=C1C(\C=1C(=CC(OS([O-])=O)=CC=1)OS([O-])=O)=C\1C=C(C)\C(=[NH+]/CC)\C=C/1 NLIVDORGVGAOOJ-MAHBNPEESA-M 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Abstract
The invention relates to a compound for sugar saccharide recognition, in particular to a method for preparing a borate compound. A compound 1 passes BOC protection, and then is condensed with a compound 3 to obtain a compound 4, the reaction process is very clean, the polarity of the compounds is almost not dissolved in water, and the yield is high; the BOC is removed through hydrochloric acid methanol, and the purity and yield of an obtained compound 5 are very high. Therefore, the problem about purifying of the compound 5 is solved. A compound 6 is protected through trifluoromethylsulfonyl, then sulfonyl chloride is prepared, and the yield and purity are greatly improved. The purity of a compound 8 can be improved to 90% simply through washing, and the compound 8 is also very stable and not likely to go bad, and is easy to produce. In the reaction of synthesizing a compound 10, due to the fact that the purity of sulfonyl chloride is very high, purifying of a compound 9 is very convenient, and the yield is high. Finally, the pure compound 10 can be directly obtained without purifying trifluoromethylsulfonyl during removal.
Description
Technical field
The present invention relates to a kind of compound for carbohydrate identification, especially a kind of preparation method of borate compound.
Background technology
In US Patent No. 5631364, synthetic route is:
The shortcoming that existence three is fatal in above-mentioned operational path:
One, in the reaction of the compound 5 of synthesis, have a lot of by product polarity very large, and compound 5 is very easily water-soluble, organic solvent extraction not out, causes the low purification difficult of yield like this.
Two, compound 6 synthetic compound 11 time reaction very assorted, can not purifying, during purifying compound 11 apt to deteriorate thus can only directly down single step reaction use.
Three, cause compound 10 very difficult when synthetic compound 10 because compound 11 is impure, purify anti-phase purifying convenient to both ability convenient to both with normal-phase chromatography passable, yield is very low less than 1%.
Therefore, find simple to operate, security is high, side reaction is few, transformation efficiency is high, yield is high, environmental pollution is little, production cost is low, be suitable for the preparation method of suitability for industrialized production compound 10 is the technical problems being badly in need of at present solving.
Summary of the invention
Side reaction is caused to increase because synthesize direct polycondensation in the reaction of 5 in US Patent No. 5631364 like this because two amino can react, and product is soluble in water is not dissolved in organic solvent very much, so just can not wash, direct post product polarity of crossing easily is adsorbed by pillar greatly, causes productive rate and purity to be all difficult to improve.So in the present invention by two of compound 1 amino with BOC protection, carry out condensation reaction reaction and be totally easy to purification yield and also greatly improve.
Very assorted owing to there being the naked leakage conductance of ammonia hydrogen to cause reaction in compound 6 in synthetic compound 11 in US Patent No. 5631364, and the SULPHURYL CHLORIDE instability made can not be washed and can not be crossed column purification, synthetic compound 10 can only be directly used in, cause the purification difficult yield of compound 10 very low.Protected by fluoroform acyl group by compound 6 in the present invention, then do SULPHURYL CHLORIDE, yield purity all improves a lot, and just the purity of compound 8 can be brought up to 90% by washing, and compound 8 also very stable being not easy rotten be easy to production.In addition, the purity of the present invention due to yellow acyl chlorides in the reaction of synthetic compound 10 is very high, and just very convenient yield is also high for the purifying of such compound 9, and most rear dragging fluoroform acyl group directly need not can obtain sterling compound 10 by purifying.
A preparation method for borate compound, comprises the following steps:
(1) compound 1 obtains compound 2 by BOC protection;
(2) compound 2 and compound 3 condensation obtain compound 4;
(3) compound 4 drags BOC by hydrochloric acid methanol, obtains compound 5;
(4) compound 6 obtains compound 7 by the protection of fluoroform acyl group;
(5) compound 7 obtains compound 8 by SULPHURYL CHLORIDE;
(6) compound 5 and compound 8 synthetic compound 9;
(7) compound 9 obtains compound 10 by dragging fluoroform acyl group.
Preferably, in step (1), compound 1 is dissolved in methyl alcohol, drips the dioxane solution of BOC2O, keep temperature lower than 10 DEG C, then stirred overnight at room temperature, reaction solution is concentrated into dry adding water, with dichloromethane extraction at least 3 times, merge organic phase, be concentrated into and dryly obtain compound 2.
Preferably, in step (2), compound 3 is dissolved in DMF, is cooled to 0 DEG C to add HOBT, then the DMF solution of DCC is dripped, keep temperature lower than 10 DEG C, then stirred overnight at room temperature, filtering reacting liquid, keep temperature lower than 10 DEG C in filtrate added drop-wise to the pyridine solution of compound 2, then stirred overnight at room temperature, reaction solution is concentrated into dry, crosses post and obtains compound 4.
Preferably, in step (3), be dissolved in methyl alcohol by compound 4, be cooled to 0 DEG C to drip HCl methanol solution, keep temperature lower than 10 DEG C, then stirred overnight at room temperature, reaction solution is concentrated into and obtains compound 5.
Preferably, in step (4), be dissolved in trifluoroacetic anhydride by compound 6, Heating temperature was to 50 DEG C of reactions 8 hours, and reaction solution is concentrated into dry, obtains compound 7.
Preferably, in step (5), compound 7 is dissolved in methylene dichloride and DMF, 0 DEG C is cooled to drip oxalyl chloride, keep temperature lower than 10 DEG C, then stirred overnight at room temperature, reaction solution is concentrated into dry, then add methylene dichloride dissolve and wash with frozen water, organic phase is concentrated obtains compound 8.
Preferably, in step (6), compound 5 is dissolved in methyl alcohol and DMF, and is cooled to 0 DEG C, adds sodium bicarbonate aqueous solution; Then drip the acetonitrile solution of compound 8, keep temperature lower than 10 DEG C, then stirred overnight at room temperature; The concentrated post of reaction solution obtains the crude product of compound 8, then obtains compound 9 after reversed-phase column.
Preferably, in step (7), compound 9 is dissolved in methyl alcohol, adds salt of wormwood, stirred overnight at room temperature, and then reacting liquid filtering obtains compound 10 at mistake reversed-phase column.
Compound technical term is explained and Chinese:
Below structural formula of compound and its Chinese are described:
Compound 1 structural formula: DAP
Compound 2 structural formula: tertiary butyl 3-amino-2-hydroxypropanol
Compound 3 structural formula: 4-Carboxybenzeneboronic acid
Compound 4 structural formula: 4-((tertiary butyl 3-amino-2-hydroxy-propyl) aminocarboxyl)-phenylo boric acid (N-BOC-CPBA-DAPOL)
Compound 5 structural formula: 4-((3-amino-2-hydroxy-propyl) aminocarboxyl)-phenylo boric acid (CPBA-DAPOL)
Compound 6 structural formula: xylene cyanol blue FF
Compound 7 structural formula: borontrifluoride carbon back-xylene cyanol blue FF
Compound 8 structural formula: borontrifluoride carbon back-xylene blue AS-SO
2cl
Compound 9 structural formula: borontrifluoride carbon back-xylene blue AS-phenylo boric acid (CF3-XC-CPBA-DAPOL)
Compound 10 structural formula: xylene blue AS-phenylo boric acid (XC-CPBA--DAPOL)
Have impurity by the compound 10 prepared by the present invention few, the distinguishing features such as purity is high, be mainly used in the identification of carbohydrate, have identification highly sensitive, error is little waits beneficial effect.
In addition, although synthetic route of the present invention is compared with US5631364 and added four-step reaction and have following several advantage:
Compound 1 is protected by BOC, then obtains compound 4 with compound 3 condensation, reacts very clean in reaction, and the polarity of compound is also little water-soluble hardly, and yield is very high, then drags BOC by hydrochloric acid methanol, and the purity and the yield that obtain compound 5 are all very high.This addresses the problem the issues of purification of chemical combination 5.
Compound 6 is protected by fluoroform acyl group, then does SULPHURYL CHLORIDE, and yield purity all improves a lot, and just the purity of compound 8 can be brought up to 90% by washing, and compound 8 also very stable being not easy rotten be easy to production.
In the reaction of synthetic compound 10, due to the purifying of the very high such compound 9 of the purity of SULPHURYL CHLORIDE, just very convenient yield is also high, and most rear dragging fluoroform acyl group directly need not can obtain sterling compound 10 by purifying.
Accompanying drawing explanation
Fig. 1 the present invention is used for borate compound 10 structural representation of carbohydrate identification
Embodiment
Below in conjunction with drawings and Examples, the present invention is further illustrated.
Embodiment 1
Compound 1 (178g) is dissolved in 500mL methyl alcohol, drip the dioxane solution (400mL) of BOC2O (86.3), keep temperature lower than 10 DEG C, then stirred overnight at room temperature, reaction solution is concentrated into dry adding water, and with dichloromethane extraction (5 times), merges organic phase, be concentrated into and dryly obtain compound 2 (150g, yield: 50%).
Compound 3 (26.2g) is dissolved in 200mLDMF, 0 DEG C is cooled to add HOBT (31.2g), then the DMF (150mL) of DCC (65g) is dripped, keep temperature lower than 10 DEG C, then stirred overnight at room temperature, then filter, keep temperature lower than 10 DEG C of then stirred overnight at room temperature in filtrate added drop-wise to pyridine (200mL) solution of compound 2 (30g), reaction solution is concentrated into be done post and obtained compound 4 (30g, yield: 57%).
Compound 4 (30g) is dissolved in 100mL methyl alcohol, is cooled to 0 DEG C to drip HCl methanol solution (6M, 100mL), keep temperature lower than 10 DEG C, then stirred overnight at room temperature, reaction solution is concentrated into and obtains compound 5 (25g, yield: 100%).
Compound 6 (5.4g) is dissolved in trifluoroacetic anhydride 30mL, and Heating temperature was to 50 DEG C of reactions 8 hours, and reaction solution is concentrated into dry, obtains compound 7 (6.0g, yield: 95%).
Compound 7 (3.2g) is dissolved in 60mL methylene dichloride and 0.1mLDMF, is cooled to 0 DEG C to drip oxalyl chloride 2.5mL, keep temperature lower than 10 DEG C, then stirred overnight at room temperature; Reaction solution is concentrated into dry, then adds methylene dichloride and dissolves and wash with frozen water, and organic phase is concentrated obtains compound 8 (1.6g, yield: 52%).
Compound 5 (1.0g) to be dissolved in 1mL methyl alcohol and 5mLDMF and to be cooled to 0 DEG C, adds sodium bicarbonate aqueous solution (0.1M, 60mL); Then drip acetonitrile (25mL) solution of compound 8 (1.0g), keep temperature lower than 10 DEG C, then stirred overnight at room temperature; The concentrated post of reaction solution obtains the crude product (900mg) of compound 8, then obtains compound 9 (400mg, 30%, purity 98%) after reversed-phase column.
Compound 9 (100mg) is dissolved in 10mL methyl alcohol, adds salt of wormwood (100mg), stirred overnight at room temperature, and then reacting liquid filtering obtains compound 10 (80mg, 85%, purity 98%) at mistake reversed-phase column.
Comparative example 1
Compound 3 (26.2g) is dissolved in 200mLDMF, 0 DEG C is cooled to add HOBT (31.2g), then the DMF (150mL) of DCC (65g) is dripped, keep temperature lower than 10 DEG C, then stirred overnight at room temperature, then filter, keep temperature lower than 10 DEG C of then stirred overnight at room temperature in filtrate added drop-wise to pyridine (200mL) solution of compound 1 (15g), reaction solution is concentrated into dry, cross post and obtain compound 5 (5g, yield: 10%).
Compound 6 (3.2g) is dissolved in 60mL methylene dichloride and 0.1mLDMF, is cooled to 0 DEG C to drip oxalyl chloride 2.5mL, keep temperature lower than 10 DEG C, then stirred overnight at room temperature; Reaction solution is concentrated into dry, obtains compound 11 (3.5g, purity 10% do not find the method for purifying at present, can only be directly used in next step reaction).
Compound 5 (1.0g) to be dissolved in 1mL methyl alcohol and 5mLDMF and to be cooled to 0 DEG C, add sodium bicarbonate aqueous solution (0.1M, 60mL), acetonitrile (25mL) solution of compound 11 (10.0g, purity 10%) is then dripped; Keep temperature lower than 10 DEG C, then stirred overnight at room temperature; The concentrated post of reaction solution obtains the crude product (300mg) of compound 10, then obtains compound 10 (20mg, 0.7%, content 90%) after twice reversed-phase column.
The foregoing is only preferred embodiment of the present invention, be in conjunction with concrete preferred implementation further description made for the present invention, can not assert that specific embodiment of the invention is confined to these explanations.All any amendments done within the spirit and principles in the present invention, equivalent replacement and improvement etc., all should be included within protection scope of the present invention.
Claims (10)
1. a preparation method for borate compound, comprises the following steps:
(1) compound 1
compound 2 is obtained by BOC protection
(2) compound 2
with compound 3
condensation obtains compound 4
(3) compound 4
drag BOC by hydrochloric acid methanol, obtain compound 5
(4) compound 6
compound 7 is obtained by the protection of fluoroform acyl group
(5) compound 7
compound 8 is obtained by SULPHURYL CHLORIDE
(6) compound 5 and compound 8 synthetic compound 9
(7) compound 9 obtains compound 10 by dragging fluoroform acyl group
2. preparation method according to claim 1, it is characterized in that, in described step (1), compound 1 is dissolved in methyl alcohol, drips the dioxane solution of BOC2O, keep temperature lower than 10 DEG C, then stirred overnight at room temperature, reaction solution is concentrated into dry adding water, with dichloromethane extraction at least 3 times, merge organic phase, be concentrated into and dryly obtain compound 2.
3. preparation method according to claim 1, is characterized in that, in described step (2), compound 3 is dissolved in DMF, be cooled to 0 DEG C to add HOBT, then drip the DMF solution of DCC, keep temperature lower than 10 DEG C, then stirred overnight at room temperature, filtering reacting liquid, keeps temperature lower than 10 DEG C in filtrate added drop-wise to the pyridine solution of compound 2, then stirred overnight at room temperature, reaction solution is concentrated into dry, crosses post and obtains compound 4.
4. preparation method according to claim 1, is characterized in that, in described step (3), compound 4 is dissolved in methyl alcohol, is cooled to 0 DEG C to drip HCl methanol solution, keep temperature lower than 10 DEG C, then stirred overnight at room temperature, reaction solution is concentrated into and obtains compound 5.
5. preparation method according to claim 1, is characterized in that, in described step (4), be dissolved in trifluoroacetic anhydride by compound 6, and Heating temperature was to 50 DEG C of reactions 8 hours, and reaction solution is concentrated into dry, obtains compound 7.
6. preparation method according to claim 1, it is characterized in that, in described step (5), compound 7 is dissolved in methylene dichloride and DMF, is cooled to 0 DEG C to drip oxalyl chloride, keep temperature lower than 10 DEG C, then stirred overnight at room temperature, reaction solution is concentrated into dry, then adds methylene dichloride and dissolves and wash with frozen water, and organic phase is concentrated obtains compound 8.
7. preparation method according to claim 1, it is characterized in that, in described step (6), compound 5 is dissolved in methyl alcohol and DMF, and is cooled to 0 DEG C, adds sodium bicarbonate aqueous solution; Then drip the acetonitrile solution of compound 8, keep temperature lower than 10 DEG C, then stirred overnight at room temperature; The concentrated post of reaction solution obtains the crude product of compound 8, then obtains compound 9 after reversed-phase column.
8. preparation method according to claim 1, it is characterized in that, in described step (7), compound 9 is dissolved in methyl alcohol, adds salt of wormwood, stirred overnight at room temperature, and then reacting liquid filtering obtains compound 10 crossing reversed-phase column.
9. containing a compound prepared by method described in the arbitrary claim of claim 1-8, it is characterized in that, described compound is used for the identification of carbohydrate.
10., containing a compound prepared by method described in the arbitrary claim of claim 1-8, it is characterized in that, described compound is for the preparation of test kit.
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| CN201510964696.4A CN105503920B (en) | 2015-12-18 | 2015-12-18 | A kind of preparation method of borate compound |
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| CN105503920A true CN105503920A (en) | 2016-04-20 |
| CN105503920B CN105503920B (en) | 2017-10-20 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5631364A (en) * | 1994-03-31 | 1997-05-20 | Axis Biochemicals Asa | Labelled boronic acid derivatives |
| US20020173044A1 (en) * | 1998-09-21 | 2002-11-21 | Rudolf Pachl | Methods for determination of glycated haemoglobin |
| WO2014033258A1 (en) * | 2012-08-31 | 2014-03-06 | Axis-Shield Asa | Glycated haemoglobin assay method |
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2015
- 2015-12-18 CN CN201510964696.4A patent/CN105503920B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5631364A (en) * | 1994-03-31 | 1997-05-20 | Axis Biochemicals Asa | Labelled boronic acid derivatives |
| US20020173044A1 (en) * | 1998-09-21 | 2002-11-21 | Rudolf Pachl | Methods for determination of glycated haemoglobin |
| WO2014033258A1 (en) * | 2012-08-31 | 2014-03-06 | Axis-Shield Asa | Glycated haemoglobin assay method |
Non-Patent Citations (1)
| Title |
|---|
| FRANTZEN, FRANK ET AL.: "Glycohemoglobin filter assay for doctors offices based on boronic acid affinity principle", 《CLINICAL CHEMISTRY》 * |
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