CN109232647A - Polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- phentriazine -4- ketone and preparation method thereof - Google Patents
Polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- phentriazine -4- ketone and preparation method thereof Download PDFInfo
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- CN109232647A CN109232647A CN201811110570.0A CN201811110570A CN109232647A CN 109232647 A CN109232647 A CN 109232647A CN 201811110570 A CN201811110570 A CN 201811110570A CN 109232647 A CN109232647 A CN 109232647A
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 44
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 36
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 36
- -1 diethoxy phosphoryl oxy Chemical group 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 39
- 238000000034 method Methods 0.000 claims abstract description 16
- 230000008569 process Effects 0.000 claims abstract description 7
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 6
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 5
- 238000005580 one pot reaction Methods 0.000 claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims description 51
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 38
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 21
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 claims description 15
- 239000012074 organic phase Substances 0.000 claims description 13
- 238000010792 warming Methods 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 10
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 8
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 6
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 5
- 150000007530 organic bases Chemical class 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 2
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 239000011259 mixed solution Substances 0.000 description 11
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 10
- 229940049706 benzodiazepine Drugs 0.000 description 7
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 5
- 238000012544 monitoring process Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 4
- 229910052698 phosphorus Inorganic materials 0.000 description 4
- 239000011574 phosphorus Substances 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 2
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- AJDPNPAGZMZOMN-UHFFFAOYSA-N diethyl (4-oxo-1,2,3-benzotriazin-3-yl) phosphate Chemical compound C1=CC=C2C(=O)N(OP(=O)(OCC)OCC)N=NC2=C1 AJDPNPAGZMZOMN-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000006340 racemization Effects 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- TZRXHJWUDPFEEY-UHFFFAOYSA-N Pentaerythritol Tetranitrate Chemical compound [O-][N+](=O)OCC(CO[N+]([O-])=O)(CO[N+]([O-])=O)CO[N+]([O-])=O TZRXHJWUDPFEEY-UHFFFAOYSA-N 0.000 description 1
- 108010001441 Phosphopeptides Proteins 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- CGIHPACLZJDCBQ-UHFFFAOYSA-N acibenzolar Chemical compound SC(=O)C1=CC=CC2=C1SN=N2 CGIHPACLZJDCBQ-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- RAABOESOVLLHRU-UHFFFAOYSA-N diazene Chemical compound N=N RAABOESOVLLHRU-UHFFFAOYSA-N 0.000 description 1
- 229910000071 diazene Inorganic materials 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000021050 feed intake Nutrition 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000007040 multi-step synthesis reaction Methods 0.000 description 1
- XCVNDBIXFPGMIW-UHFFFAOYSA-N n-ethylpropan-1-amine Chemical compound CCCNCC XCVNDBIXFPGMIW-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000009466 transformation Effects 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having three nitrogen atoms as the only ring hetero atoms
- C07F9/6521—Six-membered rings
- C07F9/65218—Six-membered rings condensed with carbocyclic rings or carbocyclic ring systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Peptides Or Proteins (AREA)
Abstract
The invention discloses a kind of polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- phentriazine -4- ketone and preparation method thereof belong to amino acid polypeptide technical field.Technical solution of the present invention main points are as follows: polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- phentriazine -4- ketone, structural formula are as follows:
Description
Technical field
The invention belongs to amino acid polypeptide technical fields, and in particular to a kind of polypeptide condensing agent 1- (diethoxy phosphinylidyne oxygen
Base) -1,2,3- phentriazine -4- ketone and preparation method thereof.
Background technique
Polypeptide is a kind of important bioactive substance.Since bioactivity peptide content is few in natural products, separate pure
Change again very difficult.Therefore artificial synthesis peptide is just particularly important.Different structure transformation can be obtained by chemical synthesising peptide
Peptide, its structure activity study can be carried out by active testing.Although there are many kinds of the synthetic methods of peptide, various methods
All cut both ways.Wherein a kind of important method of Peptide systhesis is activated carboxylic method, uses earliest and is by activation of amino acid
The method of acyl chlorides, nitrine, symmetric anhydride and mixed acid anhydride, these methods are used and are made there are amino acid racemization, hazardous agents
The disadvantages of complicated for process, then gradually replaced later peptide condensation reagent method.
Ideal polypeptide condensing agent should have the characteristics that preparation is convenient, activity is high, few without racemization and side reaction.Make at present
Polypeptide condensing agent can be divided into diimine type, phosphorus ionic and urea ionic according to its structure.First peptide condensing agent
It is the N that developed in nineteen fifty-five, N'- dicyclohexylcarbodiimide (DCC) (J.Am.Chem.Soc., 1955,77:
1067.).But the N that the polypeptide condensing agent generates in the reaction, N'- dicyclohexylurea (DCU) (DCU) are molten in most of organic solvents
Solution degree very little, is difficult to eliminate.From 1975, Castro et al. design synthesized first phosphorus ionic condensation based on HOBt
Since agent BOP, I-hydroxybenzotriazole HOBt is that the phosphorus cation of Acibenzolar and carbonium ion type polypeptide condensing agent rapidly develop,
This carbonium ion polypeptide condensing agent N, N, N' with -4 (3H) -one derivatization of 3- hydroxyl -1,2,3- phentriazine still later,
N'- tetramethyl-O- (3,4- dihydro -4- oxo -1,2,3- phentriazine -3- base) urea tetrafluoroborate (TDBTU) (Organic
Synthesis,1-3,2013；PCT Int.Appl.,2005007634；Tetrahedron Letters,30(15),1927-
30；1989) it is also prepared and is applied.2014, patent (ZL 20141010745.2) reported 3- hydroxyl -1,2,3-
The isomer of phentriazine -4 (3H) -one, 1- hydroxyl -1,2, the preparation method of 3- phentriazine -4 (3H) -one, and apply
In peptide condensation (ZL 201410107410.6).Organic phosphorus condensing agent is also critically important one kind, is based on 3- hydroxyl -1,2,3-
The organic phosphorus condensing agent of phentriazine -4 (3H) -one mainly has 3- (diethoxy phosphoryl oxy) -1,2,3- phentriazine -4- ketone
(DEPBT) (CAS 165534-43-0) and 3- (2'- oxygen -1', 3', 2'- dioxaphosphinan base phosphinylidyne oxygroup) -1,2,
3- phentriazine -4- ketone (DOPBT) (CAS 156147-88-5).The shortcomings that DOPBT is that solubility property is poor, only in DMF
It can preferably dissolve, limit further applying for it.Currently, it is based on 1- hydroxyl -1,2,3- phentriazine -4 (3H) -one
Organic phosphopeptide condensing agent is there is not yet relevant report.
Summary of the invention
The technical problem to be solved by the present invention is to provide a kind of structure novel and the polypeptide condensing agent 1- (diethyls that have excellent performance
Oxygroup phosphinylidyne oxygroup) -1,2,3- phentriazine -4- ketone.
Another technical problem that the present invention solves there is provided it is a kind of it is easy to operate, easily controllable, yield is higher and logical
Cross the preparation method of polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- phentriazine -4- ketone of one pot of multistep synthesis.
The present invention adopts the following technical scheme that solve above-mentioned technical problem, polypeptide condensing agent 1- (diethoxy phosphinylidyne oxygen
Base) -1,2,3- phentriazine -4- ketone, it is characterised in that the 1- (diethoxy phosphoryl oxy) -1,2,3- phentriazine -4- ketone
Structural formula are as follows:
The preparation of polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- phentriazine -4- ketone of the present invention
Method, it is characterised in that use multistep one pot process, detailed process are as follows: ortho-nitrophenyl formylhydrazine is added in a solvent and has
Machine alkali, is warming up to back flow reaction, is cooled to 0~5 DEG C after reaction, add the carbon tetrachloride solution of diethyl phosphite into
Row reaction, is washed with water after reaction, and organic phase is dry, is spin-dried for, obtains target product polypeptide condensing agent 1- (diethoxy phosphorus
Acyloxy) -1,2,3- phentriazine -4- ketone, wherein solvent is methylene chloride, carbon tetrachloride, toluene or dimethylbenzene, and organic base is
Diisopropylethylamine or triethylamine.
Further preferably, the ortho-nitrophenyl formylhydrazine, organic base, diethyl phosphite and carbon tetrachloride feed intake mole
Than for 1:1-1.5:1-2:1-2.
The preparation of polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- phentriazine -4- ketone of the present invention
Method, it is characterised in that the reaction equation in synthesis process are as follows:
Compared with the prior art, the invention has the following beneficial effects: raw material used in synthesis process of the present invention is common
Reagent, synthetic route is simple, multistep one pot reaction mild condition and easy to operate.There is the present invention raw material to be easy to get, route is simple
Singly, the advantages that side reaction is few and gross production rate is high.
Specific embodiment
Above content of the invention is described in further details by the following examples, but this should not be interpreted as to this
The range for inventing above-mentioned theme is only limitted to embodiment below.All technologies realized based on above content of the present invention belong to this hair
Bright range.
Embodiment 1
It in reaction flask, is added ortho-nitrophenyl formylhydrazine 181g (1.0mol), methylene chloride 500mL is added, be added
Diisopropylethylamine 165mL is warming up to back flow reaction until TLC monitors the fully reacting of ortho-nitrophenyl formylhydrazine, by reaction system
It is cooled to 0 DEG C, the mixed solution of diethyl phosphite 138g (1.0mol) and carbon tetrachloride 96mL is added dropwise, uses water after reaction
Washing, organic phase is dry, is spin-dried for, obtains target product polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- benzos three
Piperazine -4- ketone I 290g, yield 97.3%, purity 98.9%.
Embodiment 2
It in reaction flask, is added ortho-nitrophenyl formylhydrazine 181g (1.0mol), solvent carbon tetrachloride 500mL is added, be added
Diisopropylethylamine 165mL is warming up to back flow reaction until TLC monitors the fully reacting of ortho-nitrophenyl formylhydrazine, by reaction system
It is cooled to 0 DEG C, the mixed solution of diethyl phosphite 138g (1.0mol) and carbon tetrachloride 96mL is added dropwise, uses water after reaction
Washing, organic phase is dry, is spin-dried for, obtains target product polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- benzos three
Piperazine -4- ketone I 280g, yield 93.6%, purity 99.0%.
Embodiment 3
It in reaction flask, is added ortho-nitrophenyl formylhydrazine 181g (1.0mol), solvent toluene 500mL is added, it is different to be added two
Propylethylamine 165mL is warming up to back flow reaction until TLC monitoring ortho-nitrophenyl formylhydrazine fully reacting, reaction system is cooled down
To 0 DEG C, the mixed solution of diethyl phosphite 138g (1.0mol) and carbon tetrachloride 96mL is added dropwise, is washed with water after reaction
It washs, organic phase is dry, is spin-dried for, obtains target product polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- phentriazines -
4- ketone I 250g, yield 83.6%, purity 99.5%.
Embodiment 4
It in reaction flask, is added ortho-nitrophenyl formylhydrazine 181g (1.0mol), solvent xylene 500mL is added, be added two
Wopropyl ethyl amine 165mL is warming up to back flow reaction until TLC monitoring ortho-nitrophenyl formylhydrazine fully reacting, reaction system is dropped
Temperature is added dropwise the mixed solution of diethyl phosphite 138g (1.0mol) and carbon tetrachloride 96mL, is washed with water after reaction to 0 DEG C
It washs, organic phase is dry, is spin-dried for, obtains target product polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- phentriazines -
4- ketone I 267g, yield 89.2%, purity 99.2%.
Embodiment 5
It in reaction flask, is added ortho-nitrophenyl formylhydrazine 181g (1.0mol), methylene chloride 500mL is added, be added
Triethylamine 139mL (1.0mol) is warming up to back flow reaction until TLC monitors the fully reacting of ortho-nitrophenyl formylhydrazine, by reactant
System is cooled to 5 DEG C, and the mixed solution of diethyl phosphite 138g (1.0mol) and carbon tetrachloride 96mL is added dropwise, uses after reaction
Water washing, organic phase is dry, is spin-dried for, obtains target product polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- benzos
Triazine -4- ketone I 292g, yield 97.7%, purity 99.0%.
Embodiment 6
It in reaction flask, is added ortho-nitrophenyl formylhydrazine 181g (1.0mol), solvent carbon tetrachloride 500mL is added, be added
Triethylamine 139mL (1.0mol) is warming up to back flow reaction until TLC monitors the fully reacting of ortho-nitrophenyl formylhydrazine, by reactant
System is cooled to 5 DEG C, and the mixed solution of diethyl phosphite 138g (1.0mol) and carbon tetrachloride 96mL is added dropwise, uses after reaction
Water washing, organic phase is dry, is spin-dried for, obtains target product polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- benzos
Triazine -4- ketone I 281g, yield 94.0%, purity 99.2%.
Embodiment 7
It in reaction flask, is added ortho-nitrophenyl formylhydrazine 181g (1.0mol), solvent toluene 500mL is added, three second are added
Amine 139mL (1.0mol) is warming up to back flow reaction until TLC monitoring ortho-nitrophenyl formylhydrazine fully reacting, reaction system is dropped
Temperature is added dropwise the mixed solution of diethyl phosphite 138g (1.0mol) and carbon tetrachloride 96mL, is washed with water after reaction to 5 DEG C
It washs, organic phase is dry, is spin-dried for, obtains target product polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- phentriazines -
4- ketone I 256g, yield 85.6%, purity 99.3%.
Embodiment 8
It in reaction flask, is added ortho-nitrophenyl formylhydrazine 181g (1.0mol), solvent xylene 500mL is added, be added three
Ethamine 139mL (1.0mol) is warming up to back flow reaction until TLC monitors the fully reacting of ortho-nitrophenyl formylhydrazine, by reaction system
5 DEG C are cooled to, the mixed solution of diethyl phosphite 138g (1.0mol) and carbon tetrachloride 96mL is added dropwise, uses water after reaction
Washing, organic phase is dry, is spin-dried for, obtains target product polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- benzos three
Piperazine -4- ketone I 265g, yield 88.6%, purity 99.1%.
Embodiment 9
It in reaction flask, is added ortho-nitrophenyl formylhydrazine 181g (1.0mol), methylene chloride 500mL, is added two or two
Wopropyl ethyl amine 248mL (1.5mol), be warming up to back flow reaction until TLC monitor the fully reacting of ortho-nitrophenyl formylhydrazine, will be anti-
It answers system to be down to 3 DEG C, the mixed solution of diethyl phosphite 276g (2.0mol) and carbon tetrachloride 120mL is added dropwise, reaction terminates
After be washed with water, organic phase is dry, is spin-dried for, obtains target product polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3-
Phentriazine -4- ketone I 280g, yield 93.6%, purity 99.5%.
Embodiment 10
It in reaction flask, is added ortho-nitrophenyl formylhydrazine 181g (1.0mol), methylene chloride 500mL, three second is added
Amine 208mL (1.5mol) is warming up to back flow reaction until TLC monitoring ortho-nitrophenyl formylhydrazine fully reacting, reaction system is dropped
Temperature is added dropwise the mixed solution of diethyl phosphite 276g (2.0mol) and carbon tetrachloride 193mL, uses water after reaction to 5 DEG C
Washing, organic phase is dry, is spin-dried for, obtains target product polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- benzos three
Piperazine -4- ketone I 275g, yield 91.9%, purity 99.0%.
Embodiment 11
It in reaction flask, is added ortho-nitrophenyl formylhydrazine 181g (1.0mol), methylene chloride 500mL, three second is added
Amine 174mL (1.25mol) is warming up to back flow reaction until TLC monitoring ortho-nitrophenyl formylhydrazine fully reacting, reaction system is dropped
Temperature is added dropwise the mixed solution of diethyl phosphite 207g (1.5mol) and carbon tetrachloride 120mL, uses water after reaction to 2 DEG C
Washing, organic phase is dry, is spin-dried for, obtains target product polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- benzos three
Piperazine -4- ketone I 279g, yield 93.3%, purity 99.1%.
Embodiment above describes basic principles and main features of the invention and advantages.The technical staff of the industry should
Understand, the present invention is not limited to the above embodiments, and the above embodiments and description only describe originals of the invention
Reason, under the range for not departing from the principle of the invention, various changes and improvements may be made to the invention, these changes and improvements are each fallen within
In the scope of protection of the invention.
Claims (4)
1. polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- phentriazine -4- ketone, it is characterised in that the 1- (diethyl
Oxygroup phosphinylidyne oxygroup) -1,2,3- phentriazine -4- ketone structural formula are as follows:
2. a kind of polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- phentriazine -4- ketone described in claim 1
Preparation method, it is characterised in that use multistep one pot process, detailed process are as follows: ortho-nitrophenyl formylhydrazine is added in a solvent
And organic base, it is warming up to back flow reaction, is cooled to 0~5 DEG C after reaction, the carbon tetrachloride for adding diethyl phosphite is molten
Liquid is reacted, and is washed with water after reaction, and organic phase is dry, is spin-dried for, is obtained target product polypeptide condensing agent 1- (diethoxy
Base phosphinylidyne oxygroup) -1,2,3- phentriazine -4- ketone, wherein solvent be methylene chloride, carbon tetrachloride, toluene or dimethylbenzene, it is organic
Alkali is diisopropylethylamine or triethylamine.
3. polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- phentriazine -4- ketone according to claim 2
Preparation method, it is characterised in that: the ortho-nitrophenyl formylhydrazine, organic base, diethyl phosphite and feeding intake for carbon tetrachloride are rubbed
You are than being 1:1-1.5:1-2:1-2.
4. polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- phentriazine -4- ketone according to claim 2
Preparation method, it is characterised in that the reaction equation in synthesis process are as follows:
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| CN201811110570.0A CN109232647A (en) | 2018-09-21 | 2018-09-21 | Polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- phentriazine -4- ketone and preparation method thereof |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005007634A1 (en) * | 2003-07-18 | 2005-01-27 | Frutarom Ltd. | 3-hydroxy-4-oxo-1,2,3-triazines and derivatives thereof for amide and ester bond formation |
| CN103864705A (en) * | 2014-03-21 | 2014-06-18 | 河南师范大学 | Polypeptide condensating agent 1-hydroxy-1,2,3-phentriazine-4(3H)-one and preparation method thereof |
| CN103864885A (en) * | 2014-03-21 | 2014-06-18 | 河南师范大学 | Application of 1-hydroxy-1,2,3-phentriazine-4(3H)-one in polypeptide synthesis |
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2018
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005007634A1 (en) * | 2003-07-18 | 2005-01-27 | Frutarom Ltd. | 3-hydroxy-4-oxo-1,2,3-triazines and derivatives thereof for amide and ester bond formation |
| CN103864705A (en) * | 2014-03-21 | 2014-06-18 | 河南师范大学 | Polypeptide condensating agent 1-hydroxy-1,2,3-phentriazine-4(3H)-one and preparation method thereof |
| CN103864885A (en) * | 2014-03-21 | 2014-06-18 | 河南师范大学 | Application of 1-hydroxy-1,2,3-phentriazine-4(3H)-one in polypeptide synthesis |
Non-Patent Citations (1)
| Title |
|---|
| 尹志刚 主编: "《有机磷化合物 第1版》", 31 March 2011, 北京：化学工业出版社 * |
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