CN101372486A - Preparation of abafungin and analogues thereof - Google Patents
Preparation of abafungin and analogues thereof Download PDFInfo
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- CN101372486A CN101372486A CNA2008100463027A CN200810046302A CN101372486A CN 101372486 A CN101372486 A CN 101372486A CN A2008100463027 A CNA2008100463027 A CN A2008100463027A CN 200810046302 A CN200810046302 A CN 200810046302A CN 101372486 A CN101372486 A CN 101372486A
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- abafungin
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- TYBHXIFFPVFXQW-UHFFFAOYSA-N abafungin Chemical compound CC1=CC(C)=CC=C1OC1=CC=CC=C1C1=CSC(NC=2NCCCN=2)=N1 TYBHXIFFPVFXQW-UHFFFAOYSA-N 0.000 title claims abstract description 21
- 229950006373 abafungin Drugs 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 31
- -1 3-substituted propylamine Chemical class 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- CZXGXYBOQYQXQD-UHFFFAOYSA-N methyl benzenesulfonate Chemical compound COS(=O)(=O)C1=CC=CC=C1 CZXGXYBOQYQXQD-UHFFFAOYSA-N 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000005948 methanesulfonyloxy group Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 239000004202 carbamide Substances 0.000 abstract description 7
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 abstract description 5
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 abstract description 3
- 150000003672 ureas Chemical class 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 2
- 238000000034 method Methods 0.000 abstract 3
- OHFXUPDPPRJZES-UHFFFAOYSA-N 1,2,5,6-tetrahydropyrimidine Chemical class C1CC=NCN1 OHFXUPDPPRJZES-UHFFFAOYSA-N 0.000 abstract 1
- 238000010960 commercial process Methods 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 20
- 239000007787 solid Substances 0.000 description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 235000013877 carbamide Nutrition 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 241000233866 Fungi Species 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 230000002194 synthesizing effect Effects 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 229940126214 compound 3 Drugs 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000010792 warming Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 150000003222 pyridines Chemical class 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 235000002639 sodium chloride Nutrition 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- OTPDWCMLUKMQNO-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrimidine Chemical compound C1NCC=CN1 OTPDWCMLUKMQNO-UHFFFAOYSA-N 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010061217 Infestation Diseases 0.000 description 1
- 208000010195 Onychomycosis Diseases 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 201000007096 Vulvovaginal Candidiasis Diseases 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 238000005915 ammonolysis reaction Methods 0.000 description 1
- 230000001716 anti-fugal effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000007867 post-reaction treatment Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 201000005882 tinea unguium Diseases 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 208000010484 vulvovaginitis Diseases 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Landscapes
- Thiazole And Isothizaole Compounds (AREA)
Abstract
The invention belongs to the technical field of medicine, and discloses a method for preparing Abafungin and analogue of the Abafungin; the method is characterized in that 2-aminothiazole and carbamate are taken as materials to synthesize single substituted urea, and 1, 2, 5, 6-tetrahydropyrimidine is generated by condensing the single substituted urea and 3-substituted propylamine. The method has the advantages of few reaction steps, mild reaction steps, high yield, good product purity and low cost, and is suitable for commercial process.
Description
Technical field:
The invention belongs to medical technical field, be specifically related to the preparation method of abafungin and analogue thereof.
Background technology:
Abafungin (Abafungin, Abasol), chemistry is by name: N-(4-(2-(2, the 4-dimethyl phenoxy) phenyl)-1, the 3-thiazol-2-yl)-1,4,5,6-tetrahydropyrimidine-2-amine, it is first medicine in the aminothiazole class antifungal drug, is developed by York Pharma company.Abafungin has dual antifungic action, that is: can suppress fungi again can kill fungi, can kill the fungi that epacmastic fungi can kill stationary phase again.Simultaneously, abafungin has broad spectrum antibiotic activity, and indication comprises: refer to (toe) tinea unguium, vaginal candida infects, and bacterium merges fungi infestation vulvovaginitis, various skin bacterium dermatitis and some acne.
At present, the synthetic method of the report of abafungin mainly is by tetrahydro-pyrimidine base thiocarbamide and halogeno-benzene ketone condensation prepared thiazole ring (US4956370), and concrete route is seen following reaction scheme figure:
The synthetic difficulty of thiocarbamide wherein (compound 5), yield is low; And halogeno-benzene ketone (compound 6) will make by polystep reactions such as halogenating reactions especially, severe reaction conditions not only, and route is long, and environmental pollution is big, more than all drawbacks limited the large-scale industrial production of abafungin, cause its cost height, output is few.
Summary of the invention:
The objective of the invention is to overcome present abafungin preparation method's deficiency, provide a kind of raw material economics to be easy to get, reaction scheme is short, reaction conditions is gentle, yield is high, the preparation method of good product purity.
The objective of the invention is to be achieved through the following technical solutions:
Preparation method of the present invention is undertaken by following reaction scheme figure, R1 wherein, R2, R3, R4, R5, R6, R7, R8, R9 can be hydrogen atoms, halogen atom, nitro, methyl and trifluoromethyl can be identical, also can be different, R10 is the alkyl of C1～C4, and X is Sauerstoffatom or sulphur atom, and Y is: the chlorine atom, bromine atoms, the iodine atom is to Methyl benzenesulfonyl oxygen base and methanesulfonyloxy group.
The carbamate of thiazolamine compounds (compound 1) and Boc protection is carried out ammonolysis reaction, and (step 1) obtains hydrazine compound (compound 2).This step response feature is that reaction solvent is an aprotic polar solvent, is specially: acetonitrile or tetrahydrofuran (THF); Temperature of reaction is the reflux temperature of solvent; Reaction times is 1 to 12 hour; Compound 1 is 1:1 to 1:3 with the mol ratio of carbamate.
Hydrazine compound (compound 2) is taken off Boc protecting group (step 2) obtain compound 3 under the effect of acid.This step reaction is characterised in that to be reflected in the aprotic polar solvent to be carried out, and is specially: ethyl acetate, methylene dichloride; Removing the used acid of Boc protecting group is: hydrogenchloride or trifluoroacetic acid.
(step 3) obtains abafungin and analogue (compound 4) thereof with 3-substituted propylamine hybrid reaction with compound 3.This step reaction is characterised in that reaction solvent is a toluene; Need to add acid scavenger in the reaction, be specially: anhydrous sodium carbonate, triethylamine, pyridine; Temperature of reaction is the reflux temperature of solvent; Reactive mode refluxes for dividing water; Reaction times is 4 to 24 hours; Compound 3 is 1:1 to 1:1.5 with the molar ratio of 3-substituted propylamine.
The starting raw material that the present invention selects is simple and easy to, and cheap, reaction scheme is short, and the reaction conditions gentleness does not produce the strong acid and strong base waste material, and post-reaction treatment is easy, and preparation yield height is suitable for industrialized production.
Below the invention will be further described as embodiment by abafungin, it should be noted that reaction conditions and raw material purpose that following examples are related are the present invention is done better explanation, rather than limitation of the present invention.
Embodiment
Embodiment 1
Synthesizing of 1-tert.-butoxy-3-(4-(2-(2, the 4-dimethyl phenoxy) phenyl) thiazole-Ji-) urea
2.96 kilograms of 4-(2-(2, the 4-dimethyl phenoxy) phenyl) thiazole-2-amine and 30 liters of anhydrous tetrahydro furans are dropped into 100 liters of reactors, stir and made the solid dissolving in 30 minutes.Add 2.63 kilograms of Boc-Urethylanes subsequently, temperature slowly is warming up to backflow, kept back flow reaction 6 hours, check to HPLC to react completely.Solvent is steamed in decompression, adds 40 liters of acetic acid ethyl dissolution resistatess, washes, and each 20 liters totally twice, anhydrous sodium sulfate drying, standby.Sample for analysis is got crude product evaporate to dryness solid 10 grams, with 10 milliliters of ethyl acetate and 70 ml n-hexane recrystallizations, obtains yellow solid powder 6.8 grams.Fusing point: 103～108 ℃.
1H-NMR(CDCl
3)：1.22(s，9H)；2.32(s，3H)；2.35(s，3H)；6.01(s，br，2H)；6.58(s，1H)；6.63(d，1H)；6.81～6.85(m，2H)；6.95～7.05(m，3H)；7.48(m，1H)。
Embodiment 2
Synthesizing of 1-tert.-butoxy-3-(4-(2-(2, the 4-dimethyl phenoxy) phenyl) thiazole-Ji-) urea
2.96 kilograms of 4-(2-(2, the 4-dimethyl phenoxy) phenyl) thiazole-2-amine and 30 liters of anhydrous tetrahydro furans are dropped into 100 liters of reactors, stir and made the solid dissolving in 30 minutes.Add 3.04 kilograms of Boc-carbamic acid isopropyl esters subsequently, temperature slowly is warming up to backflow, kept back flow reaction 4 hours, check to HPLC to react completely.Solvent is steamed in decompression, adds 40 liters of acetic acid ethyl dissolution resistatess, washes, and each 20 liters totally twice, anhydrous sodium sulfate drying, standby.Sample for analysis is got crude product evaporate to dryness solid 10 grams, with 10 milliliters of ethyl acetate and 70 ml n-hexane recrystallizations, obtains yellow solid powder 6.1 grams.Fusing point: 103～106 ℃.
1H-NMR(CDCl
3)：1.22(s，9H)；2.32(s，3H)；2.35(s，3H)；6.01(s，br，2H)；6.58(s，1H)；6.63(d，1H)；6.81～6.85(m，2H)；6.95～7.05(m，3H)；7.48(m，1H)。
Embodiment 3
Synthesizing of 1-(4-(2-(2, the 4-dimethyl phenoxy) phenyl) thiazole-Ji-) urea
The ethyl acetate solution of embodiment 1 gained is dropped into 100 liters of reactors, be cooled to 0 ℃, keep adding under 0 ℃ of stirring 500 gram trifluoroacetic acids, be warming up to 25～30 ℃ of stirring reactions subsequently 5 hours, check to HPLC to react completely, drip triethylamine to reaction solution and be neutral.Wash with water, each 20 liters totally 3 times, anhydrous sodium sulfate drying, evaporate to dryness, 2.79 kilograms of orange solids.Use the acetone recrystallization, obtain 2.17 kilograms of 1-(4-(2-(2, the 4-dimethyl phenoxy) phenyl) thiazole-Ji-) ureas, the glassy yellow solid.Yield 64%.Fusing point: 119～122 ℃.
1H-NMR(CDCl
3)：2.35(s，3H)；2.37(s，3H)；6.03(s，br，3H)；6.63(s，1H)；6.68(d，1H)；6.82～6.84(m，2H)；6.98～7.18(m，3H)；7.44(m，1H)。
Embodiment 4
Synthesizing of abafungin
((2-(2 for 4-with 3.39 kilograms of 1-, the 4-dimethyl phenoxy) phenyl) thiazole-Ji-) urea and 50 liters of toluene add in 100 liters of reactors, add 1.58 kilograms of pyridines and 2.52 kilograms of 3-then to Methyl benzenesulfonyl oxygen base propylamine adding reaction solution, reaction solution is heated to backflow, divided the water back flow reaction 4 hours, and checked to HPLC to react completely.Use 20 liters of 5% sodium hydrogen carbonate solutions, 20 liters in water, 20 liters of washings of saturated aqueous common salt respectively, anhydrous sodium sulfate drying, evaporate to dryness get the blush solid.This solid with ethyl acetate/normal hexane recrystallization, is obtained abafungin, be the white powder solid, 2.72 kilograms, yield 72%.Fusing point: 189～192 ℃.
1H-NMR(CDCl
3)：1.28(t，2H)；1.61(m，2H)；2.05(m，1H)，2.32(s，3H)，2.36(s，3H)，2.67(m，2H)；4.01(s，br，1H)；6.62(s，1H)；6.68(d，1H)；6.82～6.84(m，2H)；6.94～7.10(m，3H)；7.39(m，1H)。
Embodiment 5
Synthesizing of abafungin
((2-(2 for 4-with 3.39 kilograms of 1-, the 4-dimethyl phenoxy) phenyl) thiazole-Ji-) urea and 50 liters of toluene add in 100 liters of reactors, add 1.58 kilograms of pyridines and 1.66 kilograms of 3-bromine propylamine adding reaction solutions then, reaction solution is heated to backflow, divided the water back flow reaction 24 hours, and checked to HPLC to react completely.Use 20 liters of 5% sodium hydrogen carbonate solutions, 20 liters in water, 20 liters of washings of saturated aqueous common salt respectively, anhydrous sodium sulfate drying, evaporate to dryness get the blush solid.This solid with ethyl acetate/normal hexane recrystallization, is obtained abafungin, be the white powder solid, 2.16 kilograms, yield 57%.Fusing point: 189～191 ℃.
1H-NMR(CDCl
3)：1.28(t，2H)；1.61(m，2H)；2.05(m，1H)，2.32(s，3H)，2.36(s，3H)，2.67(m，2H)；4.01(s，br1H)；6.62(s，1H)；6.68(d，1H)；6.82～6.84(m，2H)；6.94～7.10(m，3H)；7.39(m，1H)。
Claims (8)
1. the preparation method of abafungin and analogue thereof is characterized in that reaction raw materials and synthetic abafungin of reaction scheme and analogue thereof by following reaction formula representative.
2. preparation method according to claim 1, substituting group wherein: R1, R2, R3, R4, R5, R6, R7, R8, R9 can be hydrogen atom, halogen atom, nitro, methyl and trifluoromethyl.
3. substituting group according to claim 2, halogen atom wherein refers to: fluorine atom, chlorine atom, bromine atoms and iodine atom.
4. substituting group according to claim 2, in same compound, wherein R1 can be the same or different to R9.
5. preparation method according to claim 1, wherein X is Sauerstoffatom or sulphur atom.
6. preparation method according to claim 1, wherein R10 is the alkyl of C1～C4.
7. substituting group according to claim 6, R10 refers to: methyl, ethyl, propyl group, sec.-propyl, butyl, the tertiary butyl, 1-methyl-propyl and 2-methyl-propyl.
8. preparation method according to claim 1, Y is: the chlorine atom, bromine atoms, the iodine atom is to Methyl benzenesulfonyl oxygen base and methanesulfonyloxy group.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100463027A CN101372486A (en) | 2008-10-17 | 2008-10-17 | Preparation of abafungin and analogues thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CNA2008100463027A CN101372486A (en) | 2008-10-17 | 2008-10-17 | Preparation of abafungin and analogues thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101845044A (en) * | 2009-03-27 | 2010-09-29 | 重庆医药工业研究院有限责任公司 | New crystal forms of Abafungin and preparation method thereof |
| CN101762651B (en) * | 2008-12-12 | 2013-06-12 | 重庆医药工业研究院有限责任公司 | Method for measuring abafungin content and impurity by using high performance liquid chromatography |
| EP4129292A1 (en) | 2021-08-04 | 2023-02-08 | OnychoPharm GmbH | Formulation for substituted 2-aminothiazoles in the treatment of fungal and fungal-bacterial infections of the nail |
-
2008
- 2008-10-17 CN CNA2008100463027A patent/CN101372486A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101762651B (en) * | 2008-12-12 | 2013-06-12 | 重庆医药工业研究院有限责任公司 | Method for measuring abafungin content and impurity by using high performance liquid chromatography |
| CN101845044A (en) * | 2009-03-27 | 2010-09-29 | 重庆医药工业研究院有限责任公司 | New crystal forms of Abafungin and preparation method thereof |
| EP4129292A1 (en) | 2021-08-04 | 2023-02-08 | OnychoPharm GmbH | Formulation for substituted 2-aminothiazoles in the treatment of fungal and fungal-bacterial infections of the nail |
| WO2023011750A1 (en) | 2021-08-04 | 2023-02-09 | Onychopharm Gmbh | Formulation for substituted 2-aminothiazoles in the treatment of fungal and fungal-bacterial infections of the nail |
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