SE416552B - DERIVATIVES OF VINCADIFFORMIN FOR USE AS INTERMEDIATES FOR THE PREPARATION OF 10-BROMINE VINCAMIN - Google Patents
DERIVATIVES OF VINCADIFFORMIN FOR USE AS INTERMEDIATES FOR THE PREPARATION OF 10-BROMINE VINCAMINInfo
- Publication number
- SE416552B SE416552B SE7903264A SE7903264A SE416552B SE 416552 B SE416552 B SE 416552B SE 7903264 A SE7903264 A SE 7903264A SE 7903264 A SE7903264 A SE 7903264A SE 416552 B SE416552 B SE 416552B
- Authority
- SE
- Sweden
- Prior art keywords
- formula
- compound
- bromine
- vincadifformin
- intermediates
- Prior art date
Links
- 239000000543 intermediate Substances 0.000 title claims 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 title description 6
- 229910052794 bromium Inorganic materials 0.000 title description 6
- GIGFIWJRTMBSRP-UHFFFAOYSA-N DL-Vincadifformin Natural products C1C(C(=O)OC)=C2NC3=CC=CC=C3C22CCN3CCCC1(CC)C23 GIGFIWJRTMBSRP-UHFFFAOYSA-N 0.000 title description 4
- RXPRRQLKFXBCSJ-GIVPXCGWSA-N vincamine Chemical compound C1=CC=C2C(CCN3CCC4)=C5[C@@H]3[C@]4(CC)C[C@](O)(C(=O)OC)N5C2=C1 RXPRRQLKFXBCSJ-GIVPXCGWSA-N 0.000 title description 3
- RXPRRQLKFXBCSJ-UHFFFAOYSA-N dl-Vincamin Natural products C1=CC=C2C(CCN3CCC4)=C5C3C4(CC)CC(O)(C(=O)OC)N5C2=C1 RXPRRQLKFXBCSJ-UHFFFAOYSA-N 0.000 title description 2
- 238000002360 preparation method Methods 0.000 title description 2
- WKACQPMBGWZDMR-UHFFFAOYSA-N Vincamin Natural products CC=C1/CN2CCC34CC2C1C(=C3Nc5ccccc45)C=O WKACQPMBGWZDMR-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 20
- 150000001450 anions Chemical class 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical group ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 150000004965 peroxy acids Chemical class 0.000 description 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 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
- 239000012074 organic phase Substances 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- ZJAFQAPHWPSKRZ-UHFFFAOYSA-N 4-nitrobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=C([N+]([O-])=O)C=C1 ZJAFQAPHWPSKRZ-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-M fumarate(1-) Chemical compound OC(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-M 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960002726 vincamine Drugs 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D461/00—Heterocyclic compounds containing indolo [3,2,1-d,e] pyrido [3,2,1,j] [1,5]-naphthyridine ring systems, e.g. vincamine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/16—Peri-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
7903264-5 .--__ Br II vari n, X och Y har ovan angiven betydelse. Därvid användes exempelvis en persyra, t.ex. metaklorperbensoesyra, para- nitroperbensoesyra, permyrsyra eller perättiksyra. En lämplig _ reaktionstemperatur är inom intervallet O-50°C. 7903264-5. - __ Br II wherein n, X and Y have the meaning given above. In this case, for example, a peracid is used, e.g. methachloroperbenzoic acid, paranitroperbenzoic acid, permyric acid or peracetic acid. A suitable reaction temperature is in the range of 0-50 ° C.
En förening med formeln II kan framställas på så sätt att man behandlar optiskt aktiv eller racemisk 15-bromvincamindifformin, som har formeln f III antingen med en persyra, varvid en förening med formeln II, vari n = O erhålles, eller med en syra som har formeln HY, var- vid en förening med formeln II erhålles, vari n = 1.A compound of formula II can be prepared by treating optically active or racemic 15-bromovincamine difformin having the formula f III either with a peracid, wherein a compound of formula II, wherein n = 0 is obtained, or with an acid having formula HY, whereby a compound of formula II is obtained, wherein n = 1.
När n = 0 kan reaktionen genomföras under samma betingelser som för omvandlingen av en förening med formeln II till en förening med formeln I. När n betecknar l kan reaktionen genom- föras vid en temperatur från O till 20°C.When n = 0, the reaction can be carried out under the same conditions as for the conversion of a compound of formula II to a compound of formula I. When n represents 1, the reaction can be carried out at a temperature of from 0 to 20 ° C.
Det är inte nödvändigt att isolera föreningarna med formeln II såsom rena föreningar. 790326443 Exempelvis kan en förening med formeln III behandlas med minst 2 mol av en persyra, varvid en förening med formeln I direkt bildas, vari n betecknar 0. Å andra sidan kan man först behandla en förening med formeln III med en syra, som icke är en persyra, och därpå omsätta med en persyra, varvid direkt en förening med formeln I, vari n är l bildas.It is not necessary to isolate the compounds of formula II as pure compounds. For example, a compound of formula III may be treated with at least 2 moles of a peracid, whereby a compound of formula I is directly formed, wherein n represents 0. On the other hand, one may first treat a compound of formula III with an acid which is not a peracid, and then reacting with a peracid to directly form a compound of formula I, wherein n is 1.
En förening med formeln III kan framställas genom omlagring av en optiskt aktiv eller racemisk förening, som har formeln IV med klorväte eller bromvätegas. Ett lämpligt lösningsmedel är kloroform. Reaktionen kan genomföras vid en temperatur mellan 10 een 3o°c.A compound of formula III can be prepared by rearranging an optically active or racemic compound having formula IV with hydrogen chloride or hydrogen bromide gas. A suitable solvent is chloroform. The reaction can be carried out at a temperature between 30 ° C.
En förening med formeln IV kan framställas genom bromering av optiskt aktiv eller racemisk vincamindifformin, t.ex. med l molekvivalent brom vid en temperatur från -30 till -l0°C.A compound of formula IV may be prepared by bromination of optically active or racemic vincamine difformin, e.g. with 1 molar equivalent of bromine at a temperature from -30 to -10 ° C.
En förening med formeln III kan företrädesvis framställas genom reaktion av vincadifformin med l molekvivalent brom 1 närvaro av klorväte eller bromväte vid en temperatur från lo till 3o°c.A compound of formula III may preferably be prepared by reacting vincadifformin with 1 molar equivalent of bromine in the presence of hydrogen chloride or hydrogen bromide at a temperature of from 10 to 30 ° C.
När man använder optiskt aktiva utgângsmaterial erhålles de motsvarande optiskt aktiva slutföreningarna. Utgângsmateria- len är kända eller kan framställas enligt i och för sig kända metoder av kända föreningar. .7903264-5 Uppfínningen belyses närmare medelst följande exempel. Tem- peraturerna anges i Celsius-grader och är icke korrigerade.When using optically active starting materials, the corresponding optically active final compounds are obtained. The starting materials are known or can be prepared according to methods known per se from known compounds. .7903264-5 The invention is further illustrated by the following examples. The temperatures are given in degrees Celsius and are uncorrected.
Exempel 3 och 4 avser framställningen av den terapeutiskt värdefulla lO-bromvincaminen.Examples 3 and 4 relate to the preparation of the therapeutically valuable 10-bromovincamine.
Exempel 1. (-)-15-bromvincadifformin (förening enligt formeln III) a) Direkt förfarande En lösning av 20 g (-)-vincadifforminbas i 200 ml kloroform mättades vid 20° med klorvätegas. Därefter tilldroppades under 25 minuter vid samma temperatur en lösning av 9,92 g brom i 40 ml kloroform. Efter 30 minuters omröring uthäll- des reaktionslösningen på 500 ml is och 10 g natriumkarbo- nat. Den organiska fasen avskildes, tvättades och torkades.Example 1. (-) - 15-Bromovincadifformin (compound of formula III) a) Direct process A solution of 20 g of (-) - vincadifformin base in 200 ml of chloroform was saturated at 20 ° with hydrogen chloride gas. Then a solution of 9.92 g of bromine in 40 ml of chloroform was added dropwise over 25 minutes at the same temperature. After stirring for 30 minutes, the reaction solution is poured onto 500 ml of ice and 10 g of sodium carbonate. The organic phase was separated, washed and dried.
Den torkade, organiska fasen upparbetades, varvid (-)-l5- -bromvincadifformin erhölls (vätefumarat, smältpunkt -zoo-2o1°; talš” = -44si°_ (c = 1 i acetonn. _ b) Via isolering av en förening med formeln IV Till en lösning av 5 g (-)-vincadifformin och 20 ml kloro- form droppades vid -200 en lösning av 2,36 g brom i 20 ml kloroform. Därefter uthälldes reaktionsblandningen på is och natriumbikarbonat. Den organiska fasen avskildes, tvätta- des, torkades och indunstades vid 500 i vakuum. Indunstnings- återstoden absorberades på kiselgel och eluerades med kloro- form och 5% aceton. Man erhöll 3-brom-l,2-didehydroaspidos- permidin-3-karbonsyrametylester. Smältpunkt ungefär 95° (sönderdelning).The dried organic phase was worked up to give (-) - 15-bromovincadifformin (hydrogen fumarate, melting point -zoo-2o1 °; talš "= -44si ° _ (c = 1 in acetone. _ B) Via isolation of a compound with formula IV To a solution of 5 g of (-) - vincadifformin and 20 ml of chloroform was added dropwise at -200 a solution of 2.36 g of bromine in 20 ml of chloroform, then the reaction mixture was poured onto ice and sodium bicarbonate.The organic phase was separated, washed was evaporated, dried and evaporated in vacuo at 500 DEG C. The evaporation residue was absorbed onto silica gel and eluted with chloroform and 5% acetone to give 3-bromo-1,2-didehydroaspidospermidine-3-carbonic acid methyl ester Melting point about 95 ° (decomposition).
Metylestern behandlades därefter vid 200 med bromvätegas i kloroform, varvid efter upparbetning erhölls (-)-15-brom- vincadifformin. 7903264-5 Exemgel 2. 15-brom-l,2-didehydro-3-hydroxiaspidosperidin-3-karbonsyra- metylester-9-oxid (förening med formeln I, vari n = 0) Den enligt exempel la erhållna torkade, organiska fasen be- handlades portionsvis vid 200 med 20,4 g 82,5%-ig m-klorper- bensoesyra och fick stå i 30 minuter. Blandningen tvättades med en 5%-ig natriumkarbonatlösning, torkades över natrium- sulfat och indunstades i vakuum vid 500. Återstoden försat- tes med 200 ml aceton, varvid titelföreningen utkristallise- rade, smältpunkt (ur aceton/kloroform) 202-205°(sönderdel- ning).The methyl ester was then treated at 200 with bromine hydrogen gas in chloroform to give (-) - 15-bromovincadifformin after work-up. Example 90 2. 15-Bromo-1,2-didehydro-3-hydroxyaspidosperidine-3-carboxylic acid methyl ester-9-oxide (compound of formula I, wherein n = 0) The dried organic phase obtained according to Example 1a is was traded portionwise at 200 with 20.4 g of 82.5% m-chloroperbenzoic acid and allowed to stand for 30 minutes. The mixture was washed with a 5% sodium carbonate solution, dried over sodium sulphate and evaporated in vacuo at 500. The residue was added with 200 ml of acetone, the title compound crystallized out, melting point (from acetone / chloroform) 202-205 ° (dec. - ning).
Exemgel 3. (+)-[(3s,14s,16si1-lo-bromvincamin 20 g av en lösning av den enligt exempel 2 erhållna 9-oxiden, 400 ml isättika, 40 ml vatten och 17,4 g trifenylfosfin om- rördes 4 timmar vid 500. Reaktionsblandningen indunstades i vakuum och återstoden behandlades med natriumhydroxid1ös~ ning. Den bildade basen upptogs i kloroform och fromatografe- rades på kiselgel. Härvid eluerades (+)-10~bromvincaminbas med kloroform innehållande 3% metanol. Smp. 202-205°; lalšo = +3s,2° (C = 1 1 cHcl3>. En polär fraktiøn innehöll I(3s,l4R,las)1-lo-bromepivincamin, amp. 195-l96°= [a1š° = -a,6° (c = 1 cHcl3), vilken på 1 och för sig känn sätt kan omvandlas i (+)-10-bromvincamin.Example gel 3. (+) - [(3s, 14s, 16si1-10-bromovincamine 20 g of a solution of the 9-oxide obtained according to Example 2, 400 ml of glacial acetic acid, 40 ml of water and 17.4 g of triphenylphosphine were stirred 4 hours at 500. The reaction mixture was evaporated in vacuo and the residue was treated with sodium hydroxide solution, the base formed was taken up in chloroform and fromitographed on silica gel, eluting with (+) - 10-bromovincamine base with chloroform containing 3% methanol. °; lalšo = + 3s, 2 ° (C = 1 1 cHcl3>. A polar fraction contained I (3s, 14R, las) 1-lo-bromepivincamine, amp. 195-196 ° = [a1š ° = -a, 6 ° (c = 1 cHcl3), which in a manner known per se can be converted into (+) - 10-bromovincamine.
Exemgel 4. (+)-[(3S,l4S,l6S)]-l0-bromvincamin En lösning av 4,17 g (-)-15-bromvincadifformin i 100 ml to- luen försattes med l,l5 g trifluorättiksyra. Blandningen, innehållande en förening med formeln II, vari n = l och Y betecknar trifluoracetat, hölls vid 5°, och härpå infördes portionsvis 2,00 g p-nitroperbensoesyra. Efter uppvärmning till rumstemperatur förvarades lösningen 15 timmar. Lösning- en indunstades i vakuum och återstoden, innehållande en förening med formeln I, vari n = 1 och Y = trifluoracetat, . 7903264-5 . upptogs i en blandning av 45 ml isättika och 5 ml vatten.Example gel 4. (+) - [(3S, 14S, 16S)] - 10-bromovincamine A solution of 4.17 g of (-) - 15-bromovincadifformin in 100 ml of toluene was added with 1.5 g of trifluoroacetic acid. The mixture, containing a compound of formula II, wherein n = 1 and Y represents trifluoroacetate, was kept at 5 °, and 2.00 g of p-nitroperbenzoic acid were introduced portionwise thereto. After warming to room temperature, the solution was stored for 15 hours. The solution was evaporated in vacuo and the residue containing a compound of formula I, wherein n = 1 and Y = trifluoroacetate,. 7903264-5. was taken up in a mixture of 45 ml of glacial acetic acid and 5 ml of water.
Lösningen omrördes 2 timmar vid rumstemperatur och inställ- des därefter vid 50° med 10%-ig natriumhydroxid på pH 9.The solution was stirred for 2 hours at room temperature and then adjusted at 50 ° with 10% sodium hydroxide to pH 9.
Härpå extraherade man tre gånger med diklormetan. Därefter tvättade man med vatten, torkade över natriumsulfat och in- dunstade till torrhet. Härpâ kromatograferades produkten såsom 1 exempel 3, varvid titelföreningen och [(3S,14R,l6S)]- -l0-bromepivincamin erhölls. _ ,_ lM-»fz U . _ _It was then extracted three times with dichloromethane. It was then washed with water, dried over sodium sulphate and evaporated to dryness. The product was then chromatographed as in Example 3 to give the title compound and [(3S, 14R, 16S)] - 10-bromepivincamine. _, _ lM- »fz U. _ _
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE7903264A SE416552B (en) | 1979-04-11 | 1979-04-11 | DERIVATIVES OF VINCADIFFORMIN FOR USE AS INTERMEDIATES FOR THE PREPARATION OF 10-BROMINE VINCAMIN |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE7903264A SE416552B (en) | 1979-04-11 | 1979-04-11 | DERIVATIVES OF VINCADIFFORMIN FOR USE AS INTERMEDIATES FOR THE PREPARATION OF 10-BROMINE VINCAMIN |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SE7903264L SE7903264L (en) | 1979-06-28 |
| SE416552B true SE416552B (en) | 1981-01-19 |
Family
ID=20337800
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE7903264A SE416552B (en) | 1979-04-11 | 1979-04-11 | DERIVATIVES OF VINCADIFFORMIN FOR USE AS INTERMEDIATES FOR THE PREPARATION OF 10-BROMINE VINCAMIN |
Country Status (1)
| Country | Link |
|---|---|
| SE (1) | SE416552B (en) |
-
1979
- 1979-04-11 SE SE7903264A patent/SE416552B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| SE7903264L (en) | 1979-06-28 |
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| SU453832A3 (en) | METHOD OF PREPARATION Having applied this method, the authors obtained irregular and halogen-steroids of the Erengan series with valuable properties. The proposed method for obtaining the halo-15 steroids of the pregan series of the formula I \ = 2t L • Where Z is two aliphatic, aromatic or araliphatic hydrocarbon residues, or group ~ .C == Z— cycloalkylideic / / group and X is a fluorine or chlorine atom, consists in the fact that in the compound of formula II there are 'dH.FCHoF20, where RI and Rj are each free or etherified: 1 - or to the ether of oxygram or Ri together with R2 - group 2530 where RI and R2 have the indicated values epoxide ring cleaved action halo- geivodoroda HX, wherein X has the abovementioned meaning, or using an agent-releasing this galogeivodorod and the resulting halogen- gndrin simultaneously or sequentially dehydrated by treatment with hydrogen knslotoy halogen. |