Tadalafil citrate hmoov(Cov khoom sib xyaw ua ke tadalafil), ib qho grey-}}}}}}}}}}}}}}}}}} stifications: tadalafil hmoov thiab tadalafil hmoov thiab tadalafil hmoov thiab tadalafil hmoov. Nws yog xaiv thiab thim rov qab inhibitor ntawm cancix guanosine Monoposphate (CGMP) {{{}}}}}}}}}). Thaum muaj kev cuam tshuam sib deev ua rau kev tso tawm hauv zos ntawm Nitric Oxide, PDE5 yog inhibited los ntawm cov leeg nqaij, uas ua rau cov nqaij mos lwj, thiab erection, xws li asexual kev txhawb zog. Cov kev ua lag luam loj tshaj plaws ntawm cov hmoov dawb tadalafil hmoov yog mas UAS.
|
Tshuaj Cov Qauv |
C28H27N3O11 |
|
Muaj pes tsawg leej |
581 |
|
Molecular hnyav |
582 |
|
m/z |
581 (100.0%), 582 (30.3%), 583 (2.7%), 583 (2.3%), 583 (1.7%), 582 (1.1%) |
|
Kev Ntsuam Xyuas |
C, 57.83; H, 4.68; N, 7.23; O, 30.26 |
|
Morphological |
hmoov |
|
Xim |
dawb rau beige |
|
Melting point |
298-300 Degree C |
|
Kub taw tes |
679.1 ± 55.0 Degree (kwv yees) |
|
Ceev |
1.51 ± 0.1 g / cm3 (kwv yees) |
|
Kev Cia |
Muab ntim rau hauv qhuav, 2 - 8 degree |
|
so |
soluble 20 mg / ml |
|
Acidity Coefficient (PKA) |
16.68 ± 0.40 (kwv yees) |
|
Flash point |
2 Qib |
Optical activity [ ] / D + 68 to + 78℃, c=1 in chloroform-d , warning word Danger , Hazard description H225-H302 + H312 + H332-H319-H315-H335 , Hazardous Mark F, Xn , Hazard category code 11-20 / 21 / 22/6, cov lus qhia txog kev nyab xeeb 16-36 / 37, Wgk Lub teb chaws Yelemees 3, RTECS UQ4431050
Peb yog tus xa khoom ntawmTadalafil citrate hmoov.
Cov lus hais: Bloom Tech (Txij xyoo 2008), ua tiav chem - tech yog cov neeg pabcuam ntawm peb.
Cov kauj ruam rau synthesizing tadalafil los ntawm d - tryptophan thiab compound ntawm cov mis 1 yog raws li nram no:
Ua ntej
Reve React D - tryptophan thiab cov mis 1 nrog ib qho alkaline reagent (xws li sodium methane kua). Qhov no yuav deprotonate cov pawg carboxyl hauv d - tryptophan thiab tsim kom muaj kev sib raug zoo ions.
Tshuaj Muaj Tshuaj: C11H12N2O2+ Nach3→ d Tryptophan anion + ch3Na
Npuab
Cov tsim tawm tsis zoo ions d - Tryptophilic reagent xws li carbene lossis nitrite chloride. Cov kauj ruam no yog hu ua kev tshem tawm. Nyob rau theem no, ib hydrogen atom nyob rau hauv qhov tsis zoo ion yuav raug hloov los ntawm hluav taws xob hluav taws xob, sib sau ua ke nruab nrab.
Tshuaj Muaj Tshuaj: D Tryptophan Anion + Ch2{{0= c=o → Intermediate
Peb
Txuas ntxiv mus rau kauj ruam tom ntej ntawm cov tshuaj tiv thaiv, rov qab kho nrab nrog lwm electrophilic reagent (xws li Benzyl Magnesium Bromide) los tsim cov khoom ua ntej ntawm cov khoom lag luam.
Tshuaj lom neeg: intermediate + ch2Pmgbr → tadalafil precursor
Thaum kawg,
Cov kev tiv thaiv / deprotive kev tawm tsam tau ua rau lub prefeor ntawm tadalafil los tsim kom muaj qhov kawg tadalafil compound. Cov kauj ruam no suav nrog kev tiv thaiv ntawm cov pab pawg hydroxyl (siv cov pab pawg tiv thaiv xws li cov pab pawg ua kom me me (siv cov pab pawg ua haujlwm).
Thaum kawg, tom qab cov txheej txheem ntawm cov tshuaj lom neeg thiab cov kauj ruam kev tiv thaiv / tsis muaj kev tiv thaiv / tsis muaj txiaj ntsig los hloov mus rau Tadalafil kom tau txais cov khoom lag luam.
Lub hauv paus ntawm inorganic impurities nyob rau hauv tadalafil citrate citrate hmoov: lub cim xeeb cab kuj "ntawm cov saw hlau ntau lawm
Tadalafil citrate hmoovyog xaiv cov phosphodiesterease 5 (PDE5) Inhibitor, thiab nws cov khoom siv citrate (Tadalafil citrate) yog ib qho khoom siv tseem ceeb rau kev kho erectile (ed) thiab Pah). Txawm li cas los xij, cov peev xwm inorganic impurities nyob rau hauv nws cov hmoov txheej txheem tsis muaj tsuas yog cuam tshuam rau qhov chaw dig muag hauv kev tswj hwm zoo los ntawm kev tswj hwm zoo "ntawm cov khoom lag luam.
Cov Khoom Siv Raw Khoom Siv: "Cov Khoom Branding" ntawm ntuj thiab hluavtaws raw khoom
Mineral Pollation ntawm ntuj raw cov ntaub ntawv
Qee qhov tseem ceeb intermediates nyob rau hauv cov synthesis ntawm tadalafil, xws li 3,4-MethylenedioxyBidenakoic acid ester, tej zaum yuav tshwm sim los ntawm cov nroj tsuag nroj tsuag, tej zaum yuav pib cog cov khoom siv. Piv txwv li, safrole extracted los ntawm kua txob nroj tsuag yog ib tug ua ntej muaj cov ntxhia methylities xws li calcium, magnesium, thiab hlau. Noj cov kua txob cog puag hauv Nagpur, Is Nrias teb ua ib qho piv txwv, cov av hlau ion ntawm 0.05% -0.1% hauv kev rho tawm. Cov hlau ions yuav siv tau ruaj khov ua ke nyob rau hauv cov synthesis, uas yog qhov nyuaj kom tshem tawm los ntawm cov kev ua kom muaj kev ntshiab.
Catalyst tseem nyob hauv cov ntaub ntawv hluavtaws nyoos
Nyob rau hauv cov tshuaj synthesis txoj kev, kev xaiv ntawm catallyst ncaj qha cuam tshuam cov inorganic impurity spectrum. Piv txwv li, palladium carbon (PD / C) lossis Raney Nickel (Raney Ni) feem ntau siv los ua cov pyridine indole nplhaib ntawm Tadalafil tub ntxhais. Cov ntaub ntawv Batch los ntawm cov tuam txhab hauv tsev los qhia tias PER / C CATHALSTs (5% {8% {8% { Tsis tas li ntawd, txhuas impurities (los ntawm cov txheej ntawm sab hauv phab ntsa ntawm lub pej thuam distillation pej xeem. Aluminium cov ntsiab lus nyob rau hauv ib lub batch ntawm n, n-DMFETHYRFORMAMIDE (DMF) Rov qab daws tau 0.3 mg / l.
Cov txheej txheem hluavtaws: molecular hneev taw ntawm cov kev tawm tsam
Los ntawm cov khoom ntawm oxidation -} kev phiv ntau ntxiv
Cov kauj ruam tseem ceeb hauv synthesis ntawm tadalafil suav nrog oxidation ntawm lub nplhaib indole thiab qhov txo ntawm lub nplhaib pyridine. Piv txwv li, hauv cov txheej txheem hloov pauv 3,4-methylenedioxybenzoic acid meter rau indolone, mNO ₂) raws li kev tsim ntawm cov khoom seem qis qis ntawm Manganese (MN-α). Cov ntaub ntawv hluavtaws ntawm qee qhov chaw kuaj sim taw qhia tias thaum ntau npaum li cas ntawm MNO ₂ yog 1.2 npaug ntawm cov ntsiab lus manganese, cov ntsiab lus ntawm manganese cov ntsiab lus ncav cuag 0.008%. In addition, in the Raney nickel catalyzed hydrogenation reaction, the wear of nickel particles may introduce nanoscale nickel impurities, and their bioavailability is 3-5 times higher than that of bulk nickel.
Ntsev seem los ntawm kev cuam tshuam kev cuam tshuam
Polyphosphate (PPA) feem ntau siv los ua tus neeg sawv cev hws thaum tsim cov pyrazine indole pob txha ntawm tadalafil. Tom qab cov tshuaj tiv thaiv, PPA yuav tsum tau muab tshem tawm los ntawm kev ntxuav dej, tab sis phosphate ions (po ⁻) yuav ua rau insoluble phosphate poovses precium thiab magnesium. Cov ntaub ntawv los ntawm kev sim batch qhia tias tsis tau ua kom zoo dua kev ntxuav, cov nqi ntawm calcium phosphate hauv cov khoom tau mus txog 0.02%. Ib qho ntxiv, thaum siv cov sodium hydride (nah) raws li lub hauv paus, tseem ceeb sodium chloride (kub) yuav cuam tshuam nrog qhov kub thiab txias, ua kom nws solubility, thiab nws solubility yog cuam tshuam rau hauv cov khoom muaju thaum tsis tshua muaj txiaj ntsig.
Kev tswj nruab nrab: "Lub qhov muag tsis pom kev" ntawm cov txheej txheem lim dej
Kabmob Hloov hauv Recrystallized Cov Tshuaj
Lub purification ntawm tadalafil intermediates yog feem ntau ua tiav los ntawm recrystallization, tab sis cov kev xaiv ntawm cov kuab tshuaj tawm tsam kev tawm tsam kev tshem tawm. Piv txwv li, thaum siv ethanol dej sib xyaw cov kuab tshuaj, chloride ions (cl ⁻) hauv dej yuav yog los ntawm kev ua tiav ntawm ion pauv resins. Cov ntaub ntawv teev ntawm cov tuam txhab kws tshuaj qhia tau tias thaum cov tshuaj chlorine hauv cov khoom siv 0.05%, deb tshaj qhov chaw muag tshuaj nce mus txog 0.01%). Tsis tas li ntawd, Silicon impurities (los ntawm distillation tower cov khoom siv, thiab lawv cov nyiaj rov qab tau zoo nrog tus naj npawb ntawm cov rov qab.
Cov tshuaj paug hauv kab chromatography
Silica gel kem chromatography yog ib qho kev siv ua kom huv si rau kev ua kom Tadalafil Intermediates, tab sis silica gel fillers yuav qhia cov hlau impurities xws li txhuas thiab hlau. Ib qho kev kawm piv txog qhov uas impurity spectra ntawm cov sib txawv ntawm cov silicone gel thiab pom tias muaj 50 ppm, ua rau muaj 0.001% nce hauv cov khoom. Tsis tas li ntawd, cov txheej txheem txawb siv hauv cov txheej txheem chromatography (xws li Dichhlorompethalane methanol) yuav yaj cov hlau ions ntawm silica gel, sib sau soluble impurities.
Kev npaj ua: Synergistic nyhuv ntawm kev zam thiab khoom siv
Kev pab nyiaj ntawm inorganic impurities nyob rau hauv cov ntaub ntawv
Kev xaiv ntawm kev zam tshwj xeeb cuam tshuam rau theem ntawm inorganic impurities nyob rau hauvTadalafil citrate hmoovcov qauv tsim. Piv txwv li, thaum siv cov cellulose microcrystalline (MCC) raws li cov lim dej (NAOH) siv hauv cov txheej txheem mcroxide yuav khaws sodium ions (Nae). Cov khoom siv sodium hauv MCC cov khoom lag luam los ntawm qee tus neeg xa khoom tau mus txog 0.01%, ua rau muaj kev nce 0.002% nce ntxiv hauv cov sodium hauv kev tsim. Tsis tas li ntawd, thaum magnesium stearate (Mgroant stearate (mgretting ntawm nws cov ntsiab lus magnesium (thiab cov qauv ntawm cov qauv muaj peev xwm ncav cuag 0.005%.
Hnav thiab corrosion ntawm cov khoom siv khoom siv
Cov khoom xaiv ntawm kev npaj cov cuab yeej ua yog qhov tseem ceeb rau kev tswj hwm inorganic immurities. Piv txwv li, stainless hlau reactors yuav tso cov chromium thiab nickel ions hauv acidic tej yam kev mob (xws li citric acidution). Lub Tuam Txhab Xyuas Lub Tuam Tsev Tshawb Xyuas los ntawm cov tuam txhab tshuaj saib xyuas tau hais tias tom qab muaj 5 xyoos cov ntsiab lus Chromium ntau ntxiv los ntawm 0.001% mus rau 0.003%. Tsis tas li ntawd, lub cib siv nyob rau hauv cov txheej txheem ntub dej (xws li 30 mesh stainless hlau sab cib, thiab cov seem yog kev sib txhuam nrog kev siv lub sijhawm ntawm cov sieve.
Kev Xeem Ntawv Kawg: Txoj kev txwv txuj ci thiab kev pheej hmoo ntawm 'tsis tseeb negatives'
Cov dig muag me ntsis ntawm kev kuaj ib txwm muaj
Nyob rau hauv lub tsev pheebsuab tam sim no, kev kuaj pom ntawm inorganic impurities nyob rau atomicafil feem ntau yog nyob ntawm atomploscopy (icp {{} ms). Txawm li cas los xij, cov txheej txheem no muaj kev rhiab tsawg rau kev kuaj xyuas Nanoscale impurities xws li nickel nanoparticles. Ib qho kev tshawb fawb qhia tau hais tias kev kuaj pom ntawm icp {{ms rau nickel hais nrog ib tug me me<50 nm is 0.1 ppm, while the actual residual amount may be lower than this value. In addition, traditional methods are difficult to distinguish the chemical forms of inorganic impurities (such as free nickel and nickel complexes), leading to bias in risk assessment.
Kev simulating cuam tshuam hauv cov kua txiv plab
Tadalafil npaj yuav tsum tau tso cov khoom xyaw ua kom nquag plias nyob rau hauv lub plab zom mov, tab sis inorganic impurities yuav hloov pauv solubility vim yog pH hloov. Piv txwv, calcium phosphate muaj solubility qis hauv pastric acid (pH 1.2), tab sis nws solubility tseem nce hauv plab hnyuv (pH 6.8). Qee yam hauv kev tso tawm vitro tawm uas muaj cov roj ntsha uas muaj cov roj ntsha tsis zoo, uas yuav hloov cov tshuaj ua kom huv lossis cov khoom sib dhos.
Cim npe nrov: Tadalafil Citrate Hmoov CASRate Case 171596-29-5-5, Chaw tsim khoom, chaw tsim khoom, chaw tsim khoom, lag luam Wholesale, yuav, nqi, loj, rau muag