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【结 构 式】 
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【分子编号】23634 【品名】acetylene 【CA登记号】74-86-2 |
【 分 子 式 】C2H2 【 分 子 量 】26.03788 【元素组成】C 92.26% H 7.74% |
合成路线1
该中间体在本合成路线中的序号：(C)Compound can be prepared in two different ways: 1) By dehydration of 13beta-ethyl-11beta,17beta-dihydroxy-17alpha-ethynyl-gona-4,9-diene-3-one (IV) with 60% formic acid at 100 C or with perchloric acid in methylene chloride containing acetonitrile. 2) The ketalization of 13beta-ethyl-gona-4,9,11-triene-3,17-dione (I) by means of glycol (A) and oxalic acid in dichloroethane affords 3-ethylenedioxy-13beta-ethyl-gona-4,9,11-trien-17-one (II), which is then treated with methylmagnesium bromide (B) and acetylene (C) in THF to yield 3-ethylenedioxy-13beta-ethyl-17beta-hydroxy-17alpha-ethynyl-gona-4,9,11-triene (III). Finally, this compound is hydrolyzed in an acidic medium.
| 【1】 Bertin, D.; Pierdet, A.; 19-Nor-delta(4,9,11)-gonatriene-3-ones. DE 1618810; FR 1503984; GB 1128787; US 3484462 . |
| 【2】 Bertin, D.; Pierdet, A; Process for the preparation of unsaturated 19-nor steroids. DE 1618815; FR 1479352; GB 1128788; US 3478067 . |
| 【3】 Nomine, G.; et al.; New Steroid compounds, compositions incorporating them and processes for their preparation. GB 1069709 . |
| 【4】 Nomine, G.; et al.; Novel 13beta-alkyl-4,9,11-gonatriene-3-ones. DE 1291337; DE 1593307; FR 1426077; FR 1453214; FR 1492782; NL 6607609; US 3248294; US 3257278 . |
| 【5】 Castaner, J.; Thorpe, P.; R-2323. Drugs Fut 1977, 2, 2, 131. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 11295 | Polyethylene glycol;1,2-Ethanediol;Monoethylene glycol; Ethylene glycol | 107-21-1 | C2H6O2 | 详情 | 详情 |
| (B) | 33623 | bromo(methyl)magnesium | 75-16-1 | CH3BrMg | 详情 | 详情 |
| (I) | 33619 | (8S,13R,14S)-13-ethyl-7,8,13,14,15,16-hexahydro-1H-cyclopenta[a]phenanthrene-3,17(2H,6H)-dione | C19H22O2 | 详情 | 详情 | |
| (II) | 33620 | C21H26O3 | 详情 | 详情 | ||
| (III) | 33621 | C23H28O3 | 详情 | 详情 | ||
| (IV) | 33622 | (8S,11S,13S,14S,17R)-13-ethyl-17-ethynyl-11,17-dihydroxy-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one | C21H26O3 | 详情 | 详情 | |
| (C) | 23634 | acetylene | 74-86-2 | C2H2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：RU-16117 is synthesized from D9(11)-estradiol (I). After protecting the hydroxyl groups by the formation of a benzyl ether (II), the double bond is hydrated by hydroboration, followed by oxidation with hydrogen peroxide in alkali. The alcohol thus formed (III) is treated with sodium hydride and then methyliodide (IV). After deprotection of the 3 and 17 hydroxyl groups (V), the C-17 hydroxyl is oxidized to a ketone by chromic oxidation (VI) and the 17-alpha-ethynyl group is introduced directly with potassium acetylide.
| 【1】 Bouton, M.M.; Raynaud, J.P.; Azadian-Boulanger, G.; Bucourt, .; Pierdet, A.; Torelli, V.; Nédélec, L.; Dérivés 11-alpha-méthoxylés de l'estradiol: Activité anti-estrogène du 11-alpha-méthoxy éthynyl estradiol: RU-16117. Eur J Med Chem 1978, 13, 4, 313-319. |
| 【2】 Précigous, G.; Analyse Radiocristallographique de Molécules Oestrogènes et Androgènes et Etude de leur Affinité et de leur Spécificité. Ph. D. Thesis, Univ. Bordeaux I 1978. |
| 【3】 Azadian-Boulanger, G.; Raynaud, J.P.; RU-16117. Drugs Fut 1985, 10, 5, 926. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 | |
| 23634 | acetylene | 74-86-2 | C2H2 | 详情 | 详情 | |
| (I) | 29791 | (8S,13S,14S)-13-methyl-7,8,12,13,14,15,16,17-octahydro-6H-cyclopenta[a]phenanthrene-3,17-diol | C18H22O2 | 详情 | 详情 | |
| (II) | 29792 | (8S,13S,14S)-3,17-bis(benzyloxy)-13-methyl-7,8,12,13,14,15,16,17-octahydro-6H-cyclopenta[a]phenanthrene; benzyl (8S,13S,14S)-17-(benzyloxy)-13-methyl-7,8,12,13,14,15,16,17-octahydro-6H-cyclopenta[a]phenanthren-3-yl ether | C32H34O2 | 详情 | 详情 | |
| (III) | 29793 | (8S,9S,11R,13S,14S)-3,17-bis(benzyloxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-11-ol | C32H36O3 | 详情 | 详情 | |
| (IV) | 29794 | (8S,9S,11R,13S,14S)-3,17-bis(benzyloxy)-11-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene; benzyl (8S,9S,11R,13S,14S)-17-(benzyloxy)-11-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl ether | C33H38O3 | 详情 | 详情 | |
| (V) | 29795 | (8S,9S,11R,13S,14S)-11-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3,17-diol | C19H26O3 | 详情 | 详情 | |
| (VI) | 29796 | (8S,9S,11R,13S,14S)-3-hydroxy-11-methoxy-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one | C19H24O3 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：This compound can be obtained by several related ways: 1) The reaction of 2-thioxo-1,3-dithiole-4,5-dicarboxylic acid (I) with methyl iodide in refluxing nitromethane gives 2-(methylsulfanyl)-1,3-dithiolium iodide (II), which is finally condensed with diisopropyl malonate (III), by means of NaH in refluxing THF. 2) The cyclization of sodium acetylide (IV) with sulfur and carbon disulfide gives 1,3-dithiole-2-thione (V), which is treated first with dimethyl sulfate and then with sodium perchlorate yielding 2-(methylsulfanyl)-1,3-dithiolium perchlorate (V). Finally, this compound is condensed with diisopropyl malonate (III) by means of NaH as before. 3) 1,3-Dithiole-2-thione (V) can also be obtained by cyclization of ethylene carbonate (VII) with carbon disulfide by means of K2CO3 and hexabutyldistannathiane. 4) 1,3-Dithiole-2-thione (V) can also be obtained by cyclization of ethylene trithiocarbonate (VIII) with acetylene at 110-45 C, although with low yields. 5) The selective hydrolysis of 2-(4-acetoxy-1,3-dithiol-2-ylidene)malonic acid diisopropyl ester (IX) gives the corresponding 4-hydroxy derivative (X), which is finally dehydrated with either, chlorosulfonic acid or sulfuric acid or thionyl chloride and DBU or phosphorous trichloride or phosphorous oxychloride.
| 【1】 Fujinami, T.; et al.; The preparation of cyclic dithia and thiaza compounds by the reaction of potassium carbonate with heterocumulenes and alkylene dibromides or carbonate catalyzed by organostannyl compounds. Bull Chem Soc Jpn 1982, 55, 4, 1174. |
| 【2】 Mayer, R.; et al.; Synthesis of 1,3-dithiol-2-thiones (' Isotrithione'). Angew Chem. Int Ed Engl 1964, 76, 3, 143. |
| 【3】 Jones, F.N.; O'Connor, B.R.; Reactions of ethylene di- and trithiocarbonates with acetylenes. Anomalous reaction with bromocyanoacetylene to give a thioacyl bromide. J Org Chem 1970, 35, 6, 2002. |
| 【4】 Kurono, H.; Hirano, A.; Taninaka, K. (Nihon Nohyaku Co., Ltd.); 1,3-Dithiol-2-ylidene malonic esters. DE 2545569; US 4035387 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 23634 | acetylene | 74-86-2 | C2H2 | 详情 | 详情 | |
| (I) | 34902 | 2-thioxo-1,3-dithiole-4,5-dicarboxylic acid | C5H2O4S3 | 详情 | 详情 | |
| (II) | 34903 | 1,3-dithiol-2-ylidene(methyl)sulfonium iodide | C4H5IS3 | 详情 | 详情 | |
| (III) | 30735 | diisopropyl malonate | 13195-64-7 | C9H16O4 | 详情 | 详情 |
| (IV) | 34904 | ethynylsodium | 1066-26-8 | C2HNa | 详情 | 详情 |
| (V) | 34905 | 1,3-dithiole-2-thione | 930-35-8 | C3H2S3 | 详情 | 详情 |
| (VI) | 34906 | 1,3-dithiol-2-ylidene(methyl)sulfonium perchlorate | C4H5ClO4S3 | 详情 | 详情 | |
| (VII) | 32802 | 1,3-dioxolan-2-one | 96-49-1 | C3H4O3 | 详情 | 详情 |
| (VIII) | 34907 | 1,3-dithiolane-2-thione | 822-38-8 | C3H4S3 | 详情 | 详情 |
| (IX) | 34908 | diisopropyl 2-[4-(acetoxy)-1,3-dithiolan-2-ylidene]malonate | C14H20O6S2 | 详情 | 详情 | |
| (X) | 34909 | diisopropyl 2-(4-hydroxy-1,3-dithiolan-2-ylidene)malonate | C12H18O5S2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：By condensation of 7-methyl-3,17,19-trioxo-DELTA4-androstene (I) with acetylene by means of potassium in liquid ammonia.
| 【1】 Solomon, M.; Harryvan, E.A.; Process for the preparation of delta[5,(10)]-3-keto-19-nor-steroids. BE 0700390; DE 1618747; FR 1527563; GB 1177845; US 3475465 . |
| 【2】 Castaner, J.; Serradell, M.N.; Blancafort, P.; Hillier, K.; Tibolone. Drugs Fut 1981, 6, 5, 302. |
合成路线5
该中间体在本合成路线中的序号：Compound can be prepared in several related ways: 1) The condensation of N-(1-phenylisopropyl)methylamine (I) with 1,2-dibromopropene (A) by heating at 100 C gives N-(1-phenylisopropyl)-N-methyl-2-bromopropenylamine (II), which is then dehydrobrominated and isomerized by treating with KOH in refluxing ethanol water. 2) By heating a mixture of (I) and propargyl bromide (B) at 100 C. 3) By reductocondensation of (I) with propargyl aldehyde (C) by means of amalgamated Al in ethanol. 4) By condensation of (I) with formaldehyde and acetylene by means of CuCl in hot dioxane. 5) By condensation of 1-phenylisopropyl chloride (III) with N-methylpropargylamine (IV) by heating at 80 C in a sealed tube.
| 【1】 Ecsery, Z.; et al.; AT 252901 . |
| 【2】 Ecsery, Z.; et al.; AT 251560 . |
| 【3】 Ecsery, Z.; et al.; Verfahren zur Herstellung von Phenylisopropylaminen. DE 1568277; NL 6605956 . |
| 【4】 Ecsery, Z.; et al.; Verfahren zur Herstellung von Phenylisopropylaminen. CH 530953; DE 1227447 . |
| 【5】 Roberts, P.J.; Castaner, J.; Selegiline. Drugs Fut 1979, 4, 2, 128. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 23634 | acetylene | 74-86-2 | C2H2 | 详情 | 详情 | |
| (B) | 11176 | 3-Bromopropyne; 3-Bromo-1-propyne | 106-96-7 | C3H3Br | 详情 | 详情 |
| (A) | 33322 | (E)-1,2-dibromo-1-propene | 26391-16-2 | C3H4Br2 | 详情 | 详情 |
| (I) | 33321 | N-methyl-N-[(1R)-1-methyl-2-phenylethyl]amine; (2R)-N-methyl-1-phenyl-2-propanamine | 537-46-2 | C10H15N | 详情 | 详情 |
| (II) | 33323 | N-[(E)-3-bromo-2-butenyl]-N-methyl-N-[(1R)-1-methyl-2-phenylethyl]amine; (E)-3-bromo-N-methyl-N-[(1R)-1-methyl-2-phenylethyl]-2-buten-1-amine | C14H20BrN | 详情 | 详情 | |
| (III) | 33324 | 1-[(2R)-2-chloropropyl]benzene | C9H11Cl | 详情 | 详情 | |
| (IV) | 33325 | N-methyl-2-propyn-1-amine; N-methyl-N-(2-propynyl)amine | C4H7N | 详情 | 详情 | |
| (C) | 23544 | propiolaldehyde | C3H2O | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：Reaction of 9a-hydroxyandrost-4-ene-3,17-dione (I) with benzenesulfinyl chloride and pyridine gives the corresponding sulfinate (II), which by treatment with TsOH in refluxing chloroform yields androsta-4,9(11)-diene-3,17-dione (III). Reaction of the androstadienedione (III) with acetylene by means of potassium tert-butoxide in THF affords the 17a-ethynyl derivative (IV), which is treated with phenylsulfenyl chloride and TEA at 70 C to provide the sulfenate ester (V). Rearrange-ment of sulfenate (V) by warming at 40 C gives the allene sulfoxide (VI), which is treated with sodium methoxide in methanol at 25 C to yield the enol ether sulfoxide (VII). Then, by refluxing in methanol, an equilibrium between sulfoxide (VII) and sulfenate (VIII) occurs. Reaction of the non-isolated sulfenate (VIII) with the thiophile trimethyl phosphite affords the 17a-hydroxy enol ether (IX), which is finally converted to anecortave acetate by either treatment with peracetic acid and NaHCO3 in dichloromethane or bromination with Br2 and pyridine in dichloromethane to give compound (X) followed by treatment with KOAc, KI and AcOH in refluxing acetone.
| 【1】 Van Rheenen, V.; Shephard, K.P.; New synthesis of cortico steroids from 17-keto steroids: Application and stereochemical study of the unsaturated sulfoxide-sulfenate rearrangement. J Org Chem 1979, 44, 9, 1582. |
| 【2】 Castaner, J.; Sorbera, L.A.; Leeson, P.A.; Bayes, M.; Anecortave Acetate. Drugs Fut 2002, 27, 11, 1039. |
| 【3】 Shephard, K.P.; Van Rheenen, V.H. (Pharmacia Corp.); Process for the preparation of 17alpha-hydroxyprogesterones and corticoids from androstenes. US 4041055 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 23634 | acetylene | 74-86-2 | C2H2 | 详情 | 详情 | |
| (I) | 28065 | (8S,9R,10S,13S,14S)-9-hydroxy-10,13-dimethyl-7,8,9,10,11,12,13,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17(2H,6H)-dione | C19H26O3 | 详情 | 详情 | |
| (II) | 56594 | (8S,10S,13S,14S)-10,13-dimethyl-3,17-dioxo-1,2,3,6,7,8,10,11,12,13,14,15,16,17-tetradecahydro-9H-cyclopenta[a]phenanthren-9-yl benzenesulfinate | C25H30O4S | 详情 | 详情 | |
| (III) | 56595 | (8S,10R,13S,14S)-10,13-dimethyl-7,8,10,12,13,14,15,16-octahydro-1H-cyclopenta[a]phenanthrene-3,17(2H,6H)-dione | C19H24O2 | 详情 | 详情 | |
| (IV) | 56596 | (8S,10R,13S,14S,17R)-17-ethynyl-17-hydroxy-10,13-dimethyl-1,2,6,7,8,10,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one | C21H26O2 | 详情 | 详情 | |
| (V) | 56597 | (8S,10R,13S,14S,17R)-17-ethynyl-10,13-dimethyl-3-oxo-2,3,6,7,8,10,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl benzenesulfenate | C27H30O2S | 详情 | 详情 | |
| (VI) | 56598 | (8S,10R,13S,14S)-10,13-dimethyl-17-[2-(phenylsulfinyl)ethenylidene]-1,2,6,7,8,10,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one | C27H30O2S | 详情 | 详情 | |
| (VII) | 56599 | (8S,10R,13S,14S)-17-[(E)-1-methoxy-2-(phenylsulfinyl)ethylidene]-10,13-dimethyl-1,2,6,7,8,10,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one | C28H34O3S | 详情 | 详情 | |
| (VIII) | 56600 | (8S,10R,13S,14S,17R)-17-(1-methoxyvinyl)-10,13-dimethyl-3-oxo-2,3,6,7,8,10,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl benzenesulfenate | C28H34O3S | 详情 | 详情 | |
| (IX) | 56601 | (8S,10R,13S,14S,17R)-17-hydroxy-17-(1-methoxyvinyl)-10,13-dimethyl-1,2,6,7,8,10,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one | C22H30O3 | 详情 | 详情 | |
| (X) | 56602 | (8S,10R,13S,14S,17R)-17-(2-bromoacetyl)-17-hydroxy-10,13-dimethyl-1,2,6,7,8,10,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one | C21H27BrO3 | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(A)2) Intermediate (IX) can also be obtained as follows: The cyclization of 4-cyanobenzoic acid methyl ester (XII) with acetylene at 15 Atm by means of cobaltocene in toluene at 180 C gives 4-(2-pyridyl)benzoic acid methyl ester (XIII), which is saponified with NaOH in methanol to the corresponding acid (XIV). The activation of (XIV) with isobutyl chloroformate yields the mixed anhydride (XV), which is condensed with N-(tert-butoxycarbonyl)-L-phenylalaninal (XVI) and KCN in dichloromethane, affording (XVII). The reaction of (XVII) with tert-butyl carbazate (V) by means of acetic acid in methanol gives hydrazone (XVIII), which is reduced to hydrazine (XIX) by means of sodium cyanoborohydride in THF. The isomerization of (XIX) by means of 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTDE) in hot diglyme yields hydrazide (XX), which is finally reduced to intermediate (IX) with diisobutylaluminum hydride in dichloromethane/THF.
| 【1】 Fassler, A.; Steiner, H.; Bold, G.; Capraro, H.-G. (Novartis AG); Process for the preparation of hydrazine derivs. useful as intermediates for the preparation of peptide analogues. WO 9746514 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 23634 | acetylene | 74-86-2 | C2H2 | 详情 | 详情 |
| (V) | 10893 | tert-butyl 1-hydrazinecarboxylate; tert-butyl carbazate | 870-46-2 | C5H12N2O2 | 详情 | 详情 |
| (IX) | 23445 | tert-butyl 2-[(2S,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl]-2-[4-(2-pyridinyl)benzyl]-1-hydrazinecarboxylate | C32H42N4O5 | 详情 | 详情 | |
| (XII) | 10169 | methyl 4-cyanobenzoate；4-Cyanobenzoic acid methyl ester | 1129-35-7 | C9H7NO2 | 详情 | 详情 |
| (XIII) | 23449 | methyl 4-(2-pyridinyl)benzoate | C13H11NO2 | 详情 | 详情 | |
| (XIV) | 23450 | 4-(2-pyridinyl)benzoic acid | C12H9NO2 | 详情 | 详情 | |
| (XV) | 23451 | 4-(2-Pyridyl)benzoic acid isobutoxycarbonyl anhydride | C17H17NO4 | 详情 | 详情 | |
| (XVI) | 14540 | tert-butyl N-[(1S)-1-benzyl-2-oxoethyl]carbamate | C14H19NO3 | 详情 | 详情 | |
| (XVII) | 23453 | (1R,2S)-2-[(tert-butoxycarbonyl)amino]-1-cyano-3-phenylpropyl 4-(2-pyridinyl)benzoate | C27H27N3O4 | 详情 | 详情 | |
| (XVIII) | 23454 | tert-butyl 2-((E,2R,3S)-3-[(tert-butoxycarbonyl)amino]-4-phenyl-2-[[4-(2-pyridinyl)benzoyl]oxy]butylidene)-1-hydrazinecarboxylate | C32H38N4O6 | 详情 | 详情 | |
| (XIX) | 23455 | tert-butyl 2-((2S,3S)-3-[(tert-butoxycarbonyl)amino]-4-phenyl-2-[[4-(2-pyridinyl)benzoyl]oxy]butyl)-1-hydrazinecarboxylate | C32H40N4O6 | 详情 | 详情 | |
| (XX) | 23457 | tert-butyl 2-[(2S,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl]-2-[4-(2-pyridinyl)benzoyl]-1-hydrazinecarboxylate | C32H40N4O6 | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(XIV)4-Bromo-3-fluorotoluene (I) is converted into the Grignard reagent (II) with magnesium in boiling Et2O, and subsequently added to cyclopropylacetonitrile (III) to produce ketone (IV). Condensation of (IV) with hydroxylamine affords oxime (V), which is further alkylated with benzyl bromide to yield the O-benzyl oxime (VI). Asymmetric reduction of oxime (VI) with borane in the presence of the aminoalcohol chiral auxiliary (VII) provides the (S)-amine (VIII). Reaction of amine (VIII) with ammonium thiocyanate and benzoyl chloride, followed by treatment with hydrazine hydrate, gives rise to the thiourea (IX). Friedel-Crafts acylation of 4-chloro-2-methoxytoluene (X) with 2-bromopropionyl bromide (XI) employing AlCl3 furnishes the bromo ketone (XII). Then, condensation of thiourea (IX) with bromo ketone (XII) in the presence of Et3N in boiling EtOH gives rise to the aminothiazole (XIII). Finally, alkylation of the amino group of (XIII) with propargyl bromide (XIV) and NaH furnishes the title compound
| 【1】 Roger, P.; Gully, D.; Pradines, A.; Fontaine, E.; Geslin, M. (Sanofi-Synthelabo); Aminothiazole derivs. and their use as CRF receptor ligands. EP 1200419; FR 2796380; JP 2003505380; WO 0105776 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 60397 | 4-bromo-2-fluoro-1-methylbenzene | C7H6BrF | 详情 | 详情 | |
| (II) | 60398 | bromo(3-fluoro-4-methylphenyl)magnesium | C7H6BrFMg | 详情 | 详情 | |
| (III) | 16824 | 2-cyclopropylacetonitrile; Cyclopropylacetonitrile | 6542-60-5 | C5H7N | 详情 | 详情 |
| (IV) | 60399 | 2-cyclopropyl-1-(3-fluoro-4-methylphenyl)-1-ethanone | C12H13FO | 详情 | 详情 | |
| (V) | 60400 | 2-cyclopropyl-1-(3-fluoro-4-methylphenyl)-1-ethanone oxime | C12H14FNO | 详情 | 详情 | |
| (VI) | 60401 | 2-cyclopropyl-1-(3-fluoro-4-methylphenyl)-1-ethanone O-benzyloxime | C19H20FNO | 详情 | 详情 | |
| (VII) | 10103 | (2R)-2-Amino-3-methyl-1,1-diphenyl-1-butanol | 56755-20-5 (hydrochloride) | C17H21NO | 详情 | 详情 |
| (VIII) | 60402 | (1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)-1-ethanamine; (1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethylamine | C12H16FN | 详情 | 详情 | |
| (IX) | 60403 | N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]thiourea | C13H17FN2S | 详情 | 详情 | |
| (X) | 60405 | 5-chloro-2-methylphenyl methyl ether; 4-chloro-2-methoxy-1-methylbenzene | C8H9ClO | 详情 | 详情 | |
| (XI) | 13127 | 2-Bromopropionyl bromide; 2-Bromopropanoyl bromide | 563-76-8 | C3H4Br2O | 详情 | 详情 |
| (XII) | 60404 | 2-bromo-1-(2-chloro-4-methoxy-5-methylphenyl)-1-propanone | C11H12BrClO2 | 详情 | 详情 | |
| (XIII) | 60406 | 4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-1,3-thiazol-2-amine; N-[4-(2-chloro-4-methoxy-5-methylphenyl)-5-methyl-1,3-thiazol-2-yl]-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]amine | C24H26ClFN2OS | 详情 | 详情 | |
| (XIV) | 23634 | acetylene | 74-86-2 | C2H2 | 详情 | 详情 |
合成路线9
该中间体在本合成路线中的序号：(III)The known oxazolidine methansulfonate (I) is reacted with NaN3 in hot DMF to produce azide (II). Then, condensation of azide (II) with acetylene (III) at 90 C in a pressure vessel gives rise to the target triazole derivative.
| 【1】 Phillips, O.A.; Udo, E.E.; Ali, A.A.M.; Al-Hassawi, N.; Synthesis and antibacterial activity of 5-substituted oxazolidinones. Bioorg Med Chem 2003, 11, 1, 35. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 17019 | [(5R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-1,3-oxazolan-5-yl]methyl methanesulfonate | 174649-09-3 | C15H19FN2O6S | 详情 | 详情 |
| (II) | 17020 | (5R)-5-(azidomethyl)-3-(3-fluoro-4-morpholinophenyl)-1,3-oxazolan-2-one | C14H16FN5O3 | 详情 | 详情 | |
| (III) | 23634 | acetylene | 74-86-2 | C2H2 | 详情 | 详情 |