|
【结 构 式】 
|
【分子编号】10928 【品名】Ethanamine 【CA登记号】75-04-7 |
【 分 子 式 】C2H7N 【 分 子 量 】45.08432 【元素组成】C 53.28% H 15.65% N 31.07% |
合成路线1
该中间体在本合成路线中的序号：(A)The oxidation of 2',3'-isopropylideneadenosine (I) with potassium permanganate gives 2',3'-isopropylideneadenosine-5'-carboxylic acid (II) which with SOCl2 affords 2',3'-isopropylideneadenosine-5'-carbonyl chloride (III), which is treated first with dry liquid ethylamine and then hydrolyzed with aqueous hydrochloric acid.
| 【1】 Stein, H.H.; Prasad, R.N.; US 4029884 . |
| 【2】 Stein, H.H.; Prasad, R.N.; US 3830796 . |
| 【3】 Stein, H.H.; Prasad, R.N.; US 3914414 . |
| 【4】 Stein, H.H.; Prasad, R.N.; US 3914415 . |
| 【5】 Stein, H.H.; Prasad, R.N; US 3931401 . |
| 【6】 Serradell, M.N.; Blancafort, P.; Castaner, J.; Hopkins, S.J.; NECA. Drugs Fut 1981, 6, 10, 627. |
| 【7】 Stein, H.H.; Prasad, R.N.; US 3966917 . |
| 【8】 Tietje, K.; Prasad, R.N.; N1,N6-Etheno-adenosine 5'-(N-ethylcarboxamide). Nucleic Acid Chemistry 1978, 2, 701-707. |
| 【9】 Harman, R.E.; et al.; Permanganate oxidation of purine nucleosides. Chem Ind 1969, 1141. |
| 【10】 Savic, M.; Brondyk, H.; Egan, R.S.; Bariana, D.S.; Fung, A.; Tietje, K.; Prasad, R.N.; Stein, H.H.; Modifications of the 5' position of purine nucleosides. 2. Synthesis and some cardiovascular properties of adenosine-5'-(N-substituted)carboxamides. J Med Chem 1980, 23, 3, 313-319. |
| 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) | 10928 | Ethanamine | 75-04-7 | C2H7N | 详情 | 详情 |
| (I) | 17560 | [(3aR,4R,6R,6aS)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methanol | 362-75-4 | C13H17N5O4 | 详情 | 详情 |
| (II) | 39020 | (3aR,4S,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carboxylic acid | C13H15N5O5 | 详情 | 详情 | |
| (III) | 39021 | (3aR,4S,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carbonyl chloride | C13H14ClN5O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)2-Methoxy-5-(N-methylmethanesulfonamido)-N-tetrahydrofurfurylbenzamide (II), which is prepared from (I) and tetrahydrofurfurylamine, is treated with SOCl2 in dichloroethane to give the dichloro compound (III). Treatment of (III) with EtNH2 gives title compound.
| 【1】 Masaru, O.; Hiroshi, M. (Shionogi & Co. Ltd.); Meta-sulfonamido-benzamides. DE 2803651; ES 466366; FR 2378758; GB 1557019; US 4328155; US 4328344; US 4330472; US 4350635; US 4351770; US 44313663 . |
| 【2】 Ogata, M.; 710723-S. Drugs Fut 1985, 10, 9, 758. |
| 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) | 27331 | 2-methoxy-5-[methyl(methylsulfonyl)amino]benzoic acid | C10H13NO5S | 详情 | 详情 | |
| (II) | 27333 | 2-methoxy-5-[methyl(methylsulfonyl)amino]-N-(tetrahydro-3-furanylmethyl)benzamide | C15H22N2O5S | 详情 | 详情 | |
| (III) | 27334 | N-(2,5-dichloropentyl)-2-methoxy-5-[methyl(methylsulfonyl)amino]benzamide | C15H22Cl2N2O4S | 详情 | 详情 | |
| (IV) | 27335 | Tetrahydro-2-furanylmethanamine; Tetrahydrofurfurylamine | 4795-29-3 | C5H11NO | 详情 | 详情 |
| (V) | 10928 | Ethanamine | 75-04-7 | C2H7N | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(E)The methylation of 2,3,5-trimethylphenol (I) with MeI and KOH in 10% aqueous ethanol gives 2,3,5-trimethylanisole (II), which is formylated with DMF and POCl3 yielding 2,3,6-trimethyl-p-anisylaldehyde (III). The condensation of (III) with acetone (B) by means of NaOH affords 4-(4-methoxy-2,3,6-trimethylphenyl)but-3-en-2-one (IV), which by a Grignard reaction with ethynylmagnesium bromide (C) in THF is converted into the acetylenic alcohol (V). Partial hydrogenation of (V) with H2 over Pd/C in hexane gives dienic alcohol (VI), which is condensed with triphenylphosphine hydrobromide in benzene affording 5-(4-methoxy-2,3,6 trimethylphenyl)-3-methylpenta-2,4-diene-1-triphenylphosphonium bromide (VII). A Wittig condensation of (VII) with butyl 3-formylcrotonate (VIII) by means of NaH in DMF gives butyl 9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoate (IX), which is hydrolyzed with KOH in refluxing ethanol-water yielding the corresponding free acid (X). This acid is converted into the acyl chloride (XI) by treatment with PCl3 in refluxing benzene. Finally, this compound is treated with ethylamine (E) in ether. The butyl 3-formylcrotonate (VIII) is obtained as follows: The oxidation of dibutyl tartrate (XII) with lead tetraacetate in benzene gives butyl glyoxalate (XIII), which is then condensed with propionaldehyde (XIV) by heating at 110 C with dibutyl-amine (D).
| 【1】 Bollag, W.; et al.; Polyene derivatives. BE 0813002; FR 2223037; GB 1468401; GB 1468402 . |
| 【2】 Bollag, W.; et al.; Antidandruff compositions containing 9-(4-lower alkoxy-2,3,6-trilower-alkylphenyl)-3,7-dimethyl-nona-2,4,6,8-tetraen-1-oic acid lower alkyl amides. DE 2542366; ES 441173; FR 2330381; GB 1504350; JP 51057840; US 4021574 . |
| 【3】 Castaner, J.; Hillier, K.; Motretinide. Drugs Fut 1978, 3, 2, 126. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (E) | 10928 | Ethanamine | 75-04-7 | C2H7N | 详情 | 详情 |
| (B) | 23199 | 2-Propanone; Acetone; beta-ketopropane; chevron acetone;propan-2-one； Dimethyl formaldehyde; Dimethyl ketone; dimethylketal; Ketone propane; Methyl ketone; Propanone; Pyroacetic acid; Pyroacetic ether | 67-64-1 | C3H6O | 详情 | 详情 |
| (A) | 33491 | Dimethylformamide | 68-12-2 | C3H7NO | 详情 | 详情 |
| (D) | 33492 | N,N-dibutylamine; N-butyl-1-butanamine | 111-92-2 | C8H19N | 详情 | 详情 |
| (I) | 33479 | 2,3,5-trimethylphenol | 697-82-5 | C9H12O | 详情 | 详情 |
| (II) | 33480 | 1-methoxy-2,3,5-trimethylbenzene; methyl 2,3,5-trimethylphenyl ether | 20469-61-8 | C10H14O | 详情 | 详情 |
| (III) | 33481 | 4-methoxy-2,3,6-trimethylbenzaldehyde | C11H14O2 | 详情 | 详情 | |
| (IV) | 33482 | (E)-4-(4-methoxy-2,3,6-trimethylphenyl)-3-buten-2-one | 54757-47-0 | C14H18O2 | 详情 | 详情 |
| (V) | 33483 | (E)-1-(4-methoxy-2,3,6-trimethylphenyl)-3-methyl-1-penten-4-yn-3-ol | C16H20O2 | 详情 | 详情 | |
| (VI) | 33484 | (1E)-1-(4-methoxy-2,3,6-trimethylphenyl)-3-methyl-1,4-pentadien-3-ol | C16H22O2 | 详情 | 详情 | |
| (VII) | 33485 | [(2E,4E)-5-(4-methoxy-2,3,6-trimethylphenyl)-3-methyl-2,4-pentadienyl](triphenyl)phosphonium bromide | C34H36BrOP | 详情 | 详情 | |
| (VIII) | 33486 | butyl (E)-3-methyl-4-oxo-2-butenoate | C9H14O3 | 详情 | 详情 | |
| (IX) | 33487 | butyl (2E,4E,6E,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoate | C25H34O3 | 详情 | 详情 | |
| (X) | 33488 | (2E,4E,6E,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid | C21H26O3 | 详情 | 详情 | |
| (XI) | 33489 | (2E,4E,6E,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoyl chloride | C21H25ClO2 | 详情 | 详情 | |
| (XII) | 33490 | Dibutyl tartrate | 87-92-3 | C12H22O6 | 详情 | 详情 |
| (XIII) | 30937 | butyl 2-oxoacetate | C6H10O3 | 详情 | 详情 | |
| (XIV) | 15966 | propionaldehyde | 123-38-6 | C3H6O | 详情 | 详情 |
| (C) | 17778 | ETHYNYLMAGNESIUM BROMIDE; bromo(ethynyl)magnesium | 4301-14-8 | C2HBrMg | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(XIII)2) Hexadeuteroethyl alcohol (IX) is treated with red phosphorus and I2 at reflux temperature to give pentadeuteroethyl iodide (X), which is condensed with potassium phthalimide (XI) in DMF, yielding N-(pentadeuteroethyl)phthalimide (XII). The hydrolysis of (XII) with hydrazine and HCl affords pentadeuteroethylamine (XIII), which is condensed with 1-methylpiperidin-4-one (III) and formaldehyde (XIV) in a Mannich reaction to give 3-methyl-7-(pentadeuteroethyl)-3,7-diazabicyclo[3.3.1]nonan-9-one (XV). The reduction of (XV) with NaBH4 as before yields the diastereomeric mixture (XVI + XVII). Finally, the alpha-isomer (XVI) is condensed with 4-chlorobenzoyl chloride (VIII) as before to give the pentadeuterium-labeled bisaramil.
| 【1】 Mlinko, S.; Simon Trompler, E.; Szammer, J.; Synthesis of bisaramil labelled with carbon-14 and deuterium. J Label Compd Radiopharm 1994, 34, 4, 313. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 10919 | 1-Methyl-4-piperidone; 1-Methyltetrahydro-4(1H)-pyridinone; N-Methyl-4-piperidone;1-methylpiperidin-4-one | 1445-73-4 | C6H11NO | 详情 | 详情 |
| (VIII) | 10295 | p-Chlorobenzoyl chloride; 4-Chlorobenzoyl chloride | 122-01-0 | C7H4Cl2O | 详情 | 详情 |
| (IX) | 10924 | Ethyl alcohol; Ethanol | 1516-08-1 | C2H6O | 详情 | 详情 |
| (IX) | 44687 | Ethanol-d6 | C2H6O | 详情 | 详情 | |
| (X) | 10925 | Iodoethane;ethyl iod | 75-03-6 | C2H5I | 详情 | 详情 |
| (X) | 44688 | 1-iodoethane-d5 | C2H5I | 详情 | 详情 | |
| (XI) | 10926 | (1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)potassium | C8H4KNO2 | 详情 | 详情 | |
| (XII) | 10927 | 2-Ethyl-1H-isoindole-1,3(2H)-dione | 5022-29-7 | C10H9NO2 | 详情 | 详情 |
| (XII) | 44689 | 2-ethyl-1H-isoindole-1,3(2H)-dione | C10H9NO2 | 详情 | 详情 | |
| (XIII) | 10928 | Ethanamine | 75-04-7 | C2H7N | 详情 | 详情 |
| (XIII) | 44690 | ethylamine; 1-ethanamine | C2H7N | 详情 | 详情 | |
| (XV) | 10929 | 3-Ethyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-one | C10H18N2O | 详情 | 详情 | |
| (XV) | 44691 | 3-ethyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-one | C10H18N2O | 详情 | 详情 | |
| (XVI) | 10921 | 3-Ethyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-ol | C10H20N2O | 详情 | 详情 | |
| (XVI) | 44692 | 3-ethyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-ol | C10H20N2O | 详情 | 详情 | |
| (XVII) | 10922 | 3-Ethyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-ol | C10H20N2O | 详情 | 详情 | |
| (XVII) | 44693 | 3-ethyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-ol | C10H20N2O | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(II)Alkylation of ethylamine (II) with 3-chloro-1-propanol (I) in a pressure vessel furnished 3-(ethylamino)-1-propanol (III). After protection of the secondary amine group of (III) upon treatment with benzyl chloroformate, the resultant N-(3-hydroxypropyl)carbamate (IV) was activated as the mesylate ester (V) with methanesulfonyl chloride and triethylamine.
| 【1】 Mignonac, S.; Guy, A.; De Lamer, V. (Sanofi-Synthelabo); Preparation of polyamine(s), substd. on terminal nitrogen atoms. FR 2714052 . |
| 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) | 19490 | 3-chloro-1-propanol | 627-30-5 | C3H7ClO | 详情 | 详情 |
| (II) | 10928 | Ethanamine | 75-04-7 | C2H7N | 详情 | 详情 |
| (III) | 59216 | 3-(ethylamino)-1-propanol | C5H13NO | 详情 | 详情 | |
| (IV) | 59217 | benzyl ethyl(3-hydroxypropyl)carbamate | C13H19NO3 | 详情 | 详情 | |
| (V) | 59218 | 3-[[(benzyloxy)carbonyl](ethyl)amino]propyl methanesulfonate | C14H21NO5S | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(III)Activation of butyric acid derivative (I) with isobutyl chloroformate (II) by means of Et3N in THF, followed by coupling with ethylamine (III) in THF in the presence of Et3N, yields butyramide derivative (IV). Reduction of (IV) by means of (-)-B-chlorodiisopinocampheylborane (Ipc2BCl) in THF, followed by reaction with diethanolamine (A), affords hydroxy derivative (V), whose carbonyl group is removed by means of sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al) in toluene/THF, followed by treatment with H2SO4 to provide compound (VI) . Separately, the synthesis of intermediate (XIV) is performed as follows: condensation of pentamethylene chlorohydrin (VII) with 3,4-dihydro-2H-pyran (VIII) by means of p-toluenesulfonic acid in Et2O furnishes 5-chloropentyl-2-tetrahydropyranyl ether (IX), which is then subjected to reaction with acetone (X) in THF by means of Mg in the presence of 1,2-dibromoethane (B) to provide tetrahydropyranyl ether (XI). Conversion of hydroxy derivative (XI) into the corresponding fluoro derivative (XII) is performed by reaction with diethylaminosulfur trifluoride (DAST) in CH2Cl2, and posterior reaction of (XII) with pyridinium p-toluenesulfonate in EtOH furnishes 6-fluoro-6-methyl-1-heptanol (XIII). Finally, intermediate (XIV) is obtained by reaction of (XIII) with NBS and PPh3 in benzene. Condensation of secondary amine (VI) with intermediate (XIV) by means of NaHCO3 in refluxing acetonitrile provides methanesulfonamide (XV), which is finally converted into the target product by formation of the hemifumarate salt by treatment with fumaric acid (XVI) in acetone.
| 【1】 Hester, J.B.; Progress toward the development of a safe and effective agent for treating reentrant cardiac arrhythmias: Synthesis and evaluation of ibutilide analogues with enhanced metabolic stability and diminished proarrhythmic potential. J Med Chem 2001, 44, 7, 1099. |
| 【2】 Hester, J.B. Jr.; Gibson, J.K. (Pharmacia Corp.); Antiarrhythmic (S)-enantiomers of methanesulfonamides. EP 0802900; JP 1999500418; WO 9621643 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (B) | 10252 | 1,2-Dibromoethane; Ethylene dibromide | 106-93-4 | C2H4Br2 | 详情 | 详情 |
| (A) | 24273 | 2-[(2-hydroxyethyl)amino]-1-ethanol | 111-42-2 | C4H11NO2 | 详情 | 详情 |
| (I) | 14625 | 4-[4-[(methylsulfonyl)amino]phenyl]-4-oxobutyric acid | C11H13NO5S | 详情 | 详情 | |
| (II) | 14932 | isobutyryl chloride; 2-methylpropanoyl chloride | 79-30-1 | C4H7ClO | 详情 | 详情 |
| (III) | 10928 | Ethanamine | 75-04-7 | C2H7N | 详情 | 详情 |
| (IV) | 48114 | N-ethyl-4-[4-[(methylsulfonyl)amino]phenyl]-4-oxobutanamide | C13H18N2O4S | 详情 | 详情 | |
| (V) | 48115 | (4S)-N-ethyl-4-hydroxy-4-[4-[(methylsulfonyl)amino]phenyl]butanamide | C13H20N2O4S | 详情 | 详情 | |
| (VI) | 48116 | N-[4-[(1S)-4-(ethylamino)-1-hydroxybutyl]phenyl]methanesulfonamide | C13H22N2O3S | 详情 | 详情 | |
| (VII) | 48117 | 5-chloro-1-pentanol | C5H11ClO | 详情 | 详情 | |
| (VIII) | 13684 | 3,4-Dihydro-2H-pyran;2,3-Dihydro-4H-pyran; 5,6-Dihydro-4H-pyran;Dihydropyran | 110-87-2 | C5H8O | 详情 | 详情 |
| (IX) | 48118 | 2-[(5-chloropentyl)oxy]tetrahydro-2H-pyran; 5-chloropentyl tetrahydro-2H-pyran-2-yl ether | C10H19ClO2 | 详情 | 详情 | |
| (X) | 23199 | 2-Propanone; Acetone; beta-ketopropane; chevron acetone;propan-2-one； Dimethyl formaldehyde; Dimethyl ketone; dimethylketal; Ketone propane; Methyl ketone; Propanone; Pyroacetic acid; Pyroacetic ether | 67-64-1 | C3H6O | 详情 | 详情 |
| (XI) | 48119 | 2-methyl-6-(tetrahydro-2H-pyran-2-yloxy)-2-hexanol | C12H24O3 | 详情 | 详情 | |
| (XII) | 48120 | 5-fluoro-5-methylhexyl tetrahydro-2H-pyran-2-yl ether; 2-[(5-fluoro-5-methylhexyl)oxy]tetrahydro-2H-pyran | C12H23FO2 | 详情 | 详情 | |
| (XIII) | 48121 | 6-fluoro-6-methyl-1-heptanol | C8H17FO | 详情 | 详情 | |
| (XIV) | 48122 | 1-bromo-6-fluoro-6-methylheptane | C8H16BrF | 详情 | 详情 | |
| (XV) | 48123 | N-(4-[(1S)-4-[ethyl(6-fluoro-6-methylheptyl)amino]-1-hydroxybutyl]phenyl)methanesulfonamide | C21H37FN2O3S | 详情 | 详情 | |
| (XVI) | 23808 | Fumaric acid; (E)-2-butenedioic acid | 110-17-8 | C4H4O4 | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(V)The protection of the NH2 group of L-serine (I) with Ts-Cl and TEA gives N-tosyl-L-serine (II), which is converted into the N-methylamide (III). The cyclization of (III) by means of diisopropylazodicarboxylate (DIAD) yields the N-tosylaziridine (IV), which is treated with ethylamine (V) to afford the diaminopropionamide (VI). The reduction of the amide group of (VI) with LiAlH4 provides the triaminopropane (VII), which is submitted to a reductive cyclization with glyoxal and BH3/TEA to give the perhydro-1,4-diazepine (VIII). Ts deprotection in (VIII) by means of HBr affords the 1-ethyl-4-methylperhydro-1,4-diazepin-6(R)-amine (IX), which is condensed with 5-bromo-2-methoxy-6-(methylamino)pyridine-3-carboxylic acid (X) by means of ethyl chloroformate and TEA to yield the target amide (XI). Finally, this compound is treated with fumaric acid (XII) in ethanol to afford the desired fumarate salt.
| 【1】 Hirokawa, Y.; et al.; Process development of the synthetic route to (R)-6-amino-1-ethyl-4-methylhexahydro-1,4-diazepine. Org Process Res Dev 2002, 6, 1, 28. |
| 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) | 20915 | methyl (2S)-2-amino-3-hydroxypropanoate | 5680-80-8 | C4H9NO3 | 详情 | 详情 |
| (II) | 54002 | methyl (2S)-3-hydroxy-2-{[(4-methylphenyl)sulfonyl]amino}propanoate | n/a | C11H15NO5S | 详情 | 详情 |
| (III) | 54003 | (2S)-3-hydroxy-N-methyl-2-{[(4-methylphenyl)sulfonyl]amino}propanamide | n/a | C11H16N2O4S | 详情 | 详情 |
| (IV) | 54004 | (2S)-N-methyl-1-[(4-methylphenyl)sulfonyl]-2-aziridinecarboxamide | n/a | C11H14N2O3S | 详情 | 详情 |
| (V) | 10928 | Ethanamine | 75-04-7 | C2H7N | 详情 | 详情 |
| (VI) | 54005 | (2S)-3-(ethylamino)-N-methyl-2-{[(4-methylphenyl)sulfonyl]amino}propanamide | n/a | C13H21N3O3S | 详情 | 详情 |
| (VII) | 54006 | N-{(1R)-2-(ethylamino)-1-[(methylamino)methyl]ethyl}-4-methylbenzenesulfonamide | n/a | C13H23N3O2S | 详情 | 详情 |
| (VIII) | 54007 | N-[(6S)-1-ethyl-4-methyl-1,4-diazepan-6-yl]-4-methylbenzenesulfonamide | n/a | C15H25N3O2S | 详情 | 详情 |
| (IX) | 17802 | (6S)-1-ethyl-4-methyl-1,4-diazepan-6-ylamine; (6S)-1-ethyl-4-methyl-1,4-diazepan-6-amine | C8H19N3 | 详情 | 详情 | |
| (X) | 17801 | 5-bromo-2-methoxy-6-(methylamino)nicotinic acid | C8H9BrN2O3 | 详情 | 详情 | |
| (XI) | 53998 | 5-bromo-N-[(6S)-1-ethyl-4-methyl-1,4-diazepan-6-yl]-2-methoxy-6-(methylamino)nicotinamide | n/a | C16H26BrN5O2 | 详情 | 详情 |
| (XII) | 23808 | Fumaric acid; (E)-2-butenedioic acid | 110-17-8 | C4H4O4 | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(VI)The hydrolysis of the 1-isopentyl-4-nitro-1H-pyrrole-2-carboxylic acid ethyl ester (I) with NaOH in hot ethanol gives the carboxylic acid (II), which is treated with refluxing SOCl2 to yield the acyl chloride (III). The reaction of (III) with 3-aminopropionitrile (IV) in toluene affords the carboxamide (V), which is treated with ethylamine (VI) and HCl in ethanol to provide the N-ethylamidino derivative (VII). The reduction of the nitro group of (VII) with H2 over Pd/C in methanol gives the aminopyrrole (VIII), which is finally condensed with bis pentafluorophenyl terephthalate (XI) to afford the target terephthalamide. The activated ester bis pentafluorophenyl terephthalate (XI) has been obtained by esterification of terephthalic acid (IX) with pentafluorophenyl trifluoroacetate (X) by means of DIEA in DMF.
| 【1】 Roberts, C.D.; Keicher, J.D.; Dyatkina, N.B.; et al.; Minor groove DNA binders as antimicrobial agents. 1. Pyrrole tetraamides are potent antibacterials against vancomycin resistant Enteroccoci and methicillin resistant Staphylococcus aureus. J Med Chem 2002, 45, 4, 805. |
| 【2】 Nelson, P.H.; Muchowski, J.M.; Dyatkina, N.B.; Shi, D.-F.; Zhang, W.; Liehr, S.J.R.; Velligan, M.D.; Botyanszki, J.; Roberts, C.D.; Khorlin, A. (Genelabs Technologies, Inc.); Novel cpds. possessing antibacterial, antifungal or antitumor activity. WO 0200650 . |
| 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) | 54019 | ethyl 1-isopentyl-4-nitro-1H-pyrrole-2-carboxylate | C12H18N2O4 | 详情 | 详情 | |
| (II) | 54020 | 1-isopentyl-4-nitro-1H-pyrrole-2-carboxylic acid | C10H14N2O4 | 详情 | 详情 | |
| (III) | 54021 | 1-isopentyl-4-nitro-1H-pyrrole-2-carbonyl chloride | C10H13ClN2O3 | 详情 | 详情 | |
| (IV) | 38094 | 3-aminopropanenitrile | 151-18-8 | C3H6N2 | 详情 | 详情 |
| (V) | 54022 | N-(2-cyanoethyl)-1-isopentyl-4-nitro-1H-pyrrole-2-carboxamide | C13H18N4O3 | 详情 | 详情 | |
| (VI) | 10928 | Ethanamine | 75-04-7 | C2H7N | 详情 | 详情 |
| (VII) | 54028 | N-[3-(ethylamino)-3-iminopropyl]-1-isopentyl-4-nitro-1H-pyrrole-2-carboxamide | C15H25N5O3 | 详情 | 详情 | |
| (VIII) | 54029 | 4-amino-N-[3-(ethylamino)-3-iminopropyl]-1-isopentyl-1H-pyrrole-2-carboxamide | C15H27N5O | 详情 | 详情 | |
| (IX) | 54025 | 1,4-Benzenedicarboxylic acid; Benzene-1,4-dicarboxylic acid; p-Benzenedicarboxylic acid; p-Phthalic acid; Terephthalic acid | 100-21-0 | C8H6O4 | 详情 | 详情 |
| (X) | 54026 | Trifluoroacetic acid pentafluorophenylester | 14533-84-7 | C8F8O2 | 详情 | 详情 |
| (XI) | 54027 | bis(2,3,4,5,6-pentafluorophenyl) terephthalate | C20H4F10O4 | 详情 | 详情 |