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【结 构 式】 
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【分子编号】18161 【品名】2-(1-pyrrolidinyl)ethylamine; 2-(1-pyrrolidinyl)-1-ethanamine; 1-Pyrrolidineethanamine 【CA登记号】7154-73-6 |
【 分 子 式 】C6H14N2 【 分 子 量 】114.19064 【元素组成】C 63.11% H 12.36% N 24.53% |
合成路线1
该中间体在本合成路线中的序号：(IV)Enediyne compound (I) as an unseparable 2:1 mixture of diastereoisomers was hydrolyzed with barium hydroxide in methanol-dichloromethane at 0 C to provide a mixture of alcohols (II), which were immediately converted into carbonyl imidazole intermediates (III) by treatment with carbonyldiimidazole (CDI) and 4-(dimethylamino)pyridine (DMAP) in cold dichloromethane. Reaction of (III) with an excess of 2-(1-pyrrolidinyl)ethylamine (IV) in dichloromethane at 0 C yielded a 2:1 mixture of diastereoisomeric carbamates, which on treatment with 0.01 M HCl gave the corresponding hydrochlorides.
| 【1】 Unno, R.; et al.; Synthesis and antitumor activity of water-soluble enediyne compounds related to dynemicin A. Bioorg Med Chem 1997, 5, 5, 987-999. |
| 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) | 18158 | 4-chlorophenyl (1R,9S,16S,18S)-16-(acetoxy)-17-oxa-8-azatetracyclo[7.7.2.0(1,18).0(2,7)]octadeca-2,4,6,12-tetraene-10,14-diyne-8-carboxylate | C25H16ClNO5 | 详情 | 详情 | |
| (II) | 18159 | 4-chlorophenyl (1S,9S,16S,18S)-16-hydroxy-17-oxa-8-azatetracyclo[7.7.2.0(1,18).0(2,7)]octadeca-2,4,6,12-tetraene-10,14-diyne-8-carboxylate | C23H14ClNO4 | 详情 | 详情 | |
| (III) | 18160 | 4-chlorophenyl (1R,9S,16S,18S)-16-[(1H-imidazol-1-ylcarbonyl)oxy]-17-oxa-8-azatetracyclo[7.7.2.0(1,18).0(2,7)]octadeca-2,4,6,12-tetraene-10,14-diyne-8-carboxylate | C27H16ClN3O5 | 详情 | 详情 | |
| (IV) | 18161 | 2-(1-pyrrolidinyl)ethylamine; 2-(1-pyrrolidinyl)-1-ethanamine; 1-Pyrrolidineethanamine | 7154-73-6 | C6H14N2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)Vilsmeier formylation of ethyl 2,4-dimethylindole-3-carboxylate (I) by means of POCl3 and DMF leads to aldehyde (II). Subsequent ester group hydrolysis in (II) under alkaline conditions furnishes acid (III), which is then coupled to N-(2-aminoethyl)pyrrolidine (IV) employing EDC/HOBt to afford the corresponding amide (V). Chemoselective reduction of the 3-carbonyl group of 5-fluoroisatin (VI) upon heating with hydrazine hydrate gives rise to 5-fluorooxindole (VII). Finally, condensation of (VII) with aldehyde (V) under Knoevenagel conditions provides the title compound
| 【1】 Wei, C.C.; Miller, T.; Tang, P.C.; Nematalla, A.S.; Li, X.; Liang, C.; Shirazian, S.; Su, L.; Vojkovsky, T. (Sugen, Inc.); Pyrrole substd. 2-indolinone protein kinase inhibitors. EP 1255752; US 2002156292; US 6573293; WO 0160814 . |
| 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) | 60380 | ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate | 2199-51-1 | C9H13NO2 | 详情 | 详情 |
| (II) | 60381 | ethyl 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylate | 2199-59-9 | C10H13NO3 | 详情 | 详情 |
| (III) | 60382 | 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid | 253870-02-9 | C8H9NO3 | 详情 | 详情 |
| (IV) | 18161 | 2-(1-pyrrolidinyl)ethylamine; 2-(1-pyrrolidinyl)-1-ethanamine; 1-Pyrrolidineethanamine | 7154-73-6 | C6H14N2 | 详情 | 详情 |
| (V) | 60383 | 5-formyl-2,4-dimethyl-N-[2-(1-pyrrolidinyl)ethyl]-1H-pyrrole-3-carboxamide | C14H21N3O2 | 详情 | 详情 | |
| (VI) | 21552 | 5-fluoro-1H-indole-2,3-dione | 443-69-6 | C8H4FNO2 | 详情 | 详情 |
| (VII) | 60384 | 5-fluoro-1,3-dihydro-2H-indol-2-one | 56341-41-4 | C8H6FNO | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(IV)In a related, scale-up procedure, 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (I) is condensed to 5-fluorooxindole (II) in the presence of pyrrolidine and AcOH to furnish adduct (III). This is then condensed with N-(2-aminoethyl)pyrrolidine (IV) in the presence of BOP to produce the target amide
| 【1】 Wei, C.C.; Miller, T.; Tang, P.C.; Nematalla, A.S.; Li, X.; Liang, C.; Shirazian, S.; Su, L.; Vojkovsky, T. (Sugen, Inc.); Pyrrole substd. 2-indolinone protein kinase inhibitors. EP 1255752; US 2002156292; US 6573293; WO 0160814 . |
| 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) | 60382 | 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid | 253870-02-9 | C8H9NO3 | 详情 | 详情 |
| (II) | 60384 | 5-fluoro-1,3-dihydro-2H-indol-2-one | 56341-41-4 | C8H6FNO | 详情 | 详情 |
| (III) | 60386 | 5-[(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid | 356068-93-4 | C16H13FN2O3 | 详情 | 详情 |
| (IV) | 18161 | 2-(1-pyrrolidinyl)ethylamine; 2-(1-pyrrolidinyl)-1-ethanamine; 1-Pyrrolidineethanamine | 7154-73-6 | C6H14N2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(IX)The title compound is prepared by solid phase synthesis employing a Rink amide resin. Acylation of the resin with chloroacetyl chloride (I) affords the chloroacetyl resin (II). Subsequent chloride displacement with s-butylamine (III) provides the aminoacid-bound resin (IV). A new acylation of (IV) with chloroacetyl chloride (I) yields the chloroacetamide (V), which is then displaced by cyclopropylamine (VI), yielding the dipeptide derivative (VII). Then, a further coupling of (VII) with acid chloride (I), followed by displacement of the resultant chloroacetamide resin (VIII) with N-(2-aminoethyl)pyrrolidine (IX) gives rise to the tripeptide resin (X). Finally, cleavage of the dipeptide amide from the solid support is accomplished by treatment with trifluoroacetic acid in CH2Cl2
| 【1】 Montoliu, C.; et al.; Prevention of in vivo excitotoxicity by a family of trialkylglycines, a novel class of neuroprotectants. J. Pharm. Exp. Ther. 2002, 301, 1, 29. |
| 【2】 Felipo Orts, V.; Montoliu Felix, C.; Ferrer Montiel, A.; Planells Cases, R.; Merino Fernandez, J.M.; Perez Paya, E.; Sanchez Baeza, F.; Humet, M.; Messeguer Peypoch, A. (DiverDrugs SL); N-Alkylglycine trimeres capable of protecting neurons against excitotoxic aggressions and compsns. containing said trimeres. WO 0228885 . |
| 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) | 11296 | 2-Chloroacetyl chloride; Chloroacetic chloride | 79-04-9 | C2H2Cl2O | 详情 | 详情 |
| (II) | 28964 | 2-chloroacetamide | 79-07-2 | C2H4ClNO | 详情 | 详情 |
| (III) | 61462 | sec-butyl amine; 2-Butanamine, (+-)-; 2-Aminobutane; 2-Butylamine; 2-Butanamine; 2-aminobutane base; butafume; deccotane; frucote; Butanamine; Methylpropylamine; SEC-BUTYLAMINE; (+/-)-sec-Butylamine; (+/-)-2-Aminobutane; Sec-Aminobutane; Sec-Butylamine; 2-Aminobutan; (+/-)-2-Butylamine; sec-Butylamine; Butylamine (sec); SBA; METHYL-n-PROPYLAMINE; (+/-)-2-Aminobutane | 13952-84-6 | C4H11N | 详情 | 详情 |
| (IV) | 61463 | 2-(sec-butylamino)acetamide | C6H14N2O | 详情 | 详情 | |
| (V) | 61464 | 2-[sec-butyl(2-chloroacetyl)amino]acetamide | C8H15ClN2O2 | 详情 | 详情 | |
| (VI) | 12263 | Cyclopropylamine; Cyclopropanamine | 765-30-0 | C3H7N | 详情 | 详情 |
| (VII) | 61465 | 2-{sec-butyl[2-(cyclopropylamino)acetyl]amino}acetamide | C11H21N3O2 | 详情 | 详情 | |
| (VIII) | 61466 | 2-(sec-butyl{2-[(2-chloroacetyl)(cyclopropyl)amino]acetyl}amino)acetamide | C13H22ClN3O3 | 详情 | 详情 | |
| (IX) | 18161 | 2-(1-pyrrolidinyl)ethylamine; 2-(1-pyrrolidinyl)-1-ethanamine; 1-Pyrrolidineethanamine | 7154-73-6 | C6H14N2 | 详情 | 详情 |
| (X) | 61467 | 2-(sec-butyl{2-[cyclopropyl(2-{[2-(1-pyrrolidinyl)ethyl]amino}acetyl)amino]acetyl}amino)acetamide | C19H35N5O3 | 详情 | 详情 |