|
【结 构 式】 
|
【分子编号】10108 【品名】N-Methyl(1-naphthyl)methanamine; N-Methyl-N-(1-naphthylmethyl)amine; 1-Methyl-1-naphthalenemethylamine 【CA登记号】65473-13-4 |
【 分 子 式 】C12H13N 【 分 子 量 】171.24196 【元素组成】C 84.17% H 7.65% N 8.18% |
合成路线1
该中间体在本合成路线中的序号：(IV)1) The Grignard reaction of 1-bromonaphthalene (I) with Mg in THF and then with [14C]-labeled CO2 gives the corresponding 1-naphthoic acid (II), which by reaction with SO2Cl2 and then with methylamine yields [14C]-N-methyl-1-naphthalenecarboxamide (III). The reduction of (III) with LiAlH4 in refluxing THF affords the corresponding amine (IV). Finally, this compound is condensed with 1-bromo-6,6-dimethylhept-2-en-4-yne (V) by means of Na2CO3 in DMF, and treated with ethanolic HCl.
| 【1】 Andres, H.; Carbon-14 labelling of terbinafine, an antimycotic agent. J Label Compd Radiopharm 1989, 27, 11, 1307. |
| 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) | 10105 | 1-Bromonaphthalene | 90-11-9 | C10H7Br | 详情 | 详情 |
| (II) | 10106 | 1-Naphthoic acid | 86-55-5 | C11H8O2 | 详情 | 详情 |
| (II) | 44581 | 1-naphthoic acid | C11H8O2 | 详情 | 详情 | |
| (III) | 10107 | N-Methyl-1-naphthamide | 3400-33-7 | C12H11NO | 详情 | 详情 |
| (III) | 44582 | N-methyl-1-naphthamide | C12H11NO | 详情 | 详情 | |
| (IV) | 10108 | N-Methyl(1-naphthyl)methanamine; N-Methyl-N-(1-naphthylmethyl)amine; 1-Methyl-1-naphthalenemethylamine | 65473-13-4 | C12H13N | 详情 | 详情 |
| (IV) | 44583 | N-methyl(1-naphthyl)methanamine; N-methyl-N-(1-naphthylmethyl)amine | C12H13N | 详情 | 详情 | |
| (V) | 10109 | (E)-1-Bromo-6,6-dimethyl-2-hepten-4-yne | 78629-21-7 | C9H13Br | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)The condensation of N-(1-naphthylmethyl)methylamine (IV) with formaldehyde and 5,5-dimethylhexadiine (V) by means of Cu2Cl2 also gives (III), which is then reduced selectively with diisobutylaluminum hydride in toluene.
| 【1】 Stutz, A.; SF-86327 and related compounds: Synthetic methods. Int Con Chemother 1983, 116, 5-8. |
| 【2】 Serradell, M.N.; Castaner, J.; SF-86327. Drugs Fut 1984, 9, 6, 425. |
| 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) | 30535 | N-(6,6-dimethyl-2,4-heptadiynyl)-N-methyl-N-(1-naphthylmethyl)amine; N,6,6-trimethyl-N-(1-naphthylmethyl)-2,4-heptadiyn-1-amine | C21H23N | 详情 | 详情 | |
| (IV) | 10108 | N-Methyl(1-naphthyl)methanamine; N-Methyl-N-(1-naphthylmethyl)amine; 1-Methyl-1-naphthalenemethylamine | 65473-13-4 | C12H13N | 详情 | 详情 |
| (V) | 30536 | 5,5-dimethyl-1,3-hexadiyne | C8H10 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(IV)By reductocondensation of amino (IV) with 6,6-dimethylhept-2-en-4-ynal (VI) by means of NaBH4 in methanol.
| 【1】 Stutz, A. (Novartis AG); Propenylamines, pharmaceutical compositions containing them and their use as pharmaceuticals. EP 0024587; JP 56032440; JP 63313753; Us 4755534 . |
| 【2】 Serradell, M.N.; Castaner, J.; SF-86327. Drugs Fut 1984, 9, 6, 425. |
合成路线4
该中间体在本合成路线中的序号：(IV)The condensation of propenal (VII) with tert-butylacetylene (VIII) by means of butyllithium gives 6,6-dimethylhept-1-en-4-yn-3-ol (IX), which is rearranged with HBr to the allyl isomer 6,6-dimethylhept-2-en-4-yn-1-yl bromide (X). Finally, this compound is condensed with amine (IV) by means of Na2CO3 in DMF.
| 【1】 Stutz, A.; SF-86327 and related compounds: Synthetic methods. Int Con Chemother 1983, 116, 5-8. |
| 【2】 Stutz, A. (Novartis AG); Propenylamines, pharmaceutical compositions containing them and their use as pharmaceuticals. EP 0024587; JP 56032440; JP 63313753; Us 4755534 . |
| 【3】 Serradell, M.N.; Castaner, J.; SF-86327. Drugs Fut 1984, 9, 6, 425. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 10108 | N-Methyl(1-naphthyl)methanamine; N-Methyl-N-(1-naphthylmethyl)amine; 1-Methyl-1-naphthalenemethylamine | 65473-13-4 | C12H13N | 详情 | 详情 |
| (VII) | 17668 | acrylaldehyde; Acrolein | 107-02-8 | C3H4O | 详情 | 详情 |
| (VIII) | 30538 | 4,4-dimethyl-2-pentyne | 999-78-0 | C7H12 | 详情 | 详情 |
| (IX) | 30539 | 6,6-dimethyl-1-hepten-4-yn-3-ol | C9H14O | 详情 | 详情 | |
| (X) | 30540 | (E)-1-bromo-5,5-dimethyl-1-hexen-3-yne | C8H11Br | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(II)By condensation of cyannamyl chloride (I) with methyl (1-naphtylmethyl)amine (II) by means of Na2CO3 in DMF.
| 【1】 Berney, D.; Process for the preparation of novel N-(3-phenyl-2-propenyl)naphthylmethylamines. BE 0853976; CH 620896; JP 61171416 . |
| 【2】 Castaner, J.; Blancafort, P.; Serradell, M.N.; Naftifungin. Drugs Fut 1980, 5, 3, 141. |
合成路线6
该中间体在本合成路线中的序号：(I)By condensation of N-methyl-1-naphthylmethylamine (I) with 4-(tert-butyl)benzyl bromide (II) by means of Na2CO3 in DMF, followed by acidification with HCl in ethanol.
| 【1】 Arai, K.; Arita, M.; Sedino, T.; Komoto, N.; Hirose, S. (Mitsui Toatsu Chem.; Inc.); Benzylamine derivatives, process for production thereof, and use thereof. EP 0221781 . |
| 【2】 Prous, J.; Castaner, J.; KP-363. Drugs Fut 1989, 14, 4, 315. |
合成路线7
该中间体在本合成路线中的序号：(IV)The intermediate naphthylmethyl amine (IV) was prepared from 1-naphthaldehyde (I) by two related procedures. Reduction of (II) with NaBH4 gave alcohol (II), which was converted to the corresponding chloride with SOCl2 and then condensed with methylamine. Alternatively, condensation of aldehyde (I) with methylamine using TiCl4 as the dehydrating reagent produced aldimine (III), which was then reduced to amine (IV) by means of NaBH4.
| 【1】 Zhou, Y.; Zhang, W.; Li, K.; Jiang, Y.; Li, Y.; Wang, X.; The synthesis and antifungal activity of the substituted naphthalenemethanamines. Chin Journal of Medicinal Chemistry 1999, 9, 7, 7. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 11021 | Methanamine; Methylamine | 74-89-5 | CH5N | 详情 | 详情 | |
| (I) | 12314 | 1-Naphthaldehyde | 66-77-3 | C11H8O | 详情 | 详情 |
| (II) | 35129 | 1-naphthylmethanol | 4780-79-4 | C11H10O | 详情 | 详情 |
| (III) | 35130 | N-[(Z)-1-naphthylmethylidene]methanamine; N-methyl-N-[(Z)-1-naphthylmethylidene]amine | C12H11N | 详情 | 详情 | |
| (IV) | 10108 | N-Methyl(1-naphthyl)methanamine; N-Methyl-N-(1-naphthylmethyl)amine; 1-Methyl-1-naphthalenemethylamine | 65473-13-4 | C12H13N | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(IV)2,4-Dichlorobenzoic acid (V) was converted to acid chloride (VI) using SOCl2. Further Friedel-Crafts condensation of (VI) with toluene in the presence of AlCl3 produced benzophenone (VII). Benzylic bromination of (VII) with N-bromosuccinimide gave bromide (VIII). Finally, displacement of the bromine of (VIII) by means of amine (IV) furnished the title compound.
| 【1】 Zhou, Y.; Zhang, W.; Li, K.; Jiang, Y.; Li, Y.; Wang, X.; The synthesis and antifungal activity of the substituted naphthalenemethanamines. Chin Journal of Medicinal Chemistry 1999, 9, 7, 7. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 10108 | N-Methyl(1-naphthyl)methanamine; N-Methyl-N-(1-naphthylmethyl)amine; 1-Methyl-1-naphthalenemethylamine | 65473-13-4 | C12H13N | 详情 | 详情 |
| (V) | 33443 | 2,4-dichlorobenzoic carboxylic acid; 2,4-dichlorobenzoic acid | 50-84-0 | C7H4Cl2O2 | 详情 | 详情 |
| (VI) | 35131 | 2,4-dichlorobenzoyl chloride; 2,4-Dichlorophenacylchloride | 89-75-8 | C7H3Cl3O | 详情 | 详情 |
| (VII) | 35132 | (2,4-dichlorophenyl)(4-methylphenyl)methanone | C14H10Cl2O | 详情 | 详情 | |
| (VIII) | 35133 | [4-(bromomethyl)phenyl](2,4-dichlorophenyl)methanone | C14H9BrCl2O | 详情 | 详情 |
合成路线9
该中间体在本合成路线中的序号：(VIII)The title compound was prepared by solid-phase synthesis using a 2-chlorotrityl resin, chloride form. N2-(Benzyloxycarbonyl)-L-2,3-diaminopropionic acid (I) was protected as the Fmoc derivative (II) upon treatment with N-(Fmoc-oxy)succinimide. After attachment of the protected diaminoacid (II) to the chloride resin, the Fmoc group was selectively removed by means of piperidine in DMF to give the resin-bound Cbz-2,3-diaminopropionic acid (III). Acylation of the free amino function of (III) with 4-(chloromethyl)benzoyl chloride (IV) provided amide (V). The chloride group of (V) was then displaced with 2-(aminomethyl)benzimidazole (VI), yielding resin (VII). The required urea functionality (IX) was obtained by coupling (VII) with cyclohexyl isocyanate (VIII). Finally, cleavage of the carboxylic acid from the resin (IX) was achieved by treatment with trifluoroacetic acid in moist dichloromethane.
| 【1】 Neustadt, B.R.; Smith, E.M. (Schering Corp.); Benzimidazole cpds. that are vitronectin receptor antagonists. EP 1135374; WO 0032578 . |
| 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),(III) | 18008 | (2S)-3-amino-2-[[(benzyloxy)carbonyl]amino]propionic acid; N(alpha)-Z-L-2,3-diaminopropionic acid | 35761-26-3 | C11H14N2O4 | 详情 | 详情 |
| (II) | 49111 | (2S)-2-[[(benzyloxy)carbonyl]amino]-3-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propionic acid | C26H24N2O6 | 详情 | 详情 | |
| (IV) | 49112 | 4-(Chloromethyl)benzoyl chloride; p-(Chloromethyl)benzoyl chloride | 876-08-4 | C8H6Cl2O | 详情 | 详情 |
| (V) | 49113 | (2S)-2-[[(benzyloxy)carbonyl]amino]-3-[[4-(chloromethyl)benzoyl]amino]propionic acid | C19H19ClN2O5 | 详情 | 详情 | |
| (VI) | 49114 | 1H-benzimidazol-2-ylmethylamine; 1H-benzimidazol-2-ylmethanamine | C8H9N3 | 详情 | 详情 | |
| (VII) | 49115 | (2S)-3-[(4-[[(1H-benzimidazol-2-ylmethyl)amino]methyl]benzoyl)amino]-2-[[(benzyloxy)carbonyl]amino]propionic acid | C27H27N5O5 | 详情 | 详情 | |
| (VIII) | 10108 | N-Methyl(1-naphthyl)methanamine; N-Methyl-N-(1-naphthylmethyl)amine; 1-Methyl-1-naphthalenemethylamine | 65473-13-4 | C12H13N | 详情 | 详情 |
| (IX) | 49116 | (2S)-3-[[4-([(1H-benzimidazol-2-ylmethyl)[(cyclohexylamino)carbonyl]amino]methyl)benzoyl]amino]-2-[[(benzyloxy)carbonyl]amino]propionic acid | C34H38N6O6 | 详情 | 详情 |