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【结 构 式】 
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【分子编号】17908 【品名】1,3-benzothiazol-6-ylamine; 1,3-benzothiazol-6-amine; 6-Aminobenzothiazole 【CA登记号】533-30-2 |
【 分 子 式 】C7H6N2S 【 分 子 量 】150.20412 【元素组成】C 55.98% H 4.03% N 18.65% S 21.35% |
合成路线1
该中间体在本合成路线中的序号：(I)Reaction of 6-aminobenzothiazole (I) with phosgene in refluxing tolene affords isocyanate (II). Alkylation of 6-fluoro-3-(4-piperidinyl)-1,2-bensisoxazole hydrochloride (III) with 3-bromopropanol (IV) in the presence of potassium carbonate in acetone gave alcohol (V). Finally, condensation of this alcohol (V) with isocyanate (II) in DMF at 100 C yielded the title carbamate.
| 【1】 Hansen, J.B.; Jeppesen, L.; Gronvald, F.C. (Novo Nordisk A/S); Chemical cpds., their preparation and use. EP 0679085; JP 1995502268; US 5378714; WO 9310742 . |
| 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) | 17908 | 1,3-benzothiazol-6-ylamine; 1,3-benzothiazol-6-amine; 6-Aminobenzothiazole | 533-30-2 | C7H6N2S | 详情 | 详情 |
| (II) | 17909 | 6-isocyanato-1,3-benzothiazole; 1,3-benzothiazol-6-yl isocyanate | C8H4N2OS | 详情 | 详情 | |
| (III) | 17910 | 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole | C12H13FN2O | 详情 | 详情 | |
| (IV) | 12573 | 3-Bromo-1-propanol; 3-Bromopropanol | 627-18-9 | C3H7BrO | 详情 | 详情 |
| (V) | 17912 | 3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-1-propanol | C15H19FN2O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VIII)Treatment of 3-aminobenzyl alcohol (I) with isopropyl isocyanate produced urea (II). Mesylation of alcohol (III), followed by reaction with LiBr gave benzyl bromide (III). Then, alkylation of 3-azidobenzazepine (IV) with (III) under phase-transfer conditions afforded (V). The azido group of (V) was reduced to amine (VI) by catalytic hydrogenation over Pd/C. Subsequent treatment of (VI) with carbonyl diimidazole produced isocyanate (VII). This was finally converted to the target compound by condensation with 6-aminobenzothiazole (VIII).
| 【1】 Hara, H.; Murakami, Y.; Okada, T.; et al.; 1,3-Disubstituted benzazepines as novel, potent, selective neuropeptide Y Y1 receptor antagonists. J Med Chem 1999, 42, 14, 2621. |
| 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) | 26153 | (3-aminophenyl)methanol | 1877-77-6 | C7H9NO | 详情 | 详情 |
| (II) | 26154 | N-[3-(hydroxymethyl)phenyl]-N'-isopropylurea | C11H16N2O2 | 详情 | 详情 | |
| (III) | 26155 | N-[3-(bromomethyl)phenyl]-N'-isopropylurea | C11H15BrN2O | 详情 | 详情 | |
| (IV) | 20891 | 3-azido-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one | C10H10N4O | 详情 | 详情 | |
| (V) | 26156 | N-[3-[(3-azido-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)methyl]phenyl]-N'-isopropylurea | C21H24N6O2 | 详情 | 详情 | |
| (VI) | 26157 | N-[3-[(3-amino-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)methyl]phenyl]-N'-isopropylurea | C21H26N4O2 | 详情 | 详情 | |
| (VII) | 26158 | N-[3-[(3-isocyanato-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)methyl]phenyl]-N'-isopropylurea | C22H24N4O3 | 详情 | 详情 | |
| (VIII) | 17908 | 1,3-benzothiazol-6-ylamine; 1,3-benzothiazol-6-amine; 6-Aminobenzothiazole | 533-30-2 | C7H6N2S | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)The condensation of 6-aminobenzothiazole (I) with ethyl 2-(methylsulfanyl)acetate (II) in the presence of tert-butyl hypochlorite produced the oxindole derivative (III). The methylsulfanyl group was then reductively removed using zinc in acetic acid to afford (IV). Reaction of (IV) with diethoxymethyl acetate in refluxing HOAc furnished the ethoxymethylene derivative (V). This was finally condensed with sulfapyridine (VI) to give the title compound.
| 【1】 Frye, S.V.; Davis, S.T.; Lackey, K.E.; Dickerson, S.H.; Luzzio, M.J.; Kuyper, L.F.; Veal, J.M.; Hunter, R.N. III; Walker, D.H.; Harris, P.A. (Glaxo Group Ltd.); Substd. oxindole derivs. as protein tyrosine kinase and as protein serine/threonine kinase inhibitors. EP 1009738; WO 9915500 . |
| 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) | 17908 | 1,3-benzothiazol-6-ylamine; 1,3-benzothiazol-6-amine; 6-Aminobenzothiazole | 533-30-2 | C7H6N2S | 详情 | 详情 |
| (II) | 48543 | Ethyl methylthioacetate; (Methylthio)acetic acid ethyl ester; ethyl 2-(methylsulfanyl)acetate | 4455-13-4 | C5H10O2S | 详情 | 详情 |
| (III) | 48544 | 8-(methylsulfanyl)-6,8-dihydro-7H-[1,3]thiazolo[5,4-e]indol-7-one | C10H8N2OS2 | 详情 | 详情 | |
| (IV) | 48545 | 6,8-dihydro-7H-[1,3]thiazolo[5,4-e]indol-7-one | C9H6N2OS | 详情 | 详情 | |
| (V) | 48546 | 8-[(Z)-ethoxymethylidene]-6H-[1,3]thiazolo[5,4-e]indol-7-one | C12H10N2O2S | 详情 | 详情 | |
| (VI) | 48547 | 2-(4-Aminobenzenesulfonamido)pyridine; 4-Amino-N-2-pyridylbenzenesulfonamide; Sulfapyridine | 144-83-2 | C11H11N3O2S | 详情 | 详情 |