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【结 构 式】 
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【分子编号】27396 【品名】3-bromo-4-hydroxy-2,2-dimethyl-6-chromanecarbonitrile 【CA登记号】 |
【 分 子 式 】C12H12BrNO2 【 分 子 量 】282.13682 【元素组成】C 51.09% H 4.29% Br 28.32% N 4.96% O 11.34% |
合成路线1
该中间体在本合成路线中的序号：(IV)1) The cyclization of 4-cyanophenol (I) with 3-chloro-3-methylbutine (II) by means of benzyltrimethylammonium hydroxide in methanol-CH2Cl2 gives 6-cyano-2,2-dimethyl-2H-benzo[b]pyran (III), which is treated with N-bromosuccinimide in DMSO to afford 6-cyano-trans-3-bromo-3,4-dihydro-2,2-dimethyl 2H benzo[b]pyran-4-ol (IV). Epoxidation of (IV) by means of NaOH in dioxane-water yields 6-cyano-3-(4-dihydro-3,4-epoxy-2,2-dimethyl-2H-benzo[b]pyran (V), which is finally treated with 4-aminobutyric acid (VI) and NaHCO3 in refluxing ethanol. 2) By reaction of epoxide (V) with 2-pyrrolidone (X) by means of NaH in DMSO.
| 【1】 Evans, J.M.; Buckingham, R.E.; Willcocks, K. (SmithKline Beecham plc); Benzopyrans. EP 0076075; JP 3014573; JP 5202034; US 4446113 . |
| 【2】 Faruk, E.A. (SmithKline Beecham plc); Antihypertensive chromenes and chromans. EP 0093535; US 4510152 . |
| 【3】 Castaner, J.; Mannhold, R.; BRL-34915. Drugs Fut 1986, 11, 3, 175. |
| 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) | 27394 | Trimethylbenzylammonium Hydroxide; N,N,N-trimethyl(phenyl)methanaminium hydroxide; Triton B; Benzyltrimethylammonium hydroxide | 100-85-6 | C10H17NO | 详情 | 详情 |
| (I) | 25109 | 4-hydroxybenzonitrile | 767-00-0 | C7H5NO | 详情 | 详情 |
| (II) | 22416 | 3-chloro-3-methyl-1-butyne | 1111-97-3 | C5H7Cl | 详情 | 详情 |
| (III) | 27395 | 2,2-dimethyl-2H-chromene-6-carbonitrile | C12H11NO | 详情 | 详情 | |
| (IV) | 27396 | 3-bromo-4-hydroxy-2,2-dimethyl-6-chromanecarbonitrile | C12H12BrNO2 | 详情 | 详情 | |
| (V) | 12861 | 2,2-Dimethyl-1a,7b-dihydro-2H-oxireno[2,3-c]chromene-6-carbonitrile | C12H11NO2 | 详情 | 详情 | |
| (VI) | 13620 | 4-Amino-n-butyric acid; 4-Aminobutyric acid;Piperidinic acid;Piperidic acid | 56-12-2 | C4H9NO2 | 详情 | 详情 |
| (X) | 27397 | 2-Pyrrolidinone | 616-45-5 | C4H7NO | 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 reaction of epoxide (V) with ammonia in ethanol gives 4-amino-6-cyano-3,4-dihydro-2,2-dimethyl-trans-2H-benzo[b]pyran-3-ol (VII), which is condensed with 4-chlorobutyryl chloride (VIII) by means of NaOH in CHCl3 yielding 6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(4-chlorobutyrylamino)-2H-benzo[blpyran 3-ol (IX). Finally, this compound is cyclized by means of NaH in THF.
| 【1】 Faruk, E.A. (SmithKline Beecham plc); Antihypertensive chromenes and chromans. EP 0093535; US 4510152 . |
| 【2】 Evans, J.M.; Buckingham, R.E.; Willcocks, K. (SmithKline Beecham plc); Benzopyrans. EP 0076075; JP 3014573; JP 5202034; US 4446113 . |
| 【3】 Castaner, J.; Mannhold, R.; BRL-34915. Drugs Fut 1986, 11, 3, 175. |
| 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) | 27394 | Trimethylbenzylammonium Hydroxide; N,N,N-trimethyl(phenyl)methanaminium hydroxide; Triton B; Benzyltrimethylammonium hydroxide | 100-85-6 | C10H17NO | 详情 | 详情 |
| (I) | 25109 | 4-hydroxybenzonitrile | 767-00-0 | C7H5NO | 详情 | 详情 |
| (II) | 22416 | 3-chloro-3-methyl-1-butyne | 1111-97-3 | C5H7Cl | 详情 | 详情 |
| (III) | 27395 | 2,2-dimethyl-2H-chromene-6-carbonitrile | C12H11NO | 详情 | 详情 | |
| (IV) | 27396 | 3-bromo-4-hydroxy-2,2-dimethyl-6-chromanecarbonitrile | C12H12BrNO2 | 详情 | 详情 | |
| (V) | 12861 | 2,2-Dimethyl-1a,7b-dihydro-2H-oxireno[2,3-c]chromene-6-carbonitrile | C12H11NO2 | 详情 | 详情 | |
| (VII) | 27398 | (3S,4R)-4-amino-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromene-6-carbonitrile | C12H14N2O2 | 详情 | 详情 | |
| (VIII) | 11265 | 4-Chlorobutanoyl chloride; 4-Chlorobutyric acid chloride | 4635-59-0 | C4H6Cl2O | 详情 | 详情 |
| (IX) | 27399 | 4-chloro-N-[(3S,4R)-6-cyano-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]butanamide | C16H19ClN2O3 | 详情 | 详情 |