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【结 构 式】 
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【分子编号】31758 【品名】tert-butyl (1R)-2-hydroxy-1-methylethylcarbamate 【CA登记号】 |
【 分 子 式 】C8H17NO3 【 分 子 量 】175.22792 【元素组成】C 54.84% H 9.78% N 7.99% O 27.39% |
合成路线1
该中间体在本合成路线中的序号：(II)D-Alaninol (I) was protected as the tert-butyl carbamate (II) and then converted to mesylate (III). Displacement of the mesylate group of (III) with NaCN furnished nitrile (IV), which was hydrogenated over Raney Nickel to give diamine (V). Condensation of (V) with benzaldehyde (VI) in the presence of molecular sieves produced imine (VII) and subsequent reduction by means of NaBH4 gave rise to the benzyl amine (VIII). This amine was alkylated with 4-chlorobutyronitrile (IX) to afford nitrile (X), which was further converted to the triamino compound (XI) by hydrogenation over Raney Nickel. Reaction of (XI) with methyl 2-[(phenoxycarbonyl)oxy]acetate (XII) provided carbamate (XIII). The ester group of (XIII) was then hydrolyzed with NaOH to give carboxylic acid (XIV).
| 【1】 Lebreton, L.; et al.; Structure - Immunosuppressive activity relationships of new analogues of 15-deoxyspergualin. 2. Structural modifications of the spermidine moiety. J Med Chem 1999, 42, 23, 4749. |
| 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) | 21414 | (2R)-2-Amino-1-propanol; D-Alaninol; D-(-)-Alaninol | 35320-23-1 | C3H9NO | 详情 | 详情 |
| (II) | 31758 | tert-butyl (1R)-2-hydroxy-1-methylethylcarbamate | C8H17NO3 | 详情 | 详情 | |
| (III) | 31803 | (2R)-2-[(tert-butoxycarbonyl)amino]propyl methanesulfonate | C9H19NO5S | 详情 | 详情 | |
| (IV) | 31804 | tert-butyl (1R)-2-cyano-1-methylethylcarbamate | C9H16N2O2 | 详情 | 详情 | |
| (V) | 31805 | tert-butyl (1R)-3-amino-1-methylpropylcarbamate | C9H20N2O2 | 详情 | 详情 | |
| (VI) | 10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 |
| (VII) | 31806 | tert-butyl (1R)-1-methyl-3-[[(E)-benzylidene]amino]propylcarbamate | C16H24N2O2 | 详情 | 详情 | |
| (VIII) | 31807 | tert-butyl (1R)-3-(benzylamino)-1-methylpropylcarbamate | C16H26N2O2 | 详情 | 详情 | |
| (IX) | 11179 | 4-Chlorobutanenitrile; 4-Chlorobutyronitrile | 628-20-6 | C4H6ClN | 详情 | 详情 |
| (X) | 31808 | tert-butyl (1R)-3-[benzyl(3-cyanopropyl)amino]-1-methylpropylcarbamate | C20H31N3O2 | 详情 | 详情 | |
| (XI) | 31809 | tert-butyl (1R)-3-[(4-aminobutyl)(benzyl)amino]-1-methylpropylcarbamate | C20H35N3O2 | 详情 | 详情 | |
| (XII) | 22341 | methyl 2-[(phenoxycarbonyl)oxy]acetate | C10H10O5 | 详情 | 详情 | |
| (XIII) | 31810 | methyl (6R)-9-benzyl-2,2,6-trimethyl-4,15-dioxo-3,16-dioxa-5,9,14-triazaoctadecan-18-oate | C24H39N3O6 | 详情 | 详情 | |
| (XIV) | 31811 | (6R)-9-benzyl-2,2,6-trimethyl-4,15-dioxo-3,16-dioxa-5,9,14-triazaoctadecan-18-oic acid | C23H37N3O6 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)Protection of D-alaninol (I) with di-tert-butyl dicarbonate gave rise to carbamate (II). Subsequent Mitsunobu coupling of (II) with 2-mercaptobenzothiazole (III) furnished thioether (IV), which was deprotected with HCl in EtOAc. The resulting amine (V) was condensed with dichloropurine (VI) to afford the chloroadenosine derivative (VII). Finally, cleavage of the acetate esters of (VII) was achieved by treatment with NaOMe in MeOH.
| 【1】 Lau, J.; Judge, M.E.; Sheardown, M.J.; Petersen, H.; Shalmi, M.; Knutsen, L.J.S.; Hansen, A.J.; Thomsen, C.; Weis, J.U.; N-substituted adenosines as novel neuroprotective A1 agonists with diminished hypotensive effects. J Med Chem 1999, 42, 18, 3463. |
| 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) | 21414 | (2R)-2-Amino-1-propanol; D-Alaninol; D-(-)-Alaninol | 35320-23-1 | C3H9NO | 详情 | 详情 |
| (II) | 31758 | tert-butyl (1R)-2-hydroxy-1-methylethylcarbamate | C8H17NO3 | 详情 | 详情 | |
| (III) | 24677 | 1,3-benzothiazol-2-ylhydrosulfide | 149-30-4 | C7H5NS2 | 详情 | 详情 |
| (IV) | 31759 | tert-butyl (1R)-2-(1,3-benzothiazol-2-ylsulfanyl)-1-methylethylcarbamate | C15H20N2O2S2 | 详情 | 详情 | |
| (V) | 31760 | (2R)-1-(1,3-benzothiazol-2-ylsulfanyl)-2-propanamine; (1R)-2-(1,3-benzothiazol-2-ylsulfanyl)-1-methylethylamine | C10H12N2S2 | 详情 | 详情 | |
| (VI) | 25228 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(2,6-dichloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C16H16Cl2N4O7 | 详情 | 详情 | |
| (VII) | 31761 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-[[(1R)-2-(1,3-benzothiazol-2-ylsulfanyl)-1-methylethyl]amino]-2-chloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C26H27ClN6O7S2 | 详情 | 详情 |