【结 构 式】 |
【分子编号】47323 【品名】2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl)acetic acid 【CA登记号】 |
【 分 子 式 】C15H19N3O3 【 分 子 量 】289.33428 【元素组成】C 62.27% H 6.62% N 14.52% O 16.59% |
合成路线1
该中间体在本合成路线中的序号:(III)Solid phase synthesis: Attachment of 8-Fmoc-3-carboxymethyl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one (I) to Wang resin by means of 2,6-dichlorobenzoyl chloride (A) in DMF in the presence of pyridine, followed by treatment with benzoyl chloride (B) in dichloromethane in the presence of pyridine, provides resin-anchored derivative (II). Treatment of resin (II) with piperidine in DMF allows Fmoc removal to yield deprotected piperidine derivative (III), which is then converted into the target compound by alkylation with 1-(bromomethyl)naphthalene (IV) by heating in DMSO in the presence of DIEA, followed by cleavage of the molecule from the resin by heating with NaOMe in THF/MeOH. Alternatively, the conversion of (III) into the desired compound can be achieved by reductive amination between resin (III) and aldehyde (V) by means of NaBH3CN in THF in the presence of HOAc to afford anchored derivative (VI), followed by cleavage from the resin by heating with NaOMe in THF/MeOH.
【1】 Watson, B.; Thomsen, C.; Hohlweg, R. (Novo Nordisk A/S); Novel 1,3,8-triazaspiro[4.5]decanones with high affinity for opioid receptor subtypes. EP 1080091; WO 9959997 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(B) | 10463 | Benzoyl chloride | 98-88-4 | C7H5ClO | 详情 | 详情 |
(A) | 25087 | 2,6-dichlorobenzoyl chloride | 4659-45-4 | C7H3Cl3O | 详情 | 详情 |
(I),(II) | 47322 | 2-[8-[(9H-fluoren-9-ylmethoxy)carbonyl]-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl]acetic acid | C30H29N3O5 | 详情 | 详情 | |
(III) | 47323 | 2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl)acetic acid | C15H19N3O3 | 详情 | 详情 | |
(IV) | 47324 | 1-(bromomethyl)naphthalene | 3163-27-7 | C11H9Br | 详情 | 详情 |
(V) | 12314 | 1-Naphthaldehyde | 66-77-3 | C11H8O | 详情 | 详情 |
(VI) | 47325 | 2-[8-(1-naphthylmethyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl]acetic acid | C26H27N3O3 | 详情 | 详情 |