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【结 构 式】

【分子编号】64410

【品名】tert-butyl 4-(4-iodobutyl)-5-oxo-1,4-diazepane-1-carboxylate

【CA登记号】

【 分 子 式 】C14H25IN2O3

【 分 子 量 】396.26865

【元素组成】C 42.43% H 6.36% I 32.02% N 7.07% O 12.11%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(VII)

4-Bromothioanisole (I) is converted into the corresponding Grignard reagent (II), which is subsequently condensed with N-Cbz-alanine morpholide (III) to furnish the N-Cbz aminoketone (IV). Keto group reduction in (IV) by means of NaBH4, followed by intramolecular cyclization in boiling toluene leads to the chiral oxazolidinone (V). After oxidation of the methylsulfanyl group of (V) to the corresponding sulfone (VI), N-alkylation with the iodobutyl diazepinone (VII) in the presence of potassium tert-amyloxide furnishes adduct (VIII). The oxazolidinone ring of (VIII) is then subjected to reductive cleavage under transfer hydrogenation conditions to produce the secondary amine (IX). Conversion of amine (IX) into the N-propyl derivative (X) is effected by reductive alkylation with propionaldehyde in the presence of NaBH(OAc)3. The N-Boc group of (X) is finally cleaved under acidic conditions to afford the title compound.

1 Maag, H.; Fisher, L.E.; Prince, A.; Repke, D.B.; Dvorak, C.A.; Harris, R.N. III; Green, K.L.; Stabler, R.S. (F. Hoffmann-La Roche AG); Substd. 1-aminoalkyl-lactams and their use as muscarinic receptor antagonists. JP 2003534330; US 2002004501; US 6667301; WO 0190081 .
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) 19266 4-bromophenyl methyl sulfide; 1-bromo-4-(methylsulfanyl)benzene 104-95-0 C7H7BrS 详情 详情
(II) 54517 bromo[4-(methylsulfanyl)phenyl]magnesium C7H7BrMgS 详情 详情
(III) 64406 benzyl (1S)-1-methyl-2-(4-morpholinyl)-2-oxoethylcarbamate C15H20N2O4 详情 详情
(IV) 64407 benzyl (1S)-1-methyl-2-[4-(methylsulfanyl)phenyl]-2-oxoethylcarbamate C18H19NO3S 详情 详情
(V) 64408 (4S)-4-methyl-5-[4-(methylsulfanyl)phenyl]-1,3-oxazolidin-2-one C11H13NO2S 详情 详情
(VI) 64409 (4S)-4-methyl-5-[4-(methylsulfonyl)phenyl]-1,3-oxazolidin-2-one C11H13NO4S 详情 详情
(VII) 64410 tert-butyl 4-(4-iodobutyl)-5-oxo-1,4-diazepane-1-carboxylate C14H25IN2O3 详情 详情
(VIII) 64411 tert-butyl 4-(4-{(4S)-4-methyl-5-[4-(methylsulfonyl)phenyl]-2-oxo-1,3-oxazolidin-3-yl}butyl)-5-oxo-1,4-diazepane-1-carboxylate C25H37N3O7S 详情 详情
(IX) 64412 tert-butyl 4-[4-({(1S)-1-methyl-2-[4-(methylsulfonyl)phenyl]ethyl}amino)butyl]-5-oxo-1,4-diazepane-1-carboxylate C24H39N3O5S 详情 详情
(X) 64405 tert-butyl 4-{4-[{(1S)-1-methyl-2-[4-(methylsulfonyl)phenyl]ethyl}(propyl)amino]butyl}-5-oxo-1,4-diazepane-1-carboxylate C27H45N3O5S 详情 详情
Extended Information