(3S,4S)-4-amino-3,4-dihydro-2H-chromen-3-ol -Drug Synthesis Database

【结构式】

【分子编号】56265

【品名】(3S,4S)-4-amino-3,4-dihydro-2H-chromen-3-ol

【CA登记号】

【分子式】C₉H₁₁NO₂

【分子量】165.19188

【元素组成】C 65.44% H 6.71% N 8.48% O 19.37%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XVIII)

Bromochromanone (XVI) was prepared by bromination of 4-chromanone (XV). Subsequent reduction of (XVI) with NaBH4 provided bromohydrin (XVII). Ritter reaction of (XVII) with acetonitrile and sulfuric acid, followed by acidic hydrolysis, led to racemic cis-3-bromo-4-chromanol, which was then resolved by means of (S)-(+)-mandelic acid. The desired (S,S)-isomer (XVIII) was coupled with hydrocinnamic acid (XIX) giving amide (XX). After protection of hydroxy amide (XX) as the acetonide (XXI), the lithium enolate of amide (XXI) was alkylated with allyl bromide (XXII) to furnish the (S)-2-benzyl-4-pentenamide (XXIII) as the main diastereoisomer. Halogenation of (XXIII) with N-iodosuccinimide in H2O-EtOAc afforded iodohydrin (XXIV), which was cyclized to epoxide (XXV) in the presence of NaOMe.

参考文献中间体

合成目标

【1】 gamma-Hydroxy-2-(fluoroalkylaminocarbonyl)-1-piperazinepentanamides as HIV protease inhibitors. EP 1242426; WO 0138332 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XV)	14461	2,3-Dihydro-4H-chromen-4-one; 4-Chromanone	491-37-2	C₉H₈O₂	详情	详情
(XVI)	56263	3-bromo-2,3-dihydro-4H-chromen-4-one		C₉H₇BrO₂	详情	详情
(XVII)	56264	3-bromo-4-chromanol		C₉H₉BrO₂	详情	详情
(XVIII)	56265	(3S,4S)-4-amino-3,4-dihydro-2H-chromen-3-ol		C₉H₁₁NO₂	详情	详情
(XIX)	49181	Hydrocinnamic acid; 3-Phenylpropionic acid; Benzylacetic acid	501-52-0	C₉H₁₀O₂	详情	详情
(XX)	56266	N-[(3S,4S)-3-hydroxy-3,4-dihydro-2H-chromen-4-yl]-3-phenylpropanamide		C₁₈H₁₉NO₃	详情	详情
(XXI)	56267	1-[(3aS,9bS)-2,2-dimethyl-3a,9b-dihydro-2H-chromeno[4,3-d][1,3]oxazol-1(4H)-yl]-3-phenyl-1-propanone		C₂₁H₂₃NO₃	详情	详情
(XXII)	11463	3-Bromo-1-propene; 3-Bromopropene；allyl bromide	106-95-6	C₃H₅Br	详情	详情
(XXIII)	56268	(2S)-1-[(3aS,9bS)-2,2-dimethyl-3a,9b-dihydro-2H-chromeno[4,3-d][1,3]oxazol-1(4H)-yl]-2-benzyl-4-penten-1-one		C₂₄H₂₇NO₃	详情	详情
(XXIV)	56269	(2R,4S)-1-[(3aS,9bS)-2,2-dimethyl-3a,9b-dihydro-2H-chromeno[4,3-d][1,3]oxazol-1(4H)-yl]-2-benzyl-4-hydroxy-5-iodo-1-pentanone		C₂₄H₂₈INO₄	详情	详情
(XXV)	56270	(2R)-1-[(3aS,9bS)-2,2-dimethyl-3a,9b-dihydro-2H-chromeno[4,3-d][1,3]oxazol-1(4H)-yl]-2-benzyl-3-[(2S)oxiranyl]-1-propanone		C₂₄H₂₇NO₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIII)

Coupling of acid (XII) with (S,S)-4-aminochroman-3-ol (XIII) in the presence of HBTU provides amide (XIV). Finally, desilylation of (XIV) with tetrabutylammonium fluoride gives rise to the target compound.

参考文献中间体

合成目标

【1】 Bohn, J.; Lu, Z.; Raghavan, S.; Charest, M.; Stahlhut, M.; Rutkowski, C.A.; Himmelberger, A.L.; Olsen, D.B.; Scheleif, W.A.; Carella, A.; Gabryelski, L.; Jin, L.; Lin, J.H.; Tata, J.R.; Chapman, K.; Synthesis of highly potent HIV protease inhibitors with activity against protease resistant virus. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 205.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XII)	65062	(2R,4S)-2-benzyl-4-{[tert-butyl(dimethyl)silyl]oxy}-5-[(4R)-4-({[(3,5-dimethyl-4-isothiazolyl)methyl]amino}carbonyl)-5,5-dimethyl-1,3-thiazolidin-3-yl]-5-oxopentanoic acid	C₃₀H₄₅N₃O₅S₂Si	详情	详情
(XIII)	56265	(3S,4S)-4-amino-3,4-dihydro-2H-chromen-3-ol	C₉H₁₁NO₂	详情	详情
(XIV)	65092	(4R)-3-((2S,4R)-4-benzyl-2-{[tert-butyl(dimethyl)silyl]oxy}-5-{[(3S,4S)-3-hydroxy-3,4-dihydro-2H-chromen-4-yl]amino}-5-oxopentanoyl)-N-[(3,5-dimethyl-4-isothiazolyl)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide	C₃₉H₅₄N₄O₆S₂Si	详情	详情

Extended Information