6-Fluorospiro[chroman-4,4'-imidazolidine]-2',4'-dione -Drug Synthesis Database

【结构式】

【分子编号】10057

【品名】6-Fluorospiro[chroman-4,4'-imidazolidine]-2',4'-dione

【CA登记号】69684-83-9

【分子式】C₁₁H₉FN₂O₃

【分子量】236.2025432

【元素组成】C 55.94% H 3.84% F 8.04% N 11.86% O 20.32%

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：(IV)

The synthesis of [2H]-, [3H]- and [14C]-radiolabeled sorbinil has been described: [2H]- and [3H]-sorbinil are prepared by chlorination of sorbinil (I) with Cl2 and FeCl2 in dry DMF to give the 8-chloro derivative (II), which is then reduced with deuterium or tritium over Pd/C in ethanol. [14C]-Labeled sorbinil is prepared by cyclization of 6-fluoro-3,4-dihydro-2H-benzo[b]pyran-4-one (III) with [14C]-potassium cyanide and ammonium carbonate in hot ethanol-water to give radiolabeled racemic sorbinil, which is then submitted to optical resolution with brucine in ethanol.

参考文献中间体

合成目标

【1】 Howard, H.R.; Sarges, R.; Evans, M.; Synthesis of H-2-labelled, H-3-labelled and C-14-labelled CP-45,634 (sorbinil). J Label Compd Radiopharm 1991, 29, 6, 703.

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)	10054	(S)-6-Fluorospiro(chroman-4,4'-imidazolidine)-2',5'-dione	68367-52-2	C₁₁H₉FN₂O₃	详情	详情
(II)	10055	(S)-8-Chloro-6-fluorospiro(chroman-4,4'-imidazolidine)-2',5'-dione		C₁₁H₈ClFN₂O₃	详情	详情
(III)	10056	6-Fluoro-2,3-dihydro-4H-chromen-4-one; 6-Fluoro-4-chromanone	66892-34-0	C₉H₇FO₂	详情	详情
(IV)	10057	6-Fluorospiro[chroman-4,4'-imidazolidine]-2',4'-dione	69684-83-9	C₁₁H₉FN₂O₃	详情	详情
(IV)	44570			C₁₁H₉FN₂O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Racemic sorbinil (I) is hydrolyzed with barium hydroxide in refluxing water to give amino acid (II), which by reaction with potassium cyanate in water yields (RS)-6-fluoro-4-ureido-2,3-dihydro-4H-1-benzoyran-4-carboxylic acid (III). The optical resolution of (III) with D-(+)-(1-phenylethyl)amine or L-(-)-ephedrine affords 6-fluoro-4(S)-ureido-2,3-dihydro-4H-1-benzopyran-4-carboxylic acid (IV), which is finally cyclized to sorbinil by means of hot acetic acid.

参考文献中间体

合成目标

【1】 Cue, B.W. Jr.; Moore, B.S. (Pfizer Inc.); Sorbinyl by optical resolution of precursor 6-fluoro-4-ureidochroman-4-carboxylic acid. JP 1988211278; JP 1988211281; JP 1988211282; US 4435578 .

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)	10057	6-Fluorospiro[chroman-4,4'-imidazolidine]-2',4'-dione	69684-83-9	C₁₁H₉FN₂O₃	详情	详情
(II)	20834	4-amino-6-fluoro-4-chromanecarboxylic acid		C₁₀H₁₀FNO₃	详情	详情
(III)	20838	4-[(aminocarbonyl)amino]-6-fluoro-4-chromanecarboxylic acid		C₁₁H₁₁FN₂O₄	详情	详情
(IV)	20839	(4R)-4-[(aminocarbonyl)amino]-6-fluoro-3,4-dihydro-2H-chromen-4-yl formate		C₁₁H₁₁FN₂O₄	详情	详情

Extended Information