1-bromo-3-fluoropropane -Drug Synthesis Database

【结构式】

【分子编号】19812

【品名】1-bromo-3-fluoropropane

【CA登记号】352-91-0

【分子式】C₃H₆BrF

【分子量】140.9830432

【元素组成】C 25.56% H 4.29% Br 56.68% F 13.48%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(X)

The cyclization of N-benzyl-N'-propylurea (I) with cyanacetic acid (II) in hot acetic anhydride gives 6-amino-1-benzyl-3-propyluracil (III), which is nitrosated with NaNO2/acetic acid and reduced with sodium dithionite to yield 5,6-diamino-1-benzyl-3-propyluracil (IV). The cyclization of (IV) with cyclopentylcarbonyl chloride (V) by means of NaOH in refluxing ethanol affords 3-benzyl-8-cyclopentyl-1-propylxanthine (VI), which is acylated with pivaloyl chloride (VII)/Na2CO3 in DMF giving the expected 7-acyl derivative (VIII). The debenzylation of (VIII) by hydrogenation over Pd/C as usual yields 8-cyclopentyl-7-pivaloyl-1-propylxanthine (IX), which is condensed with 1-bromo-3-fluoropropane (X) by means of Na2CO3 in DMF to afford 8-cyclopentyl-3-(3-fluoropropyl)-7-pivaloyl-1-propylxanthine (XI). Finally, this compound is deprotected with NaOH in DMSO/water.

参考文献中间体

合成目标

【1】 Holschbach, M.H.; et al.; A1 adenosine receptor antagonists as ligands for positron emission tomography (PET) and single-photon emission tomography (SPET). J Med Chem 1998, 41, 4, 555.

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)	19803	N-benzyl-N'-propylurea		C₁₁H₁₆N₂O	详情	详情
(II)	12591	Cyanoacetic Acid; 2-Cyanoacetic acid	372-09-8	C₃H₃NO₂	详情	详情
(III)	19805	6-amino-1-benzyl-3-propyl-2,4(1H,3H)-pyrimidinedione		C₁₄H₁₇N₃O₂	详情	详情
(IV)	19806	5,6-diamino-1-benzyl-3-propyl-2,4(1H,3H)-pyrimidinedione		C₁₄H₁₈N₄O₂	详情	详情
(V)	19807	1,4-cyclopentadiene-1-carbonyl chloride		C₆H₅ClO	详情	详情
(VI)	19808	3-benzyl-8-cyclopentyl-1-propyl-3,7-dihydro-1H-purine-2,6-dione		C₂₀H₂₄N₄O₂	详情	详情
(VII)	13597	2,2-Dimethylpropanoyl chloride; Pivaloyl chloride	3282-30-2	C₅H₉ClO	详情	详情
(VIII)	19810	3-benzyl-8-cyclopentyl-7-(2,2-dimethylpropanoyl)-1-propyl-3,7-dihydro-1H-purine-2,6-dione		C₂₅H₃₂N₄O₃	详情	详情
(IX)	19811	8-cyclopentyl-7-(2,2-dimethylpropanoyl)-1-propyl-3,7-dihydro-1H-purine-2,6-dione		C₁₈H₂₆N₄O₃	详情	详情
(X)	19812	1-bromo-3-fluoropropane	352-91-0	C₃H₆BrF	详情	详情
(XI)	19813	8-Cyclopentyl-3-(3-fluoropropyl)-7-pivaloyl-1-propylxanthine		C₂₁H₃₁FN₄O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

3beta-(4-Iodophenyl)nortropane-2beta-carboxylic acid methyl ester (I) was alkylated with 1-bromo-3-fluoropropane (II) in triethylamine to give the N-fluoropropyl derivative (III). Stannylation of the iodophenyl ring of (III) by Pd(0)-catalyzed reaction with hexamethylditin afforded the corresponding 4-(trimethylstannyl)phenyl tropane (IV). The 123I-labeled compound was then prepared by iododestannylation of (IV) with Na[123I] in the presence of peracetic acid.

参考文献中间体

合成目标

【1】 Gao, Y.; Baldessarini, R.J.; Innis, R.B.; Zea-Ponce, Y.; Baldwin, R.M.; Campbell, A.; Neumeyer, J.L.; Kula, N.S.; Wang, S.; Milius, R.A.; N-omega-Fluoroalkyl analogs of (1R)-2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane (beta-CIT): Radiotracers for positron emission tomography and single photon emission computed tomography imaging of dopamine transporters. J Med Chem 1994, 37, 11, 1558.

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)	38868	methyl (1S,2S,3S,5R)-3-(4-iodophenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate		C₁₅H₁₈INO₂	详情	详情
(II)	19812	1-bromo-3-fluoropropane	352-91-0	C₃H₆BrF	详情	详情
(III)	38869	methyl (1S,2S,3S,5R)-8-(3-fluoropropyl)-3-(4-iodophenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate		C₁₈H₂₃FINO₂	详情	详情
(IV)	38870	methyl (1S,2S,3S,5R)-8-(3-fluoropropyl)-3-[4-(trimethylstannyl)phenyl]-8-azabicyclo[3.2.1]octane-2-carboxylate		C₂₁H₃₂FNO₂Sn	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VII)

Conjugate addition of 4-(trimethylsilyl)phenylmagnesium bromide (II) to anhydroecgonine methyl ester (I) afforded regioselectively the 2-beta-carbomethoxy-3-beta-aryl tropane (III). Bromodesilylation of (III) using NaBr and N-chlorosuccinimide gave the bromophenyl derivative (IV). Amine demethylation was accomplished by reaction of (IV) with 1-chloroethyl chloroformate, followed by hydrolysis and decarboxylation of the intermediate carbamate (V) upon treatment with methanol. The resulting secondary amine (VI) was then alkylated with 3-fluoropropyl bromide (VII) to furnish the title fluoropropyl amine.

参考文献中间体

合成目标

【1】 Gu, X.-H.; et al.; Synthesis and biological evaluation of a series of novel N- or O-fluoroalkyl derivatives of tropane: Potential positron emission tomography (PET) imaging agents for the dopamine transporter. Bioorg Med Chem Lett 2001, 11, 23, 3049.

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)	21118	methyl (1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate		C₁₀H₁₅NO₂	详情	详情
(II)	50257	bromo[4-(trimethylsilyl)phenyl]magnesium		C₉H₁₃BrMgSi	详情	详情
(III)	50258	methyl (1R,2S,3S,5S)-8-methyl-3-[4-(trimethylsilyl)phenyl]-8-azabicyclo[3.2.1]octane-2-carboxylate		C₁₉H₂₉NO₂Si	详情	详情
(IV)	50264	methyl (1R,2S,3S,5S)-3-(4-bromophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate		C₁₆H₂₀BrNO₂	详情	详情
(V)	50265	8-(1-chloroethyl) 2-methyl (1R,2S,3S,5S)-3-(4-bromophenyl)-8-azabicyclo[3.2.1]octane-2,8-dicarboxylate		C₁₈H₂₁BrClNO₄	详情	详情
(VI)	50266	methyl (1R,2S,3S,5S)-3-(4-bromophenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate		C₁₅H₁₈BrNO₂	详情	详情
(VII)	19812	1-bromo-3-fluoropropane	352-91-0	C₃H₆BrF	详情	详情

Extended Information