2-Bromomalonaldehyde -Drug Synthesis Database

【结构式】

【分子编号】14278

【品名】2-Bromomalonaldehyde

【CA登记号】

【分子式】C₃H₃BrO₂

【分子量】150.95962

【元素组成】C 23.87% H 2% Br 52.93% O 21.2%

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：(II)

Racemic lometrexol has been prepared.

参考文献中间体

合成目标

【1】 Harrington, P.M.; Shih, C.; Grindey, G.B.; Gossett, L.S.; Moran, R.G.; Taylor, S.C.; Synthesis and structure-activity relationship studies of 5,10-dideazatetrahydrofolic acid (DDATHF). Chemistry and Biology of Pteridines (1989): Pteridines and Folic Acid Derivatives. H.-C. Curtius, S. Ghisla and N. Blau (Eds.). de Gruyter, New York 1990, 1035.
【2】 Taylor, E.C.; Wong, G.S.K.; Convergent and efficient palladium-effected synthesis of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF). J Org Chem 1989, 54, 15, 3618.
【3】 Castaner, J.; Prous, J.; Lometrexol. Drugs Fut 1993, 18, 2, 121.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
	51602	1-Propyne	C₃H₄	详情	详情
(I)	14277	2,6-Diamino-4(3H)-pyrimidinone	C₄H₆N₄O	详情	详情
(II)	14278	2-Bromomalonaldehyde	C₃H₃BrO₂	详情	详情
(III)	14279	2-Amino-6-bromopyrido[2,3-d]pyrimidin-4(3H)-one	C₇H₅BrN₄O	详情	详情
(IV)	14280	N-(6-Bromo-4-oxo-3,4-dihydropyrido[2,3-d]pyrimidin-2-yl)-2,2-dimethylpropanamide	C₁₂H₁₃BrN₄O₂	详情	详情
(V)	14281	2,2-Dimethyl-N-[4-oxo-6-[2-(trimethylsilyl)ethynyl]-3,4-dihydropyrido[2,3-d]pyrimidin-2-yl]propanamide	C₁₇H₂₂N₄O₂Si	详情	详情
(VI)	14282	N-(6-Ethynyl-4-oxo-3,4-dihydropyrido[2,3-d]pyrimidin-2-yl)-2,2-dimethylpropanamide	C₁₄H₁₄N₄O₂	详情	详情
(VII)	14283	diethyl (2S)-2-[(4-iodobenzoyl)amino]pentanedioate	C₁₆H₂₀INO₅	详情	详情
(VIII)	14284	diethyl (2S)-2-[[4-(2-[2-[(2,2-dimethylpropanoyl)amino]-4-oxo-3,4-dihydropyrido[2,3-d]pyrimidin-6-yl]ethynyl)benzoyl]amino]pentanedioate	C₃₀H₃₃N₅O₇	详情	详情
(IX)	14285	tert-butyl 4-ethynylbenzoate	C₁₃H₁₄O₂	详情	详情
(X)	14286	tert-butyl 4-bromobenzoate	C₁₁H₁₃BrO₂	详情	详情
(XI)	14287	diethyl (2S)-2-[(4-ethynylbenzoyl)amino]pentanedioate	C₁₈H₂₁NO₅	详情	详情
(XII)	14288	tert-butyl 4-(2-[2-[(2,2-dimethylpropanoyl)amino]-4-oxo-3,4-dihydropyrido[2,3-d]pyrimidin-6-yl]ethynyl)benzoate	C₂₅H₂₆N₄O₄	详情	详情
(XIII)	14289	4-(2-[2-[(2,2-Dimethylpropanoyl)amino]-4-oxo-3,4-dihydropyrido[2,3-d]pyrimidin-6-yl]ethynyl)benzoic acid	C₂₁H₁₈N₄O₄	详情	详情
(XIV)	11013	diethyl (2S)-2-aminopentanedioate	C₉H₁₇NO₄	详情	详情
(XV)	14291	diethyl (2S)-2-[[4-(2-[2-[(2,2-dimethylpropanoyl)amino]-4-oxo-3,4,5,6,7,8-hexahydropyrido[2,3-d]pyrimidin-6-yl]ethyl)benzoyl]amino]pentanedioate	C₃₀H₄₁N₅O₇	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

In an alternative synthesis, 2,4,6-triaminopyrimidine (VI) was condensed with bromomalonaldehyde (VII) under acidic conditions to give pyridopyrimidine (VIII), which was protected with pivaloyl anhydride in pyridine, yielding the bispivaloylamide (IX). Palladium-catalyzed Heck coupling of (IX) with styrene (X) afforded (XI). Subsequent ozonolysis of the styryl derivative (XI), followed by reductive workup with dimethyl sulfide gave aldehyde (XII). Reduction of (XII) to the corresponding alcohol with NaBH4, followed by bromination with PPh3 and Br2 provided bromide (XIII). The N-methyl aniline (XIV) was synthesized by direct alkylation of 3,4,5-trimethoxyaniline (IV) with methyl iodide. Nucleophilic displacement of the bromide (XIII) with aniline (XIV) afforded the tertiary amine (XV). The pivaloyl protecting groups of (XV) were finally removed by treatment with methanolic NaOMe.

参考文献中间体

合成目标

【1】 Gangjee, A.; et al.; Synthesis and dihydrofolate reductase inhibitory activities of 2,4-diamino-5-deaza and 2,4-diamino-5, 10-dideaza lipophilic antifolates. J Med Chem 1997, 40, 4, 470.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	31545	3,4,5-trimethoxyaniline; 3,4,5-trimethoxyphenylamine；3,4,5-Trimethoxybenzenamine；[3,4,5-Tris(methyloxy)phenyl]amine	24313-88-0	C₉H₁₃NO₃	详情	详情
(VI)	28977	2,6-diamino-4-pyrimidinylamine	1004-38-2	C₄H₇N₅	详情	详情
(VII)	14278	2-Bromomalonaldehyde		C₃H₃BrO₂	详情	详情
(VIII)	31547	6-bromopyrido[2,3-d]pyrimidine-2,4-diamine; 2-amino-6-bromopyrido[2,3-d]pyrimidin-4-ylamine		C₇H₆BrN₅	详情	详情
(IX)	31548	N-[6-bromo-2-[(2,2-dimethylpropanoyl)amino]pyrido[2,3-d]pyrimidin-4-yl]-2,2-dimethylpropanamide		C₁₇H₂₂BrN₅O₂	详情	详情
(X)	19649	1-vinylbenzene	100-42-5	C₈H₈	详情	详情
(XI)	31549	N-[2-[(2,2-dimethylpropanoyl)amino]-6-[(E)-2-phenylethenyl]pyrido[2,3-d]pyrimidin-4-yl]-2,2-dimethylpropanamide		C₂₅H₂₉N₅O₂	详情	详情
(XII)	31550	N-[2-[(2,2-dimethylpropanoyl)amino]-6-formylpyrido[2,3-d]pyrimidin-4-yl]-2,2-dimethylpropanamide		C₁₈H₂₃N₅O₃	详情	详情
(XIII)	31554	3-bromo-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-5-one		C₁₁H₁₁BrO	详情	详情
(XIV)	31552	3,4,5-trimethoxy-N-methylaniline; N-methyl-N-(3,4,5-trimethoxyphenyl)amine		C₁₀H₁₅NO₃	详情	详情
(XV)	31553	N-(2-[(2,2-dimethylpropanoyl)amino]-6-[[3,4,5-trimethoxy(methyl)anilino]methyl]pyrido[2,3-d]pyrimidin-4-yl)-2,2-dimethylpropanamide		C₂₈H₃₈N₆O₅	详情	详情

Extended Information