5-(chloromethyl)furo[2,3-d]pyrimidine-2,4-diamine; 2-amino-5-(chloromethyl)furo[2,3-d]pyrimidin-4-ylamine -Drug Synthesis Database

【结构式】

【分子编号】18884

【品名】5-(chloromethyl)furo[2,3-d]pyrimidine-2,4-diamine; 2-amino-5-(chloromethyl)furo[2,3-d]pyrimidin-4-ylamine

【CA登记号】

【分子式】C₇H₇ClN₄O

【分子量】198.61164

【元素组成】C 42.33% H 3.55% Cl 17.85% N 28.21% O 8.06%

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：(III)

2,6-Diamino-4-hydroxypyrimidine (I) was cyclized with 1,3-dichloroacetone (II) in DMF at room temperature, and the resulting unstable furopyrimidine (III) was rapidly purified by a short column of silica gel and stored at -20 C. Then, the nucleophilic displacement reaction of chloride (III) with 2-naphthalenethiol (IV) in the presence of potassium carbonate in DMSO yielded the desired thioether.

参考文献中间体

合成目标

【1】 Gangjee, A.; et al.; Selective Pneumocystis carinii dihydrofolate reductase inhibitors: Design, synthesis, and biological evaluation of new 2,4-diamino-5-substituted-furo[2, 3-d]pyrimidines. J Med Chem 1998, 41, 8, 1263.

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)	14811	2,4-Diamino-6-hydroxypyrimidine; 2,6-diamino-4-pyrimidinol	56-06-4	C₄H₆N₄O	详情	详情
(II)	63907	1,3-dichloroacetone		C₃H₄Cl₂O	详情	详情
(III)	18884	5-(chloromethyl)furo[2,3-d]pyrimidine-2,4-diamine; 2-amino-5-(chloromethyl)furo[2,3-d]pyrimidin-4-ylamine		C₇H₇ClN₄O	详情	详情
(IV)	15234	2-Naphthalenethiol; 2-Naphthylhydrosulfide	91-60-1	C₁₀H₈S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Condensation of 2,6-diaminopyrimidin-4-one (I) with 1,3-dichloroacetone (II) affords the furopyrimidine (III). Subsequent reaction of (III) with tributylphosphine provides the phosphonium salt (IV). Treatment of 4-hydroxypropiophenone (V) with trifluoromethanesulfonic anhydride leads to the aryl triflate (VI). This is then subjected to palladium-catalyzed carbonylation under modified Gerlach's conditions to furnish ethyl 4-propionylbenzoate (VII). Wittig condensation between the phosphorane derived from (IV) and keto ester (VII) produces olefin (VIIIa-b) as a mixture of Z/E isomers. Subsequent hydrogenation of (VIIIa-b) over Pd/C gives (IX). The methyl ester group of (IX) is hydrolyzed under alkaline conditions to afford acid (X), which is then activated as the mixed anhydride (XI) with isobutyl chloroformate and triethylamine.

参考文献中间体

合成目标

【1】 Mcguire, J.J.; Zeng, Y.; Gangjee, A.; Kisliuk, R.L.; Synthesis of N-[4-[ethyl-2-(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid as an antifolate. J Med Chem 2002, 45, 9, 1942.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIIIa)	58984	methyl 4-[(Z)-2-(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)-1-ethylethenyl]benzoate		C₁₈H₁₈N₄O₃	详情	详情
(VIIIb)	58985	methyl 4-[(E)-2-(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)-1-ethylethenyl]benzoate		C₁₈H₁₈N₄O₃	详情	详情
(I)	14277	2,6-Diamino-4(3H)-pyrimidinone		C₄H₆N₄O	详情	详情
(II)	63907	1,3-dichloroacetone		C₃H₄Cl₂O	详情	详情
(III)	18884	5-(chloromethyl)furo[2,3-d]pyrimidine-2,4-diamine; 2-amino-5-(chloromethyl)furo[2,3-d]pyrimidin-4-ylamine		C₇H₇ClN₄O	详情	详情
(IV)	58981	tributyl[(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)methyl]phosphonium chloride		C₁₉H₃₄ClN₄OP	详情	详情
(V)	58982	4'-Hydroxypropiophenone; 4-Hydroxypropiophenone; Ethyl 4-Hydroxyphenyl ktone; p-Hydroxypropiophenone; Paroxypropione	70-70-2	C₉H₁₀O₂	详情	详情
(VI)	58983	4-propionylphenyl trifluoromethanesulfonate		C₁₀H₉F₃O₄S	详情	详情
(VII)	11008	methyl 4-propionylbenzoate		C₁₁H₁₂O₃	详情	详情
(IX)	58988	methyl 4-{1-[(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)methyl]propyl}benzoate		C₁₈H₂₀N₄O₃	详情	详情
(X)	58986	4-{1-[(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)methyl]propyl}benzoic acid		C₁₇H₁₈N₄O₃	详情	详情
(XI)	58987			C₂₂H₂₆N₄O₅	详情	详情

Extended Information