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【结 构 式】

【分子编号】26657

【品名】O-methyl isourea; [Amino(imino)methoxy]methane

【CA登记号】52328-05-9

【 分 子 式 】C2H6N2O

【 分 子 量 】74.08252

【元素组成】C 32.43% H 8.16% N 37.81% O 21.6%
与该中间体有关的原料药合成路线共 21 条
合成路线1合成路线2合成路线3合成路线4合成路线5合成路线6合成路线7合成路线8合成路线9合成路线10合成路线11合成路线12合成路线13合成路线14合成路线15合成路线16合成路线17合成路线18合成路线19合成路线20合成路线21

合成路线1

该中间体在本合成路线中的序号：(IV)

The reaction of 1,2,3,5-tetra-O-acetyl-beta-D-ribofuranose (I) with dry HCl in ether-acetic anhydride gives 1-chloro-2,3,5-tri-O-acetyl-beta-D-ribofuranose (II), which by reaction with silver isocyanate in dry xylene is converted into 2,3,5-tri-O-acetyl-beta-D-ribofuranosylisocyanate (III). The reaction of (III) with 2-methylisourea (IV) in dry CHCl3 affords 1-(2,3,5-tri-O-acetyl-3-D-ribofuranosyl)-4-methylisobiuret (V), which is cyclized by reaction with ethyl orthoformate at 135 C yielding 1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-4-methoxy-2-oxo-1,2-dihydro-1,3,5-triazine (VI). Finally, this compound is treated with ammonia in dry methanol.

参考文献 中间体
合成目标
【1】 Sorm, F.; Piskala, A.; Nucleic acid components and their analogues. LI. Synthesis of 1-glycosyl derivatives of 5-azauracil and 5-azacytosine. Coll Czech Chem Commun 1964, 29, 2060-76.
【2】 Von Hoff, D.D.; Azacitidine. Drugs Fut 1980, 5, 8, 392.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(A) 12304 N-[(3R)-9-(2-cyanoethyl)-2,3,4,9-tetrahydro-1H-carbazol-3-yl]-4-fluorobenzenesulfonamide C21H20FN3O2S 详情 详情
(I) 33835 (2R,3R,4R,5S)-4,5-bis(acetoxy)-2-[(acetoxy)methyl]tetrahydro-3-furanyl acetate 13035-61-5 C13H18O9 详情 详情
(II) 39189 (2R,3S,4R,5S)-4-(acetoxy)-2-[(acetoxy)methyl]-5-chlorotetrahydro-3-furanyl acetate C11H15ClO7 详情 详情
(III) 39190 (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-isocyanatotetrahydro-3-furanyl acetate C12H15NO8 详情 详情
(IV) 26657 O-methyl isourea; [Amino(imino)methoxy]methane 52328-05-9 C2H6N2O 详情 详情
(V) 39191 (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-[([[(E)-amino(methoxy)methylidene]amino]carbonyl)amino]tetrahydro-3-furanyl acetate C14H21N3O9 详情 详情
(VI) 39192 (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-[4-methoxy-2-oxo-1,3,5-triazin-1(2H)-yl]tetrahydro-3-furanyl acetate C15H19N3O9 详情 详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The reaction of methyl acetoacetate (I) with 3,4-difluorobenzaldehyde (II) in hot benzene gives the corresponding benzylidene derivative (III), which is cyclized with O-methylisourea (IV) by means of NaHCO3 in hot DMF yielding the dihydropyrimidine (V). The condensation of (V) with 4-nitrophenyl chloroformate (VI) by means of DMAP in dichloromethane affords the 4-nitrophenyl ester (VII), which is brominated with Br2 in chloroform to the bromomethyl compound (VIII). The cyclization of (VIII) by heating at 130 C affords the furopyrimidine (X), which is treated with propylamine derivative (X) in THF or dichloromethane to furnish the target amide.

参考文献 中间体
合成目标
【1】 Chiu, G.; Tian, D.; Lagu, B.; et al.; Synthesis and evaluation of furo[3,4-d]pyrimidinones as selective alpha1a-adrenergic receptor antagonists. Bioorg Med Chem Lett 2000, 10, 2, 175.
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) 11791 methyl 3-oxobutanoate; Methyl acetoacetate 105-45-3 C5H8O3 详情 详情
(II) 26654 3,4-difluorobenzaldehyde 34036-07-2 C7H4F2O 详情 详情
(III) 38075 methyl (Z)-2-acetyl-3-(3,4-difluorophenyl)-2-propenoate C12H10F2O3 详情 详情
(IV) 26657 O-methyl isourea; [Amino(imino)methoxy]methane 52328-05-9 C2H6N2O 详情 详情
(V) 38076 methyl 6-(3,4-difluorophenyl)-2-methoxy-4-methyl-1,6-dihydro-5-pyrimidinecarboxylate C14H14F2N2O3 详情 详情
(VI) 16605 4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene 7693-46-1 C7H4ClNO4 详情 详情
(VII) 38077 5-methyl 1-(4-nitrophenyl) 6-(3,4-difluorophenyl)-2-methoxy-4-methyl-1,5(6H)-pyrimidinedicarboxylate C21H17F2N3O7 详情 详情
(VIII) 38078 5-methyl 1-(4-nitrophenyl) 4-(bromomethyl)-6-(3,4-difluorophenyl)-2-methoxy-1,5(6H)-pyrimidinedicarboxylate C21H16BrF2N3O7 详情 详情
(IX) 38079 4-nitrophenyl 4-(3,4-difluorophenyl)-2-methoxy-5-oxo-5,6-dihydrofuro[2,3-d]pyrimidine-3(4H)-carboxylate C20H13F2N3O7 详情 详情
(X) 25450 methyl 1-(3-aminopropyl)-4-phenyl-4-piperidinecarboxylate C16H24N2O2 详情 详情

合成路线3

该中间体在本合成路线中的序号：(VIII)

The Knoevenagel condensation between benzyl propionylacetate (V) and 2,4-difluorobenzaldehyde (VI) afforded the benzylidene derivative (VII), which was cyclized with O-methylisourea hemisulfate (VIII), yielding the dihydropyrimidine (IX). This compound, upon reaction with 4-nitrophenyl chloroformate, regioselectively produced the carbamate ester (X). Resolution of the enantiomers of (X) was achieved by condensation with the chiral auxiliary (S)-(-)-alpha-methylbenzylamine (XI) to obtain a mixture of diastereomeric amides, which were separated by flash chromatography. The alpha-methylbenzylaminocarbonyl moiety was then removed from the desired diastereomer (+)-(XII) by treatment with DBU, and the resulting chiral dihydropyridine was again condensed with 4-nitrophenyl chloroformate to give (+)-(X). Coupling of the chiral carbamate (+)-(X) with amine (IV) provided adduct (XIII), which on treatment with aqueous HCl gave the dihydropyrimidinone (XIV). After catalytic hydrogenolysis of the benzyl ester of (XIV), the resulting acid was converted to the title amide by reaction with ammonia in the presence of EDC and DMAP.

参考文献 中间体
合成目标
【1】 Marzabadi, M.R.; Murali Dhar, T.G.; Nagarathnam, D.; et al.; Design and synthesis of novel alpha1a adrenoceptor-selective antagonists. 2. Approaches to eliminate opioid agonist metabolites via modification of linker and 4-methoxycarbonyl-4-phenylpiperidine moiety. J Med Chem 1999, 42, 23, 4778.
【2】 Lagu, B.; Nagarathnam, D.; Miao, S.W.; et al.; Design and synthesis of novel alpha1a adrenoceptor-selective antagonists. 1. Structure-activity relationship in dihydropyrimidinones. J Med Chem 1999, 42, 23, 4764.
【3】 Wong, W.C.; Lagu, B.; Nagarathnam, D.; Marzabadi, M.R.; Gluchowski, C. (Synaptic Pharmaceutical Corp.); Dihydropyrimidines and uses thereof. EP 1021185; JP 2000506904; WO 9742956 .
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) 43079 1-(3-aminopropyl)-4-phenyl-4-piperidinecarbonitrile C15H21N3 详情 详情
(V) 43080 benzyl 3-oxopentanoate 4949-45-5 C12H14O3 详情 详情
(VI) 26654 3,4-difluorobenzaldehyde 34036-07-2 C7H4F2O 详情 详情
(VII) 43081 benzyl (Z)-3-(2,4-difluorophenyl)-2-propionyl-2-propenoate C19H16F2O3 详情 详情
(VIII) 26657 O-methyl isourea; [Amino(imino)methoxy]methane 52328-05-9 C2H6N2O 详情 详情
(IX) 43082 benzyl 6-(2,4-difluorophenyl)-4-ethyl-2-methoxy-1,6-dihydro-5-pyrimidinecarboxylate C21H20F2N2O3 详情 详情
(X) 43084 5-benzyl 1-(4-nitrophenyl) 6-(2,4-difluorophenyl)-4-ethyl-2-methoxy-1,5(6H)-pyrimidinedicarboxylate C28H23F2N3O7 详情 详情
(XI) 10039 (1R)-1-Phenylethylamine; (1R)-1-Phenyl-1-ethanamine.; L-alpha-Phenylethylamine 3886-69-9 C8H11N 详情 详情
(XII) 43083 benzyl 6-(2,4-difluorophenyl)-4-ethyl-2-methoxy-1-([[(1R)-1-phenylethyl]amino]carbonyl)-1,6-dihydro-5-pyrimidinecarboxylate C30H29F2N3O4 详情 详情
(XIII) 43085 benzyl 1-([[3-(4-cyano-4-phenyl-1-piperidinyl)propyl]amino]carbonyl)-6-(2,4-difluorophenyl)-4-ethyl-2-methoxy-1,6-dihydro-5-pyrimidinecarboxylate C37H39F2N5O4 详情 详情
(XIV) 43086 benzyl 3-([[3-(4-cyano-4-phenyl-1-piperidinyl)propyl]amino]carbonyl)-4-(2,4-difluorophenyl)-6-ethyl-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate C36H37F2N5O4 详情 详情

合成路线4

该中间体在本合成路线中的序号：(IV)

The Knoevenagel condensation between methyl acetoacetate (I) and 3,4-difluorobenzaldehyde (II) afforded the benzylidene derivative (III), which was cyclized with O-methylisourea hemisulfate (IV), yielding the dihydropyrimidine (V). This compound, upon reaction with 4-nitrophenyl chloroformate, regioselectively produced the carbamate ester (VI) (1,2). Treatment of (VI) with aqueous HCl gave the dihydropyrimidinone (VII), which was subsequently coupled with 3-bromopropylamine·HBr (VIII) to give the bromopropyl amide (IX) (1). The intermediate N-(2-carboxamidophenyl)piperazine (XIII) was obtained by condensation of 2-bromobenzonitrile (X) with piperazine (XI), followed by partial hydrolysis of the nitrile group with H2SO4. The title compound was finally obtained by condensation between piperazine (XIII) and bromide (IX) in the presence of KI and K2CO3 in refluxing acetone.

参考文献 中间体
合成目标
【1】 Lagu, B.; Nagarathnam, D.; Miao, S.W.; et al.; Design and synthesis of novel alpha1a adrenoceptor-selective antagonists. 1. Structure-activity relationship in dihydropyrimidinones. J Med Chem 1999, 42, 23, 4764.
【2】 Marzabadi, M.R.; Murali Dhar, T.G.; Nagarathnam, D.; et al.; Design and synthesis of novel alpha1a adrenoceptor-selective antagonists. 2. Approaches to eliminate opioid agonist metabolites via modification of linker and 4-methoxycarbonyl-4-phenylpiperidine moiety. J Med Chem 1999, 42, 23, 4778.
【3】 Wong, W.C.; Lagu, B.; Nagarathnam, D.; Marzabadi, M.R.; Gluchowski, C. (Synaptic Pharmaceutical Corp.); Dihydropyrimidines and uses thereof. EP 1021185; JP 2000506904; WO 9742956 .
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) 11791 methyl 3-oxobutanoate; Methyl acetoacetate 105-45-3 C5H8O3 详情 详情
(II) 26654 3,4-difluorobenzaldehyde 34036-07-2 C7H4F2O 详情 详情
(III) 38075 methyl (Z)-2-acetyl-3-(3,4-difluorophenyl)-2-propenoate C12H10F2O3 详情 详情
(IV) 26657 O-methyl isourea; [Amino(imino)methoxy]methane 52328-05-9 C2H6N2O 详情 详情
(V) 38076 methyl 6-(3,4-difluorophenyl)-2-methoxy-4-methyl-1,6-dihydro-5-pyrimidinecarboxylate C14H14F2N2O3 详情 详情
(VI) 43072 5-benzyl 1-(4-nitrophenyl) 6-(3,4-difluorophenyl)-2-methoxy-4-methyl-1,5(6H)-pyrimidinedicarboxylate C27H21F2N3O7 详情 详情
(VII) 43073 5-benzyl 1-(4-nitrophenyl) 6-(3,4-difluorophenyl)-4-methyl-2-oxo-3,6-dihydro-1,5(2H)-pyrimidinedicarboxylate C26H19F2N3O7 详情 详情
(VIII) 25449 3-bromo-1-propanamine; 3-bromopropylamine 18370-81-5 C3H8BrN 详情 详情
(IX) 43074 benzyl 3-[[(3-bromopropyl)amino]carbonyl]-4-(3,4-difluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate C23H22BrF2N3O4 详情 详情
(X) 15541 o-bromobenzonitrile; 2-bromobenzonitrile 2042-37-7 C7H4BrN 详情 详情
(XI) 10355 Diethylenediamine; Piperazine 110-85-0 C4H10N2 详情 详情
(XII) 43075 2-(1-piperazinyl)benzonitrile C11H13N3 详情 详情
(XIII) 43076 2-(1-piperazinyl)benzamide C11H15N3O 详情 详情

合成路线5

该中间体在本合成路线中的序号：(III)

The reaction of ethylenediamine (I) with Boc2O in dioxane gives the monocarbamate (II), which is condensed with O-methylisourea (III) to yield the aminoguanidine carbamate (IV). The cleavage of the carbamate group of (IV) by means of HCl in methanol affords the aminoguanidine (V), which is condensed with 1-methyl-4-nitropyrrole-2-carbonyl chloride (VI) by means of NaHCO3 in dioxane/water to provide the amide (VII). The reduction of the nitro group of (VII) by means of H2 over Pd/C in 1N HCl affords the 4-aminopyrrole-2-carboxamide (VIII), which is condensed with the acid chloride (VI) as before to give the diamide (IX). Reduction of the nitro group of (IX) under the same conditions described above yields the amino diamide (X), which is condensed with the 14-labeled acid chloride (XI) as described above to afford the triamide (XII). Further reduction of the nitro group of (XII) gives the amino triamide (XIII), which is finally condensed with 4-(2-bromopropenamido)-1-methylpyrrole-2-carbonyl chloride (XIV) by means of NaHCO3 in dioxane/water to yield the target 14C labeled pentaamide compound.

参考文献 中间体
合成目标
【1】 Fontana, E.; Pignatti, A.; Synthesis of brostallicin (PNU-166196A) labelled with 2H and 14C. Label. Cop. & Radiopharm. 2002, 45, 11, 899.
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) 14754 ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine 107-15-3 C2H8N2 详情 详情
(II) 13241 N-Boc-ethylenediamine;tert-butyl (2-aminoethyl)carbamate；tert-butyl 2-aminoethylcarbamate; tert-Butyl n-(2-aminoethyl)carbamate 57260-73-8 C7H16N2O2 详情 详情
(III) 26657 O-methyl isourea; [Amino(imino)methoxy]methane 52328-05-9 C2H6N2O 详情 详情
(IV) 41436 tert-butyl 2-[[amino(imino)methyl]amino]ethylcarbamate C8H18N4O2 详情 详情
(V) 41437 N-(2-aminoethyl)guanidine C3H10N4 详情 详情
(VI) 27852 1-methyl-4-nitro-1H-pyrrole-2-carbonyl chloride C6H5ClN2O3 详情 详情
(VII) 41445 N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-4-nitro-1H-pyrrole-2-carboxamide C9H14N6O3 详情 详情
(VIII) 41446 4-amino-N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-1H-pyrrole-2-carboxamide C9H16N6O 详情 详情
(IX) 41447 N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-4-[[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrole-2-carboxamide C15H20N8O4 详情 详情
(X) 41448 N-(2-[[amino(imino)methyl]amino]ethyl)-4-[[(4-amino-1-methyl-1H-pyrrol-2-yl)carbonyl]amino]-1-methyl-1H-pyrrole-2-carboxamide C15H22N8O2 详情 详情
(XI) 65171 1-methyl-4-nitro-1H-pyrrole-2-carbonyl chloride 28494-51-1 C6H5ClN2O3 详情 详情
(XII) 41443 N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-4-[[(1-methyl-4-[[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrole-2-carboxamide C21H26N10O5 详情 详情
(XIII) 61732 4-amino-N-(5-{[(5-{[(2-{[amino(imino)methyl]amino}ethyl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide C21H28N10O3 详情 详情
(XIV) 41441 4-[(2-bromoacryloyl)amino]-1-methyl-1H-pyrrole-2-carbonyl chloride C9H8BrClN2O2 详情 详情

合成路线6

该中间体在本合成路线中的序号：(III)

The reaction of deuterium labeled ethylenediamine (I) with Boc2O in dioxane gives the monocarbamate (II), which is condensed with O-methylisourea (III) to yield the labeled aminoguanidine carbamate (IV). The cleavage of the carbamate group of (IV) by means of HCl in methanol affords the aminoguanidine (V), which is condensed with 1-methyl-4-nitropyrrole-2-carbonyl chloride (VI) by means of NaHCO3 in dioxane/water to provide the amide (VII). The reduction of the nitro group of (VII) by means of H2 over Pd/C in 1N HCl affords the 4-aminopyrrole-2-carboxamide (VIII), which is condensed with the acid chloride (VI) as before to give the diamide (IX). Reduction of the nitro group of (IX) under the same conditions described above yields the amino diamide (X), which is condensed with acid chloride (VI) as described above to afford the triamide (XI). Further reduction of the nitro group of (XI) gives the amino triamide (XII), which is finally condensed with 4-(2-bromopropenamido)-1-methylpyrrole-2-carbonyl chloride (XIII) by means of NaHCO3 in dioxane/water to yield the target deuterium labeled pentaamide compound.

参考文献 中间体
合成目标
【1】 Fontana, E.; Pignatti, A.; Synthesis of brostallicin (PNU-166196A) labelled with 2H and 14C. Label. Cop. & Radiopharm. 2002, 45, 11, 899.
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) 14754 ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine 107-15-3 C2H8N2 详情 详情
(II) 13241 N-Boc-ethylenediamine;tert-butyl (2-aminoethyl)carbamate；tert-butyl 2-aminoethylcarbamate; tert-Butyl n-(2-aminoethyl)carbamate 57260-73-8 C7H16N2O2 详情 详情
(III) 26657 O-methyl isourea; [Amino(imino)methoxy]methane 52328-05-9 C2H6N2O 详情 详情
(IV) 41436 tert-butyl 2-[[amino(imino)methyl]amino]ethylcarbamate C8H18N4O2 详情 详情
(V) 41437 N-(2-aminoethyl)guanidine C3H10N4 详情 详情
(VI) 27852 1-methyl-4-nitro-1H-pyrrole-2-carbonyl chloride C6H5ClN2O3 详情 详情
(VII) 41445 N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-4-nitro-1H-pyrrole-2-carboxamide C9H14N6O3 详情 详情
(VIII) 41446 4-amino-N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-1H-pyrrole-2-carboxamide C9H16N6O 详情 详情
(IX) 41447 N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-4-[[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrole-2-carboxamide C15H20N8O4 详情 详情
(X) 41448 N-(2-[[amino(imino)methyl]amino]ethyl)-4-[[(4-amino-1-methyl-1H-pyrrol-2-yl)carbonyl]amino]-1-methyl-1H-pyrrole-2-carboxamide C15H22N8O2 详情 详情
(XI) 41443 N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-4-[[(1-methyl-4-[[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrole-2-carboxamide C21H26N10O5 详情 详情
(XII) 41444 N-(2-[[amino(imino)methyl]amino]ethyl)-4-[[(4-[[(4-amino-1-methyl-1H-pyrrol-2-yl)carbonyl]amino]-1-methyl-1H-pyrrol-2-yl)carbonyl]amino]-1-methyl-1H-pyrrole-2-carboxamide C21H28N10O3 详情 详情
(XIII) 41441 4-[(2-bromoacryloyl)amino]-1-methyl-1H-pyrrole-2-carbonyl chloride C9H8BrClN2O2 详情 详情

合成路线7

该中间体在本合成路线中的序号：(IV)

The reaction of 3,4-difluorobenzaldehyde (I) with methyl 4-methoxyacetoacetate (II) by means of piperidinium acetate in benzene gives the 3-benzylidene derivative (III), which is cyclized with O-methylisourea (IV) yielding dihydropyrimidine (V). The optical resolution of dihydropyrimidine (V) can also be performed as follows: Dihydropyrimidine (V) is condensed with 4-nitrophenyl chloroformate (VI) by means of DMAP giving the 4-nitrophenyl ester (VII), which is treated with (R)-(+)-alpha-methylbenzylamine [(R)-MBA] yielding amide (VIII) as mixture of diastereomers that is separated by column chromatography. The (+) isomer was then treated with DBU in hot toluene to provide the dihydropyrimidine (+)(IX), already reported. The intermediate 2-(trans-4-cyano-4-phenylcyclohexyl)ethylamine (XII) has been obtained by reductocondensation of 4-cyano-4-phenylcyclohexanone (XIII) with ethylenediamine (XIV) by means of p-toluenesulfonic acid and NaBH4 and separation of the isomers by careful chromatography.

参考文献 中间体
合成目标
【1】 Nagarathnam, D.; et al.; Design, synthesis and evaluation of dihydropyrimidinones as alpha-1A selective antagonists: 7. Modification of the piperidine moiety into 4-aminocyclohexane; identification and structure-activity relationship of SNAP 6991 analogs. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 110.
【2】 Nagarathnam, D.; Wong, W.C.; Miao, S.W.; Patane, M.A.; Gluchowski, C. (Merck & Co., Inc.; Synaptic Pharmaceutical Corp.); Dihydropyrimidines and uses thereof. EP 0866708; JP 2000500470; WO 9717969 .
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) 26654 3,4-difluorobenzaldehyde 34036-07-2 C7H4F2O 详情 详情
(II) 26655 methyl 4-methoxy-3-oxobutanoate;Methyl 4-methoxyacetoacetate;Methyl 4-methoxy-3-oxo-butanoate 41051-15-4 C6H10O4 详情 详情
(III) 26656 methyl (Z)-3-(3,4-difluorophenyl)-2-(2-methoxyacetyl)-2-propenoate C13H12F2O4 详情 详情
(IV) 26657 O-methyl isourea; [Amino(imino)methoxy]methane 52328-05-9 C2H6N2O 详情 详情
(V) 26658 methyl 6-(3,4-difluorophenyl)-2-methoxy-4-(methoxymethyl)-1,6-dihydro-5-pyrimidinecarboxylate C15H16F2N2O4 详情 详情
(VI) 16605 4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene 7693-46-1 C7H4ClNO4 详情 详情
(VII) 26659 5-methyl 1-(4-nitrophenyl) 6-(3,4-difluorophenyl)-2-methoxy-4-(methoxymethyl)-1,5(6H)-pyrimidinedicarboxylate C22H19F2N3O8 详情 详情
(VIII) 26660 methyl 6-(3,4-difluorophenyl)-2-methoxy-4-(methoxymethyl)-1-[[(1-phenylethyl)amino]carbonyl]-1,6-dihydro-5-pyrimidinecarboxylate C24H25F2N3O5 详情 详情
(IX) 26658 methyl 6-(3,4-difluorophenyl)-2-methoxy-4-(methoxymethyl)-1,6-dihydro-5-pyrimidinecarboxylate C15H16F2N2O4 详情 详情
(X) 16606 Isobutyramide; 2-methylpropanamide 563-83-7 C4H9NO 详情 详情
(XI) 26659 5-methyl 1-(4-nitrophenyl) 6-(3,4-difluorophenyl)-2-methoxy-4-(methoxymethyl)-1,5(6H)-pyrimidinedicarboxylate C22H19F2N3O8 详情 详情
(XII) 26661 5-methyl 1-(4-nitrophenyl) 6-(3,4-difluorophenyl)-4-(methoxymethyl)-2-oxo-3,6-dihydro-1,5(2H)-pyrimidinedicarboxylate C21H17F2N3O8 详情 详情
(XIII) 26662 4-[(2-aminoethyl)amino]-1-phenylcyclohexanecarbonitrile C15H21N3 详情 详情
(XIV) 26663 4-oxo-1-phenylcyclohexanecarbonitrile 25115-74-6 C13H13NO 详情 详情
(XV) 14754 ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine 107-15-3 C2H8N2 详情 详情

合成路线8

该中间体在本合成路线中的序号：(IV)

The reaction of 3,4-difluorobenzaldehyde (I) with methyl 4-methoxyacetoacetate (II) by means of piperidinium acetate in benzene gives the 3-benzylidene derivative (III), which is cyclized with O-methylisourea (IV) yielding dihydropyrimidine (V). The optical resolution of (V) by chiral chromatography affords the (+)(IX) isomer, which is condensed with 4-nitrophenyl chloroformate (VI) by means of DMAP in dichloromethane giving the active 4-nitrophenyl ester (+)(X). The hydrolysis of the enol methyl ether of (X) with HCl in ether/dichloromethane yields the pyrimidinone (+)(XI), which is finally condensed with 2-(trans-4-cyano-4-phenylcyclohexyl)ethylamine (XII) in dichloromethane. The intermediate 2-(trans-4-cyano-4-phenylcyclohexyl)ethylamine (XII) has been obtained by reductocondensation of 4-cyano-4-phenylcyclohexanone (XIII) with ethylenediamine (XIV) by means of p-toluenesulfonic acid and NaBH4 and separation of the isomers by careful chromatography.

参考文献 中间体
合成目标
【1】 Nagarathnam, D.; et al.; Design, synthesis and evaluation of dihydropyrimidinones as alpha-1A selective antagonists: 7. Modification of the piperidine moiety into 4-aminocyclohexane; identification and structure-activity relationship of SNAP 6991 analogs. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 110.
【2】 Nagarathnam, D.; Wong, W.C.; Miao, S.W.; Patane, M.A.; Gluchowski, C. (Merck & Co., Inc.; Synaptic Pharmaceutical Corp.); Dihydropyrimidines and uses thereof. EP 0866708; JP 2000500470; WO 9717969 .
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) 26654 3,4-difluorobenzaldehyde 34036-07-2 C7H4F2O 详情 详情
(II) 26655 methyl 4-methoxy-3-oxobutanoate;Methyl 4-methoxyacetoacetate;Methyl 4-methoxy-3-oxo-butanoate 41051-15-4 C6H10O4 详情 详情
(III) 26656 methyl (Z)-3-(3,4-difluorophenyl)-2-(2-methoxyacetyl)-2-propenoate C13H12F2O4 详情 详情
(IV) 26657 O-methyl isourea; [Amino(imino)methoxy]methane 52328-05-9 C2H6N2O 详情 详情
(V) 26658 methyl 6-(3,4-difluorophenyl)-2-methoxy-4-(methoxymethyl)-1,6-dihydro-5-pyrimidinecarboxylate C15H16F2N2O4 详情 详情
(IX) 26658 methyl 6-(3,4-difluorophenyl)-2-methoxy-4-(methoxymethyl)-1,6-dihydro-5-pyrimidinecarboxylate C15H16F2N2O4 详情 详情
(X) 16606 Isobutyramide; 2-methylpropanamide 563-83-7 C4H9NO 详情 详情
(XI) 26659 5-methyl 1-(4-nitrophenyl) 6-(3,4-difluorophenyl)-2-methoxy-4-(methoxymethyl)-1,5(6H)-pyrimidinedicarboxylate C22H19F2N3O8 详情 详情
(XII) 26661 5-methyl 1-(4-nitrophenyl) 6-(3,4-difluorophenyl)-4-(methoxymethyl)-2-oxo-3,6-dihydro-1,5(2H)-pyrimidinedicarboxylate C21H17F2N3O8 详情 详情
(XIII) 26662 4-[(2-aminoethyl)amino]-1-phenylcyclohexanecarbonitrile C15H21N3 详情 详情
(XIV) 26663 4-oxo-1-phenylcyclohexanecarbonitrile 25115-74-6 C13H13NO 详情 详情
(XV) 14754 ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine 107-15-3 C2H8N2 详情 详情

合成路线9

该中间体在本合成路线中的序号：(XIX)

Methyl 4-methoxyacetoacetate (XIV) was transesterified with 3-hydroxypropionitrile (XV) at 180 C to yield the 2-cyanoethyl ester (XVI). Subsequent condensation between 3,4-difluorobenzaldehyde (XVII) and ketoester (XVI) in the presence of piperidine acetate furnished the benzylidene derivative (XVIII), which was cyclized with O-methylisourea hemisulfate (XIX) to produce the racemic pyrimidine (XX). Resolution of (XX) was achieved via conversion to the 4-nitrophenyl carbamate (XXI), which was then condensed with (R)-1-phenylethylamine (XXII) to afford a separable mixture of diastereoisomeric amides. The desired isomer (XXIII) was treated with DBU in hot toluene to give the (+)-pyrimidine (XXIV). This was again converted to the corresponding 4-nitrophenyl carbamate (XXV) by reaction with 4-nitrophenyl chloroformate and DMAP.

参考文献 中间体
合成目标
【1】 Wong, W.C.; Lagu, B.; Nagarathnam, D.; Marzabadi, M.R.; Gluchowski, C. (Synaptic Pharmaceutical Corp.); Dihydropyrimidines and uses thereof. EP 1021185; JP 2000506904; WO 9742956 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XIV) 26655 methyl 4-methoxy-3-oxobutanoate;Methyl 4-methoxyacetoacetate;Methyl 4-methoxy-3-oxo-butanoate 41051-15-4 C6H10O4 详情 详情
(XV) 14029 Ethylene cyanohydrin; ECN; 3-Hydroxypropanenitrile 109-78-4 C3H5NO 详情 详情
(XVI) 48390 2-cyanoethyl 4-methoxy-3-oxobutanoate C8H11NO4 详情 详情
(XVII) 26654 3,4-difluorobenzaldehyde 34036-07-2 C7H4F2O 详情 详情
(XVIII) 48391 2-cyanoethyl (Z)-3-(3,4-difluorophenyl)-2-(2-methoxyacetyl)-2-propenoate C15H13F2NO4 详情 详情
(XIX) 26657 O-methyl isourea; [Amino(imino)methoxy]methane 52328-05-9 C2H6N2O 详情 详情
(XX) 48392 2-cyanoethyl 6-(3,4-difluorophenyl)-2-methoxy-4-(methoxymethyl)-1,6-dihydro-5-pyrimidinecarboxylate C17H17F2N3O4 详情 详情
(XXI) 48393 5-(2-cyanoethyl) 1-(4-nitrophenyl) 6-(3,4-difluorophenyl)-2-methoxy-4-(methoxymethyl)-1,5(6H)-pyrimidinedicarboxylate C24H20F2N4O8 详情 详情
(XXII) 10039 (1R)-1-Phenylethylamine; (1R)-1-Phenyl-1-ethanamine.; L-alpha-Phenylethylamine 3886-69-9 C8H11N 详情 详情
(XXIII) 48394 2-cyanoethyl (6S)-6-(3,4-difluorophenyl)-2-methoxy-4-(methoxymethyl)-1-([[(1R)-1-phenylethyl]amino]carbonyl)-1,6-dihydro-5-pyrimidinecarboxylate C26H26F2N4O5 详情 详情
(XXIV) 48395 2-cyanoethyl (6S)-6-(3,4-difluorophenyl)-2-methoxy-4-(methoxymethyl)-1,6-dihydro-5-pyrimidinecarboxylate C17H17F2N3O4 详情 详情
(XXV) 48396 5-(2-cyanoethyl) 1-(4-nitrophenyl) (6S)-6-(3,4-difluorophenyl)-2-methoxy-4-(methoxymethyl)-1,5(6H)-pyrimidinedicarboxylate C24H20F2N4O8 详情 详情

合成路线10

该中间体在本合成路线中的序号：(II)

Condensation of 2-methyl-4-phenyl-3-oxobutanoic acid methyl ester (I) with O-methyl isourea (II) led to the formation of 5-methyl-6-benzyl-3,4-dihydro-2-methoxy-4-oxopyrimidine (III). Subsequent displacement of the methoxy group linked at C-2 of the pyrimidine ring by treatment with isobutoxy sodium salt (IV) furnished 2-isobutoxy-5-methyl-6-benzyl-3,4-dihydro-4-oxopyrimidine.

参考文献 中间体
合成目标
【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159.
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) 51789 methyl (Z)-3-hydroxy-2-methyl-4-phenyl-2-butenoate C12H14O3 详情 详情
(II) 26657 O-methyl isourea; [Amino(imino)methoxy]methane 52328-05-9 C2H6N2O 详情 详情
(III) 51790 6-benzyl-2-methoxy-5-methyl-4(3H)-pyrimidinone C13H14N2O2 详情 详情
(IV) 51779 sodium 2-butanolate C4H9NaO 详情 详情

合成路线11

该中间体在本合成路线中的序号：(II)

Condensation of 4-phenyl-3-oxobutanoic acid methyl ester (I) with O-methyl isourea (II) led to the formation of 6-benzyl-3,4-dihydro-2-methoxy-4-oxopyrimidine (III). Subsequent displacement of the methoxy group linked at C-2 of the pyrimidine ring by treatment with isobutoxy sodium salt (IV) furnished 2-isobutoxy-6-benzyl-3,4-dihydro-4-oxopyrimidine

参考文献 中间体
合成目标
【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159.
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) 51791 methyl (Z)-3-hydroxy-4-phenyl-2-butenoate C11H12O3 详情 详情
(II) 26657 O-methyl isourea; [Amino(imino)methoxy]methane 52328-05-9 C2H6N2O 详情 详情
(III) 51792 6-benzyl-2-methoxy-4(3H)-pyrimidinone C12H12N2O2 详情 详情
(IV) 51779 sodium 2-butanolate C4H9NaO 详情 详情

合成路线12

该中间体在本合成路线中的序号：(II)

Condensation of 4-phenyl-3-oxobutanoic acid methyl ester (I) with O-methyl isourea (II) led to the formation of 6-benzyl-3,4-dihydro-2-methoxy-4-oxopyrimidine (III). Subsequent displacement of the methoxy group linked at C-2 of the pyrimidine ring by treatment with cyclohexoxy sodium salt (IV) furnished 2-cyclohexoxy-6-benzyl-3,4-dihydro-4-oxopyrimidine.

参考文献 中间体
合成目标
【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159.
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) 51791 methyl (Z)-3-hydroxy-4-phenyl-2-butenoate C11H12O3 详情 详情
(II) 26657 O-methyl isourea; [Amino(imino)methoxy]methane 52328-05-9 C2H6N2O 详情 详情
(III) 51792 6-benzyl-2-methoxy-4(3H)-pyrimidinone C12H12N2O2 详情 详情
(IV) 51780 sodium cyclohexanolate C6H11NaO 详情 详情

合成路线13

该中间体在本合成路线中的序号：(II)

Condensation of 2-methyl-4-phenyl-3-oxobutanoic acid methyl ester (I) with O-methyl isourea (II) led to the formation of 5-methyl-6-benzyl-3,4-dihydro-2-methoxy-4-oxopyrimidine (III). Subsequent displacement of the methoxy group linked at C-2 of the pyrimidine ring by treatment with alkoxy or cyclohexoxy potassium salt furnished 2-cyclohexoxy-5-methyl-6-benzyl-3,4-dihydro-4-oxopyrimidine

参考文献 中间体
合成目标
【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159.
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) 51789 methyl (Z)-3-hydroxy-2-methyl-4-phenyl-2-butenoate C12H14O3 详情 详情
(II) 26657 O-methyl isourea; [Amino(imino)methoxy]methane 52328-05-9 C2H6N2O 详情 详情
(III) 51790 6-benzyl-2-methoxy-5-methyl-4(3H)-pyrimidinone C13H14N2O2 详情 详情
(IV) 51780 sodium cyclohexanolate C6H11NaO 详情 详情

合成路线14

该中间体在本合成路线中的序号：(II)

Condensation of 4-(3-methylphenyl)-3-oxobutanoic acid methyl ester (I) with O-methyl isourea (II) led to the formation of 6-(3-methylbenzyl)-3,4-dihydro-2-methoxy-4-oxopyrimidine (III). Subsequent displacement of the methoxy group linked at C-2 of the pyrimidine ring by treatment with cyclohexoxy potassium salt furnished 2-cyclohexoxy-5-methyl-6-benzyl-3,4-dihydro-4-oxopyrimidine

参考文献 中间体
合成目标
【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159.
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) 51787 methyl (Z)-3-hydroxy-4-(3-methylphenyl)-2-butenoate C12H14O3 详情 详情
(II) 26657 O-methyl isourea; [Amino(imino)methoxy]methane 52328-05-9 C2H6N2O 详情 详情
(III) 51788 2-methoxy-6-(3-methylbenzyl)-4(3H)-pyrimidinone C13H14N2O2 详情 详情
(IV) 51780 sodium cyclohexanolate C6H11NaO 详情 详情

合成路线15

该中间体在本合成路线中的序号：(II)

Condensation of 2-methyl-4-(3-methylbenzyl)-3-oxobutanoic acid methyl ester (I) with O-methyl isourea (II) led to the formation of 5-methyl-6-(3-methylbenzyl)-3,4-dihydro-2-methoxy-4-oxopyrimidine (III). Subsequent displacement of the methoxy group linked at C-2 of the pyrimidine ring by treatment with cyclohexoxy potassium salt furnished 2-cyclohexoxy-5-methyl-6-(3-methylphenyl)-3,4-dihydro-4-oxopyrimidine

参考文献 中间体
合成目标
【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159.
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) 51785 methyl (Z)-3-hydroxy-2-methyl-4-(3-methylphenyl)-2-butenoate C13H16O3 详情 详情
(II) 26657 O-methyl isourea; [Amino(imino)methoxy]methane 52328-05-9 C2H6N2O 详情 详情
(III) 51786 2-methoxy-5-methyl-6-(3-methylbenzyl)-4(3H)-pyrimidinone C14H16N2O2 详情 详情
(IV) 51780 sodium cyclohexanolate C6H11NaO 详情 详情

合成路线16

该中间体在本合成路线中的序号：(II)

Condensation of 4-(3,5-dimethylphenyl)-3-oxobutanoic acid methyl ester (I) with O-methyl isourea (II) led to the formation of 6-(3,5-dimethylbenzyl)-3,4-dihydro-2-methoxy-4-oxopyrimidine (III). Subsequent displacement of the methoxy group linked at C-2 of the pyrimidine ring by treatment with cyclohexoxy potassium salt furnished 2-cyclohexoxy-6-(3,5-dimethylphenyl)-3,4-dihydro-4-oxopyrimidine

参考文献 中间体
合成目标
【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159.
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) 51783 methyl (Z)-4-(3,5-dimethylphenyl)-3-hydroxy-2-butenoate C13H16O3 详情 详情
(II) 26657 O-methyl isourea; [Amino(imino)methoxy]methane 52328-05-9 C2H6N2O 详情 详情
(III) 51784 6-(3,5-dimethylbenzyl)-2-methoxy-4(3H)-pyrimidinone C14H16N2O2 详情 详情
(IV) 51780 sodium cyclohexanolate C6H11NaO 详情 详情

合成路线17

该中间体在本合成路线中的序号：(II)

Condensation of 2-methyl-4-(3,5-dimethylphenyl)-3-oxobutanoic acid methyl ester (I) with O-methyl isourea (II) led to the formation of 5-methyl-6-(3,5-dimethylbenzyl)-3,4-dihydro-2-methoxy-4-oxopyrimidine (III). Subsequent displacement of the methoxy group linked at C-2 of the pyrimidine ring by treatment with cyclohexoxy potassium salt furnished 2-cyclohexoxy-5-methyl-6-(3,5-dimethylphenyl)-3,4-dihydro-4-oxopyrimidine

参考文献 中间体
合成目标
【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159.
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) 51781 methyl (Z)-4-(3,5-dimethylphenyl)-3-hydroxy-2-methyl-2-butenoate C14H18O3 详情 详情
(II) 26657 O-methyl isourea; [Amino(imino)methoxy]methane 52328-05-9 C2H6N2O 详情 详情
(III) 51782 6-(3,5-dimethylbenzyl)-2-methoxy-5-methyl-4(3H)-pyrimidinone C15H18N2O2 详情 详情
(IV) 51780 sodium cyclohexanolate C6H11NaO 详情 详情

合成路线18

该中间体在本合成路线中的序号：(II)

Condensation of 2-methyl-4-(3-methylbenzyl)-3-oxobutanoic acid methyl ester (I) with O-methyl isourea (II) led to the formation of 5-methyl-6-(3-methylbenzyl)-3,4-dihydro-2-methoxy-4-oxopyrimidine (III). Subsequent displacement of the methoxy group linked at C-2 of the pyrimidine ring by treatment with sec-butoxy potassium salt furnished 2-sec-butoxy-5-methyl-6-(3-methylphenyl)-3,4-dihydro-4-oxopyrimidine

参考文献 中间体
合成目标
【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159.
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) 51785 methyl (Z)-3-hydroxy-2-methyl-4-(3-methylphenyl)-2-butenoate C13H16O3 详情 详情
(II) 26657 O-methyl isourea; [Amino(imino)methoxy]methane 52328-05-9 C2H6N2O 详情 详情
(III) 51786 2-methoxy-5-methyl-6-(3-methylbenzyl)-4(3H)-pyrimidinone C14H16N2O2 详情 详情
(IV) 51779 sodium 2-butanolate C4H9NaO 详情 详情

合成路线19

该中间体在本合成路线中的序号：(II)

Condensation of 4-(3-methylphenyl)-3-oxobutanoic acid methyl ester (I) with O-methyl isourea (II) led to the formation of 6-(3-methylbenzyl)-3,4-dihydro-2-methoxy-4-oxopyrimidine (III). Subsequent displacement of the methoxy group linked at C-2 of the pyrimidine ring by treatment with sec-butoxy potassium salt furnished 2-sec-butoxy-5-methyl-6-benzyl-3,4-dihydro-4-oxopyrimidine

参考文献 中间体
合成目标
【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159.
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) 51787 methyl (Z)-3-hydroxy-4-(3-methylphenyl)-2-butenoate C12H14O3 详情 详情
(II) 26657 O-methyl isourea; [Amino(imino)methoxy]methane 52328-05-9 C2H6N2O 详情 详情
(III) 51788 2-methoxy-6-(3-methylbenzyl)-4(3H)-pyrimidinone C13H14N2O2 详情 详情
(IV) 51779 sodium 2-butanolate C4H9NaO 详情 详情

合成路线20

该中间体在本合成路线中的序号：(II)

Condensation of 2-methyl-4-(3,5-dimethylphenyl)-3-oxobutanoic acid methyl ester (I) with O-methyl isourea (II) led to the formation of 5-methyl-6-(3,5-dimethylbenzyl)-3,4-dihydro-2-methoxy-4-oxopyrimidine (III). Subsequent displacement of the methoxy group linked at C-2 of the pyrimidine ring by treatment with sec-butoxy potassium salt furnished 2-sec-butoxy-5-methyl-6-(3,5-dimethylphenyl)-3,4-dihydro-4-oxopyrimidine

参考文献 中间体
合成目标
【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159.
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) 51781 methyl (Z)-4-(3,5-dimethylphenyl)-3-hydroxy-2-methyl-2-butenoate C14H18O3 详情 详情
(II) 26657 O-methyl isourea; [Amino(imino)methoxy]methane 52328-05-9 C2H6N2O 详情 详情
(III) 51782 6-(3,5-dimethylbenzyl)-2-methoxy-5-methyl-4(3H)-pyrimidinone C15H18N2O2 详情 详情
(IV) 51779 sodium 2-butanolate C4H9NaO 详情 详情

合成路线21

该中间体在本合成路线中的序号：(II)

Condensation of 4-(3,5-dimethylphenyl)-3-oxobutanoic acid methyl ester (I) with O-methyl isourea (II) led to the formation of 6-(3,5-dimethylbenzyl)-3,4-dihydro-2-methoxy-4-oxopyrimidine (III). Subsequent displacement of the methoxy group linked at C-2 of the pyrimidine ring by treatment with sec-butoxy potassium salt furnished 2-sec-butoxy-6-(3,5-dimethylphenyl)-3,4-dihydro-4-oxopyrimidine

参考文献 中间体
合成目标
【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159.
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) 51783 methyl (Z)-4-(3,5-dimethylphenyl)-3-hydroxy-2-butenoate C13H16O3 详情 详情
(II) 26657 O-methyl isourea; [Amino(imino)methoxy]methane 52328-05-9 C2H6N2O 详情 详情
(III) 51784 6-(3,5-dimethylbenzyl)-2-methoxy-4(3H)-pyrimidinone C14H16N2O2 详情 详情
(IV) 51779 sodium 2-butanolate C4H9NaO 详情 详情
Extended Information