Yaozh News Star Club Edu TOP100 Customer Service APP
Iphone Download Android Download
  • English
  • 简体中文
Login Register
Search
Current Location： Home > Feedback Help Print

【结 构 式】

【分子编号】11990

【品名】Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole

【CA登记号】6160-65-2

【 分 子 式 】C7H6N4S

【 分 子 量 】178.2176

【元素组成】C 47.18% H 3.39% N 31.44% S 17.99%
与该中间体有关的原料药合成路线共 24 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22合成路线23合成路线24

合成路线1

该中间体在本合成路线中的序号：(IV)

1) The cyclization of ethyl 3(S)-hydroxybutanoate (I) with N-anisylcinnamylideneamine (II) gives 1-(4-anisyl)-3alpha-[1(S)-hydroxyethyl]-4-(2-phenylvinyl)azetidin-2-one (III), which is esterified with thiocarbonyldiimidazole (IV) yielding the thioester (V). The reduction of (V) with NaBH4 in hot DMSO affords 1-(4-anisyl)-3alpha-ethyl-4-(2-phenylvinyl)azetidin-2-one (VI), which is oxidized with KMnO4 - NaClO4, giving the carboxylic acid (VII). The oxidative decarboxylation of (VII) with lead tetraacetate yields 4-acetoxy-1-(4-anisyl)-3alpha-ethylazetidin-2-one (VIII), which is submitted to dearylation with ammonium cerium (IV) nitrate to afford 4-acetoxy-3alpha-ethylazetidin-2-one (IX). The condensation of (IX) with 4-nitrobenzyl 2-diazo-3-(tert-butyldimethylsilyloxy)-3-butenoate (X) gives the diazo keto ester (XI), which is cyclized yielding 4-nitrobenzyl 6-ethyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate (XII). The reaction of (XII) with diphenyl chlorophosphate affords the enol phosphate (XIII), which is condensed with N-acetylcysteamine (XIV) to give 4-nitrobenzyl ester of PS-5 (XV). Finally, this compound is deprotected by hydrogenation with H2 over Pd/C.

参考文献 中间体
合成目标
【1】 Georg, G.I.; Kant, J.; An asymmetric synthesis of carbapenem antibiotic (+)-PS-5 from ethyl 3-hydroxybutanoate. J Org Chem 1988, 53, 3, 692-5.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
16074 Diphenyl phosphoryl chloride; 1,1'-Diphenylphosphoryl chloride; Chlorodiphenyl Phosphate; Diphenyl chlorophosphate; Diphenylchlorophosphate 2524-64-3 C12H10ClO3P 详情 详情
44204 N,N-diethyl-2-propanamine; N,N-diethyl-N-isopropylamine C7H17N 详情 详情
(I) 20021 (3S)-3-Hydroxybutanoic acid ethyl ester 56816-01-4 C6H12O3 详情 详情
(II) 20022 4-methoxy-N-[(Z,2E)-3-phenyl-2-propenylidene]aniline; N-(4-methoxyphenyl)-N-[(Z,2E)-3-phenyl-2-propenylidene]amine C16H15NO 详情 详情
(III) 20023 (3S)-3-(1-hydroxyethyl)-1-(4-methoxyphenyl)-4-[(E)-2-phenylethenyl]-2-azetidinone C20H21NO3 详情 详情
(IV) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(V) 20025 O-(1-[(3S)-1-(4-methoxyphenyl)-2-oxo-4-[(E)-2-phenylethenyl]azetidinyl]ethyl) 1H-imidazole-1-carbothioate C24H23N3O3S 详情 详情
(VI) 20026 (3R)-3-ethyl-1-(4-methoxyphenyl)-4-[(E)-2-phenylethenyl]-2-azetidinone C20H21NO2 详情 详情
(VII) 20027 (3R)-3-ethyl-1-(4-methoxyphenyl)-4-oxo-2-azetidinecarboxylic acid C13H15NO4 详情 详情
(VIII) 20028 (3R)-3-ethyl-1-(4-methoxyphenyl)-4-oxoazetidinyl acetate C14H17NO4 详情 详情
(IX) 20029 (3R)-3-ethyl-4-oxoazetidinyl acetate C7H11NO3 详情 详情
(X) 20030 2-Diazo-3-(tert-butyldimethylsilyloxy)-3-butenoic acid 4-nitrobenzyl ester C17H23N3O5Si 详情 详情
(XI) 20031 (2R,3R)-2-Diazo-4-(3-ethyl-4-oxoazetidin-2-yl)-3-oxobutyric acid 4-nitrobenzyl ester C16H16N4O6 详情 详情
(XII) 20032 4-nitrobenzyl (5R,6R)-6-ethyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate C16H16N2O6 详情 详情
(XIII) 20033 4-nitrobenzyl (5R,6R)-3-[(diphenoxyphosphoryl)oxy]-6-ethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate C28H25N2O9P 详情 详情
(XIV) 20034 N-(2-sulfanylethyl)acetamide 1190-73-4 C4H9NOS 详情 详情
(XV) 20035 4-nitrobenzyl (5R,6R)-3-[[2-(acetamido)ethyl]sulfanyl]-6-ethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate C20H23N3O6S 详情 详情

合成路线2

该中间体在本合成路线中的序号：(III)

This compound is prepared by two related ways: 1) The partial silylation of adenosine (I) with tert-butyldimethylsilyl chloride and imidazole gives 5'-O-(tert-butyldimethylsilyl)adenosine (II), which by reaction with 1,1'-thiocarbonyldiimidazole (III) in hot DMF is converted into 5'-O-(tert-butyldimethylsilyl)-2',3'-O-thionocarbonyladenosine (IV). The desulfurization of (IV) with 1,3-dimethyl-2-phenyl-1,3,2-diazaphospholidine (V) or triethyl phosphite in THF yields 5'-O-(tert-butyldimethylsilyl)-2',3'-didehydro-2',3'-dideoxyadenosine (VI), which is deprotected with tetrabutylammonium fluoride in THF affording 2',3'-didehydro-2',3'-dideoxyadenosine (VII). Finally, this compound is hydrogenated with H2 over Pd/C in methanol. 2) The reaction of silylated adenosine (II) with CS2 and NaOH in DMSO, followed by methylation with methyl iodide gives 5'-O-(tert-butyldimethylsilyl)-2',3'-bis-O-[(methylthio)thiocarbonyl]ad enosine (VIII), which is desulfurized with tributyltin hydride and AIBN in refluxing toluene to yield the dideoxy-didehydroadenosine (VI), already obtained.

参考文献 中间体
合成目标
【1】 Chu, C.K.; Bhadti, V.S.; Doboszewski, B.; Gu, Z.P.; Kosugi, Y.; Pullaiah, K.C.; Van Roey, P.; General syntheses of 2',3'-dideoxynucleosides and 2',3'-didehydro-2',3'-dideoxynucleosides. J Org Chem 1989, 54, 2217-25.
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) 11988 Adenosine; (2R,3R,4S,5R)-2-(6-Amino-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol 58-61-7 C10H13N5O4 详情 详情
(II) 11989 (2R,3R,4S,5R)-2-(6-Amino-9H-purin-9-yl)-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)tetrahydro-3,4-furandiol C16H27N5O4Si 详情 详情
(III) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(IV) 11991 (3aR,4R,6R,6aR)-4-(6-Amino-9H-purin-9-yl)-6-([[tert-butyl(dimethyl)silyl]oxy]methyl)tetrahydrofuro[3,4-d][1,3]dioxole-2-thione C17H25N5O4SSi 详情 详情
(V) 11992 1,3-Dimethyl-2-phenyl-1,3,2-diazaphospholane; 1,3-DIMETHYL-2-PHENYL-1,3,2-DIAZAPHOSPHOLIDINE 1,3-Dimethy?2-phenyl-1,3,2-diazaphospholidine 22429-12-5 C10H15N2P 详情 详情
(VI) 11993 9-[(2R,5S)-5-([[tert-Butyl(dimethyl)silyl]oxy]methyl)-2,5-dihydro-2-furanyl]-9H-purin-6-ylamine; 9-[(2R,5S)-5-([[tert-Butyl(dimethyl)silyl]oxy]methyl)-2,5-dihydro-2-furanyl]-9H-purin-6-amine C16H25N5O2Si 详情 详情
(VII) 11994 [(2S,5R)-5-(6-Amino-9H-purin-9-yl)-2,5-dihydro-2-furanyl]methanol 7057-48-9 C10H11N5O2 详情 详情
(VIII) 11995 O-((2R,3R,4R,5R)-2-(6-Amino-9H-purin-9-yl)-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)-4-[[(methylsulfanyl)carbothioyl]oxy]tetrahydro-3-furanyl) S-methyl carbonodithioate C20H31N5O4S4Si 详情 详情

合成路线3

该中间体在本合成路线中的序号：(III)

Compound (I) as a 2:1 mixture of diastereoisomers was hydrolyzed with barium hydroxide to afford a mixture of alcohols (II). Further reaction with thiocarbonyldiimidazole (III) and dimethylamino-pyridine (DMAP) gave thiocarbamate (IV), which was finally reduced with tributyltin hydride and azabis(isobutyronitrile) (AIBN) in refluxing benzene.

参考文献 中间体
合成目标
【1】 Unno, R.; et al.; Structure-activity relationships of cyclic enediynes related to dynemicin A-II. Synthesis and antitumor activity of 9- and 12-substituted enediynes equipped with aryl carbamate moieties. Bioorg Med Chem 1997, 5, 5, 903.
【2】 Unno, R.; et al.; Structure-activity relationships of cyclic enediynes related to dynemicin A-I. Synthesis and antitumor activity of 9-acetoxy enediynes equipped with aryl carbamate moieties. Bioorg Med Chem 1997, 5, 5, 883.
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) 17773 4-chlorophenyl (1R,9S,16R,18S)-16-(acetoxy)-17-oxa-8-azatetracyclo[7.7.2.0(1,18).0(2,7)]octadeca-2,4,6,12-tetraene-10,14-diyne-8-carboxylate C25H16ClNO5 详情 详情
(II) 17774 4-chlorophenyl (1S,9S,16R,18S)-16-hydroxy-17-oxa-8-azatetracyclo[7.7.2.0(1,18).0(2,7)]octadeca-2,4,6,12-tetraene-10,14-diyne-8-carboxylate C23H14ClNO4 详情 详情
(III) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(IV) 17776 4-chlorophenyl (1R,9S,16R,18S)-16-[(1H-imidazol-1-ylcarbothioyl)oxy]-17-oxa-8-azatetracyclo[7.7.2.0(1,18).0(2,7)]octadeca-2,4,6,12-tetraene-10,14-diyne-8-carboxylate C27H16ClN3O4S 详情 详情

合成路线4

该中间体在本合成路线中的序号：(V)

The hydrolysis of 6,7-dichloro-3-nitro-2-naphthoic acid ethyl ester (I) with NaOH in ethanol gives the expected free acid (II), which is treated with diphenylphosphoroazidate and triethylamine in DMF to yield 6,7-dichloro-3-nitro-2-naphthylamine (III). The reduction of (III) with H2 over RaNi in ehanol/ethyl acetate affords the corresponding diamine (IV), which is cyclized with thiocarbonyldi-imidazole (V) in refluxing benzene to give 6,7-dichloro-2,3-dihydro-1H-naphtho[2,3-d]imidazole-2-thione (VI). The methylation of (VI) with methyl iodide in dry DMF yields the corresponding methylsulfanyl derivative (VII), which is condensed with 1-O-acetyl-2,3,5-tri-O-ben-zoyl-beta-D-ribofuranose (VIII) by means of trimethylsilyl trifluoro-methanesulfonate (TMSOTf) and N,O-bis(trimethylsilyl)acetamide (BSA) in dichloromethane affording the benzoylated ribofuranoside (IX). The debenzoylation of (IX) with ammonia in methanol gives the free ribofuranoside (X), which is finally treated with Cl2/CCl4 in methanol to eliminate the methylsulfanyl group.

参考文献 中间体
合成目标
【1】 Zhu, Z.J.; et al.; Synthesis of 2,6, 7-trichloro-1-(beta-D-ribofuranosyl)naphtho[2, 3-d]imidazole: A linear dimensional analogue of the antiviral agent TCRB. J Org Chem 1998, 63, 4, 977.
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) 26976 ethyl 6,7-dichloro-3-nitro-2-naphthoate C13H9Cl2NO4 详情 详情
(II) 26977 6,7-dichloro-3-nitro-2-naphthoic acid C11H5Cl2NO4 详情 详情
(III) 26978 6,7-dichloro-3-nitro-2-naphthalenamine C10H6Cl2N2O2 详情 详情
(IV) 26979 3-amino-6,7-dichloro-2-naphthylamine C10H8Cl2N2 详情 详情
(V) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(VI) 26980 6,7-dichloro-1,3-dihydro-2H-naphtho[2,3-d]imidazole-2-thione C11H6Cl2N2S 详情 详情
(VII) 26981 6,7-dichloro-1H-naphtho[2,3-d]imidazol-2-yl methyl sulfide C12H8Cl2N2S 详情 详情
(VIII) 26984 (2R,3R,4R,5S)-5-(acetoxy)-4-(benzoyloxy)-2-[(benzoyloxy)methyl]tetrahydro-3-furanyl benzoate C28H24O9 详情 详情
(IX) 26982 (2R,3R,4R,5R)-4-(benzoyloxy)-2-[(benzoyloxy)methyl]-5-[6,7-dichloro-2-(methylsulfanyl)-1H-naphtho[2,3-d]imidazol-1-yl]tetrahydro-3-furanyl benzoate C38H28Cl2N2O7S 详情 详情
(X) 26983 (2R,3R,4S,5R)-2-[6,7-dichloro-2-(methylsulfanyl)-1H-naphtho[2,3-d]imidazol-1-yl]-5-(hydroxymethyl)tetrahydro-3,4-furandiol C17H16Cl2N2O4S 详情 详情

合成路线5

该中间体在本合成路线中的序号：(II)

Condensation of 2-amino-5-bromopyridine (I) with 1,1-thiocarbonyl diimidazole (II) furnished the thiocarbonyl derivative (III). Further reaction of (III) with 1-(2-aminoethyl)piperidine (IV) gave the target thiourea.

参考文献 中间体
合成目标
【1】 Mao, C.; Vig, R.; Venkatachalam, T.K.; Sudbeck, E.A.; Uckun, F.M.; Structure-based design of N-[2-(1-piperidinylethyl)]-N'-[2-(5-bromopyridyl)]-thiourea and N-[2-(1-piperazinylethyl)]-N'-[2-(5-bromopyridyl)]-thiourea as potent non-nucleoside inhibitors of HIV-1 reverse transcriptase. Bioorg Med Chem Lett 1998, 8, 16, 2213.
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(III) 24645 N-(5-bromo-2-pyridinyl)-1H-imidazole-1-carbothioamide C9H7BrN4S 详情 详情
(IV) 24646 2-(1-piperidinyl)-1-ethanamine 27578-60-5 C7H16N2 详情 详情

合成路线6

该中间体在本合成路线中的序号：(II)

Condensation of 2-amino-5-bromopyridine (I) with 1,1-thiocarbonyl diimidazole (II) furnished the thiocarbonyl derivative (III). Further reaction of (III) with 1-(2-aminoethyl)piperazine (IV) gave the target thiourea.

参考文献 中间体
合成目标
【1】 Mao, C.; Vig, R.; Venkatachalam, T.K.; Sudbeck, E.A.; Uckun, F.M.; Structure-based design of N-[2-(1-piperidinylethyl)]-N'-[2-(5-bromopyridyl)]-thiourea and N-[2-(1-piperazinylethyl)]-N'-[2-(5-bromopyridyl)]-thiourea as potent non-nucleoside inhibitors of HIV-1 reverse transcriptase. Bioorg Med Chem Lett 1998, 8, 16, 2213.
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(III) 24645 N-(5-bromo-2-pyridinyl)-1H-imidazole-1-carbothioamide C9H7BrN4S 详情 详情
(IV) 24647 2-(1-piperazinyl)-1-ethanamine 140-31-8 C6H15N3 详情 详情

合成路线7

该中间体在本合成路线中的序号：(II)

2-Amino-5-bromopyridine (I) was condensed with 1,1-thiocarbonyldiimidazole (II) in acetonitrile to furnish the precursor thiocarbonyl derivative (III). Further reaction of (III) with 2-chlorophenethylamine (IV) in DMF at 100 C gave the target thiourea.

参考文献 中间体
合成目标
【1】 Vig, R.; Mao, C.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Sudbeck, E.A.; Uckun, F.M.; Rational design and synthesis of phenethyl-5-bromopyridyl thiourea derivatives as potent non-nucleoside inhibitors of HIV reverse transcriptase. Bioorg Med Chem 1998, 6, 10, 1789.
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(III) 26465 methyl (2S,3R)-3-cyclopropyl-2,3-dihydroxypropanoate C7H12O4 详情 详情
(IV) 31334 2-chlorophenethylamine; 2-(2-chlorophenyl)-1-ethanamine 13078-80-3 C8H10ClN 详情 详情

合成路线8

该中间体在本合成路线中的序号：(II)

2-Amino-5-bromopyridine (I) was condensed with 1,1-thiocarbonyldiimidazole (II) in acetonitrile to furnish the precursor thiocarbonyl derivative (III). Further reaction of (III) with 3-chlorophenethylamine (IV) in DMF at 100 C gave the target thiourea.

参考文献 中间体
合成目标
【1】 Vig, R.; Mao, C.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Sudbeck, E.A.; Uckun, F.M.; Rational design and synthesis of phenethyl-5-bromopyridyl thiourea derivatives as potent non-nucleoside inhibitors of HIV reverse transcriptase. Bioorg Med Chem 1998, 6, 10, 1789.
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(III) 26465 methyl (2S,3R)-3-cyclopropyl-2,3-dihydroxypropanoate C7H12O4 详情 详情
(IV) 31335 3-chlorophenethylamine; 2-(3-chlorophenyl)-1-ethanamine 13078-79-0 C8H10ClN 详情 详情

合成路线9

该中间体在本合成路线中的序号：(II)

By condensation of 2-(4-chlorophenyl)ethylamine (I) with thiocarbonyldiimidazole (II) in refluxing acetonitrile.

参考文献 中间体
合成目标
【1】 Zhu, Z.; et al.; N,N'-Di(phenethyl)thiourea liquid-phase combinatorial libraries: Synthesis and apoptosis induction. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 023.
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) 29459 4-chlorophenethylamine; 2-(4-chlorophenyl)-1-ethanamine 156-41-2 C8H10ClN 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情

合成路线10

该中间体在本合成路线中的序号：(II)

2-Amino-5-bromopyridine (I) was condensed with 1,1-thiocarbonyldiimidazole (II) in acetonitrile to furnish the precursor thiocarbonyl derivative (III). Further reaction of (III) with 2-fluorophenethylamine (IV) in DMF at 100 C gave the target thiourea.

参考文献 中间体
合成目标
【1】 Vig, R.; Mao, C.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Sudbeck, E.A.; Uckun, F.M.; Rational design and synthesis of phenethyl-5-bromopyridyl thiourea derivatives as potent non-nucleoside inhibitors of HIV reverse transcriptase. Bioorg Med Chem 1998, 6, 10, 1789.
【2】 Uckun, F.M. (Parker Hughes Institute); NNI for treatment of multi-drug resistant HIV. WO 0056736 .
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(III) 26465 methyl (2S,3R)-3-cyclopropyl-2,3-dihydroxypropanoate C7H12O4 详情 详情
(IV) 31333 2-fluorophenethylamine; 2-(2-fluorophenyl)-1-ethanamine C8H10FN 详情 详情

合成路线11

该中间体在本合成路线中的序号：(II)

The reaction of 5-bromopyridin-2-amine (I) with thiocarbonyldiimidazole (II) in acetonitrile gives the thioamide (III), which is finally condensed with 2-(2,5-dimethoxyphenyl)ethylamine (IV) in DMF at 100 C.

参考文献 中间体
合成目标
【1】 Vig, R.; Mao, C.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Sudbeck, E.A.; Uckun, F.M.; Rational design and synthesis of phenethyl-5-bromopyridyl thiourea derivatives as potent non-nucleoside inhibitors of HIV reverse transcriptase. Bioorg Med Chem 1998, 6, 10, 1789.
【2】 Uckun, F.M. (Parker Hughes Institute); NNI for treatment of multi-drug resistant HIV. WO 0056736 .
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(III) 24645 N-(5-bromo-2-pyridinyl)-1H-imidazole-1-carbothioamide C9H7BrN4S 详情 详情
(IV) 36889 2,5-dimethoxyphenethylamine; 2-(2,5-dimethoxyphenyl)-1-ethanamine 3600-86-0 C10H15NO2 详情 详情

合成路线12

该中间体在本合成路线中的序号：(II)

2-Amino-5-bromopyridine (I) was condensed with 1,1-thiocarbonyldiimidazole (II) in acetonitrile to furnish the precursor thiocarbonyl derivative (III). Further reaction of (III) with 3-fluorophenethylamine (IV) in DMF at 100 C gave the target thiourea.

参考文献 中间体
合成目标
【1】 Vig, R.; Mao, C.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Sudbeck, E.A.; Uckun, F.M.; Rational design and synthesis of phenethyl-5-bromopyridyl thiourea derivatives as potent non-nucleoside inhibitors of HIV reverse transcriptase. Bioorg Med Chem 1998, 6, 10, 1789.
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(III) 26465 methyl (2S,3R)-3-cyclopropyl-2,3-dihydroxypropanoate C7H12O4 详情 详情
(IV) 31336 3-fluorophenethylamine; 2-(3-fluorophenyl)-1-ethanamine C8H10FN 详情 详情

合成路线13

该中间体在本合成路线中的序号：(A)

Condensation of protected ketone (I) with 2-benzyloxy-1-trimethylsilyloxyphenoxyethane (II) by means of Sn(OTf)2 and chiral amine (III) in propionitrile affords aldolic reaction product (IV), which is then dehydroxylated by treatment with thiocarbonyl diimidazole (A) in THF followed by reduction with Bu3SnH in refluxing toluene to provide the protected hydroxyester (V). Reduction of the ester group of (V) with DIBAL in CH2Cl2 followed by Swern oxidation with (COCl)2, DMSO and Et3N in dichloromethane yields aldehyde (VI), which is then condensed with 2-methoxypropene (VII) and 2-methoxyaniline (VIII) in the presence of yterbium triflate (Yb(OTf)3) in THF/H2O to furnish a mixture of diastereoisomers from which anti-(IX) is separated. Derivative anti-(IX) is treated with HF in THF for TBS removal and cyclization is induced by reaction with PPh3 and CBr4 in CH2Cl2, affording piperidine (X). Next, treatment of (X) with cerium ammonium nitrate (CAN) in acetonitrile/H2O allows N-protecting group removal, giving piperidine derivative (XI). Alternatively, (XI) can be obtained as follows: Treatment of aldehyde (VI) with 2-methoxyaniline (VIII) and PMB-protected 2-methoxypropene (XII) in the presence of scandium trisdodecylsulfate (STDS) in THF/H2O yields a mixture of diastereoisomers from which anti-(XIII) is separated. Derivative anti-(XIII) is then converted into (XI) by following the same procedure as for the conversion of anti-(IX) into (XI). Derivative (XI) is then subjected to: (i) N-protection by means of Boc2O; (ii) treatment with lithium hexamethyl disilazide (LHMDS) followed by trimethylsilyl chloride (TMSCl); (iii) oxidation of the silylenol ether by means of MCPBA; and (iv) bromination with PPh3 and CBr4. After all these steps bromo derivative (XIV) is obtained. Finally, coupling of (XIV) with 4-hydroxyquinazoline (XV) using KOH followed by Boc removal by treatment with refluxing HCl furnishes the target compound.

参考文献 中间体
合成目标
【1】 Wataya, Y.; Ueno, M.; Suzuki, R.; Kim, H.-S.; Kobayashi, S.; Ishitani, H.; Catalytic asymmetric synthesis of antimalarial alkaloids febrifubine and isofebrifugine and their biological actvity. J Org Chem 1999, 64, 18, 6833.
【2】 Kobayashi, S.; Kim, H.-S.; Wataya, Y. (Japan Science and Technology Corp.); Febrifugine and isofebrifugine and processes for the preparation of both. EP 1076057; WO 0052005 .
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) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(I) 44768 4-[[tert-butyl(dimethyl)silyl]oxy]-2-butanone C10H22O2Si 详情 详情
(II) 44769 benzyl (Z)-2-phenoxy-2-[(trimethylsilyl)oxy]ethenyl ether; [[(Z)-2-(benzyloxy)-1-phenoxyethenyl]oxy](trimethyl)silane C18H22O3Si 详情 详情
(III) 44770 N-[[(2S)-1-methylpyrrolidinyl]methyl]-N-(1-naphthyl)amine; N-[[(2S)-1-methylpyrrolidinyl]methyl]-1-naphthalenamine 82160-07-4 C16H20N2 详情 详情
(IV) 44771 phenyl (2S,3R)-2-(benzyloxy)-5-[[tert-butyl(dimethyl)silyl]oxy]-3-hydroxypentanoate C24H34O5Si 详情 详情
(V) 44773 phenyl (2S)-2-(benzyloxy)-5-[[tert-butyl(dimethyl)silyl]oxy]pentanoate C24H34O4Si 详情 详情
(VI) 44774 (2S)-2-(benzyloxy)-5-[[tert-butyl(dimethyl)silyl]oxy]pentanal C18H30O3Si 详情 详情
(VII) 17354 isopropenyl methyl ether; 2-methoxy-1-propene 116-11-0 C4H8O 详情 详情
(VIII) 25193 2-methoxyphenylamine; 2-methoxyaniline 517-28-2 C7H9NO 详情 详情
(IX) 44777 　 C27H42NO4Si 详情 详情
(X) 44778 1-[(2R,3S)-3-(benzyloxy)-1-(2-methoxyphenyl)piperidinyl]acetone C22H27NO3 详情 详情
(XI) 44779 1-[(2R,3S)-3-(benzyloxy)piperidinyl]acetone C15H21NO2 详情 详情
(XII) 44780 1-methoxy-4-(3-methoxy-3-butenyl)benzene; 4-(3-methoxy-3-butenyl)phenyl methyl ether C12H16O2 详情 详情
(XIII) 44781 　 C35H50NO5Si 详情 详情
(XIV) 44782 tert-butyl (2R,3S)-3-(benzyloxy)-2-(3-bromo-2-oxopropyl)-1-piperidinecarboxylate C20H28BrNO4 详情 详情
(XV) 44783 4-quinazolinol C8H6N2O 详情 详情

合成路线14

该中间体在本合成路线中的序号：(III)

Alternatively, 2-amino-5-bromopyridine (I) was reacted with 1,1'-thiocarbonyldiimidazole (III) in acetonitrile yielding thioimidazolide (IV), which was then condensed with 2-(1-cyclohexenyl)ethylamine (V) in hot DMF.

参考文献 中间体
合成目标
【1】 Maher, D.; Mao, C.; Pendergrass, S.; Venkatachalam, T.K.; Zhu, D.; Tuel-Ahlgren, L.; Uckun, F.M.; N-[2-(1-Cyclohexenyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea and N'-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-chloropyridyl)]-thiourea as potent inhibitors of multidrug-resistant human immunodeficiency virus-1. Bioorg Med Chem Lett 1999, 9, 18, 2721.
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(III) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(IV) 24645 N-(5-bromo-2-pyridinyl)-1H-imidazole-1-carbothioamide C9H7BrN4S 详情 详情
(V) 36902 2-(1-cyclohexen-1-yl)ethylamine; 2-(1-cyclohexen-1-yl)-1-ethanamine; 2-(1-Cyclohexenyl)ethylamine 3399-73-3 C8H15N 详情 详情

合成路线15

该中间体在本合成路线中的序号：(III)

Alternatively, 2-amino-5-chloropyridine (I) was reacted with 1,1'-thiocarbonyldiimidazole (III) in acetonitrile yielding thioimidazolide (IV), which was then condensed with 2-(1-cyclohexenyl)ethylamine (V) in hot DMF.

参考文献 中间体
合成目标
【1】 Maher, D.; Mao, C.; Pendergrass, S.; Venkatachalam, T.K.; Zhu, D.; Tuel-Ahlgren, L.; Uckun, F.M.; N-[2-(1-Cyclohexenyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea and N'-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-chloropyridyl)]-thiourea as potent inhibitors of multidrug-resistant human immunodeficiency virus-1. Bioorg Med Chem Lett 1999, 9, 18, 2721.
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) 18559 5-Chloro-2-pyridinylamine; 5-Chloro-2-pyridinamine; 2-Amino-5-chloropyridine 1072-98-6 C5H5ClN2 详情 详情
(III) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(IV) 36903 　 C9H7ClN4S 详情 详情
(V) 36902 2-(1-cyclohexen-1-yl)ethylamine; 2-(1-cyclohexen-1-yl)-1-ethanamine; 2-(1-Cyclohexenyl)ethylamine 3399-73-3 C8H15N 详情 详情

合成路线16

该中间体在本合成路线中的序号：(II)

Reaction of 2-amino-5-bromopyridine (I) with thiocarbonyl diimidazole (II) provided the thioimidazolide (III). This was then coupled with 2-(2-thienyl)ethyl amine (IV) to furnish the target thiourea.

参考文献 中间体
合成目标
【1】 Maher, D.; Mao, C.; Tuel-Ahlgren, L.; Uckun, F.M.; Zhu, D.; Pendergrass, S.; Venkatachalam, T.K.; N'-[2-(2-Thiophene)ethyl]-N'-[2-(5-bromopyridyl)] thiourea as a potent inhibitor of NNI-resistant and multidrug-resistant human immunodeficiency virus-1. Bioorg Med Chem Lett 1999, 9, 24, 3411.
【2】 Ventatachalam, T.K.; Uckun, F.M. (Parker Hughes Institute); Thiophene-ethyl thiourea cpds. and use. US 6124324; WO 0078755 .
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(III) 24645 N-(5-bromo-2-pyridinyl)-1H-imidazole-1-carbothioamide C9H7BrN4S 详情 详情
(IV) 35253 2-(2-thienyl)ethylamine; 2-(2-thienyl)-1-ethanamine; 2-Thiophene ethylamine 30433-91-1 C6H9NS 详情 详情

合成路线17

该中间体在本合成路线中的序号：(IV)

2-Phenyl-3,4-dihydro-2H-1-benzothiopyran-4-one (I) was converted to oxime (II) upon treatment with hydroxylamine, and subsequently reduced to amine (III) by means of Zn and HOAc. Condensation of (III) with thiocarbonyl diimidazole (IV) produced the thioimidazolide (V), that was displaced with 2-bromoethyl amine (VI) to furnish thiourea (VII). Finally, cyclization of the N-(bromoethyl)thiourea (VII) in the presence of Et3N produced the target thiazoline derivative.

参考文献 中间体
合成目标
【1】 Lewis, J.J.; Bare, T.M.; Horchler, C.L.; et al.; Selective alpha2C-adrenoceptor agonist activity of imidazole, imidazoline, and imidazoline-related derivatives. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 268.
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) 41083 2-phenyl-2,3-dihydro-4H-thiochromen-4-one C15H12OS 详情 详情
(II) 41084 2-phenyl-2,3-dihydro-4H-thiochromen-4-one oxime C15H13NOS 详情 详情
(III) 41085 2-phenyl-4-thiochromanamine; 2-phenyl-3,4-dihydro-2H-thiochromen-4-ylamine C15H15NS 详情 详情
(IV) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(V) 41086 N-(2-phenyl-3,4-dihydro-2H-thiochromen-4-yl)-1H-imidazole-1-carbothioamide C19H17N3S2 详情 详情
(VI) 38475 2-bromoethylamine; 2-bromo-1-ethanamine C2H6BrN 详情 详情
(VII) 41087 N-(2-bromoethyl)-N'-(2-phenyl-3,4-dihydro-2H-thiochromen-4-yl)thiourea C18H19BrN2S2 详情 详情

合成路线18

该中间体在本合成路线中的序号：(III)

2-Amino-5-chloropyridine-3-sulfonamide (II) was obtained by the reaction of 2-amino-5-chloropyridine (I) with chlorosulfonic acid, followed by treatment of the sulfonyl chloride intermediate with aqueous ammonia. Condensation of amino sulfonamide (II) with thiocarbonyldiimidazole (III) produced the imidazolyl pyridothiadiazine (IV). Nucleophilic substitution of the imidazolyl group with 1,2,2-trimethylpropylamine (V) in a sealed vessel at 180 C furnished the corresponding amino pyridothiadiazine.

参考文献 中间体
合成目标
【1】 de Tullio, P.; Quedraogo, R.; Pirotte, B.; et al.; 3-Alkylamino-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1,1-dioxides structurally related to diazoxide and pinacidil as potassium channel openers acting on vascular smooth muscle cells: Design, synthesis, and pharmacological evaluation. J Med Chem 2000, 43, 8, 1456.
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) 18559 5-Chloro-2-pyridinylamine; 5-Chloro-2-pyridinamine; 2-Amino-5-chloropyridine 1072-98-6 C5H5ClN2 详情 详情
(II) 46289 2-amino-5-chloro-3-pyridinesulfonamide C5H6ClN3O2S 详情 详情
(III) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(IV) 46290 7-chloro-3-(1H-imidazol-1-yl)-2H-pyrido[2,3-e][1,2,4]thiadiazine-1,1(4H)-dione C9H6ClN5O2S 详情 详情
(V) 30977 (2R)-3,3-dimethyl-2-butanamine; (1R)-1,2,2-trimethylpropylamine C6H15N 详情 详情

合成路线19

该中间体在本合成路线中的序号：(II)

Reaction of 2-amino-5-bromopyridine (I) with thiocarbonyldiimidazole (II) afforded the thioimidazolide (III). This was then condensed with 4-methylphenetylamine (IV) in hot DMF to produce the required thiourea.

参考文献 中间体
合成目标
【2】 Ventalachalam, T.K.; Uckum, F.M. (Parker Hughes Institute); Phenethyl-thiourea cpds. and use. US 6207688 .
【1】 Uckun, F.M.; Zhu, D.; Pendergrass, S.; Mao, C.; Tuel-Ahlgren, L.; Venkatachalam, T.K.; Maher, D.; N-[2-(4-Methylphenyl)ethyl]-N'-[2-(5-bromopyridyl)]thiourea as a potent inhibitor of NNRTI-resistant and multidrug-resistant human immunodeficiency virus type 1. Antivir Chem Chemother 2000, 11, 2, 135.
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(III) 24645 N-(5-bromo-2-pyridinyl)-1H-imidazole-1-carbothioamide C9H7BrN4S 详情 详情
(IV) 46291 4-methylphenethylamine; 2-(4-methylphenyl)-1-ethanamine C9H13N 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-amino-5-bromopyridine (I) with thiocarbonyl diimidazole (II) gave rise to thioimidazolide (III), which was then condensed with (R)-1-phenylethylamine (IV) to yield the title thiourea.

参考文献 中间体
合成目标
【1】 Mao, C.; Venkatachalam, T.K.; Uckun, F.M.; Sudbeck, E.A.; Stereochemistry of halopyridyl and thiazolyl thiourea compounds is a major determinant of their potency as nonnucleoside inhibitors of HIV-1 reverse transcriptase. Bioorg Med Chem Lett 2000, 10, 18, 2071.
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) 12123 5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine 1072-97-5 C5H5BrN2 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(III) 24645 N-(5-bromo-2-pyridinyl)-1H-imidazole-1-carbothioamide C9H7BrN4S 详情 详情
(IV) 10039 (1R)-1-Phenylethylamine; (1R)-1-Phenyl-1-ethanamine.; L-alpha-Phenylethylamine 3886-69-9 C8H11N 详情 详情

合成路线21

该中间体在本合成路线中的序号：(II)

Reaction of 2-aminothiazole (I) with thiocarbonyldiimidazole (II) in acetonitrile gave the intermediate thioimidazolide (III). This was then condensed with 2-furylmethylamine (IV) in hot DMF to yield the title thiourea derivative.

参考文献 中间体
合成目标
【1】 Venkatachalam, T.K.; Sudbeck, E.A.; Mao, C.; Uckun, F.M.; Anti-HIV activity of aromatic and heterocyclic thiazolyl thiourea compounds. Bioorg Med Chem Lett 2001, 11, 4, 523.
【2】 Uckun, F.M.; Venkatachalam, T.K. (Parker Hughes Institute); Aromatic and heterocyclic thiazolyl thiourea cpds. and use. WO 0232889 .
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) 19795 2-Thiazolamine; 1,3-thiazol-2-amine; 1,3-thiazol-2-ylamine 96-50-4 C3H4N2S 详情 详情
(II) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(III) 51395 N-(1,3-thiazol-2-yl)-1H-imidazole-1-carbothioamide C7H6N4S2 详情 详情
(IV) 51396 1-(2-Furyl)methylamine; 2-Aminomethylfuran; 2-Furfurylamine; Furfurylamine 617-89-0 C5H7NO 详情 详情

合成路线22

该中间体在本合成路线中的序号：(III)

2,6-Difluorophenethylamine (II) was prepared by reduction of nitrile (I) with either NaBH4 in the presence of CoCl2 or borane in THF. Reaction of amine (II) with thiocarbonyldiimidazole (III) furnished the thioimidazolide (IV). This was finally condensed with 2-amino-5-chloropyridine (V), yielding the corresponding thiourea.

参考文献 中间体
合成目标
【1】 Lind, P.T.; Noreen, R.; Ternansky, R.J.; Morin, J.M. Jr. (Medivir AB); Cpds. and methods for inhibition of HIV and related viruses. WO 9303022 .
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) 46429 2-(2,6-difluorophenyl)acetonitrile C8H5F2N 详情 详情
(II) 46430 2-(2,6-difluorophenyl)-1-ethanamine; 2,6-difluorophenethylamine C8H9F2N 详情 详情
(III) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(IV) 46431 N-(2,6-difluorophenethyl)-1H-imidazole-1-carbothioamide C12H11F2N3S 详情 详情
(V) 18559 5-Chloro-2-pyridinylamine; 5-Chloro-2-pyridinamine; 2-Amino-5-chloropyridine 1072-98-6 C5H5ClN2 详情 详情

合成路线23

该中间体在本合成路线中的序号：(V)

2-(2-Thienyl)ethylamine (I) was protected as the N-Boc derivative (II) with Boc2O in CHCl3. Regioselective halogenation of the thiophene ring of (II) with concomitant Boc group cleavage by means of bromine in cold HOAc yielded the 5-bromothiophene (III). The thioimidazolide (VI) was prepared by reaction of 2-amino-5-chloropyridine (IV) with thiocarbonyl diimidazole (V). Finally, condensation of (VI) with amine (III) in hot DMF furnished the target thiourea.

参考文献 中间体
合成目标
【1】 Uckun, F.M.; Sudbeck, E.A.; Venkatachalam, T.K.; Regiospecific synthesis, X-ray crystal structure and biological activities of 5-bromothiophenethyl thioureas. Tetrahedron Lett 2001, 42, 38, 6629.
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) 35253 2-(2-thienyl)ethylamine; 2-(2-thienyl)-1-ethanamine; 2-Thiophene ethylamine 30433-91-1 C6H9NS 详情 详情
(II) 52887 tert-butyl 2-(2-thienyl)ethylcarbamate C11H17NO2S 详情 详情
(III) 52888 2-(5-bromo-2-thienyl)-1-ethanamine; 2-(5-bromo-2-thienyl)ethylamine C6H8BrNS 详情 详情
(IV) 18559 5-Chloro-2-pyridinylamine; 5-Chloro-2-pyridinamine; 2-Amino-5-chloropyridine 1072-98-6 C5H5ClN2 详情 详情
(V) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(VI) 36903 　 C9H7ClN4S 详情 详情

合成路线24

该中间体在本合成路线中的序号：(V)

Conjugate addition of acrylonitrile (II) to 4-phenylpiperidine (I) affords the piperidinopropionitrile (III). Catalytic hydrogenation of the cyano group of (III) in the presence of Raney nickel and methanolic ammonia leads to diamine (IV). This is further converted into isothiocyanate (VI) by reaction with thiocarbonyl diimidazole (V). Subsequent addition of sodium cyanamide to isothiocyanate (VI) yields the intermediate N-cyano isothiourea sodium salt (VII).

参考文献 中间体
合成目标
【1】 Poindexter, G.S.; Sit, S.-Y.; Swann, R.T.; Bruce, M.A.; Morton, M.A.; Huang, Y.; Breitenbucher, J.G. (Bristol-Myers Squibb Co.); Dihydropyridine NPY antagonists: Cyanoguanidine derivs.. US 6001836; WO 9854136 .
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) 58479 4-phenylpiperidine 771-99-3 C11H15N 详情 详情
(II) 10847 Acrylonitrile 107-13-1 C3H3N 详情 详情
(III) 58480 3-(4-phenyl-1-piperidinyl)propanenitrile C14H18N2 详情 详情
(IV) 58481 3-(4-phenyl-1-piperidinyl)-1-propanamine; 3-(4-phenyl-1-piperidinyl)propylamine C14H22N2 详情 详情
(V) 11990 Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole 6160-65-2 C7H6N4S 详情 详情
(VI) 58482 1-(3-isothiocyanatopropyl)-4-phenylpiperidine; 3-(4-phenyl-1-piperidinyl)propyl isothiocyanate C15H20N2S 详情 详情
(VII) 58483 sodium 1-(3-{[(cyanoimino)(sulfido)methyl]amino}propyl)-4-phenylpiperidine C16H21N4NaS 详情 详情
Extended Information