Yaozh News Star Club Edu BBS 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】23660

【品名】2-Bromoacetic acid

【CA登记号】79-08-3

【 分 子 式 】C2H3BrO2

【 分 子 量 】138.94862

【元素组成】C 17.29% H 2.18% Br 57.51% O 23.03%
与该中间体有关的原料药合成路线共 18 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1

该中间体在本合成路线中的序号：(I)

The esterification of bromoacetic acid (I) with benzyl alcohol (II) gives the corresponding ester (III), which by reaction with triphenylphosphine (IV) in hot toluene yields the phosphonium bromide (V). The reaction of (V) with NaOH in water-dichloromethane affords benzyl(triphenylphosphoranylidene) acetate (VI), which is submitted to a Wittig condensation with 5-(hydroxymethyl)-2-pyrrolidone (VII) in the presence of Dess-Martin periodinane (DMPI) giving benzyl 3-(5-oxo-2-pyrrolidinyl)-2(E) propenoate (VIII). The acylation of (VIII) with 4-methoxybenzoyl chloride (IX) by means of triethylamine in hot toluene yields the corresponding amide (X), which is finally hydrogenated and deprotected with H2 over Pd/C in THF.

参考文献 中间体
合成目标
【1】 Huang, C.C.; Synthesis of carbon-14 labeled 1-(4-methoxybenzoyl. J Label Compd Radiopharm 1987, 24, 6, 675.
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) 23660 2-Bromoacetic acid 79-08-3 C2H3BrO2 详情 详情
(II) 18710 Benzyl alcohol; Phenylmethanol 100-51-6 C7H8O 详情 详情
(III) 12869 benzyl 2-bromoacetate 5437-45-6 C9H9BrO2 详情 详情
(IV) 12437 Triphenylphosphine; Triphenyl phosphine 603-35-0 C18H15P 详情 详情
(V) 22667 [2-(benzyloxy)-2-oxoethyl](triphenyl)phosphonium bromide C27H24BrO2P 详情 详情
(VI) 22668 benzyl 2-(triphenylphosphoranylidene)acetate C27H23O2P 详情 详情
(VII) 10079 5-(Hydroxymethyl)-2-pyrrolidinone 62400-75-3 C5H9NO2 详情 详情
(VIII) 22670 benzyl (E)-3-(5-oxo-2-pyrrolidinyl)-2-propenoate C14H15NO3 详情 详情
(IX) 22671 4-Methoxybenzoyl chloride; p-Methoxybenzoyl chloride; 4-Anisoyl chloride 100-07-2 C8H7ClO2 详情 详情
(X) 22672 benzyl (E)-3-[1-(4-methoxybenzoyl)-5-oxo-2-pyrrolidinyl]-2-propenoate C22H21NO5 详情 详情

合成路线2

该中间体在本合成路线中的序号：(I)

The title compound has also been obtained by solid phase synthesis. Bromoacetic acid (I) is coupled to hydroxymethyl polystyrene resin by means of DIC/DMAP to produce the bromoacetyl resin (II). Bromide displacement with tert-butyl carbazate (III) leads to the N-Boc hydrazino ester (IV), which is further deprotected to (V) employing trifluoroacetic acid. The hydrazinoacetic acid-bound resin (V) is then condensed with 5-(p-nitrophenyl)furfural (VI) to furnish hydrazone (VII). Acylation of resin (VII) with p-nitrophenyl chloroformate (VIII) produces the p-nitrophenyl carbamate (IX), which upon treatment with ammonia gives rise to the semicarbazone (X). Finally, concomitant intramolecular ring closure and resin cleavage of (X) produces the target aminohydantoin derivative (XI) (4, 5).

参考文献 中间体
合成目标
【1】 Wilson, L.J.; Li, M.; Portlock, D.E.; Solid phase synthesis of 1-aminohydantoin libraries. Tetrahedron Lett 1998, 39, 29, 5135.
【2】 Portlock, D.E.; Li, M.; Wilson, L.J. (The Procter & Gamble Co.); Solid phase synthesis of 1-aminohydantoins. WO 9942450 .
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) 23660 2-Bromoacetic acid 79-08-3 C2H3BrO2 详情 详情
(II) 12309 methyl 2-bromoacetate; methyl bromoacetate 96-32-2 C3H5BrO2 详情 详情
(III) 12091 1-Methylhydrazine; Monomethyl hydrazine 60-34-4 CH6N2 详情 详情
(IV) 63589 2-[2-(tert-butoxycarbonyl)hydrazino]acetic acid C7H14N2O4 详情 详情
(V) 63590 2-hydrazinoacetic acid C2H6N2O2 详情 详情
(VI) 63583 5-(4-nitrophenyl)-2-furaldehyde C11H7NO4 详情 详情
(VII) 63591 2-(2-{(E)-[5-(4-nitrophenyl)-2-furyl]methylidene}hydrazino)acetic acid C13H11N3O5 详情 详情
(VIII) 16605 4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene 7693-46-1 C7H4ClNO4 详情 详情
(IX) 63592 2-(1-[(4-nitrophenoxy)carbonyl]-2-{(E)-[5-(4-nitrophenyl)-2-furyl]methylidene}hydrazino)acetic acid C20H14N4O9 详情 详情
(X) 63593 2-(1-(aminocarbonyl)-2-{(E)-[5-(4-nitrophenyl)-2-furyl]methylidene}hydrazino)acetic acid C14H12N4O6 详情 详情
(XI) 63586 1-({(E)-[5-(4-nitrophenyl)-2-furyl]methylidene}amino)-2,4-imidazolidinedione C14H10N4O5 详情 详情

合成路线3

该中间体在本合成路线中的序号：(I)

A new synthesis of [14C]-labeled E-1040 with the label in the quinuclidine ring has been reported: The reduction of [14C]-labeled bromoacetic acid (I) with borane-dimethyl sulfide complex in ethyl ether gives 2-bromoethanol (II), which is condensed with piperidine-4-carboxamide (III) by means of K2CO3 and KI in refluxing isopropanol, yielding the [14C]-labeled 1-(2-hydroxyethyl)piperidine-4-carboxamide (IV). The reaction of (IV) with SOCl2 in refluxing acetonitrile affords the 1-(2-chloroethyl)piperidine-4-carbonitrile (V), which is cyclized by means of lithium diisopropylamide in THF, giving the quinuclidine (VI). The hydrolysis of (VI) with sulfuric acid gives [14C]-labeled quinuclidine-4-carboxamide (VII), which is finally condensed with the 3-chloromethylcephalosporin (VIII) by means of Na in acetone and a treatment with trifluoroacetic acid.

参考文献 中间体
合成目标
【1】 Woolley, G.T.; Sugiyama, I.; Yamauchi, H.; Mizuo, H.; Synthesis of 14C-labelled cefclidin (E1040). J Label Compd Radiopharm 1992, 31, 9, 663.
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) 23660 2-Bromoacetic acid 79-08-3 C2H3BrO2 详情 详情
(I) 45074 2-bromoacetic acid C2H3BrO2 详情 详情
(II) 10059 Ethylene bromohydrin; 2-Bromo-1-ethanol 540-51-2 C2H5BrO 详情 详情
(II) 45075 2-bromo-1-ethanol C2H5BrO 详情 详情
(III) 11762 4-Piperidinecarboxamide; Isonipecotamide 39546-32-2 C6H12N2O 详情 详情
(IV) 11763 1-(2-Hydroxyethyl)-4-piperidinecarboxamide C8H16N2O2 详情 详情
(IV) 45076 1-(2-hydroxyethyl)-4-piperidinecarboxamide C8H16N2O2 详情 详情
(V) 11764 1-(2-Chloroethyl)-4-piperidinecarbonitrile C8H13ClN2 详情 详情
(V) 45077 1-(2-chloroethyl)-4-piperidinecarbonitrile C8H13ClN2 详情 详情
(VI) 11765 4-Quinuclidinecarbonitrile C8H12N2 详情 详情
(VI) 45078 4-quinuclidinecarbonitrile C8H12N2 详情 详情
(VII) 11766 4-Quinuclidinecarboxamide C8H14N2O 详情 详情
(VII) 45079 4-quinuclidinecarboxamide C8H14N2O 详情 详情
(VIII) 11767 4-methoxybenzyl (6R,7R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(methoxyimino)acetyl]amino]-3-(chloromethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate C21H21ClN6O6S2 详情 详情

合成路线4

该中间体在本合成路线中的序号：(II)

Treatment of 2-(trityloxy)ethanol (I) with bromoacetic acid (II) and n-BuLi in THF affords ethoxyacetic acid derivative (III), which is then converted into ethyl ester (IV) by means of EtOH and DCC in CH2Cl2 in the presence of 4-pyrrolidinopyridine. Reaction of (IV) with Grignard reagent, prepared from 2-bromo-3-methylthiophene (V) and Mg turnings in THF, provides compound (VI), which is then converted into the corresponding tosylate derivative (VII) by treatment with BuLi and p-toluenesulfonyl chloride (p-TsCl) in toluene. Reaction of (VII) with (R)-ethyl nipecotate (VIII) and K2CO3 yields ethyl ester (IX), which is finally hydrolyzed with aqueous NaOH in EtOH followed by treatment with diluted HCl.

参考文献 中间体
合成目标
【1】 Knutsen, L.J.S.; Andersen, K.E.; Lau, J.; et al.; Synthesis of novel GABA uptake inhibitors. 3. Diaryloximine and diarylvinyl ether derivatives of nipecotic acid and guvacine as anticonvulsant agents. J Med Chem 1999, 42, 18, 3447.
【2】 Knutsen, L.J.S.; Jorgensen, A.S.; Andersen, K.E.; Sonnewald, U. (Novo Nordisk A/S); Novel N-substd. azaheterocyclic carboxylic acids. EP 0374801; JP 1990223551; US 5071859; US 5214057 .
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) 42978 2-(trityloxy)-1-ethanol C21H20O2 详情 详情
(II) 23660 2-Bromoacetic acid 79-08-3 C2H3BrO2 详情 详情
(III) 42979 2-[2-(trityloxy)ethoxy]acetic acid C23H22O4 详情 详情
(IV) 42980 ethyl 2-[2-(trityloxy)ethoxy]acetate C25H26O4 详情 详情
(V) 12443 2-Bromo-3-methylthiophene 14282-76-9 C5H5BrS 详情 详情
(VI) 42981 2-[[2,2-bis(3-methyl-2-thienyl)vinyl]oxy]-1-ethanol C14H16O2S2 详情 详情
(VII) 42982 2-[[2,2-bis(3-methyl-2-thienyl)vinyl]oxy]ethyl 4-methylbenzenesulfonate C21H22O4S3 详情 详情
(VIII) 12453 ethyl (3R)hexahydro-3-pyridinecarboxylate C8H15NO2 详情 详情
(IX) 42983 ethyl (3R)-1-(2-[[2,2-bis(3-methyl-2-thienyl)vinyl]oxy]ethyl)-3-piperidinecarboxylate C22H29NO3S2 详情 详情

合成路线5

该中间体在本合成路线中的序号：(V)

The condensation of pyridoxal 5-phosphate (I) with ethylenediamine (II) in methanol by means of NaOH gives the corresponding diimine (III), which is reduced with hydrogen over Pt/C in methanol/water yielding the expected diamine (IV). The reaction of (IV) with bromoacetic acid (V) by means of NaOH in methanol/water affords the N,N'-diacetic acid derivative (VI), which is finally treated with MnCl2 in water containing NaOH.

参考文献 中间体
合成目标
【1】 Rocklage, S.M.; Cacheris, W.P.; Quay, S.C.; Hahn, F.E.; Raymond, K.N.; Manganese(II) N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'-bis(phosphate). Synthesis and characterization of a paramagnetic chelate for magnetic resonance imaging enhancement. Inorg Chem 1989, 28, 477-85.
【2】 Graul, A.; Leeson, P.; Castaner, J.; Mangafodipir Trisodium. Drugs Fut 1997, 22, 9, 974.
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) 14753 Pyridoxal 5'-phosphate; (4-formyl-5-hydroxy-6-methyl-3-pyridinyl)methyl dihydrogen phosphate 54-47-7 C8H10NO6P 详情 详情
(II) 14754 ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine 107-15-3 C2H8N2 详情 详情
(III) 14759 [5-hydroxy-4-[([2-[((E)-[3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]-4-pyridinyl]methylidene)amino]ethyl]imino)methyl]-6-methyl-3-pyridinyl]methyl dihydrogen phosphate C18H24N4O10P2 详情 详情
(IV) 14756 [5-hydroxy-4-[([2-[([3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]-4-pyridinyl]methyl)amino]ethyl]amino)methyl]-6-methyl-3-pyridinyl]methyl dihydrogen phosphate C18H28N4O10P2 详情 详情
(V) 23660 2-Bromoacetic acid 79-08-3 C2H3BrO2 详情 详情
(VI) 14758 2-[[2-[(carboxymethyl)([3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]-4-pyridinyl]methyl)amino]ethyl]([3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]-4-pyridinyl]methyl)amino]acetic acid C22H32N4O14P2 详情 详情

合成路线6

该中间体在本合成路线中的序号：(A)

The macrocyclic tetraamine (I) was protected as the triaminomethane derivative (VIII) by treatment with either triethyl orthoformate (4) or with dimethylformamide dimethylacetal (5). Alkylation of (VIII) with bromoacetic acid gave rise to the N-formyl N',N'',N'''-tris(carboxymethyl) compound (IX). After basic hydrolysis of the formamide function of (IX), the resultant N-deprotected amine (X) was condensed with epoxide (II) to yield (XI). Further complexation with GdCl3 and ketal group hydrolysis led to the target compound

参考文献 中间体
合成目标
【1】 Murru, M.; Ripa, G.; Scala, A.; Viscardi, C.F.; Ausonio, M.; Scotti, C.; Cossuta, P. (Bracco SpA; Dibra SpA); A process for the preparation of macrocyclic chelants and the chelates thereof with paramagnetic metal ions. WO 9856775 .
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) 23660 2-Bromoacetic acid 79-08-3 C2H3BrO2 详情 详情
(I) 14855 1,4,7,10-tetraazacyclododecane; Cyclen 294-90-6 C8H20N4 详情 详情
(II) 60022 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane C7H12O3 详情 详情
(VIII) 60028 octahydro-5H-2a,4a,7,9a-tetraazacycloocta[cd]pentalene C9H18N4 详情 详情
(IX) 60029 2-[4-formyl-7,10-bis(2-hydroxy-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid C15H26N4O7 详情 详情
(X) 60030 trisodium 2-[4,10-bis(2-oxido-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetate C14H23N4Na3O6 详情 详情
(XI) 60031 trisodium 2-[4-[(5R,6S)-6-hydroxy-2,2-dimethyl-1,3-dioxepan-5-yl]-7,10-bis(2-oxido-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetate C21H35N4Na3O9 详情 详情

合成路线7

该中间体在本合成路线中的序号：(A)

In a related method for obtaining the precursor (V), epoxide (II) was condensed with the tosyl-protected tetraamine (XIII) in an autoclave at 170 C to give (XIV). The N-tosyl groups of (XIV) were then removed by treatment with lithium metal in liquid ammonia, yielding intermediate (III), which was then subjected to alkylation with bromoacetic acid, followed by acid hydrolysis

参考文献 中间体
合成目标
【1】 Platzek, J.; Gries, H.; Weinmann, H.-J.; Schuhmann-Giampieri, G.; Press, W.-R. (Schering AG); 1,4,7,10-Tetraazacyclododecane-butyl-triols, process for their preparation, and pharmaceutical agents containing these cpds.. DE 4009119; EP 0448191; US 2002176823; US 6399043 .
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) 23660 2-Bromoacetic acid 79-08-3 C2H3BrO2 详情 详情
(II) 30022 1-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-propen-1-ol C15H20O3 详情 详情
(III) 60023 (5S,6R)-2,2-dimethyl-6-(1,4,7,10-tetraazacyclododecan-1-yl)-1,3-dioxepan-5-ol C15H32N4O3 详情 详情
(V) 60025 2-[4-[(1R,2S)-2,3-dihydroxy-1-(hydroxymethyl)propyl]-7,10-bis(2-hydroxy-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid C18H34N4O9 详情 详情
(XIII) 60032 1,4,7-tris[(4-methylphenyl)sulfonyl]-1,4,7,10-tetraazacyclododecane C29H38N4O6S3 详情 详情
(XIV) 60033 (5S,6R)-2,2-dimethyl-6-{4,7,10-tris[(4-methylphenyl)sulfonyl]-1,4,7,10-tetraazacyclododecan-1-yl}-1,3-dioxepan-5-ol C36H50N4O9S3 详情 详情

合成路线8

该中间体在本合成路线中的序号：(A)

A different synthesis started from the previously reported tetraaza cyclopentaacenaphthylene (XV). Treatment of (XV) with a solution of piperazine at pH 6 gave rise to the bicyclic lactam (XVI). Alkylation of (XVI) with bromoacetic acid, followed by basic lactam hydrolysis furnished the tris(carboxymethyl) derivative (X), which was processed as in Scheme 3.

参考文献 中间体
合成目标
【1】 Argese, M.; Ripa, G. (Bracco SpA; Dibra SpA); 1,4,7,10-Tetraazabicyclo[8.2.2]tetradecan-2-one, a process for the preparation thereof and the use thereof for the preparation of tetraazamacrocycles. EP 0998476; JP 2002511884; WO 9905145 .
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) 23660 2-Bromoacetic acid 79-08-3 C2H3BrO2 详情 详情
(X) 60030 trisodium 2-[4,10-bis(2-oxido-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetate C14H23N4Na3O6 详情 详情
(XV) 60034 1,4,7,10-tetraazatricyclo[8.2.2.2~4,7~]hexadecane C12H24N4 详情 详情
(XVI) 60035 1,4,7,10-tetraazabicyclo[8.2.2]tetradecan-11-one C10H20N4O 详情 详情
(XVII) 60036 2-[7-(2-hydroxy-2-oxoethyl)-11-oxo-1,4,7,10-tetraazabicyclo[8.2.2]tetradec-4-yl]acetic acid C14H24N4O5 详情 详情

合成路线9

该中间体在本合成路线中的序号：(II)

A new synthesis for ziprasidone hydrochloride has been reported: The condensation of 6-chloroindolin-2-one (I) with bromoacetic acid (II) by means of polyphosphoric acid (PPA) gives 5-(bromoacetyl)-6-chloroindolin-2-one (III), which is reduced with triethylsilane and trifluoroacetic acid to the corresponding 2-bromoethyl derivative (IV). Finally, this compound is condensed with 4-(3-benzisothiazolyl)piperazine (V) by means of Na2CO3 in DMF or isobutyl methyl ketone.

参考文献 中间体
合成目标
【1】 Howard, H.R.; Lowe, J.A. III, Seeger, T.F.; et al.; 3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents. J Med Chem 1996, 39, 1, 143.
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) 16275 6-chloro-1,3-dihydro-2H-indol-2-one 56341-37-8 C8H6ClNO 详情 详情
(II) 23660 2-Bromoacetic acid 79-08-3 C2H3BrO2 详情 详情
(III) 16283 5-(2-bromoacetyl)-6-chloro-1,3-dihydro-2H-indol-2-one C10H7BrClNO2 详情 详情
(IV) 16284 5-(2-bromoethyl)-6-chloro-1,3-dihydro-2H-indol-2-one C10H9BrClNO 详情 详情
(V) 16280 3-piperazino-1,2-benzisothiazole; 1,2-Benzisothiazole-3-(1-piperazinyl) 87691-87-0 C11H13N3S 详情 详情

合成路线10

该中间体在本合成路线中的序号：

The reaction of 3-bromopropanol (I) with thiourea in refluxing water gives 3-sulfanylpropanol (II), which is cyclized with 2-phenylacetaldehyde (III) by means of p-toluenesulfonic acid in refluxing toluene yielding 2-benzyl-1,3-oxathiane (IV). The reductive cleavage of (IV) with Ca in liquid ammonia affords 3-(2-phenylethoxy)propanethiol (V), which is condensed with bromoacetic acid by means of NaH in DMF providing 2-[3-(2-phenylethoxy)propylsulfanyl]acetic acid (VI). The oxidation of (VI) with potassium peroxymonosulfate (oxone) gives the corresponding sulfonylacetic acid (VII), which is condensed with benzothiazolone (VIII) by means of DCC, HOBT and triethylamine in DMF yielding the correponding amide (IX). Finally, this compound is reduced with borane/THF yielding the target compound.

参考文献 中间体
合成目标
【1】 Bonnert, R.V.; Brown, R.C.; Chapman, D.; Cheshire, D.R.; Dixon, J.; Ince, F.; Kinchin, E.C.; Lyons, A.J.; Davis, A.M.; Hallam, C.; Harper, S.T.; Unitt, J.F.; Dougall, I.G.; Jackson, D.M.; McKechnie, K.; Young, A.; Simpson, W.T.; Dual D2-receptor and beta2-adrenoceptor agonists for the treatment of airway diseases. 1. Discovery and biological evaluation of some 7-(2-aminoethyl)-4-hydroxybenzothiazol-2(3H)-one analogues. J Med Chem 1998, 41, 25, 4915.
【2】 Bonnert, R.V.; Brown, R.C.; Cage, P.A.; et al.; Dual D2-receptor and beta2-adrenoceptor agonists for the treatment of airways diseases. 15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998, Edinburgh) 1998, Abst P.275.
【3】 Bonnert, R.V.; Brown, R.C.; Chapman, D.; et al.; Dual D2-receptor and beta2-adrenoceptor agonists for the treatment of airways diseases. 15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998, Edinburgh) 1998, Abst P.276.
【4】 Bonnert, R.V.; Brown, R.C.; Cheshire, D.R.; Ince, F. (AstraZeneca AB); 7-(2-Aminoethyl)-benzothiazolones. EP 0649418; JP 1996503923; US 5648370; WO 9324473 .
【5】 Castañer, J.; Graul, A.; Viozan. Drugs Fut 2000, 25, 2, 165.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
10180 Thiourea 62-56-6 CH4N2S 详情 详情
23660 2-Bromoacetic acid 79-08-3 C2H3BrO2 详情 详情
(I) 12573 3-Bromo-1-propanol; 3-Bromopropanol 627-18-9 C3H7BrO 详情 详情
(II) 25939 3-sulfanyl-1-propanol 19721-22-3 C3H8OS 详情 详情
(III) 18456 2-phenylacetaldehyde 122-78-1 C8H8O 详情 详情
(IV) 25940 2-benzyl-1,3-oxathiane C11H14OS 详情 详情
(V) 25941 3-(phenethyloxy)propylhydrosulfide; 3-(phenethyloxy)-1-propanethiol C11H16OS 详情 详情
(VI) 25942 2-[[3-(phenethyloxy)propyl]sulfanyl]acetic acid C13H18O3S 详情 详情
(VII) 25943 2-[[3-(phenethyloxy)propyl]sulfonyl]acetic acid C13H18O5S 详情 详情
(VIII) 25944 7-(2-aminoethyl)-4-hydroxy-1,3-benzothiazol-2(3H)-one C9H10N2O2S 详情 详情
(IX) 25945 N-[2-(4-hydroxy-2-oxo-2,3-dihydro-1,3-benzothiazol-7-yl)ethyl]-2-[[3-(phenethyloxy)propyl]sulfonyl]acetamide C22H26N2O6S2 详情 详情

合成路线11

该中间体在本合成路线中的序号：

The reaction of 3-bromopropanol (I) with thiourea in refluxing water gives 3-sulfanylpropanol (II), which is cyclized with 2-phenylacetaldehyde (III) by means of p-toluenesulfonic acid in refluxing toluene yielding 2-benzyl-1,3-oxathiane (IV). The reductive cleavage of (IV) with Ca in liquid ammonia affords 3-(2-phenylethoxy)propanethiol (V), which is condensed with bromoacetic acid by means of NaH in DMF providing 2-[3-(2-phenylethoxy)propylsulfanyl]acetic acid (VI). The oxidation of (VI) with potassium peroxymonosulfate (oxone) gives the corresponding sulfonylacetic acid (VII).The condensation of sulfonylacetic acid (VII) with dimethoxybenzothiazole derivative (X) by means of DCC, HOBT and triethylamine in DMF gives the corresponding amide (XI), which is reduced with borane/THF yielding intermediate (XII). Finally, this compound is demethylated with concentrated HBr or HCl.

参考文献 中间体
合成目标
【1】 Bonnert, R.V.; Brown, R.C.; Cage, P.A.; et al.; Dual D2-receptor and beta2-adrenoceptor agonists for the treatment of airways diseases. 15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998, Edinburgh) 1998, Abst P.275.
【2】 Bonnert, R.V.; Brown, R.C.; Chapman, D.; et al.; Dual D2-receptor and beta2-adrenoceptor agonists for the treatment of airways diseases. 15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998, Edinburgh) 1998, Abst P.276.
【3】 Bonnert, R.V.; Brown, R.C.; Chapman, D.; Cheshire, D.R.; Dixon, J.; Ince, F.; Kinchin, E.C.; Lyons, A.J.; Davis, A.M.; Hallam, C.; Harper, S.T.; Unitt, J.F.; Dougall, I.G.; Jackson, D.M.; McKechnie, K.; Young, A.; Simpson, W.T.; Dual D2-receptor and beta2-adrenoceptor agonists for the treatment of airway diseases. 1. Discovery and biological evaluation of some 7-(2-aminoethyl)-4-hydroxybenzothiazol-2(3H)-one analogues. J Med Chem 1998, 41, 25, 4915.
【4】 Bonnert, R.V.; Brown, R.C.; Cheshire, D.R.; Ince, F. (AstraZeneca AB); 7-(2-Aminoethyl)-benzothiazolones. EP 0649418; JP 1996503923; US 5648370; WO 9324473 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
10180 Thiourea 62-56-6 CH4N2S 详情 详情
23660 2-Bromoacetic acid 79-08-3 C2H3BrO2 详情 详情
(I) 12573 3-Bromo-1-propanol; 3-Bromopropanol 627-18-9 C3H7BrO 详情 详情
(II) 25939 3-sulfanyl-1-propanol 19721-22-3 C3H8OS 详情 详情
(III) 18456 2-phenylacetaldehyde 122-78-1 C8H8O 详情 详情
(IV) 25940 2-benzyl-1,3-oxathiane C11H14OS 详情 详情
(V) 25941 3-(phenethyloxy)propylhydrosulfide; 3-(phenethyloxy)-1-propanethiol C11H16OS 详情 详情
(VI) 25942 2-[[3-(phenethyloxy)propyl]sulfanyl]acetic acid C13H18O3S 详情 详情
(VII) 25943 2-[[3-(phenethyloxy)propyl]sulfonyl]acetic acid C13H18O5S 详情 详情
(X) 25946 2-(2,4-dimethoxy-1,3-benzothiazol-7-yl)ethylamine; 2-(2,4-dimethoxy-1,3-benzothiazol-7-yl)-1-ethanamine C11H14N2O2S 详情 详情
(XI) 25947 N-[2-(2,4-dimethoxy-1,3-benzothiazol-7-yl)ethyl]-2-[[3-(phenethyloxy)propyl]sulfonyl]acetamide C24H30N2O6S2 详情 详情
(XII) 25948 N-[2-(2,4-dimethoxy-1,3-benzothiazol-7-yl)ethyl]-N-(2-[[3-(phenethyloxy)propyl]sulfonyl]ethyl)amine; 2-(2,4-dimethoxy-1,3-benzothiazol-7-yl)-N-(2-[[3-(phenethyloxy)propyl]sulfonyl]ethyl)-1-ethanamine C24H32N2O5S2 详情 详情

合成路线12

该中间体在本合成路线中的序号：(II)

Acylation of L-leucine benzyl ester (I) with bromoacetic acid (II) in the presence of DCC and DMAP gave bromoacetamide (III), which upon reaction with triphenyl phosphine was converted to phosphonium salt (IV). After treatment of (IV) with Et3N, the resulting ylide was condensed with N-Boc-L-leucine (V) to yield the acyl- phosphonate (VI). Acid deprotection of the N-Boc group of (VI) provided amine (VII), which was condensed with the depsipeptide (VIII) using EDC and HOBt yielding (IX). Removal of the N-Fmoc group from tetrapeptide (IX) was effected by treatment with piperidine in DMF, and the resulting amino compound was further condensed with protected L-asparagine (X) to furnish peptide (XI). After hydrogenolytic removal of the benzyl and carbobenzoxy groups of (XI), treatment with diphenyl phosphoryl azide and NaHCO3 produced the cyclic depsipeptide (XII).

参考文献 中间体
合成目标
【1】 Wasserman, H.H.; et al.; The chemistry of vicinal tricarbonyls: Total syntheses of elastase inhibitors YM-47141 and YM-47142. Helv Chim Acta 2000, 83, 9, 2607.
【2】 Wasserman, H.H.; et al.; Total syntheses of depsipeptide elastase inhibitor. J Am Chem Soc 1999, 121, 6, 1401.
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) 22252 Benzyl (2S)-2-amino-4-methylpentanoate; Benzyl (S)-leucinate C13H19NO2 详情 详情
(II) 23660 2-Bromoacetic acid 79-08-3 C2H3BrO2 详情 详情
(III) 23661 benzyl (2S)-2-[(2-bromoacetyl)amino]-4-methylpentanoate C15H20BrNO3 详情 详情
(IV) 23662 benzyl (2S)-4-methyl-2-[[2-(triphenylphosphoranyl)acetyl]amino]pentanoate C33H36NO3P 详情 详情
(V) 23663 (2S)-2-[(tert-butoxycarbonyl)amino]-4-methylpentanoic acid；N-Boc-L-leucine C11H21NO4 详情 详情
(VI) 23664 benzyl (2S)-2-[[(4S)-4-[(tert-butoxycarbonyl)amino]-6-methyl-3-oxo-2-(triphenylphosphoranylidene)heptanoyl]amino]-4-methylpentanoate C44H53N2O6P 详情 详情
(VII) 23665 benzyl (2S)-2-[[(4S)-4-amino-6-methyl-3-oxo-2-(triphenylphosphoranylidene)heptanoyl]amino]-4-methylpentanoate C39H45N2O4P 详情 详情
(VIII) 23666 (2S,3S)-2-[(tert-butoxycarbonyl)amino]-3-[((2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propanoyl)oxy]butyric acid C27H32N2O8 详情 详情
(IX) 23667 benzyl (5R,8S,9S,12S,17S)-9-[(tert-butoxycarbonyl)amino]-1-(9H-fluoren-9-yl)-12,17-diisobutyl-5,8-dimethyl-3,6,10,13,15-pentaoxo-14-(triphenylphosphoranylidene)-2,7-dioxa-4,11,16-triazaoctadecan-18-oate C66H75N4O11P 详情 详情
(X) 23668 　 C13H16N2O5 详情 详情
(XI) 23669 　 C64H79N6O13P 详情 详情
(XII) 23670 　 C49H65N6O10P 详情 详情

合成路线13

该中间体在本合成路线中的序号：(II)

Acylation of L-leucine benzyl ester (I) with bromoacetic acid (II) in the presence of DCC and DMAP gave bromoacetamide (III), which upon reaction with triphenyl phosphine was converted to phosphonium salt (IV). After treatment of (IV) with Et3N, the resulting ylide was condensed with N-Boc-L-leucine (V) to yield the acyl- phosphonate (VI). Acid deprotection of the N-Boc group of (VI) provided amine (VII), which was condensed with the depsipeptide (VIII) using EDC and HOBt yielding (IX). Removal of the N-Fmoc group from tetrapeptide (IX) was effected by treatment with piperidine in DMF, and the resulting amino compound was further condensed with protected L-asparagine (X) to furnish peptide (XI). After hydrogenolytic removal of the benzyl and carbobenzoxy groups of (XI), treatment with diphenyl phosphoryl azide and NaHCO3 produced the cyclic depsipeptide (XII).

参考文献 中间体
合成目标
【1】 Wasserman, H.H.; et al.; The chemistry of vicinal tricarbonyls: Total syntheses of elastase inhibitors YM-47141 and YM-47142. Helv Chim Acta 2000, 83, 9, 2607.
【2】 Wasserman, H.H.; et al.; Total syntheses of depsipeptide elastase inhibitor. J Am Chem Soc 1999, 121, 6, 1401.
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) 22252 Benzyl (2S)-2-amino-4-methylpentanoate; Benzyl (S)-leucinate C13H19NO2 详情 详情
(II) 23660 2-Bromoacetic acid 79-08-3 C2H3BrO2 详情 详情
(III) 23661 benzyl (2S)-2-[(2-bromoacetyl)amino]-4-methylpentanoate C15H20BrNO3 详情 详情
(IV) 23662 benzyl (2S)-4-methyl-2-[[2-(triphenylphosphoranyl)acetyl]amino]pentanoate C33H36NO3P 详情 详情
(V) 23663 (2S)-2-[(tert-butoxycarbonyl)amino]-4-methylpentanoic acid；N-Boc-L-leucine C11H21NO4 详情 详情
(VI) 23664 benzyl (2S)-2-[[(4S)-4-[(tert-butoxycarbonyl)amino]-6-methyl-3-oxo-2-(triphenylphosphoranylidene)heptanoyl]amino]-4-methylpentanoate C44H53N2O6P 详情 详情
(VII) 23665 benzyl (2S)-2-[[(4S)-4-amino-6-methyl-3-oxo-2-(triphenylphosphoranylidene)heptanoyl]amino]-4-methylpentanoate C39H45N2O4P 详情 详情
(VIII) 23666 (2S,3S)-2-[(tert-butoxycarbonyl)amino]-3-[((2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propanoyl)oxy]butyric acid C27H32N2O8 详情 详情
(IX) 23667 benzyl (5R,8S,9S,12S,17S)-9-[(tert-butoxycarbonyl)amino]-1-(9H-fluoren-9-yl)-12,17-diisobutyl-5,8-dimethyl-3,6,10,13,15-pentaoxo-14-(triphenylphosphoranylidene)-2,7-dioxa-4,11,16-triazaoctadecan-18-oate C66H75N4O11P 详情 详情
(X) 23668 　 C13H16N2O5 详情 详情
(XI) 23669 　 C64H79N6O13P 详情 详情
(XII) 23670 　 C49H65N6O10P 详情 详情

合成路线14

该中间体在本合成路线中的序号：(XIII)

Further coupling and deprotection cycles incorporating peptoid N-Fmoc-N-benzylglycine (X), and twice peptoid (VIII), yielded the peptoid-resins (XI) and (XII), respectively. Bromoacetic acid (XIII) was subsequently coupled to resin (XII) to afford the bromoacetamido peptoid-resin (XIV).

参考文献 中间体
合成目标
【1】 Hamy, F.; et al.; An inhibitor of the Tat/TAR RNA interaction that effectively suppresses HIV-1 replication. Proceedings of the National Academy of Sciences of the United States of America 1997, 94, 8, 3548.
【2】 Felder, E.; Hamy, F.; Heizmann, G.; Klimkait, T.; Lazdins, J.K. (Novartis AG); Antiviral peptoid cpds.. EP 0832110; WO 9640759 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VIII) 42845 2-([(9H-fluoren-9-ylmethoxy)carbonyl][3-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]propyl]amino)acetic acid C35H44N4O7S 详情 详情
(IX) 42846 tert-butyl (5R,8R)-5-[([(1R)-1-[[(2R)-2-(aminocarbonyl)pyrrolidinyl]carbonyl]-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butyl]amino)carbonyl]-8-[4-[(tert-butoxycarbonyl)amino]butyl]-17-imino-7 C67H114N14O15S2 详情 详情
(X) 42848 2-[benzyl[(9H-fluoren-9-ylmethoxy)carbonyl]amino]acetic acid C24H21NO4 详情 详情
(XI) 42849 tert-butyl (5R,8R)-5-[([(1R)-1-[[(2R)-2-(aminocarbonyl)pyrrolidinyl]carbonyl]-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butyl]amino)carbonyl]-12-[2-(benzylamino)acetyl]-8-[4-[(tert-butoxycarbo C76H123N15O16S2 详情 详情
(XII) 42850 　 C116H187N23O24S4 详情 详情
(XIII) 23660 2-Bromoacetic acid 79-08-3 C2H3BrO2 详情 详情
(XIV) 42851 　 C118H188BrN23O25S4 详情 详情

合成路线15

该中间体在本合成路线中的序号：(VI)

The deprotection of the resin (I) with piperidine in DMF gives the amino-resin (II), which is condensed with N-Fmoc-L-proline (III) by means of diisopropylcarbodiimide (DIC) in DMF to yield the anchored proline (IV). The deprotection of (IV) with piperidine in DMF affords compound (V) with a free NH group, which is condensed with 2-bromoacetic acid (VI) by means of DIC DMF to provide the bromoacetyl proline resin (VII). The condensation of (VII) with 6-(2-aminoethylamino)pyridine-3-carbonitrile (VIII) in DMSO to give the resin anchored precursor (IX), which is finally cleaved by means of trifluoroacetic anhydride (TFAA) in THF to furnish the target pyrrolidine-carbonitrile. Alternatively, the acylation of L-prolinamide (X) with 2-bromoacetyl bromide (XI) by means of TEA and DMAP in dichloromethane gives the 1-(2-bromoacetyl)-L-prolinamide (XII), which is dehydrated by means of TFAA in dichloromethane to yield the pyrrolidine-carbonitrile (XIII). Finally, this compound is condensed with 6-(2-aminoethylamino)pyridine-3-carbonitrile (VIII) in THF to furnish the target pyrrolidine-carbonitrile.

参考文献 中间体
合成目标
【1】 Mangold, B.L.; Mone, M.D.; Dunning, B.E.; Russell, M.E.; Brinkman, J.A.; Weldon, S.C.; Hughes, T.E.; Naderi, G.B.; Villhauer, E.B.; 1-[2-[(5-Cyanopyridin-2-yl)amino]-ethylamino]acetyl-2-(S)-pyrrolidine-carbonitrile: A potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties. J Med Chem 2002, 45, 12, 2362.
【2】 Villhauer, E.B. (Novartis AG); N-Substd. 2-cyanopyrrolidines. JP 2000511559; WO 9819998 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(V),(X) 36137 (2S)-2-pyrrolidinecarboxamide;L-prolinamide 7531-52-4 C5H10N2O 详情 详情
(VII),(XII) 54331 (2S)-1-(2-bromoacetyl)-2-pyrrolidinecarboxamide n/a C7H11BrN2O2 详情 详情
(I) 28722 9H-fluoren-9-ylmethyl carbamate 84418-43-9 C15H13NO2 详情 详情
(III) 34762 (2S)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-pyrrolidinecarboxylic acid 71989-31-6 C20H19NO4 详情 详情
(IV) 42841 9H-fluoren-9-ylmethyl (2R)-2-(aminocarbonyl)-1-pyrrolidinecarboxylate C20H20N2O3 详情 详情
(VI) 23660 2-Bromoacetic acid 79-08-3 C2H3BrO2 详情 详情
(VIII) 54332 6-[(2-aminoethyl)amino]nicotinonitrile n/a C8H10N4 详情 详情
(IX) 54333 (2S)-1-[2-({2-[(5-cyano-2-pyridinyl)amino]ethyl}amino)acetyl]-2-pyrrolidinecarboxamide n/a C15H20N6O2 详情 详情
(XI) 14005 2-Bromoacetyl bromide; Bromoacetyl bromide 598-21-0 C2H2Br2O 详情 详情
(XIII) 54334 (2S)-1-(2-bromoacetyl)-2-pyrrolidinecarbonitrile n/a C7H9BrN2O 详情 详情

合成路线16

该中间体在本合成路线中的序号：(V)

The condensation of protected L-proline (I) with RINK RESIN (II) by means of TBTU, HOBT and DIEA in DMF gives the protected, rein bounded proline (III), which is deprotected by means of piperidine in DMF to yield the resin bounded proline (IV). The condensation of (IV) with 2-bromoacetic acid (V) by means of DIC in the same solvent affords the acyl proline (VI), which is treated with ethylene-1,2-diamine (VII) to provide the aminoacetyl proline (VIII). The condensation of (VIII) with 2-acetyldimedone (IX) gives the regioselectively monoprotected diaminoproline compound (X), which is treated with Boc2O and DIEA in dioxane to protect the secondary amino group of (X) and yield (XI). The selective elimination of the dimedone protecting group with hydrazine in DMF affords compound (XII) selectively monoprotected at the secondary amino group, which is condensed with 6-chloropyridine-3-carbonitrile (XIII) by means of DIEA in NMP to provide the resin adduct (XIV). The cleavage of the resin group of (XIV) by means of TFA and TFAA in dichloromethane takes place with simultaneous dehydration of the carboxamide group and removal of the Boc protecting group affording the trifluoroacetamido derivative (XV). Finally, the trifluoroacetyl group is removed by means of NH3 in aqueous methanol to give rise to the target pyridine carbonitrile derivative.

参考文献 中间体
合成目标
【1】 Willand, N.; et al.; Solid and solution phase syntheses of the 2-cyanopyrrolidide DPP-IV inhihitor NVP-DPP728. Tetrahedron 2002, 58, 28, 5741.
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) 34762 (2S)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-pyrrolidinecarboxylic acid 71989-31-6 C20H19NO4 详情 详情
(III) 42841 9H-fluoren-9-ylmethyl (2R)-2-(aminocarbonyl)-1-pyrrolidinecarboxylate C20H20N2O3 详情 详情
(IV) 36137 (2S)-2-pyrrolidinecarboxamide;L-prolinamide 7531-52-4 C5H10N2O 详情 详情
(V) 23660 2-Bromoacetic acid 79-08-3 C2H3BrO2 详情 详情
(VI) 54331 (2S)-1-(2-bromoacetyl)-2-pyrrolidinecarboxamide n/a C7H11BrN2O2 详情 详情
(VII) 14754 ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine 107-15-3 C2H8N2 详情 详情
(VIII) 57168 (2S)-1-{2-[(2-aminoethyl)amino]acetyl}-2-pyrrolidinecarboxamide C9H18N4O2 详情 详情
(IX) 57169 2-(1-hydroxyethylidene)-5,5-dimethyl-1,3-cyclohexanedione C10H14O3 详情 详情
(X) 57170 (2S)-1-{2-[(2-{[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl]amino}ethyl)amino]acetyl}-2-pyrrolidinecarboxamide C19H30N4O4 详情 详情
(XI) 57171 tert-butyl 2-[(2S)-2-(aminocarbonyl)pyrrolidinyl]-2-oxoethyl(2-{[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl]amino}ethyl)carbamate C24H38N4O6 详情 详情
(XII) 57172 tert-butyl 2-[(2S)-2-(aminocarbonyl)pyrrolidinyl]-2-oxoethyl(2-aminoethyl)carbamate C14H26N4O4 详情 详情
(XIII) 57164 2-Chloro-5-cyanopyridine; 6-Chloro-3-cyanopyridine; 6-Chloronicotinonitrile 33252-28-7 C6H3ClN2 详情 详情
(XIV) 57173 tert-butyl 2-[(2S)-2-(aminocarbonyl)pyrrolidinyl]-2-oxoethyl{2-[(5-cyano-2-pyridinyl)amino]ethyl}carbamate C20H28N6O4 详情 详情
(XV) 57174 N-{2-[(5-cyano-2-pyridinyl)amino]ethyl}-N-{2-[(2S)-2-cyanopyrrolidinyl]-2-oxoethyl}-2,2,2-trifluoroacetamide C17H17F3N6O2 详情 详情

合成路线17

该中间体在本合成路线中的序号：(IV)

Ring opening of cyclohexene oxide (I) with phenylmagnesium bromide in the presence of CuI, followed by acetylation of the resulting alcohol (II) gave the racemic trans-2-phenylcyclohexyl acetate (III). Enzymatic resolution of (III) using porcine liver acetone powder yielded the desired (-)-alcohol (II) along with unreacted (+)-acetate (III). Condensation of the sodium alkoxide of benzyl alcohol with bromoacetic acid (IV) afforded benzyloxyacetic acid (V), which was then coupled with the chiral alcohol (-)-(II) to give ester (VI). Hydrogenolysis of the O-benzyl group of (VI), followed by silylation of the resulting hydroxyacetate ester (VII) with triisopropylsilyl chloride, furnished (VIII). Imine (XI) was prepared by condensation of 3-methyl-2-butenal (IX) with p-anisidine (X). The asymmetric cyclocondensation reaction of the lithium enolate derived from ester (VIII) with imine (XI) yielded the chiral beta-lactam (XII). Oxidative removal of the p-methoxyphenyl protecting group of (XII) and then reprotection of the lactam N atom with Boc2O furnished the intermediate N-Boc lactam (XIII).

参考文献 中间体
合成目标
【1】 Strum, M.; Tynebor, R.; Pera, P.; Bernacki, R.J.; Ojima, I.; Synthesis and SAR of advanced second generation taxoids. 221st ACS Natl Meet (April 1 2001, San Diego) 2001, Abst MEDI 132.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(rac)-(III) 51206 (1R,2S)-2-phenylcyclohexyl acetate C14H18O2 详情 详情
(rac)-(II) 51208 (1R,2S)-2-phenylcyclohexanol C12H16O 详情 详情
(-)-(II) 51209 (-)-(1R,2S)-2-phenylcyclohexanol C12H16O 详情 详情
(+)-(III) 51210 (1S,2R)-2-phenylcyclohexyl acetate C14H18O2 详情 详情
(I) 17986 7-oxabicyclo[4.1.0]heptane; cyclohexene oxide 286-20-4 C6H10O 详情 详情
(IV) 23660 2-Bromoacetic acid 79-08-3 C2H3BrO2 详情 详情
(V) 51207 2-(benzyloxy)acetic acid C9H10O3 详情 详情
(VI) 51211 (1R,2S)-2-phenylcyclohexyl 2-(benzyloxy)acetate C21H24O3 详情 详情
(VII) 51212 (1R,2S)-2-phenylcyclohexyl 2-hydroxyacetate C14H18O3 详情 详情
(VIII) 19151 (1R,2S)-2-phenylcyclohexyl 2-[(triisopropylsilyl)oxy]acetate C23H38O3Si 详情 详情
(IX) 19152 3-methyl-2-butenal 107-86-8 C5H8O 详情 详情
(X) 10478 p-Anisidine; 4-Methoxyaniline; 4-Methoxyphenylamine 104-94-9 C7H9NO 详情 详情
(XI) 19154 4-methoxy-N-[(E)-3-methyl-2-butenylidene]aniline; N-(4-methoxyphenyl)-N-[(E)-3-methyl-2-butenylidene]amine C12H15NO 详情 详情
(XII) 19155 (3R,4S)-1-(4-methoxyphenyl)-4-(2-methyl-1-propenyl)-3-[(triisopropylsilyl)oxy]-2-azetidinone C23H37NO3Si 详情 详情
(XIII) 19157 tert-butyl (2S,3R)-2-(2-methyl-1-propenyl)-4-oxo-3-[(triisopropylsilyl)oxy]-1-azetidinecarboxylate C21H39NO4Si 详情 详情

合成路线18

该中间体在本合成路线中的序号：(III)

The hydrolysis of the known thioacetate (I) with NaOH in THF gives the thiol (II), which is condensed with 14C-labelled bromoacetic acid (III) by means of NaOH in water to yield the sulfanyl-acetic acid (IV). The reduction of (IV) with LiAlH4 in THF affords the sulfanylethanol derivative (V); which is condensed with 3-(4-hydroxyphenyl)propionic acid methyl ester (VI) by means of DEAD and PPh3 in toluene to provide the labelled aryl ether (VII).The hydrolysis of the ester group of (VII) by means of KOH in ethanol/water gives the propionic acid (VIII), which is converted into the trifluoromethyl ketone (IX) by reaction with oxalyl chloride, trifluoroacetic anhydride and pyridine in toluene/dichloromethane. Finally, the oxidation of the sulfanyl group of (IX) with MCPBA in dichloromethane affords the target labelled sulfone.

参考文献 中间体
合成目标
【1】 Dischino, D.D.; Banville, J.; Remillard, R.; Synthesis of carbon-14 labeled 4-[4-[2-[2-[bis(4-chlorophenyl)methoxy]ethylsulfonyl][1-14C]ethoxy]phenyl]-1,1,1-trifluoro-2-butanone. J Label Compd Radiopharm 2003, 46, 2, 167.
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) 64511 S-{2-[bis(4-chlorophenyl)methoxy]ethyl} ethanethioate C17H16Cl2O2S 详情 详情
(II) 64512 2-[bis(4-chlorophenyl)methoxy]ethylhydrosulfide; 2-[bis(4-chlorophenyl)methoxy]-1-ethanethiol C15H14Cl2OS 详情 详情
(III) 23660 2-Bromoacetic acid 79-08-3 C2H3BrO2 详情 详情
(III) 64514 2-bromoacetic acid C2H3BrO2 详情 详情
(IV) 64513 2-({2-[bis(4-chlorophenyl)methoxy]ethyl}sulfanyl)acetic acid C17H16Cl2O3S 详情 详情
(IV) 64515 2-({2-[bis(4-chlorophenyl)methoxy]ethyl}sulfanyl)acetic acid C17H16Cl2O3S 详情 详情
(V) 50507 2-([2-[bis(4-chlorophenyl)methoxy]ethyl]sulfanyl)-1-ethanol C17H18Cl2O2S 详情 详情
(V) 64516 2-({2-[bis(4-chlorophenyl)methoxy]ethyl}sulfanyl)-1-ethanol C17H18Cl2O2S 详情 详情
(VI) 30341 methyl 3-(4-hydroxyphenyl)propanoate; 4-Hydroxyphenylpropionic acid methyl ester; 3-(4-Hydroxyphenyl)propionic acid methyl ester 5597-50-2 C10H12O3 详情 详情
(VII) 50508 methyl 3-[4-[2-([2-[bis(4-chlorophenyl)methoxy]ethyl]sulfanyl)ethoxy]phenyl]propanoate C27H28Cl2O4S 详情 详情
(VII) 64517 methyl 3-{4-[2-({2-[bis(4-chlorophenyl)methoxy]ethyl}sulfanyl)ethoxy]phenyl}propanoate C27H28Cl2O4S 详情 详情
(VIII) 50509 3-[4-[2-([2-[bis(4-chlorophenyl)methoxy]ethyl]sulfanyl)ethoxy]phenyl]propionic acid C26H26Cl2O4S 详情 详情
(VIII) 64518 3-{4-[2-({2-[bis(4-chlorophenyl)methoxy]ethyl}sulfanyl)ethoxy]phenyl}propanoic acid C26H26Cl2O4S 详情 详情
(IX) 50510 4-[4-[2-([2-[bis(4-chlorophenyl)methoxy]ethyl]sulfanyl)ethoxy]phenyl]-1,1,1-trifluoro-2-butanone C27H25Cl2F3O3S 详情 详情
(IX) 64519 4-{4-[2-({2-[bis(4-chlorophenyl)methoxy]ethyl}sulfanyl)ethoxy]phenyl}-1,1,1-trifluoro-2-butanone C27H25Cl2F3O3S 详情 详情
Extended Information