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【结 构 式】 
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【分子编号】27243 【品名】[2-(chloromethoxy)ethyl](trimethyl)silane 【CA登记号】76513-69-4 |
【 分 子 式 】C6H15ClOSi 【 分 子 量 】166.7227 【元素组成】C 43.23% H 9.07% Cl 21.26% O 9.6% Si 16.85% |
合成路线1
该中间体在本合成路线中的序号：(II)Protection of the carboxyl group of Boc-L-threonine (I) with [2-(chloromethoxy)ethyl]trimethylsilane (SEM-Cl) (II) by means of Li2CO3 affords protected threonine (III). Separately, Z-L-tyrosine (IV) is treated with dimethyl sulfate and KOH in THF with tetrabutylammonium hydrogen sulfate as a catalyst to furnish N,O-dimethyl-L-tyrosine (V), which is then converted into secondary amine (VI) by coupling with protected threonine (III) either by means of 2,4,6-trichlorobenzoyl chloride in THF and DMAP in benzene or with isopropenyl chloroformate, Et3N and DMAP, followed by elimination of the carbobenzyloxy group by hydrogenation over Pd/C. Coupling of Z-L-leucine (IX) to L-proline methyl ester (X) by means of DCC, HOBt and NMM in CH2Cl2, followed by hydrolysis with LiOH, affords Z-leucylproline (VII), which is then coupled to amine (VI) by means of BOPCl and Et3N in CH2Cl2, and then subjected to deprotection with hydrofluoric acid in acetonitrile affording intermediate (VIII).
| 【1】 Li, W.-R.; et al.; Total synthesis and structural investigations of didemnins A, B, and C. J Am Chem Soc 1990, 112, 21, 7659. |
| 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) | 50745 | N-BOC-L-threonine; Boc-Threonine; N-tert-Butoxycarbonyl-L-threonine; N-(tert-Butoxycarbonyl)-L-threonine; BOC-L-Threonine | 2592-18-9 | C9H17NO5 | 详情 | 详情 |
| (II) | 27243 | [2-(chloromethoxy)ethyl](trimethyl)silane | 76513-69-4 | C6H15ClOSi | 详情 | 详情 |
| (III) | 50746 | [2-(trimethylsilyl)ethoxy]methyl (2S,3R)-2-[(tert-butoxycarbonyl)amino]-3-hydroxybutanoate | C15H31NO6Si | 详情 | 详情 | |
| (IV) | 39328 | (2S)-2-[[(benzyloxy)carbonyl]amino]-3-(4-hydroxyphenyl)propionic acid | C17H17NO5 | 详情 | 详情 | |
| (V) | 50747 | (2S)-2-[[(benzyloxy)carbonyl](methyl)amino]-3-(4-methoxyphenyl)propionic acid | C19H21NO5 | 详情 | 详情 | |
| (VI) | 50748 | (2S,3R)-2-[(tert-butoxycarbonyl)amino]-3-[[(2S)-3-(4-methoxyphenyl)-2-(methylamino)propanoyl]oxy]butyric acid | C20H30N2O7 | 详情 | 详情 | |
| (VII) | 50749 | (2S)-1-((2S)-2-[[(benzyloxy)carbonyl]amino]-4-methylpentanoyl)-2-pyrrolidinecarboxylic acid | C19H26N2O5 | 详情 | 详情 | |
| (VIII) | 50750 | (2S,3R)-3-[[(2S)-2-[[[(2S)-1-((2S)-2-[[(benzyloxy)carbonyl]amino]-4-methylpentanoyl)pyrrolidinyl]carbonyl](methyl)amino]-3-(4-methoxyphenyl)propanoyl]oxy]-2-[(tert-butoxycarbonyl)amino]butyric acid | C39H54N4O11 | 详情 | 详情 | |
| (IX) | 22838 | (2S)-2-[[(benzyloxy)carbonyl]amino]-4-methylpentanoic acid | C14H19NO4 | 详情 | 详情 | |
| (X) | 29552 | methyl (2S)-2-pyrrolidinecarboxylate | 2133-40-6 | C6H11NO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)Swern oxidation of N-(benzyloxycarbonyl)-(R)-phenylalaninol (I) gave aldehyde (II), which was subjected to a vanadium-mediated pinacol coupling to yield diol (III). Protection of the hydroxyl groups of (III) by reaction with [2-(trimethylsilyl)-ethoxy]methyl chloride (SEMCl) (IV) and DIEA in DMF provided trimethylsilyl)ethoxymethyl ether (V), whose N-benzyloxycarbonyl groups were removed by hydrogenolysis over Pd/C to afford diamine (VI). Finally, cyclization of diamine (VI) with carbonyldiimidazole produced the cyclic urea (VII).
| 【3】 Lam, P.Y.; Eyermann, C.J.; Hodge, C.N.; Jadhav, P.K.; DeLucca, G.V. (DuPont Pharmaceuticals Co.); Cyclic ureas and analogues useful as retroviral protease inhibitors. EP 0607334; EP 0686151; EP 0765873; JP 1995500324; JP 1996509700; US 5610294; WO 9307128; WO 9419329 . |
| 【1】 Hodge, C.N.; et al.; Improved cyclic urea inhibitors of the HIV-1 protease: Synthesis, potency, resistance profile, human pharmacokinetics and X-ray crystal structure of DMP 450. Chem Biol 1996, 3, 4, 301. |
| 【2】 Lam, P.Y.S.; et al.; Cyclic HIV protease inhibitors. Synthesis, conformational analysis, P2/P2' structure-activity relationship, and molecular recognition of cyclic ureas. J Med Chem 1996, 39, 18, 3514. |
| 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) | 27228 | benzyl (1R)-1-benzyl-2-hydroxyethylcarbamate | C17H19NO3 | 详情 | 详情 | |
| (II) | 27884 | benzyl (1R)-1-benzyl-2-oxoethylcarbamate | C17H17NO3 | 详情 | 详情 | |
| (III) | 19618 | benzyl (1R,2S,3S,4R)-1-benzyl-4-[[(benzyloxy)carbonyl]amino]-2,3-dihydroxy-5-phenylpentylcarbamate | C34H36N2O6 | 详情 | 详情 | |
| (IV) | 27243 | [2-(chloromethoxy)ethyl](trimethyl)silane | 76513-69-4 | C6H15ClOSi | 详情 | 详情 |
| (V) | 19920 | benzyl (1R,2S,3S,4R)-1-benzyl-4-[[(benzyloxy)carbonyl]amino]-5-phenyl-2,3-bis[[2-(trimethylsilyl)ethoxy]methoxy]pentylcarbamate | C46H64N2O8Si2 | 详情 | 详情 | |
| (VI) | 19921 | (1R,2S,3S,4R)-4-amino-1-benzyl-5-phenyl-2,3-bis[[2-(trimethylsilyl)ethoxy]methoxy]pentylamine; (2R,3S,4S,5R)-1,6-diphenyl-3,4-bis[[2-(trimethylsilyl)ethoxy]methoxy]-2,5-hexanediamine | C30H52N2O4Si2 | 详情 | 详情 | |
| (VII) | 19922 | (4R,5S,6S,7R)-4,7-dibenzyl-5,6-bis[[2-(trimethylsilyl)ethoxy]methoxy]-1,3-diazepan-2-one | C31H50N2O5Si2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(VIII)5-Methyluracil (VII) was protected with SEM-Cl (VIII) to yield the 1-SEM derivative (IX), which was subsequently alkylated with 1-bromo-3-chloropropane (X) under phase-transfer conditions to provide chloride (XI). Alkylation of piperazine (VI) with chloride (XI) in the presence of NaI and K2CO3 furnished adduct (XII). The title compound was then obtained by deprotection of (XII) upon treatment with tetrabutylammonium fluoride in THF.
| 【1】 Bantle, G.W.; Elworthy, T.R.; Guzman, A.; Jaime-Figueroa, S.; Lopez-Tapia, F.J.; Morgans, D.J. Jr.; Perez-Medrano, A.; Pfister, J.R.; Sjogren, E.B.; Talamas, F.X. (F. Hoffmann-La Roche AG); Pyrimidinedione, pyrimidinetrione, triazinedione, tetrahydroquinazolinedione derivs. as alpha1-adrenergic receptor antagonists. EP 0748800; JP 1997100269 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 54367 | 1-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]piperazine; 5-fluoro-2-(1-piperazinyl)phenyl 2,2,2-trifluoroethyl ether | C12H14F4N2O | 详情 | 详情 | |
| (VII) | 12204 | 5-Methyl-2,4(1H,3H)-pyrimidinedione; Thymine | 65-71-4 | C5H6N2O2 | 详情 | 详情 |
| (VIII) | 27243 | [2-(chloromethoxy)ethyl](trimethyl)silane | 76513-69-4 | C6H15ClOSi | 详情 | 详情 |
| (IX) | 54368 | 5-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-2,4(1H,3H)-pyrimidinedione | C11H20N2O3Si | 详情 | 详情 | |
| (X) | 10358 | 1-Bromo-3-chloropropane | 109-70-6 | C3H6BrCl | 详情 | 详情 |
| (XI) | 54369 | 3-(3-chloropropyl)-5-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-2,4(1H,3H)-pyrimidinedione | C14H25ClN2O3Si | 详情 | 详情 | |
| (XII) | 54370 | 3-(3-{4-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]-1-piperazinyl}propyl)-5-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-2,4(1H,3H)-pyrimidinedione | C26H38F4N4O4Si | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(VII)Condensation of methyl 3-amino-4-methoxybenzoate (I) with cyclopropyl cyanide (II) in the presence of p-toluenesulfonic acid at 180 C gave amidine (III). Subsequent reaction of (III) with sodium hypochlorite in methanolic HCl, followed by treatment of the intermediate chloroimine with aqueous Na2CO3, furnished the benzimidazole (IV). The ester group of (IV) was reduced to alcohol (V) with DIBAL-H, and then oxidized to aldehyde (VI) using activated MnO2. Protection of the imidazole N-H of (VI) was effected by means of 2-(trimethylsilyl)ethoxymethyl chloride (VII) and NaH to afford the 1-(2-trimethylsilyl)ethoxymethylimidazole (VIII) accompanied by some amounts of the 3-substituted analogue. The Baeyer-Villiger rearrangement of the formyl group employing m-chloroperbenzoic acid then produced phenol (IX), together with the 3-protected imidazole. The pyridylmethanol derivative (XIII) was obtained from 4-nitro-3,5-dimethylpyridine N-oxide (X) through conversion to the bromopyridine (XI) with PBr3, followed by lithium-halogen exchange and condensation with DMF to give aldehyde (XII), and then reduction of (XII) with NaBH4 to (XIII). Condensation of the hydroxybenzimidazole (IX) with pyridylmethanol (XIII) using diisopropylazodicarboxylate and triphenylphosphine gave ether (XIV), which was finally deprotected with HCl in boiling aqueous methanol to yield the target compound.
| 【1】 Cox, P.J.; Bower, S.; Aldous, D.J.; Astles, P.C.; McGarry, D.G.; Hulme, C.; Regan, J.R.; Huang, F.-C.; Djuric, S.W.; Moriarty, K.J.; Mathew, R.M.; Poli, G.B. (Aventis Pharma SA); Substd. azabicyclic cpds. and their use as inhibitors of the production of TNF and cyclic AMP phosphodiesterase. EP 0934307; JP 2000509719; WO 9748697 . |
| 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) | 25130 | methyl 3-amino-4-methoxybenzoate | 24812-90-6 | C9H11NO3 | 详情 | 详情 |
| (II) | 27238 | cyclopropanecarbonitrile | 5500-21-0 | C4H5N | 详情 | 详情 |
| (III) | 27239 | methyl 3-[[cyclopropyl(imino)methyl]amino]-4-methoxybenzoate | C13H16N2O3 | 详情 | 详情 | |
| (IV) | 27240 | methyl 2-cyclopropyl-4-methoxy-1H-benzimidazole-7-carboxylate | C13H14N2O3 | 详情 | 详情 | |
| (V) | 27241 | (2-cyclopropyl-4-methoxy-1H-benzimidazol-7-yl)methanol | C12H14N2O2 | 详情 | 详情 | |
| (VI) | 27242 | 2-cyclopropyl-4-methoxy-1H-benzimidazole-7-carbaldehyde | C12H12N2O2 | 详情 | 详情 | |
| (VII) | 27243 | [2-(chloromethoxy)ethyl](trimethyl)silane | 76513-69-4 | C6H15ClOSi | 详情 | 详情 |
| (VIII) | 27244 | 2-cyclopropyl-4-methoxy-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-benzimidazole-7-carbaldehyde | C18H26N2O3Si | 详情 | 详情 | |
| (IX) | 27245 | 2-cyclopropyl-4-methoxy-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-benzimidazol-7-ol | C17H26N2O3Si | 详情 | 详情 | |
| (X) | 27246 | 3,5-dimethyl-4-nitro-1-pyridiniumolate | C7H8N2O3 | 详情 | 详情 | |
| (XI) | 27247 | 4-bromo-3,5-dimethylpyridine | C7H8BrN | 详情 | 详情 | |
| (XII) | 27248 | 3,5-dimethylisonicotinaldehyde | C8H9NO | 详情 | 详情 | |
| (XIII) | 27249 | (3,5-dimethyl-4-pyridinyl)methanol | C8H11NO | 详情 | 详情 | |
| (XIV) | 27250 | [2-cyclopropyl-7-[(3,5-dimethyl-4-pyridinyl)methoxy]-4-methoxy-1H-benzimidazol-1-yl]methyl 2-(trimethylsilyl)ethyl ether | C25H35N3O3Si | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(II)The alkylation of 2-phenyl-4-pentenenitrile (I) with 2-(trimethylsilyl)ethoxymethyl chloride (II) in the presence of LDA afforded (III), which was reduced to aldehyde (IV) by means of DIBAL. Reductive amination of (III) with methylamine and NaBH(OAc)3 produced amine (V) and subsequent condensation with benzenesulfonyl chloride (VI) yielded sulfonamide (VII). A two-step oxidation of (VII) with osmium tetroxide and N-methylmorpholine-N-oxide, followed by sodium periodate cleavage of the resulting diol (VIII) generated aldehyde (IX). Further reductive amination of (IX) with piperidine derivative (X) gave adduct (XI). The (trimethylsilyl)ethoxy protecting group of (XI) was finally cleaved by means of trifluoroacetic acid to furnish the title compound.
| 【1】 Cladwell, C.G.; Chen, P.; Donnelly, K.F.; et al.; Discovery of potent human CCR5 antagonists for the treatment of HIV-1 infection-IV. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 120. |
| 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) | 39738 | 2-phenyl-3-butenenitrile | C10H9N | 详情 | 详情 | |
| (II) | 27243 | [2-(chloromethoxy)ethyl](trimethyl)silane | 76513-69-4 | C6H15ClOSi | 详情 | 详情 |
| (III) | 39739 | 2-phenyl-2-[[2-(trimethylsilyl)ethoxy]methyl]-3-butenenitrile | C16H23NOSi | 详情 | 详情 | |
| (IV) | 39740 | 2-phenyl-2-[[2-(trimethylsilyl)ethoxy]methyl]-4-pentenal | C17H26O2Si | 详情 | 详情 | |
| (V) | 39741 | N-methyl-N-(2-phenyl-2-[[2-(trimethylsilyl)ethoxy]methyl]-4-pentenyl)amine; N-methyl-2-phenyl-2-[[2-(trimethylsilyl)ethoxy]methyl]-4-penten-1-amine | C18H31NOSi | 详情 | 详情 | |
| (VI) | 14713 | benzenesulfonyl chloride | 98-09-9 | C6H5ClO2S | 详情 | 详情 |
| (VII) | 39742 | N-methyl-N-(2-phenyl-2-[[2-(trimethylsilyl)ethoxy]methyl]-4-pentenyl)benzenesulfonamide | C24H35NO3SSi | 详情 | 详情 | |
| (VIII) | 39743 | N-(4,5-dihydroxy-2-phenyl-2-[[2-(trimethylsilyl)ethoxy]methyl]pentyl)-N-methylbenzenesulfonamide | C24H37NO5SSi | 详情 | 详情 | |
| (IX) | 39744 | N-methyl-N-(4-oxo-2-phenyl-2-[[2-(trimethylsilyl)ethoxy]methyl]butyl)benzenesulfonamide | C23H33NO4SSi | 详情 | 详情 | |
| (X) | 39745 | benzyl ethyl(4-piperidinyl)carbamate | C15H22N2O2 | 详情 | 详情 | |
| (XI) | 39746 | benzyl ethyl[1-(4-[methyl(phenylsulfonyl)amino]-3-phenyl-3-[[2-(trimethylsilyl)ethoxy]methyl]butyl)-4-piperidinyl]carbamate | C38H55N3O5SSi | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(XV)Synthesis of intermediate (XVI): The reaction of the nitrone (XIII) first with hydroxylamine and then with formic acid gives hydroxamate (XIV), which is protected with 2-(trimethylsilylethoxymethyl chloride (A), DIEA and DMAP in CH2Cl2 to affords the protected ester (XV). Finally the methyl ester group of (XV) is hydrolyzed with NaOH in THF/water to afford the acid intermediate (XVI).
| 【1】 Yokokawa, F.; et al.; Total synthesis of amamistatin A, an antiproliferative linear peptide from an actinomycete. Tetrahedron 2000, 56, 19, 3027. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIII) | 42027 | ((4R)-4-[[(benzyloxy)carbonyl]amino]-5-methoxy-5-oxopentyl)(1-methylethylidene)ammoniumolate | C17H24N2O5 | 详情 | 详情 | |
| (XIV) | 42028 | methyl (2R)-2-[[(benzyloxy)carbonyl]amino]-5-[formyl(hydroxy)amino]pentanoate | C15H20N2O6 | 详情 | 详情 | |
| (XV) | 27243 | [2-(chloromethoxy)ethyl](trimethyl)silane | 76513-69-4 | C6H15ClOSi | 详情 | 详情 |
| (XVI) | 42029 | methyl (12R)-12-[[(benzyloxy)carbonyl]amino]-8-formyl-2,2-dimethyl-5,7-dioxa-8-aza-2-silatridecan-13-oate | C21H34N2O7Si | 详情 | 详情 | |
| (XVII) | 42030 | (12R)-12-[[(benzyloxy)carbonyl]amino]-8-formyl-2,2-dimethyl-5,7-dioxa-8-aza-2-silatridecan-13-oic acid | C20H32N2O7Si | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(VI)The condensation of 4-chloro-2,6-pyridinedicarboxylic acid (I) with morpholine (II) afforded the morpholinopyridinedicarboxylic acid (III), which was further esterified with MeOH and HCl to produce diester (IV). Reduction of (IV) with NaBH4 and CaCl2 gave hydroxy ester (V). After protection of the hydroxyl group of (V) as the trimethylsilylethoxymethyl derivative (VII), the ester group was hydrolyzed under basic conditions yielding acid (VIII). This was then subjected to a Curtius rearrangement with DPPA in the presence of tert-butanol to generate the tert-butyl carbamate (IX). Alkylation of carbamate (IX) with 3-methoxy-5-nitrobenzyl bromide (X) and NaH furnished the N-benzyl carbamate derivative (XI). The nitro group of (XI) was then reduced to amine (XII) by catalytic hydrogenation over Pd/C.
| 【1】 Fukami, T.; Mase, T.; Tsuchiya, Y.; Kanatani, A.; Fukuroda, T. (Banyu Pharmaceutical Co., Ltd.); Aminopyridine derivs.. EP 0889034; US 6011039; WO 9734873 . |
| 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) | 58799 | 4-chloro-2,6-pyridinedicarboxylic acid | C7H4ClNO4 | 详情 | 详情 | |
| (II) | 10388 | Morpholine | 110-91-8 | C4H9NO | 详情 | 详情 |
| (III) | 58800 | 4-(4-morpholinyl)-2,6-pyridinedicarboxylic acid | C11H12N2O5 | 详情 | 详情 | |
| (IV) | 58801 | dimethyl 4-(4-morpholinyl)-2,6-pyridinedicarboxylate | C13H16N2O5 | 详情 | 详情 | |
| (V) | 58802 | ethyl 6-(hydroxymethyl)-4-(4-morpholinyl)-2-pyridinecarboxylate | C13H18N2O4 | 详情 | 详情 | |
| (VI) | 27243 | [2-(chloromethoxy)ethyl](trimethyl)silane | 76513-69-4 | C6H15ClOSi | 详情 | 详情 |
| (VII) | 58803 | ethyl 4-(4-morpholinyl)-6-({[2-(trimethylsilyl)ethoxy]methoxy}methyl)-2-pyridinecarboxylate | C19H32N2O5Si | 详情 | 详情 | |
| (VIII) | 58804 | 4-(4-morpholinyl)-6-({[2-(trimethylsilyl)ethoxy]methoxy}methyl)-2-pyridinecarboxylic acid | C17H28N2O5Si | 详情 | 详情 | |
| (IX) | 58805 | tert-butyl 4-(4-morpholinyl)-6-({[2-(trimethylsilyl)ethoxy]methoxy}methyl)-2-pyridinylcarbamate | C21H37N3O5Si | 详情 | 详情 | |
| (X) | 58806 | 3-(bromomethyl)-5-nitrophenyl methyl ether; 1-(bromomethyl)-3-methoxy-5-nitrobenzene | C8H8BrNO3 | 详情 | 详情 | |
| (XI) | 58807 | tert-butyl 3-methoxy-5-nitrobenzyl[4-(4-morpholinyl)-6-({[2-(trimethylsilyl)ethoxy]methoxy}methyl)-2-pyridinyl]carbamate | C29H44N4O8Si | 详情 | 详情 | |
| (XII) | 58808 | tert-butyl 3-amino-5-methoxybenzyl[4-(4-morpholinyl)-6-({[2-(trimethylsilyl)ethoxy]methoxy}methyl)-2-pyridinyl]carbamate | C29H46N4O6Si | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(XIII)Lithiation of thiazole (X) with butyllithium, and then addition to hexafluoroacetone (XI) in cold Et2O gives the carbinol adduct (XII), which is subsequently protected with 2-(trimethylsilyl)ethoxymethyl chloride (XIII), yielding the SEM ether (XIV). A further metalation of (XIV) with butyllithium, followed by addition to aldehyde (IX) provides alcohol (XV). Bromination of (XV), with simultaneous SEM group cleavage to afford (XVI), is accomplished by treatment with thionyl bromide and pyridine. Alkylation of the potassium enolate of ethyl 3-pyridylacetate N-oxide (XVII) with bromide (XVI) gives ester (XVIII). Finally, decarboethoxylation of (XVIII) by means of LiOH, followed by resolution of the racemic mixture using chiral HPLC furnishes the title enantiomer.
| 【1】 Girard, M.; Frenette, R.; Hamel, P.; Guay, D.; Ducharme, Y.; Blouin, M.; Friesen, R.; Cote, B.; Martins, E.; Laliberte, S. (Merck Frosst Canada Inc.); Tri-aryl-substd.-ethane PDE4 inhibitors. EP 1272488; US 6399636; WO 0170738 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 59749 | 3-(cyclopropyloxy)-4-(difluoromethoxy)benzaldehyde | C11H10F2O3 | 详情 | 详情 | |
| (X) | 23000 | 1,3-thiazole | 288-47-1 | C3H3NS | 详情 | 详情 |
| (XI) | 44260 | 1,1,1,3,3,3-hexafluoroacetone | 684-16-2 | C3F6O | 详情 | 详情 |
| (XII) | 59750 | 1,1,1,3,3,3-hexafluoro-2-(1,3-thiazol-2-yl)-2-propanol | C6H3F6NOS | 详情 | 详情 | |
| (XIII) | 27243 | [2-(chloromethoxy)ethyl](trimethyl)silane | 76513-69-4 | C6H15ClOSi | 详情 | 详情 |
| (XIV) | 59751 | 2-(2,2,2-trifluoro-1-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methoxy}ethyl)-1,3-thiazole; [2,2,2-trifluoro-1-(1,3-thiazol-2-yl)-1-(trifluoromethyl)ethoxy]methyl 2-(trimethylsilyl)ethyl ether | C12H17F6NO2SSi | 详情 | 详情 | |
| (XV) | 59752 | [3-(cyclopropyloxy)-4-(difluoromethoxy)phenyl][2-(2,2,2-trifluoro-1-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methoxy}ethyl)-1,3-thiazol-5-yl]methanol | C23H27F8NO5SSi | 详情 | 详情 | |
| (XVI) | 59753 | 2-(5-{bromo[3-(cyclopropyloxy)-4-(difluoromethoxy)phenyl]methyl}-1,3-thiazol-2-yl)-1,1,1,3,3,3-hexafluoro-2-propanol | C17H12BrF8NO3S | 详情 | 详情 | |
| (XVII) | 59754 | 3-(2-ethoxy-2-oxoethyl)-1-pyridiniumolate | C9H11NO3 | 详情 | 详情 | |
| (XVIII) | 59755 | 3-(2-[3-(cyclopropyloxy)-4-(difluoromethoxy)phenyl]-1-(ethoxycarbonyl)-2-{2-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]-1,3-thiazol-5-yl}ethyl)-1-pyridiniumolate | C26H22F8N2O6S | 详情 | 详情 |