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【结 构 式】 
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【分子编号】14103 【品名】2-Thiophenecarbonyl chloride 【CA登记号】5271-67-0 |
【 分 子 式 】C5H3ClOS 【 分 子 量 】146.59692 【元素组成】C 40.97% H 2.06% Cl 24.18% O 10.91% S 21.87% |
合成路线1
该中间体在本合成路线中的序号：(I)The reaction of 2-thiophenecarbonyl chloride (I) with fluorobenzene (A) by means of AlCl3 gives (4-fluorophenyl)(2-thienyl)ketone (II), which is then condensed with diethyl methylmalonate (B) by means of NaH in benzene-HMPA to yield diethyl 2-methyl-2-[4-(2-thienylcarbonyl)phenyl]malonate (III); this product is finally hydrolyzed and partially decarboxylated with refluxing aqueous NaOH.
| 【1】 Van Daele, P.G.H.; et al.; Synthesis of alpha-methyl-4-(2-thienylcarbonyl)benzene acetic acid, suprofen and derivatives. Arzneim-Forsch Drug Res 1975, 25, 10, 1495-1501. |
| 【2】 Castaner, J.; Chatterjee, S.S.; Suprofen. Drugs Fut 1976, 1, 3, 148. |
| 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) | 17466 | Fluorobenzene | 462-06-6 | C6H5F | 详情 | 详情 |
| (B) | 30310 | diethyl 2-methylmalonate | 609-08-5 | C8H14O4 | 详情 | 详情 |
| (I) | 14103 | 2-Thiophenecarbonyl chloride | 5271-67-0 | C5H3ClOS | 详情 | 详情 |
| (II) | 34018 | (4-fluorophenyl)(2-thienyl)methanone | 579-49-7 | C11H7FOS | 详情 | 详情 |
| (III) | 34019 | diethyl 2-methyl-2-[4-(2-thienylcarbonyl)phenyl]malonate | C19H20O5S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)Reaction of thiophene-2-carboxylic acid (VIII) with oxalyl chloride and PPh3 gives the corresponding acyl chloride (IX), which is condensed with vinyltributylstannane, yielding 1-(2-thienyl)-2-propen-1-one (X). The addition of HCl to the double bond of (X) affords 3-chloro-1-(2-thienyl)-1-propanone (XI), which is reduced with BH3 and the chiral (R)-oxazaborolidine catalyst (XII) in THF to give (S)-3-chloro-1-(2-thienyl)-1-propanol (XIII) (4). Treatment of (XIII) with NaI in acetone affords the (S)-3-iodopropanol derivative (XIV), which is condensed with methylamine in THF to provide (S)-3-(methylamino)-1-(2-thienyl)-1-propanol (XV). Finally, this compound is condensed with 1-fluoronaphthalene (V) by means of NaH in DMA. The Friedel-Crafts condensation of thiophene (XVI) with 3-chloropropionyl chloride (XVII) by means of SnCl4 in benzene gives the previously reported 3-chloro-1-(2-thienyl)-1-propanone (XI), which is reduced with NaBH4 in ethanol to yield the racemic alcohol (XVIII). Optical resolution of (XVIII) performed by means of immobilized CALB (Novozyme 435, Novo-Nordisk A/S) affords the previously reported (S)-alcohol (XIII).
| 【1】 Sorbera, L.A.; Castaner, R.M.; Castaner, J.; Duloxetine oxalate. Drugs Fut 2000, 25, 9, 907. |
| 【2】 Wheeler, W.J.; Kuo, F.; An asymmetric synthesis of duloxetine hydrochloride, a mixed uptake inhibitor of serotonin and norepinephrine, and its C-14 labeled isotopomers. J Label Compd Radiopharm 1995, 36, 3, 213. |
| 【3】 Hoff, B.H.; Liu, H.; Anthonsen, T.; Chemo-enzymatic synthesis of the antidepressant duloxetine and its enantiomer. Chirality 2000, 12, 1, 26. |
| 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) | 40503 | 1-fluoronaphthalene | 321-38-0 | C10H7F | 详情 | 详情 |
| (VIII) | 40505 | 2-thiophenecarboxylic acid | 527-72-0 | C5H4O2S | 详情 | 详情 |
| (IX) | 14103 | 2-Thiophenecarbonyl chloride | 5271-67-0 | C5H3ClOS | 详情 | 详情 |
| (X) | 40506 | 1-(2-thienyl)-2-propen-1-one | C7H6OS | 详情 | 详情 | |
| (XI) | 40507 | 3-chloro-1-(2-thienyl)-1-propanone | C7H7ClOS | 详情 | 详情 | |
| (XII) | 20631 | (R)-Methyl oxazaborolidine; (3aR)-1-methyl-3,3-diphenyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole | 112022-83-0 | C18H20BNO | 详情 | 详情 |
| (XIII) | 40509 | (1S)-3-chloro-1-(2-thienyl)-1-propanol | C7H9ClOS | 详情 | 详情 | |
| (XIV) | 40510 | (1S)-3-iodo-1-(2-thienyl)-1-propanol | C7H9IOS | 详情 | 详情 | |
| (XV) | 40511 | (1S)-3-(methylamino)-1-(2-thienyl)-1-propanol | 116539-55-0 | C8H13NOS | 详情 | 详情 |
| (XVI) | 13297 | Thiophene | 110-02-1 | C4H4S | 详情 | 详情 |
| (XVII) | 18936 | 3-chloropropanoyl chloride | 625-36-5 | C3H4Cl2O | 详情 | 详情 |
| (XVIII) | 40508 | 3-chloro-1-(2-thienyl)-1-propanol | C7H9ClOS | 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 reaction of thiophene-2-[14C]carboxylic acid (VII) with oxalyl chloride and PPh3 gives the corresponding labeled acyl chloride (VIII), which is condensed with vinyltributylstannane, yielding 1-(2-thienyl)-[1-14C]prop-2-en-1-one (IX). The addition of HCl to the double bond of (IX) affords 3-chloro-1-(2-thienyl)-[1-14C]propan-1-one (X), which is reduced with BH3 and the chiral (R)-oxazaborolidine catalyst (XI) in THF to give (S)-3-chloro-1-(2-thienyl)-[1-14C]propan-1-ol (XII). Treatment of (XII) with NaI in acetone affords the labeled (S)-3-iodopropanol derivative (XIII), which is condensed with methylamine in THF to provide (S)-3-(methylamino)-1-(2-thienyl)-[1-14C]propan-1-ol (XIV). Finally, this compound is condensed with 1-fluoronaphthalene (V) by means of NaH in DMA.
| 【1】 Sorbera, L.A.; Castaner, R.M.; Castaner, J.; Duloxetine oxalate. Drugs Fut 2000, 25, 9, 907. |
| 【2】 Wheeler, W.J.; Kuo, F.; An asymmetric synthesis of duloxetine hydrochloride, a mixed uptake inhibitor of serotonin and norepinephrine, and its C-14 labeled isotopomers. J Label Compd Radiopharm 1995, 36, 3, 213. |
| 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) | 40503 | 1-fluoronaphthalene | 321-38-0 | C10H7F | 详情 | 详情 |
| (VII) | 40505 | 2-thiophenecarboxylic acid | 527-72-0 | C5H4O2S | 详情 | 详情 |
| (VII) | 45145 | 2-thiophenecarboxylic acid | C5H4O2S | 详情 | 详情 | |
| (VIII) | 14103 | 2-Thiophenecarbonyl chloride | 5271-67-0 | C5H3ClOS | 详情 | 详情 |
| (VIII) | 45146 | 2-thiophenecarbonyl chloride | C5H3ClOS | 详情 | 详情 | |
| (IX) | 40506 | 1-(2-thienyl)-2-propen-1-one | C7H6OS | 详情 | 详情 | |
| (IX) | 45147 | 1-(2-thienyl)-2-propen-1-one | C7H6OS | 详情 | 详情 | |
| (X) | 40507 | 3-chloro-1-(2-thienyl)-1-propanone | C7H7ClOS | 详情 | 详情 | |
| (X) | 45148 | 3-chloro-1-(2-thienyl)-1-propanone | C7H7ClOS | 详情 | 详情 | |
| (XI) | 20631 | (R)-Methyl oxazaborolidine; (3aR)-1-methyl-3,3-diphenyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole | 112022-83-0 | C18H20BNO | 详情 | 详情 |
| (XII) | 40509 | (1S)-3-chloro-1-(2-thienyl)-1-propanol | C7H9ClOS | 详情 | 详情 | |
| (XII) | 45149 | (1S)-3-chloro-1-(2-thienyl)-1-propanol | C7H9ClOS | 详情 | 详情 | |
| (XIII) | 40510 | (1S)-3-iodo-1-(2-thienyl)-1-propanol | C7H9IOS | 详情 | 详情 | |
| (XIII) | 45150 | (1S)-3-iodo-1-(2-thienyl)-1-propanol | C7H9IOS | 详情 | 详情 | |
| (XIV) | 40511 | (1S)-3-(methylamino)-1-(2-thienyl)-1-propanol | 116539-55-0 | C8H13NOS | 详情 | 详情 |
| (XIV) | 45151 | (1S)-3-(methylamino)-1-(2-thienyl)-1-propanol | C8H13NOS | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(II)The reaction of thiophene-2-carboxylic acid (I) with oxalyl chloride and PPh3 gives the corresponding acyl chloride (II), which is condensed with vinyltributylstannane to yield 1-(2-thienyl)-2-propen-1-one (III). The addition of HCl to the double bond of (III) affords 3-chloro-1-(2-thienyl)-1-propanone (IV), which is reduced with BH3 and the chiral (S)-oxazaborolidine catalyst (V) in THF to give the (R)-3-chloro-1-(2-thienyl)-1-propanol (VI). The condensation of (VI) with [1-14C]-1-naphthol (VII) by means of DEAD and PPh3 in THF affords the labeled naphthyl ether derivative (VIII), which is treated with NaI in acetone to give the labeled iodo derivative (IX). Finally, this compound is treated with methylamine in hot THF.
| 【1】 Wheeler, W.J.; Kuo, F.; Approaches to an asymmetric synthesis of duloxetine, a mixed uptake inhibitor of serotonin and norepinephrine, and its C-14 labeled analogs. Synthesis and Applications of Isotopically Labelled Compounds 1994, 597-603. |
| 【2】 Sorbera, L.A.; Castaner, R.M.; Castaner, J.; Duloxetine oxalate. Drugs Fut 2000, 25, 9, 907. |
| 【3】 Wheeler, W.J.; Kuo, F.; An asymmetric synthesis of duloxetine hydrochloride, a mixed uptake inhibitor of serotonin and norepinephrine, and its C-14 labeled isotopomers. J Label Compd Radiopharm 1995, 36, 3, 213. |
| 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) | 40505 | 2-thiophenecarboxylic acid | 527-72-0 | C5H4O2S | 详情 | 详情 |
| (II) | 14103 | 2-Thiophenecarbonyl chloride | 5271-67-0 | C5H3ClOS | 详情 | 详情 |
| (III) | 40506 | 1-(2-thienyl)-2-propen-1-one | C7H6OS | 详情 | 详情 | |
| (IV) | 40507 | 3-chloro-1-(2-thienyl)-1-propanone | C7H7ClOS | 详情 | 详情 | |
| (V) | 28292 | (S)-Methyl oxazaborolidine; (3aS)-1-methyl-3,3-diphenyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole | 112022-81-8 | C18H20BNO | 详情 | 详情 |
| (VI) | 40512 | (1R)-3-chloro-1-(2-thienyl)-1-propanol | C7H9ClOS | 详情 | 详情 | |
| (VII) | 22935 | alpha-naphthol; 1-naphthol | 90-15-3 | C10H8O | 详情 | 详情 |
| (VII) | 45152 | 1-naphthol | C10H8O | 详情 | 详情 | |
| (VIII) | 40513 | (1S)-3-chloro-1-(2-thienyl)propyl 1-naphthyl ether; 2-[(1S)-3-chloro-1-(1-naphthyloxy)propyl]thiophene | C17H15ClOS | 详情 | 详情 | |
| (VIII) | 45153 | (1S)-3-chloro-1-(2-thienyl)propyl 1-naphthyl ether; 2-[(1S)-3-chloro-1-(1-naphthyloxy)propyl]thiophene | C17H15ClOS | 详情 | 详情 | |
| (IX) | 40514 | (1S)-3-iodo-1-(2-thienyl)propyl 1-naphthyl ether; 2-[(1S)-3-iodo-1-(1-naphthyloxy)propyl]thiophene | C17H15IOS | 详情 | 详情 | |
| (IX) | 45154 | 2-[(1S)-3-iodo-1-(1-naphthyloxy)propyl]thiophene; (1S)-3-iodo-1-(2-thienyl)propyl 1-naphthyl ether | C17H15IOS | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(II)Triethylamine is added to thiolactic acid (I) and 2-thiophencarbonyl chloride (II) in tetrahydrofuran. Mix is cooled at -5 C under agitation and thionyl chloride is added keeping the temperature between 0 and 10 C. A solution of homocysteine thiolactone hydrochloride and triethylamine in water is then added to the reaction, keeping the temperature below 10 C. The reaction is carried out for 1 h at room temperature under agitation, after which the solvent is evaporated at reduced pressure. Water is used to wash and diethyl ether to extract. The organic phase is dried on Na2SO4 anhydrous and the solvent is eliminated at reduced pressure. The raw product obtained from a mix of dichloromethane/diethyl ether (60/40) is crystallized (MR-889).
| 【1】 Quadro, G.; MR-889. Drugs Fut 1990, 15, 10, 997. |
| 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) | 24361 | 2-sulfanylpropionic acid; 2-mercaptopropionic acid | 57965-30-7 | C3H6O2S | 详情 | 详情 |
| (II) | 14103 | 2-Thiophenecarbonyl chloride | 5271-67-0 | C5H3ClOS | 详情 | 详情 |
| (III) | 31190 | 2-[(2-thienylcarbonyl)sulfanyl]propionic acid | C8H8O3S2 | 详情 | 详情 | |
| (IV) | 31191 | S-(2-chloro-1-methyl-2-oxoethyl) 2-thiophenecarbothioate | C8H7ClO2S2 | 详情 | 详情 | |
| (V) | 22495 | 3-aminodihydro-2(3H)-thiophenone | 10593-85-8 | C4H7NOS | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(VI)The synthesis of [14C]-labeled tenidap sodium has been reported: The chlorination of [14C]-2,3-dihydro-1H-indole-2,3-dione (I) with sulfuryl chloride and triethylamine in hot acetonitrile gives the 5-chloro derivative (II), which is partially reduced by treatment with hydrazine hydrate in refluxing ethanol, followed by a treatment with KOH in the same refluxing solvent, to yield 5-chloro-2,3-dihydro-1H-indol-2-one (III). The reaction of (III) with chlorosulfonyl isocyanate (IV) in refluxing dichloromethane affords 5-chloro-2-oxo-2,3-dihydro-1H-indole-1-carboxamide (V), which is condensed with 2-thienylcarbonyl chloride (VI) by means of dimethylaminopyridine (DMAP) and triethylamine (TEA) in DMF, giving tenidap (VII). Finally, this compound is treated with NaHCO3 in hot acetone.
| 【1】 Hale, K.J.; Lennon, J.A.; Hobbs, C.J.; Javaid, M.H.; Manaviazar, S.; Asymmetric synthesis of the C17-C27 segment of the antineoplasticmacrolide bryostatin 1. J Label Compd Radiopharm 1995, 36, 8, 1359. |
| 【2】 Johnson, D.L.; Melvin, L.S.; Falkner, F.C.; Rusek, F.W.; Robinson, R.P.; Synthesis of C-14 isotopic isomers of tenidap - A novel antiinflammatory agent. J Label Compd Radiopharm 1996, 38, 3, 207. |
| 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) | 14098 | 2,3-Indolinedione; 1H-Indole-2,3-dione; Isatin | 91-56-5 | C8H5NO2 | 详情 | 详情 |
| (I) | 45196 | C8H5NO2 | 详情 | 详情 | ||
| (II) | 14099 | 5-Chloro-1H-indole-2,3-dione; 5-Chloroisatin | 17630-76-1 | C8H4ClNO2 | 详情 | 详情 |
| (II) | 45197 | C8H4ClNO2 | 详情 | 详情 | ||
| (III) | 14100 | 5-Chlorooxindole; 5-Chloro-1,3-dihydro-2H-indol-2-one | 17630-75-0 | C8H6ClNO | 详情 | 详情 |
| (III) | 45198 | C8H6ClNO | 详情 | 详情 | ||
| (IV) | 14101 | Chlorosulfonyl isocyanate | 1189-71-5 | CClNO3S | 详情 | 详情 |
| (V) | 14096 | 5-Chloro-2-oxo-1-indolinecarboxamide | C9H7ClN2O2 | 详情 | 详情 | |
| (V) | 45199 | C9H7ClN2O2 | 详情 | 详情 | ||
| (VI) | 14103 | 2-Thiophenecarbonyl chloride | 5271-67-0 | C5H3ClOS | 详情 | 详情 |
| (VII) | 14104 | 5-Chloro-3-[(Z)-hydroxy(2-thienyl)methylidene]-2-oxo-1H-indole-1(2H)-carboxamide | C14H9ClN2O3S | 详情 | 详情 | |
| (VII) | 45200 | C14H9ClN2O3S | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(IV)A new synthesis of tenidap has been developed: The reaction of 5-chloroindolin-2-one (I) with phenyl chloroformate and Et3N in THF gives 5-chloro-2-(phenoxycarbonyloxy)indole-1-carboxylic acid phenyl ester (II), which is treated with ammonium carbonate in DMF at 5 C yielding 5-chloro-2-oxoindoline-1-carboxylic acid phenyl ester (III). Compound (III) is acylated with 2-thienylcarbonyl chloride (IV) and DMAP in DMF and then acidified with conc. HCl affording 5-chloro-3-[1-hydroxy-1-(2-thienyl)methylene]-2-oxoindoline-1-carboxylic acid phenyl ester (V), which is finally treated with ammonium carbonate in DMF at 75-80 C for 5 h and acidified with conc. HCl.
| 【1】 Siming, G.; Porcs-Makkay, M.; New practical synthesis of tenidap. Org Process Res Dev 2000, 4, 1, 10. |
| 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) | 14100 | 5-Chlorooxindole; 5-Chloro-1,3-dihydro-2H-indol-2-one | 17630-75-0 | C8H6ClNO | 详情 | 详情 |
| (II) | 40474 | phenyl 5-chloro-2-[(phenoxycarbonyl)oxy]-1H-indole-1-carboxylate | C22H14ClNO5 | 详情 | 详情 | |
| (III) | 40475 | phenyl 5-chloro-2-oxo-1-indolinecarboxylate | C15H10ClNO3 | 详情 | 详情 | |
| (IV) | 14103 | 2-Thiophenecarbonyl chloride | 5271-67-0 | C5H3ClOS | 详情 | 详情 |
| (V) | 40476 | phenyl 5-chloro-3-[(Z)-hydroxy(2-thienyl)methylidene]-2-oxo-1H-indole-1(2H)-carboxylate | C20H12ClNO4S | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(II)Amine (I) was acylated with 2-thiophenecarbonyl chloride (II) in a mixture of ethyl acetate and a saturated solution of NaHCO3 to give amide (III). Then, removal of both trichloroethoxycarbonyl protecting groups was effected by treatment with zinc dust in methanol and acetic acid to provide the title compound.
| 【1】 Ali, S.M.; et al.; Butitaxel analogues: Synthesis and structure-activity relationships. J Med Chem 1997, 40, 2, 236-241. |
| 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) | 18162 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-[[(2R,3S)-3-amino-2-hydroxy-4,4-dimethylpentanoyl]oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12-bis[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl | C42H51Cl6NO16 | 详情 | 详情 | |
| (II) | 14103 | 2-Thiophenecarbonyl chloride | 5271-67-0 | C5H3ClOS | 详情 | 详情 |
| (III) | 18164 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1-hydroxy-15-([(2R,3S)-2-hydroxy-4,4-dimethyl-3-[(2-thienylcarbonyl)amino]pentanoyl]oxy)-10,14,17,17-tetramethyl-11-oxo-9,12-bis[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C47H53Cl6NO17S | 详情 | 详情 |
合成路线9
该中间体在本合成路线中的序号：(XIV)Bromination of 5-aminopyrazole (XI) with Br2 in AcOH gives 4-bromo-5-aminopyrazole (XII), which is cyclized with N-[3-[3-(dimethylamino)-2-propenoyl]phen-yl]-N-methylacetamide (X) in AcOH to yield the 3-bromo-pyrazolo[1,5-a]pyrimidine derivative (XIII). Finally, this compound can be condensed with either 2-thienylcarbonyl chloride (XIV) by means of Zn or Mg or with 2-thienylboronic acid (XV) and CO by means of a Pd(0) catalyst.
| 【1】 Sorbera, L.A.; Castaner, J.; Martin, L.; Indiplon. Drugs Fut 2003, 28, 8, 739. |
| 【2】 Wilcoxen, K.M.; Gross, R.S. (Neurocrine Biosciences Inc.); Synthesis of substd. pyrazolopyrimidines. WO 0110868 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 59947 | N-{3-[(E)-3-(dimethylamino)-2-propenoyl]phenyl}-N-methylacetamide | C14H18N2O2 | 详情 | 详情 | |
| (XI) | 56012 | 1H-pyrazol-5-amine; 1H-pyrazol-5-ylamine | 916420-28-5 | C3H5N3 | 详情 | 详情 |
| (XII) | 62961 | 4-bromo-1H-pyrazol-5-ylamine; 4-bromo-1H-pyrazol-5-amine | C3H4BrN3 | 详情 | 详情 | |
| (XIII) | 62962 | N-[3-(3-bromopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-N-methylacetamide | C15H13BrN4O | 详情 | 详情 | |
| (XIV) | 14103 | 2-Thiophenecarbonyl chloride | 5271-67-0 | C5H3ClOS | 详情 | 详情 |
| (XV) | 62963 | 2-thiophenylboronic acid | C4H5BO2S | 详情 | 详情 |
合成路线10
该中间体在本合成路线中的序号：(XIV)Cyclization of 2-aminopyrazole (XI) with the acetamide (X) in AcOH gives the pyrazolo[1,5-a]pyrimidine derivative (XVI), which is finally acylated with 2-thienylcarbonyl chloride (XIV) by means of AlCl3.
| 【1】 Sorbera, L.A.; Castaner, J.; Martin, L.; Indiplon. Drugs Fut 2003, 28, 8, 739. |
| 【2】 Wilcoxen, K.M.; Gross, R.S. (Neurocrine Biosciences Inc.); Synthesis of substd. pyrazolopyrimidines. WO 0110868 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 59947 | N-{3-[(E)-3-(dimethylamino)-2-propenoyl]phenyl}-N-methylacetamide | C14H18N2O2 | 详情 | 详情 | |
| (XI) | 56012 | 1H-pyrazol-5-amine; 1H-pyrazol-5-ylamine | 916420-28-5 | C3H5N3 | 详情 | 详情 |
| (XIV) | 14103 | 2-Thiophenecarbonyl chloride | 5271-67-0 | C5H3ClOS | 详情 | 详情 |
| (XVI) | 62964 | N-methyl-N-(3-pyrazolo[1,5-a]pyrimidin-7-ylphenyl)acetamide | C15H14N4O | 详情 | 详情 |
合成路线11
该中间体在本合成路线中的序号：(IV)The precursor aldehyde (VI) was prepared as follows. 4-Nitrobenzaldehyde (I) was protected as the ethylene acetal (II) and subsequently reduced by catalytic hydrogenation in the presence of PtO2 to furnish aniline (III). Acylation of (III) with 2-thiophenecarbonyl chloride (IV) provided amide (V). The ethylene acetal group of (V) was then hydrolyzed to the target aldehyde (VI) under acidic conditions.
| 【1】 Folkes, A.; et al.; Synthesis and in vitro evaluation of a series of diketopiperazine inhibitors of plasminogen activator inhibitor-1. Bioorg Med Chem Lett 2001, 11, 19, 2589. |
| 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) | 18184 | 4-Nitrobenzaldehyde | 555-16-8 | C7H5NO3 | 详情 | 详情 |
| (II) | 53126 | 2-(4-nitrophenyl)-1,3-dioxolane | n/a | C9H9NO4 | 详情 | 详情 |
| (III) | 53127 | 4-(1,3-dioxolan-2-yl)aniline; 4-(1,3-dioxolan-2-yl)phenylamine | n/a | C9H11NO2 | 详情 | 详情 |
| (IV) | 14103 | 2-Thiophenecarbonyl chloride | 5271-67-0 | C5H3ClOS | 详情 | 详情 |
| (V) | 53128 | N-[4-(1,3-dioxolan-2-yl)phenyl]-2-thiophenecarboxamide | n/a | C14H13NO3S | 详情 | 详情 |
| (VI) | 53129 | N-(4-formylphenyl)-2-thiophenecarboxamide | n/a | C12H9NO2S | 详情 | 详情 |