Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][SH:7])=[CH:4][CH:3]=1.Br[CH:11]([CH3:17])[C:12]([O:14][CH2:15][CH3:16])=[O:13].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CC(C)=O>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][S:7][CH:11]([CH3:17])[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:4][CH:3]=1
Reactant: SCc1ccc(Cl)cc1
Reactant: CCOC(=O)C(C)Br
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)C(C)SCc1ccc(Cl)cc1

Procedure:
A mixture of 19.5 ml (0.15 mol) of 4-chlorobenzylmercaptan, 27.1 g (0.15 mol) of ethyl α-bromopropionate, 21 g of potassium carbonate and 0.1 g of potassium iodide in 100 ml of anhydrous acetone is kept under reflux for 6 hrs. It is filtered, the precipitate is washed with acetone and the filtrate is evaporated in vacuo. 200 ml of ether are added to the residue and the mixture is washed with dilute NaOH, dilute HCl and water, dried and evapoated in vacuo.
Reaction SMILES: C([O:3][P:4]([CH:9]([C:36]#[N:37])[CH2:10][C:11]([CH2:34][CH3:35])=[CH:12][CH2:13][C:14]1[C:15]([O:27]CC[Si](C)(C)C)=[C:16]2[C:20](=[C:21]([CH3:25])[C:22]=1[O:23][CH3:24])[CH2:19][O:18][C:17]2=[O:26])(=[O:8])[O:5]CC)C>C(O)(C(F)(F)F)=O.C(Cl)Cl>[C:36]([CH:9]([P:4](=[O:3])([OH:5])[OH:8])[CH2:10][C:11]([CH2:34][CH3:35])=[CH:12][CH2:13][C:14]1[C:15]([OH:27])=[C:16]2[C:20](=[C:21]([CH3:25])[C:22]=1[O:23][CH3:24])[CH2:19][O:18][C:17]2=[O:26])#[N:37]
Reactant: CCOP(=O)(OCC)C(C#N)CC(=CCc1c(OC)c(C)c2c(c1OCC[Si](C)(C)C)C(=O)OC2)CC
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCC(=CCc1c(O)c2c(c(C)c1OC)COC2=O)CC(C#N)P(=O)(O)O
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 68.7 %

Procedure:
{1-Cyano-3-ethyl-5-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-pent-3-enyl}-phosphonic acid diethyl ester (19.5 mg, 0.035 mmol) was dissolved in a solution of 10% TFA/CH2Cl2 (2 mL) and stirred at room temperature for 10 minutes. The reaction mixture was dried under reduced pressure and purified by RP-HPLC to provide 9.5 mg (61%) of the desired product. This material was dissolved in DMF (0.5 mL) and DCM (0.5 mL) and TMSBr (27 μL, 0.2 mmol) and 2,6-lutidine (23 μL, 0.2 mmol) were added. The reaction solution was allowed stir at room temperature overnight before quenching with MeOH. The reaction mixture was dried under reduced pressure and the residue was purified by RP HPLC using a C18 column with a gradient of H2O, 0.1% TFA-acetonitrile, 0.1% TFA to provide 5.1 mg (65%) of the desired product as a white solid. 1H NMR (300 MHz, CD3OD) δ 1.10 (t, 3H), 2.16 (s, 3H), 2.23-2.52 (m, 3H), 2.67 (m, 1H), 3.05-3.20 (m, 1H), 3.48 (d, J=7.2, 2H), 3.81 (s, 3H), 5.26 (s, 2H), 5.43 (t, J=7.2 Hz, 1H) ppm; 31P (121.4 MHz, CD3OD) δ 14.18 ppm; MS (m/z) 394 [M−H]−, 396 [M+H]+.
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]1[CH:13]=[C:12]([Br:14])[CH:11]=[C:10]2[C:5]=1[NH:6][C:7](=[O:16])[C:8](=[O:15])[NH:9]2.[C:17](OC(=O)C)(=[O:19])[CH3:18].C(N(CC)CC)C>CN(C)C=O>[Br:14][C:12]1[CH:11]=[C:10]2[C:5]([NH:6][C:7](=[O:16])[C:8](=[O:15])[NH:9]2)=[C:4]([CH2:3][NH:2][C:17](=[O:19])[CH3:18])[CH:13]=1
Reactant: NCc1cc(Br)cc2[nH]c(=O)c(=O)[nH]c12
Reactant: CC(=O)OC(C)=O
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(=O)NCc1cc(Br)cc2[nH]c(=O)c(=O)[nH]c12

Procedure:
50 mg (0.19 mmol) of 5-aminomethyl-7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline hydrochloride are suspended in 4 ml of N,N-dimethylformamide and stirred at 20° C. for 24 hours with 0.02 ml (1.2 equiv.) of acetic anhydride and 0.059 ml (2.2 equiv.) of triethylamine. The solvent is concentrated by evaporation, and the solid is suspended in diethyl ether, filtered off and washed with methanol and diethyl ether. After drying under a high vacuum, the title compound is obtained in the form of a white solid.
Reaction SMILES: [C:1]([C:13]1[CH:22]=[C:21]2[C:16]([CH:17]=[CH:18][C:19]([O:23][CH3:24])=[CH:20]2)=[CH:15][CH:14]=1)#[C:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].CCCCCC>C1(C)C=CC=CC=1.[Pd]>[CH2:1]([C:13]1[CH:22]=[C:21]2[C:16]([CH:17]=[CH:18][C:19]([O:23][CH3:24])=[CH:20]2)=[CH:15][CH:14]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCCC#Cc1ccc2ccc(OC)cc2c1
Agent: [Pd]
Solvent: CCCCCC
Solvent: Cc1ccccc1
Product: CCCCCCCCCCCCc1ccc2ccc(OC)cc2c1
Yield: 96 %

Procedure:
Using 7-methoxy-2-naphthyltrifluoromethanesulfonate (30.63 g, 0.10 mol) and 1-dodecyne (20.79 g, 0.125 mol), 7-dodecyn-1-yl-2-methoxynaphthalene was synthesized by the same operation as that in the method for synthesizing 7-decyl-2-methoxynaphthalene according to Example 3, and subjected to column chromatography (silica gel, developed with a mixture of toluene and hexane) to obtain a light yellow oil product of 7-dodecyn-1-yl-2-methoxynaphthalene (32.0 g, quantitative). The obtained 7-dodecyn-1-yl-2-methoxynaphthalene (total amount) was subjected to catalytic reduction in toluene (316 ml) under a hydrogen atmosphere by adding 10% Pd/C (2.11 g). The obtained product was subjected to column chromatography (silica gel, developed with a mixture of toluene and hexane) to obtain 7-dodecyl-2-methoxynaphthalene (compound (3)-14, 31.10 g, yield of 96%).
Reaction SMILES: [N+:1]([C:4]1[CH:18]=[CH:17][CH:16]=[CH:15][C:5]=1[CH2:6][CH:7]([NH2:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([O-:3])=[O:2].[CH:19]1([C:25](Cl)=[O:26])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1>C1(C)C=CC=CC=1.N1C=CC=CC=1>[CH:19]1([C:25]([NH:14][CH:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:6][C:5]2[CH:15]=[CH:16][CH:17]=[CH:18][C:4]=2[N+:1]([O-:3])=[O:2])=[O:26])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1
Reactant: NC(Cc1ccccc1[N+](=O)[O-])c1ccccc1
Reactant: O=C(Cl)C1CCCCC1
Solvent: c1ccncc1
Solvent: Cc1ccccc1
Product: O=C(NC(Cc1ccccc1[N+](=O)[O-])c1ccccc1)C1CCCCC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
10.0 g of 2-nitro-α-phenylphenethylamine in 75 ml of toluene is added dropwise to a stirred, cooled solution of 14.4 ml of cyclohexylcarbonyl chloride in 75 ml of toluene and 25 ml of pyridine. After complete addition the mixture is stirred at room temperature for 2 hours. The mixture is allowed to stand overnight, after which the tan precipitate is collected and washed with 100 ml of ether. The precipitate is recrystallized from 350 ml of methanol to give yellow needles, mp 210°-212° C. of N-cyclohexanecarbonyl-2-nitro-α-phenylphenethylamine.
Reaction SMILES: [C:1]([CH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][N:4]1[C:9]([C:11]1[N:12]=[C:13]([CH3:22])[S:14][C:15]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:10])#[CH:2].Br[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(N(CC)CC)C>CN(C=O)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:22][C:13]1[S:14][C:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:11]([C:9]([N:4]2[CH2:5][CH2:6][CH2:7][CH2:8][CH:3]2[C:1]#[C:2][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:10])[N:12]=1
Reactant: C#CC1CCCCN1C(=O)c1nc(C)sc1-c1ccccc1
Reactant: Brc1ccccc1
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cc1nc(C(=O)N2CCCCC2C#Cc2ccccc2)c(-c2ccccc2)s1
Temperature: 90 °C
Reaction time: 8 h

Procedure:
A solution of (2-ethynylpiperidin-1-yl)(2-methyl-5-phenyl-1,3-thiazol-4-yl)methanone (25 mg, 0.081 mmol), bromobenzene (23 mg, 0.15 mmol), CuI (4.6 mg, 0.024 mmol), and triethylamine (0.15 mL, 1.1 mmol) in DMF (0.5 mL) was purged subsurface with nitrogen. Palladium tetrakis (9.3 mg, 0.0081 mmol) was added and the reaction was heated at 90° C. overnight. The reaction was stirred over excess Quadrapure TU overnight, then filtered and dried. The residue was subjected to purification via reverse phase HPLC to provide the title compound which gave a high resolution mass spectrum (ES+) m/z of 387.1527, calculated for M+H+ [C24H22N2OS: 387.1526].
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH:28]2OCCO2)[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]1[N:12]=[C:13]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:14][C:15]=1[CH3:16].[O:33]1[CH2:37][C:36](=[O:38])[NH:35][C:34]1=[O:39].N1CCCCC1>C(O)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH:28]=[C:37]2[O:33][C:34](=[O:39])[NH:35][C:36]2=[O:38])[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]1[N:12]=[C:13]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:14][C:15]=1[CH3:16]
Reactant: O=C1COC(=O)N1
Reactant: COc1cc(CCCCCC2OCCO2)ccc1OCc1nc(-c2ccccc2)oc1C
Solvent: C1CCNCC1
Solvent: CC(=O)O
Product: COc1cc(CCCCCC=C2OC(=O)NC2=O)ccc1OCc1nc(-c2ccccc2)oc1C
Reaction time: 16 h

Procedure:
A mixture of 2-[5-[3-methoxy-4-(5-methyl-2-phenyl-4-oxazolylmethoxy)phenyl]pentyl]-1,3-dioxolan (3.6 g), 2,4-oxazolidinedione (1.7 g), piperidine (0.72 g) and acetic acid (50 ml) was stirred for 16 hours under reflux. The reaction mixture was concentrated under reduced pressure, which was dissolved in ethyl acetate. The solution was successively washed with a saturated aqueous solution of sodium hydrogencarbonate, water, 1N HCl and water, followed by drying (MgSO4). The ethyl acetate layer was concentrated under reduced pressure, which was subjected to column chromatography on silica gel. From the fraction eluted with chloroform-methanol (50:1), was obtained 5-[6-[3-methoxy-4-(5-methyl-2-phenyl-4-oxazolylmethoxy)phenyl]hexylidene]-2,4-oxazolidinedione as an oily product. The oily product was dissolved in tetrahydrofuran (THF) (80 ml), to which was added palladium-carbon (5%, 1.0 g). The mixture was subjected to catalytic hydrogenation under 1 atmospheric pressure at room temperature. The catalyst was filtered off, and the filtrate was concentrated under reduced pressure. The concentrate was subjected to column chromatography on silica gel. From the fraction eluted with chloroform-methanol (50:1), was obtained 5-[6-[3-methoxy-4-(5-methyl-2-phenyl-4-oxazolylmethoxy)phenyl]hexyl]-2,4-oxazolidinedione, which was recrystallized from ethyl acetate-isopropyl ether to give colorless prisms, m.p.113-117° C.
Reaction SMILES: C1(C)C=CC(S(O)(=O)=O)=CC=1.[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][C:22]([C:25](O)([CH3:29])[CH2:26][CH2:27][NH2:28])=[CH:21][CH:20]=2)=[CH:15][CH:14]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[OH-].[Na+]>C1(C)C=CC=CC=1>[F:12][C:13]1[CH:14]=[CH:15][C:16]([C:19]2[CH:24]=[CH:23][C:22]([C:25]([CH3:29])=[CH:26][CH2:27][NH2:28])=[CH:21][CH:20]=2)=[CH:17][CH:18]=1
Reactant: CC(O)(CCN)c1ccc(-c2ccc(F)cc2)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Product: CC(=CCN)c1ccc(-c2ccc(F)cc2)cc1

Procedure:
25.9 g of 3-(4'-fluoro-4-biphenylyl)-3-hydroxybutylamine p-toluenesulfonate are boiled with 1 g of p-toluenesulfonic acid in 500 ml of toluene for 2 hours under a water separator, and the mixture is cooled and worked up with sodium hydroxide solution to give 3-(4'-fluoro-4-biphenylyl)-2-buten-1-yl-amine.
Reaction SMILES: [CH2:1]([C:3]1[NH:4][CH:5]=[CH:6][CH:7]=1)[CH3:2].C[Mg]Br.[C:11]([C:13]1[CH:18]=[CH:17][C:16]([C:19](=[O:27])SC2C=CC=CN=2)=[CH:15][CH:14]=1)#[N:12].[Cl-].[NH4+]>C1(C)C=CC=CC=1.O1CCCC1>[CH2:1]([C:3]1[NH:4][C:5]([C:19]([C:16]2[CH:15]=[CH:14][C:13]([C:11]#[N:12])=[CH:18][CH:17]=2)=[O:27])=[CH:6][CH:7]=1)[CH3:2]
Reactant: CCc1ccc[nH]1
Reactant: N#Cc1ccc(C(=O)Sc2ccccn2)cc1
Agent: C[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CCc1ccc(C(=O)c2ccc(C#N)cc2)[nH]1
Reaction time: 0.67 h

Procedure:
To a solution of 2-ethyl-1H-pyrrole in toluene (120 mL) was added dropwise 1M methylmagnesium bromide in tetrahydrofuran (170 mL) in a dry ice-acetone bath below −60° C. over 30 minutes. Then the mixture was stirred in an ice-water bath for 40 minutes. To this reaction mixture was added S-(2-pyridinyl) 4-cyanobenzenecarbothioate (15.2 g) portionwise over 10 minutes in a dryice-acetone bath. After 1.5 hours stirring, saturated ammonium chloride (100 mL) was added therein and the reaction mixture was allowed to ambient temperature. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with 1N sodium hydroxide (100 mL) twice, water, and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was triturated with isopropyl ether to give 4-[(5-ethyl-1H-pyrrol-2-yl)carbonyl]benzonitrile (12.7 g) as a pale yellow solid.
Reaction SMILES: [N:1]([C@@H:4]1[C@:8](C(=O)C)([OH:9])[C@@H:7]([CH:13](C(=O)C)[OH:14])[O:6][C@H:5]1[N:18]1[CH:25]=[CH:24][C:22](=O)[NH:21][C:19]1=[O:20])=[N+:2]=[N-:3].C(O)C.S(Cl)(Cl)=O.C[N:34](C)C=O>>[N:1]([C@@H:4]1[C@H:8]([OH:9])[C@@H:7]([CH2:13][OH:14])[O:6][C@H:5]1[N:18]1[CH:25]=[CH:24][C:22]([NH2:34])=[N:21][C:19]1=[O:20])=[N+:2]=[N-:3]
Reactant: CN(C)C=O
Reactant: CC(=O)C(O)[C@H]1O[C@@H](n2ccc(=O)[nH]c2=O)[C@H](N=[N+]=[N-])[C@@]1(O)C(C)=O
Solvent: CCO
Solvent: O=S(Cl)Cl
Product: [N-]=[N+]=N[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1n1ccc(N)nc1=O
Temperature: 25 °C
Reaction time: 48 h

Procedure:
1 g. 2'-Azido-2'-desoxy-3',5'-diacetyl-uridine (see J. Hobbs, H. Sternbach, M. Sprinzl and F. Eckstein, Biochemistry, 12, 5138/1973) was mixed with 14 ml. ethanol-free chloroform and 0.14 ml. dimethyl formamide and then mixed with 2 ml. thionyl chloride. The reaction mixture was boiled under reflux, with the exclusion of moisture, for 6 hours. After cooling, the reaction mixture was evaporated in a vacuum and the residue treated with ammoniacal methanol (30 ml. dry methanol plus 30 ml. methanol saturated with ammonia). The solution was stirred for 2 days at ambient temperature and then left to stand for 2 days at 37° C. Thin layer chromatography (methanol/chloroform mixture (4/6 v/v) on silica gel plates, Herck 60 F 254) shows mainly a product with an Rf value of 0.62. The solution was evaporated, the residue applied to two plates coated with silica gel for preparative thin layer chromatography (Merck 60 F 254, 2 mm. layer thickness, 20×40 cm.) and developed with a chloroform/methanol mixture (6/4 v/v). The main bands were scraped off, the material was eluted with methanol and applied to an ion exchanger column (Dowex 1×2, OH, 1.7×21.5 cm.). After washing with water, the product was eluted with 30% aqueous methanol. The solution obtained was evaporated and the residue recrystallized from ethanol. 2'-Azido-2'-desoxycytidine was obtained in a yield of 12310 A270 units (1.32 mMol; 47% of theory). The product melts at 215° C.
Reaction SMILES: Cl[C:2]1[CH:11]=[C:10]([CH:12]([CH3:14])[CH3:13])[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[NH2:15][NH2:16]>>[NH:15]([C:2]1[CH:11]=[C:10]([CH:12]([CH3:14])[CH3:13])[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1)[NH2:16]
Reactant: NN
Reactant: CC(C)c1cc(Cl)nc2ncccc12
Product: CC(C)c1cc(NN)nc2ncccc12
Yield: 92 %

Procedure:
A solution of chloro-4-isopropyl-1,8-naphthyridine (690 mg, 3.4 mmol) in NH2NH2 was reacted as outlined in Scheme 1 above to give the desired title compound (620 mg, 92%). Spectroscopic data: 1H NMR (300 MHz, CDCl3) δ ppm 1.35 (d, J=6.74 Hz, 6 H) 3.45-3.59 (m, 1 H) 6.70 (br. s., 1 H) 7.21 (dd, J=8.06, 4.54 Hz, 1 H) 8.19 (d, J=7.62 Hz, 1 H) 8.79 (br. s., 1 H).
Reaction SMILES: [Br:1][C:2]1[CH:23]=[C:22]([O:24][CH3:25])[C:5]2[N:6]([CH2:18][CH2:19][O:20][CH3:21])[C:7]([C:9]3[CH:14]=[CH:13][C:12]([CH:15]([CH3:17])[CH3:16])=[CH:11][CH:10]=3)=[N:8][C:4]=2[CH:3]=1.[Br:26]Br.CCOC(C)=O>C(O)(=O)C>[Br:26][C:3]1[C:4]2[N:8]=[C:7]([C:9]3[CH:14]=[CH:13][C:12]([CH:15]([CH3:17])[CH3:16])=[CH:11][CH:10]=3)[N:6]([CH2:18][CH2:19][O:20][CH3:21])[C:5]=2[C:22]([O:24][CH3:25])=[CH:23][C:2]=1[Br:1]
Reactant: COCCn1c(-c2ccc(C(C)C)cc2)nc2cc(Br)cc(OC)c21
Reactant: BrBr
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: COCCn1c(-c2ccc(C(C)C)cc2)nc2c(Br)c(Br)cc(OC)c21
Temperature: 25 °C
Reaction time: 3 h
Yield: 6.2 %

Procedure:
To a solution of 403 mg (1.0 mmol) 5-bromo-2-(4-isopropyl-phenyl)-7-methoxy-1-(2-methoxy-ethyl)-1H-benzoimidazole in 8 ml glacial acetic acid, 240 mg (1.5 mmol) bromine is slowly added at 10° C. The reaction mixture is allowed to warm to room temperature and is stirred for 3 h. 250 ml EtOAc are added and this solution is washed 1 n NaOH (2×), water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue is recrystallized from EtOAc/hexane to afford 30 mg of the title compound as colorless crystals.
Reaction SMILES: [CH:1]1([NH2:4])[CH2:3][CH2:2]1.[Cl:5][C:6]1[CH:10]=[C:9]([C:11](Cl)=[O:12])[NH:8][C:7]=1[C:14]([O:16][CH3:17])=[O:15]>C1COCC1>[Cl:5][C:6]1[CH:10]=[C:9]([C:11]([NH:4][CH:1]2[CH2:3][CH2:2]2)=[O:12])[NH:8][C:7]=1[C:14]([O:16][CH3:17])=[O:15]
Reactant: COC(=O)c1[nH]c(C(=O)Cl)cc1Cl
Reactant: NC1CC1
Solvent: C1CCOC1
Product: COC(=O)c1[nH]c(C(=O)NC2CC2)cc1Cl
Yield: 70.3 %

Procedure:
Cycloproplyamine (0.166 g, 2.90 mmol) was added to a solution of methyl 3-chloro-5-(chlorocarbonyl)-1H-pyrrole-2-carboxylate (0.150 g, 0.580 mmol) in THF and the resulting solution stirred until no starting material was evident by TLC. The solvent was evaporated and purification was accomplished by silica gel column chromatography (30-100% EtOAc/hexanes) to afford the title compound (0.099 g, 70%) as a white solid. 1H NMR (400 MHz, Acetone-d6) δ ppm 10.81 (br. s., 1H), 7.71 (br. s., 1H), 6.78 (s, 1H), 3.84 (s, 3H), 2.79-2.92 (m, 1H), 0.73 (d, 2H), 0.57 (d, 2 H) LCMS: m/z 243.1 (M+1).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[C:14]([CH2:15][CH2:16][CH:17]=O)=[CH:13][C:12]([CH2:19][CH2:20][CH2:21][CH3:22])=[N:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[F:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[F:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[N:30]1[CH2:35][CH2:34][N:33]([CH2:17][CH2:16][CH2:15][C:14]2[N:10]([C:7]3[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=3)[N:11]=[C:12]([CH2:19][CH2:20][CH2:21][CH3:22])[CH:13]=2)[CH2:32][CH2:31]1
Reactant: CCCCc1cc(CCC=O)n(-c2ccc([N+](=O)[O-])cc2)n1
Reactant: Fc1ccccc1N1CCNCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Product: CCCCc1cc(CCCN2CCN(c3ccccc3F)CC2)n(-c2ccc([N+](=O)[O-])cc2)n1

Procedure:
260 mg (90.0%) of target compound was obtained by using a method same as in Example 1 by using 3-(1-(4-nitrophenyl)-3-butyl-1H-pyrazol-5-yl)propanal (187 mg, 0.625 mmol), 1-(2-fluorophenyl)piperazine (148 mL, 0.937 mmol), and NaBH(OAc)3 (198 mg, 0.936 mmol).
Reaction SMILES: [C:1]([OH:22])(=O)[CH2:2][CH2:3][CH2:4][C:5]#[C:6][CH2:7][C:8]#[C:9][CH2:10][C:11]#[C:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].C1N=CN(C(N2C=NC=C2)=O)C=1.[OH:35][C:36]1[CH:42]=[CH:41][C:39]([NH2:40])=[CH:38][CH:37]=1>O>[OH:35][C:36]1[CH:42]=[CH:41][C:39]([NH:40][C:1](=[O:22])[CH2:2][CH2:3][CH2:4][C:5]#[C:6][CH2:7][C:8]#[C:9][CH2:10][C:11]#[C:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])=[CH:38][CH:37]=1
Reactant: Nc1ccc(O)cc1
Reactant: CCCCCCCCC#CCC#CCC#CCCCC(=O)O
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: O
Product: CCCCCCCCC#CCC#CCC#CCCCC(=O)Nc1ccc(O)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 65.2 %

Procedure:
In the same manner as in the above example, the intermediate formed from 1 g of 5,8,11-eicosatriynoic acid and 0.7 g of CDI is treated with 0.727 g of para-hydroxyaniline. The medium is then stirred for 24 hours at room temperature. Water is then added gradually to the mixture until all the product formed precipitates. It is drained and dried and then recrystallized in isopropyl ether. 0.85 g of N-(para-hydroxyphenyl)-5,8,11-eicosatriynamide is obtained in the form of beige-white crystals of melting point 121° C.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:12]([NH2:18])[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].C(=O)([O-])O.[Na+].C(OC(N1[C:33](=[O:34])[C:32]2=[CH:35][CH:36]=[CH:37][CH:38]=[C:31]2[C:30]1=[O:39])=O)C.Cl>C(#N)C.O>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:12]([N:18]2[C:33](=[O:34])[C:32]3[C:31](=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:30]2=[O:39])[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2]
Reactant: CCOC(=O)N1C(=O)c2ccccc2C1=O
Reactant: CCOc1cc(C(N)CS(C)(=O)=O)ccc1OC
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC#N
Solvent: O
Product: CCOc1cc(C(CS(C)(=O)=O)N2C(=O)c3ccccc3C2=O)ccc1OC
Temperature: 25 °C
Reaction time: 0.03 h
Yield: 69.9 %

Procedure:
A mixture of 1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethylamine (200 mg, 0.73 mmol) and sodium hydrogen carbonate (80 mg, 0.95 mmol) in acetonitrile and water(2 mL each) was stirred under nitrogen at room temperature for 2 minutes. To the resulting solution was added N-ethoxycarbonylphthalimide (170 mg, 0.78 mmol). After 17 hours, the resulting solution was stirred with hydrochloric acid (2 mL, 4 N), and water (30 mL) at room temperature for 30 minutes. The resulting suspension was filtered and the solid was washed with water (2×25 mL), and then dried in a vacuum oven overnight (60° C., <1 torr) to yield 2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]isoindoline-1,3dione as a solid (206 mg, 70% yield): mp, 151.0-152.0° C.; 1H NMR (CDCl3); δ 1.46 (t, J=6.9 Hz, 3H, CH3), 2.84 (s, 3H, CH3), 3.78 (dd, J=4.8, 14.4 Hz, I H, CHH), 3.84 (s, 3H, CH3), 4.10 (q, J=7 Hz, 2H, CH2), 4.54 (dd, J=10.1, 14.4 Hz, 1H, CHH), 5.90 (dd, J=4.8, 1 0.1 Hz, 1H, NCH), 6.83 (d, J=8.5 Hz, 1H, Ar), 7.11-7.15 (m, 2H, Ar), 7.67-7.73 (m, 2H, Ar), 7.80-7.84 (m, 2H, Ar); 13C NMR (CDCl3) δ 14.63, 41.49, 48.84, 54.82, 55.89, 64.45, 111.43, 112.50, 120.43, 123.51, 129.56, 131.58, 134.17, 148.57, 149.63, 167.80; Anal Calcd for C20H21NO6S: C, 59.54; H, 5.25; N, 3.47. Found: C, 59.66; H, 5.28; N, 3.29.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].[NH2:11][CH2:12][CH2:13][N:14]1[CH2:19][CH2:18][N:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[O:26][CH3:27])[CH2:16][CH2:15]1.C(=O)([O-])[O-].[K+].[K+].O>C(O)CCC>[N+:8]([C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[NH:11][CH2:12][CH2:13][N:14]1[CH2:15][CH2:16][N:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[O:26][CH3:27])[CH2:18][CH2:19]1)([O-:10])=[O:9]
Reactant: COc1ccccc1N1CCN(CCN)CC1
Reactant: O=[N+]([O-])c1ccccc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCCCO
Product: COc1ccccc1N1CCN(CCNc2ccccc2[N+](=O)[O-])CC1
Reaction time: 32 h
Yield: 32.1 %

Procedure:
A mixture of 3.03 g of 2-chloronitrobenzene, 4.52 g of 1-(2-aminoethyl)-4-(2-methoxyphenyl)piperazine, and 3.18 g of anhydrous potassium carbonate in 30 mL of n-butanol was stirred for 32 h at reflux. After cooling, the mixture was poured into H2O, then extracted with EtOAc and the organic phase dried on Na2SO4. The crude obtained by evaporating the solvent was purified by flash chromatography (EtOAc-petrolium ether 4:6) and the residue obtained after evaporation of the solvents was taken up with Et2O, stirred and filtered giving 2.2 g (31%) of the title compound. Melting point: 117-118° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[S:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[NH:21][C:20](=[O:25])[CH:19]=[CH:18]2.[OH:26]O>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[S:9]([CH2:10][CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[NH:21][C:20](=[O:25])[CH:19]=[CH:18]2)=[O:26]
Reactant: O=c1ccc2cc(OCCCCSc3cc(Cl)ccc3Cl)ccc2[nH]1
Reactant: OO
Product: O=c1ccc2cc(OCCCCS(=O)c3cc(Cl)ccc3Cl)ccc2[nH]1

Procedure:
Prepared analogous to Example 123 from 6-[4-(2,5-dichloro-phenyl-mercapto)-butoxy]-carbostyril and hydrogen peroxide.