Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:4]([C:28](=[O:39])[CH:29]([O:35][C:36](=[O:38])[CH3:37])[CH2:30][O:31][C:32](=[O:34])[CH3:33])[C:5]1[C:6]([I:27])=[C:7]([CH2:22][O:23][C:24](=[O:26])[CH3:25])[C:8]([I:21])=[C:9]([C:19]=1[I:20])[C:10]([NH:12][CH2:13][CH2:14][O:15][C:16](=[O:18])[CH3:17])=[O:11])[CH:2]=[CH2:3].[OH2:40].C([O:45]O)(C)(C)C.C[N+]1([O-])CCOCC1>CC(C)=O.[Os](=O)(=O)(=O)=O>[OH:40][CH:2]([CH2:3][OH:45])[CH2:1][N:4]([C:28](=[O:39])[CH:29]([O:35][C:36](=[O:38])[CH3:37])[CH2:30][O:31][C:32](=[O:34])[CH3:33])[C:5]1[C:6]([I:27])=[C:7]([CH2:22][O:23][C:24](=[O:26])[CH3:25])[C:8]([I:21])=[C:9]([C:19]=1[I:20])[C:10]([NH:12][CH2:13][CH2:14][O:15][C:16](=[O:18])[CH3:17])=[O:11]
Reactant: C=CCN(C(=O)C(COC(C)=O)OC(C)=O)c1c(I)c(COC(C)=O)c(I)c(C(=O)NCCOC(C)=O)c1I
Reactant: O
Reactant: CC(C)(C)OO
Agent: O=[Os](=O)(=O)=O
Agent: C[N+]1([O-])CCOCC1
Solvent: CC(C)=O
Product: CC(=O)OCCNC(=O)c1c(I)c(COC(C)=O)c(I)c(N(CC(O)CO)C(=O)C(COC(C)=O)OC(C)=O)c1I
Temperature: 25 °C
Reaction time: 24 h

Procedure:
5-[N′-(2-Propenyl)-2,3 -diacetoxypropionylamino]-3-acetoxymethyl-N-(2-acetoxyethyl)-2,4,6-triiodobenzamide (8.73 g, 9.90 mmol) was dissolved in acetone (360 ml) and water (40 ml) and the solution was cooled in an ice-bath. Osmium tetroxide (110 mg, 0.43 mmol), and an excess of t-butylhydroperoxide was added. 4-Methyl-morpholine N-oxide (2,32 g, 19.8 mmol) was added and the mixture was stirred at room temperature for 24 h. The reaction was then quenched by addition of a saturated solution of sodium hydrogen sulphite (120 ml). The acetone was evaporated, and the residue was extracted with ethyl acetate (2×70 ml). The organic extracts were washed with water (50 ml), dried (Na2SO4), and the solvent was evaporated. The residue was chromatographed on a column of silica using a mixture of ethyl acetate/acetone (1/1) as the eluent.Yield: 5.82 g (64%).
Reaction SMILES: [C:1]([C:5]1[C:6]([OH:13])=[C:7]([CH:10]=[CH:11][CH:12]=1)[CH:8]=[O:9])([CH3:4])([CH3:3])[CH3:2].Cl[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21](OO)=O)[CH:16]=1>ClCCl>[CH2:21]([O:13][C:6]1[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:12][CH:11]=[CH:10][C:7]=1[CH:8]=[O:9])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:15][CH:16]=1
Reactant: CC(C)(C)c1cccc(C=O)c1O
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CC(C)(C)c1cccc(C=O)c1OCc1ccccc1
Reaction time: 8 h
Yield: 80 %

Procedure:
A solution of 3-tert-butyl-2-hydroxybenzaldehyde (20 g, 74.53 mmol) in dichloromethane (400 mL) was treated with m-chloroperbenzoic acid (70%, 20 g) in 3 portions at room temperature. Stirring was continued overnight. The reaction mixture was diluted with dichloromethane (to 1 L) and washed with saturated sodium bicarbonate (2×400 mL) and water (500 mL). The organic layer was dried over sodium sulfate and filtered. The solvent was removed in a rotary evaporator. The residue was taken up in methanol (375 mL), potassium hydroxide (7.5 g) was added and this mixture was stirred at room temperature overnight. The solvent was removed in a rotary evaporator. The residue was taken up in water (250 mL) and made acidic with 6N hydrochloric acid. The aqueous phase was extracted with ethyl acetate (800 mL). The organic extract was washed with water (300 mL), dried over sodium sulfate and the solvent was removed in a rotary evaporator. The crude product was purified by chromatography on silica (350 g) with 5% ethyl acetate in heptane (4 L). Pure 9 (16 g, 83%) was isolated.
Reaction SMILES: [H-].[Na+].[CH2:3]([O:5][CH2:6][C:7]1[N:8]([CH2:20][C:21]([CH3:24])([OH:23])[CH3:22])[C:9]2[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[N:12]=[CH:11][C:10]=2[N:19]=1)[CH3:4].[CH:25]([S:27]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)(=[O:29])=[O:28])=[CH2:26]>O1CCCC1>[CH2:3]([O:5][CH2:6][C:7]1[N:8]([CH2:20][C:21]([O:23][CH2:26][CH2:25][S:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)(=[O:28])=[O:29])([CH3:24])[CH3:22])[C:9]2[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[N:12]=[CH:11][C:10]=2[N:19]=1)[CH3:4]
Reactant: CCOCc1nc2cnc3ccccc3c2n1CC(C)(C)O
Reactant: C=CS(=O)(=O)c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOCc1nc2cnc3ccccc3c2n1CC(C)(C)OCCS(=O)(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 28.2 %

Procedure:
Solid sodium hydride (30 mg of 60% dispersion in mineral oil, 0.72 mmol) was added to a stirred solution of 1-[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol (2.15 g, 7.2 mmol) and phenyl vinyl sulfone (2.42 g, 14.4 mmol) in anhydrous tetrahydrofuran (29 mL). The reaction mixture was stirred at ambient temperature for about 1 hour, and then it was quenched with water (50 mL) and extracted with ethyl acetate (3×50 mL). The combined extracts were washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to provide crude product as an oil. This material was purified by column chromatography (silica gel eluting with 95/5 dichloromethane/methanol) to provide 0.95 g of 2-ethoxymethyl-1-{2-[2-(phenylsulfonyl)ethoxy]-2-methylpropyl}-1H-imidazo[4,5-c]quinoline as a colorless foam.
Reaction SMILES: CC(C)([O-])C.[K+].[F:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[OH:14].[C:15]1(=O)[O:18][CH2:17][CH2:16]1.Cl>O1CCCC1>[F:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:9]=1[O:14][CH2:15][CH2:16][C:17]2=[O:18]
Reactant: O=C1CCO1
Reactant: Oc1ccccc1F
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: C1CCOC1
Product: O=C1CCOc2c(F)cccc21
Reaction time: 1 h

Procedure:
Potassium t-butoxide (2.42 g) was added to a solution of the compound 1-1 (2.20 g) in tetrahydrofuran (100 ml) at room temperature. After stirring for five minutes at the same temperature, beta-propiolactone (2.71 ml) was added. Because of heat generation, the mixture was moved to an ice bath and stirred at the same temperature for one hour. After further stirring at room temperature for four hours, the mixture was made acidic with 1 N hydrochloric acid to terminate the reaction. The aqueous layer was extracted with ethyl acetate, and the organic layer was washed with brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was crystallized by adding a mixed solvent of 20% ethyl acetate-hexane to obtain the title compound (1.44 g).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:20])[CH:8]=[C:9]([C:18]#[N:19])[C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)=[O:5])[CH3:2].F[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[N+:28]([O-:30])=[O:29].C1OCCOCCOCCOCCOCCOC1.O>C(#N)C.C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:20])[CH:8]=[C:9]([C:18]#[N:19])[C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([O:17][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[N+:28]([O-:30])=[O:29])=[CH:13][CH:12]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1c(-c2ccc(O)cc2)c(C#N)cn1C
Reactant: O=[N+]([O-])c1ccccc1F
Agent: C1COCCOCCOCCOCCOCCO1
Solvent: ClCCl
Solvent: CC#N
Solvent: O
Product: CCOC(=O)c1c(-c2ccc(Oc3ccccc3[N+](=O)[O-])cc2)c(C#N)cn1C
Yield: 69.3 %

Procedure:
Add together 4-cyano-3-(4-hydroxyphenyl)-1-methyl-1H-pyrrole-2-carboxylic acid ethyl ester (prepared in example E-11) (600 mg, 2.22 mmol), 1-fluoro-2-nitrobenzene (313 mg, 1.0 Eq.), potassium fluoride/alumina (322 mg, 2.5 Eq.), and 18-crown-6 (60 mg, 0.1 Eq.) in acetonitrile (25 mL) and stir at reflux for 18 hours under a nitrogen atmosphere. Cool mixture and add water and methylene chloride (50 mL each) and stir vigorously. Separate layers and wash the organic layer once with water, dry over potassium carbonate, filter, and concentrate under reduced vacuum to give 762 mg as a dark solid. Purify the material by silica gel chromatography (Chromatotron™) eluting with methylene chloride to provide 602 mg of the title compound as a yellow solid. Mass spectrum (m/e): 392.2 (M*+1): (Bruker 300) 1NMR δ (CDCl3) 7.93-8.00 (1H, d), 7.50-7.57 (1H, t), 7.35-7.40 (2H, d), 7.19-7.29 (2H, m), 7.03-7.13 (2H, m), 4.05-4.20 (2H, dd), 3.95-4.10 (3H, s), 1.00-1.10 (3H, t).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH3:19])[N:5]=[C:6]([NH:8][S:9]([C:12]2[CH:13]=[CH:14][C:15]([NH2:18])=[CH:16][CH:17]=2)(=[O:11])=[O:10])[N:7]=1.[Ag:20].CC1C=CN=C(NS(C2C=CC(N)=CC=2)(=O)=O)N=1>>[CH3:19][C:4]1[N:5]=[C:6]([NH:8][S:9]([C:12]2[CH:13]=[CH:14][C:15]([NH2:18])=[CH:16][CH:17]=2)(=[O:11])=[O:10])[N:7]=[C:2]([CH3:1])[CH:3]=1.[Ag+:20]
Reactant: [Ag]
Agent: Cc1cc(C)nc(NS(=O)(=O)c2ccc(N)cc2)n1
Agent: Cc1ccnc(NS(=O)(=O)c2ccc(N)cc2)n1
Product: [Ag+]

Procedure:
Silver Sulfamethazine was prepared using 27.83 grams of sulfamethazine following procedure 1 (i.e. the procedure used for silver sulfamerazine) to give a fine white powder showing some crystallinity.
Reaction SMILES: O.[NH2:2][NH2:3].C(O[C:7](=[C:9]([C:12]#[N:13])[C:10]#[N:11])[CH3:8])C.O>CCO>[NH2:11][C:10]1[NH:3][N:2]=[C:7]([CH3:8])[C:9]=1[C:12]#[N:13]
Reactant: CCOC(C)=C(C#N)C#N
Reactant: NN
Solvent: O
Solvent: CCO
Product: Cc1n[nH]c(N)c1C#N
Temperature: 95 °C
Reaction time: 8 h
Yield: 71.1 %

Procedure:
Hydrazine monohydrate (6.8 ml, 0.14 mol) was dissolved in EtOH (10 ml) and cooled to 0° C. (1-Ethoxyethylidene)malononitrile (10 g, 0.073 mol) was added slowly and the mixture was heated at 95° C. for 2 h. After cooling to rt, water (20 ml) was added and the mixture was allowed to stand at rt overnight. The mixture was concentrated under reduced pressure and the resulting residue treated with EtOH (6 ml) and water (6 ml). After cooling in an ice/water bath for 10 min, the resulting precipitate was collected by filtration to give 6.34 g of 5-amino-3-methyl-1H-pyrazole-4-carbonitrile.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C:12]3[O:13][C:14]4[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][C:15]=4[CH:16]=3)=[N:9]2)=[CH:4][CH:3]=1.[H-].[Na+].[Cl:24][CH2:25][C:26]1[C:27]([CH2:32]Cl)=[CH:28][CH:29]=[CH:30][CH:31]=1>O1CCCC1>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C:12]3[O:13][C:14]4[CH:20]=[CH:19][C:18]([O:21][CH2:32][C:27]5[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=5[CH2:25][Cl:24])=[CH:17][C:15]=4[CH:16]=3)=[N:9]2)=[CH:4][CH:3]=1
Reactant: Oc1ccc2oc(-c3ccc4ccc(Cl)cc4n3)cc2c1
Reactant: ClCc1ccccc1CCl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: ClCc1ccccc1COc1ccc2oc(-c3ccc4ccc(Cl)cc4n3)cc2c1
Reaction time: 0.25 h
Yield: 53.7 %

Procedure:
To a cooled suspension of 7-chloro-2-(5-hydroxybenzofuran-2-yl)quinoline (0.71 g) in tetrahydrofuran (12 ml), sodium hydride (60% in mineral oil, 0.125 g) was added below 10° c. After being stirred for 15 minutes, α,α'-dichloro-o-xylene (1.68 g) was added to the mixture. After subsequently being stirred at ambient temperature for 1.5 hours, the mixture was refluxed for 25 hours. After the solvent was removed under reduced pressure, the residue was subjected to column chromatography on silica gel (25 g) and eluted with a mixture of chloroform and n-hexane (1:1). The fractions containing object compound were combined and concentrated under reduced pressure give 7-chloro-2-[5-(2-chloromethylbenzyloxy)benzofuran-2-yl]quinoline (0.56 g).
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[CH:4][CH:3]=1.[NH:11]1[CH:15]=[CH:14][CH:13]=[N:12]1>>[N:11]1([C:2]2[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][CH:3]=2)[CH:15]=[CH:14][CH:13]=[N:12]1
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: c1cn[nH]c1
Product: Nc1ccc(-n2cccn2)cc1

Procedure:
The title compound is obtained as described in Example 18a/b using 1-fluoro-4-nitrobenzene (Fluka, Buchs, Switzerland) and 1H-pyrazole (Fluka, Buchs, Switzerland). Title compound: ES-MS: 160.2 (M+H)+; analytical HPLC: tret=3.61 minutes (Grad 2).
Reaction SMILES: [NH2:1][C:2]1[C:3]([CH3:8])=[CH:4][CH:5]=[CH:6][CH:7]=1.S(=O)(=O)(O)O.[S-:14][C:15]#[N:16].[NH4+]>CO>[C:3]1([CH3:8])[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[NH:1][C:15]([NH2:16])=[S:14]
Reactant: N#C[S-]
Reactant: Cc1ccccc1N
Agent: O=S(=O)(O)O
Agent: [NH4+]
Solvent: CO
Product: Cc1ccccc1NC(N)=S
Yield: 89.9 %

Procedure:
In a reactor, 107.2 g of o-toluidine and 250 ml of methanol were charged and 54 g of conc. sulfuric acid was charged with stirring and 87.5 g of ammonium thiocyanate was admixed with the mixture. The mixture was heated to reflux methanol for 20 hours and the precipitate was separated by a filtration and the filtrate was concentrated and washed with water and dried to obtain 149.6 g of o-tolylthiourea. The product was analyzed by a high speed liquid chromatography to find a purity of 74.6% and an yield of 67.1% as a pure product. The purity and the yield were too low.
Reaction SMILES: [CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[CH2:13][O:14][C:15]1[N:20]=[N:19][C:18]([NH2:21])=[CH:17][CH:16]=1.C(N(CC)CC)C.[Cl:29][CH2:30][CH2:31][CH2:32][C:33](Cl)=[O:34]>C1COCC1>[Cl:29][CH2:30][CH2:31][CH2:32][C:33]([NH:21][C:18]1[N:19]=[N:20][C:15]([O:14][CH2:13][C:3]2[C:4]([C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=3)=[N:5][O:6][C:2]=2[CH3:1])=[CH:16][CH:17]=1)=[O:34]
Reactant: Cc1onc(-c2ccccc2)c1COc1ccc(N)nn1
Reactant: O=C(Cl)CCCCl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Cc1onc(-c2ccccc2)c1COc1ccc(NC(=O)CCCCl)nn1
Temperature: 25 °C
Reaction time: 1 h
Yield: 54.7 %

Procedure:
To a solution of 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-pyridazin-3-ylamine (1.0 g, 3.5 mmol) in THF (15 ml) was added triethylamine (0.59 mL, 4.3 mmol). The mixture was cooled in an ice bath and a solution of 4-chlorobutyryl chloride (0.48 mL, 4.3 mmol) in THF (5 mL) was added dropwise. After stirring for 1 h at room temperature the precipitate was filtered and the organic phase was evaporated. The residue was dissolved in methanol (20 mL), sodium bicarbonate (1 spatula) was added and the mixture was stirred at room temperature for 1 h. The solvent was evaporated and the residue was extracted (dichloromethane/water). Then the organic phase was dried over sodium sulfate and concentrated. Purification by chromatography (SiO2, heptane/ethyl acetate=100:0 to 60:40) afforded the title compound (740 mg, 54%) (as the least polar component of two formed in the reaction) which was obtained as a white solid. MS: m/e=387.3 [M+H]+.
Reaction SMILES: [H-].[Na+].[SH:3][C:4]1[NH:5][C:6]2[CH:12]=[CH:11][CH:10]=[CH:9][C:7]=2[N:8]=1.[CH2:13](Cl)/[CH:14]=[C:15](/[CH2:17][CH2:18][CH:19]=[C:20]([CH3:22])[CH3:21])\[CH3:16].[OH-].[Na+]>CN(C)C=O>[CH3:16]/[C:15](/[CH2:17][CH2:18][CH:19]=[C:20]([CH3:22])[CH3:21])=[CH:14]\[CH2:13][S:3][C:4]1[NH:8][C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[N:5]=1
Reactant: Sc1nc2ccccc2[nH]1
Reactant: CC(C)=CCC/C(C)=C/CCl
Agent: [H-]
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Product: CC(C)=CCC/C(C)=C/CSc1nc2ccccc2[nH]1
Temperature: 25 °C
Reaction time: 5 h
Yield: 110 %

Procedure:
To a suspension of sodium hydride (NaH) (0.69 g, 30 mmol) in dimethylformamide (DMF) (100 mL) was added 2-mercaptobenzimidazole (4.5 g, 10 mmol) in DMF (20 mL) at 0° C. under N2. To the resultant solution was added geranyl chloride (5.16 g, 10 mmol) over 30 minutes. The reaction was stirred for five hours at ambient temperature under N2 then treated with 2N NaOH and extracted with diethyl ether (Et2O). The Et2O extract was washed with saturated NaCl, concentrated in vacuo, dissolved in methylene chloride, and dried over Na2SO4. Recrystallization from Et2O gave white crystalline 2-[(3,7-dimethyl-2,6(E)-octadienyl)-thio]-1H-1,3-benzimidazole (3.15 g, 36.6%). m.p. 98°-100° C. NMR (CDCl3):δ7.4(m, 2H), 7.1(m, 2H) 5.3(t,J=8 Hz, 1H) 5.0(m 1H) , 3.90(d, J= 10 Hz, 2H , 2.00(m, 4H), 1.65(m, 9H).
Reaction SMILES: [CH2:1]([N:8]1[C@H:13]([CH3:14])[CH2:12][N:11]([C@H:15]([C:23]2[CH:35]=[CH:34][C:26]([C:27]([N:29]([CH2:32][CH3:33])[CH2:30][CH3:31])=[O:28])=[CH:25][CH:24]=2)[C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([OH:22])[CH:17]=2)[C@@H:10]([CH3:36])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.I[CH2:38][C:39]([O:41]CC)=[O:40]>>[CH2:1]([N:8]1[C@H:13]([CH3:14])[CH2:12][N:11]([C@@H:15]([C:16]2[CH:17]=[C:18]([CH:19]=[CH:20][CH:21]=2)[O:22][CH2:38][C:39]([OH:41])=[O:40])[C:23]2[CH:24]=[CH:25][C:26]([C:27]([N:29]([CH2:32][CH3:33])[CH2:30][CH3:31])=[O:28])=[CH:34][CH:35]=2)[C@@H:10]([CH3:36])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)CI
Reactant: CCN(CC)C(=O)c1ccc([C@H](c2cccc(O)c2)N2C[C@@H](C)N(Cc3ccccc3)C[C@@H]2C)cc1
Product: CCN(CC)C(=O)c1ccc([C@H](c2cccc(OCC(=O)O)c2)N2C[C@@H](C)N(Cc3ccccc3)C[C@@H]2C)cc1
Yield: 84.6 %

Procedure:
Alkylation of 4-((alpha-R)-alpha-((2S,5R)-4-benzyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide (Example 12) with ethyl iodoacetate, and subsequent hydrolysis of the ester as in Example 14 gave the title compound (84.6%) 1H NMR (0.1-M NaOD in CD3OD, 300 MHz); δ 1.10 (d, J=5.0 Hz, 3H); 1.11 (d, J=5.8 Hz, 3H; both doublets superimposed on m, 3H); 1.23 (m, 3H); 2.03 (m, 2H); 2.57 (m, 2H); 2.69 (m, 2H); 3.30 (m, 3H, superimposed on br m, 2H); 3.88 (d, J=13.1 Hz, 1H); 4.35 (s, 2H); 5.16 (s, 1H): 6.83 (m, 2H); 6.88 (s, 1H); 7.25 (m, 8H); 7.52 (d, J=8.1 Hz, 2H). Mass spectrum: (PFAB, glycerol matrix subtracted): m/z: 544.8, ((M+1)+, 82%).
Reaction SMILES: [CH3:1][S:2]([O:5]S(C)(=O)=O)(=O)=[O:3].C(N(CC)CC)C.[C:17]1([CH2:23][C@H:24]([NH2:27])[CH:25]=[CH2:26])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C(Cl)Cl>[CH3:1][S:2]([NH:27][C@H:24]([CH:25]=[CH2:26])[CH2:23][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)(=[O:5])=[O:3]
Reactant: C=C[C@@H](N)Cc1ccccc1
Reactant: CS(=O)(=O)OS(C)(=O)=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C=C[C@H](Cc1ccccc1)NS(C)(=O)=O
Reaction time: 1 h

Procedure:
2.36 g (13.6 mmol) of methansulfonic acid anhydride and 1.88 ml (13.6 mmol) of triethylamine are added at 0° C. to a solution of 1 g (6.8 mmol) of 1-phenyl-3-buten-2(S)-amine from Example 16b) in 10 ml methylene chloride and the mixture is stirred for 1 h. The reaction mixture is washed with water and saturated sodium hydrogen carbonate solution and the organic phase is filtered through cotton wadding and concentrated by evaporation to yield 2(S)-methylsulfonylamino-1-phenyl-3-butene. 1 g (4.4 mmol) of that crude product is dissolved in 30 ml of methylene chloride, 3.05 g (17.7 mmol) of 4-chloroperbenzoic acid are added at RT and stirring is carried out for 18 h. The reaction solution is washed 5 times with 10% aqueous sodium sulfite solution, filtered through cotton wadding and fully concentrated by evaporation. According to 1H-NMR the crude product contains both the (2R)- and the (2S)-epimer in a ratio of 4:1. 1 H-NMR (200 MHz, CD3OD): 2.30 and 2.52 (2 s, together 3H), 2.6 to 3.2 (m, 5H), 3.55 (m, 1H) 7.32 (m, 5H).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[Cl:12][C:13]1[CH:14]=[C:15]([CH:17]=[CH:18][CH:19]=1)[NH2:16].C([O-])(=O)C.[Na+]>C(O)CO>[Cl:8][C:6]1[CH:5]=[CH:4][C:3]([N+:9]([O-:11])=[O:10])=[C:2]([NH:16][C:15]2[CH:17]=[CH:18][CH:19]=[C:13]([Cl:12])[CH:14]=2)[CH:7]=1
Reactant: Nc1cccc(Cl)c1
Reactant: O=[N+]([O-])c1ccc(Cl)cc1Cl
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: OCCO
Product: O=[N+]([O-])c1ccc(Cl)cc1Nc1cccc(Cl)c1

Procedure:
A mixture of 50 g of 2,4-dichloro-1-nitrobenzene, 40 ml of 3-chloroaniline and 43 g of anhydrous sodium acetate in 220 ml of ethylene glycol is refluxed for 72 hours. After cooling, the precipitate formed is filtered off and washed with water to give 39 g of the expected product after crystallization from iso ether. M.p.=112° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[NH:9][C:10]([NH:20][O:21][CH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][O:23]1)=[N:11]C(=O)C1C=CC=CC=1.[OH-].[Na+]>O.C(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[NH:9][C:10]([NH2:11])=[N:20][O:21][CH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][O:23]1
Reactant: O=C(N=C(NOC1CCCCO1)Nc1c(Cl)cccc1Cl)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: NC(=NOC1CCCCO1)Nc1c(Cl)cccc1Cl
Yield: 87.5 %

Procedure:
38.5 g 1-(2,6-dichlorophenyl)-2-benzoyl-3-tetrahydropyranyloxyguanidine are heated to a boil with 900 ml 5% NaOH (in a mixture water/ethanol 1:1) for 2 hours. After cooling, 25.1 g 1-(2,6-dichlorophenyl)-2-tetrahydropyranyloxyguanidine having a melting point of 178°-180° C. is obtained.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH:6]=O.[NH2:8][C:9]1[CH:21]=[CH:20][C:19]2[C:18]3[C:13](=[CH:14][C:15]([NH2:22])=[CH:16][CH:17]=3)[CH2:12][C:11]=2[CH:10]=1.[C:23](O)([C:25](F)(F)F)=O>C(O)(C)C>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH:6]=[N:8][C:9]1[CH:10]=[C:11]2[C:19]([C:18]3[CH:17]=[CH:16][C:15]([N:22]=[CH:3][C:2]4[S:1][CH:5]=[CH:23][CH:25]=4)=[CH:14][C:13]=3[CH2:12]2)=[CH:20][CH:21]=1
Reactant: Nc1ccc2c(c1)Cc1cc(N)ccc1-2
Reactant: O=C(O)C(F)(F)F
Reactant: O=Cc1cccs1
Solvent: CC(C)O
Product: C(=Nc1ccc2c(c1)Cc1cc(N=Cc3cccs3)ccc1-2)c1cccs1

Procedure:
2-Thiophenecarboxaldehyde (131 mg, 1.2 mmol) was added to 2,7-diaminofluorene (100 mg, 0.51 mmol) in anhydrous isopropanol and refluxed for 2 days with a catalytic amount of TFA. The solvent was evaporated and no further purification was required. The title compound was obtained as a yellow powder. (196 mg, mmol, 100%) M.p.: 201° C. 1H-NMR (300 MHz, [D] DMSO): δ=7.88 (d, 2H, 3J=11 Hz), 7.81 (d, 2H, 3J=6.5), 7.69 (d, 2H, 3J=4), 7.50 (s, 2H), 7.30 (d, 2H, 3J=11 Hz), 7.22 (t, 2H, 3J=5.0 Hz), 3.96 (s, 2H). 13C-NMR (300 MHz, [D] DMSO): δ=152.91, 148.43, 142.22, 139.53, 129.74, 127.43, 127.10, 125.82, 123.63, 120.34, 36.52. HR-MS: m/z target 385.08277, measured 385.08388, mass error (ppm) 2.89. C.V. −1.36, −0.77, −0.10, 1.27 V. In 0.1 M TBAPF6 as supporting electrolyte in degassed anhydrous acetonitrile λmax=381 nm. λem=318 and 606 nm. Eg=452 nm, 63.23 Kcal/mol. ΔE=298.8 nm, 95.65 Kcal/mol.
Reaction SMILES: [C:1]([NH:5][C:6]1[C:15]2[CH:14]=[CH:13][CH:12]=[C:11]([C:16]([NH:18][C:19]3[CH:24]=[C:23]([NH:25][C:26]([NH:28][C:29]4[CH:34]=[CH:33][C:32](Cl)=[C:31]([C:36]([F:39])([F:38])[F:37])[CH:30]=4)=[O:27])[CH:22]=[CH:21][C:20]=3[CH3:40])=[O:17])[C:10]=2[CH:9]=[CH:8][N:7]=1)([CH3:4])([CH3:3])[CH3:2].[F:41]C1C=CC(C(F)(F)F)=CC=1N=C=O>>[C:1]([NH:5][C:6]1[C:15]2[CH:14]=[CH:13][CH:12]=[C:11]([C:16]([NH:18][C:19]3[CH:24]=[C:23]([NH:25][C:26]([NH:28][C:29]4[CH:30]=[C:31]([C:36]([F:39])([F:38])[F:37])[CH:32]=[CH:33][C:34]=4[F:41])=[O:27])[CH:22]=[CH:21][C:20]=3[CH3:40])=[O:17])[C:10]=2[CH:9]=[CH:8][N:7]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: O=C=Nc1cc(C(F)(F)F)ccc1F
Reactant: Cc1ccc(NC(=O)Nc2ccc(Cl)c(C(F)(F)F)c2)cc1NC(=O)c1cccc2c(NC(C)(C)C)nccc12
Product: Cc1ccc(NC(=O)Nc2cc(C(F)(F)F)ccc2F)cc1NC(=O)c1cccc2c(NC(C)(C)C)nccc12
Yield: 42 %

Procedure:
The procedures of Steps (1), (2) and (3) of Example 12 were repeated step by step, except for using 1-fluoro-2-isocyanato-4-trifluoromethyl benzene instead of benzene in Step (1) of Example 12 to obtain the title compound (60 mg, 42%).
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][C:7]([NH2:11])=[CH:6][CH:5]=2.[N:12]1([CH2:18][CH2:19][NH:20][C:21]([C:23]2[S:31][C:30]3[C:25](=[N:26][CH:27]=[CH:28][C:29]=3Cl)[CH:24]=2)=[O:22])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1>>[N:12]1([CH2:18][CH2:19][NH:20][C:21]([C:23]2[S:31][C:30]3[C:25](=[N:26][CH:27]=[CH:28][C:29]=3[NH:11][C:7]3[CH:8]=[C:9]4[C:4](=[CH:5][CH:6]=3)[NH:3][C:2]([CH3:1])=[CH:10]4)[CH:24]=2)=[O:22])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1
Reactant: Cc1cc2cc(N)ccc2[nH]1
Reactant: O=C(NCCN1CCCCC1)c1cc2nccc(Cl)c2s1
Product: Cc1cc2cc(Nc3ccnc4cc(C(=O)NCCN5CCCCC5)sc34)ccc2[nH]1

Procedure:
The title compound was prepared from 2-methyl-1H-indol-5-ylamine and 7-chloro-thieno[3,2-b]pyridine-2-carboxylic acid (2-piperidin-1-yl-ethyl)-amide by a procedure analogous to Example 1C. MS: 434 (MH+); HPLC Rf: 3.82 min.; HPLC purity 99%.