Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]([CH:9]=O)[C:7]=1[CH3:8].[ClH:11].[C:12]([CH2:15][O:16][NH2:17])([OH:14])=[O:13].C(CON)(O)=O.C([O-])(=O)C.[Na+].[OH-].[Na+]>O.C(O)C>[Cl:11][CH:15]([O:16][N:17]=[CH:9][C:6]1[C:7]([CH3:8])=[CH:2][CH:3]=[CH:4][CH:5]=1)[C:12]([OH:14])=[O:13]
Reactant: Cc1c(Cl)cccc1C=O
Reactant: Cl
Reactant: NOCC(=O)O
Agent: CC(=O)[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: Cc1ccccc1C=NOC(Cl)C(=O)O

Procedure:
A warm solution of 1.5 gm. (0.01 mole) of 6-chloro-o-tolualdehyde in 15 ml. of ethanol was stirred into a solution of 1.1 gm. (0.010 equiv.) of carboxymethoxylamine hemihydrochloride and 1.3 gm. (0.016 equivs.) of anhyd. sodium acetate in 15 ml. water. After heating a half hour on the steam bath, the reaction mixture was cooled and adjusted to pH 8 with 5% aqueous sodium hydroxide. The mixture was extracted with ether, and the ether extract was discarded. The alkaline-aqueous phase was then adjusted to pH 5 with hydrochloric acid and was evaporated to 25 ml. volume. It was then acidified to pH 1.5-2.0 with cooling in ice bath. The solid was removed by filtration, was washed with cold water, and was dried in air to obtain 1.5 gm. (68%) of crude product melting at 121°-6° C. Recrystallization from aqueous-ethanol yielded 1.4 gm. of product melting at 124°-7° C. (dried at 65° C. in vacuo).
Reaction SMILES: [CH:1]([S:4]([CH2:7][C@H:8]1[C@@H:13]([N:14]2[CH2:18][CH2:17][C@H:16]([NH:19][C:20](=[O:31])[C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=3)[C:15]2=[O:32])[CH2:12][CH2:11][N:10](C(OC(C)(C)C)=O)[CH2:9]1)(=[O:6])=[O:5])([CH3:3])[CH3:2].F[C:41](F)(F)[C:42](O)=O.[C:47]([O-])(O)=O.[Na+]>C(Cl)Cl>[CH:41]([N:10]1[CH2:11][CH2:12][C@H:13]([N:14]2[CH2:18][CH2:17][C@H:16]([NH:19][C:20](=[O:31])[C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:29])([F:28])[F:30])[CH:22]=3)[C:15]2=[O:32])[C@H:8]([CH2:7][S:4]([CH:1]([CH3:3])[CH3:2])(=[O:5])=[O:6])[CH2:9]1)([CH3:42])[CH3:47].[CH:1]([S:4]([CH2:7][C@H:8]1[C@@H:13]([N:14]2[CH2:18][CH2:17][C@H:16]([NH:19][C:20](=[O:31])[C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:28])([F:30])[F:29])[CH:22]=3)[C:15]2=[O:32])[CH2:12][CH2:11][NH:10][CH2:9]1)(=[O:5])=[O:6])([CH3:3])[CH3:2]
Reactant: CC(C)S(=O)(=O)C[C@@H]1CN(C(=O)OC(C)(C)C)CC[C@@H]1N1CC[C@H](NC(=O)c2cccc(C(F)(F)F)c2)C1=O
Reactant: O=C([O-])O
Reactant: O=C(O)C(F)(F)F
Agent: [Na+]
Solvent: ClCCl
Product: CC(C)N1CC[C@H](N2CC[C@H](NC(=O)c3cccc(C(F)(F)F)c3)C2=O)[C@H](CS(=O)(=O)C(C)C)C1
Product: CC(C)S(=O)(=O)C[C@@H]1CNCC[C@@H]1N1CC[C@H](NC(=O)c2cccc(C(F)(F)F)c2)C1=O
Reaction time: 4 h

Procedure:
A sample of (3R,4S)-tert-butyl 3-(isopropylsulfonylmethyl)-4-((S)-2-oxo-3-(3-(trifluoromethyl)benzamido)pyrrolidin-1-yl)piperidine-1-carboxylate (0.688 g) was dissolved in CH2Cl2 (10 mL) prior to the addition of trifluoroacetic acid (0.92 mL, 11.9 mMol). After 4 h, the reaction was made basic with saturated NaHCO3. Extracted with CH2Cl2. The organic layer was washed with brine and dried (MgSO4). Concentrated and dried in vacuo to yield the desired product, N-((S)-1-((3R,4S)-3-(isopropylsulfonylmethyl)piperidin-4-yl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethyl)benzamide) (0.482 g, yield=85%). MS found: (M+H)+=476.31
Reaction SMILES: Cl.[NH2:2][C:3]1[C:11]([OH:12])=[C:10]2[C:6]([CH2:7][CH2:8][CH:9]2[CH2:13][CH2:14][NH:15][C:16](=[O:18])[CH3:17])=[CH:5][CH:4]=1.[C:19]1([CH2:25][C:26](Cl)=[O:27])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.O>N1C=CC=CC=1>[C:16]([NH:15][CH2:14][CH2:13][CH:9]1[C:10]2[C:6](=[CH:5][CH:4]=[C:3]([NH:2][C:26](=[O:27])[CH2:25][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:11]=2[OH:12])[CH2:7][CH2:8]1)(=[O:18])[CH3:17]
Reactant: CC(=O)NCCC1CCc2ccc(N)c(O)c21
Reactant: O=C(Cl)Cc1ccccc1
Agent: Cl
Solvent: O
Solvent: c1ccncc1
Product: CC(=O)NCCC1CCc2ccc(NC(=O)Cc3ccccc3)c(O)c21
Reaction time: 0.25 h
Yield: 23.8 %

Procedure:
N-[2-(6-Amino-7-hydroxy-2,3-dihydro-1H-inden-1-yl)ethyl]acetamide hydrochloride (100 mg, 0.369 mmol) was dissolved in pyridine (4 mL), phenylacetyl chloride (53.5 μL, 0.406 mmol) was added under ice-cooling, and the mixture was stirred for 15 min. Water was added to the reaction solution, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=80/20→100/0) to give the title compound (31.0 mg, yield 24%).
Reaction SMILES: CO[C:3]1([O:14]C)[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](=[O:13])[CH:5]=[CH:4]1.[C:16]1([CH3:34])[CH:21]=[CH:20][C:19]([S:22]([N:25]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:27]=[CH:26]2)(=[O:24])=[O:23])=[CH:18][CH:17]=1>>[OH:14][C:3]1([C:26]2[N:25]([S:22]([C:19]3[CH:20]=[CH:21][C:16]([CH3:34])=[CH:17][CH:18]=3)(=[O:24])=[O:23])[C:33]3[C:28]([CH:27]=2)=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](=[O:13])[CH:5]=[CH:4]1
Reactant: COC1(OC)C=CC(=O)c2ccccc21
Reactant: Cc1ccc(S(=O)(=O)n2ccc3ccccc32)cc1
Product: Cc1ccc(S(=O)(=O)n2c(C3(O)C=CC(=O)c4ccccc43)cc3ccccc32)cc1
Yield: 23 %

Procedure:
The title compound was prepared from 4,4-dimethoxy-4H-naphthalen-1-one and 1-(toluene4-sulfonyl)-1H-indole, according to Method E, described above. Yield 23%; mp 110-112° C.; 1H NMR (CDCl3) δ 8.35-8.39 (dd, J=8 Hz, 1H), 8.04 (d, J=8 Hz,1H), 7.74-7.97 (m, 6H), 7.32-7.48 (m, 6H), 6.53 (d, J=10 Hz,1H), 2.52 (s, 3H); 13C NMR (CDCl3) δ 189.7, 154.0, 150.2, 149.8, 148.8, 143.6, 140.1, 137.9, 135.7, 134.8, 133.6, 132.3, 131.7, 131.3, 130.7, 129.3, 126.6, 120.4, 120.3, 74.8, 26.6; MS (AP+) m/z 430.09 (M++1), 412.14.
Reaction SMILES: BrBr.[F:3][C:4]1[CH:9]=[C:8]([CH2:10][C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[CH:14]=2)=O)[CH:7]=[CH:6][N:5]=1.C(N(CC)CC)C.[NH2:27][C:28]([NH2:30])=[S:29].C(=O)([O-])O.[Na+]>C(O)(=O)C.C(#N)C>[F:3][C:4]1[CH:9]=[C:8]([C:10]2[S:29][C:28]([NH2:30])=[N:27][C:11]=2[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[CH:14]=2)[CH:7]=[CH:6][N:5]=1
Reactant: Cc1cccc(C(=O)Cc2ccnc(F)c2)c1
Reactant: NC(N)=S
Agent: BrBr
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CC(=O)O
Solvent: CC#N
Product: Cc1cccc(-c2nc(N)sc2-c2ccnc(F)c2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 35 %

Procedure:
Bromine (1.9 mL, 37 mmol) was added to a solution of 2-(2-fluoro-4-pyridyl)-1-(3-methylphenyl)ethanone (8.5 g, 37 mmol) in acetic acid (50 mL) and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated. Triethylamine (5.2 mL, 37 mmol) was added to a mixture of this residue and thiourea (3.0 g, 40 mmol) in acetonitrile (50 mL) and the mixture was stirred at 80° C. for 2 hours. A saturated aqueous solution of sodium hydrogencarbonate (50 mL) was added to the reaction mixture and the precipitated solid was collected by filtration. After the resulting solid was washed with water, it was dried. The crude crystals were recrystallized from ethanol to obtain 3.7 g (yield 35%) of the title compound.
Reaction SMILES: Cl[C:2]1[C:7]([Cl:8])=[CH:6][C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.[S:13]([O-:16])([OH:15])=[O:14].[Na+:17].C(O)C>O>[F:10][C:9]([F:12])([F:11])[C:5]1[CH:6]=[C:7]([Cl:8])[C:2]([S:13]([O-:16])(=[O:15])=[O:14])=[N:3][CH:4]=1.[Na+:17]
Reactant: FC(F)(F)c1cnc(Cl)c(Cl)c1
Reactant: O=S([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: O=S(=O)([O-])c1ncc(C(F)(F)F)cc1Cl
Yield: 103 %

Procedure:
In a flask, 2,3-dichloro-5-(trifluoromethyl)pyridine (10.8 g, 50 mmol), sodium hydrogen sulfite (20.8 g, 200 mmol), ethanol (100 ml) and water (100 ml) were charged and heated under reflux for 41 hours. After evaporating off the solvent from the reaction mixture, conc. hydrochloric acid was added to the residue and then evaporated to dryness. This residue was extracted with methanol, and the metanol phase was filtered and evaporated to dryness to obtain quantitatively sodium 5-trifluoromethyl-3-chloropyridine-2-sulfonate (14.6 g). Decomposition point, 322°-334° C.
Reaction SMILES: [CH3:1][N:2]([CH3:22])[C:3](=[O:21])[O:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([NH:11][C:12]([C:14]2([NH2:20])[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[O:13])[CH:6]=1.Cl[C:24]1[C:25]2[C:32]([CH3:33])=[CH:31][NH:30][C:26]=2[N:27]=[CH:28][N:29]=1.C(N(CC)C(C)C)(C)C>C(O)(C)C>[CH3:1][N:2]([CH3:22])[C:3](=[O:21])[O:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([NH:11][C:12]([C:14]2([NH2:20])[CH2:19][CH2:18][N:17]([C:24]3[C:25]4[C:32]([CH3:33])=[CH:31][NH:30][C:26]=4[N:27]=[CH:28][N:29]=3)[CH2:16][CH2:15]2)=[O:13])[CH:6]=1
Reactant: Cc1c[nH]c2ncnc(Cl)c12
Reactant: CN(C)C(=O)Oc1cccc(NC(=O)C2(N)CCNCC2)c1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(C)O
Product: Cc1c[nH]c2ncnc(N3CCC(N)(C(=O)Nc4cccc(OC(=O)N(C)C)c4)CC3)c12
Temperature: 120 °C
Yield: 54 %

Procedure:
3-(4-aminopiperidine-4-carboxamido)phenyl dimethylcarbamate from step B (0.109 g, 0.36 mmol), 4-chloro-5-methyl-7H-pyrrolo[2,3-d]pyrimidine (0.060 g, 0.36 mmol), and N,N-diisopropylethylamine (0.277 g, 2.14 mmol) were combined in isopropanol (5 mL) and heated in a sealed tube at 120° C. for 18 hours. The mixture was concentrated, and the residue was purification by silica gel chromatography (0-10% MeOH/CH2Cl2) to afford the title compound (0.085 g, 55%) as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:17]([N+:18]([O-])=O)=[CH:16][C:6]2[CH2:7][CH2:8][N:9]([CH2:12][CH2:13][O:14][CH3:15])[CH2:10][CH2:11][C:5]=2[CH:4]=1.O.NN>[Pd].CO>[CH3:1][O:2][C:3]1[C:17]([NH2:18])=[CH:16][C:6]2[CH2:7][CH2:8][N:9]([CH2:12][CH2:13][O:14][CH3:15])[CH2:10][CH2:11][C:5]=2[CH:4]=1
Reactant: COCCN1CCc2cc(OC)c([N+](=O)[O-])cc2CC1
Agent: [Pd]
Agent: NN
Solvent: O
Solvent: CO
Product: COCCN1CCc2cc(N)c(OC)cc2CC1
Temperature: 70 °C
Yield: 93.3 %

Procedure:
Into a 1-neck round-bottom flask was added 7-methoxy-3-(2-methoxy-ethyl)-8-nitro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (2.4 g, 8.56 mmol), hydrazine monohydrate (20 mL, 0.4 mol), and palladium on carbon (10% wt, 50% wet; 400 mg), in methanol (80 mL). The reaction mixture was heated at 70° C. for 3 hours. The reaction mixture was filtered through Celite and was concentrated. The residue was partitioned between diluted NaHCO3 and ethyl acetate. The aqueous phase was extracted with another portion of ethyl acetate, dried (MgSO4), and concentrated to afford 8-methoxy-3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (2.00 g, 93%). 1H-NMR (CDCl3) δ 6.55 (s, 1H), 6.49 (s, 1H), 3.81 (s, 3H), 3.63 (br s, 2H), 3.53 (t, J=5.8 Hz, 2H), 3.36 (s, 3H), 2.60-2.90 (m, 10H); LC/MS (ESI+): 251.10 (M+H).
Reaction SMILES: [OH-].[K+].[CH2:3]([C:9]1[C:10]2[NH:14][C:13]([C:15]([C:49]3[CH:54]=[CH:53][C:52]([C:55]([O:57]C)=[O:56])=[CH:51][CH:50]=3)=[C:16]3[N:48]=[C:19]([C:20]([CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47])=[C:21]4[NH:41][C:24](=[C:25]([C:31]5[CH:36]=[CH:35][C:34]([C:37]([O:39]C)=[O:38])=[CH:33][CH:32]=5)[C:26]5[CH:27]=[CH:28][C:29]=1[N:30]=5)[CH:23]=[CH:22]4)[CH:18]=[CH:17]3)=[CH:12][CH:11]=2)[CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].O.Cl>CO.C1COCC1>[C:37]([C:34]1[CH:33]=[CH:32][C:31]([C:25]2[C:24]3[NH:41][C:21]([C:20]([CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47])=[C:19]4[N:48]=[C:16]([C:15]([C:49]5[CH:50]=[CH:51][C:52]([C:55]([OH:57])=[O:56])=[CH:53][CH:54]=5)=[C:13]5[NH:14][C:10](=[C:9]([CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])[C:29]6[CH:28]=[CH:27][C:26]=2[N:30]=6)[CH:11]=[CH:12]5)[CH:17]=[CH:18]4)=[CH:22][CH:23]=3)=[CH:36][CH:35]=1)([OH:39])=[O:38]
Reactant: CCCCCCc1c2nc(c(-c3ccc(C(=O)OC)cc3)c3ccc([nH]3)c(CCCCCC)c3nc(c(-c4ccc(C(=O)OC)cc4)c4ccc1[nH]4)C=C3)C=C2
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: CCCCCCc1c2nc(c(-c3ccc(C(=O)O)cc3)c3ccc([nH]3)c(CCCCCC)c3nc(c(-c4ccc(C(=O)O)cc4)c4ccc1[nH]4)C=C3)C=C2
Reaction time: 48 h

Procedure:
In a typical experiment, a solution of KOH (200 mg, 3.6 mmol) in methanol (1 ml) was added to a stirred solution of 5,15-dihexyl-10,20-bis-(4-methoxycarbonylphenyl)-porphyrin (31 mg, 0.04 mmol) in THF (8 ml) and the reaction mixture was stirred for 2 d. Water (50 ml) and hydrochloric acid were then added until the pH was adjusted to 4-6. The aqueous layer was extracted with dichloromethane (2×100 ml) and the organic layer was separated, washed with water until neutral and dried over sodium sulfate. The solvent was evaporated and the title compound 5,15-bis-(4-carboxyphenyl)-10,20-dihexyl-porphyrin was obtained after recrystallization from dichloromethane/aqueous methanol (26 mg, 87%).
Reaction SMILES: [C:1]([NH2:9])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.[CH2:16]=O>CO>[N:10]1([CH2:16][NH:9][C:1](=[O:8])[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1
Reactant: C1CCNCC1
Reactant: C=O
Reactant: NC(=O)c1ccccc1
Solvent: CO
Product: O=C(NCN1CCCCC1)c1ccccc1
Reaction time: 0.17 h
Yield: 893.3 %

Procedure:
Benzamide (0.5 g, 0.4 mmol) was dissolved in 5 mL of methanol. To this stirred solution piperidine (0.35 mL, 0.4 mol) was added and the resulting solution was cooled in an ice bath. Formaldehyde (0.31 mL, 0.4 mol, 37% in water) was added dropwise. The solution was stirred for 10 min and then it was refluxed for 4 h. After cooling, the solvents were evaporated to give Mannich base 15 as a white solid 0.78 g (87% yield).
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][Si:5]([O:12][CH2:13][CH3:14])([O:9][CH2:10][CH3:11])[O:6][CH2:7][CH3:8].[S].[S-2:16].[Na+].[Na+].[SH2:19]>O.C(O)C>[CH2:7]([O:6][Si:5]([CH2:4][CH2:3][CH2:2][S:16][S:19][CH2:2][CH2:3][CH2:4][Si:5]([O:6][CH2:7][CH3:8])([O:12][CH2:13][CH3:14])[O:9][CH2:10][CH3:11])([O:12][CH2:13][CH3:14])[O:9][CH2:10][CH3:11])[CH3:8]
Reactant: [S-2]
Reactant: CCO[Si](CCCCl)(OCC)OCC
Reactant: S
Agent: [Na+]
Agent: [S]
Solvent: CCO
Solvent: O
Product: CCO[Si](CCCSSCCC[Si](OCC)(OCC)OCC)(OCC)OCC
Reaction time: 1.5 h

Procedure:
A mixture of 129 l of ethanol and 129 l of 3-chloropropyltriethoxysilane is placed in the reactor of comparison example 1. 13.85 kg of sulfur in the form of a powder are metered in. 35.6 kg of virtually anhydrous sodium sulfide is then added. The temperature of the reactor contents rises to 82° C. on account of the exothermic reaction. The reaction mixture is kept for a further 1.5 hours at 82-83° C. and then cooled. The reaction mixture is worked up as in comparison example 1. An almost water-white product is obtained. HPLC analysis confirms in this case too the presence of a polysulfane mixture with a mean chain length of 2, though the mixture has a high monosulfane content.
Reaction SMILES: [OH:1][CH:2]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([C:13]2[C:14](=[O:32])[NH:15][C:16](=[O:31])[C:17]=2[C:18]2[C:26]3[C:21](=[CH:22][C:23]([N+:27]([O-:29])=[O:28])=[CH:24][CH:25]=3)[N:20]([CH3:30])[CH:19]=2)=[CH:5]1)[CH3:3].C(Cl)CCl.CN(C1C=CC=CN=1)C.[CH3:46][O:47][C:48]1[C:56]([O:57][CH3:58])=[CH:55][CH:54]=[CH:53][C:49]=1[C:50](O)=[O:51]>C(Cl)Cl>[CH3:30][N:20]1[C:21]2[C:26](=[CH:25][CH:24]=[C:23]([N+:27]([O-:29])=[O:28])[CH:22]=2)[C:18]([C:17]2[C:16](=[O:31])[NH:15][C:14](=[O:32])[C:13]=2[C:6]2[C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[N:4]([CH:2]([O:1][C:50](=[O:51])[C:49]3[CH:53]=[CH:54][CH:55]=[C:56]([O:57][CH3:58])[C:48]=3[O:47][CH3:46])[CH3:3])[CH:5]=2)=[CH:19]1
Reactant: COc1cccc(C(=O)O)c1OC
Reactant: CC(O)n1cc(C2=C(c3cn(C)c4cc([N+](=O)[O-])ccc34)C(=O)NC2=O)c2ccccc21
Agent: CN(C)c1ccccn1
Solvent: ClCCl
Solvent: ClCCCl
Product: COc1cccc(C(=O)OC(C)n2cc(C3=C(c4cn(C)c5cc([N+](=O)[O-])ccc45)C(=O)NC3=O)c3ccccc32)c1OC
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 51.1 %

Procedure:
To a solution of 3-[1-(1-hydroxy-ethyl)-1H-indol-3-yl]-4-(1-methyl-6-nitro-1H-indol-3-yl)-pyrrole-2,5-dione (165.3 mg, 0.678 mmol) (from step d) above), EDC.HCL (284.5 mg, 1.484 mmol), and dimethylaminopyridine (185.5 mg, 1.58 mmol) in 20 mL of CH2Cl2 was added 2,3-dimethoxybenzoic acid (287.4 mg, 0.668 mmol). The solution was stirred at room temperature for 0.5 hour, washed with saturated NaHCO3, brine, dried over magnesium sulfate, and evaporated. The residue was purified by flash chromatography using EtOAc/hexanes to give 203 mg of 2,3-dimethoxy-benzoic acid 1-{3-[4-(1-methyl-6-nitro-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-indol-1-yl}-ethyl ester. (Yield 50%).
Reaction SMILES: [F:1][C:2]([F:14])([F:13])[CH2:3][O:4][CH2:5][C:6]1[N:11]=[C:10]([NH2:12])[CH:9]=[CH:8][CH:7]=1.[F:15][C:16]([F:28])([F:27])[C:17]1[CH:18]=[C:19]([S:23](Cl)(=[O:25])=[O:24])[CH:20]=[CH:21][CH:22]=1>>[F:14][C:2]([F:1])([F:13])[CH2:3][O:4][CH2:5][C:6]1[N:11]=[C:10]([NH:12][S:23]([C:19]2[CH:20]=[CH:21][CH:22]=[C:17]([C:16]([F:15])([F:27])[F:28])[CH:18]=2)(=[O:25])=[O:24])[CH:9]=[CH:8][CH:7]=1
Reactant: Nc1cccc(COCC(F)(F)F)n1
Reactant: O=S(=O)(Cl)c1cccc(C(F)(F)F)c1
Product: O=S(=O)(Nc1cccc(COCC(F)(F)F)n1)c1cccc(C(F)(F)F)c1

Procedure:
This material was prepared in analogy to example 1 from 6-(2,2,2-Trifluoro-ethoxymethyl)-pyridin-2-ylamine (0.08 g) and 3-(trifluoromethyl)-benzenesulfonyl chloride (0.104 g) as alight yellow gum (0.066 g). MS (ESI−): 413.1 ([M−H]−).
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:9])[C:7]=1[CH3:8].[C:10]([Cu])#[N:11].CCOC(C)=O>CN(C=O)C>[Br:9][C:6]1[C:7]([CH3:8])=[C:2]([C:10]#[N:11])[CH:3]=[N:4][CH:5]=1
Reactant: Cc1c(Br)cncc1Br
Reactant: N#C[Cu]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Cc1c(Br)cncc1C#N

Procedure:
A mixture of 3,5-dibromo-4-methylpyridine (16 g, 64 mmol) and CuCN (6.2 g, 69 mmol) in 150 mL of DMF was refluxed for 4 hours before cooled down. The reaction mixture was poured to 1 L of EtOAc with stirring and the precipitate was removed by filtration. The filtrate was washed with water, brine, dried over anhydrous Na2SO4 and concentrated. The residue was purified by column chromatography to afford 5-bromo-4-methylpyridine-3-carbonitrile.
Reaction SMILES: [NH2:1][C@H:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[N:4]([CH3:19])[C:3]1=[O:20].[I:21][C:22]1[CH:30]=[CH:29][CH:28]=[CH:27][C:23]=1[C:24](Cl)=[O:25].C(N(CC)CC)C>CCOC(C)=O>[CH3:19][N:4]1[C:5]2[CH:18]=[CH:17][CH:16]=[CH:15][C:6]=2[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:8][C@H:2]([NH:1][C:24](=[O:25])[C:23]2[CH:27]=[CH:28][CH:29]=[CH:30][C:22]=2[I:21])[C:3]1=[O:20]
Reactant: CN1C(=O)[C@@H](N)N=C(c2ccccc2)c2ccccc21
Reactant: O=C(Cl)c1ccccc1I
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: CN1C(=O)[C@@H](NC(=O)c2ccccc2I)N=C(c2ccccc2)c2ccccc21
Reaction time: 1 h

Procedure:
Equimolar amounts of 3(S)-amino-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one, o-iodobenzoylchloride and triethylamine were mixed at room temperature and stirred 1 hour. Flash chromatography of the reaction solution on silica gel (5% Et2O in CH2Cl2) provided the title compound as a crystalline solid from EtOAc: m.p. 115°-120° C. (physical change), 173°-175° C. (melt).
Reaction SMILES: [Zn:1].[C:2]([O-:21])(=[O:20])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]>>[C:2]([O-:21])(=[O:20])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].[Zn+2:1].[C:2]([O-:21])(=[O:20])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]
Reactant: [Zn]
Agent: CCCCCCCCCCCCCCCCCC(=O)[O-]
Product: [Zn+2]

Procedure:
A method of forming an aqueous dispersion of particles of zinc stearate includes the steps of forming a mixture of at least one surfactant and water, heating the mixture to a temperature of from about 40° C. to less than a melting temperature of zinc stearate, adding a metal-containing stearate to the mixture under agitation, adding to the mixture a solution of a zinc salt in water, whereby upon inclusion of both the metal-containing stearate and the zinc salt in the mixture, the zinc salt reacts with the metal-containing stearate to form the particles of zinc stearate, continuing the heating and agitation following completion of the latter of the adding of the solution of zinc salt or the adding of the metal-containing stearate to continue the reaction, and cooling to obtain the aqueous dispersion of particles of zinc stearate. The method forms a stable aqueous dispersion of nanometer sized zinc stearate particles particularly useful in coating toner particles.
Reaction SMILES: O[CH2:2][C:3]1[C:7]([CH3:8])=[C:6]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=2)[S:5][C:4]=1[C:15]1[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:40]([O:44][C:45]([NH:47][O:48][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])=[O:46])([CH3:43])([CH3:42])[CH3:41].CCOC(/N=N/C(OCC)=O)=O>C1COCC1.O>[C:40]([O:44][C:45]([N:47]([CH2:2][C:3]1[C:7]([CH3:8])=[C:6]([C:9]2[CH:10]=[CH:11][N:12]=[CH:13][CH:14]=2)[S:5][C:4]=1[C:15]1[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=1)[O:48][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])=[O:46])([CH3:43])([CH3:42])[CH3:41]
Reactant: Cc1c(-c2ccncc2)sc(-c2ccncc2)c1CO
Reactant: CC(C)(C)OC(=O)NOC(=O)OC(C)(C)C
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: C1CCOC1
Product: Cc1c(-c2ccncc2)sc(-c2ccncc2)c1CN(OC(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Reaction time: 23 h
Yield: 35.6 %

Procedure:
To a stirred solution of 3-hydroxymethyl-2,5-di(4-pyridyl)-4-methylthiophene (0.282 g), triphenylphosphine(0.446 g), and N,O-di-(tert-butoxycarbonyl)hydroxylamine (0.224 g), in THF (20 mL) was added diethylazodicarboxylate (0.296 g) under nitrogen. After stirring for 23 hours, the reaction mixture was poured into water (50 mL) and the whole was extracted with CH2Cl2 (100 mL). The organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by flash chromatography eluting with ethyl acetate-CH2Cl2-MeOH (1:1:0.04). The resulting product was purified by column chromatography on silica(NH-silica gel, FUJI SILISIA CHEMICAL LTD. DM2035)(ethyl acetate-CH2Cl2-MeOH=1:1:0.04) to give the subtitle compound (0.17 g).
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[C:8]([O:14][CH3:15])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[C:16]1(C)C=CC=CC=1.CO.C[Si](C=[N+]=[N-])(C)C>CCOCC>[CH3:16][O:5][C:4](=[O:6])[C:3]1[CH:7]=[C:8]([O:14][CH3:15])[C:9]([N+:11]([O-:13])=[O:12])=[CH:10][C:2]=1[F:1]
Reactant: Cc1ccccc1
Reactant: COc1cc(C(=O)O)c(F)cc1[N+](=O)[O-]
Agent: C[Si](C)(C)C=[N+]=[N-]
Solvent: CCOCC
Solvent: CO
Product: COC(=O)c1cc(OC)c([N+](=O)[O-])cc1F
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Into a round bottom flask, 2-fluoro-5-methoxy-4-nitro-benzoic acid (2.84 g, 0.0132 mol;), toluene (25 mL, 0.23 mol), methanol (5 mL, 0.1 mol;) were added. 2.00 M of trimethylsilyldiazomethane in ether (7.92 mL) was added drop wise at 5° C. The reaction was stirred at room temperature for 2 hours. The solvent was removed under vacuum to afford a yellow solid. The solid was triturated with 10% Et2O and hexane to give 2-fluoro-5-methoxy-4-nitro-benzoic acid methyl ester as an off white solid (2.84, 93%). 1H-NMR (DMSO-D6, 400 MHz): δ 8.06 (d, 1H), 7.70 (d, 1H). 4.14 (s, 3H), 3.91 (s, 3H).