Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:19]([NH:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[CH:23]=3)=[O:20])=[CH:14][CH:13]=2)=[C:6]2[C:10]=1[C:9](=[O:11])[NH:8][CH2:7]2.[C:29](Cl)(=[O:31])[CH3:30]>C1COCC1>[CH3:28][C:24]1[CH:23]=[C:22]([NH:21][C:19]([NH:18][C:15]2[CH:14]=[CH:13][C:12]([C:5]3[CH:4]=[CH:3][C:2]([NH:1][C:29](=[O:31])[CH3:30])=[C:10]4[C:6]=3[CH2:7][NH:8][C:9]4=[O:11])=[CH:17][CH:16]=2)=[O:20])[CH:27]=[CH:26][CH:25]=1
Reactant: Cc1cccc(NC(=O)Nc2ccc(-c3ccc(N)c4c3CNC4=O)cc2)c1
Reactant: CC(=O)Cl
Solvent: C1CCOC1
Product: CC(=O)Nc1ccc(-c2ccc(NC(=O)Nc3cccc(C)c3)cc2)c2c1C(=O)NC2
Temperature: 25 °C
Reaction time: 8 h
Yield: 77.4 %

Procedure:
A suspension of Example 3 (0.088 g, 0.24 mmol) in THF (2 mL) was treated dropwise via syringe with acetyl chloride (0.017 mL, 0.24 mmol), stirred at room temperature overnight, quenched with water, cooled to 0° C., and filtered. The filter cake was dried to give 77 mg of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 2.17 (s, 3H); 2.28 (s, 3H); 4.55 (s, 2H); 6.80 (d, J=7.1 Hz, 1H); 7.16 (t, J=7.8 Hz, 1H); 7.24 (d, J=8.1 Hz, 1H); 7.31 (br s, 1H); 7.50 (d, J=8.8 Hz, 2H); 7.56 (d, J=8.8 Hz, 2H); 7.61 (d, J=8.5 Hz, 1H); 8.38 (d, J=8.1 Hz, 1H); 8.62 (s, 1H); 8.78 (s, 1H); 8.96 (s, 1H); 10.58 (s, 1H); MS (ESI(+)) m/e 415 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=2)=[N+]=[N-])[CH:6]=[CH:7][CH:8]=1.COC1C=C(C=CC=1)C(=NN)C1C=CC=C(OC)C=1.[O:39]=[CH:40][C:41](=[CH2:43])[CH3:42]>ClCCl.CCCCCCC.[O-2].[O-2].[Mn+4]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=3)[CH2:42][C:41]2([CH3:43])[CH:40]=[O:39])[CH:6]=[CH:7][CH:8]=1
Reactant: COc1cccc(C(=[N+]=[N-])c2cccc(OC)c2)c1
Reactant: C=C(C)C=O
Agent: [Mn+4]
Agent: COc1cccc(C(=NN)c2cccc(OC)c2)c1
Agent: [O-2]
Solvent: CCCCCCC
Solvent: ClCCl
Product: COc1cccc(C2(c3cccc(OC)c3)CC2(C)C=O)c1
Temperature: 40 °C
Reaction time: 16 h

Procedure:
A solution of bis(3-methoxyphenyl)diazomethane, prepared as in Example 84 from 3,3'-dimethoxybenzophenone hydrazone (18.7 g) and activated manganese dioxide (24.3 g) in dichloromethane (125 mL) was added to a solution of methacrolein (10.8 mL) in heptane (70 mL) over 10 minutes at 40° C. The mixture was stirred at 40° C. for 16 hours, and then after the dichloromethane was distilled off, at 85° C. for 1 hour. The solvent was removed in vacuo and the residue was purified by HPLC (ethyl acetate-hexane; 1:5) to yield 8.0 g of 2,2-bis(3-methoxyphenyl)1-methylcyclopropanecarboxaldehyde. Crystallization of the material from ethyl acetate-hexane provided 6.2 g of the aldehyde, mp 122°-123° C.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][OH:6].[Si:10](Cl)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11].C(N(CC)CC)C>C(Cl)Cl>[Si:10]([O:6][CH2:5][C:4]1[CH:3]=[C:2]([CH:9]=[CH:8][CH:7]=1)[NH2:1])([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]
Reactant: Nc1cccc(CO)c1
Reactant: CC(C)(C)[Si](C)(C)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)OCc1cccc(N)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 56.7 %

Procedure:
To a solution of 3-aminobenzyl alcohol (2.00 g, 16.2 mmol) and tert-butyldimethylsilyl chloride (2.90 g, 19.4 mmol) in CH2Cl2 (32.5 mL) was added triethylamine (7.45 mL, 53.5 mmol). The reaction mixture was stirred for 18 hours at ambient temperature and was then partitioned between ethyl acetate and H2O. The organic phase was washed twice with H2O, twice with brine, dried over MgSO4, filtered, and concentrated in vacuo. 3-(O-t-butyldimethylsilyloxymethyl)aniline (2.18 g, 57%) was obtained as a yellow oil by chromatography on silica gel (30% ethyl acetate/hexane). 1H NMR (300 MHz, CDCl3) δ7.10 (1H, t, J=7.5 Hz), 6.67-6.72 (2H, m), 6.56 (1H, br d, J=7.5 Hz), 4.66 (2H, s), 3.63 (2H, br s), 0.94 (9H, s), 0.09 (6H, s). MS m/e 238(M+H)+, 255 (M+NH4)+.
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].C(OC(=O)C)(=O)C.S(=O)(=O)(O)O.[C:17]([NH:23][C:24]1[CH:33]=[CH:32][C:27]([C:28]([O:30][CH3:31])=[O:29])=[CH:26][CH:25]=1)(=[O:22])[CH2:18][CH2:19][CH2:20][CH3:21]>>[N+:1]([C:25]1[CH:26]=[C:27]([CH:32]=[CH:33][C:24]=1[NH:23][C:17](=[O:22])[CH2:18][CH2:19][CH2:20][CH3:21])[C:28]([O:30][CH3:31])=[O:29])([O-:4])=[O:2]
Reactant: O=[N+]([O-])O
Reactant: CCCCC(=O)Nc1ccc(C(=O)OC)cc1
Agent: O=S(=O)(O)O
Solvent: CC(=O)OC(C)=O
Product: CCCCC(=O)Nc1ccc(C(=O)OC)cc1[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 1 h
Yield: 76 %

Procedure:
Fuming nitric acid (1.4 ml) was added dropwise to acetic anhydride (12 ml) under ice-cooling and then was added conc. sulfuric acid (0.1 ml). To the stirred mixture was added methyl 4-valerylaminobenzoate (2.3 g) under ice-cooling, followed by stirring for one hour. To the resultant mixture was added ice water, and the crystals separated out were recrystallized from ethyl acetate - hexane to give yellow prisms (2.14 g, 76%),
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[C:8](F)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[Cl:11][C:12]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:13]=1[OH:20].C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[Cl:1][C:2]1[CH:9]=[C:8]([O:20][C:13]2[CH:14]=[CH:15][C:16]([O:18][CH3:19])=[CH:17][C:12]=2[Cl:11])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]
Reactant: COc1ccc(O)c(Cl)c1
Reactant: N#Cc1ccc(F)cc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: COc1ccc(Oc2ccc(C#N)c(Cl)c2)c(Cl)c1
Temperature: 120 °C
Reaction time: 2 h

Procedure:
A solution of 3.0 g (19.28 mmol) of 2-chloro-4-fluorobenzonitrile and 3.06 g (19.28 mmol) of 2-chloro-4-methoxyphenol in 77 mL DMSO was combined with 5.32 g (38.57 mmol) of potassium carbonate and stirred for 2 h at 120° C. Then the mixture was evaporated to dryness in vacuo, the residue was taken up in dichloromethane and washed once with semisaturated potassium carbonate solution and twice with water. The organic phase was dried on sodium sulphate and evaporated down.
Reaction SMILES: [CH3:1][C:2](=[CH:4][CH2:5][CH2:6]/[C:7](=[CH:9]/[CH2:10][OH:11])/[CH3:8])[CH3:3].OC/C=C(/C)\CCC=C(C)C.C(N(CC)CC)C.[C:30](Cl)(=[O:42])[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41]>C1(C)C=CC=CC=1>[C:30]([O:11][CH2:10]/[CH:9]=[C:7](/[CH2:6][CH2:5][CH:4]=[C:2]([CH3:1])[CH3:3])\[CH3:8])(=[O:42])[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41]
Reactant: CCCCCCCCCCCC(=O)Cl
Reactant: CC(C)=CCC/C(C)=C/CO
Agent: CC(C)=CCC/C(C)=C\CO
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CCCCCCCCCCCC(=O)OC/C=C(\C)CCC=C(C)C
Temperature: 25 °C

Procedure:
A mixture of geraniol and nerol (approximately 70:30 by weight) in the amount of 50.00 g (0.324 mol) and triethylamine in the amount of 36.08 g (0.357 mol) are combined with 300 mL of toluene. The reaction mixture is heated to reflux and lauroyl chloride in the amount 70.92 g (0.324 mol) isadded dropwise over 15 min. After heating for an additional 30 min, the product mixture is cooled to room temperature and filtered. The filtrate is washed three times with 100 niL of saturated NaHCO3, 100 mL of water, and dried over MgSO4. After filtration, the filtrate is concentrated by rotary evaporation followed by Kugelrohr distillation. Purity of the product is determined by thin layer chromatography and the structure confirmed by 13C and 1H NMR.
Reaction SMILES: [C:1]([S:9][C:10]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:11]=1[CH:12]=[CH:13][N:14]=[CH:15]2)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4]C=1.C[O-].[Na+].[N+:23](C1C=CC(F)=CC=1)([O-:25])=[O:24].O>CO.C(Cl)(Cl)Cl>[N+:23]([C:6]1[CH:7]=[CH:2][C:1]([S:9][C:10]2[CH:19]=[CH:18][CH:17]=[C:16]3[C:11]=2[CH:12]=[CH:13][N:14]=[CH:15]3)=[CH:4][CH:5]=1)([O-:25])=[O:24]
Reactant: O=C(Sc1cccc2cnccc12)c1ccccc1
Reactant: O=[N+]([O-])c1ccc(F)cc1
Agent: C[O-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: CO
Solvent: O
Product: O=[N+]([O-])c1ccc(Sc2cccc3cnccc23)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 90.9 %

Procedure:
5-Benzoylsulfanylisoquinoline 1.41 g (5.3 mmol) was dissolved in a mixture solution of methanol (50 ml) and chloroform (5 ml), sodium methoxide 500 mg (9.3 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, the resulting residue was dissolved in DMF 50 ml, 4-nitrofluorobenzene 0.75 g (5.3 mmol) was added, and the mixture was heated and stirred at 100° C. for 3.5 hours. After cooling, water was added to the reaction mixture, the resulting precipitate was collected and washed with water to obtain 5-(4-nitrophenylsulfanyl)isoquinoline 1.36 g (90.9%).
Reaction SMILES: [C:1]1([NH:7][C:8]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:17]([NH:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:18].[NH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>[Ru]>[C:11]1([NH:10][C:8]([NH:7][C:1]2[CH:2]=[CH:3][C:4]([CH3:17])=[CH:5][CH:6]=2)=[O:9])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[CH:17]([NH:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:18].[NH2:26][C:27]1[CH:32]=[CH:31][C:30]([CH3:1])=[CH:29][CH:28]=1
Reactant: O=C(Nc1ccccc1)Nc1ccccc1
Reactant: Nc1ccccc1
Agent: [Ru]
Agent: O=CNc1ccccc1
Product: Cc1ccc(N)cc1
Product: Cc1ccc(NC(=O)Nc2ccccc2)cc1

Procedure:
Watanabe et al. (J. Chem. Soc., Chem. Commun. (1990) 549) reported a synthesis of N,N'-diphenylurea in 92% yield by dehydrogenating formanilide in the presence of aniline and a ruthenium catalyst: ##STR2## Watanabe et al. prepared numerous symmetric N,N'-diarylureas in this manner. In contrast, N-phenyl-N'-p-tolylurea was not obtained selectively from the reaction of formanilide and p-toluidine. Instead, a mixture of three ureas--N,N'-diphenylurea (19%), N,N'-di-p-tolylurea (21%), and the unsymmetric product, N-phenyl-N'-p-tolylurea (38%)--was obtained: ##STR3##
Reaction SMILES: C(N(CC)CC)C.[C:8]([CH:10]([CH3:14])[C:11](=O)[CH3:12])#[N:9].C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH3:26][NH:27][CH2:28][C:29]#[N:30].Cl>C(Cl)(Cl)Cl.O>[NH2:9][C:8]1[C:10]([CH3:14])=[C:11]([CH3:12])[N:27]([CH3:26])[C:28]=1[C:29]#[N:30]
Reactant: CC(=O)C(C)C#N
Reactant: CNCC#N
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Solvent: O
Product: Cc1c(N)c(C#N)n(C)c1C
Temperature: 50 °C
Reaction time: 5 h

Procedure:
10.3 ml (0.74 mole) of triethylamine, 7.2 g (0.74 mole) of 3-cyanobutan-2-one and 0.5 g of p-toluenesulfonic acid are successively added to a suspension of 7.8 g (0.74 mole) of N-methylaminoacetonitrile hydrochloride in 70 ml of chloroform, and the mixture is boiled for 5 hours, using a water separator. After it has been boiled, the mixture is washed twice with 10 ml of water each time and dried over sodium sulfate; the solvent is then stripped off in vacuo. In order to remove all of the chloroform, the residue is twice taken up in 100 ml (each time) of dry ethanol, and the mixture concentrated each time in vacuo. The resulting oil is warmed (bath temperature of 50° C.) in 100 ml of 1 N sodium ethylate/ethanol for 2 hours; some of the ethanol is removed. The mixture is then taken up in 100 ml of water and extracted several times with methylene chloride. After being dried over sodium sulfate and concentrated on a rotary evaporator, the extracts yield a solid residue, which is recrystallized from diisopropyl ether.
Reaction SMILES: [Cl:1][C:2]1[CH:14]=[CH:13][C:5]([CH:6]=[CH:7][C:8](=[O:12])[C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.[CH2:15](N(CC)CC)[CH3:16]>C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:6]=[CH:7][C:8](=[O:12])[C:9]([O:11][CH2:15][CH3:16])=[O:10])=[CH:13][CH:14]=1
Reactant: CCN(CC)CC
Reactant: O=C(O)C(=O)C=Cc1ccc(Cl)cc1
Solvent: CCOC(C)=O
Product: CCOC(=O)C(=O)C=Cc1ccc(Cl)cc1
Reaction time: 1 h
Yield: 99 %

Procedure:
To the p-chlorobenzalpyruvic acid from step A in wet ethyl acetate was added triethylamine (11.1 g, 0.11 moL) at a rate less than 0.5 mL/min followed by azeotropic removal of water. Ethyl chloroformate (11.9 g, 0.11 moL) was then added at room temperature over a one hour period and the batch aged one hour to effect complete reaction. Workup followed, as in Example 1, to afford ethyl p-chlorobenzalpyruvate in 99% yield.
Reaction SMILES: [C:1]([C:4]1[CH:42]=[CH:41][C:7]([O:8][C:9]([C:35](=[O:40])[C:36]([CH3:39])([CH3:38])[CH3:37])=[C:10]([N:24]2[C@H:27](SCC)[C@@H:26]([C@H:31]([OH:33])[CH3:32])[C:25]2=[O:34])[C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=2)=[S:12])=[CH:6][CH:5]=1)([OH:3])=[O:2].[Cl:43]Cl>C(Cl)(Cl)Cl.C(Cl)(Cl)(Cl)Cl>[C:1]([C:4]1[CH:42]=[CH:41][C:7]([O:8][C:9]([C:35](=[O:40])[C:36]([CH3:39])([CH3:38])[CH3:37])=[C:10]([N:24]2[C@@H:27]([Cl:43])[C@@H:26]([C@H:31]([OH:33])[CH3:32])[C:25]2=[O:34])[C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=2)=[S:12])=[CH:6][CH:5]=1)([OH:3])=[O:2]
Reactant: CCS[C@@H]1[C@@H]([C@@H](C)O)C(=O)N1C(C(=S)OCc1ccc([N+](=O)[O-])cc1)=C(Oc1ccc(C(=O)O)cc1)C(=O)C(C)(C)C
Reactant: ClCl
Solvent: ClC(Cl)Cl
Solvent: ClC(Cl)(Cl)Cl
Product: C[C@@H](O)[C@H]1C(=O)N(C(C(=S)OCc2ccc([N+](=O)[O-])cc2)=C(Oc2ccc(C(=O)O)cc2)C(=O)C(C)(C)C)[C@H]1Cl
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 76.2 %

Procedure:
To a stirred solution of 10 g of 4-nitrobenzyl 3-(4-carboxyphenoxy)-2-(4(R)-ethylthio-3(S)- [1(R)-hydroxyethyl]azetidin-2-on-1-yl)-3-trimethylacetylthiopropenoate in 60 ml of chloroform at -60° C. was added a solution of 192 mmoles of chlorine in 17.8 ml of carbon tetrachloride. After 30 minutes, the reaction mixture was left to warm to room temperature, and the solvent was then removed in vacuo. Chromatography over silica gel using hexane-ethyl acetate-formic acid mixtures afforded 7.3 g of the title compound as a pale yellow foam.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH:12]([NH:14][C:15](=[O:31])[CH2:16][C:17]2[N:21]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([C:29]#[N:30])=[CH:25][CH:24]=3)[CH:20]=[N:19][CH:18]=2)[CH2:11][CH:10]([C:32]([O:34][CH3:35])=[O:33])[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:35][O:34][C:32]([C@H:10]1[CH2:11][C@@H:12]([NH:14][C:15](=[O:31])[CH2:16][C:17]2[N:21]([CH2:22][C:23]3[CH:24]=[CH:25][C:26]([C:29]#[N:30])=[CH:27][CH:28]=3)[CH:20]=[N:19][CH:18]=2)[CH2:13][NH:8][CH2:9]1)=[O:33]
Reactant: COC(=O)C1CC(NC(=O)Cc2cncn2Cc2ccc(C#N)cc2)CN(C(=O)OC(C)(C)C)C1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COC(=O)[C@@H]1CNC[C@H](NC(=O)Cc2cncn2Cc2ccc(C#N)cc2)C1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
1-(t-Butoxycarbonyl)-3-methoxycarbonyl-5-[N-(1-(4-cyanobenzyl)-1H-imidazol-5-yl)acetylamino]piperidine (44.6 mg, 0.093 mmol) was dissolved in CH2Cl2 (6 mL). Trifluoroacetic acid (3 mL) was added and the solution was stirred at ambient temperature for 4 h. The solution was concentrated under reduced pressure to give the title compound without futher purification.
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH:8]O>>[C:1]1([C:6](=[CH:5][CH:4]=[CH:3][CH:2]=1)[OH:8])[OH:7].[C:1]1([CH:6]=[CH:5][C:4]([OH:8])=[CH:3][CH:2]=1)[OH:7]
Reactant: OO
Reactant: Oc1ccccc1
Product: Oc1ccc(O)cc1
Product: Oc1ccccc1O

Procedure:
Examples 1-5 were effected as stated below. Into a 50 ml.-volume flask with a flat bottom, which was equipped with a reflux condenser, a thermometer, a stirrer and an outlet for liquid, were charged 10 g. (106 m. moles) of phenol, 8.20 m. moles of the ketone indicated in Table 2 and 0.300 g. (5.29 m. moles) of a 60 percent hydrogen peroxide solution and the flask was dipped in an oil bath at 170° C. The reaction mixture was stirred to conduct the reaction for 120 minutes. The reaction mixture was analyzed by gas chromatography and yields of catechol and hydroquinone are shown in Table 2 on hydrogen peroxide basis as defined hereinbelow. ##EQU1##
Reaction SMILES: [C:1]([O:5][CH2:6][CH2:7][C:8]1([CH2:34][CH2:35][O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[S:12][C:11]2[CH:13]=[C:14]3[S:18][C:17]([CH2:26][CH2:27][O:28][C:29]([CH3:32])([CH3:31])[CH3:30])([CH2:19][CH2:20][O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[S:16][C:15]3=[CH:33][C:10]=2[S:9]1)([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.[I:46]I.S(=O)(O)[O-].[Na+]>CCCCCC.O1CCCC1>[C:29]([O:28][CH2:27][CH2:26][C:17]1([CH2:19][CH2:20][O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[S:18][C:14]2[C:13]([I:46])=[C:11]3[S:12][C:8]([CH2:34][CH2:35][O:36][C:37]([CH3:40])([CH3:39])[CH3:38])([CH2:7][CH2:6][O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[S:9][C:10]3=[CH:33][C:15]=2[S:16]1)([CH3:32])([CH3:31])[CH3:30]
Reactant: II
Reactant: CC(C)(C)OCCC1(CCOC(C)(C)C)Sc2cc3c(cc2S1)SC(CCOC(C)(C)C)(CCOC(C)(C)C)S3
Agent: O=S([O-])O
Agent: [Li]CCCC
Agent: [Na+]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CC(C)(C)OCCC1(CCOC(C)(C)C)Sc2cc3c(c(I)c2S1)SC(CCOC(C)(C)C)(CCOC(C)(C)C)S3
Temperature: -20 °C
Reaction time: 0.33 h

Procedure:
A dry flask under argon was charged with 2,2,6,6-tetra(t-butoxyethyl)benzo[1,2-d:4,5-d']bis(1,3)dithiole (60.0 g, 95.08 mmol) and dry tetrahydrofuran (2000 ml). The mixture was cooled to -20° C. and n-Butyl lithium (76 ml of a 2.5M solution in hexane, 0.19 mol) was added over 3 minutes. The mixture was stirred for 20 minutes at -20° C. and then a solution of iodine (120 g, 0.475 mol) in tetrahydrofuran (500 ml) was added. The reaction mixture was poured into an aqueous sodium bisulphite solution and extracted with diethyl ether. The organic phase was washed once with an aqueous solution of sodium bisulphite and once with brine, dried (MgSO4) and evaporated. The product was purified by chromatography on silica gel using a mixture of CH2Cl2 and ethyl acetate as the eluent. Yield: 36.7 g (51 i).
Reaction SMILES: OC1C(C2(CO)C3C(=CC=CC=3)N([CH2:20][CH2:21][CH2:22][N:23]3[C:31](=[O:32])[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[C:24]3=[O:33])C2=O)=CC2OCOC=2C=1.O[C:38]1[C:39]([C:47]2([CH2:57][OH:58])[C:55]3[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=3)[NH:49][C:48]2=[O:56])=[CH:40][C:41]2[O:45][CH2:44][O:43][C:42]=2[CH:46]=1>>[O:56]=[C:48]1[C:47]2([C:39]3=[CH:40][C:41]4[O:45][CH2:44][O:43][C:42]=4[CH:46]=[C:38]3[O:58][CH2:57]2)[C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[N:49]1[CH2:20][CH2:21][CH2:22][N:23]1[C:31](=[O:32])[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24]1=[O:33]
Reactant: O=C1c2ccccc2C(=O)N1CCCN1C(=O)C(CO)(c2cc3c(cc2O)OCO3)c2ccccc21
Reactant: O=C1Nc2ccccc2C1(CO)c1cc2c(cc1O)OCO2
Product: O=C1c2ccccc2C(=O)N1CCCN1C(=O)C2(COc3cc4c(cc32)OCO4)c2ccccc21
Yield: 45 %

Procedure:
Following the procedure as described in EXAMPLE 1, and making non-critical variations using 2-{3-[3-(6-hydroxy-1,3-benzodioxol-5-yl)-3-(hydroxymethyl)-2-oxo-2,3-dihydro-1H-indol-1-yl]propyl}-1H-isoindole-1,3(2H)-dione to replace 142-cyclopropylethyl)-3-(6-hydroxy-1,3-benzodioxol-5-yl)-3-(hydroxymethyl)-1,3-dihydro-2H-indol-2-one, the title compound was obtained in 45% yield: 1H NMR (300 MHz, CDCl3) δ 7.83-7.80 (m, 2H), 7.70-7.68 (m, 2H), 7.28-7.26 (m, 1H), 7.15 (d, 1H), 7.05-7.00 (m, 1H), 6.86 (d, 1H), 6.48 (s, 1H), 6.23 (s, 1H), 5.85-5.83 (m, 2H), 4.91 (d, 1H), 4.65 (d, 1H), 3.94-3.68- (m, 4H), 2.15-2.10- (m, 2H); 13C NMR (75 MHz, CDCl3) δ 177.4, 168.2, 155.9, 148.8, 142.4, 141.9, 134.0, 132.5, 132.0, 128.9, 124.1, 123.4, 123.3, 119.4, 108.4, 103.2, 101.5, 93.6, 80.4, 58.2, 38.0, 35.6, 26.8; MS (ES+) m/z 469.3 (M+1), 491.3 (M+23).
Reaction SMILES: Cl[CH2:2][N:3]1[C:13](=[O:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[S:4]1(=[O:6])=[O:5].[N+:15]([C:18]1[CH:24]=[CH:23][C:21]([O-:22])=[CH:20][CH:19]=1)([O-:17])=[O:16].[Na+]>C1COCC1>[N+:15]([C:18]1[CH:24]=[CH:23][C:21]([O:22][CH2:2][N:3]2[C:13](=[O:14])[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[S:4]2(=[O:6])=[O:5])=[CH:20][CH:19]=1)([O-:17])=[O:16]
Reactant: O=[N+]([O-])c1ccc([O-])cc1
Reactant: O=C1c2ccccc2S(=O)(=O)N1CCl
Agent: [Na+]
Solvent: C1CCOC1
Product: O=C1c2ccccc2S(=O)(=O)N1COc1ccc([N+](=O)[O-])cc1
Temperature: 50 °C
Yield: 21.3 %

Procedure:
A mixture of 2-(chloromethyl) saccharin (3 g, 12.9 mmol) and sodium p-nitrophenoxide (2.55 g, 12.9 mmol) in THF (50 ml) was heated overnight at 50° C. and then refluxed for 45 minutes. The reaction mixture was cooled, poured into a dilute sodium bicarbonate/ice solution and extracted twice with ethyl acetate. The combined organic extracts were washed with sodium bicarbonate solution and water, dried (Na2SO4), and taken to dryness in vacuo. Chromatography (silica gel; MDC) afforded an oil that was crystallized from hot cyclohexane/ether. The resultant solid was recrystallized from ethanol to afford 0.92 g of 2-(4-nitrophenoxymethyl)-saccharin as white shiny platelets, mp 162°-164° C. 1H nmr (90 MHz, CDCl3, DMSO-d6):5.95 (2H, s). FDMS m/e 334 (M+).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH:11]=O)[C:5]([OH:7])=[O:6].[CH2:13]([NH2:17])[CH2:14][CH2:15][CH3:16].C1C=CC=CC=1>O>[Cl:1][CH:2]1[C:10](=[C:11]=[N:17][CH2:13][CH2:14][CH2:15][CH3:16])[CH:9]=[CH:8][C:4]([C:5]([OH:7])=[O:6])=[CH:3]1
Reactant: O=Cc1ccc(C(=O)O)cc1Cl
Reactant: CCCCN
Solvent: O
Solvent: c1ccccc1
Product: CCCCN=C=C1C=CC(C(=O)O)=CC1Cl

Procedure:
3-Chloro-4-formylbenzoic acid (5 g, 0.027 mole), butylamine (2 g, 0.027 mole) and benzene (75 ml) were refluxed for 2 hours using a flask fitted with a Dean-Stark water separator. The solvent was removed by distillation in vacuo to give 3-chloro-4-(butyliminomethylene) benzoic acid to which was added nitropropane (8.9 g, 0.1 mole) and acetic acid (21 ml). The mixture was refluxed for 10 minutes then cooled in ice. The mixture was treated with water and the solid that separated removed by filtration, washed with water, dried and recrystallized from a mixture of acetic acid and water (2:1) to give 4.7 g of the desired product, m.p. 179°-180° C.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([C:14]3[CH:15]=[C:16]([C:32]([NH:34][CH2:35][CH2:36][CH2:37][N:38]([CH3:40])[CH3:39])=[O:33])[C:17](=[O:31])[N:18]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=4)[C:19]=3[CH3:20])=[CH:12][CH:11]=[N:10]2)=[CH:5][CH:4]=1)#[N:2].[C:41]1([S:47]([O:50]C)(=[O:49])=[O:48])[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.[CH3:52]C1CCCO1>CC(C)=O>[C:41]1([S:47]([O-:50])(=[O:49])=[O:48])[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([C:14]3[CH:15]=[C:16]([C:32]([NH:34][CH2:35][CH2:36][CH2:37][N+:38]([CH3:52])([CH3:40])[CH3:39])=[O:33])[C:17](=[O:31])[N:18]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:29])([F:28])[F:30])[CH:22]=4)[C:19]=3[CH3:20])=[CH:12][CH:11]=[N:10]2)=[CH:5][CH:4]=1)#[N:2]
Reactant: CC1CCCO1
Reactant: COS(=O)(=O)c1ccccc1
Reactant: Cc1c(-c2ccnn2-c2ccc(C#N)cc2)cc(C(=O)NCCCN(C)C)c(=O)n1-c1cccc(C(F)(F)F)c1
Solvent: CC(C)=O
Product: Cc1c(-c2ccnn2-c2ccc(C#N)cc2)cc(C(=O)NCCC[N+](C)(C)C)c(=O)n1-c1cccc(C(F)(F)F)c1
Product: O=S(=O)([O-])c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 90 %

Procedure:
A solution of 5-(1-(4-cyanophenyl)-1H-pyrazol-5-yl)-N-(3-(dimethylamino)propyl)-6-methyl-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxamide (5 g, 9.12 mmol) and methyl benzenesulfonate (1.67 g, 9.52 mmol) in acetone (50 mL) was heated at 55° C. for 4 h. After cooling the reaction mixture to room temperature, 2-methyltetrahydrofuran (50 mL) was added. The resulting mixture was stirred overnight. The precipitate was filtered and dried in vacuum oven to give the title product as a light brown solid (6 g, 90%); 1H NMR (400 MHz, DMSO-d6) δ 9.35 (t, 1 H), 7.97 (s, 1 H), 7.83-7.94 (m, 4 H), 7.73-7.83 (m, 2 H), 7.64 (d, 1 H), 7.60 (d, 2 H), 7.46-7.56 (m, 2 H), 7.15-7.31 (m, 3 H), 6.65 (d, 1 H), 3.14-3.24 (m, 4 H), 2.94 (s, 9 H), 1.78-1.90 (m, 2 H), 1.75 (s, 3 H).