Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([O-:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[K+].C1(C)C([C:16]([O-:18])=[O:17])=CC=CC=1O.[K+].C(=O)=O>>[OH:7][C:1]1[CH:6]=[CH:5][C:4]([C:16]([OH:18])=[O:17])=[CH:3][CH:2]=1
Reactant: Cc1c(O)cccc1C(=O)[O-]
Reactant: [O-]c1ccccc1
Agent: O=C=O
Agent: [K+]
Product: O=C(O)c1ccc(O)cc1
Yield: 79.6 %

Procedure:
A pressure vessel was charged with 6.65 grams of potassium phenolate and 7.40 grams of potassium ortho-cresolate both in dry powder form. With stirring, reaction was carried out at a carbon dioxide pressure of 7 kg/cm2 (G) and 220° to 240° C. for ten minutes. The equimolar mixture of potassium phenolate and potassium ortho-cresolate has a eutectic point of 209° C. in peak value as measured by differential thermal analysis (same throughout the examples). An analysis of the product at the end of reaction showed a para-hydroxybenzoic acid yield of 79.6% on the basis of the potassium phenolate.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[CH:5][C:6]2[NH:7][C:8]3[C:13]([C:14]=2[CH:15]=1)=[CH:12][CH:11]=[CH:10][CH:9]=3)#[N:2].[Li]CCCC.[O:21]1[CH:23]([CH2:24][O:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:22]1.O>C1COCC1>[OH:21][CH:23]([CH2:24][O:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH2:22][N:7]1[C:6]2[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:15][C:14]=2[C:13]2[C:8]1=[CH:9][CH:10]=[CH:11][CH:12]=2
Reactant: N#Cc1ccc2[nH]c3ccccc3c2c1
Reactant: c1ccc(OCC2CO2)cc1
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Product: N#Cc1ccc2c(c1)c1ccccc1n2CC(O)COc1ccccc1
Temperature: -78 °C
Reaction time: 2 h

Procedure:
To a solution of 3-cyano-9H-carbazole (0.4998 g, 2.6 mmol, 1 equiv) in THF (40 mL) was added nBuLi (1.6 M in hexane, 3.25 mL, 5.2 mmol, 2 equiv). The mixture was stirred at −78° C. for 2 hours. 1,2-epoxy-3-phenoxypropane (0.7809 g, 5.2 mmol, 2 equiv) was added and the mixture was stirred at 45° C. overnight. Water (50 mL) was added and the mixture was extracted by dichloromethane (3×30 mL). The combined dichloromethane layers were washed by brine (2×30 mL) and then dried over Na2SO4. The solvent was removed under reduced pressure, and the product was chromatographed on silica gel with dichloromethane to yield 0.7736 g white foamed solid (86%).
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([F:12])=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.[NH2:19][C:20]1[C:21](=[O:33])[N:22]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[CH:23]=[CH:24][CH:25]=1>ClCCl.CN(C=O)C>[F:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([F:12])=[CH:7][C:3]=1[C:4]([NH:19][C:20]1[C:21](=[O:33])[N:22]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[CH:23]=[CH:24][CH:25]=1)=[O:6]
Reactant: Nc1cccn(-c2ccc(F)cc2)c1=O
Reactant: O=C(O)c1cc(F)c(F)cc1F
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C(Nc1cccn(-c2ccc(F)cc2)c1=O)c1cc(F)c(F)cc1F
Temperature: 25 °C
Reaction time: 2 h
Yield: 66.8 %

Procedure:
To a solution of 2,4,5-trifluorobenzoic acid (Aldrich, 704 mg, 4.0 mmol) in dichloromethane (20 mL), was added oxalyl chloride (Aldrich, 0.70 mL, 8.0 mmol) dropwise, followed by two drops of DMF. The reaction mixture was stirred at room temperature for 2 h, and concentrated in vacuo. Toluene (20 mL) was added and the reaction mixture was evaporated in vacuo to remove the excess oxalyl chloride. The residue was dissolved in dichloromethane (20 mL). Half of this acid chloride solution was added to a mixture of 3-amino-1-(4-fluorophenyl)pyridin-2(1H)-one (306 mg, 1.5 mmol) in dichloromethane (5 mL) and TEA (0.5 mL, Aldrich) at 0° C. The reaction mixture was stirred at room temperature for 1 h. The precipitate that formed was collected by filtration, and washed with methanol, to afford the desired product (363 mg, 67% yield) as a solid. MS(ESI+) m/z 363.25 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[O:17][CH3:18])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:6].[Cl:19][C:20]1[CH:21]=[C:22](I)[CH:23]=[C:24]([Cl:26])[CH:25]=1.C(=O)([O-])[O-].[K+].[K+]>ClCCl.[Cu]I>[Cl:19][C:20]1[CH:21]=[C:22]([NH:1][C:2]2[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=2[O:17][CH3:18])[C:5]([NH:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:6])[CH:23]=[C:24]([Cl:26])[CH:25]=1
Reactant: Clc1cc(Cl)cc(I)c1
Reactant: COc1ccc(C(=O)Nc2ccccc2)cc1N
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: COc1ccc(C(=O)Nc2ccccc2)cc1Nc1cc(Cl)cc(Cl)c1
Yield: 9.3 %

Procedure:
Prepared according to the procedure of Example 33 using 3-amino-4-methoxy-N-phenyl-benzamide (2.0 g, 8.3 mmol), 3,5-dichloroiodobenzene (4.5 g, 16.5 mmol), potassium carbonate (2.9 g, 21.0 mmol), and copper(I) iodide (0.5 g, 2.6 mmol) to give a gummy residue which was subjected to chromatography on a column of silica gel in dichloromethane to afford the product (0.3 g); m.p. 207-208° C. after recrystallization from ethanol.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:7][C:8]([CH3:31])=[C:9]([CH2:11][O:12][C:13]2[CH:28]=[CH:27][C:16]([CH2:17][O:18][C:19]3[C:23]([CH:24]=O)=[CH:22][N:21]([CH3:26])[N:20]=3)=[CH:15][C:14]=2[O:29][CH3:30])[N:10]=1.[CH2:32](P(=O)(OCC)OCC)[P:33](=[O:40])([O:37][CH2:38][CH3:39])[O:34][CH2:35][CH3:36].CN(C)C=O.[H-].[Na+]>O>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:7][C:8]([CH3:31])=[C:9]([CH2:11][O:12][C:13]2[CH:28]=[CH:27][C:16]([CH2:17][O:18][C:19]3[C:23](/[CH:24]=[CH:32]/[P:33](=[O:40])([O:37][CH2:38][CH3:39])[O:34][CH2:35][CH3:36])=[CH:22][N:21]([CH3:26])[N:20]=3)=[CH:15][C:14]=2[O:29][CH3:30])[N:10]=1
Reactant: CCOP(=O)(CP(=O)(OCC)OCC)OCC
Reactant: COc1cc(COc2nn(C)cc2C=O)ccc1OCc1nc(-c2ccco2)oc1C
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOP(=O)(/C=C/c1cn(C)nc1OCc1ccc(OCc2nc(-c3ccco3)oc2C)c(OC)c1)OCC
Reaction time: 15 h
Yield: 54.4 %

Procedure:
To a mixture of 3-[(4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1-methyl-1H-pyrazole-4-carbaldehyde (0.60 g), tetraethyl methylenediphosphonate (0.43 g) and N,N-dimethylformamide (20 mL) was added sodium hydride (60% in oil, 0.070 g) at room temperature, and the mixture was stirred at the same temperature for 15 hrs. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-hexane (4:1 to 9:1, v/v) to give diethyl (E)-2-{3-[(4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1-methyl-1H-pyrazol-4-yl}ethenylphosphonate as colorless crystals (0.43 g, yield 55%). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 72-73° C.
Reaction SMILES: [NH2:1][C:2]1[C:7]([O:8][CH2:9][C:10]2[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=2[Cl:17])=[CH:6][CH:5]=[CH:4][N:3]=1.[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]=[C:26]=[S:27])=[CH:21][CH:20]=1.C1(C)C=CC=CC=1>CCOCC>[Cl:17][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]([Cl:16])[C:10]=1[CH2:9][O:8][C:7]1[C:2]([NH:1][C:26]([NH:25][C:22]2[CH:23]=[CH:24][C:19]([Cl:18])=[CH:20][CH:21]=2)=[S:27])=[N:3][CH:4]=[CH:5][CH:6]=1
Reactant: Nc1ncccc1OCc1c(Cl)cccc1Cl
Reactant: S=C=Nc1ccc(Cl)cc1
Solvent: Cc1ccccc1
Solvent: CCOCC
Product: S=C(Nc1ccc(Cl)cc1)Nc1ncccc1OCc1c(Cl)cccc1Cl

Procedure:
A mixture of 2-amino-3-(2,6-dichlorobenzyloxy)pyridine (5 g, 0.018 mol), 4-chlorophenyl isothiocyanate (3.76 g, 0.022 mol) and toluene (20 ml) was heated under reflux for 3 hours, then cooled and diluted with ether to induce crystallisation of the product, which was recrystallised from ethanol/ether. Yield 6.69 g (82%), m.p. 179°-180 ° C.
Reaction SMILES: [CH2:1]([O:6][C:7]1[CH:12]=[C:11]([O:13][CH:14]([CH3:19])[C:15](O)([CH3:17])[CH3:16])[N:10]=[CH:9][N:8]=1)[C:2]#[C:3][CH2:4][CH3:5].CCN(S(F)(F)[F:26])CC.O>C(Cl)(Cl)Cl>[F:26][C:15]([CH3:17])([CH3:16])[CH:14]([CH3:19])[O:13][C:11]1[CH:12]=[C:7]([O:6][CH2:1][C:2]#[C:3][CH2:4][CH3:5])[N:8]=[CH:9][N:10]=1
Reactant: CCC#CCOc1cc(OC(C)C(C)(C)O)ncn1
Reactant: CCN(CC)S(F)(F)F
Solvent: ClC(Cl)Cl
Solvent: O
Product: CCC#CCOc1cc(OC(C)C(C)(C)F)ncn1
Reaction time: 0.17 h
Yield: 51.2 %

Procedure:
First, 0.31 g of 4-(2-pentynyloxy)-6-(2-hydroxy-1,2-dimethylpropyloxy)pyrimidine was dissolved in 3 ml of chloroform, to which 0.5 ml of a solution containing 0.24 g of DAST in chloroform was added dropwise at 0° C., followed by stirring for 10 minutes. The reaction mixture was then poured into water, which was extracted three times with chloroform. The combined organic layers were washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel column chromatography to give 0.16 g of 4-(2-fluoro-1,2-dimethylpropyloxy)-6-(2-pentynyloxy)pyrimidine (the present compound (17)).
Reaction SMILES: C(O[C:4](=[O:21])[C:5]1[CH:10]=[CH:9][CH:8]=[N:7][C:6]=1[NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=1)C.O1CCCC1.[NH2-].[Na+].[CH2:29]([N:31]=[C:32]=[O:33])[CH3:30]>O>[N+:18]([C:14]1[CH:13]=[C:12]([N:11]2[C:6]3[N:7]=[CH:8][CH:9]=[CH:10][C:5]=3[C:4](=[O:21])[N:31]([CH2:29][CH3:30])[C:32]2=[O:33])[CH:17]=[CH:16][CH:15]=1)([O-:20])=[O:19]
Reactant: CCN=C=O
Reactant: CCOC(=O)c1cccnc1Nc1cccc([N+](=O)[O-])c1
Agent: [NH2-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CCn1c(=O)c2cccnc2n(-c2cccc([N+](=O)[O-])c2)c1=O
Reaction time: 1 h
Yield: 54.9 %

Procedure:
To a solution of 5.7 g of 2-(m-nitroanilino)nicotinic acid ethyl ester and 50 ml of dry tetrahydrofuran was added 1.1 g of sodium amide and the solution was stirred for one hour. To this was added dropwise under cooling 2.9 g of ethyl isocyanate and this mixture was reacted at 60°C for 10 hours. After the reaction was complete, the solvent was distilled off from the mixture, and to the residue obtained was added water to precipitate a crude product. This product was collected by filtration and recrystallized from methanol to give 3.4 g of 1-(m-nitrophenyl)-3-ethylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione as colorless needles, melting at 210°-211°C.
Reaction SMILES: [Cl:1][C:2]1[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][C:3]=1[O:4][CH:5]([CH3:10])[C:6]([O:8][CH3:9])=[O:7].[Br:16]N1C(=O)CCC1=O>N(C1(C#N)CCCCC1)=NC1(C#N)CCCCC1.FC1C=CC=CC=1>[Br:16][CH2:15][C:12]1[CH:13]=[CH:14][C:2]([Cl:1])=[C:3]([CH:11]=1)[O:4][CH:5]([CH3:10])[C:6]([O:8][CH3:9])=[O:7]
Reactant: O=C1CCC(=O)N1Br
Reactant: COC(=O)C(C)Oc1cc(C)ccc1Cl
Agent: N#CC1(N=NC2(C#N)CCCCC2)CCCCC1
Solvent: Fc1ccccc1
Product: COC(=O)C(C)Oc1cc(CBr)ccc1Cl
Yield: 87.3 %

Procedure:
Into 150 ml of fluorobenzene was dissolved 5.61 g of methyl 2-(2-chloro-5-methylphenoxy)propionate obtained above; 4.37 g of N-bromosuccinimide and then 0.2 g of 1,1′-azobis(cyclohexanecarbonitrile) were added, and the mixture was stirred under reflux for 2 hours. After the reaction was completed, the solution was allowed to left for cooling; the reaction solution was filtered; the filtrate was concentrated under reduced pressure; and the residue was subjected to silica gel chromatography to give 6.59 g of methyl 2-[5-(bromomethyl)-2-chlorophenoxy]propionate.
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[C:6]([N:13]([CH3:15])[CH3:14])[N:5]=[C:4]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([NH:23][CH3:24])=[CH:19][CH:18]=2)[N:3]=1.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.[Cl:42][C:43]1[CH:51]=[CH:50][C:46]([C:47](O)=[O:48])=[CH:45][CH:44]=1>CCOC(C)=O>[Cl:1][C:2]1[C:7]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[C:6]([N:13]([CH3:14])[CH3:15])[N:5]=[C:4]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([N:23]([C:47](=[O:48])[C:46]3[CH:50]=[CH:51][C:43]([Cl:42])=[CH:44][CH:45]=3)[CH3:24])=[CH:19][CH:18]=2)[N:3]=1
Reactant: O=C(O)c1ccc(Cl)cc1
Reactant: CNc1ccc(Cc2nc(Cl)c(CC(=O)OC)c(N(C)C)n2)cc1
Agent: On1nnc2ccccc21
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: COC(=O)Cc1c(Cl)nc(Cc2ccc(N(C)C(=O)c3ccc(Cl)cc3)cc2)nc1N(C)C
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A solution of methyl {4-chloro-6-(dimethylamino)-2-[4-(methylamino)benzyl]pyrimidin-5-yl}acetate (0.080 g, 0.23 mmol), 1-hydroxybenzotriazole (0.043 g, 0.32 mmol), triethylamine (0.11 mL, 0.80 mmol), and 4-chlorobenzoic acid (0.043 g, 0.28 mmol) was treated with WSCI (0.066 g, 0.34 mmol) at room temperature and the reaction mixture was stirred at room temperature for 16 hours. EtOAc was then added and the organic layer was washed sequentially with 0.5N HCl, saturated NaHCO3, and brine, dried over anhydrous Na2SO4, filtered, and concentrated to dryness to give the crude product methyl [4-chloro-2-{4-[(4-chloro-benzoyl)(methyl)amino]benzyl}-6-(dimethylamino)pyrimidin-5-yl]acetate.
Reaction SMILES: [C:1]1([C:7]([Cl:10])([Cl:9])[Cl:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:11][S:12](O)(=[O:14])=[O:13]>>[Cl:11][S:12]([C:3]1[CH:2]=[C:1]([C:7]([Cl:10])([Cl:9])[Cl:8])[CH:6]=[CH:5][CH:4]=1)(=[O:14])=[O:13]
Reactant: ClC(Cl)(Cl)c1ccccc1
Reactant: O=S(=O)(O)Cl
Product: O=S(=O)(Cl)c1cccc(C(Cl)(Cl)Cl)c1

Procedure:
Benzotrichloride is chlorosulfonated with chlorosulfonic acid to yield m-chlorosulfonylbenzotrichloride, and the product is heated to obtain m-chlorosulfonylbenzoylchloride. (U.S. Pat. No. 3,290,370)
Reaction SMILES: [Cl:1][C:2]1[CH:28]=[CH:27][C:5]([C:6]([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][CH:17]=2)[N:14]([CH3:18])[C:13](=[O:19])[CH:12]=[C:11]3[C:20]2[CH:25]=[CH:24][CH:23]=[C:22](I)[CH:21]=2)=[O:7])=[CH:4][CH:3]=1.CN(C)C=O.[CH3:34][Si:35]([C:38]#[CH:39])([CH3:37])[CH3:36].[Al]>C(NCC)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Cl:1][C:2]1[CH:28]=[CH:27][C:5]([C:6]([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][CH:17]=2)[N:14]([CH3:18])[C:13](=[O:19])[CH:12]=[C:11]3[C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([C:39]#[C:38][Si:35]([CH3:37])([CH3:36])[CH3:34])[CH:21]=2)=[O:7])=[CH:4][CH:3]=1
Reactant: C#C[Si](C)(C)C
Reactant: Cn1c(=O)cc(-c2cccc(I)c2)c2cc(C(=O)c3ccc(Cl)cc3)ccc21
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: [Al]
Solvent: CCNCC
Solvent: CN(C)C=O
Product: Cn1c(=O)cc(-c2cccc(C#C[Si](C)(C)C)c2)c2cc(C(=O)c3ccc(Cl)cc3)ccc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
6-(4-Chloro-benzoyl)-4-(3-iodo-phenyl)-1-methyl-1H-quinolin-2-one (9.98 g, 20.0 mMol) was suspended in diethylamine (300 mL). To this solution was added 50 mL of anhydrous N,N-dimethylformamide (DMF), (trimethylsilyl)acetylene (8.5 mL) and bis(triphenylphosphine)-palladium(II) chloride (1.40 g, 2.00 mMol). The flask was covered with aluminum foil and then copper(I) iodide (780 mg, 4.09 mMol) was added causing the reaction mixture to exotherm. After stirring overnight under an atmosphere of dry N2 at ambient temperature, the reaction mixture was concentrated under vacuum and the residue was chromatographed on flash silica gel eluting with a gradient of DCM to MeOH/DCM (2:98) to give 8.55 g of the titled product as a solid.
Reaction SMILES: C=O.[C:3](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:17][C:18]1[CH:44]=[CH:43][C:21]([CH2:22][NH:23][C:24]([C:26]2[C:27](=[O:42])[C:28]3[CH:35]=[C:34]([CH2:36][NH:37][CH2:38][CH:39]([OH:41])[CH3:40])[O:33][C:29]=3[N:30]([CH3:32])[CH:31]=2)=[O:25])=[CH:20][CH:19]=1.C(=O)(O)[O-].[Na+]>C(Cl)CCl>[Cl:17][C:18]1[CH:44]=[CH:43][C:21]([CH2:22][NH:23][C:24]([C:26]2[C:27](=[O:42])[C:28]3[CH:35]=[C:34]([CH2:36][N:37]([CH2:38][CH:39]([OH:41])[CH3:40])[CH3:3])[O:33][C:29]=3[N:30]([CH3:32])[CH:31]=2)=[O:25])=[CH:20][CH:19]=1
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Reactant: CC(O)CNCc1cc2c(=O)c(C(=O)NCc3ccc(Cl)cc3)cn(C)c2o1
Agent: C=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCCl
Product: CC(O)CN(C)Cc1cc2c(=O)c(C(=O)NCc3ccc(Cl)cc3)cn(C)c2o1
Temperature: 25 °C
Reaction time: 18 h
Yield: 58.2 %

Procedure:
Aq. formaldehyde (0.19 mL) and sodium triacetoxy borohydride (0.526 g) were added to a suspension of N-(4-chlorobenzyl)-2-(((2-hydroxypropyl)-amino)methyl)-7-methyl-4-oxo-4,7-dihydrofuro[2,3-b]pyridine-5-carboxamide (Example 33, 0.500 g) in],2-dichloroethane (50 mL). The reaction mixture was stirred at room temperature for 18 h. A sat. aq. sodium bicarbonate solution (30 mL) was added. The aqueous layer was separated and extracted with CH2Cl2 (4×50 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo. The resulting solid was purified by column chromatography (CH2Cl2/methanol; 97/3, 96/4) followed by recrystallization from ethyl acetate to yield 0.301 g of the title compound as a white solid. Physical characteristics. M.p. 152° C.; 1H NMR (400 MHz, DMSO-d6) δ 10.65, 8.55, 7.41-7.32, 6.87, 4.55, 4.35, 3.92, 3.80-3.73, 3.69, 2.36-2.31, 2.28-2.20, 1.04; MS (EST+) m/z 418 (M+H)+.
Reaction SMILES: [CH3:1][Se:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[S:9]([NH2:12])(=[O:11])=[O:10].C(N=[C:18]=[O:19])CCC.C(Cl)(Cl)=O>>[CH3:1][Se:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[S:9]([N:12]=[C:18]=[O:19])(=[O:11])=[O:10]
Reactant: C[Se]c1ccccc1S(N)(=O)=O
Reactant: CCCCN=C=O
Agent: O=C(Cl)Cl
Product: C[Se]c1ccccc1S(=O)(=O)N=C=O
Temperature: 25 °C
Yield: 127.5 %

Procedure:
A solution of 2-(methylselenyl)benzenesulfonamide (6.25 g, 25.0 mmol), n-butyl isocyanate (2.81 mL, 25.0 mmol), and 1,4-diaza[2.2.2]bicyclooctane (0.1 g, 1 mmol) in mixed xylenes was heated at reflux for 0.5 hours. Phosgene was then added at such a rate that the internal temperature stayed at 133° C. or above. When consumption of phosgene ceased, the solution was cooled to room temperature and then filtered under nitrogen. Rotary evaporation gave 2-(methylselenyl)benzenesulfonyl isocyanate as a brown oil (8.8 g). This was used immediately without further purification or characterization.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][C:3]([C:6]2[C:15]3[C:10](=[CH:11][C:12]([S:16][C:17]4[CH:22]=[C:21]([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)[CH:20]=[C:19]([F:29])[CH:18]=4)=[CH:13][CH:14]=3)[O:9][C:8](=[O:30])[CH:7]=2)=[CH:2]1.C1C=C(Cl)C=C(C(OO)=[O:39])C=1.C(Cl)Cl>C(Cl)(Cl)Cl>[O:1]1[CH:5]=[CH:4][C:3]([C:6]2[C:15]3[C:10](=[CH:11][C:12]([S:16]([C:17]4[CH:22]=[C:21]([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)[CH:20]=[C:19]([F:29])[CH:18]=4)=[O:39])=[CH:13][CH:14]=3)[O:9][C:8](=[O:30])[CH:7]=2)=[CH:2]1
Reactant: O=c1cc(-c2ccoc2)c2ccc(Sc3cc(F)cc(-c4ccccc4)c3)cc2o1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Product: O=c1cc(-c2ccoc2)c2ccc(S(=O)c3cc(F)cc(-c4ccccc4)c3)cc2o1
Reaction time: 2 h

Procedure:
To a solution of 4-(3-furyl)-7-(5-phenyl-3-fluorophenylthio)coumarin (Example 17) (106 mg) in CHCl3 (3 mL) was added m-CPBA (88 mg; 50%). After 2 h, CH2Cl2 was added and the resulting solution was washed with 10% aq. NaHSO3, saturated aq. NaHCO3, dried (MgSO4) and concentrated. Chromatography of the residue (silica gel; hexane/EtOAc (7:3)) provided the title compound as a solid.
Reaction SMILES: [C:1]1([NH2:8])[CH:6]=[CH:5][C:4]([NH2:7])=[CH:3][CH:2]=1.[O:9]1[CH2:13][CH2:12][CH2:11][C:10]1=O>C([O-])(O)=O.[Na+]>[NH2:7][C:4]1[CH:5]=[CH:6][C:1]([N:8]2[CH2:13][CH2:12][CH2:11][C:10]2=[O:9])=[CH:2][CH:3]=1
Reactant: Nc1ccc(N)cc1
Reactant: O=C1CCCO1
Agent: O=C([O-])O
Agent: [Na+]
Product: Nc1ccc(N2CCCC2=O)cc1

Procedure:
800 mg Benzene-1,4-diamine and 600 μl Dihydro-furan-2-one were heated for 1 h to 200° C. under microwave irradiation (200 W, CEM Discover™ apparatus). Finally, 10 mL saturated NaHCO3 solution were added and the mixture was directly purified by chromatography on silica gel eluting with a gradient of DCM/MeOH 100%->50%. The fractions containing the product were combined and the solvent evaporated under reduced pressure. Yield: 860 mg.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.[CH3:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]=C=O)=[CH:14][CH:13]=1.O>[O-]CC.[Na+].CO>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([NH:18][C:15]2[CH:16]=[CH:17][C:12]([CH3:11])=[CH:13][CH:14]=2)=[O:8])=[CH:9][CH:10]=1
Reactant: Cc1ccc(N=C=O)cc1
Reactant: Cc1ccc(C(=O)O)cc1
Agent: CC[O-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: Cc1ccc(NC(=O)c2ccc(C)cc2)cc1
Temperature: 35 °C
Reaction time: 0.87 h

Procedure:
p-Methylbenzoic acid (95.31 grams, 0.70 mole), sodium ethoxide catalyst (0.2144 gram, 0.225% wt. of the p-methylbenzoic acid used) and N,N'-dimethylacetamide (575 grams) are added to a reactor equipped with a reflux condenser and stirred under a nitrogen atmosphere at 35° C. to provide a solution. p-Methylphenyl isocyanate (97.87 grams, 0.735 mole) is added over a two minute period inducing an exotherm to 40° C. At this time, heating of the reactor commences and a 160° C. temperature is achieved 52 minutes later. After three hours at the 160° C. reaction temperature, the reactor is cooled to 30° C. the the contents poured into deionized water (3.50 liters). A precipitated white crystalline product is recovered by filtration of the aqueous slurry then dried in a vacuum oven at 80° C. and 5 mm Hg for fifteen hours. The dry product and methanol (700 milliliters) are stirred together with heating to provide a solution at 63° C. After cooling the methanol solution to 4° C. for fourteen hours, a white crystalline product is filtered off and dried at 70° C. and 5 mm Hg in a vacuum oven to a constant weight of 135.6 grams. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of the product confirms the product structure of 4,4'-dimethylbenzanilide (amide carbonyl absorbance at 1649 cm-1 and amide N--H stretching absorbance at 3349 and 3290 (shoulder) cm-1.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[CH:13]=[CH:14][C:15]([O:17][CH2:18][CH2:19][CH2:20]Br)=[CH:16][C:11]=3[S:10][N:9]=2)=[CH:4][CH:3]=1.[CH3:22][O:23][CH2:24][CH2:25][NH:26][CH2:27][CH2:28][O:29][CH3:30]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[CH:13]=[CH:14][C:15]([O:17][CH2:18][CH2:19][CH2:20][N:26]([CH2:27][CH2:28][O:29][CH3:30])[CH2:25][CH2:24][O:23][CH3:22])=[CH:16][C:11]=3[S:10][N:9]=2)=[CH:4][CH:3]=1
Reactant: BrCCCOc1ccc2c(-c3ccc(Br)cc3)nsc2c1
Reactant: COCCNCCOC
Product: COCCN(CCCOc1ccc2c(-c3ccc(Br)cc3)nsc2c1)CCOC

Procedure:
According to the method in example 5, 3-(4-Bromo-phenyl)-6-(3-bromo-propoxy)-benzo[d]isothiazole and bis(2-methoxyethyl) amine were converted to yield [3-[3-(4-Bromo-phenyl)-benzo[d]isothiazol-6-yloxy]-propyl]-bis-(2-methoxy-ethyl)-amine as orange oil, MS: 479 (MH+, 1Br).
Reaction SMILES: [C:1]([C:3]1[CH2:20][CH2:19][C@@:18]2([CH3:21])[C:5](=[CH:6][CH2:7][C@@H:8]3[C@@H:17]2[CH2:16][CH2:15][C@@:13]2([CH3:14])[C@H:9]3[CH2:10][CH2:11][C@@H:12]2[C:22](=[O:30])SC2C=CC=CN=2)[CH:4]=1)#[N:2].[Cl:31][C:32]1[CH:45]=[CH:44][C:35]([CH:36]([NH2:43])[C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[CH:34][CH:33]=1>>[Cl:31][C:32]1[CH:33]=[CH:34][C:35]([CH:36]([NH:43][C:22]([C@H:12]2[CH2:11][CH2:10][C@H:9]3[C@H:8]4[C@H:17]([CH2:16][CH2:15][C@:13]23[CH3:14])[C@:18]2([CH3:21])[C:5]([CH:4]=[C:3]([C:1]#[N:2])[CH2:20][CH2:19]2)=[CH:6][CH2:7]4)=[O:30])[C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[CH:44][CH:45]=1
Reactant: C[C@]12CC[C@H]3[C@@H](CC=C4C=C(C#N)CC[C@@]43C)[C@@H]1CC[C@@H]2C(=O)Sc1ccccn1
Reactant: NC(c1ccccc1)c1ccc(Cl)cc1
Product: C[C@]12CC[C@H]3[C@@H](CC=C4C=C(C#N)CC[C@@]43C)[C@@H]1CC[C@@H]2C(=O)NC(c1ccccc1)c1ccc(Cl)cc1
Yield: 70 %

Procedure:
Following a procedure similar to that described in Example 3(b), but using S-2-pyridyl 3-cyanoandrosta-3,5 -diene-17β-thiocarboxylate [prepared as described in Example 3(a)] and 4-chlorobenzhydrylamine as starting materials, in relative proportions similar to those used in that Example, the title compound was obtained in a yield of 70%.