Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:8]([S:10]SCC)[CH3:9].C(S)C>C(O)CC.CCCO.CCCO.CCCO.CCCO.[Zr].[Zr]>[CH2:8]([S:10][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=1[OH:7])[CH3:9]
Reactant: Oc1ccccc1
Reactant: CCSSCC
Agent: [Zr]
Solvent: CCS
Solvent: CCCO
Product: CCSc1ccccc1O
Temperature: 200 °C
Yield: 41.2 %

Procedure:
To phenol (35.3 g, 0.37 moles) was added 10.6 g of zirconium n-propoxide in n-propanol consisting of 21.6% zirconium (0.025 mole) and 10.8% free n-propanol. The mixture was distilled at atmospheric pressure removing n-propanol. Ethyl disulfide (30.6 g, 0.25 moles) was added, and the mixture was heated under nitrogen while ethyl mercaptan was removed continuously by distillation. Heating was continued for a total of 6.5 hours during which temperature slowly increased to 200° C. Distillation of the mixture at 0.5 mm mercury to a maximum head temperature of 84° C. yielded 31.7 g of distillate. GC analysis indicated the distillate contained 12.4 g of phenol (35% recovered) and 15.9 g of ortho-(ethylthio)phenol (41% yield).
Reaction SMILES: [C:1]1([C:7]2[N:12]=[CH:11][C:10]([C:13]3[N:14]=[C:15]([CH:18]4[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]4)[NH:16][CH:17]=3)=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:25]1[N+:30]([O-])=[N:29][CH:28]=[CH:27][CH:26]=1>CS(C)=O.O>[C:1]1([C:7]2[N:12]=[CH:11][C:10]([C:13]3[N:14]=[C:15]([CH:18]4[CH2:23][CH2:22][N:21]([C:28]5[N:29]=[N:30][CH:25]=[CH:26][CH:27]=5)[CH2:20][CH2:19]4)[NH:16][CH:17]=3)=[CH:9][N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: c1ccc(-c2ncc(-c3c[nH]c(C4CCNCC4)n3)cn2)cc1
Reactant: [O-][n+]1ncccc1Cl
Solvent: CS(C)=O
Solvent: O
Product: c1ccc(-c2ncc(-c3c[nH]c(C4CCN(c5cccnn5)CC4)n3)cn2)cc1

Procedure:
The title compound is prepared in a similar manner described above using Buchwald-Hartwig amination conditions or as described in PCT International Application 2006/058338, 1 Jun. 2006. In this case, a solution consisting of 2-phenyl-5-(2-(piperidin-4-yl)-1H-imidazol-4-yl)pyrimidine and 6-chloropyridazine 1-oxide (preparation of this reagent can be found in PCT International Application 2007/106670, 20 Sep. 2007 and Chemical and Pharmaceutical Bulletin, 1963, 11, 261-263) in dimethylsulfoxide is heated at 80° C. for 18 hours. The reaction mixture is cooled, diluted with water and the organic material is extracted with ethyl acetate. The organic phase is washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue is chromatographed on silica to afford the title compound.
Reaction SMILES: Cl[CH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=1.[C-:13]#[N:14].[K+]>CN(C=O)C.[I-].[K+]>[C:3]1([CH2:2][C:13]#[N:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=1
Reactant: [C-]#N
Reactant: ClCc1cccc2ccccc12
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Product: N#CCc1cccc2ccccc12
Temperature: 25 °C
Reaction time: 16 h
Yield: 98 %

Procedure:
1-Chloromethylnaphthalene (5.00 ml, 33 mmol) was dissolved in N,N'-dimethylformamide (50 ml) and potassium cyanide (4.31 g, 66 mmol) and potassium iodide (0.1 g) were added and the resulting mixture was stirred at room temperature for 16 hours. The reaction mixture was partitioned between water (150 ml) and diethyl ether (2×100 ml). The combined organic phases were washed with water (100 ml), dried (MgSO4), filtered and concentrated in vacuo affording 5.41 g (98%) of 1-naphtylacetonitrile as an oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][C:10]([C:12]1[CH:17]=[CH:16][C:15](F)=[CH:14][CH:13]=1)=[O:11].[NH:19]1[CH:23]=[N:22][CH:21]=[N:20]1.[Na].CN(C)C(=O)C>C1(C)C(C)=CC=CC=1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][C:10]([C:12]1[CH:17]=[CH:16][C:15]([N:19]2[CH:23]=[N:22][CH:21]=[N:20]2)=[CH:14][CH:13]=1)=[O:11]
Reactant: c1nc[nH]n1
Reactant: O=C(Cc1ccc(F)cc1F)c1ccc(F)cc1
Agent: [Na]
Solvent: Cc1ccccc1C
Solvent: CC(=O)N(C)C
Product: O=C(Cc1ccc(F)cc1F)c1ccc(-n2cncn2)cc1
Temperature: 100 °C
Reaction time: 18 h
Yield: 17.5 %

Procedure:
A mixture of 2-(2,4-difluorophenyl)-1-(4-fluorophenyl)-1-ethanone (5.0 g, 20 mmol-see EP-A-0069442), sodium 1,2,4-triazole (2.18 g, 24 mmol) and N,N-dimethylacetamide (100 ml) was stirred at 100° C. for 18 hours. The mixture was diluted with xylene (300 ml) and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (500 ml) and washed with water (3×50 ml). The organic solution was dried (MgSO4) and concentrated under reduced pressure. Purification by flash chromatography (eluting with ethyl acetate:dichloromethane 1:1) gave a white solid (1.05 g, 18%), which was characterised by 1H-N.M.R. spectroscopy.
Reaction SMILES: [N:1]1[CH:6]=[C:5]([C:7]2[CH:8]=[C:9]([CH:13]=[CH:14][CH:15]=2)[C:10]([OH:12])=O)[CH:4]=[N:3][CH:2]=1.O=S(Cl)Cl.[F:20][C:21]([F:31])([F:30])[S:22][C:23]1[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][CH:24]=1>C(Cl)Cl>[N:3]1[CH:4]=[C:5]([C:7]2[CH:8]=[C:9]([CH:13]=[CH:14][CH:15]=2)[C:10]([NH:27][C:26]2[CH:28]=[CH:29][C:23]([S:22][C:21]([F:31])([F:20])[F:30])=[CH:24][CH:25]=2)=[O:12])[CH:6]=[N:1][CH:2]=1
Reactant: O=C(O)c1cccc(-c2cncnc2)c1
Reactant: Nc1ccc(SC(F)(F)F)cc1
Solvent: ClCCl
Solvent: O=S(Cl)Cl
Product: O=C(Nc1ccc(SC(F)(F)F)cc1)c1cccc(-c2cncnc2)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 3-pyrimidin-5-yl-benzoic acid (100 mg, 0.50 mmol) and SOCl2 (73 μL, 1.0 mmol) was heated under reflux for 4 h. The solvent was evaporated off under reduced pressure and the residue was dissolved in DCM (5 mL) and slowly added to a mixture of 4-((trifluoromethyl)thio)aniline (106 mg, 0.55 mmol) and TEA (140 μL, 1.0 mmol) in DCM (5 mL). The mixture was stirred at RT overnight. The solvent was evaporated off under reduced pressure and the residue was suspended in EtOAc (10 mL), filtered through a 10 μm Isolute® fritted cartridge and the filtrate was evaporated to dryness under reduced pressure to give the crude product which was purified by preparative HPLC to afford the title compound. LC-MS (Condition 4) tR=1.19 min, m/z=375.9 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 7.67-7.78 (m, 3H) 7.93-8.02 (m, 2H) 8.04-8.10 (m, 2H) 8.38 (t, J=1.83 Hz, 1H) 9.21-9.29 (m, 3H) 10.63 (s, 1H).
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:22])[C:8]=2[NH:12][C:13](=[O:21])[CH2:14][CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)[N:3]=1.[CH2:23]([Sn](CCCC)(CCCC)C=C)[CH2:24]CC>CN(C)C=O.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.C(C1C=C(C)C=C(C(C)(C)C)C=1O)(C)(C)C>[Cl:22][C:7]1[C:8]([NH:12][C:13](=[O:21])[CH2:14][CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([CH:23]=[CH2:24])[CH:11]=[CH:10]2
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Reactant: O=C(CC1CCCCC1)Nc1c(Cl)ccc2nc(Cl)ccc12
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: Cc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Solvent: CN(C)C=O
Product: C=Cc1ccc2c(NC(=O)CC3CCCCC3)c(Cl)ccc2n1
Temperature: 80 °C
Yield: 61.5 %

Procedure:
To a solution of N-(2,6-dichloro-5-quinolinyl)-cyclohexaneacetamide (Example 1(a)) (2 g) in dimethylformamide (6 mL) was added tributyl(vinyl)tin (3.63 g), 2,6-di-tert-butyl-4-methylphenol (50 mg) and dichlorobis(triphenylphosphine)palladium (0.25 g). The reaction was heated at 80° C. under nitrogen for 6 hours and then cooled to room temperature. The mixture was filtered through diatomaceous earth and poured into water and dichloromethane. The organic layer was separated and the aqueous was further extracted with dichloromethane. The combined organic layers were dried, filtered and evaporated. Purification (SiO2, methanol:dichloromethane 5:95 as eluant) gave the sub-titled compound (1.2 g).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([NH:14][C:15]([C:17]2[NH:18][C:19]([CH3:24])=[C:20]([Cl:23])[C:21]=2[Cl:22])=[O:16])[C@H:10]([CH2:25]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:37][NH2:38]>C1COCC1.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([NH:14][C:15]([C:17]2[NH:18][C:19]([CH3:24])=[C:20]([Cl:23])[C:21]=2[Cl:22])=[O:16])[C@H:10]([CH2:25][NH:38][CH3:37])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CN
Reactant: Cc1ccc(S(=O)(=O)OC[C@@H]2CN(C(=O)OC(C)(C)C)CC[C@@H]2NC(=O)c2[nH]c(C)c(Cl)c2Cl)cc1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CNC[C@@H]1CN(C(=O)OC(C)(C)C)CC[C@@H]1NC(=O)c1[nH]c(C)c(Cl)c1Cl
Temperature: 100 °C

Procedure:
Cis(±)tert-butyl-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-({[(4-methylphenyl)sulfonyl]oxy}methyl)-piperidine-1-carboxylate (Intermediate 72; 500 mg, 0.89 mmol) was dissolved in 5 ml of a 2.0 M THF solution containing MeNH2. The reaction vessel was sealed and heated to 100° C. for 2 h. The mixture was cooled to room temperature and diluted with EtOAc, then washed with water. The organic layer was dried over Na2SO4, filtered and concentrated to a crude solid foam which was used without further purification. MS (ES)MH+: 419 for C18H28Cl2N4O3.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][C:5](=[O:8])[NH:6][CH:7]=1.[C:9]1([C:15]([CH:17](Cl)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:16])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C(N(CC)CC)C.C(O)C>[Cl:1][C:2]1[CH:3]=[N:4][C:5](=[O:8])[N:6]([CH:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:15](=[O:16])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:7]=1
Reactant: O=c1ncc(Cl)c[nH]1
Reactant: O=C(c1ccccc1)C(Cl)c1ccccc1
Solvent: CCN(CC)CC
Solvent: CCO
Product: O=C(c1ccccc1)C(c1ccccc1)n1cc(Cl)cnc1=O
Yield: 40.3 %

Procedure:
A solution of 5-chloropyrimidin-2-one (406 mg) and desyl chloride (2-chloro-2-phenyl acetophenone) (692 mg) in triethylamine (1 ml) and ethanol (20 ml) was stirred at ambient temperature for one hour, then heated at reflux for 11/2 hours. After evaporation of solvents, the residue was dissolved in ethyl acetate (150 ml). The solution was washed with water (100 ml), dried (MgSO4) and evaporated to a foam which was crystallised from ethyl acetate to give the title pyrimidinone (393 mg,); m.p. 145°-146°; λmaxEtOH 230 nm (ε 15960), 250 nm (ε 15000), 335 nm (ε 4700), λinf 262.5 nm (ε 8400), 269 n, (ε 4420).
Reaction SMILES: [OH-].[Li+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]([CH:10]=[CH:11][C:12]=1[N:13]1[CH:17]=[C:16]([CH3:18])[N:15]=[CH:14]1)[CH:8]=O.[F:19][C:20]1[C:25]([F:26])=[C:24]([F:27])[CH:23]=[CH:22][C:21]=1[C@H:28]1[N:36]2[C@@H:31]([CH2:32][CH2:33][CH:34](P(=O)(OCC)OCC)[C:35]2=[O:37])[CH2:30][CH2:29]1.C(O)C>O1CCCC1>[F:19][C:20]1[C:25]([F:26])=[C:24]([F:27])[CH:23]=[CH:22][C:21]=1[C@H:28]1[N:36]2[C@@H:31]([CH2:32][CH2:33]/[C:34](=[CH:8]\[C:7]3[CH:10]=[CH:11][C:12]([N:13]4[CH:17]=[C:16]([CH3:18])[N:15]=[CH:14]4)=[C:5]([O:4][CH3:3])[CH:6]=3)/[C:35]2=[O:37])[CH2:30][CH2:29]1
Reactant: CCOP(=O)(OCC)C1CC[C@H]2CC[C@@H](c3ccc(F)c(F)c3F)N2C1=O
Reactant: COc1cc(C=O)ccc1-n1cnc(C)c1
Agent: [Li+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Product: COc1cc(/C=C2\CC[C@H]3CC[C@@H](c4ccc(F)c(F)c4F)N3C2=O)ccc1-n1cnc(C)c1
Temperature: 0 °C
Reaction time: 12 h
Yield: 58.5 %

Procedure:
Lithium hydroxide (0.177 g) was added to a mixed solution of 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde (0.40 g) and diethyl [(3S,8aR)-3-(2,3,4-trifluorophenyl)-5-oxooctahydroindolizin-6-yl]phosphonate (2.0 g) in tetrahydrofuran (4 mL)-ethanol (16 mL), and the reaction solution was stirred under shading at room temperature for 12 hours. The reaction solution was poured into ice water, followed by extraction with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (heptane-ethyl acetate system) to obtain 0.506 g of the title compound as a colorless solid. The property values of the compound are as follows.
Reaction SMILES: [Br:1]Br.[CH2:3]([C:10]1[CH:31]=[C:30]([O:32][CH3:33])[C:13]2[N:14]([CH2:26][CH2:27][O:28][CH3:29])[C:15]([C:17]3[CH:22]=[CH:21][C:20]([CH:23]([CH3:25])[CH3:24])=[CH:19][CH:18]=3)=[N:16][C:12]=2[CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.CCOC(C)=O>C(O)(=O)C>[CH2:3]([C:10]1[CH:31]=[C:30]([O:32][CH3:33])[C:13]2[N:14]([CH2:26][CH2:27][O:28][CH3:29])[C:15]([C:17]3[CH:22]=[CH:21][C:20]([CH:23]([CH3:25])[CH3:24])=[CH:19][CH:18]=3)=[N:16][C:12]=2[C:11]=1[Br:1])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: COCCn1c(-c2ccc(C(C)C)cc2)nc2cc(Cc3ccccc3)cc(OC)c21
Reactant: BrBr
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: COCCn1c(-c2ccc(C(C)C)cc2)nc2c(Br)c(Cc3ccccc3)cc(OC)c21
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 69.9 %

Procedure:
6 μl (0.122 mmol) bromine are added to a solution of 48 mg (0.116 mmol) 5-benzyl-2-(4-isopropyl-phenyl)-7-methoxy-1-(2-methoxy-ethyl)-1H-benzoimidazole in 6 ml glacial acetic acid. The reaction mixture is stirred at room temperature for 10 min. 25 ml EtOAc are added and this solution is washed 4N NaOH (2×), water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue is recrystallized from dichloromethane/diethyl ether/hexane to afford 40 mg of the title compound as colorless crystals.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:19]=[CH:18][C:12]2[C@H:13]([NH:16][OH:17])[CH2:14][O:15][C:11]=2[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[N:21]([CH:23]=[O:24])C.C(O)(=O)C.[O-]C#N.[K+]>O>[CH2:1]([O:8][C:9]1[CH:19]=[CH:18][C:12]2[C@H:13]([N:16]([OH:17])[C:23]([NH2:21])=[O:24])[CH2:14][O:15][C:11]=2[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: ON[C@@H]1COc2cc(OCc3ccccc3)ccc21
Reactant: CN(C)C=O
Agent: N#C[O-]
Agent: [K+]
Solvent: CC(=O)O
Solvent: O
Product: NC(=O)N(O)[C@@H]1COc2cc(OCc3ccccc3)ccc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 83 %

Procedure:
To a stirred solution of (S)-N-(6-benzyloxy-2,3-dihydrobenzofuran-3-yl)hydroxylamine (10.0 kg, 38.9 moles), DMF (50.0 L), and acetic acid (3.34 L) cooled to 5° C. was added in one portion, a cooled (0° C.) solution of potassium cyanate (4.73 kg, 58.3 moles) in water (9.0 L). This was added at such a rate that the internal temperature did not exceed 10° C. The resultant suspension was stirred for 30 min at room temperature. Water (213 L) was added and the mixture stirred for 1 hour at ambient temperature. The product was collected by centrifugation and the wet cake washed with water (425 L) and 95% ethanol (40 L). The product was isolated an dried at 45°-50° C. under vacuum to afford the crude product (11.4, 97%) as an off white solid. The crude product (11.0 kg) was recrystallized from DMF/TBME (110 L/233 L) and washed with TBME (89 L) to afford the desired compound (9.1 kg, 83%) as a white solid after drying at 45°-50° C. under vacuum. The product was greater than 99% e.e. as determined by chiral HPLC.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]3[N:14]=[CH:15][NH:16][CH:17]=3)=[C:11]([CH3:18])[N:10]=[N:9]2)=[CH:4][CH:3]=1.Cl[C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][N:21]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]3[N:14]=[CH:15][N:16]([C:20]4[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][N:21]=4)[CH:17]=3)=[C:11]([CH3:18])[N:10]=[N:9]2)=[CH:4][CH:3]=1
Reactant: Cc1nnn(-c2ccc(F)cc2)c1-c1c[nH]cn1
Reactant: FC(F)(F)c1ccc(Cl)nc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1nnn(-c2ccc(F)cc2)c1-c1cn(-c2ccc(C(F)(F)F)cn2)cn1
Temperature: 120 °C
Yield: 61.4 %

Procedure:
A mixture of 1-(4-fluoro-phenyl)-5-(1H-imidazol-4-yl)-4-methyl-1H-[1,2,3]triazole (100 mg, 0.411 mmol), 2-chloro-5(trifluoromethyl)pyridine (75 mg, 0.411 mmol) and potassium carbonate (114 mg, 0.82 mmol) in DMF (2.0 mL) was stirred under Ar in a sealed flask and heated at 120° C. for 48 h. After cooling to room temperature the mixture was poured into water and the solid that formed was filtered off and purified by chromatography (silica, 0 to 100% ethyl acetate in heptane) to afford the title compound (98 mg, 60%) as a white solid. MS: m/e=389.2 [M+H]+.
Reaction SMILES: [C:1]1([CH:11]=O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C([O-])(=O)C.[NH4+].[N+:18]([CH3:21])([O-:20])=[O:19].C(OC(=O)C)C>CCCCCC>[N+:18](/[CH:21]=[CH:11]/[C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1)([O-:20])=[O:19]
Reactant: O=Cc1cccc2ccccc12
Reactant: C[N+](=O)[O-]
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: O=[N+]([O-])/C=C/c1cccc2ccccc12
Yield: 62 %

Procedure:
7.81 g (50 mmol) of 1-naphthaldehyde and 1.54 g (20 mmol) of ammonium acetate were added to 70 ml of nitromethane and heated under reflux for 3 hours (see: J. Org. Chem., 1984, 49, 4761). 100 ml of ethylacetate was added and the resulting mixture was washed with 50 ml of water and 50 ml of brine. The organic layer was collected and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was subjected to column chromatography (eluent: hexane/ethylacete=90/10, v/v) to give 6.27 g( 0.031 mmol, Yield 62%) of the title compound.
Reaction SMILES: [Cl:1][C:2]1[C:10]([F:11])=[C:9]2[C:5]([C:6]([S:20][C:21]3[C:22]([F:32])=[C:23]([CH:29]=[CH:30][CH:31]=3)[C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:7][N:8]2[C:12]2[CH:13]=[N:14][N:15]([CH2:17][CH2:18][CH3:19])[CH:16]=2)=[CH:4][CH:3]=1.C1C(=O)N([Br:40])C(=O)C1>C(Cl)(Cl)(Cl)Cl.O>[Br:40][C:7]1[N:8]([C:12]2[CH:13]=[N:14][N:15]([CH2:17][CH2:18][CH3:19])[CH:16]=2)[C:9]2[C:5]([C:6]=1[S:20][C:21]1[C:22]([F:32])=[C:23]([CH:29]=[CH:30][CH:31]=1)[C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:4][CH:3]=[C:2]([Cl:1])[C:10]=2[F:11]
Reactant: O=C1CCC(=O)N1Br
Reactant: CCCn1cc(-n2cc(Sc3cccc(C(=O)OCC)c3F)c3ccc(Cl)c(F)c32)cn1
Solvent: ClC(Cl)(Cl)Cl
Solvent: O
Product: CCCn1cc(-n2c(Br)c(Sc3cccc(C(=O)OCC)c3F)c3ccc(Cl)c(F)c32)cn1
Reaction time: 16 h
Yield: 42.9 %

Procedure:
To a stirred solution of compound 2 (200 mg, 0.42 mmol) in CCl4 (3 mL) under inert atmosphere was added NBS (150 mg, 0.84 mmol) at RT and stirred for 16 h. The reaction was monitored by TLC and LC-MS; after completion of the reaction, the reaction mixture was diluted with water (20 mL) and extracted with CH2Cl2 (2×20 mL). The combined organic extracts were washed with brine (15 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. This was purified by silica gel column chromatography using 10-15% EtOAc/Hexanes to afford compound 3 (100 mg, 43%) as an off-white solid. 1H NMR (400 MHz, CDCl3): δ 7.71-7.67 (m, 1H), 7.66 (s, 1H), 7.64 (s, 1H), 7.31 (d, J=8.8 Hz, 1H), 7.18-7.15 (m, 1H), 7.00-6.96 (m, 2H), 4.40 (q, J=7.2 Hz, 2H), 4.18 (t, J=7.2 Hz, 2H), 2.02-1.93 (m, 2H), 1.40 (t, J=7.2 Hz, 3H), 0.97 (t, J=7.2 Hz, 3H); LC-MS (ESI): 98.1%; m/z 556.2 (M+2); (column: X Select CSH C-18, 50×3.0 mm, 3.5 μm); RT 4.94 min; 5 mM NH4OAc: ACN; 0.8 mL/min).
Reaction SMILES: [CH3:1][C:2]1[C:7]([OH:8])=[C:6]([CH2:9]Cl)[C:5]([CH:11]=[CH2:12])=[CH:4][N:3]=1.[C:13](=[S:16])([S-:15])[S-:14].[Na+:17].[Na+]>O.CO>[C:13](=[S:14])([S-:16])[S:15][CH2:9][C:6]1[C:5]([CH:11]=[CH2:12])=[CH:4][N:3]=[C:2]([CH3:1])[C:7]=1[OH:8].[Na+:17]
Reactant: C=Cc1cnc(C)c(O)c1CCl
Reactant: S=C([S-])[S-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: C=Cc1cnc(C)c(O)c1CSC(=S)[S-]
Temperature: 50 °C
Reaction time: 4 h

Procedure:
2-Methyl-3-hydroxy-4-chloromethyl-5-vinylpyridine (20 g.) is suspended in water/methanol (100:25 v/v) and treated with disodium trithiocarbonate (33%) (45 g.). The mixture is stirred at b 50° C. for 4 hours under nitrogen and adjusted to pH 6.2-6.5 with dilute acid. The precipitate is recrystallized from DMF/water to give sodium (2-methyl-3-hydroxy-5-vinyl-4-pyridinyl)methyl trithiocarbonate.
Reaction SMILES: [H-].[Na+].[F:3][C:4]([F:21])([F:20])[CH:5]([OH:19])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:7]=1.[F:22][C:23]([F:37])([F:36])[C:24]([C:27]1[CH:32]=[CH:31][C:30]([O:33][CH2:34][CH3:35])=[CH:29][CH:28]=1)=[CH:25]Cl.C(O)(=O)C>CN(C)C=O>[F:22][C:23]([F:36])([F:37])[C:24]([C:27]1[CH:32]=[CH:31][C:30]([O:33][CH2:34][CH3:35])=[CH:29][CH:28]=1)=[CH:25][O:19][CH:5]([C:4]([F:20])([F:21])[F:3])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:7]=1
Reactant: CCOc1ccc(C(=CCl)C(F)(F)F)cc1
Reactant: OC(c1cccc(Oc2ccccc2)c1)C(F)(F)F
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CN(C)C=O
Product: CCOc1ccc(C(=COC(c2cccc(Oc3ccccc3)c2)C(F)(F)F)C(F)(F)F)cc1
Temperature: -40 °C
Reaction time: 6 h

Procedure:
Sodium hydride (0.11 g of a 50% dispersion in oil) was added to a stirred solution of α-trifluoromethyl-3-phenoxybenzyl alcohol (0.6 g, prepared according to the method of UK Patent Specification No. 1,561,575) in dry dimethylformamide. After effervescence had subsided, the resulting mixture was added dropwise to a stirred solution of EZ-1,1,1-trifluoro-2-(4-ethoxyphenyl)-3-chloroprop-2-ene (1.12 g) in dry dimethylformamide (10 cm3), the temperature of the reaction mixture being maintained at -40° C. The reaction mixture was then allowed to warm to the ambient temperature, and was stirred for 6 hours. The mixture was acidified with dilute aqueous acetic acid solution and the product extracted into diethyl ether. The combined ethereal layers were dried over anhydrous magnesium sulphate and the solvent evaporated under reduced pressure. The crude product was purified by column chromatography on a silica gel support, eluting with dichloromethane containing 3% by volume hexane.
Reaction SMILES: [C:1]12([S:11][C:12]3[C:13](=[O:20])[O:14][C:15]([CH3:19])=[CH:16][C:17]=3[OH:18])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[OH:21]O>C(O)(=O)C>[C:1]12([S:11]([C:12]3[C:13](=[O:20])[O:14][C:15]([CH3:19])=[CH:16][C:17]=3[OH:18])=[O:21])[CH2:8][CH:7]3[CH2:9][CH:3]([CH2:4][CH:5]([CH2:6]3)[CH2:10]1)[CH2:2]2
Reactant: Cc1cc(O)c(SC23CC4CC(CC(C4)C2)C3)c(=O)o1
Reactant: OO
Solvent: CC(=O)O
Product: Cc1cc(O)c(S(=O)C23CC4CC(CC(C4)C2)C3)c(=O)o1
Temperature: 0 °C
Reaction time: 19 h

Procedure:
To a solution of 2.0 g. (0.0068 mole) of 3-(1-adamantylthio)-4-hydroxy-6-methyl-2-pyrone in 50 ml. of glacial acetic acid was added 0.78 g. (0.0070 mole) of 30% hydrogen peroxide and the solution allowed to stand at room temperature for 19 hours. The solution was then poured into ice water, and the resulting white solid precipitate was collected on a filter and recrystallized from ethanol to give the pure product 3-(1-adamantylsulfinyl)-4-hydroxy-6-methyl- 2-pyrone as 1.67 g. (80 percent) of colorless needles, m.p. 174.5°C.