Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]([C:10]([F:13])([F:12])[F:11])=[CH2:9])[CH:5]=[C:4]([Cl:14])[C:3]=1[Cl:15].[CH2:16]([N:23]([CH2:29]OC)[CH2:24][Si](C)(C)C)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl.C(OCC)(=O)C>[CH2:16]([N:23]1[CH2:29][CH2:9][C:8]([C:6]2[CH:5]=[C:4]([Cl:14])[C:3]([Cl:15])=[C:2]([Cl:1])[CH:7]=2)([C:10]([F:13])([F:12])[F:11])[CH2:24]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: C=C(c1cc(Cl)c(Cl)c(Cl)c1)C(F)(F)F
Reactant: COCN(Cc1ccccc1)C[Si](C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: FC(F)(F)C1(c2cc(Cl)c(Cl)c(Cl)c2)CCN(Cc2ccccc2)C1
Temperature: 0 °C
Reaction time: 5 h
Yield: 55.1 %

Procedure:
To a stirred solution of 1,2,3-trichloro-5-(1-trifluoromethyl-vinyl)benzene (5 g, 18.21 mmol) in dry DCM (50 mL) was added benzyl-methoxymethyl-trimethylsilanylmethyl-amine (Preparation 29, 18.64 mL, 72.86 mmol). Resulting reaction mixture was cooled to 0° C. and TFA (0.14 mL, 1.825 mmol) was added slowly. Reaction mixture was stirred at room temperature for 5 hours. After complete consumption of starting material, reaction mixture was concentrated in vacuo to afford yellow thick oil, which was dissolved in ethyl acetate (50 mL) and washed with saturated sodium bicarbonate solution (3×50 mL). Organic layer was dried over anhydrous sodium sulfate, concentrated in vacuo to afford crude compound which was purified by column chromatography using 230-400 mesh silica to afford product as oily liquid (4.1 g, 55.11%). 1H-NMR (400 MHz, CDCl3) δ: 2.28-2.32 (m, 1H), 2.53-2.62 (m, 1H), 2.67-2.73 (m, 1H), 2.79-2.84 (m, 1H), 3.05 (s, 2H), 3.61-3.70 (m, 2H), 7.26-7.35 (m, 5H), 7.42 (s, 2H). (m/z): 407.9 (M+H).
Reaction SMILES: [CH3:1][N:2]1[CH:7]2[CH2:8][CH2:9][CH:3]1[CH2:4][CH:5]([O:10][C:11]1[CH:18]=[CH:17][C:14]([C:15]#N)=[CH:13][CH:12]=1)[CH2:6]2.C(O)=[O:20]>[Ni]>[CH3:1][N:2]1[CH:7]2[CH2:8][CH2:9][CH:3]1[CH2:4][CH:5]([O:10][C:11]1[CH:18]=[CH:17][C:14]([CH:15]=[O:20])=[CH:13][CH:12]=1)[CH2:6]2
Reactant: O=CO
Reactant: CN1C2CCC1CC(Oc1ccc(C#N)cc1)C2
Agent: [Ni]
Product: CN1C2CCC1CC(Oc1ccc(C=O)cc1)C2
Temperature: 100 °C
Reaction time: 2 h

Procedure:
The title compound was synthesized by referring to Chem. Pharm. Bull., 1991, 39, 1440. To a solution of 4-(8-methyl-8-azabicyclo[3.2.1]oct-3-yloxy)benzonitrile (300 mg) in formic acid (5 ml) was added Raney nickel (50% suspension in water) (1 ml), and the solution was stirred for 2 hours at 100° C. After filtration through celite pad and several wash with tetrahydrofuran and methanol, the solvent was evaporated in vacuo, and the resulting residue was neutralized by adding a saturated aqueous solution of sodium bicarbonate. After extraction with chloroform and washing with brine, the solution was dried over anhydrous magnesium sulfate, then the solvent was evaporated in vacuo to provide the title compound (266 mg).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[CH:6]=[CH:7][C:8]3[C:17]([C:18]=2[CH:19]=1)=[CH:16][CH:15]=[C:14]1[C:9]=3[CH:10]=[CH:11][CH:12]=[CH:13]1.[C:20]([C:24]1[CH:29]=[CH:28][C:27]([NH:30][C:31]2[CH:36]=[CH:35][C:34]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)=[CH:33][CH:32]=2)=[CH:26][CH:25]=1)([CH3:23])([CH3:22])[CH3:21].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.CC(C)([O-])C.[Na+]>CC1C=CC=CC=1C.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[C:34]1([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH:33]=[CH:32][C:31]([N:30]([C:27]2[CH:28]=[CH:29][C:24]([C:20]([CH3:23])([CH3:21])[CH3:22])=[CH:25][CH:26]=2)[C:2]2[CH:3]=[CH:4][C:5]3[CH:6]=[CH:7][C:8]4[C:17]([C:18]=3[CH:19]=2)=[CH:16][CH:15]=[C:14]2[C:9]=4[CH:10]=[CH:11][CH:12]=[CH:13]2)=[CH:36][CH:35]=1
Reactant: Brc1ccc2ccc3c4ccccc4ccc3c2c1
Reactant: CC(C)(C)c1ccc(Nc2ccc(-c3ccccc3)cc2)cc1
Agent: [Pd]
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Agent: CC(C)(C)[O-]
Solvent: Cc1ccccc1C
Product: CC(C)(C)c1ccc(N(c2ccc(-c3ccccc3)cc2)c2ccc3ccc4c5ccccc5ccc4c3c2)cc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
In a drybox, 3-bromochrysene (0.869 g, 2.83 mmol) and N-(4-tert-butylphenyl)biphenyl-4-amine (0.9 g, 2.97 mmol) were combined in a thick-walled glass tube and dissolved in 20 ml of dry o-xylene. Tris(tert-butyl)phosphine (0.01 g) and tris(dibenzylideneacetone) dipalladium(0) (0.023 g) were dissolved in 10 ml of dry o-xylene and stirred for 10 minutes. The catalyst solution was added to the reaction mixture, stirred for 5 minutes and followed by sodium tert-butoxide (0.27 g, 2.83 mmol) and 25 ml of dry o-xylene. After another 10 minutes, the reaction flask was brought out of the drybox, attached to a nitrogen line and stirred at 75° C. overnight. Next day, reaction mixture was cooled to room temperature and filtered through a one-inch plug of silica gel and one inch of celite, washing with dichloromethane. Removal of volatiles under reduced pressure gave a solid which was triturated with diethyl ether. Yield 1.27 g (85.2%). Identity of the product was established by 1H NMR. The compound properties are given in Table 1.
Reaction SMILES: [CH2:1]([NH2:7])[CH:2]1O[CH2:5][CH2:4][CH2:3]1.[ClH:8].S(Cl)([Cl:11])=O>>[ClH:11].[Cl:8][CH:2]([CH2:3][CH2:4][CH2:5][Cl:11])[CH2:1][NH2:7]
Reactant: O=S(Cl)Cl
Reactant: NCC1CCCO1
Agent: Cl
Product: NCC(Cl)CCCCl

Procedure:
reacting tetrahydrofurfurylamine with gaseous hydrochloric acid and thionyl chloride at temperatures up to 110° C. to produce 2,5 dichloropentylamine hydrochloride,
Reaction SMILES: [F:1][C:2]1[CH:13]=[CH:12][C:5]2[NH:6][C:7](=[O:11])[O:8][C:9](=[O:10])[C:4]=2[CH:3]=1.[H-].[Na+].[CH3:16]I>CN(C=O)C>[F:1][C:2]1[CH:13]=[CH:12][C:5]2[N:6]([CH3:16])[C:7](=[O:11])[O:8][C:9](=[O:10])[C:4]=2[CH:3]=1
Reactant: CI
Reactant: O=c1[nH]c2ccc(F)cc2c(=O)o1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cn1c(=O)oc(=O)c2cc(F)ccc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 56.9 %

Procedure:
A solution of Compound 35 (3 g, 16.57 mmol) in DMF was added slowly to a suspension of NaH (60% in mineral oil, 0.729 g, 18.23 mmol) in DMF and further stirred at room temperature for 1 h. Then, neat methyl iodide (1.14 mL, 18.23 mmol) was added and the solution further stirred at room temperature for 3 h. The solution was poured into ice water and the solids formed were filtered, washed several times by water, and dried. The solids were suspended in hexane, sonicated briefly, filtered, and washed by hexane to yield 1.84 g (57%) of white solids. M.P. 133° C. 1H NMR (DMSO-d6): δ3.90 (s, 3H), 7.51 (dd, J=4.0, 8.8 Hz, 1H), 7.77 (m, 12). Anal. (C9H6FNO3) C, H, N.
Reaction SMILES: [O:1]1[C:3]2([CH2:8][CH2:7][S:6][CH2:5][CH2:4]2)[CH2:2]1.[OH:9][C:10]1[CH:15]=[C:14]([CH3:16])[C:13]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([CH:23]=[O:24])[CH:18]=2)=[C:12]([CH3:25])[CH:11]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[OH:1][C:3]1([CH2:2][O:9][C:10]2[CH:15]=[C:14]([CH3:16])[C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([CH:23]=[O:24])[CH:18]=3)=[C:12]([CH3:25])[CH:11]=2)[CH2:8][CH2:7][S:6][CH2:5][CH2:4]1
Reactant: C1CC2(CCS1)CO2
Reactant: Cc1cc(O)cc(C)c1-c1cccc(C=O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1cc(OCC2(O)CCSCC2)cc(C)c1-c1cccc(C=O)c1
Yield: 78.1 %

Procedure:
To a solution of 1-oxa-6-thiaspiro[2.5]octane (6.33 g, 48.6 mmol) and 4′-hydroxy-2′,6′-dimethylbiphenyl-3-carbaldehyde (10.0 g, 44.2 mmol) in N,N-dimethylformamide (150 mL) was added potassium carbonate (6.11 g, 44.2 mmol) at room temperature with stirring and the mixture was stirred at 100° C. for 12 hrs. The reaction mixture was concentrated under reduced pressure. To the residue was added 1 M hydrochloric acid to neutralize the solution and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, concentrated under reduced pressure and crystallized by adding diisopropyl ether to the obtained oil. The crystals were collected by filtration to give the title compound (12.3 g, yield 78%) as colorless crystals.
Reaction SMILES: [N-:1]=[N+]=[N-].[Na+].[CH3:5][O:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[C:13](=[O:17])[CH2:12][CH2:11][CH2:10]2.C(=O)([O-])[O-].[K+].[K+]>Cl>[CH3:5][O:6][C:7]1[CH:16]=[CH:15][C:14]2[C:13](=[O:17])[NH:1][CH2:12][CH2:11][CH2:10][C:9]=2[CH:8]=1
Reactant: [N-]=[N+]=[N-]
Reactant: COc1ccc2c(c1)CCCC2=O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Product: COc1ccc2c(c1)CCCNC2=O
Temperature: 25 °C
Reaction time: 20 h

Procedure:
Sodium azide (0.37 g) was slowly added in portions to a stirring ice-cold suspension of 6-methoxy-3,4-dihydro-2H-naphthalen-1-one in 10 mL of concentrated hydrochloric acid. The mixture was allowed to slowly warm to room temperature and stirred for 20 h. The mixture was poured onto ice and carefully neutralized with solid potassium carbonate. The resulting mixture was extracted with two 50 mL aliquots of dichloromethane. The organic material was dried over sodium sulfate and the solvent was evaporated. Chromatography (ethyl acetate) gave 0.45 g of 7-methoxy-2,3,4,5-tetrahydrobenzo[c]azepine-1-one.
Reaction SMILES: [C:1]([N:4]1[C:22](=[O:23])[NH:21][C:20](=[O:24])[C@@:5]21[O:9][C@@H:8]([CH2:10]I)[C@H:7]([O:12][C:13](=[O:15])[CH3:14])[C@H:6]2[O:16][C:17](=[O:19])[CH3:18])(=[O:3])[CH3:2].[C:25]([O-:28])(=[S:27])[CH3:26].C[N+](C)(C)C>COCCOC.ClCCl>[C:1]([N:4]1[C:22](=[O:23])[NH:21][C:20](=[O:24])[C@@:5]21[O:9][C@@H:8]([CH2:10][S:27][C:25](=[O:28])[CH3:26])[C@H:7]([O:12][C:13](=[O:15])[CH3:14])[C@H:6]2[O:16][C:17](=[O:19])[CH3:18])(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@H]1[C@H](CI)O[C@]2(C(=O)NC(=O)N2C(C)=O)[C@@H]1OC(C)=O
Reactant: CC([O-])=S
Agent: C[N+](C)(C)C
Solvent: ClCCl
Solvent: COCCOC
Product: CC(=O)O[C@H]1[C@H](CSC(C)=O)O[C@]2(C(=O)NC(=O)N2C(C)=O)[C@@H]1OC(C)=O
Temperature: 45 °C
Yield: 94.4 %

Procedure:
To a solution of (2R, 3R, 4R, 5S)-6-acetyl-2-iodomethyl-3, 4-diacetoxy-1-oxa-6,8-diazaspiro (4,4) nonane-7, 9-dione (598 mg, 1.32 mm) in anhydrous DME (10 ml) is added, under N2, tetramethylammonium thioacetate (353 mg, 2.37 mm) in one portion. The resulting mixture is heated at 45° C. for 4 hours, then diluted with dichloromethane and washed with brine, dried, and evaporated for dryness. The crude product is purified by thin-layer chromatography to give (2R, 3R, 4R, 5S)-6-acetyl-2-acetylthiomethyl-3, 4-diacetoxy-1-oxa-6, 8-diazaspiro (4,4) nonane-7, 9-dione (500 mg) as a hygroscopic foam.
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]([C:14]2[CH:15]=[C:16]3[C:21](=[CH:22][C:23]=2[O:24][CH3:25])[NH:20][C:19](=[O:26])[CH2:18][CH2:17]3)[CH:7]=[CH:8][C:9]=1[C:10]([F:13])([F:12])[F:11].Br[CH2:28][C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][C:30]=1[F:36]>CN(C)C=O>[F:36][C:30]1[CH:31]=[C:32]([F:35])[CH:33]=[CH:34][C:29]=1[CH2:28][N:20]1[C:21]2[C:16](=[CH:15][C:14]([C:6]3[CH:7]=[CH:8][C:9]([C:10]([F:11])([F:12])[F:13])=[C:4]([F:3])[CH:5]=3)=[C:23]([O:24][CH3:25])[CH:22]=2)[CH2:17][CH2:18][C:19]1=[O:26]
Reactant: COc1cc2c(cc1-c1ccc(C(F)(F)F)c(F)c1)CCC(=O)N2
Reactant: Fc1ccc(CBr)c(F)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1cc2c(cc1-c1ccc(C(F)(F)F)c(F)c1)CCC(=O)N2Cc1ccc(F)cc1F
Yield: 52 %

Procedure:
To a suspension of 95% sodium hydride in anhydrous N,N-dimethylformamide (2 mL) at room temperature in a dry flask equipped with an inlet of dry nitrogen was added a solution of 6-(3-fluoro-4-(trifluoromethyl)phenyl)-7-methoxy-3,4-dihydroquinolin-2(1H)-one, prepared a shown above (53 mg, 0.10 mmol) in N,N-dimethylformamide (1 mL) with stirring. The reaction mixture was stirred for 30 minutes, followed by addition of 1-(bromomethyl)-2,4-difluorobenzene (207 mg, 1.0 mmol), and the reaction mixture stirred overnight. The reaction was followed by LCMS and stirring was continued as needed until the starting material was consumed. The reaction mixture was quenched by addition of saturated aqueous ammonium chloride (5 mL) with stirring, concentrated under reduced pressure, diluted with ethyl acetate (20 mL) and dilute aqueous ammonium chloride (10 mL). The aqueous phase was extracted with ethyl acetate (3×20 mL), and the combined organic phase was successively washed with 2N sodium carbonate (20 mL), 30% aqueous ammonium chloride (20 mL), brine (20 mL), and dried over magnesium sulfate. Evaporation of the solvent under reduced pressure gave a crude mixture that was purified by reverse phase HPLC with a gradient of acetonitrile/water (2% to 98%) to afford 1-(2,4-difluorobenzyl)-6-(3-fluoro-4-(trifluoromethyl)phenyl)-7-methoxy-3,4-dihydroquinolin-2(1H)-one (25 mg, 0.05 mmol, 52%). LCMS mz 466.0 (M+H), 487.9 (M+Na), anal HPLC >98% in purity. 1H NMR (400 MHz; CDCl3) δ7.58 (t, J=7.8 Hz, 1H); 7.34 (m, 2H); 7.21 (m, 1H); 7.10 (s, 1H); 6.80-6.89 (m, 2H); 6.57 (s, 1H); 5.24 (s, 2H); 3.70 (s, 3H); 2.94 (m, 2H); 2.81 (m, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2OC(=O)[S:10][N:9]=2)=[CH:4][CH:3]=1.[C:14]([C:16]([O:18][CH2:19][CH3:20])=[O:17])#[N:15]>CCCCCCCCCCCC>[CH2:19]([O:18][C:16]([C:14]1[S:10][N:9]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[N:15]=1)=[O:17])[CH3:20]
Reactant: CCOC(=O)C#N
Reactant: O=c1oc(-c2ccc(Cl)cc2)ns1
Solvent: CCCCCCCCCCCC
Product: CCOC(=O)c1nc(-c2ccc(Cl)cc2)ns1
Temperature: 150 °C
Yield: 30.6 %

Procedure:
To a solution of 5-(4-chlorophenyl)-[1,3,4]oxathiazol-2-one (0.60 g, 2.80 mmol) in n-dodecane (0.80 ml) was added ethyl cyanoformate (1.10 ml, 11.20 mmol). The resulting reaction mixture was refluxed for 20 h at 150° C. After the completion of the reaction (TLC monitoring), added ice-cold water and extracted with ethyl acetate (3×75 ml). The combined organic layer was dried over Na2SO4, filtered and concentrated under vacuum. The crude residue was purified over silica gel (100-200 M, 20% EtOAc—Hexane) to get the product (0.23 g, 30%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:9][NH2:10])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[C:11]([O:16][CH2:17][CH3:18])(=[O:15])[C:12]([CH3:14])=O.S(=O)(=O)(O)O.C(=O)(O)[O-].[Na+]>O.C(OCC)(=O)C.C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][N:10]=[C:12]([CH3:14])[C:11]([O:16][CH2:17][CH3:18])=[O:15])[CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: CCOC(=O)C(C)=O
Reactant: NNc1cc(Cl)cc(Cl)c1
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CCO
Solvent: O
Solvent: CCOC(C)=O
Product: CCOC(=O)C(C)=NNc1cc(Cl)cc(Cl)c1
Reaction time: 3 h

Procedure:
Combine 3,5-dichlorophenylhydrazine (300 g) and ethanol (2 L). Add ethyl pyruvate (153.6 mL) and sulfuric acid (25 mL). After 3 hours, evaporate in vacuo to obtain a residue. Cover the residue with ethyl acetate and water. Add solid sodium bicarbonate until the aqueous layer is neutralized. Separate the layers and extract the aqueous layer with ethyl acetate. Combine the organic layers, dry over MgSO4, filter, and evaporate in vacuo to give ethyl pyruvate-3,5-dichlorophenylhydrazone.
Reaction SMILES: [F:1][C:2]1[C:21]([N+:22]([O-])=O)=[CH:20][CH:19]=[C:18]([F:25])[C:3]=1[C:4]([NH:6][C:7]1[CH:8]=[C:9]2[C:15]([O:16][CH3:17])=[N:14][NH:13][C:10]2=[N:11][CH:12]=1)=[O:5].[Sn](Cl)Cl>C(OCC)(=O)C>[NH2:22][C:21]1[C:2]([F:1])=[C:3]([C:18]([F:25])=[CH:19][CH:20]=1)[C:4]([NH:6][C:7]1[CH:8]=[C:9]2[C:15]([O:16][CH3:17])=[N:14][NH:13][C:10]2=[N:11][CH:12]=1)=[O:5]
Reactant: COc1n[nH]c2ncc(NC(=O)c3c(F)ccc([N+](=O)[O-])c3F)cc12
Agent: Cl[Sn]Cl
Solvent: CCOC(C)=O
Product: COc1n[nH]c2ncc(NC(=O)c3c(F)ccc(N)c3F)cc12
Temperature: 25 °C
Yield: 84.4 %

Procedure:
2,6-Difluoro-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-nitrobenzamide (762.3 mg, 2.183 mmol) was dissolved in ethyl acetate (21.8 mL) and treated with tin (II) chloride dehydrate (2463 mg, 10.91 mmol). The reaction mixture was heated to reflux for 2 hours and then allowed to cool to ambient temperature. The reaction mixture was quenched with saturated sodium carbonate and filtered. The filtrate was washed with water (2×), sodium bicarbonate (2×), and brine (1×), dried over sodium sulfate, and concentrated to afford 3-amino-2,6-difluoro-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamide (588.2 mg, 1.842 mmol, 84.4% yield) as a solid. 1H NMR (400 MHz, d6-DMSO) δ 12.629-12.519 (s, 1H), 10.980-10.883 (s, 1H), 8.675-8.583 (s, 1H), 8.544-8.458 (s, 1H), 6.993-6.811 (m, 2H), 5.297-5.188 (s, 2H), 4.093-3.973 (s, 3H); MS (APCI-pos) m/z=320.3 (M+H).
Reaction SMILES: [CH:1]1[C:14]2[C:5](=[CH:6][C:7]3[C:12]([CH:13]=2)=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH:4]=[CH:3][CH:2]=1.[Ce].CO>COCCOC>[CH:4]1[C:5]2[CH2:6][C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH2:13][C:14]=2[CH:1]=[CH:2][CH:3]=1
Reactant: c1ccc2cc3ccccc3cc2c1
Agent: [Ce]
Solvent: CO
Solvent: COCCOC
Product: c1ccc2c(c1)Cc1ccccc1C2
Yield: 59 %

Procedure:
1.14 mmole of anthracene is reacted with 4.57 m atoms of cerium as powder in 7.5 ml of DME in the conditions of example 9 with application of ultrasound, thus producing anthracenecerium. After action of a methanol excess and the usual treatment, 9,10-dihydroanthracene was isolated with a yield of 59%.
Reaction SMILES: [N+:1]([C:4]1[CH:15]=[CH:14][C:7]([CH2:8][N:9]2[CH:13]=[CH:12][CH:11]=[N:10]2)=[CH:6][CH:5]=1)([O-])=O>C(OCC)(=O)C.[Pt]>[N:9]1([CH2:8][C:7]2[CH:14]=[CH:15][C:4]([NH2:1])=[CH:5][CH:6]=2)[CH:13]=[CH:12][CH:11]=[N:10]1
Reactant: O=[N+]([O-])c1ccc(Cn2cccn2)cc1
Agent: [Pt]
Solvent: CCOC(C)=O
Product: Nc1ccc(Cn2cccn2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 66.5 %

Procedure:
A solution of 1-(4-nitrobenzyl)-1H-pyrazole (0.375 g, 1.85 mmol) in ethyl acetate (15 mL) was treated with Pt/C (0.018 g, 0.09 mmol) and the mixture stirred at rt for 16 h under a hydrogen atmosphere. After this time, the mixture was filtered through celite, washed with ethyl acetate, and the filtrate was concentrated. The residue was purified by column chromatography (silica, hexanes/ethyl acetate) to afford the title compound (0.213 g, 57%) as a yellow solid. MW=173.21. 1H NMR (CDCl3, 300 MHz) δ 7.58-7.47 (m, 1H), 7.32 (d, J=2.1 Hz, 1H), 7.09-7.01 (m, 2H), 6.68-6.59 (m, 2H), 6.24 (t, J=2.1 Hz, 1H), 5.19 (s, 2H), 3.69 (s, 2H); APCI MS m/z 174 [M+H]+.
Reaction SMILES: Cl[CH2:2][C:3](=[O:9])[CH2:4][C:5]([O:7][CH3:8])=[O:6].[F:10][C:11]1[CH:12]=[C:13]([SH:19])[CH:14]=[C:15]([O:17][CH3:18])[CH:16]=1.CN(C=O)C>O>[F:10][C:11]1[CH:12]=[C:13]([S:19][CH2:2][C:3](=[O:9])[CH2:4][C:5]([O:7][CH3:8])=[O:6])[CH:14]=[C:15]([O:17][CH3:18])[CH:16]=1
Reactant: COc1cc(F)cc(S)c1
Reactant: COC(=O)CC(=O)CCl
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)CC(=O)CSc1cc(F)cc(OC)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of methyl 4-chloroacetoacetate (1.871 mL), K2OC3 (2.210 g), 3-fluoro-5-methoxybenzenethiol (2.3 g) and DMF (30 mL) was stirred at room temperature for 1 h. The mixture was poured into water and extracted with EtOAc. The organic layer was separated, washed successively with water and brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/hexane) to give the title compound (2.87 g).
Reaction SMILES: [CH2:1]([C:5]1[CH:6]=[C:7]([CH:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][CH:20]([CH3:22])[CH3:21])[CH:14]=2)O)[CH:8]=[CH:9][CH:10]=1)[CH:2]([CH3:4])[CH3:3].C(Cl)(=O)C([Cl:26])=O>ClCCl>[CH2:1]([C:5]1[CH:6]=[C:7]([CH:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][CH:20]([CH3:22])[CH3:21])[CH:14]=2)[Cl:26])[CH:8]=[CH:9][CH:10]=1)[CH:2]([CH3:4])[CH3:3]
Reactant: CC(C)Cc1cccc(C(O)c2cccc(CC(C)C)c2)c1
Reactant: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Product: CC(C)Cc1cccc(C(Cl)c2cccc(CC(C)C)c2)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of bis(3-isobutylphenyl)methanol (2.87 g) and oxalyl chloride (1 ml) in dichloromethane (10 ml) was stirred at 25° C. for 2 hours. After evaporation of the solvent, the oily residue was distilled to give bis(3-isobutylphenyl)chloromethane (2.45 g) as pale yellow oil.
Reaction SMILES: C([O:4][C:5]1[CH:35]=[CH:34][CH:33]=[CH:32][C:6]=1[C:7]([NH:9][C:10]1[CH:11]=[C:12]([CH:16]=[C:17]([NH:19][C:20](=[O:31])[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[O:27]C(=O)C)[CH:18]=1)[C:13]([NH2:15])=[O:14])=[O:8])(=O)C.C(=O)([O-])[O-].[Na+].[Na+]>>[C:7]([NH:9][C:10]1[CH:11]=[C:12]([CH:16]=[C:17]([NH:19][C:20](=[O:31])[C:21]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[OH:27])[CH:18]=1)[C:13]([NH2:15])=[O:14])(=[O:8])[C:6]1[C:5](=[CH:35][CH:34]=[CH:33][CH:32]=1)[OH:4]
Reactant: CC(=O)Oc1ccccc1C(=O)Nc1cc(NC(=O)c2ccccc2OC(C)=O)cc(C(N)=O)c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: NC(=O)c1cc(NC(=O)c2ccccc2O)cc(NC(=O)c2ccccc2O)c1
Yield: 83 %

Procedure:
In the manner similar to that described in Example 4, 3,5-bis(2'-acetoxybenzamido)-benzamide obtained in Example 12 was hydrolyzed with sodium carbonate. Recrystallization of the hydrolized product from a mixture of ethanol and water gave 3,5-bis(salicylamido)-benzamide having a melting point between 276° - 277°C. (Yield; 83%)
Reaction SMILES: [NH2:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH2:18][C@H:19]([OH:21])[CH3:20])=[CH:14][CH:15]=3)[N:10]=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[CH3:24][N:25]1[C:29]([CH3:30])=[C:28]([C:31](O)=[O:32])[C:27](=[O:34])[N:26]1[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>C(Cl)Cl.O>[OH:21][C@H:19]([CH3:20])[CH2:18][O:17][C:13]1[CH:12]=[C:11]2[C:16]([C:7]([O:6][C:5]3[CH:4]=[CH:3][C:2]([NH:1][C:31]([C:28]4[C:27](=[O:34])[N:26]([C:35]5[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=5)[N:25]([CH3:24])[C:29]=4[CH3:30])=[O:32])=[CH:23][CH:22]=3)=[CH:8][CH:9]=[N:10]2)=[CH:15][CH:14]=1
Reactant: Cc1c(C(=O)O)c(=O)n(-c2ccccc2)n1C
Reactant: C[C@@H](O)COc1ccc2c(Oc3ccc(N)cc3)ccnc2c1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2cccnc21
Solvent: O
Solvent: ClCCl
Product: Cc1c(C(=O)Nc2ccc(Oc3ccnc4cc(OC[C@@H](C)O)ccc34)cc2)c(=O)n(-c2ccccc2)n1C
Temperature: 43 °C
Reaction time: 12 h
Yield: 13.3 %

Procedure:
To a solution of (R)-1-((4-(4-aminophenoxy)quinolin-7-yl)oxy)propan-2-ol (2.5 g, 11.9 mmol), 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carb oxylic acid (2.0 g, 8.6 mmol) and HOAT (0.2 g, 1.6 mmol) in DCM (35 mL) was added EDCI (1.9 g, 9.7 mmol). The reaction mixture was stirred at 43° C. for 12 hours, then cooled to room temperature and diluted with a mixture of DCM and H2O (50 mL/50 mL). The organic phase was separated, dried over Na2SO4 and concentrated in vacuo. The residue was purified by a column chromatography on silica gel (EtOAc) to afford the title compound as a yellow solid (0.6 g, 14.3%).
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][C:11]([NH:22][C:23](=[O:28])[C:24]([F:27])([F:26])[F:25])([CH2:14][NH:15][C:16](=[O:21])[C:17]([F:20])([F:19])[F:18])[CH2:10][CH2:9]1)=O)(C)(C)C.[ClH:29]>O1CCOCC1.CO>[ClH:29].[F:27][C:24]([F:25])([F:26])[C:23]([NH:22][C:11]1([CH2:14][NH:15][C:16](=[O:21])[C:17]([F:20])([F:19])[F:18])[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1)=[O:28]
Reactant: CC(C)(C)OC(=O)N1CCC(CNC(=O)C(F)(F)F)(NC(=O)C(F)(F)F)CC1
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Product: O=C(NCC1(NC(=O)C(F)(F)F)CCNCC1)C(F)(F)F
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 4-(2,2,2-trifluoro-acetylamino)-4-[(2,2,2-trifluoro-acetylamino)-methyl]-piperidine-1-carboxylic acid tert-butyl ester (5.25 g, 12.5 mmol) in dioxane (50 ml) is added 4 M HCl in dioxane (15 ml) and the reaction mixture is stirred at room temperature for 3 hours. The reaction mixture is concentrated in vacuo and the off-white solid obtained dissolved in the minimum amount of MeOH and re-precipitated by adding diethyl ether. The supernatant solvent mixture is decanted and the product is washed again with diethyl ether and dried under vacuum to afford 2,2,2-Trifluoro-N-{4-[(2,2,2-trifluoro-acetylamino)-methyl]-piperidin-4-yl}-acetamide hydrochloride; [M+H]+ 322.
Reaction SMILES: [CH2:1]1CCN2C(=NCCC2)CC1.[C:12]1([CH2:18][C:19]([OH:21])=[O:20])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C(Cl)Cl.O>[C:12]1([CH2:18][C:19]([O:21][CH3:1])=[O:20])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: C1CCC2=NCCCN2CC1
Reactant: O=C(O)Cc1ccccc1
Solvent: O
Solvent: ClCCl
Product: COC(=O)Cc1ccccc1
Temperature: 90 °C

Procedure:
DBU (3.35 g, 22.0 mmol) was added to a mixture of phenylacetic acid (3.0 g, 22.0 mmol) in DMC (30 mL) and the resulting mixture was heated to reflux (90° C.) for 24 hours. The reaction mixture was cooled to ambient temperature and diluted with CH2Cl2 (50 mL) and water (40 mL). The organic layer was separated and washed in sequence with 2 M HCl (2×40 mL), saturated aqueous NaHCO3 (40 mL) and water (2×40 mL). The organic layer was dried over Na2SO4, filtered and concentrated under vacuum to give methyl phenylacetate as an oil.