Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[C:13]1[O:17][C:16]([C:18]2[CH:27]=[CH:26]C3N[C:23](=O)[NH:24][C:20]=3[CH:19]=2)=[N:15][N:14]=1.IC.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH3:40][N:41]([CH:43]=[O:44])[CH3:42]>C(OCC)(=O)C>[CH3:40][N:41]1[C:42]2[CH:26]=[CH:27][C:18]([C:16]3[O:17][C:13]([C:3]4[C:4]([C:7]5[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=5)=[N:5][O:6][C:2]=4[CH3:1])=[N:14][N:15]=3)=[CH:19][C:20]=2[N:24]([CH3:23])[C:43]1=[O:44]
Reactant: CN(C)C=O
Reactant: Cc1onc(-c2ccccc2)c1-c1nnc(-c2ccc3[nH]c(=O)[nH]c3c2)o1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Solvent: CI
Solvent: CCOC(C)=O
Product: Cc1onc(-c2ccccc2)c1-c1nnc(-c2ccc3c(c2)n(C)c(=O)n3C)o1
Reaction time: 18 h
Yield: 13 %

Procedure:
5-[5-(5-Methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazol-2-yl]-1,3-dihydro-benzoimidazol-2-one (200 mg, 0.56 mmol) was heated in DMF (2 mL) until the suspension turned into solution. After the solution was cooled to ambient temperature iodomethane (38 μL, 0.61 mmol) was added and stirred for 18 h at this temperature. The resulting suspension was diluted with DMF (2 mL) and warmed until the reaction mixture became homogeneous. A solution of potassium bis(trimethylsilyl)amide (0.91 M in THF, 673 μL, 0.61 mmol) was added and stirred for 1 h at ambient temperature. Additional iodomethane (38 μL, 0.61 mmol) was added and stirring was continued for another 18 h. Additional potassium bis(trimethylsilyl)amide (0.91 M in THF, 673 μL, 0.61 mmol) was added, stirred for 15 min at ambient temperature, treated with iodomethane (0.38 μL, 0.61 mmol) and stirred for 5 h at this temperature. The reaction mixture was diluted with ethyl acetate (20 mL) and washed with aqueous sodium carbonate (saturated, 20 mL), water (20 mL) and brine (20 mL). The combined aqueous layers were extracted with ethyl acetate (20 mL) and the combined organic layers were dried over sodium sulfate. Purification by chromatography (SiO2, heptane:ethyl acetate:dichloromethane=40:40:20 to 10:70:20) afforded the title compound (29 mg, 13%) as a white solid. MS: m/e=388.1 [M+H]+.
Reaction SMILES: [CH:1]([C@H:4]1[C@H:7]([CH2:8][CH2:9][OH:10])[NH:6][C:5]1=[O:11])([CH3:3])[CH3:2].C(Cl)Cl.[C:15](Cl)(=[O:17])[CH3:16]>N1C=CC=CC=1>[CH:1]([CH:4]1[CH:7]([CH2:8][CH2:9][O:10][C:15](=[O:17])[CH3:16])[NH:6][C:5]1=[O:11])([CH3:3])[CH3:2]
Reactant: CC(C)[C@@H]1C(=O)N[C@H]1CCO
Reactant: CC(=O)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(=O)OCCC1NC(=O)C1C(C)C
Reaction time: 0.25 h

Procedure:
Trans-3-isopropyl-4-(2-hydroxyethyl)-2-azetidinone from Step B, is dissolved in 10 ml. CH2Cl2 and cooled to 0° C. Pyridine 0.75 ml is added and then 0.392 ml of acetyl chloride is added dropwise. The mixture is stirred at 0° for 15 min and then at 25° C. for another 15 minutes. The reaction mixture is evaporated to dryness. The residue is chromatographed on silica gel using 50% EtOAc/C6H6 as eluant to give 0.652 g 3-isopropyl-4-(2-acetoxyethyl)-azetidinone.
Reaction SMILES: [CH3:1][O:2][CH2:3][N:4]1[C:10]2[CH:11]=[C:12]([O:15][CH3:16])[CH:13]=[CH:14][C:9]=2[N:8]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:7][C:6](=[N:23][OH:24])[C:5]1=[O:25].[CH2:26]([N:29]=[C:30]=[O:31])[CH2:27][CH3:28].C(N(CC)CC)C>O1CCCC1>[CH3:1][O:2][CH2:3][N:4]1[C:10]2[CH:11]=[C:12]([O:15][CH3:16])[CH:13]=[CH:14][C:9]=2[N:8]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:7][C:6](=[N:23][O:24][C:30]([NH:29][CH2:26][CH2:27][CH3:28])=[O:31])[C:5]1=[O:25]
Reactant: COCN1C(=O)C(=NO)CN(c2ccccc2)c2ccc(OC)cc21
Reactant: CCCN=C=O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCCNC(=O)ON=C1CN(c2ccccc2)c2ccc(OC)cc2N(COC)C1=O
Temperature: 25 °C
Yield: 62.4 %

Procedure:
1-Methoxymethyl-2-oxo-3-hydroxyimino-5-phenyl-8-methoxy-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (1.0 g) was dissolved in tetrahydrofuran (10 ml), propyl isocyanate (0.62 g) and triethylamine (0.74 g) were added thereto, the mixture was refluxed for 2 hours and 30 minutes. The reaction mixture was allowed to cool to room temperature, crystals so precipitated were collected by filtration, and the crystals were washed with diisopropyl ether, to thereby obtain 0.78 g of the titled compound as white crystals.
Reaction SMILES: [Mg].C1COCC1.[C:7]([O:10][C:11]1[C:16]([CH3:17])=[CH:15][CH:14]=[CH:13][C:12]=1[CH:18](Br)[CH2:19][CH2:20]Br)(=[O:9])[CH3:8].Cl>O.II>[C:7]([O:10][C:11]1[C:16]([CH3:17])=[CH:15][CH:14]=[CH:13][C:12]=1[CH:18]1[CH2:20][CH2:19]1)(=[O:9])[CH3:8]
Reactant: CC(=O)Oc1c(C)cccc1C(Br)CCBr
Agent: Cl
Agent: II
Agent: [Mg]
Solvent: C1CCOC1
Solvent: O
Product: CC(=O)Oc1c(C)cccc1C1CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 113.5 %

Procedure:
A 500 ml four-necked round-bottomed flask was equipped with a magnetic stirrer bar, a thermometer, a reflux condenser and a drying tube. Magnesium (2.50 g, 102.8 mmol) and anhydrous THF (30 ml) were added thereto under a nitrogen atmosphere. Iodine (63 mg) was added to the mixture and the mixture was stirred at room temperature for 30 minutes. Subsequently, 2-(1,3-dibromopropyl)-6-methylphenyl acetate (30.0 g, 85.7 mmol) and anhydrous THF (90 ml) were added to the mixture at 80° C. over 15 minutes. After the mixture was stirred at 80° C. for 30 minutes, the mixture was further stirred at room temperature for 1.5 hours. 1M Hydrochloric acid (100 ml) was added dropwise to the reaction mixture such that the temperature of the reaction mixture did not exceed 40° C. The mixture was diluted with water (100 ml) and extracted with a 10% ethyl acetate-90% hexane (V/V) solvent mixture (3×200 ml). The organic layer was combined and it was successively washed with water (2×200 ml) and a saturated aqueous NaCl solution (50 ml), followed by drying with anhydrous sodium sulfate (100 g). After the solid was removed by filtration, the filtrate was concentrated to obtain 18.5 g of 2-cyclopropyl-6-methylphenyl acetate as a brown gum.
Reaction SMILES: [C:1]([O:5][C:6](=[O:29])[CH2:7][N:8]1[C:12]2[CH:13]=[CH:14][C:15]([F:17])=[CH:16][C:11]=2[N:10]=[C:9]1[S:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([C:26](O)=[O:27])[CH:21]=1)([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.C1C=CC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC.[NH:59]1[C:67]2[C:62](=[CH:63][CH:64]=[CH:65][CH:66]=2)[CH2:61][CH2:60]1.CN([CH:71]=[O:72])C>>[N:59]1([C:26]([C:22]2[CH:23]=[CH:24][C:25]([O:72][CH3:71])=[C:20]([CH:21]=2)[CH2:19][S:18][C:9]2[N:8]([CH2:7][C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:29])[C:12]3[CH:13]=[CH:14][C:15]([F:17])=[CH:16][C:11]=3[N:10]=2)=[O:27])[C:67]2[C:62](=[CH:63][CH:64]=[CH:65][CH:66]=2)[CH2:61][CH2:60]1
Reactant: CN(C)C=O
Reactant: c1ccc2c(c1)CCN2
Reactant: CC(C)(C)OC(=O)Cn1c(SCc2cccc(C(=O)O)c2)nc2cc(F)ccc21
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Product: COc1ccc(C(=O)N2CCc3ccccc32)cc1CSc1nc2cc(F)ccc2n1CC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of tert-butyl[2-(3-hydroxycarbonyl-benzylsulfanyl)-5-fluoro-benzoimidazol-1-yl]-acetate (Precursor 5-F-H-00b, 44.6 mg, 0.1 mmol) in dry DMF (0.8 ml) are added successively Et3N (21.1 μl, 15.2 mg, 0.15 mmol, 1.5 eq.), HOBt (23.0 mg, 0.15 mmol, 1.5 eq.), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (28.8 mg, 0.15 mmol, 1.5 eq.) and indoline (16.8 μl, 17.9 mg, 0.15 mmol, 1.5 eq.). The reaction mixture is stirred at rt overnight. The solvents are evaporated under reduced pressure, dichloromethane (4 ml) is added and the resulting organic phase is washed once with 2 ml of a 1 M NaHCO3 solution in water and once with 2 ml of a 1 M solution of sodium hydrogen sulfate in water. The acidic aqueous phase was extracted once with dichloromethane (2 ml). The combined organic phase is washed with brine. The solvent is removed under a stream of air and the resulting crude product is dried under high vacuum overnight yielding the title compound (40 mg) in 83% as a light brown oil: tR=1.20 min (LC-3), ESI-MS (pos.): m/z 548.23 [M+H]+, 1H-NMR (CDCl3): δ (ppm) 1.400 (s, 9H, tBu), 2.95 (t, 2H, NCH2CH2Ar), 3.91 (s, 3H, OCH3), 3.95 (t, 2H, NCH2CH2Ar), 4.65 (s, 2H, SCH2), 4.72 (s, 2H, CH2CO2), 6.91-7.19 (m, 7Harom), 7.45 (m, 1Harom), 7.52 (m, 1Harom), 7.64 (m, 1Harom).
Reaction SMILES: [OH:1][CH:2]([CH2:16][N:17]1[CH2:22][CH2:21][CH:20]([CH2:23][O:24][C:25]2[CH:30]=[CH:29][C:28]([NH2:31])=[CH:27][CH:26]=2)[CH2:19][CH2:18]1)[CH2:3][O:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[CH2:7][CH2:8][N:9]2[CH:14]=[O:15].[C:32](OC(=O)C)(=[O:34])[CH3:33].N1C=CC=CC=1.C[O-].[Na+]>CO>[OH:1][CH:2]([CH2:16][N:17]1[CH2:18][CH2:19][CH:20]([CH2:23][O:24][C:25]2[CH:30]=[CH:29][C:28]([NH:31][C:32](=[O:34])[CH3:33])=[CH:27][CH:26]=2)[CH2:21][CH2:22]1)[CH2:3][O:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[CH2:7][CH2:8][N:9]2[CH:14]=[O:15]
Reactant: Nc1ccc(OCC2CCN(CC(O)COc3cccc4c3CCN4C=O)CC2)cc1
Reactant: CC(=O)OC(C)=O
Agent: C[O-]
Agent: [Na+]
Solvent: c1ccncc1
Solvent: CO
Product: CC(=O)Nc1ccc(OCC2CCN(CC(O)COc3cccc4c3CCN4C=O)CC2)cc1

Procedure:
3.3 g. 4-{2-Hydroxy-3-[4-(4-aminophenoxymethyl)-piperidino]-propoxy}-1-formylindoline (preparation see Example 15b) are stirred with a mixture of 25 ml. acetic anhydride and 25 ml. pyridine for 10 hours at ambient temperature, then evaporated in a vacuum and the residue dissolved in water and dichloromethane. After neutralization with sodium bicarbonate, the organic phase is distilled and the residue obtained is converted in methanol with sodium methylate solution into the desired compound. By shaking out between dichloromethane and water and evaporating the organic phase, there is obtained 1.0 g. (27% of theory) 4-{2-hydroxy-3-[4-(4-acetamidophenoxymethyl)-piperidino]-propoxy}-1-formylindoline; m.p. 177°-179° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([CH3:15])([C:12]([OH:14])=O)[CH3:11])[CH:5]=[CH:6][C:7]=1[Cl:8].[Li].[C:17]1([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:22]=[CH:21][C:20]([CH:23]([NH:30][CH3:31])[CH2:24][N:25]2[CH2:29][CH2:28][CH2:27][CH2:26]2)=[CH:19][CH:18]=1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[C:17]1([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:22]=[CH:21][C:20]([CH:23]([N:30]([CH3:31])[C:12](=[O:14])[C:10]([CH3:11])([CH3:15])[NH:9][C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=2)[CH2:24][N:25]2[CH2:29][CH2:28][CH2:27][CH2:26]2)=[CH:19][CH:18]=1
Reactant: CC(C)(Nc1ccc(Cl)c(Cl)c1)C(=O)O
Reactant: CNC(CN1CCCC1)c1ccc(-c2ccccc2)cc1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: [Li]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CN(C(=O)C(C)(C)Nc1ccc(Cl)c(Cl)c1)C(CN1CCCC1)c1ccc(-c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
N-(3,4-dichlorophenyl)-2-methylalanine, lithium salt (100 mg, 0.4 mmol), [1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]methylamine (124 mg, 0.44 mmol), triethylamine (246 uL, 1.77 mmol), and (1H-1,2,3-benzotriazol-1-yloxy)[tris(dimethylamino)]phosphonium hexafluorophosphate (BOP Reagent, 215 mg, 0.486 mmol) were added in that order to a 4 mL screw capped vial that contained 2 mL of anhydrous DMF. The reaction mixture was stirred for 20 hours at room temperature, then filtered through a 0.45 um PTFE Acrodisk, and purified by reverse-phase HPLC (Xterra Prep RP C-18, 30×150 mm, 50 mL/min, A: acetonitrile B: water, pH 10 w/NH4OH, A: 20 to 99% over 9 min, UV detection at 214 nm) to give the title compound as a white solid. MS (ES) m/e 510 [M+H]+.
Reaction SMILES: [F:1][C:2]1[CH:20]=[CH:19][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15]C(N)=O)[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.[H-].[Na+].O.[CH3:24][N:25]([CH:27]=[O:28])[CH3:26]>>[F:1][C:2]1[CH:20]=[CH:19][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:15][C:27]([N:25]4[CH2:26][C:20]5[C:2](=[CH:3][CH:4]=[CH:5][CH:19]=5)[CH2:24]4)=[O:28])[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1
Reactant: CN(C)C=O
Reactant: NC(=O)CN1CCC(c2noc3cc(F)ccc23)CC1
Agent: [H-]
Agent: [Na+]
Solvent: O
Product: O=C(CN1CCC(c2noc3cc(F)ccc23)CC1)N1Cc2ccccc2C1
Reaction time: 3 h

Procedure:
To a mixture of 2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]acetamide (2.56 g, 9.2 mmol) in DMF (40 ml) was chipped in sodium hydride (770 mg, 60% in oil, 20.1 mmol) at room temperature under N2. The mixture was heated to 65 C. for 3 hours. αα'-dibromoxylene (2.43 g, 9.2 mmol) was added and the resulting mixture was heated at 70 C. for 4 hours, then left standing overnight for 16 hours. The DMF mixture was poured into H2O (400 ml) and the organics were extracted into ethyl acetate (250 ml). The ethyl acetate solution was washed with brine and dried over MgSO4. The solvent was removed and the residue was purified by flash chromatography over a silica gel column (SiO2, 45 gm; eluted with 1% CH3OH: 99% DCM). The product thus purified as a white solid weighed 1.73 g. Recrystallization from a small amount of ethanol yielded white crystals: 1.65 g, m.p. 184°-185° C.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:18]=[CH:17][C:16](C=O)=[CH:15][C:10]=1[C:11]([O:13][CH3:14])=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:21]([O:26][CH3:27])([O:24][CH3:25])OC.C(N(CC)CC)C>CO>[CH2:1]([O:8][C:9]1[CH:18]=[CH:17][C:16]([CH:21]([O:24][CH3:25])[O:26][CH3:27])=[CH:15][C:10]=1[C:11]([O:13][CH3:14])=[O:12])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(OC)OC
Reactant: COC(=O)c1cc(C=O)ccc1OCc1ccccc1
Solvent: CO
Solvent: CCN(CC)CC
Product: COC(=O)c1cc(C(OC)OC)ccc1OCc1ccccc1
Temperature: 25 °C

Procedure:
39.1 g of methyl 2-benzyloxy-5-formyl-benzoate was dissolved in 300 ml methanol. 60 ml trimethyl orthoformate and 2 g of p-toluenesulffonic acid were added thereto, followed by heating under reflux for 4 hours. After cooling to room temperature, 5 ml triethylamine was added thereto, and the mixture was evaporated. The residue was dissolved in ethyl acetate, successively washed with water and saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate and the solvent was evaporated, to give 39.08 g of methyl 2-(benzyloxy)-5-(dimethoxymethyl)benzoate.
Reaction SMILES: [CH:1](/[CH:6]1[CH2:11][CH2:10][CH:9]([CH:12]=[O:13])[CH2:8][CH2:7]1)=[CH:2]\[CH2:3][CH2:4][CH3:5].[Cr](O)(O)(=O)=[O:15].C(O)(C)C>CC(C)=O>[CH:1](/[CH:6]1[CH2:7][CH2:8][CH:9]([C:12]([OH:15])=[O:13])[CH2:10][CH2:11]1)=[CH:2]\[CH2:3][CH2:4][CH3:5]
Reactant: O=[Cr](=O)(O)O
Reactant: CCC/C=C/C1CCC(C=O)CC1
Solvent: CC(C)=O
Solvent: CC(C)O
Product: CCC/C=C/C1CCC(C(=O)O)CC1
Reaction time: 1 h
Yield: 49.5 %

Procedure:
A solution of 1.6 g of 4-(trans-1-pentenyl)cyclohexanecarboxaldehyde in 120 ml of acetone was cooled to -10° C., treated dropwise with 8N chromic acid (about 10 ml) until the colour of the mixture remained brown-orange and stirred for 1 hour. Excess chromic acid was reduced by the addition of isopropanol. The green solution was subsequently partitioned three times in water/methylene chloride. The organic extracts were washed twice with water and the wash-water was back-extracted with methylene chloride. The organic phases were dried over magnesium sulphate and evaporated. The pale brown crystalline residue (2.01 g) was dissolved partially in 20 ml of petroleum ether. Undissolved residue was filtered off and the filtrate was evaporated. Recrystallization of the resulting residue from 60 ml of petroleum ether at -78° C. gave 866 mg (49.5%) of 4-(trans-1-pentenyl)cyclohexanecarboxylic acid as white crystals.
Reaction SMILES: [F:1][C:2]([F:19])([CH:16]([F:18])[F:17])[CH2:3][O:4][C:5]1[CH:6]=[C:7]([CH:12]=[CH:13][C:14]=1C)S([O-])(=O)=O.[OH:20][C:21]1C=C(C=CC=1)C=O.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[F:19][C:2]([F:1])([CH:16]([F:17])[F:18])[CH2:3][O:4][C:5]1[CH:6]=[C:7]([CH:12]=[CH:13][CH:14]=1)[CH:21]=[O:20]
Reactant: O=Cc1cccc(O)c1
Reactant: Cc1ccc(S(=O)(=O)[O-])cc1OCC(F)(F)C(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=Cc1cccc(OCC(F)(F)C(F)F)c1
Temperature: 92 °C
Reaction time: 22 h

Procedure:
Combine 3-(2,2,3,3-tetrafluoropropoxy)tosylate (200 g, 0.664 mol), 3-hydroxybenzaldehyde (101.7 g, 0.833 mol), dimethylformamide (1.5 L) and powdered potassium carbonate (192 g). Heat under stirring at 92° C. for about 22 h. Cool the reaction mixture to 40° C., pour over ice-water and extract with ethyl acetate. Combine organic phases, wash with 1 N sodium hydroxide (1 L and 0.5 L) and then a solution of saturated sodium hydrogen carbonate, dry over magnesium sulfate, filter, evaporate to dryness to provide a oily residue. Distill the oily residue under reduced pressure in a Claisen flask to give a first fraction of the title compound: bp 108–110° C. under 0.4–0.5 mmHg and a second fraction at 110–111° C. under 0.4–0.5 mmHg.
Reaction SMILES: [H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl[C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][C:13]=1[C:21]([F:24])([F:23])[F:22].C(O)(=O)C>CC(N(C)C)=O.ClCCl>[CH2:3]([O:10][C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][C:13]=1[C:21]([F:22])([F:23])[F:24])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: O=[N+]([O-])c1ccc(Cl)c(C(F)(F)F)c1
Reactant: OCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(=O)O
Solvent: CC(=O)N(C)C
Product: O=[N+]([O-])c1ccc(OCc2ccccc2)c(C(F)(F)F)c1
Temperature: 25 °C
Yield: 44.4 %

Procedure:
Sodium hydride (1.8 g, of a 60% dispersion in oil, 45 mmol) was added in portions to a stirred solution of benzyl alcohol (10.8 g, 100 mmol) in DMA (100 ml) with vigorous stirring under an atmosphere of nitrogen at ambient temperature. After warming to 45° C. for 30 minutes the mixture was cooled to ambient temperature and added dropwise to a stirred solution of 2-chloro-5-nitro-trifluoromethylbenzene (11.3 g, 50 mmol) in DMA (30 ml), keeping the temperature below 110° C. The mixture was stirred at 25° C. for 1 hour, then acidified with acetic acid and evaporated to give a yellow solid. The residue was dissolved in dichloromethane, washed with water then dried (MgSO4), and evaporated. The residue was suspended in a mixture of hexane (70 ml) and diethyl ether (10 ml) and the resulting solid filtered off to give 2-benzyloxy-5-nitro-trifluoromethylbenzene (6.6 g, 49%).
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3](=[O:10])[CH2:2]1.C([C:13]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:14]=1[CH:15]=[CH:16][NH:17]2)=O.[O-2].[Al+3].[O-2].[O-2].[Al+3].Cl[CH2:28]Cl>>[NH:17]1[C:18]2[C:14](=[CH:13][C:21]([CH:28]=[C:2]3[O:1][C:5]4[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=4[C:3]3=[O:10])=[CH:20][CH:19]=2)[CH:15]=[CH:16]1
Reactant: O=Cc1cccc2[nH]ccc12
Reactant: O=C1COc2ccccc21
Reactant: ClCCl
Agent: [Al+3]
Agent: [O-2]
Product: O=C1C(=Cc2ccc3[nH]ccc3c2)Oc2ccccc21
Reaction time: 2 h

Procedure:
2H-benzofuran-3-one 1 g and 4-formylindol 1.29 g were dissolved in dichloromethane 25 ml, aluminum oxide (manufactured by Merck Co., cat. No. 1076) 24.0 g was added, and the mixture was stirred for two hours, and aluminum oxide was filtered to obtain a reaction solution. Aluminum oxide was washed with dichloromethane 150 ml twice. The dichloromethane solution and the reaction solution were combined and concentrated at a temperature of 40° C. under reduced pressure. The concentrate was dissolved in methanol 20 ml, the solution was allowed to stand at room temperature for two hours. The precipitated crystals were filtered, and the resulting crystals were dried at a temperature of 60° C. for two hours under reduced pressure to obtain the desired compound 1.22 g.
Reaction SMILES: [C:1](#[N:10])[C:2]1[C:3](=[CH:6][CH:7]=[CH:8][CH:9]=1)[C:4]#[N:5].C[O-].C[O-].C[O-].[Ga+3:17]>C(O)CO>[Ga:17].[CH:7]1[CH:8]=[CH:9][C:2]2[C:3](=[C:4]3[N:5]=[C:4]4[N:10]=[C:1]([C:2]5[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=54)[N:10]=[C:1]4[NH:5][C:4]([C:3]5[CH:6]=[CH:7][CH:8]=[CH:9][C:2]=54)=[N:10][C:1]4=[N:5][C:4]([C:3]5[CH:6]=[CH:7][CH:8]=[CH:9][C:2]=54)=[N:10][C:1]=2[NH:5]3)[CH:6]=1
Reactant: [Ga+3]
Reactant: N#Cc1ccccc1C#N
Agent: C[O-]
Solvent: OCCO
Product: [Ga]
Product: c1ccc2c(c1)-c1nc-2nc2[nH]c(nc3nc(nc4[nH]c(n1)c1ccccc41)-c1ccccc1-3)c1ccccc21

Procedure:
31.8 parts of phthalonitrile, 10.1 parts of gallium trimethoxide, and 150 ml of ethylene glycol were stirred at a temperature of 200° C. in an atmosphere of nitrogen for 24 hours. The resulting product was then filtered. The product was washed with N,N-dimethylformamide and then with methanol, and then dried to obtain 25.1 parts of gallium phthalocyanine.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#N)[CH:9]=2)[CH:4]=[CH:3]1.[OH-:13].[K+].C(O)C.[OH2:18]>>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]([OH:18])=[O:13])[CH:9]=2)[CH:4]=[CH:3]1
Reactant: [OH-]
Reactant: O
Reactant: Cn1ccc2ccc(C#N)cc21
Agent: [K+]
Solvent: CCO
Product: Cn1ccc2ccc(C(=O)O)cc21

Procedure:
1-Methyl-6-cyanoindole (3.12 g, 21.9 mmole) was heated at reflux in 180 mL of ethanol/water (8:1) containing 15 g of potassium hydroxide to give 3.0 g of 1-methyl-1H-indole-6-carboxylic acid as a white solid.
Reaction SMILES: [CH3:1][N:2]([C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([CH3:33])[CH:28]=1)[C:3](=[O:26])[CH2:4][N:5]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:6](=[O:19])[CH2:7][N:8]1[C:12](=[O:13])C2=CC=CC=C2C1=O.O.NN.[CH3:37][C:38]1[CH:39]=[C:40]([N:44]=C=O)[CH:41]=[CH:42][CH:43]=1>>[CH3:1][N:2]([C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([CH3:33])[CH:28]=1)[C:3](=[O:26])[CH2:4][N:5]([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[C:6](=[O:19])[CH2:7][NH:8][C:12]([NH:44][C:40]1[CH:41]=[CH:42][CH:43]=[C:38]([CH3:37])[CH:39]=1)=[O:13]
Reactant: Cc1cccc(N(C)C(=O)CN(C(=O)CN2C(=O)c3ccccc3C2=O)c2ccccc2)c1
Reactant: Cc1cccc(N=C=O)c1
Agent: NN
Solvent: O
Product: Cc1cccc(NC(=O)NCC(=O)N(CC(=O)N(C)c2cccc(C)c2)c2ccccc2)c1
Yield: 32.2 %

Procedure:
The procedure is analogous to that described in Example 23, but 2.7 g of N-methyl-N-(3-methylphenyl)-2-(N-phenyl-2-phthalimidoacetamido)acetamide, 0.6 g of hydrazine hydrate and 0.8 g of 3-methylphenyl isocyanate are used as the starting material. The product obtained is purified by chromatography on 25 g of silica gel (0.065-0.200 mm) contained in a column 1.7 cm in diameter [eluent: methylene chloride/ethyl acetate (80-20 by volume)], collecting 25 cm3 fractions. Fractions 13 to 27 are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. After recrystallization from diethyl ether, 0.86 g of N-methyl-N-(3-methylphenyl)-2-{2-[3-(3-methylphenyl)ureido]-N-phenylacetamido}acetamide melting at 165° C. is obtained.
Reaction SMILES: S(Cl)([Cl:3])=O.O[CH2:6][C:7]1[C:20]2[C:21]3=[C:22]4[C:17](=[CH:18][CH:19]=2)[CH:16]=[CH:15][CH:14]=[C:13]4[CH:12]=[CH:11][C:10]3=[CH:9][CH:8]=1>C1C=CC=CC=1>[Cl:3][CH2:6][C:7]1[C:20]2[C:21]3=[C:22]4[C:17](=[CH:18][CH:19]=2)[CH:16]=[CH:15][CH:14]=[C:13]4[CH:12]=[CH:11][C:10]3=[CH:9][CH:8]=1
Reactant: O=S(Cl)Cl
Reactant: OCc1ccc2ccc3cccc4ccc1c2c34
Solvent: c1ccccc1
Product: ClCc1ccc2ccc3cccc4ccc1c2c34
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Thionyl chloride (15 mL, 200 mmol) was added dropwise to a suspension of 1-hydroxymethylpyrene (9.3 g, 40 mmol) in dry benzene (150 mL) at 0° C. and the mixture was stirred at room temperature overnight. Evaporation of the solvent under reduced pressure gave a creamy-white solid, m.p. 146°-148° C., yield: 9.6 g, 96%.