Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O[C:2]1([C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=2)[C:9]2[N:5]([CH:6]=[N:7][CH:8]=2)[CH2:4][CH2:3]1.S(Cl)(Cl)=O.C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl>[CH:8]1[N:7]=[CH:6][N:5]2[CH2:4][CH2:3][CH:2]([C:10]3[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=3)[C:9]=12
Reactant: N#Cc1ccc(C2(O)CCn3cncc32)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: O=S(Cl)Cl
Product: N#Cc1ccc(C2CCn3cncc32)cc1
Temperature: 25 °C

Procedure:
A solution of 4 mmol of 4-(7-hydroxyl-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)benzonitrile and 8 mmol of thionyl chloride in 30 ml of chloroform is heated at reflux for 15 hours. The reaction mixture is cooled to room temperature and poured into saturated sodium hydrogen carbonate solution. The phases are separated and the organic phase is washed with brine, dried with sodium sulphate and evaporated. From the residue the title compound is obtained by means of flash chromatography (SiO2 60F).
Reaction SMILES: [CH2:1]([CH:3]=[CH:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH3:2].ClC1C=CC=C(C(OO)=[O:20])C=1>C(Cl)(Cl)Cl>[CH2:1]([CH:3]=[CH:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]2[O:20][CH:8]2[CH:7]=1)[CH3:2]
Reactant: CCC=CCc1ccccc1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClC(Cl)Cl
Product: CCC=CCC1=CC2OC2C=C1
Reaction time: 96 h
Yield: 42.7 %

Procedure:
3.8 g of p-ethylallylbenzene was added to 5.9 g of m-chloroperbenzoic acid dissolved in 70 ml of chloroform and the mixture was allowed to stand at about 5° C for 4 days. The resulting mixture was washed with sodium hydroxide solution, Mohr's salt solution, then water and dried over anhydrous sodium sulfate. The solvent was evaporated and the concentration was distilled under reduced pressure to obtain 1.8 g (yield 43%) of p-ethylallylbenzene oxide having a boiling point of 144° to 143° C/38 mmHg as oily substance.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH:9][C:10]1[CH:15]=[C:14](Cl)[C:13](C(F)(F)F)=[CH:12][C:11]=1[N+:21]([O-:23])=[O:22].CO[C:26]1[CH:32]=[CH:31][CH:30]=[CH:29][C:27]=1N.ClC1C=C(Cl)C(C(F)(F)F)=CC=1[N+]([O-])=O>>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:26]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:27]=2)[CH:6]=[CH:5][C:4]=1[NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[N+:21]([O-:23])=[O:22]
Reactant: COc1ccccc1N
Reactant: COc1ccccc1Nc1cc(Cl)c(C(F)(F)F)cc1[N+](=O)[O-]
Agent: O=[N+]([O-])c1cc(C(F)(F)F)c(Cl)cc1Cl
Product: COc1cc(-c2ccccc2)ccc1Nc1ccccc1[N+](=O)[O-]

Procedure:
N-(2-methoxyphenyl)-2-nitro-4-trifluoromethyl-5-chloroaniline, M.p. 142°-145° C., by reaction between 2-methoxyaniline and 2-chloro-4-chloro-5-trifluoromethyl-nitrobenzene.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([OH:17])([C:13]([F:16])([F:15])[F:14])[C:9]([F:12])([F:11])[F:10])=[CH:4][C:3]=1[SH:18].Br[CH2:20][C:21](OCC)=[O:22].N1C=CC=CC=1>C(O)CO>[F:16][C:13]([F:14])([F:15])[C:8]([C:5]1[CH:6]=[CH:7][C:2]2[NH:1][C:21](=[O:22])[CH2:20][S:18][C:3]=2[CH:4]=1)([OH:17])[C:9]([F:10])([F:11])[F:12]
Reactant: Nc1ccc(C(O)(C(F)(F)F)C(F)(F)F)cc1S
Reactant: CCOC(=O)CBr
Solvent: c1ccncc1
Solvent: OCCO
Product: O=C1CSc2cc(C(O)(C(F)(F)F)C(F)(F)F)ccc2N1
Temperature: 0 °C
Yield: 52.8 %

Procedure:
To 140 ml. of ethylene glycol is added 24 gm (0.08 mole) of 4-amino-3-mercapto[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]-benzene, 14 gm. (0.08 mole) ethyl bromoacetate, and 6.4 gm. (0.08 mole) of pyridine. The solution is stirred and heated at 105°-110° for 8 hours. At the end of this period the solution is cooled and poured into 800 ml of ice-water. The resultant precipitate is filtered. The precipitate is air dried and recrystallized from ethyl acetate/hexane to give 14 gm of 7-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)-ethyl]-2H-1,4-benzothiazin-3(4H)-one, m.p. 230°-232°.
Reaction SMILES: [C:1]([O:4][C@H:5]([CH3:27])[CH2:6][CH2:7][CH2:8][CH2:9][N:10]1[C:19](=[O:20])[C:18]2[N:17]([CH2:21][O:22][CH2:23][CH3:24])[C:16](Br)=[N:15][C:14]=2[N:13]([CH3:26])[C:11]1=[O:12])(=[O:3])[CH3:2].[S-2:28].[Na+].[Na+]>C(O)C>[C:1]([O:4][C@H:5]([CH3:27])[CH2:6][CH2:7][CH2:8][CH2:9][N:10]1[C:19](=[O:20])[C:18]2[N:17]([CH2:21][O:22][CH2:23][CH3:24])[C:16]([SH:28])=[N:15][C:14]=2[N:13]([CH3:26])[C:11]1=[O:12])(=[O:3])[CH3:2]
Reactant: CCOCn1c(Br)nc2c1c(=O)n(CCCC[C@@H](C)OC(C)=O)c(=O)n2C
Reactant: [S-2]
Agent: [Na+]
Solvent: CCO
Product: CCOCn1c(S)nc2c1c(=O)n(CCCC[C@@H](C)OC(C)=O)c(=O)n2C
Temperature: 90 °C
Reaction time: 1 h

Procedure:
To a stirring solution of (R)-1-(5-acetoxyhexyl)-8-bromo-7-ethoxymethyl-3-methylxanthine (prepared as for CT13430) (1.77 g, 4.0 mmol) in ethanol (100 ml) was added sodium sulfide (4.48 g, 80 mmol). The reaction mixture was stirred at 90° C. for 1 hour. After evaporation of the solvent under reduced pressure, the crude product was purified by flash chromatography on silica gel eluting with ethyl acetate-methanol (7:1) to provide (R)-1-(5-acetoxyhexyl)-7-ethoxymethyl-8-mercapto-3-methylxanthine. This product was dissolved in methanol (100 ml). A solution of hydrogen chloride in ether (1.0 M, 1.0 ml) was added and stirred at room temperature for 24 hours. After evaporation of the solvent under reduced pressure. The crude product was purified by flash chromatography on silica gel eluting with ethyl acetate-methanol (4:1) to provide (R)-7-ethoxymethyl-1-(5-hydroxyhexyl)-8-mercapto-3-methylxanthine (0.61 g, 51% yield) as a white solid.
Reaction SMILES: CC(C)([O-])C.[K+].[NH:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[CH:8]1.Br[CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19]>C1COCC1.O1CCOCC1>[C:21]([O:20][C:18](=[O:19])[CH2:17][N:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[CH:8]1)([CH3:24])([CH3:23])[CH3:22]
Reactant: CC(C)(C)OC(=O)CBr
Reactant: c1ccc2[nH]cnc2c1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: C1COCCO1
Product: CC(C)(C)OC(=O)Cn1cnc2ccccc21
Yield: 94.7 %

Procedure:
A solution of potassium tert-butoxide (0.6 mmol) in THF (0.6 mL) was added to a solution of 1H-benzoimidazole (71 mg, 0.6 mmol) in dioxane (15 mL) under stirring. tert-Butyl bromoacetate (97 mg, 0.5 mmol) was added to the white suspension and the mixture was stirred overnight at ambient temperature. The solvents were removed in vacuum and the product was purified on a silica gel column using a gradient of ethyl acetate in heptane) to afford benzimidazol-1-yl-acetic acid tert-butyl ester (110 mg, 95%). Mass spectrum (ESI) m/z: 233.0. 1H NMR (400 MHz, MeOD) δ ppm 1.5 (s, 9 H), 5.0 (s, 2 H), 7.3 (m, 2H), 7.4 (d, J=7.1 Hz, 1H), 7.7 (d, J=6.6 Hz, 1H), 8.1 (s, 1H).
Reaction SMILES: [CH2:1]([Li])CCC.[C:6]1([S:12]([CH2:15][C:16]([CH3:30])([CH3:29])[CH2:17][CH2:18][N:19]2[CH2:24][CH2:23][CH:22]([C:25]([F:28])([F:27])[F:26])[CH2:21][CH2:20]2)(=[O:14])=[O:13])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.CI>O1CCCC1>[C:6]1([S:12]([CH:15]([CH3:1])[C:16]([CH3:30])([CH3:29])[CH2:17][CH2:18][N:19]2[CH2:20][CH2:21][CH:22]([C:25]([F:28])([F:27])[F:26])[CH2:23][CH2:24]2)(=[O:14])=[O:13])[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1
Reactant: CC(C)(CCN1CCC(C(F)(F)F)CC1)CS(=O)(=O)c1ccccc1
Reactant: [Li]CCCC
Solvent: C1CCOC1
Solvent: CI
Product: CC(C(C)(C)CCN1CCC(C(F)(F)F)CC1)S(=O)(=O)c1ccccc1
Reaction time: 0.5 h

Procedure:
A solution of n-butyllithium (1.5M, 0.13 ml, 0.2 mmol) in hexanes was added to a stirred solution of 1-(4-benzenesulfonyl-3,3-dimethyl-butyl)-4-trifluoromethylpiperidine (40 mg, 0.11 mmol) in tetrahydrofuran (2 ml) at −78° C. The mixture was stirred for 30 min. and methyl iodide (0.34 ml) was added. After 1 hour, the reaction mixture was quenched with one drop of water and concentrated in vacuo. The residue was purified on silica gel (dichloromethane:methanol) to give 1-(4-benzenesulfonyl-3,3-dimethyl-pentyl)-4-trifluoromethyl-piperidine. The title product was prepared by treatment of the amine with 1M ethereal HCl.
Reaction SMILES: I[CH2:2][C:3]([NH:5][CH2:6][C:7]([C:9]1[CH:22]=[CH:21][C:20]2[C:11](=[C:12]3[C:17](=[CH:18][C:19]=2[NH2:23])[CH:16]=[CH:15][CH:14]=[N:13]3)[N:10]=1)=[O:8])=[O:4].[NH3:24]>CN(C)C=O>[NH2:24][CH2:2][C:3]([NH:5][CH2:6][C:7]([C:9]1[CH:22]=[CH:21][C:20]2[C:11](=[C:12]3[C:17](=[CH:18][C:19]=2[NH2:23])[CH:16]=[CH:15][CH:14]=[N:13]3)[N:10]=1)=[O:8])=[O:4]
Reactant: N
Reactant: Nc1cc2cccnc2c2nc(C(=O)CNC(=O)CI)ccc12
Solvent: CN(C)C=O
Product: NCC(=O)NCC(=O)c1ccc2c(N)cc3cccnc3c2n1
Reaction time: 1 h

Procedure:
(Iodoacetyl-glycyl)-5-amino-1,10-phenanthroline (6) (Preparation 5; 32.3 mg; 77.0 μmol) was dissolved in 2 ml dimethylformamide. Into this solution, was added 10 ml concentrated ammonia. The reaction mixture was stirred for 1 hr. in the dark, and then was evaporated under vacuum. The crude product was purified by preparative thin layer chromatography (silica; 2000 μm; ammonia:95% ethanol, 1:20, v/v). Yield: 10.5 mg, 44%.
Reaction SMILES: [C:1]1([CH:7]([C:24]([F:27])([F:26])[F:25])[CH:8]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>>[C:1]1([C:7]([C:24]([F:27])([F:25])[F:26])=[C:8]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[C:9]2[CH:10]=[CH:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COc1ccc(C(c2ccc(F)cc2)C(c2ccccc2)C(F)(F)F)cc1
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Product: COc1ccc(C(=C(c2ccccc2)C(F)(F)F)c2ccc(F)cc2)cc1
Reaction time: 8 h
Yield: 51 %

Procedure:
2-Phenyl-3,3,3-trifluoro-1-(4-fluorophenyl)-1-(4-methoxyphenyl)-propane, prepared as described in Example 18, is reacted with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone under boiling for 8 hours as described in Example 7. The reaction mixture is processed, and the product is crystallized from ethanol. 2-Phenyl-3,3,3-trifluoro-1-(4-fluorophenyl)-1-(4-methoxyphenyl)-propene is obtained with a yield of 51%; m.p.: 52°-56° C.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]([NH:9][C:10]([C:13]2[NH:14][C:15](=[O:24])[C:16]([OH:23])=[C:17]([C:19]([O:21]C)=O)[N:18]=2)([CH3:12])[CH3:11])=[O:8])=[N:4][N:3]=1.[F:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30][NH2:31])=[CH:28][CH:27]=1.C(O)(=O)C.O>C(O)(C)C>[F:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30][NH:31][C:19]([C:17]2[N:18]=[C:13]([C:10]([NH:9][C:7]([C:5]3[O:6][C:2]([CH3:1])=[N:3][N:4]=3)=[O:8])([CH3:11])[CH3:12])[NH:14][C:15](=[O:24])[C:16]=2[OH:23])=[O:21])=[CH:28][CH:27]=1
Reactant: NCc1ccc(F)cc1
Reactant: COC(=O)c1nc(C(C)(C)NC(=O)c2nnc(C)o2)[nH]c(=O)c1O
Solvent: O
Solvent: CC(=O)O
Solvent: CC(C)O
Product: Cc1nnc(C(=O)NC(C)(C)c2nc(C(=O)NCc3ccc(F)cc3)c(O)c(=O)[nH]2)o1
Temperature: 82.5 °C

Procedure:
Methyl 2-(2-(5-methyl-1,3,4-oxadiazole-2-carboxamido)propan-2-yl)-1,6-dihydro-5-hydroxy-6-oxopyrimidine-4-carboxylate [V(a); 40 gms] was suspended in isopropyl alcohol (400 ml) and 4-fluorobenzyl amine (30 gms) was added to the above mixture. The reaction mixture was stirred at 80 to 85° C. After completion, reaction mass was cooled to 60° C. and acetic acid (1600 ml) and water (400 ml) was added. The resultant crystalline product was filtered and washed with mixture of water and isopropyl alcohol (1:1) and dried to give N-(4-fluorobenzyl)-2-(2-(5-methyl-1,3,4-oxadiazole-2-carboxamido) propan-2-yl)-1,6-dihydro-5-hydroxy-6-oxopyrimidine-4-carboxamide VI).
Reaction SMILES: [CH2:1]([OH:3])[CH3:2].[OH2:4]>>[OH:3][CH2:1][C@@H:2]([C@H:1]([C@@H:2]([C@@H:1]([CH2:2][OH:4])[OH:3])[OH:4])[OH:3])[OH:4]
Reactant: O
Reactant: CCO
Product: OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)CO

Procedure:
A solution is formed of the ethanol, water and sorbitol ingredients. The Pluronic F-108 is added, followed by sodium bicarbonate and zinc oxide andthe other ingredients in the listed order with high speed stirring.
Reaction SMILES: [CH2:1]1[C:5]2([CH2:10][CH2:9][CH2:8][C:7](=[O:11])[CH2:6]2)[CH2:4][CH2:3][CH2:2]1.C[Mg]Cl.[Cl-].[NH4+].CC1(O)CCCC2(CCCC2)C1>O1CCCC1>[CH2:1]1[C:5]2([CH2:10][CH2:9][CH2:8][CH:7]([OH:11])[CH2:6]2)[CH2:4][CH2:3][CH2:2]1
Reactant: O=C1CCCC2(CCCC2)C1
Agent: CC1(O)CCCC2(CCCC2)C1
Agent: C[Mg]Cl
Agent: [Cl-]
Solvent: C1CCOC1
Product: OC1CCCC2(CCCC2)C1
Temperature: 25 °C
Yield: 106.8 %

Procedure:
With stirring under nitrogen atmosphere at room temperature, a mixture of 39.1 g of 7-spiro[4.5]decanone and 100 ml of tetrahydrofuran was added dropwise to a tetrahydrofuran solution of 0.502 mol methylmagnesium chloride (which had been prepared from 12.2 g of metallic magnesium, 500 ml of tetrahydrofuran and chloromethane). The mixture was stirred overnight at room temperature, after which a saturated ammonium chloride aqueous solution was added to stop the reaction. Through ordinary work-up of extraction, washing and drying, and subsequent concentration under reduced pressure, there was obtained 42.3 g (yield 95%) of the target compound, 7-methylspiro[4.5]decan-7-ol. This compound had a purity high enough to use in the subsequent step without further purification.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:22])[CH2:5][CH2:6][C:7]1([CH3:21])[CH2:12][CH2:11][C:10]2[CH:13]=[CH:14][C:15]([OH:20])=[C:16]([CH2:17][CH2:18][CH3:19])[C:9]=2[O:8]1)[CH3:2].[C:23](OC(=O)C)(=[O:25])[CH3:24].CCOCC>N1C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:22])[CH2:5][CH2:6][C:7]1([CH3:21])[CH2:12][CH2:11][C:10]2[CH:13]=[CH:14][C:15]([O:20][C:23](=[O:25])[CH3:24])=[C:16]([CH2:17][CH2:18][CH3:19])[C:9]=2[O:8]1)[CH3:2]
Reactant: CC(=O)OC(C)=O
Reactant: CCCc1c(O)ccc2c1OC(C)(CCC(=O)OCC)CC2
Solvent: c1ccncc1
Solvent: CCOCC
Product: CCCc1c(OC(C)=O)ccc2c1OC(C)(CCC(=O)OCC)CC2
Temperature: 25 °C
Reaction time: 5 h
Yield: 63.3 %

Procedure:
To a stirred solution of 0.8 g of racemic-3,4-dihydro-7-hydroxy-2-methyl-8-n-propyl-2H-1-benzopyran-2-propanoic acid ethyl ester in 8 ml of pyridine was added 0.37 ml of acetic anhydride. The solution was stirred at room temperature for 5 hours then poured into ice-water and worked up with ether in the usual manner (the combined ether extracts were additionally washed with 1N hydrochloric acid and saturated sodium bicarbonate solutions). The oily product (1.0 g) was chromatographed on 50 g of silica gel. Elution with 19:1 toluene-ethyl acetate afforded 0.575 g (63.3%) of racemic-7-acetoxy-3,4-dihydro-2-methyl-8-n-propyl-2H-1-benzopyran-2-propanoic acid ethyl ester as a pale-yellow oil.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH2:8][CH3:9])[CH:3]=1.C([Li])CCC.[CH2:15]([Sn:19](Cl)([CH2:24][CH2:25][CH2:26][CH3:27])[CH2:20][CH2:21][CH2:22][CH3:23])[CH2:16][CH2:17][CH3:18]>C(OCC)C>[CH2:8]([C:4]1[CH:3]=[C:2]([Sn:19]([CH2:20][CH2:21][CH2:22][CH3:23])([CH2:24][CH2:25][CH2:26][CH3:27])[CH2:15][CH2:16][CH2:17][CH3:18])[CH:7]=[CH:6][N:5]=1)[CH3:9].[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH2:8][CH3:9])[CH:3]=1
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Agent: CCc1cc(Br)ccn1
Agent: [Li]CCCC
Solvent: CCOCC
Product: CCCC[Sn](CCCC)(CCCC)c1ccnc(CC)c1

Procedure:
The title compound (5 g as a yellow oil) was obtained from 3 g of 4-bromo-2-ethylpyridine from (a) above, 6.4 ml of n-butyllithium and 4.3 ml of tributyltin chloride with 50 ml of diethyl ether as solvent by a procedure analogous to that of Example 2(b) above.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH3:9])[C:4]=1[OH:10])[CH3:2].[Br-:11].[Br-].[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC>C(Cl)(Cl)Cl>[Br:11][C:7]1[CH:6]=[C:5]([CH3:9])[C:4]([OH:10])=[C:3]([CH2:1][CH3:2])[CH:8]=1
Reactant: CCc1cccc(C)c1O
Reactant: [Br-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: ClC(Cl)Cl
Product: CCc1cc(Br)cc(C)c1O
Temperature: 25 °C
Reaction time: 1 h
Yield: 182.7 %

Procedure:
Then, 16 g of 2-ethyl-6-methylphenol was dissolved in 200 ml of chloroform, followed by stirring at 0° C., to which 56.6 g of tetrabutylammonium tribromide was added in small portions. After stirring at room temperature for 1 hour, the solvent was removed by distillation under reduced pressure, and the residue was dissolved in 300 ml of diethyl ether. The solution was successively washed with 10% hydrochloric acid and water, dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude product was subjected to silica gel chromatography, which afforded 23 g of 4-bromo-2-ethyl-6-methylphenol (92% yield).
Reaction SMILES: [C-:1]#[N:2].[Na+].[Br:4][C:5]1[CH:12]=[CH:11][CH:10]=[CH:9][C:6]=1[CH2:7]Br>O.C(O)C>[Br:4][C:5]1[CH:12]=[CH:11][CH:10]=[CH:9][C:6]=1[CH2:7][C:1]#[N:2]
Reactant: BrCc1ccccc1Br
Reactant: [C-]#N
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: N#CCc1ccccc1Br
Yield: 102.2 %

Procedure:
To a suspension of 220.0 g of sodium cyanide in 265 ml of water and 380 ml of absolute ethanol, is added, while stirring, a solution of 911.0 g of o-bromobenzyl bromide in 911 ml of ethanol. The reaction proceeds exothermally, but is eventually heated under reflux for about 0.5 hour, then cooled in an ice-bath, and filtered. The solid is washed with ether, the filtrate is concentrated, the residue is suspended in 300 ml of water and extracted with three 500 ml portions of ether. The ether extracts are washed, dried, and the solvent is removed. The residue is distilled to give 730 g of the named product, bp 141°-142° (12mm).
Reaction SMILES: C([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:15]1[O:19][C:18]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[N:17][CH:16]=1)C1C=CC=CC=1>O1CCCC1.[Pd]>[OH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:15]1[O:19][C:18]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[N:17][CH:16]=1
Reactant: c1ccc(COc2ccccc2-c2cnc(-c3ccccc3)o2)cc1
Agent: [Pd]
Solvent: C1CCOC1
Product: Oc1ccccc1-c1cnc(-c2ccccc2)o1

Procedure:
0.55 g of 5-(2-benzyloxyphenyl)-2-phenyl-1,3-oxazole according to step (c) are hydrogenated in 30 ml of tetrahydrofuran in the presence of 0.1 g of Pd/C catalyst (10W) at about 60° C. (5.7 bar). After the catalyst has been separated off the solvent is distilled off in vacuo and the residue remaining is chromatographed on silica gel (dioxane:hexane 3:5).
Reaction SMILES: [C:1]1([C:7]([C:10]2[CH:23]=[CH:22][C:21]3[C:20]([C:25]4[CH:30]=[CH:29][C:28]([CH:31]=[C:32]([C:39]5[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=5)[C:33]5[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=5)=[CH:27][CH:26]=4)(O)[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[C:13]([C:46]4[CH:51]=[CH:50][C:49]([CH:52]=[C:53]([C:60]5[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=5)[C:54]5[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=5)=[CH:48][CH:47]=4)(O)[C:12]=3[CH:11]=2)([CH3:9])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[I-].[K+].O.[PH2](=O)[O-].[Na+].C(O)(=O)C>O.C1(C)C=CC=CC=1>[C:1]1([C:7]([C:10]2[CH:23]=[CH:22][C:21]3[C:12](=[C:13]([C:46]4[CH:47]=[CH:48][C:49]([CH:52]=[C:53]([C:54]5[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=5)[C:60]5[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=5)=[CH:50][CH:51]=4)[C:14]4[C:19]([C:20]=3[C:25]3[CH:30]=[CH:29][C:28]([CH:31]=[C:32]([C:39]5[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=5)[C:33]5[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=5)=[CH:27][CH:26]=3)=[CH:18][CH:17]=[CH:16][CH:15]=4)[CH:11]=2)([CH3:9])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(C)(c1ccccc1)c1ccc2c(c1)C(O)(c1ccc(C=C(c3ccccc3)c3ccccc3)cc1)c1ccccc1C2(O)c1ccc(C=C(c2ccccc2)c2ccccc2)cc1
Agent: O=[PH2][O-]
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: CC(=O)O
Solvent: Cc1ccccc1
Product: CC(C)(c1ccccc1)c1ccc2c(-c3ccc(C=C(c4ccccc4)c4ccccc4)cc3)c3ccccc3c(-c3ccc(C=C(c4ccccc4)c4ccccc4)cc3)c2c1

Procedure:
2-(2-Phenyl-2-propyl)-9,10-bis(4-(2,2-diphenylvinyl)phenyl)-9,10-dihydro-9,10-dihydroxyanthracene (5.7 g, 6.7 mmole), potassium iodide (3.3 g, 20 mmole) and sodium phosphinate monohydrate (1.1 g, 10 mmole) were dissolved into acetic acid (50 ml), and the resultant solution was stirred at 100° C. The reaction mixture was diluted with water (50 ml) and treated by extraction with toluene (300 ml). The organic layer was washed with a saturated aqueous solution of sodium chloride (50 ml) and dried with magnesium sulfate. After the solvent was removed by distillation, the obtained product was purified in accordance with the column chromatography (silica gel; hexane+30% dichloromethane), and a light yellow solid was obtained (4.5 g; 82%). The obtained product was identified to be Compound (A21) by the measurements in accordance with 1H-NMR and FD-MS.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[N+:11]([O-:13])=[O:12])[NH:7][N:6]=[CH:5]2.[C:14](OC(=O)C)(=[O:16])[CH3:15]>C(O)(=O)C>[C:14]([N:7]1[C:8]2[C:4](=[CH:3][C:2]([CH3:1])=[C:10]([N+:11]([O-:13])=[O:12])[CH:9]=2)[CH:5]=[N:6]1)(=[O:16])[CH3:15]
Reactant: CC(=O)OC(C)=O
Reactant: Cc1cc2cn[nH]c2cc1[N+](=O)[O-]
Solvent: CC(=O)O
Product: CC(=O)n1ncc2cc(C)c([N+](=O)[O-])cc21
Reaction time: 15 h
Yield: 75 %

Procedure:
Five g (28,2 m-mol) of 5-methyl-6-nitro-1H-indazole (formula 24) prepared e.g. according to the method described by E. Nolting, Ber. Dtsch. Chem. Ges. 37 (1904) 2556 were added to a mixture of acetic acid (50 ml) and acetic anhydride (100 ml). After about 15 min the acetylated compound (formula 25) crystallized from the light-yellow colored solution in the form of elongated colorless needles. To complete crystallization, the solution was left to stand for a period of 45 min at room temperature and for a period of 15 hours in a refrigerator (4°). The crystal mass formed was filtered under suction, washed well with water and dried over P2O5 under vacuum. This yielded 4.6 g (yield 75%) of the formula 25 target product. By careful evaporation of the mother liquor and allowing to stand overnight in the refrigerator, an additional portion (0.90 g) of the target product was obtained. Total yield was 5.55 g (90%). The target product melts at 185°; ir (KBr): 1715 (ester carbonyl), 1582 (aromatic), 1530 cm-1 (NO2); pmr (CDCl3): δ 2.66 (s, 3, C5 --CH3), 2.82 (s, 3, N1 --CH3CO), 7.70 (s, 1, H4), 8.18 (s, 1, H7), 8.96 (s, 1, H3); ms (70 eV): m/e 219 (35%, M+), 177 (61%, M+ -keten), 160 (100%, M+ -keten-HO).
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[C:21]([OH:22])=[CH:20][C:7]2[CH2:8][N:9]([NH:13][C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)[CH2:10][CH2:11][CH2:12][C:6]=2[CH:5]=1.[CH3:23][N:24]([CH3:28])[C:25]([Cl:27])=[O:26].C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl.ClCCl>[ClH:27].[CH3:2][O:3][C:4]1[C:21]([O:22][C:25](=[O:26])[N:24]([CH3:28])[CH3:23])=[CH:20][C:7]2[CH2:8][N:9]([NH:13][C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)[CH2:10][CH2:11][CH2:12][C:6]=2[CH:5]=1
Reactant: COc1cc2c(cc1O)CN(Nc1ccncc1)CCC2
Reactant: CN(C)C(=O)Cl
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: COc1cc2c(cc1OC(=O)N(C)C)CN(Nc1ccncc1)CCC2
Temperature: 25 °C
Yield: 52 %

Procedure:
To a solution of [7-methoxy-8-hydroxy-1,3,4,5-tetrahydrobenzo[c]azepin-2-yl]-4-pyridinylamine hydrochloride 0.25 hydrate (500 mg) in chloroform (10 ml) was added dimethylcarbamyl chloride (170 μl) and triethylamine (0.75 ml). The reaction mixture was heated under reflux for 3 hrs, then cooled to room temperature, and dichloromethane (200 ml) and saturated sodium bicarbonate solution (100 ml) were added. The aqueous phase was extracted with dichloromethane (2×5 ml), the organic extracts were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated in vacuo. The residue was chromatographed over silica gel eluting with dichloromethane:methanol (9:1). The appropriate fractions were collected and concentrated. The residue was dissolved in methanol (5 ml), and concentrated hydrochloric acid was added. The mixture was concentrated in vacuo, and the residue was crystallized from diethyl ether-dichloromethane to give 320 mg (52%) of product, mp 95-110° C.