Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CNCCNC.[C:7]1([NH:13][C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:17]=[CH:16][CH:15]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[Br:24][C:25]1[CH:30]=[CH:29][C:28](I)=[CH:27][CH:26]=1.C(O[Na])(C)(C)C>[Cu].C1(C)C(C)=CC=CC=1>[Br:24][C:25]1[CH:30]=[CH:29][C:28]([N:13]([C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:17]=[CH:16][CH:15]=2)[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[CH:27][CH:26]=1
Reactant: Brc1ccc(I)cc1
Reactant: c1ccc(Nc2cccc3ccccc23)cc1
Agent: [Cu]
Agent: CC(C)(C)O[Na]
Agent: CNCCNC
Solvent: Cc1ccccc1C
Product: Brc1ccc(N(c2ccccc2)c2cccc3ccccc23)cc1
Yield: 68.1 %

Procedure:
Adding 17.6 g of N,N′-dimethylethylenediamine into a solution prepared by mixing 21.9 g of N-phenyl-1-naphthylamine, 28.2 g of 4-bromoiodobenzene, 14.4 g of t-butoxysodium, 3.81 g of copper powder and 100 milliliter of xylene, the resultant solution was refluxed with heating under ambient atmosphere of argon gas for 24 hours. After cooling the resultant solution down to a room temperature, the solution was filtered and insolubles were removed followed by concentrating the filtrate. Refining the residue by means of a silicagel column chromatography, 25.4 g of N-(4-bromophenyl)-N-phenyl-1-naphthylamine was obtained.
Reaction SMILES: [C:1]([OH:9])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.S(Cl)([Cl:12])=O.C(C1C=CC(OCCCCO)=CC=1)(C)(C)C>ClCCl>[C:1]([Cl:12])(=[O:9])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1
Reactant: O=C(O)c1cccnc1
Reactant: O=S(Cl)Cl
Agent: CC(C)(C)c1ccc(OCCCCO)cc1
Solvent: ClCCl
Product: O=C(Cl)c1cccnc1

Procedure:
Nicotinoyl chloride was prepared by treating 100 g (0.81 mole) of nicotinic acid with 280 ml of thionyl chloride at reflux for two hours. The excess thionyl chloride was removed in vacuo and the crystalline acid chloride hydrochloride was suspended in 500 ml of dichloromethane. To the stirred mixture was added 66 g (0.30 mole) of 4-p-t-butylphenoxy-1-butanol dissolved in 400 ml of dichloromethane. After forty-eight hours the mixture was washed with one liter of saturated sodium bicarbonate. The dichloromethane solution was dried over magnesium sulfate and evaporated to a syrupy residue. The material was chromatographed on 1 kg of silica gel with elution by dichloromethanemethanol, 96:4, to afford 43.8 g (45%) of the nicotinate ester as an oil. The hydrobromide salt was prepared by treatment of a solution of 43.8 g in 800 ml of ethyl acetate with 30 ml of 4.5N hydrogen bromide in ether. The precipitate was collected, washed with pentane and dried, m.p. 132°-133° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:31]([CH3:33])[CH3:32])[C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=2)[C@H:10]([C:34](C)(C)[O:35][SiH2]C(C)(C)C)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.O.O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.CC#N.O.CC#N>C1COCC1.O>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:31]([CH3:32])[CH3:33])[C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=2)[C@H:10]([CH2:34][OH:35])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: COCCCOc1cc(C(=O)N(C[C@@H]2CN(C(=O)OC(C)(C)C)C[C@H]2C(C)(C)O[SiH2]C(C)(C)C)C(C)C)ccc1OC
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CC#N
Solvent: C1CCOC1
Solvent: O
Product: COCCCOc1cc(C(=O)N(C[C@@H]2CN(C(=O)OC(C)(C)C)C[C@H]2CO)C(C)C)ccc1OC

Procedure:
The title compound is prepared in a similar manner as described for Example 9/reaction step H, from (3S*,4R*)-3-(tert-butyl-dimethyl-silanyloxymethyl)-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (25.0 g, 41.1 mmol) and tetrabutylammonium fluoride trihydrate (19.4 g, 61.6 mmol) in THF (150 mL) as a colorless oil. MS: 495.2 [M+H]+; tR (HPLC, C18 column, 5-100% CH3CN/H2O/6 min, 100% CH3CN/1.5 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 mL/min): 4.84 min.
Reaction SMILES: [CH3:1][C:2]([N+:12]([O-])=O)([CH3:11])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.[CH3:15][C:16]([OH:18])=[O:17].CCO>[Pd].CO>[C:16]([OH:18])(=[O:17])[CH3:15].[NH2:12][C:2]([CH3:11])([CH3:1])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1
Reactant: CC(C)(Cc1ccc(O)cc1)[N+](=O)[O-]
Agent: [Pd]
Solvent: CCO
Solvent: CO
Solvent: CC(=O)O
Product: CC(C)(N)Cc1ccc(O)cc1
Temperature: 50 °C
Reaction time: 1 h
Yield: 85.9 %

Procedure:
A one-gallon high-pressure reactor was charged with 4(2-methyl-2-nitropropyl)phenol (120 g, 614 mmol), HOAc (35.2 mL, 614 mmol), 5% Palladium on carbon (24 g) wetted with 2B3 EtOH (60 mL), and MeOH (1230 mL). The mixture was heated to 50° C. with agitation (600 rpm), and the reactor was purged with N2 and pressurized to 50 psi with H2. After 15.5 h the reactor was purged with N2, and the cooled mixture was filtered. The filter cake was washed with MeOH and the filtrate was concentrated to 514 g of slurry on a rotary evaporator. To this slurry was added EtOAc (2 L) with vigorous agitation. After stirring for 1 h, the resulting crystals were filtered and washed with a small amount of EtOAc. The product was dried overnight in a 45° C. vacuum oven to yield 118.83 g (86%) of product as small white needles (mp 211°-216° C. dec). This material was 99% pure by HPLC analysis, and while another 9.00 g of material was obtained from the mother liquor it was found to be only 88% pure.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][NH:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13](/[CH:16]=[CH:17]/[CH:18]([C:23]2[CH:28]=[C:27]([Cl:29])[C:26]([Cl:30])=[C:25]([Cl:31])[CH:24]=2)[C:19]([F:22])([F:21])[F:20])=[CH:12][C:11]=1[C:32]([F:35])([F:34])[F:33].[CH:36]1([C:39](Cl)=[O:40])[CH2:38][CH2:37]1>C(Cl)Cl>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][N:8]([CH2:9][C:10]1[CH:15]=[CH:14][C:13](/[CH:16]=[CH:17]/[CH:18]([C:23]2[CH:28]=[C:27]([Cl:29])[C:26]([Cl:30])=[C:25]([Cl:31])[CH:24]=2)[C:19]([F:22])([F:21])[F:20])=[CH:12][C:11]=1[C:32]([F:35])([F:34])[F:33])[C:39]([CH:36]1[CH2:38][CH2:37]1)=[O:40]
Reactant: O=C(Cl)C1CC1
Reactant: FC(F)(F)c1cc(/C=C/C(c2cc(Cl)c(Cl)c(Cl)c2)C(F)(F)F)ccc1CNCc1ccccn1
Solvent: ClCCl
Product: O=C(C1CC1)N(Cc1ccccn1)Cc1ccc(/C=C/C(c2cc(Cl)c(Cl)c(Cl)c2)C(F)(F)F)cc1C(F)(F)F
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 482.4 %

Procedure:
(E)-1-(Pyridin-2-yl)-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzyl)methanamine (0.27 g, 0.05 mmol) was taken up in CH2Cl2 (3 mL). To this was added TEA (0.14 mL, 0.1 mmol). The reaction mixture was stirred for 10 min After 10 min, the reaction mixture was cooled to 0° C., and cyclopropylcarbonyl chloride (0.08 mL, 0.075 mmol) was added. The reaction mixture was stirred at ambient temperature for 1 h and then was washed with water and satd aq NaHCO3 solution. The organic layer was dried over anhydrous Na2SO4 and evaporated to obtain pale yellow gummy material (0.15 g, 50%): 1H NMR (400 MHz, CDCl3) δ 8.58 (d, J=4.6 Hz, 1H), 7.74 (m, 1H), 7.62 (m, 2H), 7.52 (m, 1H), 7.4 (s, 2H), 7.3 (m, 1H), 7.2 (m, 2H), 6.60 (d, J=16.0 Hz, 1H), 6.38 (dd, J=16.0, 8.0 Hz, 1H), 5.02 (s, 1H), 4.8 (s, 1H), 4.8 (d, J=10 Hz, 2H), 4.10 (m, 1H), 1.8 (m, 1H), 1.2 (m, 2H), 0.6 (m, 2H); ESIMS m/z 620.86 ([M−H]−); IR (thin film) 1645, 1115, 808 cm−1.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([N+]([O-])=O)[C:5]([C:8]#[N:9])=[N:6][CH:7]=1.[F-:13].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1>CS(C)=O>[Br:1][C:2]1[CH:3]=[C:4]([F:13])[C:5]([C:8]#[N:9])=[N:6][CH:7]=1
Reactant: [F-]
Reactant: N#Cc1ncc(Br)cc1[N+](=O)[O-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: CS(C)=O
Solvent: C1CCOC1
Product: N#Cc1ncc(Br)cc1F
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 5-bromo-3-nitropicolinonitrile (6.84 g, 30 mmol) in dimethylsulfoxide was cooled to −25° C. and treated with 1M tetra-n-butylammonium fluoride in tetrahydrofuran (60 mL, 60 mmol). The reaction mixture was stirred at ambient temperature for 1 hour. It was quenched with water and extracted with ethyl acetate. The combined organic layers were dried (Na2SO4), filtered and concentrated to provide crude title compound.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([C:14]2[S:15][C:16]([C:20]([O:22]CC)=[O:21])=[C:17]([CH3:19])[N:18]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][CH:11]([CH3:13])[CH3:12])#[N:2].[OH-].[Na+].Cl>CC(C)=O>[CH3:19][C:17]1[N:18]=[C:14]([C:5]2[CH:6]=[CH:7][C:8]([O:9][CH2:10][CH:11]([CH3:13])[CH3:12])=[C:3]([C:1]#[N:2])[CH:4]=2)[S:15][C:16]=1[C:20]([OH:22])=[O:21]
Reactant: CCOC(=O)c1sc(-c2ccc(OCC(C)C)c(C#N)c2)nc1C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)=O
Product: Cc1nc(-c2ccc(OCC(C)C)c(C#N)c2)sc1C(=O)O
Temperature: 25 °C
Yield: 36.3 %

Procedure:
Ethyl 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylate (3.0 g), acetone (30 mL), and 1 N sodium hydroxide solution (12 mL) were placed into a round bottom flask and heated to reflux. The mixture was maintained under reflux until reaction completion. After the reaction was completed, the mass was cooled to about 25° C. and the pH was adjusted to about 1 to 2 with hydrochloric acid (1.5 mL). The mass was extracted into ethyl acetate (40 mL). The ethyl acetate layer was washed with water (30 mL). The ethyl acetate layer was distilled completely under vacuum below 60° C. Acetone (30 mL) was added to the residue and the mixture was heated to reflux and maintained for about 30 minutes. The mass was then cooled to about 25° C., maintained for about 60 minutes, filtered under vacuum and the solid was washed with acetone (3 mL). The wet solid was dried at about 60° C. to a constant weight to yield 1.0 g of the title compound. Purity by HPLC: 99.5%.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([S:18](=[O:21])(=[O:20])[NH2:19])[C:10]=1[S:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:5]([OH:7])=[O:6].[OH-].[Li+].[CH2:24](Br)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.Cl>O>[CH2:24]([NH:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([S:18](=[O:20])(=[O:21])[NH2:19])[C:10]=1[S:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:5]([OH:7])=[O:6])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: BrCc1ccccc1
Reactant: Nc1cc(C(=O)O)cc(S(N)(=O)=O)c1Sc1ccccc1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Product: NS(=O)(=O)c1cc(C(=O)O)cc(NCc2ccccc2)c1Sc1ccccc1

Procedure:
A suspension of 3-amino-4-phenylthio-5-sulphamyl-benzoic acid (4.05 g) in water (100 ml) was adjusted to pH 7.5 by addition of 1N lithium hydroxide. Benzyl bromide (2.2 g) was added and, under stirring, the pH was kept at 7.5 by automatic titration with lithium hydroxide. After the base comsumption had become negligible, the pH was adjusted to 2.5 by addition of dilute hydrochloric acid. The precipitated 3-benzylamino-4-phenylthio-5-sulphamyl-benzoic acid was collected and recrystallized from ethanol, whereafter the compound was obtained with a melting point of 224°-225°C.
Reaction SMILES: [Cl:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][NH:7][C:8](=[O:13])[C:9]([CH3:12])([CH3:11])[CH3:10])=[CH:4][C:3]=1[N:16]1[C:20](=[O:21])[NH:19][C:18]([C:22]2[CH:27]=[CH:26][C:25](I)=[CH:24][CH:23]=2)=[N:17]1.[C:29]([CH:31]1[CH2:33][CH2:32]1)#[CH:30].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CS(C)=O>[Cl:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][NH:7][C:8](=[O:13])[C:9]([CH3:12])([CH3:11])[CH3:10])=[CH:4][C:3]=1[N:16]1[C:20](=[O:21])[NH:19][C:18]([C:22]2[CH:27]=[CH:26][C:25]([C:30]#[C:29][CH:31]3[CH2:33][CH2:32]3)=[CH:24][CH:23]=2)=[N:17]1
Reactant: CC(C)(C)C(=O)NCc1ccc(Cl)c(-n2nc(-c3ccc(I)cc3)[nH]c2=O)c1
Reactant: C#CC1CC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CS(C)=O
Product: CC(C)(C)C(=O)NCc1ccc(Cl)c(-n2nc(-c3ccc(C#CC4CC4)cc3)[nH]c2=O)c1
Temperature: 80 °C
Reaction time: 5.5 h
Yield: 56.8 %

Procedure:
To a solution of N-(4-chloro-3-(4,5-dihydro-3-(4-iodophenyl)-5-oxo-1,2,4-triazol-1-yl)benzyl)pivalamide (Intermediate-95, 0.100 g, 0.196 mmol) in DMSO (3.0 mL), ethynylcyclopropane (0.035 g, 0.530 mmol), TBAF (0.150 g, 0.574) and bis(triphenylphosphine)palladium(II) chloride_(catalytic) were added and the reaction mass was stirred at 80° C. for 5-6 h. After completion of the reaction, the reaction mass was quenched with water and extracted with DCM and concentrated to afford 0.050 g of the desired title product. 1H NMR (300 MHz, DMSO d6): δ 0.76-0.91 (m, 2H), 0.91-0.92 (m, 2H), 1.11 (s, 9H), 1.57 (m, 1H), 4.28 (br d, 2H), 7.31-7.34 (br d, 1H), 7.42 (br s, 1H), 7.47-7.50 (br m, 2H), 7.60 (d, J=8.4 Hz, 1H), 7.78 (d, J=8.4 Hz, 2H), 8.18 (s, 1H), 12.58 (s, 1H); MS (m/z): 449.52 (M+H)+.
Reaction SMILES: C(O[C:6]([NH:8][C:9]1[C:19]([N+:20]([O-:22])=[O:21])=[CH:18][CH:17]=[CH:16][C:10]=1[C:11]([O:13][CH2:14][CH3:15])=[O:12])=O)(C)(C)C.[H-].[Na+].[C:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[C:33]1[CH:40]=[CH:39][C:36](CBr)=[CH:35][CH:34]=1)#[N:26]>O1CCCC1.FC(F)(F)C(O)=O.C(Cl)Cl.[I-].[K+]>[C:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[C:33]1[CH:40]=[CH:39][C:36]([CH2:6][NH:8][C:9]2[C:19]([N+:20]([O-:22])=[O:21])=[CH:18][CH:17]=[CH:16][C:10]=2[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:35][CH:34]=1)#[N:26]
Reactant: CCOC(=O)c1cccc([N+](=O)[O-])c1NC(=O)OC(C)(C)C
Reactant: N#Cc1ccccc1-c1ccc(CBr)cc1
Agent: [H-]
Agent: [I-]
Agent: [K+]
Solvent: ClCCl
Solvent: C1CCOC1
Solvent: O=C(O)C(F)(F)F
Product: CCOC(=O)c1cccc([N+](=O)[O-])c1NCc1ccc(-c2ccccc2C#N)cc1
Yield: 85.4 %

Procedure:
To a solution of ethyl 2-t-butoxycarbonylamino-3-nitrobenzoate (20 g) in tetrahydrofuran (50 ml) was added, while stirring under ice-cooling, sodium hydride (60% dispersion in mineral oil, 2.8 g). The mixture was stirred at room temperature for 20 minutes and to the mixture were then added 4-(2-cyanophenyl)benzyl bromide (18 g) and potassium iodide (360 mg), followed by heating for 10 hours under reflux. The solvent was evaporated to dryness and the residue was partitioned between water (250 ml) and ether (200 ml). The organic layer was washed with water, dried and concentrated to give a yellow syrup. The syrup was dissolved in a mixture of trifluoroacetic acid (60 ml) and methylene chloride (40 ml) and the solution was stirred for one hour at room temperature. The reaction mixture was concentrated to dryness and to the residue was added ethyl ether (200 ml) to give crystals. The crystals were collected by filtration, washed with ether to give pale yellow crystals (22.1 g, 85%), m.p. 118°-119° C.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([NH2:8])[CH:5]=[CH:4][C:3]=1[CH3:9].[C:10](=[O:15])([O:12][CH2:13][CH3:14])N>C(O)C>[CH2:13]([O:12][C:10]([NH:1][C:2]1[CH:7]=[C:6]([NH:8][C:10]([O:12][CH2:13][CH3:14])=[O:15])[CH:5]=[CH:4][C:3]=1[CH3:9])=[O:15])[CH3:14]
Reactant: CCOC(N)=O
Reactant: Cc1ccc(N)cc1N
Solvent: CCO
Product: CCOC(=O)Nc1ccc(C)c(NC(=O)OCC)c1

Procedure:
275 g of a polyurea mixture based on 2,4-diamino-toluene having terminal amino tolyl groups (average molecular weight: 1500) were introduced into the apparatus described in Example 1. 513 g of 2,4-diamino-toluene, 933 g ethyl carbamate and 1250 g ethanol (approximately 96%) were subsequently added. The mixture was reacted for 6.0 hours at 200° C. After the apparatus had cooled and the pressure had been reduced, the reaction mixture was removed, filtered and analyzed by high pressure liquid chromatography (HPLC). A yield of 1100 g (68% of the theoretical yield) of 2,4-bis-(ethoxy carbonylamino)-toluene was obtained.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][NH2:5].C(N(CC)CC)C.[CH3:13][S:14](Cl)(=[O:16])=[O:15]>ClCCl>[CH3:1][O:2][CH2:3][CH2:4][NH:5][S:14]([CH3:13])(=[O:16])=[O:15]
Reactant: CS(=O)(=O)Cl
Reactant: COCCN
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COCCNS(C)(=O)=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirring solution of 2-methoxyethylamine (0.58 ml) in dichloromethane (10 ml) was added triethylamine (1.0 ml) and methanesulphonyl chloride (0.51 ml). The mixture was stirred at room temperature overnight. The solvents were removed in vacuo to give a crude product which was purified by flash chromatography to give N-(2-Methoxy-ethyl)-methanesulfonamide (0.74 g).
Reaction SMILES: [H-].[Na+].[CH2:3]([O:10][C:11]1[CH:19]=[C:18]2[C:14]([CH:15]=[CH:16][NH:17]2)=[CH:13][CH:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH2:20]1[O:23][CH:21]1[CH3:22].P([O-])(O)(O)=O.[K+]>C1COCC1.C(OCC)(=O)C>[CH2:3]([O:10][C:11]1[CH:19]=[C:18]2[C:14]([CH:15]=[CH:16][N:17]2[CH2:20][CH:21]([OH:23])[CH3:22])=[CH:13][CH:12]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: c1ccc(COc2ccc3cc[nH]c3c2)cc1
Reactant: CC1CO1
Agent: O=P([O-])(O)O
Agent: [H-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(O)Cn1ccc2ccc(OCc3ccccc3)cc21
Reaction time: 2 h

Procedure:
To a stirred, cooled (10° C.) suspension of sodium hydride (80.7 g of a 60% dispersion to in mineral oil, 2.02 mol) in anhydrous THF (1.9 L) was added a solution of 6-benzyloxyindole (375 g, 1.68 mol) in anhydrous THF (1.9 L) keeping the temperature below 25° C. After 2 h at 10° C., propylene oxide (140 mL, 2.0 mol) was added dropwise keeping the temperature below 25° C. After 48 h at 10° C., propylene oxide (71 mL, 1.0 mol) was added. After 96 h at 10° C., saturated aqueous potassium dihydrogenphosphate (3.8 L) and ethyl acetate (3.8 L) were carefully added, the layers were separated and the aqueous solution was extracted with 3.8 L of ethyl acetate. The combined organic extracts were dried over sodium sulfate and concentrated in vacuo to yield a solid (520 g, 110%, contains mineral oil).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[O:10][CH3:11].C(=O)([O-])[O-].[K+].[K+].Br[CH:19]([CH3:21])[CH3:20].O>CN(C=O)C>[CH:19]([O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[O:10][CH3:11])([CH3:21])[CH3:20]
Reactant: COc1cc(C=O)ccc1O
Reactant: CC(C)Br
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1cc(C=O)ccc1OC(C)C
Temperature: 65 °C
Reaction time: 2 h

Procedure:
A mixture of 4-hydroxy-3-methoxybenzaldehyde (100 g), potassium carbonate (182 g) and 2-bromopropane (81 ml) in DMF (500 ml) was stirred at 65° C. for 2 h. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with water and brine. The organic layer was dried (MgSO4), filtered and concentrated in vacuo.
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]([CH3:25])=[C:5]([C:21]([O:23][CH3:24])=[O:22])[CH:6]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[C:7]=1[C:8]([O:10]C)=[O:9].[OH-].[Na+]>CO.O>[CH3:24][O:23][C:21]([C:5]1[CH:6]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[C:7]([C:8]([OH:10])=[O:9])=[C:2]([CH3:1])[NH:3][C:4]=1[CH3:25])=[O:22]
Reactant: COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1c1cccc([N+](=O)[O-])c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: COC(=O)C1=C(C)NC(C)=C(C(=O)O)C1c1cccc([N+](=O)[O-])c1
Yield: 66.2 %

Procedure:
Dimethyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (17.3 g, 0.05 mole) is suspended in methanol (280 ml) and thereto a solution of NaOH (15.9 g, 0.4 mole) in water (52 ml) is added at room temperature under stirring. The reaction mixture is stirred at reflux temperature for 5 hours, cooled, water (1050 ml) is added under stirring and the resulting mixture is filtered. The precipitate is the unreacted starting compound, i.e. dimethyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate. To the clear filtrate activated carbon (1 g) is added and the mixture is stirred at 50°-60° C. for 30 minutes. After cooling the activated carbon is filtered off, the filtrate is acidified with 1 n HCl to pH 2.5 and the precipitate is filtered and washed with water (2×15 ml). Thus, there is obtained the pure title compound (11 g, 66%), m.p. 202°-206° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N+:14]([C:17]1[CH:24]=[CH:23][C:20]([CH2:21]Cl)=[CH:19][CH:18]=1)([O-:16])=[O:15].C(N(CC)CC)C>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:21][C:20]2[CH:23]=[CH:24][C:17]([N+:14]([O-:16])=[O:15])=[CH:18][CH:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: O=[N+]([O-])c1ccc(CCl)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCN(Cc2ccc([N+](=O)[O-])cc2)CC1
Temperature: 25 °C

Procedure:
10.6 g (57 mmol) of N-tert.butoxycarbonyl-piperazine are dissolved in 100 ml of dichloromethane and combined with 10.7 g (63 mmol) of 4-nitrobenzylchloride and 24 ml (171 mmol) of triethylamine. The mixture is refluxed for 12 hours. After cooling to ambient temperature the reaction solution is washed several times with water. The organic phase is dried over magnesium sulphate and then evaporated to dryness.
Reaction SMILES: [CH:1]1[C:13]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.C([Li])CCC.[CH2:19](Br)[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]>O1CCCC1.CCCCCC>[CH2:19]([CH:12]1[C:11]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[C:5]2[C:13]1=[CH:1][CH:2]=[CH:3][CH:4]=2)[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]
Reactant: CCCCCCBr
Reactant: c1ccc2c(c1)Cc1ccccc1-2
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CCCCCCC1c2ccccc2-c2ccccc21
Temperature: -78 °C
Reaction time: 1 h

Procedure:
In a 2 liter three-neck flask equipped with a stirrer and a thermometer, 100 g (0.6 mol) of fluorene was dissolved in 1 l of tetrahydrofuran and the flask was cooled sufficiently to −78° C. With an injector, 264 ml (1.32 mol) of 2.5M n-butyl lithium which was diluted in hexane was slowly added dropwise into the flask. When the addition of the same was finished, the above cooled temperature was maintained for thirty minutes, and then the flask was stirred at room temperature for one hour. Then again the resultant material was cooled down to −78° C. 88.44 ml (1.26 mol) of hexyl bromide was added into the flask using an injector. When the above procedure was finished, after keeping the temperature for thirty minutes, the flask was stirred at room temperature for 24 hours. When the reaction was finished, a small amount of cooled distilled water was poured to the resultant solution and the resultant solution was stirred for 2 to 3 minutes. When layers were separated, the organic layer was extracted using ether three times and it was washed by water several times. Then the resultant materials were dried using anhydrous magnesium sulfate and after removing the solvent, the resultant materials were purified with column, to obtain 132 g (88% t yield) of the entitled product as a pale yellowish viscous oil. 1H-NMR (CDCl3) δ 0.6-1.41 (m, 8H, CH2, 3H, CH3), 2.08-2.12 (m, 4H, CCH2), 4.07-4.18 (t, 1H, CH), 7.39-7.92 (m, 8H, Aromatic).
Reaction SMILES: C(O[C:5](=[O:7])[CH3:6])(=O)C.Br.[NH2:9][C:10]1[S:11][C:12]([Br:15])=[CH:13][N:14]=1.C(N(CC)CC)C.[OH-].[Na+]>ClCCl.O>[Br:15][C:12]1[S:11][C:10]([NH:9][C:5](=[O:7])[CH3:6])=[N:14][CH:13]=1
Reactant: Nc1ncc(Br)s1
Reactant: CC(=O)OC(C)=O
Agent: Br
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)Nc1ncc(Br)s1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
5.9 ml (42.3 mmol) of acetic anhydride are added to a solution of 10 g (38.5 mmol) of 2-amino-5-bromothiazole hydrobromide in 100 ml of dichloromethane and 11 ml (77 mmol) of triethylamine, cooled to 0° C. The reaction medium is stirred for 30 minutes at 0° C. and then for 18 hours at room temperature. After addition of water, the pH is adjusted to pH 8 with aqueous 1M sodium hydroxide solution and the reaction medium is extracted with dichloromethane. The dichloromethane phase is dried over magnesium sulfate, filtered and evaporated. The residue obtained is used in step b without purification.