Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].FC(F)(F)S(O[C:27]1[CH:36]=[CH:35][C:34]2[C:29](=[CH:30][CH:31]=[C:32]([O:37][CH3:38])[CH:33]=2)[C:28]=1[CH2:39][CH:40]=[CH2:41])(=O)=O.O>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:38][O:37][C:32]1[CH:33]=[C:34]2[C:29](=[CH:30][CH:31]=1)[C:28]([CH2:39][CH:40]=[CH2:41])=[C:27]([C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)[CH:36]=[CH:35]2
Reactant: C=CCc1c(OS(=O)(=O)C(F)(F)F)ccc2cc(OC)ccc12
Reactant: COc1ccc(B(O)O)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: C=CCc1c(-c2ccc(OC)cc2)ccc2cc(OC)ccc12
Yield: 74.7 %

Procedure:
4-Methoxyphenylboronic acid (10.15 g, 66.8 mmol), tripotassium phosphate hydrate (77.6 g, 278.3 mmol) and tetrakis(triphenylphosphine)palladium(0)(1.93 g, 1.67 mmol, 3 mol %) were added to a solution of 6-methoxy-1-(2-propenyl)-2-naphthyl trifluoromethanesulfonate (19.3 g, 55.66 mmol) in dioxane (300 ml), followed by heating under reflux for 8 hours under argon atmosphere. Water was added to the reaction mixture, which was then extracted with ethyl acetate, washed with saturated aqueous sodium chloride, and dried over anhydrous sodium sulfate. After distilling off the solvent, the residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/9), followed by recrystallization from hexane, to give 6-methoxy-2-(4-methoxyphenyl)-1-(2-propenyl)naphthalene (12.65 g, Yield 75%).
Reaction SMILES: [C:1]1(=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:7]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[NH2:8]>CO>[C:1]1(=[N:8][NH:7][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C1CCCC1
Reactant: CC(C)(C)OC(=O)NN
Solvent: CO
Product: CC(C)(C)OC(=O)NN=C1CCCC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of cyclopentanone (4.0 g, 47.5 mmol) and tert-butyl hydrazinecarboxylate (6.28 g, 47.5 mmol) in MeOH (100 mL) is stirred at rt for 2 hr. The solvent is removed in vacuo to yield the title compound as a white solid, which is used in the next step without further purification. MS (M+1): 199.1.
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:26][CH:27]1[CH2:35][CH2:34][C:33]2[N:29]([C:30]3[N:49]=[CH:48][N:47]=[C:46]([NH2:50])[C:31]=3[C:32]=2[C:36]2[CH:37]=[N:38][C:39]3[C:44]([CH:45]=2)=[CH:43][CH:42]=[CH:41][CH:40]=3)[CH2:28]1)(C(C)(C)C)(C)C>C1COCC1>[NH2:50][C:46]1[C:31]2[C:32]([C:36]3[CH:37]=[N:38][C:39]4[C:44]([CH:45]=3)=[CH:43][CH:42]=[CH:41][CH:40]=4)=[C:33]3[N:29]([C:30]=2[N:49]=[CH:48][N:47]=1)[CH2:28][CH:27]([OH:26])[CH2:35][CH2:34]3
Reactant: CC(C)(C)[Si](C)(C)OC1CCc2c(-c3cnc4ccccc4c3)c3c(N)ncnc3n2C1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: Nc1ncnc2c1c(-c1cnc3ccccc3c1)c1n2CC(O)CC1
Reaction time: 1 h
Yield: 100.3 %

Procedure:
A solution of 1 M tetrabutylammonium fluoride in THF (2.09 ml) was added to a solution of 8-(tert-butyldimethylsilyloxy)-5-(quinolin-3-yl)-6,7,8,9-tetrahydropyrimido[5,4-b]indolizin-4-amine (778 mg) obtained in Step 7 in THF (20 ml) at room temperature. The mixture was stirred at the same temperature for 1 hour, and the solvent was distilled off under reduced pressure. The resulting residue was treated with a saturated aqueous ammonium chloride solution, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was then distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: chloroform/methanol) to obtain the title compound as a light-yellow solid (580 mg).
Reaction SMILES: [C:1]([OH:5])(=[O:4])[CH:2]=[CH2:3].[C:6]([NH2:10])(=[O:9])[CH:7]=[CH2:8].[C:11]([O:15][CH2:16][CH:17]([OH:19])[CH3:18])(=[O:14])[CH:12]=[CH2:13].S(OOS([O-])(=O)=O)([O-])(=O)=O.[NH4+].[NH4+].S([O-])(OCCCCCCCCCCCC)(=O)=O.[Na+:49].[OH-].[Na+]>CO.CC(C)=O>[C:1]([O-:5])(=[O:4])[CH:2]=[CH2:3].[Na+:49].[C:11]([O:15][CH2:16][CH:17]([OH:19])[CH3:18])(=[O:14])[CH:12]=[CH2:13].[C:6]([NH2:10])(=[O:9])[CH:7]=[CH2:8]
Reactant: C=CC(=O)O
Agent: C=CC(=O)OCC(C)O
Agent: C=CC(N)=O
Agent: CCCCCCCCCCCCOS(=O)(=O)[O-]
Solvent: CC(C)=O
Solvent: CO
Product: C=CC(=O)[O-]
Reaction time: 3 h

Procedure:
A terpolymer of sodium acrylate-2-hydroxypropyl acrylate and acrylamide was prepared utilizing an emulsion polymerization process. The mole ratios of acrylic acid to acrylamide, mole percent of 2-hydroxypropyl acrylate and molecular size were varied by controlling the reaction parameters. Six representative samples of the terpolymer were prepared with the compositions of the various terpolymers being estimated based upon their total nitrogen content. In the reaction, ammonium persulfate was utilized as the polymerization initiator or catalyst. Reagent grade acetone and reagent grade anhydrous methanol were utilized to form the solvent. The emulsifier was sodium lauryl sulfate, and 2 N aqueous sodium hydroxide was utilized to neutralize the reactants. The dried products were thereafter milled and passed through a number 30 mesh screen. The reaction was conducted over a period of three hours at a reaction temperature of about 60° C.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][N:3]=1.[OH:10][C:11]1[CH:16]=[C:15]([CH3:17])[C:14]([C:18](=[O:20])[CH3:19])=[C:13]([CH3:21])[CH:12]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CCOC(C)=O.[Cu]>[CH3:9][O:8][C:5]1[CH:4]=[N:3][C:2]([O:10][C:11]2[CH:12]=[C:13]([CH3:21])[C:14]([C:18](=[O:20])[CH3:19])=[C:15]([CH3:17])[CH:16]=2)=[N:7][CH:6]=1
Reactant: CC(=O)c1c(C)cc(O)cc1C
Reactant: COc1cnc(Cl)nc1
Agent: [Cu]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COc1cnc(Oc2cc(C)c(C(C)=O)c(C)c2)nc1
Temperature: 120 °C
Yield: 24 %

Procedure:
2-Chloro-5-methoxypyrimidine (8-1, 5.13 g, 35.6 mmol) and 1-(4-hydroxy-2,6-dimethylphenyl)ethanone (4-2, 6.10 g, 37.2 mmol) were suspended in DMF (80.0 ml) and added with copper powder (0.78 g, 7.8 mmol) and potassium carbonate (15.31 g, 0.11 mol). The reaction was heated at 120° C. for 16 h. The reaction was cooled to room temperature and diluted with EtOAc (90 mL). The organic phase was washed with 15% NaOH and water, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (40% EtOAc in hexanes as eluant) to give 1-{4-((5-methoxypyrimidin-2-yl)oxy)-2,6-dimethylphenyl}ethanone (8-2, 2.33 g) as light yellow solids in 24% yield: 1H NMR (500 MHz, DMSO-d6) δ 8.41 (s, 2 H), 6.86 (s, 2 H), 3.86 (s, 3 H), 2.47 (s, 3 H), 2.18 (s, 6 H).
Reaction SMILES: C(Br)[CH:2]=[CH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:11]([OH:20])(=[O:19])[C:12]1[C:13](=[CH:15][CH:16]=[CH:17][CH:18]=1)[SH:14]>C(O)C.[OH-].[Na+]>[CH:2]([S:14][C:13]1[CH:15]=[CH:16][CH:17]=[CH:18][C:12]=1[C:11]([OH:20])=[O:19])=[CH:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: BrCC=Cc1ccccc1
Reactant: O=C(O)c1ccccc1S
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)c1ccccc1SC=Cc1ccccc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 102.2 %

Procedure:
To a solution of 1.28 g (6.49 mmol) of cinnamyl bromide in 8 ml of ethanol at room temperature under an atmosphere of nitrogen was added a solution of 1 g (6.49 mmol) of thiosalicylic acid in 5.3 ml of 10% aqueous sodium hydroxide solution. The solution was stirred at room temperature for 16 hours and the solvent then removed under reduced pressure. The residue was dissolved in water and concentrated hydrochloric acid was added. The resultant solid was filtered off and dried. There was obtained 1.7 g of 2-styrylsulfanylbenzoic acid as a white solid, MS: m/e 270 M+.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12](C(OC(C)(C)C)=O)[CH:11]=[N:10][N:9]=2)=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:12]=[CH:11][NH:10][N:9]=2)=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)n1cnnc1-c1ccc(Br)cc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Brc1ccc(-c2nc[nH]n2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Into a 2000 mL 3-necked flask was placed a solution of tert-butyl 3-(4-bromophenyl)-4H-1,2,4-triazole-4-carboxylate (80.0 g, 247 mmol) in CH2Cl2 (800 mL). To the mixture was added TFA (400 mL). The resulting solution was stirred at room temperature for 1 h. The reaction was evaporated to provide 3-(4-bromophenyl)-1H-1,2,4-triazole as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:12]([NH:13][C:14](=[O:18])OCC)=[N:11][C:10]2[C:5](=[CH:6][C:7]([O:21][CH3:22])=[C:8]([O:19][CH3:20])[CH:9]=2)[N:4]=1.[CH3:23][C:24]1[CH:25]=[C:26]([N:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[CH:27]=[CH:28][CH:29]=1>>[CH3:1][O:2][C:3]1[C:12]([NH:13][C:14]([N:33]2[CH2:34][CH2:35][N:30]([C:26]3[CH:27]=[CH:28][CH:29]=[C:24]([CH3:23])[CH:25]=3)[CH2:31][CH2:32]2)=[O:18])=[N:11][C:10]2[C:5](=[CH:6][C:7]([O:21][CH3:22])=[C:8]([O:19][CH3:20])[CH:9]=2)[N:4]=1
Reactant: Cc1cccc(N2CCNCC2)c1
Reactant: CCOC(=O)Nc1nc2cc(OC)c(OC)cc2nc1OC
Product: COc1cc2nc(NC(=O)N3CCN(c4cccc(C)c4)CC3)c(OC)nc2cc1OC
Yield: 56 %

Procedure:
Ethyl N-(2,6,7-trimethoxyquinoxalin-3-yl)carbamate and 1-(3-methylphenyl) piperazine were reacted by the same way with the example 190 to obtain the titled compound (yield, 56%) H NMR (300 MHz, CDCl3) δ 2.34 (s, 3H), 3.25-3.30 (m, 4H), 3.76-3.80 (m, 4H), 3.98 (s, 3H), 4.02 (s, 3H), 4.16 (s, 3H), 6.74-6.78 (m, 3H), 7.14-7.26 (m, 4H).
Reaction SMILES: [CH:1](=[C:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C:9]1=[O:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(OC2C=CC=CC=2)C=CC=CC=1>[C].[Pd].C1(C)C=CC=CC=1>[CH2:1]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[OH:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1CCCCC1=Cc1ccccc1
Agent: [Pd]
Solvent: c1ccc(Oc2ccccc2)cc1
Solvent: Cc1ccccc1
Product: Oc1ccccc1Cc1ccccc1
Temperature: 245 °C
Reaction time: 8 h
Yield: 96.6 %

Procedure:
In a 100-ml, four-necked flask equipped with a magnetic stirrer, a reflux condenser and a thermometer were placed 18.6 g (0.1 mole) of the 2-benzylidenecyclohexanone produced in Example 1 and 40 ml of diphenyl ether in this order. The flask inside was purged with nitrogen. Thereto was added 1.9 g (10 wt. %, 0.89 mmole as palladium) of 5% palladium carbon (a product of Wako Pure Chemical Industries, Ltd.). The system was made vacuum using an aspirator and then was returned to ordinary pressure using nitrogen; this operation was repeated three times. Then, the system was stirred at 240 to 250° C. for 8 hours and cooled to room temperature. 50 ml of toluene was added to the system. Filtration was conducted to remove the palladium carbon. The filtrate was extracted with 50 ml of a 10% aqueous sodium hydroxide solution, and this operation was repeated twice. The aqueous layer was washed with 50 ml of toluene. To the resulting aqueous layer was added 35% hydrochloric acid until the aqueous layer became acidic, after which the aqueous layer was extracted with 50 ml of ethyl acetate twice. The ethyl acetate layer was washed with water and a saturated aqueous sodium chloride solution in this order. The ethyl acetate layer was dried over anhydrous sodium sulfate and then subjected to vacuum distillation to remove ethyl acetate, to obtain 17.8 g of an oil. Yield: 97% The purity of the intended product in the oil was 95% as measured by gas chromatography.
Reaction SMILES: [CH2:1]([Mg]Br)[CH3:2].[Br:5][C:6]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:7]=1[CH:8]=[O:9].O.Cl>C(OCC)C>[Br:5][C:6]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:7]=1[CH:8]([OH:9])[CH2:1][CH3:2]
Reactant: CC[Mg]Br
Reactant: O=Cc1ccc(F)cc1Br
Agent: Cl
Solvent: CCOCC
Solvent: O
Product: CCC(O)c1ccc(F)cc1Br
Temperature: 25 °C
Reaction time: 1 h
Yield: 95.7 %

Procedure:
Add ethylmagnesium bromide (1 M in ether, 8.37 mL, 8.37 mmol) at 0° C. under nitrogen to a solution of 2-bromo-4-fluorobenzaldehyde (1 g, 4.93 mmol) in diethyl ether (15 mL). Stir the mixture for 1 h at RT. Add water slowly followed by adjusting the mixture to acidic conditions with 2 M HCl. Extract the product with chloroform/IPA (3/1). Dry over sodium sulfate. Concentrate the solution in vacuo to a yellow oil. Purify by column chromatography (30% ethyl acetate in hexane) to give the title compound as a colorless oil (1.1 g, 96%). 1H NMR (400 MHz, CD3Cl) δ 0.99 (t, J=7.2 Hz, 3H), 1.75 (m, 2H), 4.99 (m, 1H), 7.03 (m, 1H), 7.25 (m, 1H), 7.53 (m, 1H).
Reaction SMILES: [O:1]1[C@H:5]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[C@@H:2]1[CH2:3][OH:4].COCCO[AlH2-]OCCOC.[Na+]>O1CCCC1>[OH:1][C@H:5]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH2:2][CH2:3][OH:4]
Reactant: CCCCCCCCCCC[C@H]1O[C@H]1CO
Agent: COCCO[AlH2-]OCCOC
Agent: [Na+]
Solvent: C1CCOC1
Product: CCCCCCCCCCC[C@@H](O)CCO
Temperature: 0 °C
Reaction time: 12 h
Yield: 87.9 %

Procedure:
To a solution of epoxide 8 (9.00 g, 40 mmol) in tetrahydrofuran (80 mL) at -20° C. was added a solution of Red-Al (40 mL, 3M) and the reaction temperature was slowly raised to 0° C. and subsequently to room temperature and stirred for 12 h. After completion of the reaction (TLC), the excess of Red-Al was quenched with methanol (10 mL) and poured in to a conical flask containing ethyl acetate (400 mL) and rochelle salt solution (100 mL) and stirred for 2 h until clear separation of two layers occurred. The organic layer was separated, dried and concentrated to give the diol 9 as a colorless solid (8.1 g, 89%). m.p. 59°-60° C.
Reaction SMILES: C(OC([N:8]1[CH2:17][C:16]2[CH:18]=[C:19]([Cl:22])[CH:20]=[CH:21][C:15]=2[N:14]2[C:10](=[N:11][N:12]=[C:13]2[Br:23])[CH2:9]1)=O)(C)(C)C.Cl>[OH-].[Na+]>[Br:23][C:13]1[N:14]2[C:10]([CH2:9][NH:8][CH2:17][C:16]3[CH:18]=[C:19]([Cl:22])[CH:20]=[CH:21][C:15]=32)=[N:11][N:12]=1
Reactant: CC(C)(C)OC(=O)N1Cc2cc(Cl)ccc2-n2c(Br)nnc2C1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: Clc1ccc2c(c1)CNCc1nnc(Br)n1-2
Yield: 83.5 %

Procedure:
A solution of 1-bromo-8-chloro-4H,6H-2,3,5,10b-tetraaza-benzoazulene-5-carboxylic acid tert-butyl ester (3.0 g, 7.6 mmol) in 1.25 M methanolic hydrogen chloride solution (60 ml, 76 mmol) was heated at 50° C. for 10 min. The reaction mixture was poured on 1 M aqueous sodium hydroxide solution (200 ml) and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give the title compound (1.9 g, 84%) as light yellow solid. MS m/e: 255 (M+H+).
Reaction SMILES: [NH2:1][CH:2]([C:6]1[N:7]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:8](=[O:16])[C:9]2[C:14]([CH3:15])=[N:13][S:12][C:10]=2[N:11]=1)[CH:3]([CH3:5])[CH3:4].Br[CH2:25][CH2:26][CH:27]1[O:31][CH2:30][CH2:29][O:28]1>CN(C=O)C.O>[CH2:17]([N:7]1[C:8](=[O:16])[C:9]2[C:14]([CH3:15])=[N:13][S:12][C:10]=2[N:11]=[C:6]1[CH:2]([NH:1][CH2:25][CH2:26][CH:27]1[O:31][CH2:30][CH2:29][O:28]1)[CH:3]([CH3:5])[CH3:4])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: Cc1nsc2nc(C(N)C(C)C)n(Cc3ccccc3)c(=O)c12
Reactant: BrCCC1OCCO1
Solvent: CN(C)C=O
Solvent: O
Product: Cc1nsc2nc(C(NCCC3OCCO3)C(C)C)n(Cc3ccccc3)c(=O)c12
Temperature: 70 °C
Yield: 95.6 %

Procedure:
To a solution of 6-(1-amino-2-methyl-propyl)-5-benzyl-3-methyl-5H-isothiazolo[5,4-d]pyrimidin-4-one (method 30) (1.6 g, 4.88 mmol) in anhydrous DMF (20 mL), 2-(2-bromo-ethyl)-[1,3]dioxolane (0.88 g, 4.88 mmol) was added and the resulting solution was heated at 70° C. for 2 h. The reaction mixture was cooled, diluted with water and extracted with EtOAc (3×60 mL). The combined organic extracts were dried (Na2SO4) and concentrated to provide the crude product (2 g), which was used as such in the next reaction. m/z 429 (MH+); 1H-NMR (300 MHz) δ 0.88 (d, 3H), 0.96 (d, 3H), 1.54-1.62 (m, 2H), 1.86-2.05 (m, 2H), 2.18 (bs, 1H), 2.38-2.46 (m, 1H), 2.84 (s, 3H), 3.57 (d, 1H), 3.74-3.94 (m, 4H), 4.78 (t, 1H), 4.99 (d, 1H), 5.85 (d, 1H), 7.15-7.38 (m, 5H).
Reaction SMILES: [CH2:1]([O:8][C:9]([C:11]1C(C2C=CC=C([N+]([O-])=O)C2=C=O)C(OCCOC)=C(C)[NH:15][C:16]=1[CH3:17])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C(O)C>[CH2:1]([O:8][C:9](=[O:10])/[CH:11]=[C:16](\[NH2:15])/[CH3:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COCCOC1=C(C)NC(C)=C(C(=O)OCc2ccccc2)C1C1C=CC=C([N+](=O)[O-])C1=C=O
Solvent: CCO
Product: C/C(N)=C/C(=O)OCc1ccccc1
Yield: 79 %

Procedure:
Analogously to Example 1 heating a solution of 75 mmols of 3'-nitrobenzylideneacetoacetic acid 2-methoxyethyl ester and 75 mmols of β-aminocrotonic acid benzyl ester in 120 ml of ethanol gave 2,6-dimethyl-3-(2-methoxyethyloxy)-carbonyl-4-(3'-nitrophenyl)-1,4-dihydropyridine-5-carboxylic acid benzyl ester of melting point 152° C (from ethanol).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[C:12]1([CH:18]([CH2:22][CH3:23])[C:19](O)=[O:20])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O>C(=O)(O)[O-].[Na+]>[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:19](=[O:20])[CH:18]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:22][CH3:23])=[CH:8][CH:7]=1
Reactant: CCC(C(=O)O)c1ccccc1
Reactant: ClCCCOc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Product: CCC(C(=O)c1ccc(OCCCCl)cc1)c1ccccc1
Reaction time: 16 h

Procedure:
3-Chloropropoxybenzene (8g, 47 mmol) was added to a stirred solution of 2-phenylbutyric acid (8.5 g, 52 mmol) in trifluoroacetic anhydride (7.5 ml, 52 mmol) and stirring continued for 16 h. The mixture was poured into saturated sodium bicarbonate solution (100 ml), neutralized by addition of sodium bicarbonate, and extracted with ethyl acetate (3×50 ml). The combined organic extracts were washed with water (2×50 ml), dried (MgSO4), and concentrated in vacuo. The residues were distilled to give the title compound as a white waxy solid (12.01 g, 81%) bp 200° C. at 0.1 mm Hg.
Reaction SMILES: [C:1]([C@@H:4]1[CH2:8][C@@H:7]([OH:9])[CH2:6][N:5]1[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])(=O)[NH2:2].FC(F)(F)C(OC(=O)C(F)(F)F)=O>N1C=CC=CC=1>[C:1]([C@@H:4]1[CH2:8][C@@H:7]([OH:9])[CH2:6][N:5]1[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])#[N:2]
Reactant: CC(C)(C)OC(=O)N1C[C@H](O)C[C@H]1C(N)=O
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Solvent: c1ccncc1
Product: CC(C)(C)OC(=O)N1C[C@H](O)C[C@H]1C#N
Temperature: -20 °C
Yield: 72.8 %

Procedure:
(2S,4R)-tert-Butyl 2-carbamoyl-4-hydroxypyrrolidine-1-carboxylate 13c (74 g, 0.3217 mol) was dissolved in 740 mL of pyridine with stirring under argon atmosphere. The mixture was cooled to −20° C. followed by dropwise addition of trifluoroacetic anhydride (169 g, 0.804 mol). Upon completion of the addition, the reaction mixture was warmed up to room temperature. The reaction was monitored by TLC until the disappearance of the starting materials. The mixture was quenched with water and diluted with 0.8 L of ethyl acetate. The separated organic phase was washed with 500 mL of saturated brine and neutralized with 400 mL of concentrated hydrochloric acid to slight acidity. The resulting mixture was washed with 300 mL of aqueous sodium hydroxide solution (2 M) and 500 mL saturated brine successively, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain the title compound (2S,4R)-tert-butyl 2-cyano-4-hydroxypyrrolidine-1-carboxylate 13d (49.7 g, yield 73%) as a brown oil.
Reaction SMILES: Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])[CH:9]=2)[N:4]([Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[CH:3]=1.IC.[C:28]([Li])(C)(C)C>>[C:22]([Si:19]([CH3:21])([CH3:20])[N:4]1[C:5]2[C:10](=[CH:9][C:8]([O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])=[CH:7][CH:6]=2)[C:2]([CH3:28])=[CH:3]1)([CH3:25])([CH3:24])[CH3:23]
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc2c(c1)c(Br)cn2[Si](C)(C)C(C)(C)C
Reactant: [Li]C(C)(C)C
Solvent: CI
Product: Cc1cn([Si](C)(C)C(C)(C)C)c2ccc(O[Si](C)(C)C(C)(C)C)cc12

Procedure:
In analogy to the procedure described in example 27 c], 3-bromo-1-(tert-butyl-dimethyl-silanyl)-5-(tert-butyl-dimethyl-silanyloxy)-1H-indole was reacted with 1-iodomethane in the presence of tert-butyllithium to give 1-(tert-butyl-dimethyl-silanyl)-5-(tert-butyl-dimethyl-silanyloxy)-3-methyl-1H-indole as brown viscous oil.
Reaction SMILES: [Na].[C:2]([O:6][C:7]([N:9]1[CH2:15][CH2:14][CH2:13][N:12]([C:16]2[NH:20][C:19]3[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=3[N:17]=2)[CH2:11][CH2:10]1)=[O:8])([CH3:5])([CH3:4])[CH3:3].[F:25][C:26]([F:37])([F:36])[CH2:27]OS(C(F)(F)F)(=O)=O>CN(C)C=O>[C:2]([O:6][C:7]([N:9]1[CH2:15][CH2:14][CH2:13][N:12]([C:16]2[N:17]([CH2:27][C:26]([F:37])([F:36])[F:25])[C:18]3[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=3[N:20]=2)[CH2:11][CH2:10]1)=[O:8])([CH3:5])([CH3:3])[CH3:4]
Reactant: O=S(=O)(OCC(F)(F)F)C(F)(F)F
Reactant: CC(C)(C)OC(=O)N1CCCN(c2nc3ccccc3[nH]2)CC1
Agent: [Na]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCCN(c2nc3ccccc3n2CC(F)(F)F)CC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Add to a suspension of sodium hydrdide (0.029 g, 1.21 mmol) in anhydrous dimethylformamide (5 mL) a suspension of 1-(t-butoxycarbonyl)-4-(1H-benzimidazol-2-yl)[1,4]diazepan (0.38 g, 1.2 mmol, Preparation 9) in anhydrous dimethylformamide (7 mL). Stir for 3 hours at room temperature and add a large excess of 1,1,1-trifluoro-methanesulfonic acid 2,2,2-trifluoro-ethyl ester. Stir overnight at room temperature, quench the reaction with water, wash the organic phase with water, dry (MgSO4), filter and concentrate in vacuo to afford 4-[1-(2,2,2-trifluoro-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepane-1-carboxylic acid tert-butyl ester. Repeat this preparation using 2.88 mmol of 1-(t-butoxycarbonyl)-4-(1H-benzimidazol-2-yl)[1,4]diazepan. Combine the product from both reactions and purify by column chromatography on silica gel eluting with 30% ethyl acetate in hexane and concentrate the appropriate fractions to afford 0.48 g of 4-[1-(2,2,2-trifluoro-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepane-1-carboxylic acid tert-butyl ester.
Reaction SMILES: [CH3:1][N:2]1[C:6]2[C:7](=[O:13])[CH2:8][NH:9][S:10](=[O:12])(=[O:11])[C:5]=2[CH:4]=[CH:3]1.[Br:14][CH2:15][CH2:16][CH2:17]Br.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[Br:14][CH2:15][CH2:16][CH2:17][N:9]1[CH2:8][C:7](=[O:13])[C:6]2[N:2]([CH3:1])[CH:3]=[CH:4][C:5]=2[S:10]1(=[O:12])=[O:11]
Reactant: Cn1ccc2c1C(=O)CNS2(=O)=O
Reactant: BrCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: Cn1ccc2c1C(=O)CN(CCCBr)S2(=O)=O
Yield: 34.1 %

Procedure:
A suspension of 500 mg (2.5 mmol) of Compound 13, 2.5 g (12.5 mmol) of 1,3-dibromopropane and 690 mg (5 mmol) of potassium carbonate in 25 ml of acetone was refluxed for 12 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column (eluent: ethyl acetate/methylene chloride=1/40), whereby 274 mg of the title compound were obtained (yield: 34%).
Reaction SMILES: [Cl:1][C:2]1[C:10]2[C:9]3[C:11]([Cl:17])=[C:12]([Cl:16])[C:13]([Cl:15])=[CH:14][C:8]=3[O:7][C:6]=2[C:5]([N+:18]([O-])=O)=[C:4]([Cl:21])[C:3]=1[Cl:22]>C(O)C>[Cl:1][C:2]1[C:10]2[C:9]3[C:11]([Cl:17])=[C:12]([Cl:16])[C:13]([Cl:15])=[CH:14][C:8]=3[O:7][C:6]=2[C:5]([NH2:18])=[C:4]([Cl:21])[C:3]=1[Cl:22]
Reactant: O=[N+]([O-])c1c(Cl)c(Cl)c(Cl)c2c1oc1cc(Cl)c(Cl)c(Cl)c12
Solvent: CCO
Product: Nc1c(Cl)c(Cl)c(Cl)c2c1oc1cc(Cl)c(Cl)c(Cl)c12

Procedure:
The corresponding amine was prepared by reducing 1,2,3,7,8,9-hexachloro-4-nitrodibenzofuran with 1.8 mmol of NaSH in 5 ml of ethanol. The resulting 1,2,3,7,8,9-hexachloro-4-aminodibenzofuran was isolated by extracting with five times 30 ml of diethyl ether. The resulting solution was washed twice with 10 ml of water and dried over magnesium sulfate. Subsequently, the amine was removed from the desiccant and isolated again.