Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@H:6]1[C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([CH2:31][C:32]2[S:33][C:34](Br)=[CH:35][CH:36]=2)[CH:25]=1)(=[O:3])[CH3:2].CC1(C)C(C)(C)OB([C:46]2[CH:52]=[CH:51][C:49]([NH2:50])=[CH:48][CH:47]=2)O1>>[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@H:6]1[C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([CH2:31][C:32]2[S:33][C:34]([C:46]3[CH:52]=[CH:51][C:49]([NH2:50])=[CH:48][CH:47]=3)=[CH:35][CH:36]=2)[CH:25]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)OC[C@H]1O[C@@H](c2ccc(Cl)c(Cc3ccc(Br)s3)c2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: CC1(C)OB(c2ccc(N)cc2)OC1(C)C
Product: CC(=O)OC[C@H]1O[C@@H](c2ccc(Cl)c(Cc3ccc(-c4ccc(N)cc4)s3)c2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O

Procedure:
1-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl)-3-(5-bromo-2-thienylmethyl)-4-chlorobenzene obtained in Example 128-(4) and 4-(4,4,5,5-tetramethyl-1,3-dioxaborolan-2-yl)aniline were treated in a manner similar to Example 168-(1) to give 1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-3-(5-(4-aminophenyl)-2-thienylmethyl)-4-chlorobenzene as pale yellow powder. APCI-Mass m/Z 630/632 (M+H). (2) The above 1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-3-(5-(4-aminophenyl)-2-thienylmethyl)-4-chlorobenzene was treated in a manner similar to Example 106-(3) to give the desired 1-(β-D-glucopyranosyl)-3-(5-(4-aminophenyl)-2-thienylmethyl)-4-chlorobenzene as pale yellow foam. APCI-Mass m/Z 479/481 (M+NH4).
Reaction SMILES: [I:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][CH2:7][CH2:8][NH:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])=[CH:4][CH:3]=1.[C:24]([O:28][CH2:29][CH3:30])(=[O:27])[CH:25]=[CH2:26]>C(O)C>[CH2:10]([N:9]([CH2:26][CH2:25][C:24]([O:28][CH2:29][CH3:30])=[O:27])[CH2:8][CH2:7][O:6][C:5]1[CH:22]=[CH:23][C:2]([I:1])=[CH:3][CH:4]=1)[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: CCCCCCCCCCCCNCCOc1ccc(I)cc1
Reactant: C=CC(=O)OCC
Solvent: CCO
Product: CCCCCCCCCCCCN(CCOc1ccc(I)cc1)CCC(=O)OCC
Yield: 85.9 %

Procedure:
A mixture of N-2-[4-iodophenoxy]ethyldodecylamine (1.0 g, 2.3 mmol), ethyl acrylate (1.2 g, 12 mmol) and ethanol (3 ml) was stirred and refluxed for 6 h, and then concentrated in vacuo . The residue was chromatographed on silica gel (hexane/ethyl acetate 8:1) to afford the title compound (1.05 g, 86%) as a colorless oil.
Reaction SMILES: [OH:1][CH2:2][C:3]([CH2:8][OH:9])([CH2:6][OH:7])[CH2:4][OH:5].[P:10](Cl)(Cl)(Cl)=[O:11]>CC(C1C=CC(OP(OC2C=CC=CC=2)(OC2C=CC=CC=2)=O)=CC=1)C.CC(C1C=CC=C(OP(OC2C=CC=CC=2)(OC2C=CC=CC=2)=O)C=1)C.CC(C1C(OP(OC2C=CC=CC=2)(OC2C=CC=CC=2)=O)=CC=CC=1)C>[CH2:4]1[O:5][P:10]2([O:7][CH2:6][C:3]1([CH2:8][OH:9])[CH2:2][O:1]2)=[O:11]
Reactant: OCC(CO)(CO)CO
Reactant: O=P(Cl)(Cl)Cl
Agent: CC(C)c1ccc(OP(=O)(Oc2ccccc2)Oc2ccccc2)cc1
Agent: CC(C)c1cccc(OP(=O)(Oc2ccccc2)Oc2ccccc2)c1
Agent: CC(C)c1ccccc1OP(=O)(Oc1ccccc1)Oc1ccccc1
Product: O=P12OCC(CO)(CO1)CO2
Temperature: 100 °C
Yield: 75 %

Procedure:
In a 250 mL four-necked reaction flask fitted with a mechanical stirrer, pot thermometer, addition funnel, and condenser with gas outlet were placed 42.5 g (0.313 mole) of pentaerythritol and 150 mL of PHOSFLEX 41P brand of isopropylated triphenyl phosphate under nitrogen. The mixture was stirred and heated at 95° C. as 49.2 g (0.321 mole) of phosphorus oxychloride was added dropwise over five hours. The resulting white slurry was heated to 100° C. with a nitrogen gas sparge for eight hours to remove HCl. The mixture was cooled to 50° C. and filtered. The solid was washed three times with 40 mL of hexane and dried at 100° C./2 mm Hg for sixteen hours to give 42.3 g (71.2% yield) of crude pentaerythritol phosphate alcohol (2,6,7-trioxa- 1-phosphabicyclo [2.2.2]octane-4-methanol-1-oxide). The product had a 31P NMR resonance at -6.0 ppm in d6 -DMSO.
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].Cl[C:10]([O:12][CH2:13][CH3:14])=[O:11].Cl>N1C=CC=CC=1>[Cl:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH:4][C:10](=[O:11])[O:12][CH2:13][CH3:14]
Reactant: Nc1ccccc1Cl
Reactant: CCOC(=O)Cl
Agent: Cl
Solvent: c1ccncc1
Product: CCOC(=O)Nc1ccccc1Cl
Reaction time: 1 h
Yield: 98 %

Procedure:
2-Chloroaniline (1.4463 g) was dissolved in pyridine (10 ml), and to the solution was added dropwise ethyl chloroformate (1.30 ml) under ice-cooling. After the mixture was stirred for 1 hour, 1N hydrochloric acid was added and the mixture was extracted with ethyl acetate. The organic layer was washed with 1N hydrochloric acid, and then saturated brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo to give the title compound (2.2203 g, 98%).
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.CC(N=NC(C#N)(C)C)(C#N)C.[Cl:21][C:22]1[C:23]([C:32]2[N:37]3[N:38]=[CH:39][N:40]=[C:36]3[N:35]=[C:34]([CH3:41])[CH:33]=2)=[N:24][CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1.O>C(Cl)(Cl)(Cl)Cl>[Br:1][CH2:41][C:34]1[CH:33]=[C:32]([C:23]2[C:22]([Cl:21])=[CH:27][C:26]([C:28]([F:29])([F:31])[F:30])=[CH:25][N:24]=2)[N:37]2[N:38]=[CH:39][N:40]=[C:36]2[N:35]=1
Reactant: Cc1cc(-c2ncc(C(F)(F)F)cc2Cl)n2ncnc2n1
Reactant: O=C1CCC(=O)N1Br
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: O
Solvent: ClC(Cl)(Cl)Cl
Product: FC(F)(F)c1cnc(-c2cc(CBr)nc3ncnn23)c(Cl)c1
Reaction time: 8 h
Yield: 13.7 %

Procedure:
312 mg of N-bromosuccinimide and 13 mg of azobisisobutylonitrile (AIBN) were added to a solution having 500 mg of 7-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine dissolved in 3 mL of carbon tetrachloride, followed by stirring overnight under reflux with heating. After completion of the reaction, water was added to the reaction liquid, followed by extraction with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=7/3) to obtain 86 mg of the desired product.
Reaction SMILES: [P:1]([O-:6])([O:4][CH3:5])[O:2][CH3:3].[CH3:7][C:8]1[CH:15]=[CH:14][C:11]([CH:12]=[O:13])=[CH:10][CH:9]=1.Cl>>[OH:13][C@@H:12]([P:1](=[O:6])([O:4][CH3:5])[O:2][CH3:3])[C:11]1[CH:14]=[CH:15][C:8]([CH3:7])=[CH:9][CH:10]=1
Reactant: COP([O-])OC
Reactant: Cc1ccc(C=O)cc1
Agent: Cl
Product: COP(=O)(OC)[C@H](O)c1ccc(C)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 82 %

Procedure:
The solution of ALB in tetrahydrofuran (0.1M, 0.40 ml) obtained in Example 1 was concentrated at room temperature for 1 hour under reduced pressure, then 0.4 ml of toluene was added thereto under an argon atmosphere. To this solution was added dimethyl phosphite (37 μl, 0.40 mmol) at room temperature. After stirring at room temperature for 30 minutes, the reaction vessel was cooled to -40° C., and it was maintained at this temperature for 15 minutes. Then p-methylbenzaldehyde (0.40 mmol) was added thereto. After reacting for 92 hours, 1N hydrochloric acid was added thereto to stop the reaction. The mixture was extracted with ethyl acetate (10 ml×three times), and the combined extracts were washed with brine and dried over Na2SO4. The solvent was distilled, and the residue was purified by flash column chromatography (acetone/hexane=1/5, on SiO2) to obtain dimethyl (S)-hydroxy(p-methylphenyl)methylphosphonate as a final product in a yield of 82%. The chemical reaction in this Example is shown in chemical formula 29.
Reaction SMILES: [Br:1][C:2]1[CH:15]=[C:14]2[C:5]([O:6][C:7]3[C:8]([F:19])=[CH:9][C:10]([O:17][CH3:18])=[CH:11][C:12]=3[C:13]2=[O:16])=[CH:4][CH:3]=1.[CH3:20][Mg]Cl>C1COCC1>[Br:1][C:2]1[CH:15]=[C:14]2[C:5]([O:6][C:7]3[C:8]([F:19])=[CH:9][C:10]([O:17][CH3:18])=[CH:11][C:12]=3[C:13]2([CH3:20])[OH:16])=[CH:4][CH:3]=1
Reactant: COc1cc(F)c2oc3ccc(Br)cc3c(=O)c2c1
Reactant: C[Mg]Cl
Solvent: C1CCOC1
Product: COc1cc(F)c2c(c1)C(C)(O)c1cc(Br)ccc1O2
Temperature: -30 °C

Procedure:
7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-one (22 g, 68.1 mmol) was dissolved in 300 ml of THF and cooled to −30° C. in a dry ice ACN bath. Methylmagnesium chloride (34.0 mL, 102 mmol) (3M in THF) was added to the slurry maintaining temperature less than −15° C. The solution was allowed to warm to RT (undissolved solids went into solution), then quenched with saturated NH4Cl (250 mL). The aqueous layer was extracted with EtOAc (3×200 mL) and the combined organic layers were washed with brine and dried over anhydrous sodium sulfate, filtered and concentrated to afford 7-bromo-4-fluoro-2-methoxy-9-methyl-9H-xanthen-9-ol as a brown liquid that was used without further purification.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[N:9])=[CH:4][N:3]=1.[CH2:10]([O:12][C:13](=[O:18])[C:14](=O)[CH2:15]Br)[CH3:11].C(=O)([O-])O.[Na+]>C(O)C.Cl.CO>[CH2:10]([O:12][C:13]([C:14]1[N:1]=[C:2]2[CH:7]=[CH:6][C:5]([C:8]#[N:9])=[CH:4][N:3]2[CH:15]=1)=[O:18])[CH3:11]
Reactant: N#Cc1ccc(N)nc1
Reactant: CCOC(=O)C(=O)CBr
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: CO
Product: CCOC(=O)c1cn2cc(C#N)ccc2n1
Yield: 88.5 %

Procedure:
In ethanol (30 ml), 2-amino-5-cyanopyridine (2.45 g) was dissolved. The solution was added with 3-bromo-2-oxo-propionic acid ethyl ester (3.90 g) and the whole was refluxed under heating for 7 hours. The concentrated residue was dissolved in a minimum amount of a 10% hydrogen chloride/methanol solution and the solution was adjusted to pH 8 with a saturated aqueous sodium hydrogen carbonate solution. The precipitate was collected by filtration, thereby obtaining the subject compound (3.81 g) as a pale-yellow solid.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH:10]1[CH2:14][CH:13]([S:15][C:16]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:12][NH:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1C.Cl[S:43]([OH:46])(=[O:45])=[O:44]>ClCCl>[CH2:1]([O:8][CH2:9][C@@H:10]1[CH2:14][C@@H:13]([S:15][C:16]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:12][N:11]1[S:43]([OH:46])(=[O:45])=[O:44])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=S(=O)(O)Cl
Reactant: c1ccc(COCC2CC(SC(c3ccccc3)(c3ccccc3)c3ccccc3)CN2)cc1
Solvent: Cc1ccccn1
Solvent: ClCCl
Product: O=S(=O)(O)N1C[C@H](SC(c2ccccc2)(c2ccccc2)c2ccccc2)C[C@H]1COCc1ccccc1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
A solution of 2-benzyloxymethyl-4-tritylsulfanyl-pyrrolidine (0.435 g) in dichloromethane (30.0 ml) was treated with 2-picoline (2.11 ml) and chlorosulphonic acid (0.186 ml). The reaction mixture was stirred for 5 h at room temperature and evaporated to dryness. The residue was quenched with ice/water and extracted with EtOAc. The aqueous layer was saturated with sodium chloride and acidified with 1 molar HCl to pH 3.4 and extracted again with EtOAc. The organic phase was washed with brine, dried over magnesium sulphate and concentrated to obtain (2S,4R)-2-benzyloxymethyl-4-tritylsulfanyl-pyrrolidine-1-sulfonic acid (0.26 g) as an oil, MS: 544 (M−H)−.
Reaction SMILES: [CH2:1]([O:3][CH2:4][CH2:5][N:6]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:15]=[CH:16][C:17]3[N:23]([CH:24]=[O:25])[CH2:22][CH2:21][C:20]([C:26]([OH:28])=O)=[CH:19][C:18]=3[CH:29]=2)=[CH:10][CH:9]=1)[CH3:7])[CH3:2].S(Cl)(Cl)=O.[CH3:34][N:35]([CH:37]=O)[CH3:36]>>[CH2:1]([O:3][CH2:4][CH2:5][N:6]([C:8]1[CH:9]=[CH:10][C:11]([C:14]2[CH:15]=[CH:16][C:17]3[N:23]([CH:24]=[O:25])[CH2:22][CH2:21][C:20]([C:26]([NH:6][C:8]4[CH:13]=[CH:12][C:11]([CH2:37][N:35]([CH3:34])[CH:36]5[CH2:5][CH2:4][O:3][CH2:1][CH2:2]5)=[CH:10][CH:9]=4)=[O:28])=[CH:19][C:18]=3[CH:29]=2)=[CH:12][CH:13]=1)[CH3:7])[CH3:2]
Reactant: CCOCCN(C)c1ccc(-c2ccc3c(c2)C=C(C(=O)O)CCN3C=O)cc1
Reactant: CN(C)C=O
Solvent: O=S(Cl)Cl
Product: CCOCCN(C)c1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(CN(C)C4CCOCC4)cc2)CCN3C=O)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
In DMF (3.5 ml) was dissolved 7-[4-[N-(2-ethoxyethyl)-N-methylamino]phenyl]-1-formyl-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (0.17 g). To the solution was added, under ice-cooling, thionyl chloride (0.08 ml), and the mixture was stirred at room temperature for 30 minutes. Under reduced pressure, the solvent was evaporated, and the residue was dissolved in THF (25 ml). The solution was added dropwise to a solution of 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline (0.11 g) and triethylamine (0.31 ml) in THF (6.5 ml), under ice-cooling, and the mixture was stirred under nitrogen atmosphere at room temperature for 1 hour, poured into water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried with anhydrous magnesium sulfate, and the solvent was evaporated. The residue was purified with silica gel column chromatography (ethyl acetate/ethanol) to give crude crystals, which were recrystallized from ethanol to give 7-[4-[N-(2-ethoxyethyl)-N-methylamino]phenyl]-1-formyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 4) (0.14 g) as pale yellow crystals.
Reaction SMILES: [F:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][NH:7][C:8]([C:10]2O[CH:12]=[C:13]([C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])[C:14](=[O:24])[C:15]=2[O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:9])=[CH:4][CH:3]=1.C(O)C.[CH3:36][O:37][CH:38]([O:41][CH3:42])[CH2:39][NH2:40]>O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:40]([CH2:39][CH:38]([O:41][CH3:42])[O:37][CH3:36])[CH:12]=[C:13]([C:25](=[O:30])[C:26]([CH3:27])([CH3:28])[CH3:29])[C:14](=[O:24])[C:15]=2[O:16][CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)=[O:9])=[CH:31][CH:32]=1
Reactant: COC(CN)OC
Reactant: CC(C)(C)C(=O)c1coc(C(=O)NCc2ccc(F)cc2)c(OCc2ccccc2)c1=O
Solvent: CCO
Solvent: C1CCOC1
Product: COC(Cn1cc(C(=O)C(C)(C)C)c(=O)c(OCc2ccccc2)c1C(=O)NCc1ccc(F)cc1)OC
Temperature: 70 °C
Reaction time: 72 h

Procedure:
To a solution of 3-benzyloxy-5-(2,2-dimethylpropionyl)-4-oxo-4H-pyran-2-carboxylic acid 4-fluorobenzylamide (0.13 g) in tetrahydrofuran (0.5 ml)-ethanol (0.5 ml) was added aminoacetaldehyde dimethyl acetal (0.033 ml) and the mixture was stirred at 70° C. for 3 days. After cooling to room temperature, the solvent was evaporated to give 3-benzyloxy-1-(2,2-dimethoxyethyl)-5-(2,2-dimethylpropionyl)-4-oxo-1,4-dihydropyridine-2-carboxylic acid 4-fluorobenzylamide (157 mg).
Reaction SMILES: [BH4-].[Na+].[OH-].[Na+].O.[CH3:6][CH:7]([C:11](=[O:16])[CH2:12][CH:13]([CH3:15])[CH3:14])[C:8](=[O:10])[CH3:9]>CO>[CH3:6][CH:7]([CH:11]([OH:16])[CH2:12][CH:13]([CH3:15])[CH3:14])[CH:8]([OH:10])[CH3:9]
Reactant: CC(=O)C(C)C(=O)CC(C)C
Agent: [BH4-]
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CC(C)CC(O)C(C)C(C)O
Yield: 90 %

Procedure:
To the mixture of 2.5 g sodium borohydride, 0.05 g sodium hydroxide, and 25 ml water was added dropwise the mixture of 14.2 g 3,6-dimethyl-2,4-heptandione and 30 ml methanol at 0-10° C. Upon completing the addition, the solvent was removed by reduced pressure distillation. The reaction mixture was continuously extracted with 40 ml ethyl acetate for 15 hours. The solvent was removed. Distillation under reduced pressure gave colorless liquid 3,6-dimethyl-2,4-heptanediol, and the yield was 90%. IR spectrum had a strong absorption peak at 3400 cm−1, and had no absorption peak at about 1700 cm−1. This demonstrated that the reduction reaction was carried out completely.
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:6](=[C:7]([OH:12])[CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH:3]=1.[CH3:13][O:14][CH:15]([O:18][CH3:19])[CH2:16]Cl>CC(N(C)C)=O>[CH3:13][O:14][CH:15]([O:18][CH3:19])[CH2:16][O:1][C:2]1[C:11]2[C:6](=[C:7]([O:12][CH2:16][CH:15]([O:18][CH3:19])[O:14][CH3:13])[CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH:3]=1
Reactant: COC(CCl)OC
Reactant: Oc1cccc2c(O)cccc12
Solvent: CC(=O)N(C)C
Product: COC(COc1cccc2c(OCC(OC)OC)cccc12)OC
Temperature: 80 °C
Reaction time: 3 h
Yield: 52.9 %

Procedure:
72 g (0.45 mol) 1,5-dihydroxynaphthalene are dissolved in 400 ml DMAc while heating in a three-necked flask fitted with a dropping funnel, internal thermometer, column and distillation cap. Then, at an internal temperature of 110-130° C., 178 g (1.1 mol) of a 30% solution of sodium methanolate in methanol are added dropwise and the resulting methanol is distilled off continuously via the column. When all the methanol has been transferred, 136 g (1.1 mol) chloracetaldehyde dimethylacetal is added in one portion, and the reaction is allowed to continue for approximately 3 hours at 130° C. Following this, the reaction mixture is cooled to 80° C., filtered while still warm, and the filtrate is poured onto 1000 g iced water to which 15 g NaOH have been added. The precipitate is filtered off, washed thoroughly with water and then dried under vacuum at 60° C. A yield of 80 g (53%) 1,5-bis-(2,2′-dimethoxyethoxy)naphthalene is obtained. Melting point: 117° C.; IR (KBr): 1273 cm−1 (ether); MS: m/e=336 (M+), 304, 273, 241, 215, 197, 185, 171, 160, 115, 89, 75, 59, 43.
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].[CH3:11][O:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[CH:19]=[C:18](B(O)O)[CH:17]=[CH:16]2.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>C1(C)C=CC=CC=1.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>[CH3:11][O:12][C:13]1[CH:22]=[CH:21][C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=3[N+:8]([O-:10])=[O:9])[CH:19]=2)[CH:14]=1
Reactant: COc1ccc2cc(B(O)O)ccc2c1
Reactant: O=[N+]([O-])c1ccccc1I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: COc1ccc2cc(-c3ccccc3[N+](=O)[O-])ccc2c1
Temperature: 110 °C
Reaction time: 7 h
Yield: 42.8 %

Procedure:
To a suspension of 2-iodo-1-nitrobenzene (2.5 g), (6-methoxynaphthalen-2-yl)boronic acid (2.9 g) and tetrakis(triphenylphosphine)palladium(0) (600 mg) in toluene (50 ml) was added an aqueous solution of 2N sodium carbonate (15 ml) under a nitrogen atmosphere, and the solution was stirred for 7 hours at 110° C. Ethyl acetate was added thereto, the solution was filtered through celite pad, extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, and then the solvent was evaporated in vacuo. The residue was purified by silica gel column chromatography (hexane-ethyl acetate system) to provide the title compound (1.2 g).
Reaction SMILES: [CH2:1]([C:5]1([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:9][CH2:8][CH2:7][CH:6]1[OH:10])[CH2:2][CH2:3][CH3:4].N1C=CC=CC=1.[C:22](Cl)(=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C(Cl)Cl>[CH2:1]([C:5]1([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:9][CH2:8][CH2:7][CH:6]1[O:10][C:22](=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:2][CH2:3][CH3:4]
Reactant: O=C(Cl)c1ccccc1
Reactant: CCCCC1(C(=O)OCC)CCCC1O
Solvent: ClCCl
Solvent: c1ccncc1
Product: CCCCC1(C(=O)OCC)CCCC1OC(=O)c1ccccc1
Reaction time: 12 h
Yield: 93.7 %

Procedure:
10.7 grams of ethyl 1-n-butyl-2-hydroxy-cyclopentane carboxylate obtained in Example 16 were diluted with 60 ml of methylene chloride. At room temperature and with magnetic stirring, 6.108 ml of pyridine was slowly added, then 8.876 ml of benzoyl chloride was dropwise added. Upon the completion of the addition, the reaction was continued for 12 hours. Then the procedure as described in Example 23 was followed, to give 19.06 g of brown liquid. The brown liquid was purified through column chromatography to give a liquid with a purity, measured by GC, of 96.03%. Yield: 93.7%. MS: 318(M+), 273(M+—OCH2CH3), 261(M+−CH2CH2CH2CH3), 245(M+—CO2CH2CH3), 213, 197(M+—C6H5CO2), 105(base), 77.
Reaction SMILES: [NH2:1][C:2]1[C:15]2[C:6](=[CH:7][C:8]3[C:9]4[C:14]=2[C:13](=[O:16])[N:12]([CH2:17][CH2:18][N:19]([CH3:21])[CH3:20])[C:11](=[O:22])[C:10]=4[CH:23]=[CH:24][CH:25]=3)[CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.Cl[C:34]([O:36][CH2:37][CH2:38][CH2:39][CH3:40])=[O:35]>ClCCl>[CH3:21][N:19]([CH3:20])[CH2:18][CH2:17][N:12]1[C:11](=[O:22])[C:10]2[CH:23]=[CH:24][CH:25]=[C:8]3[C:9]=2[C:14](=[C:15]2[C:2]([NH:1][C:34](=[O:35])[O:36][CH2:37][CH2:38][CH2:39][CH3:40])=[CH:3][CH:4]=[CH:5][C:6]2=[CH:7]3)[C:13]1=[O:16]
Reactant: CN(C)CCN1C(=O)c2cccc3cc4cccc(N)c4c(c23)C1=O
Reactant: CCCCOC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCOC(=O)Nc1cccc2cc3cccc4c3c(c12)C(=O)N(CCN(C)C)C4=O
Temperature: 25 °C

Procedure:
100 mg of 11-amino-2-[2-(dimethylamino)ethyl]-1H-dibenzo[de,h]isoquinoline-1,3(2H)-dione (obtained in example 3) (0.30 mmole) were dissolved in 6 ml of dichloromethane. 85 μl (2 molar equivalents) of triethylamine and 77 μl (2 molar equivalents) of butyl chloroformate were respectively added. The reaction mixture was maintained at room temperature for 3 hours. The solvent was then evaporated under reduced pressure and the residue was submitted to a flash chromatography (SiO2, CH2Cl2/MeOH 95/5). 119 mg of the desired product the desired product (formula shown hereinabove) were isolated as an orange powder (yield=83%) which was characterized as follows:
Reaction SMILES: [CH2:1]([CH2:3][NH2:4])[OH:2].COC1C=CC(O)=CC=1.[C:14](Cl)(=[O:18])[C:15]([CH3:17])=[CH2:16]>C(#N)C>[OH:2][CH2:1][CH2:3][NH:4][C:14](=[O:18])[C:15]([CH3:17])=[CH2:16]
Reactant: NCCO
Reactant: C=C(C)C(=O)Cl
Agent: COc1ccc(O)cc1
Solvent: CC#N
Product: C=C(C)C(=O)NCCO
Reaction time: 1 h

Procedure:
To a 500 mL, four-neck round bottom flask equipped with a mechanical stirrer, a thermometer, a 200 mL dropping funnel, and a nitrogen inlet/outlet, 48.8 g of ethanolamine (0.8 moles), 80 mg of 4-methoxyphenol and 100 mL of acetonitrile were added. The mixture was cooled below 0° C. with an ice/water salt bath. To this solution, 41.8 g of freshly distilled methacryloyl chloride (0.4 mole) in 100 mL of acetonitrile was added through the dropping funnel. The addition rate was controlled so that the reaction temperature was kept below 0° C. At the end of addition, the pH of the reaction mixture was adjusted to 7 with either methacryloyl chloride or ethanolamine solution. While keeping the reaction solution cold (below 5° C.), the ethanolamine HCl salts were filtered out. To the filtrate, 200 mL of deionized water and 40 g of Dowex MR-3C resin, which was pre-washed with two bed volumes of 1/1 ratio acetonitrile/water mixture for three times, were added. The resin was removed by filtration after agitating for one hour. The filtrate was concentrated to about 160 g by vacuum distillation. The final solution has the following properties: HPLC and FT-IR analysis indicates there is no ester formation; HEMAA concentration: 23.5% (wt/wt); pH=6.9 at 250° C.; Conductivity=3.9 μS/cm at 25° C.; Viscosity=1.9 cPs at 25° C. The yield of HEMAA was about 73%.
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([O:10][CH2:11][CH3:12])[N:5]=[C:4]([C:13]([NH:15][CH2:16][C:17]2([O:23][CH3:24])[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)=[O:14])[CH:3]=1.[N:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:31]1[S:32][C:33]([CH:36]=O)=[CH:34][N:35]=1>>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([O:10][CH2:11][CH3:12])[N:5]=[C:4]([C:13]([NH:15][CH2:16][C:17]2([O:23][CH3:24])[CH2:18][CH2:19][N:20]([CH2:36][C:33]3[S:32][C:31]([C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][N:25]=4)=[N:35][CH:34]=3)[CH2:21][CH2:22]2)=[O:14])[CH:3]=1
Reactant: CCOc1nc(C(=O)NCC2(OC)CCNCC2)cc(N)c1C#N
Reactant: O=Cc1cnc(-c2ccccn2)s1
Product: CCOc1nc(C(=O)NCC2(OC)CCN(Cc3cnc(-c4ccccn4)s3)CC2)cc(N)c1C#N

Procedure:
According to the same procedure described in Example 101, starting with the compound prepared in Example 260 instead of the compound prepared in Example 226 and the compound prepared in Example 139 instead of 2-phenylthiazole-5-carbaldehyde, the title compound having the following physical data was obtained.