Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][N:2]1[CH2:6][CH2:5][O:4][C:3]1=[O:7].O.Cl.[O:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13](=O)[CH2:12][CH2:11]1>C(O)C>[O:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13](=[N:1][N:2]2[CH2:6][CH2:5][O:4][C:3]2=[O:7])[CH2:12][CH2:11]1
Reactant: NN1CCOC1=O
Reactant: O=C1CCOc2ccccc21
Agent: Cl
Solvent: O
Solvent: CCO
Product: O=C1OCCN1N=C1CCOc2ccccc21

Procedure:
A 62-g (0.61 mole) portion of 3-amino-2-oxazolidinone was charged in a 500-ml, 3-necked flask equipped with a thermometer, stirrer and reflux condenser, and treated successively with 92 ml of H2O, 8 ml of 10% HCl and 42 g (0.28 mole) of 4-chromanone in 200 ml ethanol. The reaction mixture was refluxed for 36 hr, stripped in vacuo to one-half volume and cooled in the refrigerator overnight. The slurry was filtered and the white crystalline solid washed with 50 ml of isopropanol then 200 ml of ether and dried. M.p. 105°-108°. Yield: 44 g (68%).
Reaction SMILES: [CH3:1][O:2][CH2:3][CH:4]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([I:18])=[CH:15][CH:16]=2)[C:11](=[O:19])[C:10]([C:20](O)=[O:21])=[CH:9]1)[CH2:5][O:6][CH3:7].[CH3:23][N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1.OC1C2N=NNC=2C=CC=1.CN1CCOCC1.Cl.C(N=C=NCCCN(C)C)C>ClCCl>[CH3:7][O:6][CH2:5][CH:4]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([I:18])=[CH:15][CH:16]=2)[C:11](=[O:19])[C:10]([C:20]([N:27]2[CH2:28][CH2:29][N:24]([CH3:23])[CH2:25][CH2:26]2)=[O:21])=[CH:9]1)[CH2:3][O:2][CH3:1]
Reactant: COCC(COC)n1cc(C(=O)O)c(=O)c2cc(I)ccc21
Reactant: CN1CCNCC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: Oc1cccc2[nH]nnc12
Solvent: ClCCl
Solvent: CN1CCOCC1
Product: COCC(COC)n1cc(C(=O)N2CCN(C)CC2)c(=O)c2cc(I)ccc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 83.4 %

Procedure:
To a solution of 1-(1,3-dimethoxypropan-2-yl)-6-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (Intermediate 78, 300 mg, 0.72 mmol) and 1-methylpiperazine (100 mg, 1.00 mmol) in dichloromethane (50 mL) was added hydroxybenzotriazole (HOBT) (110 mg, 0.72 mmol) and N-methylmorpholine (290 mg, 2.87 mmol). The reaction mixture was stirred for 1 h at room temperature and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC HCl) (234 mg, 1.29 mmol) was added. The resulting reaction mixture was stirred at room temperature over night. The reaction mixture was quenched with 2N hydrochloric acid (30 mL) and the layers were separated. The organic layer was washed with saturated sodium bicarbonate solution (40 mL), water (60 mL) and finally with brine successively and dried over anhydrous sodium sulphate, filtered and concentrated under vacuum to afford 1-(1,3-dimethoxypropan-2-yl)-6-iodo-3-[(4-methylpiperazin-1-yl)carbonyl]quinolin-4(1H)-one 300 mg (80%) as thick oil.
Reaction SMILES: [C:1]1([C:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[O:9][C:8]=2[C:16]2[CH:25]=[CH:24][C:23]([O:26]C)=[C:22]3[C:17]=2[CH:18]=[CH:19][CH:20]=[N:21]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:28]1([C:34]2[C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=3[O:36][C:35]=2[C:43]2[CH:52]=[CH:51][C:50]([OH:53])=[C:49]3[C:44]=2[CH:45]=[CH:46][CH:47]=[N:48]3)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.Br[CH2:55][C:56]#[N:57]>>[C:1]1([C:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[O:9][C:8]=2[C:16]2[CH:25]=[CH:24][C:23]([OH:26])=[C:22]3[C:17]=2[CH:18]=[CH:19][CH:20]=[N:21]3)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1.[C:28]1([C:34]2[C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=3[O:36][C:35]=2[C:43]2[CH:52]=[CH:51][C:50]([O:53][CH2:55][C:56]#[N:57])=[C:49]3[C:44]=2[CH:45]=[CH:46][CH:47]=[N:48]3)[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1
Reactant: N#CCBr
Reactant: COc1ccc(-c2oc3ccccc3c2-c2ccccc2)c2cccnc12
Agent: Oc1ccc(-c2oc3ccccc3c2-c2ccccc2)c2cccnc12
Product: N#CCOc1ccc(-c2oc3ccccc3c2-c2ccccc2)c2cccnc12
Yield: 74 %

Procedure:
5-(3-Phenyl-1-benzofuran-2-yl)-8-hydroxy-quinoline was prepared as a solid (0.185 g, 99%) from 5-(3-phenyl-1-benzofuran-2-yl)-8-methoxy-quinoline according to the procedure described in the first part of Step 4 of Example 2; Mass spectrum (+ESI, [M+H]+) m/z 338. Reaction of 5-(3-phenyl-1-benzofuran-2-yl)-8-hydroxy-quinoline with bromoacetonitrile according to the procedure described in Step 2 of Example 1 afforded the title compound as a solid (0.148 g, 74%). Mass spectrum (+ESI, [M+H]+) m/z 377. 1H NMR (400 MHz, DMSO-d6): δ 8.90-8.96 (m, 1H), 8.19 (d, 1H, J=8.1 Hz), 7.71-7.81 (m, 3H), 7.39-7.65 (m,4H), 7.25-7.39 (m, 5H), and 5.48 ppm (s, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=O)[CH2:10][CH3:11])=[CH:5][CH:4]=1.[CH3:13][O-:14].[Na+].[OH2:16].Cl>C(OC)=O.CO>[CH:13]([CH:10]([CH3:11])[C:9]([C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)=[O:16])=[O:14]
Reactant: CCC(=O)c1ccc(OC)cc1
Reactant: C[O-]
Reactant: O
Agent: Cl
Agent: [Na+]
Solvent: COC=O
Solvent: CO
Product: COc1ccc(C(=O)C(C)C=O)cc1
Reaction time: 6 h
Yield: 84 %

Procedure:
10 g (60.9 mmol) of 4′-methoxypropiophenone was dissolved in 100 ml of methyl formate. At room temperature, sodium methoxide, 15.3 g (79.2 mmol) at a concentration of 28% in methanol solution was dropwise added to the solution over a period of 30 minutes, followed by stirring at the same temperature for 6 hours. To the reaction mixture was added 100 ml of water, and the solution pH was adjusted to 1 with concentrated hydrochloric acid, followed by stirring for further 1 hour. Thereafter, the reaction mixture was extracted with 100 ml of ethyl acetate three times. The organic phase was washed with a saturated aqueous solution of sodium chloride and then dried over anhydrous magnesium sulfate. Filtration and subsequent distillation to remove the solvent gave 9.8 g (51.0 mmol) of 2-formyl-4′-methoxypropiophenone as a light yellow crystal. The yield was 84%. The product synthesized was subjected to the next reaction without purification.
Reaction SMILES: [CH3:1][C:2]([CH:4]1[CH2:6][CH2:5]1)=[O:3].[H-].[Na+].[CH3:9][S:10][C:11]1[CH:21]=[CH:20][C:14]([C:15](OCC)=[O:16])=[CH:13][CH:12]=1.Cl>O1CCOCC1>[CH:4]1([C:2](=[O:3])[CH2:1][C:15]([C:14]2[CH:20]=[CH:21][C:11]([S:10][CH3:9])=[CH:12][CH:13]=2)=[O:16])[CH2:6][CH2:5]1
Reactant: CCOC(=O)c1ccc(SC)cc1
Reactant: CC(=O)C1CC1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1COCCO1
Product: CSc1ccc(C(=O)CC(=O)C2CC2)cc1
Temperature: 60 °C
Reaction time: 0.33 h
Yield: 49.4 %

Procedure:
Cyclopropyl methyl ketone (0.84 g) was added to a suspension of sodium hydride (80%, 0.3 g) in dioxane. The mixture was stirred for 20 minutes and ethyl 4-(methylsulphenyl)benzoate (1.0 g) was added. The mixture was stirred and heated at 45° C. for 1.5 hours and at 60° C. for 2 hours. It was left to stand at room temperature overnight. Hydrochloric acid (2M) was added and the mixture was extracted with ethyl acetate, washed with water, dried (MgSO4) and filtered. The flitrate was evaporated to dryness and the residue was purified by chromatography eluted with a mixture of ethyl acetate and hexane to give 3-cyclopropyl-1-[4-(methylsulphenyl)-phenyl]-propan-1,3-dione (0.59 g) as an orange solid, NMR (CDCl3) 1.0(m,2H), 1.2(m,2H), 1.8(m, 1H), 2.5(s,3H), 6.25(s,1H), 7.25(d,2H), 7.8(d,2H), 16.35(bs,1H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]3[N:14]=[C:15]([CH3:17])[CH:16]=[C:12]3[NH:11][C:10](=O)[CH:9]=2)=[CH:4][CH:3]=1.N1C=CC=CC=1.O=P(Cl)(Cl)[Cl:27]>>[Cl:27][C:10]1[CH:9]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[N:13]2[N:14]=[C:15]([CH3:17])[CH:16]=[C:12]2[N:11]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: Cc1cc2[nH]c(=O)cc(-c3ccc(F)cc3)n2n1
Solvent: c1ccncc1
Product: Cc1cc2nc(Cl)cc(-c3ccc(F)cc3)n2n1
Temperature: 25 °C

Procedure:
7-(4-Fluorophenyl)-2-methylpyrazolo[1,5-a]pyrimidin-5(4H)-one (151 mg) is dissolved in POCl3 (10 mL) and pyridine (0.1 mL) and stirred overnight while heating. After cooling to room temperature, the reaction solvent is removed by distillation under reduced pressure. The remainder is extracted with ethyl acetate and water. The extracted organic layer is washed with 1 M NaHCO3 aqueous solution and brine and dehydrated with anhydrous MgSO4. The dehydrated organic layer is distilled under reduced pressure and purified by column chromatography to yield the target compound (156 mg). 1H NMR (CDCl3, 300 MHz); δ 8.07 (m, 2H), 7.26 (m, 2H), 6.78 (m, 1H), 6.48 (s, 1H), 2.50 (s, 3H).
Reaction SMILES: Br[C:2]1[C:7]([Br:8])=[C:6]([Cl:9])[C:5]([Br:10])=[C:4](Br)[C:3]=1[OH:12].[H][H]>[OH-].[K+].CO.[Ni]>[Br:8][C:7]1[CH:2]=[C:3]([OH:12])[CH:4]=[C:5]([Br:10])[C:6]=1[Cl:9]
Reactant: [H][H]
Reactant: Oc1c(Br)c(Br)c(Cl)c(Br)c1Br
Agent: [Ni]
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: Oc1cc(Br)c(Cl)c(Br)c1
Yield: 61 %

Procedure:
8.9 g of 2,3,5,6-tetrabromo-4-chlorophenol are dissolved in a mixture of 40 ml of 1 N methanolic KOH and 60 ml of methanol and then 4 g of Raney nickel are added to the solution. Hydrogenation is carried out with hydrogen in a shaking apparatus for 41/2 hours under normal pressure at 20° C. The uptake of hydrogen is 98% of theory. The catalyst is removed by filtration and the filtrate is concentrated. The residue is recrystallised twice from cyclohexane, affording 3.5 g of 3,5-dibromo-4-chlorophenol in the form of colourless crystals with a melting point of 121° C.
Reaction SMILES: FC(F)(F)C([O-])=O.OC1C=CC=CC=1/C=[N:12]\[C@@H:13]1[C:20](=[O:21])[N:19]2[CH:14]1[S:15][CH2:16][C:17]([S:34][C:35]1[S:36][CH:37]=[C:38]([C:40]3[CH:45]=[CH:44][N+:43]([CH3:46])=[CH:42][CH:41]=3)[N:39]=1)=[C:18]2[C:22]([O:24]CC1C=CC(OC)=CC=1)=[O:23].O.CS(O[C:57](=[O:73])/[C:58](/[C:63]1[N:67]=[C:66]([NH:68][P:69]([OH:72])([OH:71])=[O:70])[S:65][N:64]=1)=[N:59]\[O:60][CH2:61][CH3:62])(=O)=O.ClCCl>C(OC)(C)(C)C>[CH2:61]([O:60]/[N:59]=[C:58](/[C:63]1[N:67]=[C:66]([NH:68][P:69]([OH:71])([OH:72])=[O:70])[S:65][N:64]=1)\[C:57]([NH:12][C@@H:13]1[C:20](=[O:21])[N:19]2[C@@H:14]1[S:15][CH2:16][C:17]([S:34][C:35]1[S:36][CH:37]=[C:38]([C:40]3[CH:45]=[CH:44][N+:43]([CH3:46])=[CH:42][CH:41]=3)[N:39]=1)=[C:18]2[C:22]([O-:24])=[O:23])=[O:73])[CH3:62]
Reactant: COc1ccc(COC(=O)C2=C(Sc3nc(-c4cc[n+](C)cc4)cs3)CSC3[C@H](/N=C\c4ccccc4O)C(=O)N23)cc1
Reactant: CCO/N=C(\C(=O)OS(C)(=O)=O)c1nsc(NP(=O)(O)O)n1
Agent: O=C([O-])C(F)(F)F
Solvent: COC(C)(C)C
Solvent: O
Solvent: ClCCl
Product: CCO/N=C(\C(=O)N[C@@H]1C(=O)N2C(C(=O)[O-])=C(Sc3nc(-c4cc[n+](C)cc4)cs3)CS[C@H]12)c1nsc(NP(=O)(O)O)n1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A reactor is charged with 4-(2-(((7R)-7-((Z)-(2-hydroxybenzylidene)amino)-2-(((4-methoxybenzyl)oxy)carbonyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl)thio)thiazol-4-yl)-1-methylpyridin-1-ium trifluoroacetate (1 eq), water (6-9 weight % relative to the Schiff base), (Z)-2-(5-(phosphonoamino)-1,2,4-thiadiazol-3-yl)-2-(ethoxyimino)acetic methanesulfonic anhydride (2.5 eq) and dichloromethane (1.75 mL per gram of Schiff base). The mixture is stirred for three hours at room temperature, then added to methyl tertiary butyl ether over the course of 2-3 hours, resulting in the formation of a solid. The solid is filtered and the filter cake was washed with additional methyl tertiary butyl ether. The filtered solid is deprotected using conventional methods and dried under vacuum to yield the title compound.
Reaction SMILES: [O:1]1[C:6]2[CH:7]=[CH:8][C:9]([CH:11]=O)=[CH:10][C:5]=2[O:4][CH2:3]C1.[CH2:13]([N:17]1[C:21]([CH2:22][NH:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([O:31][CH2:32][CH3:33])[CH:26]=2)=[C:20]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[NH:19][CH:18]1[I:40])[CH2:14][CH2:15][CH3:16].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(O)(=O)C>[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([CH2:11][N:23]([CH2:22][C:21]3[N:17]([CH2:13][CH2:14][CH2:15][CH3:16])[CH:18]([I:40])[NH:19][C:20]=3[C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([O:31][CH2:32][CH3:33])[CH:26]=3)=[CH:10][C:5]=2[O:4][CH2:3]1
Reactant: CCCCN1C(CNCc2cccc(OCC)c2)=C(c2ccccc2)NC1I
Reactant: O=Cc1ccc2c(c1)OCCO2
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCCl
Product: CCCCN1C(CN(Cc2cccc(OCC)c2)Cc2ccc3c(c2)OCO3)=C(c2ccccc2)NC1I
Temperature: 25 °C
Reaction time: 2 h

Procedure:
2,3-Dihydro-benzo[1,4]dioxine-6-carbaldehyde (503 mg) is added to a solution of (1-butyl-2-iodo-4-phenyl-3H-imidazol-5-ylmethyl)-(3-ethoxy-benzyl)-amine (750 mg) in 10 mL of 1,2-dichlorethane followed by the addition of 10 drops of acetyl alcohol. The resulting mixture is stirred at room temperature for 2 hours. 2 Equivalents of NaBH(OAc)3 are added and the stirring is continued overnight. The reaction is quenched with 10 mL water. The organic phase is collected, washed with water and brine, and dried over Na2SO4. Concentration and purification via flash chromatography provides benzo[1,3]dioxol-5-ylmethyl-(1-butyl-2-iodo-4-phenyl-3H-imidazol-5-ylmethyl)-(3-ethoxy-benzyl)-amine (compound 4).
Reaction SMILES: [Br-].[CH:2](=[O:10])[C:3]1[C:4](=[CH:6][CH:7]=[CH:8][CH:9]=1)[OH:5].C(=O)([O-])[O-].[K+].[K+].[CH3:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]>CN(C)C=O>[C:19]1([CH2:6][CH2:4][CH2:3][CH2:9][CH2:8][CH2:7][O:5][C:4]2[CH:6]=[CH:7][CH:8]=[CH:9][C:3]=2[CH:2]=[O:10])[CH:18]=[CH:17][CH:22]=[CH:21][CH:20]=1
Reactant: O=Cc1ccccc1O
Reactant: CCCCCC
Agent: O=C([O-])[O-]
Agent: [Br-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=Cc1ccccc1OCCCCCCc1ccccc1
Temperature: 100 °C

Procedure:
A solution of 6-phenylhexanoic acid (19.8 mmoles) in sieve dried tetrahydrofuran (5 ml) was reduced with diborane in tetrahydrofuran (30 ml, 29.1 mmoles) at 0° C. for 4 hours to give 6-phenylhexanol. To an ice cold solution of the hexanol (ca. 19.8 mmoles) and carbon tetrabromide (21.98 mmoles) in methylene chloride (50 ml) was added triphenylphosphine (22.30 mmoles) in methylene chloride (50 ml) and the resulting solution was stirred for 2.5 hours. The volatiles were evaporated and the residue was taken up in ether (100 ml), cooled in ice, and filtered. The filtrate was evaporated and distilled to afford 6-phenylhexyl bromide as an oil. A mixture of the bromide (8.00 mmoles), salicylaldehyde (8.19 mmoles) and potassium carbonate (9.33 mmoles) in dimethylformamide (10 ml) was heated to 100° C. and maintained at that temperature for one hour. The cooled reaction mixture was taken up in hexane (50 ml) and washed with 5% sodium hydroxide (50 ml) and saturated sodium chloride (50 ml). The organic phase was dried over anhydrous magnesium sulfate and charcoal. Evaporation yielded a colorless oil which was purified by flash chromatography over silica gel with 5% ethyl acetate in hexane as eluant to afford the desired product as an oil.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:20]C(Cl)(Cl)C(Cl)(Cl)Cl.[C:28]([O:32][C:33]([NH:35][C@H:36]([C:39]([O:41][CH3:42])=[O:40])[CH2:37]O)=[O:34])([CH3:31])([CH3:30])[CH3:29]>ClCCCl.ClCCCl.ClCCCl.C(Cl)Cl>[C:28]([O:32][C:33]([NH:35][C@H:36]([C:39]([O:41][CH3:42])=[O:40])[CH2:37][Cl:20])=[O:34])([CH3:31])([CH3:30])[CH3:29]
Reactant: ClC(Cl)(Cl)C(Cl)(Cl)Cl
Reactant: COC(=O)[C@H](CO)NC(=O)OC(C)(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: ClCCCl
Product: COC(=O)[C@H](CCl)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 61.4 %

Procedure:
A solution of triphenylphosphine (4.55 g, 17.4 mmol) and hexachloroethane (3.9 g, 16.5 mmol) in 1,2-dichloroethane (18 mL) prepared at 0° C. was added via cannula into a flask containing a solution of methyl N-(tert-butoxycarbonyl)-L-serinate (3.2 g, 14.6 mmol) in 1,2-dichloroethane DCE (40 mL), kept at 0° C. under N2 atmosphere. After the addition was completed, the reaction mixture was further stirred at room temperature for 2 h, diluted with DCM, washed with sat NaHCO3, dried over MgSO4, filtered and concentrated. Purification made through chromatographic column of silicagel eluted with 10% to 50% EtOAc in hexane for 30 min, to afford 2.13 g (61% yield) of title compound as white crystals. MS: m/z=260.0 (MNa+).
Reaction SMILES: [C:1]1([CH:7](Br)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH:15][CH:16]1[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][CH2:24][O:25][C:26]2[CH:31]=[CH:30][C:29]([N+:32]([O-:34])=[O:33])=[CH:28][CH:27]=2)[CH2:18][CH2:17]1.OC1CCN(CCCOC2C=CC=CC=2[N+]([O-])=O)CC1>>[C:1]1([CH:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[O:15][CH:16]2[CH2:17][CH2:18][N:19]([CH2:22][CH2:23][CH2:24][O:25][C:26]3[CH:27]=[CH:28][C:29]([N+:32]([O-:34])=[O:33])=[CH:30][CH:31]=3)[CH2:20][CH2:21]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=[N+]([O-])c1ccc(OCCCN2CCC(O)CC2)cc1
Reactant: BrC(c1ccccc1)c1ccccc1
Agent: O=[N+]([O-])c1ccccc1OCCCN1CCC(O)CC1
Product: O=[N+]([O-])c1ccc(OCCCN2CCC(OC(c3ccccc3)c3ccccc3)CC2)cc1

Procedure:
The procedure of Example 1 (a) was repeated except for using diphenylmethyl bromide and 4-hydroxy-1-[3-(4-nitrophenoxy)propyl]piperidine instead of diphenylmethyl bromide and 4-hydroxy-1-[3-(2-nitrophenoxy)propyl]piperidine to give oily 4-diphenylmethoxy-1-[3-(4-nitrophenoxy)propyl]piperidine.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[CH:6]2.[N+]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)([O-])=O>C1COCC1>[CH2:11]([C:16]1[CH:21]=[CH:20][C:19]([C:8]2[CH:7]=[CH:6][C:5]3[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=3)[N:9]=2)=[CH:18][CH:17]=1)[CH2:12][CH2:3][CH2:4][CH3:5]
Reactant: O=[N+]([O-])c1ccccc1
Reactant: COc1ccc2ncccc2c1
Solvent: C1CCOC1
Product: CCCCCc1ccc(-c2ccc3cc(OC)ccc3n2)cc1
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 44.8 %

Procedure:
To the resultant mixture, a solution of 2.18 ml (15.8 mM) of 6-methoxyquinoline in 13 ml of dry THF was added dropwise in 30 minutes at the same temperature. After the addition, the dry ice-acetone bath was removed and the mixture was stirred for 1 hour and 40 minutes at room temperature. After the reaction, the reaction mixture was poured into ice water and subjected to extraction with ethyl acetate. The organic layer was washed with water and dried with anhydrous sodium sulfate, followed by evaporation under reduced pressure to obtain a residue. To the residue, 5 ml of nitrobenzene was added, followed by refluxing under stirring. The reaction mixture was subjected to reduced-pressure distillation to distill off nitrobenzene as much as possible. The resultant crude product was purified by silica gel column chromatography (eluent: toluene/ethyl acetate=100/1) and recrystallized from methanol to obtain 2.16 g of 2-(4-pentylphenyl)-6-methoxyquinoline (Yield: 44.8%). This compound showed the following phase transition series.
Reaction SMILES: NC1C=C(C(C2C=CC(OC)=C(OCC)C=2)=CC#N)C=CC=1OC.[CH3:25][O:26][C:27]1[CH:28]=[C:29]([C:36]([C:40]2[CH:45]=[C:44]([O:46][CH3:47])[CH:43]=[C:42]([O:48][CH3:49])[CH:41]=2)=[CH:37][C:38]#[N:39])[CH:30]=[CH:31][C:32]=1[N+:33]([O-])=O.O.O.[Sn](Cl)(Cl)(Cl)Cl>>[NH2:33][C:32]1[CH:31]=[CH:30][C:29]([C:36]([C:40]2[CH:45]=[C:44]([O:46][CH3:47])[CH:43]=[C:42]([O:48][CH3:49])[CH:41]=2)=[CH:37][C:38]#[N:39])=[CH:28][C:27]=1[O:26][CH3:25]
Reactant: COc1cc(OC)cc(C(=CC#N)c2ccc([N+](=O)[O-])c(OC)c2)c1
Agent: CCOc1cc(C(=CC#N)c2ccc(OC)c(N)c2)ccc1OC
Agent: Cl[Sn](Cl)(Cl)Cl
Solvent: O
Product: COc1cc(OC)cc(C(=CC#N)c2ccc(N)c(OC)c2)c1
Yield: 86.9 %

Procedure:
3-(4-Amino-3-methoxy-phenyl)-3-(3,5-dimethoxy-phenyl)-acrylonitrile was prepared analogously to 3-(3-amino-4-methoxy-phenyl)-3-(3-ethoxy-4-methoxy-phenyl)-acrylonitrile using 3-(3-methoxy-4-nitro-phenyl)-3-(3,5-dimethoxy-phenyl)-acrylonitrile (3.9 g, 11.5 mmol) and tin chloride dihydrate (12.8 g, 58.0 mmol) to afford mixture isomers of 3-(4-amino-3-methoxy-phenyl)-3-(3,5-dimethoxy-phenyl)-acrylonitrile (3.1 g, 84%) as a yellow solid: mp 114-116° c; 1H NMR (CDCl3) δ 7.04-6.45 (m, 6H), 5.60(5.46) (s, 1H), 3.86-3.70 (m, 11H); 13C NMR (CDCl3) δ 163.18, 162.98, 160.57, 146.32, 142.06, 139.34, 139.07, 138.57, 128.03, 126.37, 124.00, 122.74, 107.15, 102.02, 101.95, 91.86, 90.98, 55.69, 55.55; Anal Calcd for C18H18N2O3: C, 69.66; H, 5.85; N, 9.03. Found: C, 69.33; H, 5.67; 8.85.
Reaction SMILES: C(N(CC)CC)C.[CH2:8](Cl)[CH:9]=[CH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[CH2:18]([NH2:21])[CH:19]=[CH2:20]>O1CCCC1>[CH2:8]([NH:21][CH2:18][CH:19]=[CH2:20])[CH:9]=[CH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: ClCC=Cc1ccccc1
Reactant: C=CCN
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: C=CCNCC=Cc1ccccc1
Temperature: 60 °C
Reaction time: 10 h
Yield: 33.1 %

Procedure:
175 ml (1.27 mol) of triethylamine were added to 173 ml (1.16 mol) of cinnamyl chloride in 1,350 ml of tetrahydrofuran, the mixture was heated to 60° C., and then 105 ml (1.40 mol) of allylamine were added dropwise. The mixture was refluxed for 6 h and then stirred at room temperature for 10 h. After concentration under water pump vacuum, the contents of the flask were partitioned between methyl t-butyl ether and water (pH=10). The aqueous phase was extracted twice more with methyl t-butyl ether and subsequently the combined organic phases were extracted with a mixture of 250 ml of concentrated hydrochloric acid and 2 l of water. The aqueous phase was then extracted with 1.2 l of methylene chloride, and the methylene chloride phase washed five times with 500 ml of 10% strength hydrochloric acid each time. The combined aqueous phases were made alkaline with concentrated sodium hydroxide solution and extracted twice with methylene chloride. Drying and concentration of the organic phase resulted in 66.5 g of crude product which was distilled at 86°-88° C. under oil pump vacuum (0.25 mbar). Yield: 64 g (32%).
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:15]=[CH:14][C:13]([CH:16]([CH3:19])[C:17]#[N:18])=[C:12]([O:20][CH3:21])[CH:11]=1.O1C2C=CC=CC=2N=[C:23]1[C:31]1C=CC(C#N)=C(OC)C=1.ICCC>>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:15]=[CH:14][C:13]([CH:16]([CH2:19][CH2:23][CH3:31])[C:17]#[N:18])=[C:12]([O:20][CH3:21])[CH:11]=1
Reactant: COc1cc(-c2nc3ccccc3o2)ccc1C#N
Reactant: COc1cc(-c2nc3ccccc3o2)ccc1C(C)C#N
Solvent: CCCI
Product: CCCC(C#N)c1ccc(-c2nc3ccccc3o2)cc1OC

Procedure:
Utilizing the general procedure outlined in the synthesis of 2-[4-(1,3-benzoxazol-2-yl)-2-methoxyphenyl]propanenitrile, 4-(1,3-benzoxazol-2-yl)-2-methoxybenzonitrile (200 mg, 0.75 mmol) was reacted with 1-iodopropane (73 μL, 0.75 mmol) to afford the desired 2-[4-(1,3-benzoxazol-2-yl)-2-methoxyphenyl]pentanenitrile as a yellow solid: 1H NMR (CDCl3, 300 MHz) δ 7.87–7.84 (d, 1H), 7.79–7.75 (m, 2H), 7.60–7.54 (m, 2H), 7.38–7.35 (m, 2H), 4.27–4.23 (t, 1H), 3.98 (s, 3H), 1.89–1.82 (M, 2H), 1.57–1.53 (m, 2H), 1.00–0.95 (t, 3H). MS (ESI) 307 (M+H)+.
Reaction SMILES: [C:1]([NH:11][CH2:12][CH2:13][C:14]1[CH:21]=[CH:20][C:18]([OH:19])=[C:16]([OH:17])[CH:15]=1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[C:22](Cl)(=[O:27])[C:23]([CH3:26])([CH3:25])[CH3:24].[C:29](=[O:32])([O-])[O-].[Na+].[Na+]>N1C=CC=CC=1>[C:22]([O:17][C:16]1[CH:15]=[C:14]([CH:21]=[CH:20][C:18]=1[O:19][C:29](=[O:32])[C:5]([CH3:10])([CH3:6])[CH3:4])[CH2:13][CH2:12][NH:11][C:1]([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2])(=[O:27])[C:23]([CH3:26])([CH3:25])[CH3:24]
Reactant: O=C([O-])[O-]
Reactant: CC(C)(C)C(=O)Cl
Reactant: O=C(NCCc1ccc(O)c(O)c1)OCc1ccccc1
Agent: [Na+]
Solvent: c1ccncc1
Product: CC(C)(C)C(=O)Oc1ccc(CCNC(=O)OCc2ccccc2)cc1OC(=O)C(C)(C)C
Temperature: 25 °C
Reaction time: 12 h
Yield: 80.1 %

Procedure:
To 150 ml of a pyridine solution containing 23.0 g (98 mmol) of N-carbobenzoxydopamine obtained in Synthetic Example 1-(1), was added 24.1 g (200 mmol) of pivaloyl chloride dropwise at 5° to 10° C. After stirring at room temperature for 12 hours, the mixture was allowed to react at 35° to 40° C. for 3 hours. Further, the reaction mixture was poured into ice and a sodium carbonate solution and the stirring was continued at room temperature for 30 minutes. After extracting with diethyl ether and drying over anhydrous magnesium sulfate, the solvent was distilled off to give crude crystals. The resulting crude crystals then recrystallized from petroleum ether to obtain 27.1 g (yield: 80.1%) of the desired compound in the form of white crystals