Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][N:11]3[C:14](=[O:17])[NH:15][N:16]=[C:10]3[C:9]=2[C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2[CH:42]=[CH:41][O:40][N:39]=2)=[CH:34][CH:33]=1>CN(C=O)C.CCOC(C)=O>[O:40]1[CH:41]=[CH:42][C:38]([C:35]2[CH:36]=[CH:37][C:32]([CH2:31][N:15]3[C:14](=[O:17])[N:11]4[N:12]=[CH:13][C:8]([C:5]5[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=5)=[C:9]([C:18]5[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=5)[C:10]4=[N:16]3)=[CH:33][CH:34]=2)=[N:39]1
Reactant: BrCc1ccc(-c2ccon2)cc1
Reactant: O=c1[nH]nc2c(-c3ccncc3)c(-c3ccc(Cl)cc3)cnn12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=c1n(Cc2ccc(-c3ccon3)cc2)nc2c(-c3ccncc3)c(-c3ccc(Cl)cc3)cnn12
Temperature: 65 °C
Reaction time: 2 h

Procedure:
To a solution of 7-(4-chlorophenyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (0.27 g, 0.834 mmol), prepared as described in Example 244, in DMF (4 mL), potassium carbonate (0.23 g, 1.67 mmol) and 3-(4-(bromomethyl)phenyl)isoxazole (0.248 g, 1.04 mmol) were added. The resulting mixture was heated to 65° C. After 2 h, the reaction mixture was then cooled to RT and diluted with EtOAc (200 mL). The resultant solution was then washed with water and saturated aqueous NaCl. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography eluting with hexanes/EtOAc to give the title compound, 2-(4-(isoxazol-3-yl)benzyl)-7-(4-chlorophenyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one, as a light yellow solid. HPLC RT: 2.60 min; 1H NMR (CDCl3): δ 8.64 (d, J=1.1 Hz, 1H), 8.63 (d, J=1.7 Hz, 1H), 8.45 (d, J=1.7 Hz, 1H), 8.20 (s, 1H), 7.80 (d, J=8.2 Hz, 2H), 7.50 (d, J=8.2 Hz, 2H), 7.34 (m, 2H), 7.23 (m, 2H), 7.10 (m, 2H), 6.65 (d, J=2.2 Hz, 1H), 5.26 (s, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:19]2[C:27]3[C:22](=[C:23]([CH2:29][S:30][CH3:31])[CH:24]=[C:25]([F:28])[CH:26]=3)[NH:21][CH:20]=2)[CH:9]2C(=O)O[C:12](C)([CH3:16])[O:11][C:10]2=[O:18])=[C:4]([F:32])[CH:3]=1>N1C=CC=CC=1.C(O)C.[Cu]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:19]2[C:27]3[C:22](=[C:23]([CH2:29][S:30][CH3:31])[CH:24]=[C:25]([F:28])[CH:26]=3)[NH:21][CH:20]=2)[CH2:9][C:10]([O:11][CH2:12][CH3:16])=[O:18])=[C:4]([F:32])[CH:3]=1
Reactant: CSCc1cc(F)cc2c(C(c3ccc(Cl)cc3F)C3C(=O)OC(C)(C)OC3=O)c[nH]c12
Agent: [Cu]
Solvent: c1ccncc1
Solvent: CCO
Product: CCOC(=O)CC(c1ccc(Cl)cc1F)c1c[nH]c2c(CSC)cc(F)cc12

Procedure:
1.9 mg (0.03 mmol) of copper powder were added to 2.20 g of the compound from Example 16A with a purity of 71% (3.26 mmol) in 25 ml of pyridine and 6.7 ml of ethanol. The reaction mixture was heated under reflux for 1 h. It was concentrated, and the residue was purified by flash chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate gradient) to result in 1.22 g (88% of theory) of the target compound.
Reaction SMILES: [CH:1]1[C:6]2[C:7]3[NH:8][C:9]4[C:14]([C:15]=3[CH:16]([C:18]([OH:20])=O)[S:17][C:5]=2[CH:4]=[CH:3][CH:2]=1)=[CH:13][CH:12]=[CH:11][CH:10]=4.[CH2:21]([NH:23][CH2:24][CH3:25])[CH3:22].F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[CH2:21]([N:23]([CH2:24][CH3:25])[C:18]([CH:16]1[C:15]2[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[NH:8][C:7]=2[C:6]2[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=2[S:17]1)=[O:20])[CH3:22]
Reactant: O=C(O)C1Sc2ccccc2-c2[nH]c3ccccc3c21
Reactant: CCNCC
Agent: Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCN(CC)C(=O)C1Sc2ccccc2-c2[nH]c3ccccc3c21
Temperature: 25 °C
Reaction time: 72 h
Yield: 53 %

Procedure:
To 6,11-dihydro-5-thia-11-aza-benzo[α]fluorene-6-carboxylic acid (1.65 g, 6 mmol) in CH2Cl2 (15 ml) were added diethylamine (0.7 ml, 7 mmol), bromotripyrrolidinophosphonium hexafluorophosphate (2.75 g, 6 mmol) and diisopropylethylamine (3.1 ml, 18 mmol). The reaction was stirred at room temperature for 3 days. The reaction mixture was diluted with CH2Cl2 (100 ml), washed with 1N HCl, saturated NaHCO3 soln, brine, dried (MgSO4) and evaporated. The residue was purified by silica gel chromatography eluting with 50% EtOAc/petroleum ether to give 1.07 g (54%) of 6,11-dihydro-5-thia-11-aza-benzo[α]fluorene-6-carboxylic acid diethylamide as a yellow solid. 1H NMR (CDCl3) δ 9.23 (1H, s), 7.33 (1H, dd), 7.20 (1H, dd), 7.69-7.08 (5H, m), 6.66-6.72 (1H, m), 5.33 (1H, s), 3.34-3.76 (4H, m), 1.39 (3H, t), 1.37 (3H, t).
Reaction SMILES: [CH3:1][C:2]([CH3:20])([CH3:19])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([NH:12][C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15])[N:7]=1)=[O:4].[C:21](=O)([O:24]C)[O:22][CH3:23]>O1CCCC1.CCCCCC>[CH3:15][C:14]([CH3:17])([CH3:16])[C:13]([NH:12][C:8]1[N:7]=[C:6]([NH:5][C:3](=[O:4])[C:2]([CH3:20])([CH3:19])[CH3:1])[CH:11]=[CH:10][C:9]=1[C:21]([O:22][CH3:23])=[O:24])=[O:18]
Reactant: COC(=O)OC
Reactant: CC(C)(C)C(=O)Nc1cccc(NC(=O)C(C)(C)C)n1
Solvent: CCCCCC
Solvent: C1CCOC1
Product: COC(=O)c1ccc(NC(=O)C(C)(C)C)nc1NC(=O)C(C)(C)C
Temperature: 0 °C
Reaction time: 12 h
Yield: 15565.2 %

Procedure:
In a 5 L, 4-necked round bottom flask, immersed in ice-cold ethanol-isopropanol (isopropanol 13%, −15° C.) bath, to a solution of 2,6-bis[(2,2-dimethylpropanoyl)amino]pyridine (J. Am. Chem. Soc. 1986, 108, 3310–3318, 126 g, 454 mmol) in anhydrous tetrahydrofuran (1.5 L) was added 2.66 M solution of n-buthyllithium in hexane (598 mL) dropwise from a dropping funnel (1 L) during the period of 6 h under nitrogen atmosphere (internal temperature was maintained at −15° C.˜−5° C.). The resulting solution was stirred at 0° C. (internal temperature) for 12 h under nitrogen atmosphere. The formation of yellowish precipitate was noticed. Then the suspension was cooled to −15° C., dimethyl carbonate (194 mL, 2.3 mmol) was added in one portion. The reaction solution was stirred at 0° C. for 1 h, quenched with 1.5 L of 1 N aqueous hydrochloric acid, pH value was controlled to ˜4.5 by adding 1 N aqueous hydrochloric acid, then 600 mL of ethyl acetate was added. After the layers were separated, the organic layer was washed with 1 L of 0.2 N aqueous NaOH (1 L) and brine (500 mL). Each aqueous layer was extracted with ethyl acetate (300 mL) twice. Combined organic layer was dried over sodium sulfate (˜300 g) and concentrated. The residue was diluted with diisopropylether (300 mL) and the solution was evaoprated to remove the residual ethyl acetate azeotropically. The residue was dissolved with diisopropylether (360 mL) at 60° C. with gentle stirring, and then the small portion of the crystalline of the desired product (˜5 mg) was added as seed. The formation of a pale yellow precipitate was noticed. The resulting suspension was cooled to room temperature (during the period of 2 h), and stirred at room temperature for 2 h. The suspension was filtered through paper filter, then the cake was washed with diisopropylether (80 mL). The solid was dried under reduced pressure at room temperature for 1 day to give the title compound (120 g, 358 mmol, 79%) as a pale yellow solid.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH:7]=O)([O-:3])=[O:2].[F:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][C:21]=1[F:22])[NH:18][C:17]([C:23]1[CH:24]=[CH:25][C:26]([O:30][CH3:31])=[C:27]([NH2:29])[CH:28]=1)=[CH:16]2.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(O)(=O)C>[F:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][C:21]=1[F:22])[NH:18][C:17]([C:23]1[CH:24]=[CH:25][C:26]([O:30][CH3:31])=[C:27]([NH:29][CH2:7][C:6]3[CH:9]=[CH:10][CH:11]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[CH:28]=1)=[CH:16]2
Reactant: O=Cc1cccc([N+](=O)[O-])c1
Reactant: COc1ccc(-c2cc3cc(F)c(F)cc3[nH]2)cc1N
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(=O)O
Product: COc1ccc(-c2cc3cc(F)c(F)cc3[nH]2)cc1NCc1cccc([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 26.9 %

Procedure:
3-Nitrobenzaldehyde (0.3 g, 2.0 mmol) was added to a stirred mixture of 5-(5,6-difluoro-1H-indol-2-yl)-2-methoxy-phenylamine (0.548 g, 2.0 mmol) in methylene chloride (125 mL), followed by acetic acid (0.2 g). The resulting mixture is stirred at room temperature for 1 hour. Sodium triacetoxyborohydride (0.46 g, 2.2 mmol) was added in one portion, and the resulting homogeneous solution was stirred at room temperature for 6 days. Saturated aqueous sodium bicarbonate solution (100 mL) was added and the mixture was sired for 2 hours. The mixture was shaken, the organic layer was separated and dried over Na2SO4. The solvent was evaporated to give a yellow solid. Recrystallization from methanol gave the product (220 mg), mp 212-214° C.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10](=O)[CH3:11])[N:5]=1)(=O)[CH3:2].[CH3:13][C:14]1[CH:20]=[C:19]([CH3:21])[CH:18]=[CH:17][C:15]=1[NH2:16]>CO.C(O)(=O)C>[CH3:13][C:14]1[CH:20]=[C:19]([CH3:21])[CH:18]=[CH:17][C:15]=1[N:16]=[C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10](=[N:16][C:15]2[CH:17]=[CH:18][C:19]([CH3:21])=[CH:20][C:14]=2[CH3:13])[CH3:11])[N:5]=1)[CH3:2]
Reactant: CC(=O)c1cccc(C(C)=O)n1
Reactant: Cc1ccc(N)c(C)c1
Solvent: CO
Solvent: CC(=O)O
Product: CC(=Nc1ccc(C)cc1C)c1cccc(C(C)=Nc2ccc(C)cc2C)n1
Reaction time: 72 h

Procedure:
Chemicals 2,6-Diacetylpyridine (2.0 g, 12.3 mmol) and 2,4-dimethylaniline (8.9 g, 73.7 mmol) were dissolved in a round-bottom flask with a stirring bar, to which 50 ml of anhydrous methanol were added. Three drops of glacial acetic acid were added, and the flask was sealed. After stirring the solution for three days, 3.79 g (84%) of a yellow solid were collected and identified as the desired ligand for catalyst 5. H NMR (CDCl3) δ8.39 (d,2), 7.85 (t, 1), 7.05 (s, 2), 7.00 (d, 2), 6.60 (d, 2).
Reaction SMILES: [SH:1][CH2:2][CH2:3][C:4]([N:6]1[C@H:10]([C:11]([OH:13])=[O:12])[C@@H:9]([CH3:14])[O:8][CH2:7]1)=[O:5].[OH-:15].[Na+].II>O.C(O)C>[O:15]=[C:4]([N:6]1[C@H:10]([C:11]([OH:13])=[O:12])[C@H:9]([CH3:14])[O:8][CH2:7]1)[CH2:3][CH2:2][S:1][S:1][CH2:2][CH2:3][C:4]([N:6]1[CH:10]([C:11]([OH:13])=[O:12])[CH:9]([CH3:14])[O:8][CH2:7]1)=[O:5]
Reactant: [OH-]
Reactant: C[C@H]1OCN(C(=O)CCS)[C@@H]1C(=O)O
Agent: II
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CC1OCN(C(=O)CCSSCCC(=O)N2CO[C@@H](C)[C@H]2C(=O)O)C1C(=O)O

Procedure:
(4S-trans)-3-(3-Mercapto-1-oxopropyl)-5-methyl-4-oxazolidinecarboxylic acid from Example 1 is dissolved in water and the pH is adjusted to about 6.5 with 1 N sodium hydroxide. To this stirred solution is added dropwise 0.5 M iodine solution in 95% ethanol (6.34 g., iodine/50 ml. solution) while maintaining the pH at 5.5 to 6.5 with 1 N sodium hydroxide. Excess iodine is removed from the reaction mixture with dilute sodium thiosulfate and the solution is then concentrated, cooled and acidified with 1:1 hydrochloric acid. Solvent is added and the mixture is saturated with sodium chloride, stirred, and the layers separated. The organic layer is dried and the solvent evaporated to yield (S,S)-3,3'-[dithiobis(1-oxo-3,1-propanediyl)]bis[5-methyl-4-oxazolidinecarboxylic acid].
Reaction SMILES: [I-].[K+].[CH3:3][S:4][C:5]1[CH:6]=[CH:7][C:8]2[N:14]3[C:15]([CH2:18]Cl)=[N:16][N:17]=[C:13]3[CH2:12][N:11]=[C:10]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:9]=2[CH:26]=1.C(N[CH:31]1[CH2:33][CH2:32]1)CC>O1CCCC1>[CH3:3][S:4][C:5]1[CH:6]=[CH:7][C:8]2[N:14]3[C:15]([CH2:18][NH:11][CH2:10][CH2:9][CH2:8][CH:31]4[CH2:32][CH2:33]4)=[N:16][N:17]=[C:13]3[CH2:12][N:11]=[C:10]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:9]=2[CH:26]=1
Reactant: CSc1ccc2c(c1)C(c1ccccc1)=NCc1nnc(CCl)n1-2
Reactant: CCCNC1CC1
Agent: [I-]
Agent: [K+]
Solvent: C1CCOC1
Product: CSc1ccc2c(c1)C(c1ccccc1)=NCc1nnc(CNCCCC3CC3)n1-2

Procedure:
In the manner given in Example 2, potassium iodide and 8-(methylthio)-1-(chloromethyl)-6-phenyl-4H-s-triazolo-[4,3-a][1,4]benzodiazepine in tetrahydrofuran is treated with propylcyclopropylamine to give 8-(methylthio)-1-[(cyclopropylpropylamino)methyl]-6-phenyl-4H-s-triazolo-[4,3-a][1,4]benzodiazepine.
Reaction SMILES: [C:1](Cl)(=O)C.[Br:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]=[CH:13][C:14](=[O:18])[C:15]([OH:17])=[O:16])=[C:8]([F:19])[CH:7]=1>CO>[CH3:1][O:16][C:15](=[O:17])[C:14](=[O:18])[CH:13]=[CH:12][C:9]1[CH:10]=[CH:11][C:6]([Br:5])=[CH:7][C:8]=1[F:19]
Reactant: O=C(O)C(=O)C=Cc1ccc(Br)cc1F
Reactant: CC(=O)Cl
Solvent: CO
Product: COC(=O)C(=O)C=Cc1ccc(Br)cc1F
Yield: 81.5 %

Procedure:
Acetyl chloride (4.8 mL, 68.5 mmol) was slowly added at 0° C. to methanol (28.0 mL) under stirring. A solution of 4-(4-bromo-2-fluoro-phenyl)-2-oxo-3-butenoic acid (5.5 g, 20.1 mmol) prepared in Step 1 in methanol (5.0 mL) was added to the reaction mixture at room temperature. The reaction mixture was stirred at room temperature for 1 hour, additionally at 80° C. for 16 hours, and then filtered at room temperature to give 4.7 g of the titled compound as a yellow solid.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[F:17][C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[C:22]([F:24])[CH:23]=1.N1C=CC=CC=1>C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Cu+2]>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11](=[O:16])[C:12]([F:13])([F:14])[F:15])=[CH:7][N:8]2[C:20]2[CH:19]=[C:18]([F:17])[CH:23]=[C:22]([F:24])[CH:21]=2)=[CH:4][CH:3]=1
Reactant: OB(O)c1cc(F)cc(F)c1
Reactant: O=C(c1c[nH]c2cc(Cl)ccc12)C(F)(F)F
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=C(c1cn(-c2cc(F)cc(F)c2)c2cc(Cl)ccc12)C(F)(F)F
Temperature: 25 °C
Reaction time: 16 h
Yield: 71 %

Procedure:
To a solution of 1-(6-chloro-1H-indol-3-yl)-2,2,2-trifluoro-ethanone (described in US 2004067939) in CH2Cl2 (in the presence of 0.4 nM molecular sieve) were added anhydrous Cu(OAc)2 (2 eq.), 3,5-difluorophenylboronic acid (3 eq.) and pyridine (4 eq.). The reaction mixture was stirred at RT for 16 h under an air atmosphere, filtered over decalite, washed with CH2Cl2 and concentrated in vacuo. Chromatography (hexane/EtOAc: 9:1) gave the title compound in 71% yield.
Reaction SMILES: [CH3:1][C@@H:2]([NH2:11])[C@@H:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(N(CC)CC)C.[N:19]1([C:25](Cl)=[O:26])[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>C(Cl)Cl>[CH3:1][CH:2]([NH:11][C:25]([N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)=[O:26])[CH:3]([C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1)[OH:10]
Reactant: O=C(Cl)N1CCOCC1
Reactant: C[C@@H](N)[C@@H](O)c1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(NC(=O)N1CCOCC1)C(O)c1ccccc1
Reaction time: 16 h

Procedure:
A solution of 15.2 grams of norephedrine in 200 ml. of CH2Cl2 was cooled to 0-5° C. To this 11.0 grams of triethylamine was added with stirring. To the stirred mixture a solution of 14.9 grams of morpholine carbonyl chloride in 10 ml. of CH2Cl2 was added dropwise. The mixture was then stirred for 2 hours and left to stand at room temperature for 16 hours. The mixture was washed with water and the organic layer was dried over anhydrous sodium sulfate. The organic layer was then filtered and evaporated to a small volume. The hydroxyethylurea, N-(1-methyl-2-phenyl-2-hydroxyethyl)-4-morpholinecarboxamide was filtered off as a white solid and recrystallized from CH2Cl2.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:15])[CH:5]=[C:6](Cl)[C:7]1[CH:8]=[C:9]([CH3:13])[CH:10]=[CH:11][CH:12]=1)[CH3:2].[C:16]([O:20][C:21]([N:23]1[C:32]2[C:27](=[CH:28][CH:29]=[C:30]([CH2:33][CH2:34][O:35][C:36]3[CH:37]=[C:38]4[C:42](=[CH:43][CH:44]=3)[NH:41][CH:40]=[CH:39]4)[N:31]=2)[CH2:26][CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17]>>[C:16]([O:20][C:21]([N:23]1[C:32]2[C:27](=[CH:28][CH:29]=[C:30]([CH2:33][CH2:34][O:35][C:36]3[CH:37]=[C:38]4[C:42](=[CH:43][CH:44]=3)[N:41]([C:6]([C:7]3[CH:8]=[C:9]([CH3:13])[CH:10]=[CH:11][CH:12]=3)=[CH:5][C:4]([O:3][CH2:1][CH3:2])=[O:15])[CH:40]=[CH:39]4)[N:31]=2)[CH2:26][CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:17])[CH3:18]
Reactant: CCOC(=O)C=C(Cl)c1cccc(C)c1
Reactant: CC(C)(C)OC(=O)N1CCCc2ccc(CCOc3ccc4[nH]ccc4c3)nc21
Product: CCOC(=O)C=C(c1cccc(C)c1)n1ccc2cc(OCCc3ccc4c(n3)N(C(=O)OC(C)(C)C)CCC4)ccc21
Yield: 40 %

Procedure:
The title compound was synthesized from 3-chloro-3-m-tolyl-acrylic acid ethyl ester and 7-[2-(1H-indol-5-yloxy)-ethyl]-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester using the procedure outlined in Example 18, step (d), in a 40% yield as an E/Z isomeric mixture. 1H NMR (CDCl3) δ 7.19 (m, 2.2H), 7.04 (m, 2.6H), 6.96 (m, 1.6H), 6.86 (m, 1.6H), 6.66 (m, 2H), 6.48 (d, 0.8H, J=0.8 Hz), 6.40 (d, 0.2H, J=0.8 Hz), 6.11 (s, 0.8H), 6.04 (s, 0.2H), 4.30 (m, 2H), 3.93 (m, 2H), 3.68 (m, 2H), 3.13 (t, 2H, J=6.4), 2.65 (t, 2H, J=6.4 Hz), 2.24 (s, 3H), 1.85 (m, 2H), 1.43 (s, 9H), 0.94 (t, 3H, J=6.8 Hz).