Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[C:8](=[O:14])[CH2:7][CH2:6]2.[N:15]1[CH:20]=[CH:19][C:18]([CH:21]=O)=[CH:17][CH:16]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.O>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[C:8](=[O:14])[CH:21]([C:18]1[CH:17]=[CH:16][N:15]=[CH:20][CH:19]=1)[C:6]2=[CH2:7]
Reactant: O=Cc1ccncc1
Reactant: COc1cc2c(cc1OC)C(=O)CC2
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: C=C1c2cc(OC)c(OC)cc2C(=O)C1c1ccncc1
Yield: 95.7 %

Procedure:
5,6 Dimethoxy indanone (100 grams), Pyridine-4-carboxaldehyde (78.0 grams) and p-toluene sulfonic acid (138.4 grams) were suspended in toluene (1250 ml) and heated to reflux using water separator for 6 hours. The resulting mass was cooled to 25–40° C. and the solid was filtered off under suction. Further the wet solid was suspended in aqueous 10% sodium carbonate solution (1200 ml) and stirred for 30–60 minutes. The resulting pale yellow precipitate solid was filtered off under suction, washed with water (1000 ml) and dried at a temperature of 80° C. to afford 5,6 Dimethoxy-2-(pyridin-4yl)-methylene-indan-1one (Weight: 140 grams, 95.8%).
Reaction SMILES: [CH3:1][CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=O.[BH4-].[Na+]>>[CH3:1][C:2]1[CH2:10][C:9]2[C:4]([CH:3]=1)=[CH:5][CH:6]=[CH:7][CH:8]=2
Reactant: CC1Cc2ccccc2C1=O
Agent: [BH4-]
Agent: [Na+]
Product: CC1=Cc2ccccc2C1
Yield: 83.1 %

Procedure:
Analogously to Example D, 5.0 g (34 mmol) of 2-methyl-1-indanone (5) were reduced with 1.94 g (51 mmol) of NaBH4. The alcohol, which was not purified further, was then further reacted in the presence of 0.2 g of p-toluene-sulfonic acid in 100 ml of toluene at 80° C. Chromatography on 100 g of silica gel (hexane/methylene chloride 9:1) gave 3.68 g (82%) of 2-methylindene (6).
Reaction SMILES: [CH2:1]([C:5]1[CH:10]=[C:9](Cl)[N:8]=[C:7]([S:12][CH3:13])[N:6]=1)[CH2:2][CH:3]=[CH2:4].[O:14]1[CH:18]=[CH:17][CH:16]=[C:15]1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>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>[CH2:1]([C:5]1[CH:10]=[C:9]([C:15]2[O:14][CH:18]=[CH:17][CH:16]=2)[N:8]=[C:7]([S:12][CH3:13])[N:6]=1)[CH2:2][CH:3]=[CH2:4]
Reactant: C=CCCc1cc(Cl)nc(SC)n1
Reactant: OB(O)c1ccco1
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: C1COCCO1
Product: C=CCCc1cc(-c2ccco2)nc(SC)n1
Temperature: 110 °C

Procedure:
To a solution of 4-(3-buten-1-yl)-6-chloro-2-(methylthio)-pyrimidine (0.79 g, 3.69 mmol), 2-furanylboronic acid (0.45 g, 4.06 mmol), aq. Na2CO3 solution (2M, 4.1 mL) in dioxane (37 mL) at room temperature was added tetrakis(triphenylphosphine)palladium(0) (0.21 g, 0.185 mmol). The reaction mixture in sealed tube was stirred and refluxed at 110° C. for 18 hours. After the reaction was completed, the mixture was filtered through a pad of silica gel. The filtrate was evaporated in vacuo. The residue was dissolved in methylene chloride (30 mL). It was washed with water (30 mL×2). The organic layer was dried over MgSO4 and filtered, evaporated in vacuo. The residue was purified by column chromatography to provide the title compound. MH+247.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]2[CH:15]=[CH:14][C:11]([CH:12]=O)=[CH:10][CH:9]=2)[CH:3]=1.Cl.[NH2:17][OH:18].C(=O)([O-])O.[Na+]>C(O)C>[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]2[CH:15]=[CH:14][C:11]([CH:12]=[N:17][OH:18])=[CH:10][CH:9]=2)[CH:3]=1
Reactant: Cc1ccnc(-c2ccc(C=O)cc2)c1
Reactant: NO
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Product: Cc1ccnc(-c2ccc(C=NO)cc2)c1
Temperature: 60 °C
Reaction time: 1 h
Yield: 94 %

Procedure:
To a suspension of 4-(4-methylpyridin-2-yl)benzaldehyde (425 mg) in ethanol (5 ml) was added hydroxylamine hydrochloride (224 mg), and the mixture was stirred at 60° C. for 1 hour. After cooling, the mixture was poured into a saturated aqueous sodium hydrogencarbonate solution and extracted with dichloromethane. The organic layer was washed with water and brine, dried over sodium sulfate and evaporated under reduced pressure to give 4-(4-methylpyridin-2-yl)benzaldehyde oxime (0.43 g).
Reaction SMILES: CC(C)([O-])C.[K+].[OH:7][NH:8][C:9](=O)[CH3:10].F[C:13]1[C:20]([I:21])=[C:19]([CH3:22])[CH:18]=[CH:17]C=1C#N.C[N:24](C=O)C>>[I:21][C:20]1[C:13]2[O:7][N:8]=[C:9]([NH2:24])[C:10]=2[CH:17]=[CH:18][C:19]=1[CH3:22]
Reactant: Cc1ccc(C#N)c(F)c1I
Reactant: CC(=O)NO
Reactant: CN(C)C=O
Agent: CC(C)(C)[O-]
Agent: [K+]
Product: Cc1ccc2c(N)noc2c1I
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 81 %

Procedure:
Potassium tert-butoxide (2.20 g, 19.2 mmol) was added to a solution of N-hydroxyacetamide (1.44 g, 19.2 mmol) in N,N′-dimethylformamide (25 mL) under argon. The resulting white suspension was stirred at room temperature for 30 minutes and then 2-fluoro-3-iodo-4-methylbenzonitrile (WO2006094187, 2.00 g, 7.7 mmol) was added and the mixture was stirred at room temperature for 6 hours. Further N-hydroxyacetamide (0.29 g, 3.9 mmol) and potassium tert-butoxide (0.45 g, 3.9 mmol) were added and the mixture was stirred at room temperature overnight. The solvent was evaporated under reduced pressure and water and ethyl acetate were added. The organic layer was separated and the aqueous phase was extracted with further ethyl acetate. The combined organic layers were washed with brine, dried, (MgSO4) and evaporated. The residue was purified by flash chromatography (9:1 hexanes/ethyl acetate to ethyl acetate) to yield the title compound (1.79 g, 81%) as a solid.
Reaction SMILES: [F:1][C:2]1[CH:8]=[C:7](Br)[CH:6]=[C:5]([F:10])[C:3]=1[NH2:4].[CH3:11][O:12][C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[CH:17][CH:18]=1>>[F:1][C:2]1[CH:8]=[C:7]([C:17]2[CH:16]=[CH:15][CH:14]=[C:13]([O:12][CH3:11])[CH:18]=2)[CH:6]=[C:5]([F:10])[C:3]=1[NH2:4]
Reactant: COc1cccc(B(O)O)c1
Reactant: Nc1c(F)cc(Br)cc1F
Product: COc1cccc(-c2cc(F)c(N)c(F)c2)c1
Yield: 79.6 %

Procedure:
The title compound (992 mg) was prepared from 2,6-difluoro-4-bromo aniline (1.1 g, 5.3 mmol) and 3-methoxyphenylboronic acid (1.04 g, 6.8 mmol) as a pale-yellow liquid. 1H-NMR (δ ppm, CDCl3+DMSO-d6, 400 MHz): 7.21-7.20 (m, 1H), 6.99-6.89 (m, 3H), 6.87-6.83 (m, 1H), 6.74-6.68 (m, 1H), 3.97 (bs, 2H), 3.69 (s, 3H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[CH2:14][C:13](=[O:15])[NH:12][C:11]3[CH:16]=[C:17]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[CH:18]=[CH:19][C:10]=3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:27][C:28](OC(C)=O)=[O:29]>CC(O)=O>[F:26][C:23]1[CH:22]=[CH:21][C:20]([C:17]2[CH:18]=[CH:19][C:10]3[N:9]=[C:8]([C:4]4[CH:3]=[C:2]([NH:1][C:28](=[O:29])[CH3:27])[CH:7]=[CH:6][CH:5]=4)[CH2:14][C:13](=[O:15])[NH:12][C:11]=3[CH:16]=2)=[CH:25][CH:24]=1
Reactant: CC(=O)OC(C)=O
Reactant: Nc1cccc(C2=Nc3ccc(-c4ccc(F)cc4)cc3NC(=O)C2)c1
Solvent: CC(=O)O
Product: CC(=O)Nc1cccc(C2=Nc3ccc(-c4ccc(F)cc4)cc3NC(=O)C2)c1

Procedure:
Prepared from 4-(3-amino-phenyl)-8-(4-fluoro-phenyl)-1,3-dihydro-benzo [b][1,4]-2-one (Example 70) by treatment with Ac2O in HOAc at 80° C. Obtained as a light yellow solid (9 mg).
Reaction SMILES: I[C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.[Cl:9][C:10]1[S:14][C:13](B(O)O)=[CH:12][CH:11]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.O.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>[Cl:9][C:10]1[S:14][C:13]([C:2]2[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=2)=[CH:12][CH:11]=1
Reactant: OB(O)c1ccc(Cl)s1
Reactant: Oc1cccc(I)c1
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: O
Solvent: COCCOC
Product: Oc1cccc(-c2ccc(Cl)s2)c1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 91.8 %

Procedure:
To a solution of 3-iodophenol (1.0 g, 4.55 mmol) in DME (10 ml) was added Pd(PPh3)4 (263 mg, 0.227 mmol) at ambient temperature under N2. After stirring for 20 min., 5-chlorothiophene-2-boronic acid (886 mg, 5.45 mmol) and a solution of Na2CO3 (723 mg, 6.82 mmol) in H2O (3 ml) were added and the mixture was refluxed for 2 h. The mixture was cooled to room temperature and partitioned between ethyl acetate (30 ml) and H2O. The organic layer was washed with saturated NaHCO3 aqueous solution, H2O and then brine, dried (sodium sulfate) and evaporated in vacuo. The residue was purified by silica gel (15 g) chromatography eluting with hexane/ethyl acetate (10:1) to give 3-(5-chloro-2-thienyl)phenol (0.88 g, 91.9%).
Reaction SMILES: [Mg].II.Br[C:5]1[CH:10]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[C:8]([O:15][CH3:16])=[C:7]([C:17]([CH3:20])([CH3:19])[CH3:18])[CH:6]=1.[P:21]([O-:26])(OC)OC.Cl>C1COCC1.C1(C)C=CC=CC=1.O>[C:17]([C:7]1[CH:6]=[C:5]([PH:21](=[O:26])[C:5]2[CH:10]=[C:9]([C:11]([CH3:13])([CH3:14])[CH3:12])[C:8]([O:15][CH3:16])=[C:7]([C:17]([CH3:20])([CH3:19])[CH3:18])[CH:6]=2)[CH:10]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[C:8]=1[O:15][CH3:16])([CH3:20])([CH3:19])[CH3:18]
Reactant: COP([O-])OC
Reactant: COc1c(C(C)(C)C)cc(Br)cc1C(C)(C)C
Agent: Cl
Agent: II
Agent: [Mg]
Solvent: C1CCOC1
Solvent: O
Solvent: Cc1ccccc1
Product: COc1c(C(C)(C)C)cc([PH](=O)c2cc(C(C)(C)C)c(OC)c(C(C)(C)C)c2)cc1C(C)(C)C
Temperature: 5 °C
Reaction time: 1 h
Yield: 27.2 %

Procedure:
Under argon atmosphere, a solution of magnesium (4.0 g, 0.95 equivalents) and a small amount of iodine in THF (50 mL) was stirred at room temperature for 1 hour. After 4-bromo-2,6-di-tert-butylanisole (52 g, 0.175 mol) synthesized in Reference Example 2 was added at 46° C. to 53° C. thereto, the mixture was stirred at 5° C. for 1 hour. Then, dimethyl phosphite (11.4 g, 0.52 equivalents) was added and the mixture was stirred at 5° C. for 1 hour. After water (50 mL) was added at 3° C. and toluene (50 mL) and 6M-HCl (20 mL) were then added, the mixture was stirred at room temperature for 30 minutes. The reaction solution was allowed to separate into layers. An organic layer was washed successively with water (20 mL), a 5% NaHCO3 aqueous solution (20 mL) and a 5% NaCl aqueous solution (20 mL), dried over anhydrous magnesium sulfate and then naturally filtered. The filtrate was concentrated under reduced pressure. The residue was recrystallized from heptane to obtain the title compound (11.6 g, pale yellowish white crystal). Yield 20.5%, mp. 166.1° C.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]([Cl:12])[C:3]=1[C:4](N)=[O:5].N([O-])=[O:14].[Na+]>C(O)(=O)C.O>[Cl:1][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]([Cl:12])[C:3]=1[C:4]([OH:14])=[O:5]
Reactant: Cc1cc(Cl)c(C(N)=O)c(Cl)c1
Reactant: O=N[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: Cc1cc(Cl)c(C(=O)O)c(Cl)c1
Temperature: 5 °C
Reaction time: 0.5 h
Yield: 82.7 %

Procedure:
A stirred 0° C. solution of 2,6-dichloro-4-methylbenzamide (8.6 g, 42. mmol) in 2:1 (v/v) acetic acid-concentrated hydrochloric acid (165 ml) was treated dropwise with a solution of sodium nitrite (19.0 g, 275 mmol) in water (42 ml). The mixture was stirred 30 minutes at 5° C., slowly warmed to 85° C., and kept 1 hour. The mixture was cooled, concentrated under vacuum, and treated with cold water (50 ml). The product was filtered, washed twice with cold water, and dried 16 hours at 50° C. over phosphorus pentoxide under vacuum to provide 7.15 g (83%) of 2,6-dichloro-4-methylbenzoic acid, m.p. 139°-145° C.
Reaction SMILES: [C:1]1(=[O:7])[O:6][C:4](=O)[CH2:3][CH2:2]1.[CH:8]1[C:13]([NH2:14])=[CH:12][CH:11]=[C:10]([OH:15])[CH:9]=1>CN(C)C=O.O>[OH:15][C:10]1[CH:11]=[CH:12][C:13]([N:14]2[C:1](=[O:7])[CH2:2][CH2:3][C:4]2=[O:6])=[CH:8][CH:9]=1
Reactant: O=C1CCC(=O)O1
Reactant: Nc1ccc(O)cc1
Solvent: O
Solvent: CN(C)C=O
Product: O=C1CCC(=O)N1c1ccc(O)cc1
Temperature: 170 °C
Yield: 94 %

Procedure:
A solution of succinic anhydride (100 g, 1 mol) in dimethylformamide (50 g) was added slowly to a stirred solution of p-aminophenol (109 g, 1 mol) in dimethylformamide (150 g) at a temperature between 25° and 30° C. After 1.5 h the reaction mixture was transferred to a film evaporator in which dimethylformamide (160 g) was separated off at a pressure of 0.05 bar and a temperature of 130° C. A solution of p-toluenesulphonic acid (2 g) in methanol (18 g) was added to the residue obtained, the temperature was increased to 170° C. and dimethylformamide and water were evaporated at a pressure of 13 mbar. The brown solid material thus obtained was dissolved in dimethylformamide having a temperature of 90° C., water was added to the solution until it became turbid, the turbid solution was allowed to adopt ambient temperature and the crystals obtained were filtered off. The N-(4-hydroxyphenyl)succinimide was obtained in a yield of 94 % and with a purity of more than 99%.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4](Br)[C:5]2[O:9][CH:8]=[CH:7][C:6]=2[CH:10]=1.[C:12]([O:16][C:17]([N@:19]1[CH2:21][CH:20]1[CH3:22])=[O:18])([CH3:15])([CH3:14])[CH3:13]>>[C:12]([O:16][C:17]([NH:19][C@@H:20]([CH3:22])[CH2:21][C:4]1[C:5]2[O:9][CH:8]=[CH:7][C:6]=2[CH:10]=[C:2]([F:1])[CH:3]=1)=[O:18])([CH3:15])([CH3:14])[CH3:13]
Reactant: Fc1cc(Br)c2occc2c1
Reactant: CC1CN1C(=O)OC(C)(C)C
Product: C[C@@H](Cc1cc(F)cc2ccoc12)NC(=O)OC(C)(C)C
Yield: 45.5 %

Procedure:
Beginning with 0.94 gm (4.4 mMol) 5-fluoro-7-bromobenzofuran and 0.63 mg (4 mMol) (S)-(+)-N-tert-butoxycarbonyl-2-methylaziridine, 0.534 gm (46%) of the desired compound were prepared essentially as described in Example 10.
Reaction SMILES: [C:1]([O:5][CH2:6][CH3:7])(=[O:4])[NH:2][NH2:3].[CH3:8][N:9]1[CH:13]=[C:12]([CH:14]=O)[C:11]([C:16]2[O:17][C:18]([N+:21]([O-:23])=[O:22])=[CH:19][CH:20]=2)=[N:10]1.C(O)(=O)C.O>C(O)C>[CH2:6]([O:5][C:1]([NH:2][N:3]=[CH:14][C:12]1[C:11]([C:16]2[O:17][C:18]([N+:21]([O-:23])=[O:22])=[CH:19][CH:20]=2)=[N:10][N:9]([CH3:8])[CH:13]=1)=[O:4])[CH3:7]
Reactant: CCOC(=O)NN
Reactant: Cn1cc(C=O)c(-c2ccc([N+](=O)[O-])o2)n1
Solvent: CCO
Solvent: CC(=O)O
Solvent: O
Product: CCOC(=O)NN=Cc1cn(C)nc1-c1ccc([N+](=O)[O-])o1
Yield: 97 %

Procedure:
Add a solution of 19.5 g of ethyl carbazate in 250 ml of ethanol dropwise to 35 g of 1-methyl-3-(5-nitro-2-furyl)pyrazole-4-carboxaldehyde and 1 ml of glacial acetic acid in 400 ml of ethanol. Stir the resulting reaction mixture for 80 minutes at from 35° to 40° C, and add 650 ml of water dropwise to the thus-obtained suspension at room temperature. Cool in an ice bath and separate the produced precipitate by vacuum filtration. Wash the residue with ethanol/water (1:1) and with water to obtain a 97% yield of 1-methyl-3-(5-nitro-2-furyl)pyrazole-4-carboxaldehyde-ethoxycarbonylhydrazone [m.p. 217.5° to 219° C (with decomposition)].
Reaction SMILES: O[C@H:2]1[C@H:7]([N:8]2[CH2:12][CH2:11][CH2:10][S:9]2(=[O:14])=[O:13])[C:6]2[CH:15]=[C:16]([S:19]([CH3:22])(=[O:21])=[O:20])[CH:17]=[CH:18][C:5]=2[O:4][C:3]1([CH3:24])[CH3:23].C(OC(=O)C)(=O)C.O>N1C=CC=CC=1>[O:14]=[S:9]1(=[O:13])[CH2:10][CH2:11][CH2:12][N:8]1[C:7]1[C:6]2[CH:15]=[C:16]([S:19]([CH3:22])(=[O:20])=[O:21])[CH:17]=[CH:18][C:5]=2[O:4][C:3]([CH3:23])([CH3:24])[CH:2]=1
Reactant: CC1(C)Oc2ccc(S(C)(=O)=O)cc2[C@@H](N2CCCS2(=O)=O)[C@@H]1O
Solvent: CC(=O)OC(C)=O
Solvent: O
Solvent: c1ccncc1
Product: CC1(C)C=C(N2CCCS2(=O)=O)c2cc(S(C)(=O)=O)ccc2O1
Reaction time: 8 h
Yield: 46 %

Procedure:
A solution of trans-3,4-dihydro-3-hydroxy-4-(1,1-dioxoisothiazolidin-2-yl)-6-mesyl-2,2-dimethyl-2H-1-benzopyran (0.32 g) in pyridine (10 ml) was treated with acetic anhydride (5 ml), and the mixture was stood at room temperature overnight. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed successively with 1N hydrochloric acid, a saturated aqueous solution of sodium bicarbonate and brine, and then dried over anhydrous magnesium sulfate. Removal of the solvent under reduced pressure gave the crude product, which was purified by recrystallization from ethyl acetate to give 4-(1,1-dioxoisothiazolidin-2-yl)-6-mesyl-2,2-dimethyl-2H-1-benzopyran (0.14 g).
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8](Cl)=[N:9]2)([O-])=O.[F:15][C:16]1[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1.[CH3:26][S:27][C:28]1[CH:35]=[CH:34][CH:33]=[CH:32][C:29]=1[CH2:30][NH2:31]>>[F:15][C:16]1[CH:21]=[CH:20][C:19]([S:22]([NH:1][C:4]2[CH:13]=[CH:12][CH:11]=[C:10]3[C:5]=2[CH:6]=[CH:7][C:8]([NH:31][CH2:30][C:29]2[CH:32]=[CH:33][CH:34]=[CH:35][C:28]=2[S:27][CH3:26])=[N:9]3)(=[O:24])=[O:23])=[CH:18][CH:17]=1
Reactant: O=[N+]([O-])c1cccc2nc(Cl)ccc12
Reactant: CSc1ccccc1CN
Reactant: O=S(=O)(Cl)c1ccc(F)cc1
Product: CSc1ccccc1CNc1ccc2c(NS(=O)(=O)c3ccc(F)cc3)cccc2n1

Procedure:
The title compound, MS: m/e=454.3 (M+H+), was prepared in accordance with the general method of example 61 from 5-nitro-2-chloroquinoline, 4-fluorobenzenesulfonylchloride and 2-(methylthio)benzylamine.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:36]=[CH:35][CH:34]=[CH:33][C:10]=1[C:11]([NH:13][C:14]1[CH:32]=[CH:31][C:17]([C:18]([N:20]2[C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=3[CH2:24][CH2:23][CH2:22][CH2:21]2)=[O:19])=[CH:16][CH:15]=1)=[O:12].[C:37]([O-:40])(=[O:39])[CH3:38].[Na+].[I-].[Na+]>C(O)(=O)C>[C:37]([O:40][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:36]=[CH:35][CH:34]=[CH:33][C:10]=1[C:11]([NH:13][C:14]1[CH:32]=[CH:31][C:17]([C:18]([N:20]2[C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=3[CH2:24][CH2:23][CH2:22][CH2:21]2)=[O:19])=[CH:16][CH:15]=1)=[O:12])(=[O:39])[CH3:38]
Reactant: CC(=O)[O-]
Reactant: O=C(Nc1ccc(C(=O)N2CCCCc3ccccc32)cc1)c1ccccc1OCCCCCCBr
Agent: [I-]
Agent: [Na+]
Solvent: CC(=O)O
Product: CC(=O)OCCCCCCOc1ccccc1C(=O)Nc1ccc(C(=O)N2CCCCc3ccccc32)cc1
Yield: 55.6 %

Procedure:
A mixture of 1-{4-[2-(6-bromohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (2.00 g), sodium acetate (0.36 g), sodium iodide (0.55 g) and acetic acid (20 ml) is refluxed for 1 day. The solvent is distilled off and the resulting residue is extracted with ethyl acetate. The organic layer is washed successively with 2N aqueous sodium hydroxide solution and saturated saline solution, and dried over magnesium sulfate. The solvent is concentrated and the resulting residue is purified by silica gel column chromatography (eluent; chloroform:methanol=500:1), and recrystallized from ethanol to give 1-{4-[2-(6-acetyloxyhexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (1.07 g) as white powder, m.p. 145-146° C.
Reaction SMILES: Cl[CH2:2][O:3][CH3:4].[Br:5][C:6]1[CH:7]=[C:8]([OH:13])[CH:9]=[C:10]([Br:12])[CH:11]=1.C(N(C(C)C)CC)(C)C.O>C(Cl)Cl>[Br:5][C:6]1[CH:7]=[C:8]([O:13][CH2:2][O:3][CH3:4])[CH:9]=[C:10]([Br:12])[CH:11]=1
Reactant: Oc1cc(Br)cc(Br)c1
Reactant: COCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: O
Product: COCOc1cc(Br)cc(Br)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 101 %

Procedure:
Chloromethylmethyl ether (1.45 mL, 19.13 mmol) was added dropwise to a solution of 3,5-dibromophenol (4.38 g, 17.39 mmol) and diisopropylethylamine (3.63 mL, 20.90 mmol) in CH2Cl2 (40 mL) at 0° C. The mixture was warmed to RT, stirred for 16 h, and added to H2O (50 mL). The layers were separated, and the aqueous fraction was extracted with CH2Cl2 (2×50 mL). The combined organic fractions were washed with brine (25 mL), dried over anhydrous MgSO4, and the solvent was evaporated to provide 5.20 g (100%) of 1,3-dibromo-5-methoxymethoxy-benzene (113a).
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[NH:7])=[CH:4][CH:3]=1.[Cl:11][C:12]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:13]=1[CH:14]=[C:15]([C:18]#[N:19])[C:16]#[N:17]>>[NH2:19][CH2:18][C:15]1[C:16]([NH2:17])=[N:7][C:6]([C:5]2[CH:9]=[CH:10][C:2]([F:1])=[CH:3][CH:4]=2)=[N:8][C:14]=1[C:13]1[CH:20]=[CH:21][C:22]([Cl:24])=[CH:23][C:12]=1[Cl:11]
Reactant: N=C(N)c1ccc(F)cc1
Reactant: N#CC(C#N)=Cc1ccc(Cl)cc1Cl
Product: NCc1c(N)nc(-c2ccc(F)cc2)nc1-c1ccc(Cl)cc1Cl

Procedure:
The title compound, MS: m/e=362.9 (M+H+), was prepared from 4-fluoro-benzamidine and 2-(2,4-dichloro-benzylidene)-malononitrile in analogy to the process described in Example 11 as a solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:32])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8]([CH3:31])=[C:9]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:21][CH:20]=1)[C:10](=[O:17])[NH:11]2.Cl[CH:34]([F:36])[F:35]>>[CH3:1][O:2][C:3](=[O:32])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8]([CH3:31])=[C:9]([CH2:18][C:19]1[CH:20]=[CH:21][C:22]([C:25](=[O:30])[C:26]([CH3:28])([CH3:27])[CH3:29])=[CH:23][CH:24]=1)[C:10]([O:17][CH:34]([F:36])[F:35])=[N:11]2
Reactant: FC(F)Cl
Reactant: COC(=O)COc1ccc(F)c2[nH]c(=O)c(Cc3ccc(C(=O)C(C)(C)C)cc3)c(C)c12
Product: COC(=O)COc1ccc(F)c2nc(OC(F)F)c(Cc3ccc(C(=O)C(C)(C)C)cc3)c(C)c12

Procedure:
The title compound was prepared by the method of Preparation 10c using {3-[4-(2,2-dimethylpropionyl)benzyl]-8-fluoro-4-methyl-2-oxo-1,2-dihydroquinolin-5-yloxy}acetic acid methyl ester and chlorodifluoromethane.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])O.[Na+].Br[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]Br.O>C1(C)C=CC=CC=1.C(OCC)(=O)C>[N:1]1([C:2]2[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=2)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1
Reactant: BrCCCCCBr
Reactant: Nc1cccc(O)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: Cc1ccccc1
Product: Oc1cccc(N2CCCCC2)c1
Reaction time: 16 h

Procedure:
3-Aminophenol (500 mg) was dissolved in toluene (5.0 ml), the solution was added with sodium hydrogencarbonate (846.5 mg) and 1,5-dibromopentane (686.3 μl) at room temperature, and the mixture was stirred for 16 hours under reflux by heating. The reaction mixture was cooled, and then added with distilled water and ethyl acetate for extraction, and the organic layer was dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure to obtain the title compound (513 mg).
Reaction SMILES: [CH2:1]([C:5]1[N:6]=[C:7]([CH2:27][O:28][CH3:29])[NH:8][C:9](=[O:26])[C:10]=1[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=2)=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH3:4].C(=O)([O-])[O-].[Cs+].[Cs+].I[CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39].CN(C)C(=O)C>C(OCC)(=O)C>[CH2:1]([C:5]1[N:6]=[C:7]([CH2:27][O:28][CH3:29])[N:8]([CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])[C:9](=[O:26])[C:10]=1[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=2)=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CC(C)(C)CI
Reactant: CCCCc1nc(COC)[nH]c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC(=O)N(C)C
Solvent: CCOC(C)=O
Product: CCCCc1nc(COC)n(CC(C)(C)C)c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Temperature: 130 °C
Reaction time: 2 h
Yield: 30 %

Procedure:
A mixture of 4′-{[4-butyl-2-(methoxymethyl)-6-oxo-1,6-dihydropyrimidin-5-yl]methyl}biphenyl-2-carbonitrile (5 g), cesium carbonate (8.4 g), 1-iodo-2,2-dimethylpropane (3.4 mL) and N,N-dimethylacetamide (50 mL) was stirred at 130° C. for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with 5% aqueous potassium hydrogen sulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (1.76 g, 30%).