Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12](=O)[CH2:11][CH:10]([C:14]([O:16]C)=[O:15])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.S(Cl)(Cl)=O>CO>[Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[CH2:12][CH2:11][CH:10]([C:14]([OH:16])=[O:15])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)C1CC(=O)N(c2cccc(Cl)c2)C1
Solvent: O=S(Cl)Cl
Solvent: CO
Product: O=C(O)C1CCN(c2cccc(Cl)c2)C1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 98 %

Procedure:
Methyl 1-(3-chlorophenyl)-5-oxopyrrolidine-3-carboxylate (Ref: Tetrahedron, 62:4011-4017 (2006)). To a cold solution of MeOH (8.35 mL) (0° C.) was added thionyl chloride (0.335 mL, 4.59 mmol) dropwise. After 30 min, Intermediate 10 (1 g, 4.17 mmol) was added, and the reaction mixture was warmed to rt. The reaction mixture was then concentrated and the residue dissolved in EtOAc, washed with saturated NaHCO3, H2O and brine. The organic layers were dried over Na2SO4, filtered and concentrated to yield the desired product (1.04 g, 98%) as yellow oil. MS(ESI) m/z: 254.0 (M+H)+.
Reaction SMILES: C[C@@H]1O[C@@H](O[C@@H:9]2[C:18]3[C:13](=[C:14]([OH:32])[C:15]4[C:24](=[O:25])[C:23]5[CH:26]=[CH:27][CH:28]=[C:29]([O:30][CH3:31])[C:22]=5[C:20](=O)[C:16]=4[C:17]=3[OH:19])[CH2:12][C@@:11]([OH:36])([C:33]([CH3:35])=[O:34])[CH2:10]2)C[C@H](N)[C@@H]1O.Cl.[H][H]>CO.[Pd]>[C:33]([C@:11]1([OH:36])[CH2:12][C:13]2[C:14](=[O:32])[C:15]3[C:24]([OH:25])=[C:23]4[C:22]([C:29]([O:30][CH3:31])=[CH:28][CH:27]=[CH:26]4)=[CH:20][C:16]=3[C:17](=[O:19])[C:18]=2[CH2:9][CH2:10]1)(=[O:34])[CH3:35]
Reactant: COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(C)=O)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Solvent: CO
Product: COc1cccc2c(O)c3c(cc12)C(=O)C1=C(C[C@@](O)(C(C)=O)CC1)C3=O

Procedure:
Daunomycin hydrochloride (compound 17) (20 mg) in dry methanol (20 ml) was catalytically reduced with hydrogen gas and 5% palladium on barium sulfate (20 mg) 5.5 h at room temperature. Exposure of the mixture to the atmosphere gave a red solution which was filtered, evaporated and preparatively chromatographed on silica gel layers using chloroform/methanol (98:2) as eluant. The red band Rf 0.28-0.43 gave the product (compound 19) as a red solid (12 mg, 88%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:13][C:12]([C:14]([O:16]CC)=O)=[N:11][N:10]=2)=[CH:5][CH:4]=1.[C-]#N.[Na+].Cl.[OH:23][CH:24]1[CH2:27][NH:26][CH2:25]1.C(N(CC)CC)C>CO.ClCCl.O>[OH:23][CH:24]1[CH2:27][N:26]([C:14]([C:12]2[O:13][C:9]([C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=3)=[N:10][N:11]=2)=[O:16])[CH2:25]1
Reactant: OC1CNC1
Reactant: CCOC(=O)c1nnc(-c2ccc(OC)cc2)o1
Agent: Cl
Agent: [C-]#N
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Solvent: CCN(CC)CC
Product: COc1ccc(-c2nnc(C(=O)N3CC(O)C3)o2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 77 %

Procedure:
To a suspension of ethyl 5-(4-methoxyphenyl)-1,3,4-oxadiazole-2-carboxylate—see e.g. Journal fuer Praktische Chemie, 327, 109-116 (1985)—(0.50 g, 2.01 mmol) in dry methanol (10 mL) was added sodium cyanide (20 mg, 0.40 mmol). A solution of 3-hydroxyazetidine hydrochloride (0.26 g, 2.42 mmol) in methanol (2 mL) and then triethylamine (0.34 mL, 2.42 mmol) were added at ambient temperature. The reaction mixture was stirred at ambient temperature overnight. Water (20 mL) and dichloromethane (30 mL) were added. Some of the desired product precipitated and was filtered off. The two layers after filtration were separated and the aqueous phase was extracted twice with dichloromethane (30 mL). The combined organic layers were dried over MgSO4 and the solution was evaporated. In total, there was obtained 0.43 g (77%) of 4A as a solid. 1H NMR (400 MHz, DMSO-d6): δ 3.82 (dd, 1H), 3.84 (s, 3H), 4.30 (m, 2H), 4.55 (m, 1H), 4.77 (dd, 1H), 5.85 (d, 1H), 7.16 (d, 2H), 7.98 (d, 2H), MS (APCI+) m/z 276 [M+H]+.
Reaction SMILES: [OH2:1].[OH2:2].C[N+]([O-])(C)C.[NH:8]1[C:12]2=[N:13][CH:14]=[CH:15][CH:16]=[C:11]2[C:10]2([CH2:20][CH:19]=[CH:18][CH2:17]2)[C:9]1=O>ClCCl.[Os](=O)(=O)(=O)=O>[OH:1][CH:18]1[CH:19]([OH:2])[CH2:20][C:10]2([C:11]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[N:8]=[CH:9]2)[CH2:17]1
Reactant: O=C1Nc2ncccc2C12CC=CC2
Reactant: O
Agent: O=[Os](=O)(=O)=O
Agent: C[N+](C)(C)[O-]
Solvent: ClCCl
Product: OC1CC2(C=Nc3ncccc32)CC1O
Yield: 92.4 %

Procedure:
To a mixture of trimethylamine-N-oxide dihydrate (408 mg, 3.67 mmol) and spiro[cyclopent-3-ene-1,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (622 mg, 3.34 mmol) in dichloromethane (115 mL) was added osmium tetroxide (25 uL of 2.5% solution in 2-methyl-2-propanol). After 24 h the reaction mixture was concentrated. The crude product was loaded onto a silica gel chromatography column with a minimal amount of methanol and eluted with a gradient of 5 to 20% methanol:dichloromethane to give the title compound (0.63 g). MS: m/z=221.0 (M+1).
Reaction SMILES: [CH3:1][CH:2]([CH3:13])[CH2:3][C:4](=[N:11][OH:12])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[Br:14][CH2:15][CH2:16]Br.[OH-].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[Br:14][CH2:15][CH2:16][O:12][N:11]=[C:4]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[CH2:3][CH:2]([CH3:13])[CH3:1]
Reactant: BrCCBr
Reactant: CC(C)CC(=NO)c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [Na+]
Solvent: O
Product: CC(C)CC(=NOCCBr)c1ccccc1
Temperature: 0 °C
Reaction time: 72 h

Procedure:
A mixture of the above oxime (5.0 g, 28 mmol), 1,2-dibromoethane (25 ml) and N,N,N,N-tetrabutylammoniumbromide (1.0 g, 3 mmol) was cooled to 0° C. and 9N sodium hydroxide (35 ml) was carefully added. The mixture was stirred vigorously at room temperature for 3 days. Water (50 ml) was added and the resulting mixture extracted with dichloromethane (2×100 ml). To the combined organic phases was added water (50 ml) and pH in the aqueous phase was adjusted to 5 with 10% aqueous citric acid. The organic phase was washed with water (50 ml) and brine (50 ml) and dried (MgSO4). The solvent was evaporated in vacuo to give 8.0 g of 3-methylbutyrophenone O-(2-bromoethyl)oxime.
Reaction SMILES: O1CCN([CH2:7][C:8]2[CH:14]=[C:13]([C:15]([CH2:18][C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:17])[CH3:16])[CH:12]=[C:10]([OH:11])[C:9]=2[OH:23])CC1.[C:24]1([SH:30])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>CN(C)C=O.C(OCC)C>[S:30]([CH2:7][C:8]1[CH:14]=[C:13]([C:15]([CH2:18][C:19]([CH3:20])([CH3:21])[CH3:22])([CH3:16])[CH3:17])[CH:12]=[C:10]([OH:11])[C:9]=1[OH:23])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: CC(C)(C)CC(C)(C)c1cc(O)c(O)c(CN2CCOCC2)c1
Reactant: Sc1ccccc1
Solvent: CN(C)C=O
Solvent: CCOCC
Product: CC(C)(C)CC(C)(C)c1cc(O)c(O)c(CSc2ccccc2)c1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
A suspension of 3-morpholinomethyl-5-t-octylcatechol (564 g, 1.76 mole) and 193.4 g (1.76 mole) benzenethiol in 0.8 liter dimethylformamide was kept at 130° C. under a nitrogen atmosphere for 20 hours. The reaction mixture was cooled to 25° C. and diluted with 3,000 ml diethyl ether. The resulting solution was washed in turn with 3×1,000 ml water, 500 ml 10% hydrochloric acid, 500 ml water and 500 ml brine. The washed solution was dried over anhydrous magnesium sulfate and evaporated in vacuo to a yellow oil (548.9 g, 91% yield) of the title compound.
Reaction SMILES: C(O)CCCCCCC(C)C.[C:12]([C:15]1[C:20](C(O)=O)=[CH:19][N:18]=[N:17][CH:16]=1)([OH:14])=[O:13]>[Cu]>[C:12]([C:15]1[CH:20]=[CH:19][N:18]=[N:17][CH:16]=1)([OH:14])=[O:13]
Reactant: O=C(O)c1cnncc1C(=O)O
Agent: [Cu]
Agent: CC(C)CCCCCCCO
Product: O=C(O)c1ccnnc1

Procedure:
The isodecyl ester of 4-carboxypyridazine was prepared using the general method of Example 17 from isodecanol and 4,5-dicarboxypyridazine. The product has a boiling range of 150°-160° C. at 0.4 mm of mercury pressure. The product was evaluated as an extractant for copper by the procedure of Example 1, and the results are listed in Table 1. The results show that this compound has inferior solubility to the corresponding isooctadecyl ester of Example 17.
Reaction SMILES: [C:1]([O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][C:14]=1[O:15][C:16](=[O:18])[CH3:17])[NH:11][CH:10]=[C:9]([C:19](O)=[O:20])[C:8]2=[O:22])(=[O:3])[CH3:2].S(Cl)([Cl:25])=O>>[C:1]([O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][C:14]=1[O:15][C:16](=[O:18])[CH3:17])[NH:11][CH:10]=[C:9]([C:19]([Cl:25])=[O:20])[C:8]2=[O:22])(=[O:3])[CH3:2]
Reactant: O=S(Cl)Cl
Reactant: CC(=O)Oc1cc2[nH]cc(C(=O)O)c(=O)c2cc1OC(C)=O
Product: CC(=O)Oc1cc2[nH]cc(C(=O)Cl)c(=O)c2cc1OC(C)=O

Procedure:
6,7-Diacetoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (70 mg) was heated under reflux for 2 hours in thionyl chloride (2 mL), and then the solvent was evaporated. To the residue was added benzene (30 mL). Benzene was evaporated and the residue was vacuum dried to give 6,7-diacetoxy-1,4-dihydro-4-oxoquinoline-3-carbonyl chloride.
Reaction SMILES: [Br:1][CH2:2][C:3]([OH:5])=O.CC(N=C=NC(C)C)C.[NH2:15][C:16]1[CH:17]=[C:18]([S:22]([NH:25][C:26]2[C:35]([NH:36][C:37]3[CH:42]=[C:41]([O:43][CH3:44])[CH:40]=[C:39]([O:45][CH3:46])[CH:38]=3)=[N:34][C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[N:27]=2)(=[O:24])=[O:23])[CH:19]=[CH:20][CH:21]=1>C(Cl)Cl>[Br:1][CH2:2][C:3]([NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([S:22](=[O:23])(=[O:24])[NH:25][C:26]2[C:35]([NH:36][C:37]3[CH:42]=[C:41]([O:43][CH3:44])[CH:40]=[C:39]([O:45][CH3:46])[CH:38]=3)=[N:34][C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[N:27]=2)[CH:17]=1)=[O:5]
Reactant: COc1cc(Nc2nc3ccccc3nc2NS(=O)(=O)c2cccc(N)c2)cc(OC)c1
Reactant: O=C(O)CBr
Agent: CC(C)N=C=NC(C)C
Solvent: ClCCl
Product: COc1cc(Nc2nc3ccccc3nc2NS(=O)(=O)c2cccc(NC(=O)CBr)c2)cc(OC)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
In a 50 mL round-bottom flask was added 2-bromoacetic acid (1.87 g, 13.5 mmol), N,N-diisopropylcarbodiimide (860 mg, 6.8 mmol) and 10 mL DCM. To this mixture was added 3-amino-N-(3-(3,5-dimethoxyphenylamino) quinoxalin-2-yl)benzenesulfonamide (2.03 g, 4.5 mmol), prepared using procedures similar to those in Example 168. The reaction was stirred overnight at room temperature. Complete consumption of the starting aniline was confirmed by LCMS. The solvent was evaporated off to yield the crude product (2-bromo-N-(3-(N-(3-(3,5-dimethoxyphenylamino) quinoxalin-2-yl)sulfamoyl)phenyl)acetamide). This was used directly in the next step without further purification.
Reaction SMILES: [NH:1]1[C:9]2[CH2:8][CH2:7][NH:6][CH2:5][C:4]=2[N:3]=[CH:2]1.[CH3:10]I>>[CH3:10][N:1]1[C:9]2[CH2:8][CH2:7][NH:6][CH2:5][C:4]=2[N:3]=[CH:2]1
Reactant: CI
Reactant: c1nc2c([nH]1)CCNC2
Product: Cn1cnc2c1CCNC2

Procedure:
Operating as in Example 1, but starting from 4,5,6,7-tetrahydroimidazo-[4,5-c]-pyridine and methyl iodide, 1-Methyl-4,5,6,7-tetrahydroimidazo-[4,5-c]-pyridine is obtained as intermediate and successively reacted with methyl isothiocyanate to give 1-Methyl-5-(N-methylthiocarbamoyl)-4,5,6,7-tetrahydroimidazo-[4,5-c]-pyridine in a 78% yield, m.p. 238° C.
Reaction SMILES: [NH2:1][C:2]1[S:17][C:5]2[CH2:6][N:7]([C:10]([O:12][CH2:13][CH2:14][C:15]#[CH:16])=[O:11])[CH2:8][CH2:9][C:4]=2[C:3]=1[C:18](=[O:26])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[Cl:25].N1C=CC=CC=1.[Br:33][CH:34]([CH3:38])[C:35](Br)=[O:36].O>O1CCOCC1>[Br:33][CH:34]([CH3:38])[C:35]([NH:1][C:2]1[S:17][C:5]2[CH2:6][N:7]([C:10]([O:12][CH2:13][CH2:14][C:15]#[CH:16])=[O:11])[CH2:8][CH2:9][C:4]=2[C:3]=1[C:18](=[O:26])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[Cl:25])=[O:36]
Reactant: C#CCCOC(=O)N1CCc2c(sc(N)c2C(=O)c2ccccc2Cl)C1
Reactant: CC(Br)C(=O)Br
Solvent: C1COCCO1
Solvent: O
Solvent: c1ccncc1
Product: C#CCCOC(=O)N1CCc2c(sc(NC(=O)C(C)Br)c2C(=O)c2ccccc2Cl)C1
Yield: 70.7 %

Procedure:
1.25 g of 2-amino-3-(2-chlorobenzoyl)-6-(3-butynyloxycarbonyl)-4,5,6,7-tetrahydro-thieno[2,3-C]pyridine was dissolved in 20 ml of dioxane, to which 0.33 g of pyridine was added, followed by dropping at 0° C. 0.90 g of 2-bromopropionyl bromide. After completion of the reaction, the reaction mixture was charged into water, extracted with dichloromethane and dried with anhydrous magnesium sulfate, after which the solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography (elution solvent: dichloromethane:hexane=1:1-1:0), thereby obtaining 1.19 g of the intended compound.
Reaction SMILES: [Br:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][C:5]([CH3:11])=[CH:4][C:3]=1[CH3:12].Cl.CCO>[Fe].C(OCC)(=O)C>[Br:1][C:2]1[C:3]([CH3:12])=[CH:4][C:5]([CH3:11])=[CH:6][C:7]=1[NH2:8]
Reactant: Cc1cc(C)c(Br)c([N+](=O)[O-])c1
Agent: [Fe]
Agent: Cl
Solvent: CCO
Solvent: CCOC(C)=O
Product: Cc1cc(C)c(Br)c(N)c1
Temperature: 80 °C
Reaction time: 8 h
Yield: 76.9 %

Procedure:
A mixture of 2-bromo-1,5-dimethyl-3-nitrobenzene (1.8 g, 7.8 mmol), Fe powder (2.2 g), concentrated hydrochloric acid (0.3 mL), and EtOH (20 mL) was stirred at 80° C. overnight. Ethyl acetate (20 mL) was subsequently added. The resulting suspension was filtered and the filtrate concentrated. The residue was treated with H2O (10 mL), extracted with ethyl acetate (2×20 mL), washed with brine, dried over anhydrous Na2SO4, and concentrated to give the title compound as a solid (1.2 g, 77%).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([C:12]2[S:20][C:19]3[C:14](=[N:15][CH:16]=[CH:17][C:18]=3[O:21][C:22]3[CH:27]=[CH:26][C:25]([N+:28]([O-])=O)=[CH:24][C:23]=3[F:31])[CH:13]=2)[CH:9]=[CH:10][CH:11]=1.[BH4-].[Na+]>O.O.O.O.O.O.[Ni](Cl)Cl.CO.C1COCC1>[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([C:12]2[S:20][C:19]3[C:14](=[N:15][CH:16]=[CH:17][C:18]=3[O:21][C:22]3[CH:27]=[CH:26][C:25]([NH2:28])=[CH:24][C:23]=3[F:31])[CH:13]=2)[CH:9]=[CH:10][CH:11]=1
Reactant: O=[N+]([O-])c1ccc(Oc2ccnc3cc(-c4cccc(OCCCCl)c4)sc23)c(F)c1
Agent: Cl[Ni]Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: Nc1ccc(Oc2ccnc3cc(-c4cccc(OCCCCl)c4)sc23)c(F)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 55.7 %

Procedure:
To the nitro compound 364 (0.84 g, 1.8 mmol) and nickel chloride hexahydrate (0.87 g, 3.7 mmol) in 9:1 MeOH/THF was added sodium borohydride (0.30 g, 7.9 mmol) in small portions. The resulting mixture was stirred at r.t. for 1 h, then filtered through celite and concentrated. The residue was partitioned between water and dichloromethane, the organic phase was collected, washed with brine, dried (anhydrous MgSO4), filtered, and concentrated. The residue was purified by flash chromatography (eluent 90% ethyl acetate/hexanes) to afford 365 (0.43 g, 54% yield). LRMS (M+H): 429.1.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:11])[CH2:9][CH3:10])=[CH:4][CH:3]=1.C(O)(=O)C.[Br:16]Br>O>[Br:16][CH:9]([CH3:10])[C:8]([C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=1)=[O:11]
Reactant: CCC(=O)c1ccc(Br)cc1
Reactant: BrBr
Solvent: CC(=O)O
Solvent: O
Product: CC(Br)C(=O)c1ccc(Br)cc1
Temperature: 10 °C
Reaction time: 3 h
Yield: 64 %

Procedure:
Dissolving 5.0 g (23 mmol) of 4′-bromopropiophenon into 50 milliliter of acetic acid, and adding 3.7 g (23 mmol) of bromine while cooling with ice, stirred at the temperature of 10° C. for 3 hours. After the color of bromine disappeared, adding water and an extraction was carried out using dichloro-methane. Washing the organic layer with water, it was dried with the use of sodium sulfate. The solvent was removed by distillation and the resultant crystals were washed with hexane thereby obtaining 4.3 g of 2,4′-dibromopropiophenon (yield: 63%).
Reaction SMILES: Cl[C:2]1[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][CH:7]=1)=[O:5].[CH3:20][CH:21]1[CH2:26][CH:25]([CH3:27])[CH2:24][NH:23][CH2:22]1.C(=O)([O-])[O-].[Ca+2]>C(O)C>[CH3:20][CH:21]1[CH2:26][CH:25]([CH3:27])[CH2:24][N:23]([C:2]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][C:3]=2[C:4]([C:6]2[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][CH:7]=2)=[O:5])[CH2:22]1
Reactant: CC1CNCC(C)C1
Reactant: O=C(c1ccc(Cl)cc1)c1cc([N+](=O)[O-])ccc1Cl
Agent: O=C([O-])[O-]
Agent: [Ca+2]
Solvent: CCO
Product: CC1CC(C)CN(c2ccc([N+](=O)[O-])cc2C(=O)c2ccc(Cl)cc2)C1
Yield: 98.1 %

Procedure:
Proceeding as indicated in example 2, with 0.035 mole (10.4 g) of 2,4'-dichloro-5-nitro-benzophenone, 0.07 mole (8 cm3) of 3,5-dimethylpiperidine and 0.035 mole (5 g) of calcium carbonate in ethanol, 12.8 g (Yield: 97%) of the expected product are obtained. M.P 159° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[NH:9][N:10]=[C:11]([C:19](=[O:25])[CH:20]=[CH:21][N:22]([CH3:24])[CH3:23])[C:12](=[O:18])[CH:13]=[CH:14]N(C)C>ClCCl>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[N:9]1[CH:14]=[CH:13][C:12](=[O:18])[C:11]([C:19](=[O:25])[CH:20]=[CH:21][N:22]([CH3:24])[CH3:23])=[N:10]1
Reactant: CN(C)C=CC(=O)C(=NNc1ccc(Cl)cc1Cl)C(=O)C=CN(C)C
Solvent: ClCCl
Product: CN(C)C=CC(=O)c1nn(-c2ccc(Cl)cc2Cl)ccc1=O
Temperature: 80 °C
Reaction time: 2 h
Yield: 75.6 %

Procedure:
1,7-bis(N,N-dimethylamino)-1,6-heptadien-3,4,5-trione 4-(2,4-dichlorophenyl)hydrazone (2.10 g) was dissolved in dry dichloromethane (6 ml), silica gel (19 g) was added and solvent was removed in vacuo. The mixture was heated at 80° C. for 30 minutes and then at 120° C. for 2 hours. After cooling, the product was extracted with acetone and the acetone was removed in vacuo. The oily residue was solidified with diethyl ether to afford 1-(2,4-dichlorophenyl)-3-[3-(N,N-dimethylamino)-1-oxo-2-propenyl]4(1H)-pyridazi- none (1.40 g), m.p. 152°-154° C.
Reaction SMILES: [O-]CC.[Na+].[Br:5][C:6]1[CH:13]=[CH:12][C:9]([CH:10]=O)=[CH:8][CH:7]=1.[N:14]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[N+:15]=[N-:16].O>C(O)C.C1(C)C=CC=CC=1>[N:14](/[C:17](=[CH:10]\[C:9]1[CH:12]=[CH:13][C:6]([Br:5])=[CH:7][CH:8]=1)/[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[N+:15]=[N-:16]
Reactant: O=Cc1ccc(Br)cc1
Reactant: CCOC(=O)CN=[N+]=[N-]
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Solvent: O
Product: CCOC(=O)/C(=C/c1ccc(Br)cc1)N=[N+]=[N-]
Temperature: 25 °C
Reaction time: 2 h
Yield: 39 %

Procedure:
Into a solution of sodium ethoxide (a 20% solution in ethanol, 22.2 g) in toluene (100 ml) was added at 0° C. over a period of more than 10 minutes a solution of 4-bromobenzaldehyde (10 g) and ethyl azidoacetate (7.0 g) in toluene (50 ml). After being stirred at room temperature for 2 hours, the reaction mixture was mixed with water and was extracted with ethyl acetate. The organic layer was washed with an aqueous saturated solution of sodium chloride and was dried with magnesium sulfate. After concentration under reduced pressure, the residue was subjected to separation and purification using column chromatography (ethyl acetate/hexane 1:19) to obtain ethyl (Z)-2-azido-3-(4-bromophenyl)acrylate (6.24 g) as a yellow oily substance.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11](CC2C=CC=CC=2)[CH2:10][C@@H:9]1[CH2:21][CH2:22][CH3:23])=[O:7])([CH3:4])([CH3:3])[CH3:2]>[Pd].CO>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][C@@H:9]1[CH2:21][CH2:22][CH3:23])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CCC[C@H]1CN(Cc2ccccc2)CCN1C(=O)OC(C)(C)C
Agent: [Pd]
Solvent: CO
Product: CCC[C@H]1CNCCN1C(=O)OC(C)(C)C
Reaction time: 6 h

Procedure:
A mixture of 1.50 g (4.24 mmol; purity: 90%) (S)-4-benzyl-2-propyl-piperazine-1-carboxylic acid tert-butyl ester and 150 mg palladium on carbon in 30 mL methanol was hydrogenated at RT for 6 h at 3 bar. The catalyst was removed by filtration and the solvent was evaporated in vacuo.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[CH2:14][N:13]3[CH:21]=[CH:22][CH:23]=[C:12]3[CH2:11]2)=[O:9])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[CH3:30][N:31]([CH3:35])[CH2:32][CH2:33][NH2:34]>CS(C)=O>[CH3:30][N:31]([CH3:35])[CH2:32][CH2:33][NH:34][C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[CH2:14][N:13]3[CH:21]=[CH:22][CH:23]=[C:12]3[CH2:11]2)=[O:9])=[CH:4][CH:3]=1
Reactant: O=C(c1ccc(Cl)nc1)N1Cc2cccn2Cc2ccccc21
Reactant: CN(C)CCN
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: CN(C)CCNc1ccc(C(=O)N2Cc3cccn3Cc3ccccc32)cn1

Procedure:
A mixture of 10-[[6-chloro-3-pyridinyl]-carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (3.2 g), K2CO3 (5 g) and the 2-dimethylaminoethylamine (5 ml) is heated in dimethylsulfoxide (80 ml) for 6 hours at 100° C. (with stirring) . The reaction mixture is quenched with water and the solid which separates, is filtered off and washed well with water. Examination of the TLC (CHCl3 : MeOH; 3:1) showed the products to be sufficiently pure to be used for further reactions without purification. Yield 3.2 g, 85%, mass spectrum (CI) 376 (M+1).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][CH:10]=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:12]([NH2:14])[CH3:13]>>[CH2:12]([N:14]([CH2:10][CH2:9][NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:10][CH2:9][NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH3:13]
Reactant: CCN
Reactant: CC(C)(C)OC(=O)NCC=O
Product: CCN(CCNC(=O)OC(C)(C)C)CCNC(=O)OC(C)(C)C

Procedure:
The product from Example 14A and ethylamine were processed as described in Example 7B to provide the title compound.
Reaction SMILES: [N+:1]([C:4]1[N:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].Br[CH2:17][CH2:18][F:19].C(=O)([O-])[O-].[K+].[K+].C1COCC1>C(Cl)Cl.CO.O.CN(C=O)C>[F:19][CH2:18][CH2:17][N:13]1[CH2:12][CH2:11][N:10]([C:7]2[CH:8]=[N:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)[CH2:15][CH2:14]1
Reactant: FCCBr
Reactant: O=[N+]([O-])c1ccc(N2CCNCC2)cn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=[N+]([O-])c1ccc(N2CCN(CCF)CC2)cn1
Temperature: 85 °C
Yield: 63 %

Procedure:
A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer, reflux condenser, and nitrogen inlet was charged with 217a (598 mg, 2.87 mmol), 1-bromo-2-fluoroethane (1.09 g, 8.61 mmol), potassium carbonate (1.19 g, 8.61 mmol), THF (10 mL) and DMF (10 mL). The reaction mixture was heated at 85° C. for 14 h under nitrogen atmosphere. After this time, the mixture was diluted with 90:10 methylene chloride/methanol (100 mL) and water (75 mL), and the layers were separated. The aqueous layer was extracted with 90:10 methylene chloride/methanol (50 mL), and the combined organic layers were washed with brine (100 mL) and dried over sodium sulfate. The drying agent was removed by filtration. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by flash column chromatography (silica, 95:5 methylene chloride/methanol) to afford 217b in 63% yield (460 mg) as a yellow semi-solid: 1H NMR (500 MHz, CDCl3) d 8.16 (d, J=9.0 Hz, 1H), 8.14 (d, J=3.0 Hz, 1H), 7.21 (dd, J=9.0, 2.0 Hz, 1H), 4.67 (t, J=5.0 Hz, 1H), 4.57 (t, J=5.0 Hz, 1H), 3.49 (t, J=5.0 Hz, 4H), 2.81 (t, J=5.0 Hz, 1H), 2.75 (t, J=5.0 Hz, 1H), 2.73 (t, J=5.5 Hz, 4H); MS (ESI+) m/z 255.1 (M+H).
Reaction SMILES: [C:1]([CH2:4][C:5]1[C:9]2[C:10]([C:16](=[O:26])[CH2:17][C:18]3[C:23]([Cl:24])=[CH:22][N:21]=[CH:20][C:19]=3[Cl:25])=[CH:11][CH:12]=[C:13]([O:14][CH3:15])[C:8]=2[O:7][CH:6]=1)(O)=[O:2].[CH2:27]([NH2:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>>[CH2:27]([NH:34][C:1]([CH2:4][C:5]1[C:9]2[C:10]([C:16](=[O:26])[CH2:17][C:18]3[C:23]([Cl:24])=[CH:22][N:21]=[CH:20][C:19]=3[Cl:25])=[CH:11][CH:12]=[C:13]([O:14][CH3:15])[C:8]=2[O:7][CH:6]=1)=[O:2])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: COc1ccc(C(=O)Cc2c(Cl)cncc2Cl)c2c(CC(=O)O)coc12
Reactant: NCc1ccccc1
Product: COc1ccc(C(=O)Cc2c(Cl)cncc2Cl)c2c(CC(=O)NCc3ccccc3)coc12
Yield: 29 %

Procedure:
Substantially the same procedure as in Example 13 was repeated using Compound 151 (0.30 g) obtained in Example 151 and benzylamine (0.13 ml) to give Compound 155 (0.11 g, 29%) as white crystals.