Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:23]=[CH:24][CH:25]=1)[C:7]([NH:9][CH2:10][CH2:11][S:12][CH2:13][C:14]1[O:15][C:16]([CH2:19][N:20]([CH3:22])[CH3:21])=[CH:17][CH:18]=1)=[O:8])([O-])=O>[Fe]>[NH2:1][C:4]1[CH:5]=[C:6]([CH:23]=[CH:24][CH:25]=1)[C:7]([NH:9][CH2:10][CH2:11][S:12][CH2:13][C:14]1[O:15][C:16]([CH2:19][N:20]([CH3:21])[CH3:22])=[CH:17][CH:18]=1)=[O:8]
Reactant: CN(C)Cc1ccc(CSCCNC(=O)c2cccc([N+](=O)[O-])c2)o1
Agent: [Fe]
Product: CN(C)Cc1ccc(CSCCNC(=O)c2cccc(N)c2)o1
Yield: 75.5 %

Procedure:
To a suspension of 13 g of 3-nitro-N-[2-(5-dimethylaminomethylfuran-2-ylmethylthio)ethyl]benzamide and 8 g of metallic iron, previously washed with 2N hydrochloric acid, in a mixture of 50 ml of water and 50 ml of methanol, concentrated hydrochloric acid is added dropwise and under stirring until pH 5, then the mixture is heated two hours with reflux. After cooling, the precipitate is filtered and thoroughly washed with methanol. The solution so obtained is evaporated under reduced pressure to eliminate the methanol. The pH of the aqueous solution is adjusted to 10 with sodium hydroxide and the inorganic precipitate which forms is eliminated after washing with ethanol. The solution is extracted 4 times with 40 ml of ethyl acetate containing 10% of ethanol, the solution is dried on anhydrous sodium sulfate and evaporated to dryness. Thus, 9 g of 3-amino-N-[2-(5-dimethylaminomethylfuran-2-ylmethylthio)ethyl]benzamide are obtained as an oil.
Reaction SMILES: [C:1]([NH:9][NH2:10])(=[O:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[C:11]([O:14][C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[CH:21]=[C:20]([C:25](Cl)=[O:26])[CH:19]=[CH:18]2)(=[O:13])[CH3:12].O1CCOCC1.N1C=CC=CC=1>O>[C:1]([NH:9][NH:10][C:25]([C:20]1[CH:19]=[CH:18][C:17]2[C:22](=[CH:23][CH:24]=[C:15]([O:14][C:11](=[O:13])[CH3:12])[CH:16]=2)[CH:21]=1)=[O:26])(=[O:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: CCCCCCC(=O)NN
Reactant: CC(=O)Oc1ccc2cc(C(=O)Cl)ccc2c1
Solvent: O
Solvent: C1COCCO1
Solvent: c1ccncc1
Product: CCCCCCC(=O)NNC(=O)c1ccc2cc(OC(C)=O)ccc2c1
Temperature: 80 °C
Yield: 73.8 %

Procedure:
In a 200 ml-three-necked flask, 1.77 g (12.3 mM) of heptanohydrazide, 3,23 g (13.0 mM) of 6-acetoxy-2-naphthoyl chloride prepared in the same manner as in Example 3 and 90 ml of dioxane were placed and heated to about 80° C. To the mixture, 5.0 ml of pyridine was added at about 80° C. under stirring, followed by heating to 90°-92° C. and stirring for 1 hour at 90°-92° C. After the reaction, the reaction mixture was cooled on an iced water bath and poured into 350 ml of iced water to precipitate a crystal. The crystal was recovered by filtration, followed by washing with water and recrystallization from a mixture solvent (acetoneethyl acetate) to obtain 3.23 g of N-heptanoyl-N'-(6-acetoxy-2-naphthoyl)hydrazine (Yield: 75.4 %) ##STR137##
Reaction SMILES: [Br:1][C:2]1[C:3]([O:19][CH3:20])=[C:4]([CH2:10][CH2:11][CH2:12][CH:13]2OCCCO2)[CH:5]=[C:6]([O:8][CH3:9])[CH:7]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(OCC)(=O)C.CCCCCC>C(O)C.O1CCOCC1>[Br:1][C:2]1[C:3]([O:19][CH3:20])=[C:4]2[C:5](=[C:6]([O:8][CH3:9])[CH:7]=1)[CH:13]=[CH:12][CH2:11][CH2:10]2
Reactant: COc1cc(Br)c(OC)c(CCCC2OCCCO2)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Solvent: CCCCCC
Product: COc1cc(Br)c(OC)c2c1C=CCC2
Yield: 99 %

Procedure:
A solution of 1.10 gm (3.19 mmol) of 2-[3-(3-bromo-2,5-dimethoxyphenyl)propyl]-1,3-dioxane and 300 mg p-toluene sulphonic acid in 10 ml absolute ethanol was refluxed for 48 hours at which time tlc analysis (silica gel, 1:4 ethyl acetate:hexane) indicated the absence of the dioxane. The solvent was removed in vacuo and the residue was partitioned between ether and 5% sodium carbonate. The ether extract was washed with brine, dried with Na2SO4, filtered and the solvent was removed in vacuo. The residue was kugelrohr distilled at 0.005 mm Hg to give 0.85 gm (99%) of a colorless oil, bp 95° C. (air bath temperature), homogeneous by tlc (ibid), Rf 0.74.
Reaction SMILES: [N+:1]([O-:4])([O-])=O.[Na+].[Br:6][CH2:7][C:8](=[O:15])[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11]>O.C(O)(=O)C>[OH:4][N:1]=[C:9]([C:8]([CH2:7][Br:6])=[O:15])[C:10]([O:12][CH2:13][CH3:14])=[O:11]
Reactant: O=[N+]([O-])[O-]
Reactant: CCOC(=O)CC(=O)CBr
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: CCOC(=O)C(=NO)C(=O)CBr
Temperature: 10 °C
Reaction time: 2 h

Procedure:
A solution of sodium nitrate (12.4 g. ) in water (150 ml.) was dropwise added with stirring at 5° to 7° C. to a solution of ethyl 4-bromoacetoacetate (30 g.) in acetic acid (200 ml.) and the mixture was stirred for 2 hours at 10° C. Water (200 ml.) was added to the reaction mixture and the resultant mixture was extracted with ether (500 ml.). The extract was washed twice with water (200 ml.) and with a sodium chloride aqueous solution (200 ml.) and dried over magnesium sulfate. The solvent was distilled off under reduced pressure to give yellowish brown crystals of ethyl 2-hydroxyimino-4-bromoacetoacetate (a mixture of syn and anti isomers) (32.6 g.).
Reaction SMILES: [CH:1]([O:14][C:15]([C:17]1[N:22]2[C:23](=[O:64])[CH:24]([NH:25][C:26](=[O:63])[C:27](=[N:53][O:54][CH2:55][C:56]([O:58]C(C)(C)C)=[O:57])[C:28]3[N:29]=[C:30]([NH:33][C:34]([C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=4)([C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)[C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[S:31][CH:32]=3)[C@H:21]2[S:20][CH2:19][C:18]=1[CH2:65]Cl)=[O:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N+:67]([C:70]1[CH:77]=[C:76]([N+:78]([O-:80])=[O:79])[CH:75]=[CH:74][C:71]=1[CH:72]=O)([O-:69])=[O:68].[I-].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])O.[Na+].NC1SC=C(C(=NOC(C(O)=O)(C)C)C(NC2C(=O)N3C(C(O)=O)=C(C=CC4C=CC([N+]([O-])=O)=CC=4[N+]([O-])=O)CS[C@H]23)=O)N=1>>[CH:1]([O:14][C:15]([C:17]1[N:22]2[C:23](=[O:64])[CH:24]([NH:25][C:26](=[O:63])[C:27](=[N:53][O:54][CH2:55][C:56]([OH:58])=[O:57])[C:28]3[N:29]=[C:30]([NH:33][C:34]([C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=4)([C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=4)[C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[S:31][CH:32]=3)[C@H:21]2[S:20][CH2:19][C:18]=1[CH:65]=[CH:72][C:71]1[CH:74]=[CH:75][C:76]([N+:78]([O-:80])=[O:79])=[CH:77][C:70]=1[N+:67]([O-:69])=[O:68])=[O:16])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)CON=C(C(=O)NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(CCl)CS[C@H]12)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Reactant: O=Cc1ccc([N+](=O)[O-])cc1[N+](=O)[O-]
Agent: CC(C)(ON=C(C(=O)NC1C(=O)N2C(C(=O)O)=C(C=Cc3ccc([N+](=O)[O-])cc3[N+](=O)[O-])CS[C@H]12)c1csc(N)n1)C(=O)O
Agent: O=C([O-])O
Agent: [I-]
Product: O=C(O)CON=C(C(=O)NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(C=Cc3ccc([N+](=O)[O-])cc3[N+](=O)[O-])CS[C@H]12)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Yield: 64.2 %

Procedure:
7-[2-tert-butoxycarbonylmethoxyimino-2-(2-tritylaminothiazol-4-yl)acetamido]-3-chloromethyl-3-cephem-4-carboxylic acid benzhydryl ester (500 mg, 0.53 mmol), 2,4-dinitrobenzaldehyde (416 mg, 2.12 mmol), sodium iodide (79.4 mg, 0.53 mmol), triphenylphosphine (139 mg, 0.53 mmol) and sodium hydrogen carbonate (133.6 mg, 1.59 mmol) were used to conduct the procedure similar to that shown in (1) of Example 1 to obtain 350 mg (yield: 61%) of 7-[2-carboxymethoxyimino-2-(2-tritylaminothiazol-4-yl)acetamido]-3-(2,4-dinitrostyryl)-3-cephem-4-carboxylic acid benzhydryl ester as yellow powder.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]2[CH:8]=[C:9]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[N:10]([S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:5]2=[CH:4][CH:3]=1.[NH:25]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28].C([O-])([O-])=O.[Cs+].[Cs+].C1(C)C=CC=CC=1>C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.NC1C=CC=CC=1C1C=CC=CC=1[Pd]Cl>[CH2:23]([O:22][C:20]([C:9]1[N:10]([S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])[C:5]2[C:6](=[N:7][C:2]([N:25]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[NH:26][C:27]([O:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[O:28])=[CH:3][CH:4]=2)[CH:8]=1)=[O:21])[CH3:24]
Reactant: CC(C)(C)OC(=O)NNC(=O)OC(C)(C)C
Reactant: CCOC(=O)c1cc2nc(Cl)ccc2n1S(=O)(=O)c1ccccc1
Agent: Nc1ccccc1-c1ccccc1[Pd]Cl
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Product: CCOC(=O)c1cc2nc(N(NC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)ccc2n1S(=O)(=O)c1ccccc1
Temperature: 110 °C
Reaction time: 3.5 h

Procedure:
Ethyl 5-chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-carboxylate (1.80 g, 4.93 mmol, from Step 1), di-tert-butyl hydrazine-1,2-dicarboxylate (1.3 g, 5.4 mmol, Aldrich) and Cs2CO3 (1.6 g, 4.9 mmol, Aldrich) were combined in toluene (20 mL, 200 mmol) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine-(2′-aminobiphenyl-2-yl)(chloro)palladium (1:1) (0.39 g, 0.49 mmol, Aldrich) was added. The mixture was degassed by a stream of nitrogen through the solution for 10 minutes. The reaction was stirred at 110° C. for 3.5 hours. The reaction was cooled to room temperature, water was added and the product was extracted with five portions of EtOAc. The combined extracts were dried over sodium sulfate, filtered and concentrated. Flash chromatography, eluting with a gradient from 0-50% EtOAc in hexanes afforded product as a yellow foam (2.11 g, 76%).
Reaction SMILES: [CH3:1][C:2]1[C:6]2[C:7]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=3)=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][C:3]=1[C:20](O)=[O:21].C(Cl)(=O)C(Cl)=O.CN(C=O)C.[CH3:34][O:35][C:36](=[O:58])[C@@H:37]([NH:41][S:42]([C:45]1[CH:50]=[CH:49][C:48]([C:51]2[CH:56]=[CH:55][C:54]([NH2:57])=[CH:53][CH:52]=2)=[CH:47][CH:46]=1)(=[O:44])=[O:43])[CH:38]([CH3:40])[CH3:39]>N1C=CC=CC=1>[CH3:34][O:35][C:36](=[O:58])[C@@H:37]([NH:41][S:42]([C:45]1[CH:50]=[CH:49][C:48]([C:51]2[CH:52]=[CH:53][C:54]([NH:57][C:20]([C:3]3[O:4][C:5]4[CH:10]=[CH:9][CH:8]=[C:7]([C:11]5[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=5)[C:6]=4[C:2]=3[CH3:1])=[O:21])=[CH:55][CH:56]=2)=[CH:47][CH:46]=1)(=[O:44])=[O:43])[CH:38]([CH3:40])[CH3:39]
Reactant: COC(=O)[C@@H](NS(=O)(=O)c1ccc(-c2ccc(N)cc2)cc1)C(C)C
Reactant: Cc1c(C(=O)O)oc2cccc(-c3cccc([N+](=O)[O-])c3)c12
Agent: O=C(Cl)C(=O)Cl
Solvent: c1ccncc1
Solvent: CN(C)C=O
Product: COC(=O)[C@@H](NS(=O)(=O)c1ccc(-c2ccc(NC(=O)c3oc4cccc(-c5cccc([N+](=O)[O-])c5)c4c3C)cc2)cc1)C(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 18.8 %

Procedure:
To 100 mg (0.34 mmol) of 3-methyl-4-(3-nitro-phenyl)-benzofuran-2-carboxylic acid was added 2 mL of oxalyl chloride and the resulting mixture was refluxed for 2 h in the presence of a catalytic amount of DMF, then the excess oxalyl chloride was removed under vacuum. The residue was dissolved in 1 mL of dichloromethane and was added to a mixture of 183 mg (0.5 mmol) of (S)-2-(4′-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester and 2 mL of pyridine in an ice/water bath. The mixture was stirred at room temperature overnight. All the solvents were removed under vacuum. Column chromatography on silica gel gave 41 mg of (S)-3-methyl-2-(4′-{[3-methyl-4-(3-nitro-phenyl)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-butyric acid methyl ester as white solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([SH:9])=[CH:5][CH:4]=1.[H-].[Na+].I[C:13]1[C:14](=[O:20])[NH:15][C:16]([CH3:19])=[CH:17][CH:18]=1>CN(C=O)C.[Cu]I>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9][C:13]2[C:14](=[O:20])[NH:15][C:16]([CH3:19])=[CH:17][CH:18]=2)=[CH:5][CH:4]=1
Reactant: Cc1ccc(I)c(=O)[nH]1
Reactant: COc1ccc(S)cc1
Agent: [Cu]I
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc(Sc2ccc(C)[nH]c2=O)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 92.7 %

Procedure:
4-Methoxythiophenol (1.7 mL, 13.85 mmol) was added to a suspension of NaH 60% in oil (831 mg, 20.80 mmol) in DMF (30 mL) at 0° C., and the mixture was allowed to warm to 25° C. 3-Iodo-6-methyl-1H-pyridin-2-one (3 g, 12.78 mmol) was added to the solution at 0° C., followed by CuI (533 mg, 2.8 mmol). The reaction was stirred at 25° C. for 1 h and heated at 120° C. for 5 h. Then it was allowed to cool and partitioned between CH2Cl2 (30 mL) and 9:1 NH4Cl/NH4OH (30 mL) and stirred for 15 min. The mixture was extracted with CH2Cl2 (3×70 mL each) and the combined CH2Cl2 extracts were washed with water (3×30 mL), brine, dried and stripped in vacuo to give the crude product (3.6 g), which was further purified by washing with ether to give 2.93 g of 3-(4-methoxyphenylsulfanyl)-6-methyl-1H-pyridin-2-one which was used in the next step.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1.C([O-])([O-])=O.[K+].[K+].[CH3:16][N:17]([CH3:21])[C:18](Cl)=[O:19]>CC(C)=O>[CH3:16][N:17]([CH3:21])[C:18](=[O:19])[O:9][C:6]1[CH:7]=[CH:8][C:3]([CH2:2][OH:1])=[CH:4][CH:5]=1
Reactant: OCc1ccc(O)cc1
Reactant: CN(C)C(=O)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CN(C)C(=O)Oc1ccc(CO)cc1
Yield: 91 %

Procedure:
To a solution of 5 g (40.3 mmol) of 4-(hydroxymethyl)phenol in 500 mL of acetone was added finely powdered K2CO3 (27.83 g, 0.2 mol) and 3.71 mL (40.3 mmol) of N,N-dimethylcarbamoyl chloride. This mixture was heated under reflux overnight and then filtered. After evaporation of the solvent, a purification by column chromatography on silica gel with cyclohexane/iPrOH (9/1) and as eluent gave 7.16 g (yield: 91%) of compound of molecular formula C10H13NO3. Aspect: white powder.
Reaction SMILES: C1CO[C:3]([CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39])([CH2:4][CH2:5][C@H:6]2[C@H:10]([O:11]C3CCCCO3)[CH2:9][C@H:8]([OH:18])[C@@H:7]2[CH2:19]/[CH:20]=[CH:21]\[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([O:29][CH:30]([CH3:32])[CH3:31])=[O:28])[O:2]1.C(O)(=O)C.C1COCC1>O>[OH:11][C@@H:10]1[CH2:9][C@H:8]([OH:18])[C@H:7]([CH2:19]/[CH:20]=[CH:21]\[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([O:29][CH:30]([CH3:32])[CH3:31])=[O:28])[C@H:6]1[CH2:5][CH2:4][C:3](=[O:2])[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39]
Reactant: CCCCCCCC1(CC[C@@H]2[C@@H](C/C=C\CCCCCC(=O)OC(C)C)[C@@H](O)C[C@H]2OC2CCCCO2)OCCO1
Solvent: O
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CCCCCCCC(=O)CC[C@@H]1[C@@H](C/C=C\CCCCCC(=O)OC(C)C)[C@@H](O)C[C@H]1O
Temperature: 50 °C
Yield: 89.6 %

Procedure:
The compound (3-a)(0.305 g) was dissolved in the solvent mixture (acetic acid:THF:water=2:1:1)(6 ml) and the solution was maintained at 50° C. for 14 hours. The crude product obtained by the conventional treatment was purified on silica gel column to give the titled compound (4-a)[yield:0.213 g(90%)].
Reaction SMILES: [CH:1]1([C:7]2[C:8]3[CH:20]=[C:19]([C:21]([O:23]CC)=[O:22])[S:18][C:9]=3[NH:10][C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+]>C1COCC1.CO>[CH:1]1([C:7]2[C:8]3[CH:20]=[C:19]([C:21]([OH:23])=[O:22])[S:18][C:9]=3[NH:10][C:11]=2[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: CCOC(=O)c1cc2c(C3CCCCC3)c(-c3ccccc3)[nH]c2s1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)c1cc2c(C3CCCCC3)c(-c3ccccc3)[nH]c2s1
Yield: 54 %

Procedure:
A solution (0.07 M) of ethyl 4-cyclohexyl-5-phenyl-6H-thieno[2,3-b]pyrrole-2-carboxylate in THF/MeOH (1:1) was treated with aqueous NaOH (2 N solution, 4 eq.). The mixture was heated to reflux for 6 hours. After cooling down, the reaction was concentrated and acidified to pH 1 with aqueous HCl (6 N). The resulting mixture was dissolved with DMSO and purified by RP-HPLC (Conditions: Waters X-TERRA MS C18, 5 micron, 19×150 mm; flow: 20 mL/min; Gradient: A: H2O+0.1% TFA; B: MeCN+0.1% TFA; linear from 95% A to 5% A in 10 min) to afford the title compound (54%) as a solid.
Reaction SMILES: ClC(Cl)(Cl)[C:3]([C:5]1[N:14]2[C:8]([CH2:9][N:10]([C:19](=[O:29])[CH2:20][O:21][C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=3)[C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[CH2:13]2)=[CH:7][CH:6]=1)=[O:4].[CH3:32][C:33]1[CH:34]=[C:35]([CH:38]=[CH:39][CH:40]=1)[CH2:36][NH2:37]>>[Cl:28][C:25]1[CH:24]=[CH:23][C:22]([O:21][CH2:20][C:19]([N:10]2[C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[CH2:13][N:14]3[C:5]([C:3]([NH:37][CH2:36][C:35]4[CH:38]=[CH:39][CH:40]=[C:33]([CH3:32])[CH:34]=4)=[O:4])=[CH:6][CH:7]=[C:8]3[CH2:9]2)=[O:29])=[CH:27][CH:26]=1
Reactant: Cc1cccc(CN)c1
Reactant: O=C(COc1ccc(Cl)cc1)N1Cc2ccc(C(=O)C(Cl)(Cl)Cl)n2Cc2ccccc21
Product: Cc1cccc(CNC(=O)c2ccc3n2Cc2ccccc2N(C(=O)COc2ccc(Cl)cc2)C3)c1

Procedure:
The title compound was synthesized from 2,2,2-trichloro-1-{10-[(4-chlorophenoxy)acetyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}ethanone of Example 67 (0.3 mmol) and 3-methylbenzylamine (2.2 eq.) in the manner of Example 68, m.p. 130-131° C. MS [(+)ESI, m/z]: 500 [M+H]+ Anal. Calcd for C29H26CIN3O3: C, 69.66; H, 5.24; N, 8.40. Found: C, 69.80; H, 5.30; N, 8.42.
Reaction SMILES: F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.C(=O)([O-])[O-].[Na+].[Na+].[C:25]1(B(O)O)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.Cl[C:35]1[N:36]=[C:37]([C:42]2[CH:47]=[CH:46][N:45]=[C:44]([NH:48][C:49](=[O:51])[CH3:50])[CH:43]=2)[S:38][C:39]=1[CH:40]=[O:41]>COCCOC.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:40]([C:39]1[S:38][C:37]([C:42]2[CH:47]=[CH:46][N:45]=[C:44]([NH:48][C:49](=[O:51])[CH3:50])[CH:43]=2)=[N:36][C:35]=1[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:41]
Reactant: CC(=O)Nc1cc(-c2nc(Cl)c(C=O)s2)ccn1
Reactant: OB(O)c1ccccc1
Agent: [Pd]
Agent: CC(C)(C)[PH+](C(C)(C)C)C(C)(C)C
Agent: F[B-](F)(F)F
Solvent: O
Solvent: COCCOC
Product: CC(=O)Nc1cc(-c2nc(-c3ccccc3)c(C=O)s2)ccn1
Temperature: 80 °C
Reaction time: 10 h
Yield: 43.1 %

Procedure:
Tris(dibenzylideneacetone)dipalladium(0) (0.0162 g, 0.0177 mmol) and tri-t-butylphosphonium tetrafluoroborate (0.0103 g, 0.0355 mmol) were weighed into a round bottom flask and dissolved in DME (3 mL). The mixture was sonicated for 15 min under atmosphere of Argon. After addition of water (1 mL), sodium carbonate (0.226 g, 2.13 mmol) was added to the dark purple solution followed by phenylboronic acid (0.173 g, 1.42 mmol) and N-[4-(4-chloro-5-formyl-1,3-thiazol-2-yl)pyridin-2-yl]acetamide (0.200 g, 0.710 mmol). The resulting mixture was stirred for 10 h at 80° C., cooled to room temperature, diluted with water and extracted with DCM (3×5 mL). The organics were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The result mixture was purified by ISCO column with 0-5% MeOH in DCM in 10 min. Fractions containing product were combined and solvent was removed under reduced pressure to give crude material (0.099 g, 43%), which was used in the next step without further purification. LCMS: (FA) ES+ 324.
Reaction SMILES: CN(C)[CH:3]=[O:4].[OH:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]1[C:24]([OH:25])=[C:23]([O:26][CH3:27])[C:22]([O:28][CH3:29])=[CH:21][C:20]=1C.N1C=CC=CC=1>O=O>[OH:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]1[C:24](=[O:25])[C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[C:3](=[O:4])[C:20]=1[CH3:21]
Reactant: CN(C)C=O
Reactant: COc1cc(C)c(CCCCCCCCCCCCO)c(O)c1OC
Agent: O=O
Solvent: c1ccncc1
Product: COC1=C(OC)C(=O)C(CCCCCCCCCCCCO)=C(C)C1=O

Procedure:
To a dimethylformamide solution (30 ml) of 6-(12-hydroxydodecyl)-2,3-dimethoxy-5-methylphenol (1.7 g) are added pyridine (50 mg) and bis(4-hydroxysalicylidene)ethylenediiminocobalt(II) (36 mg), and the mixture is stirred in oxygen streams at atmospheric temperature and pressure for 72 hours. The reaction product is isolated as in Example 7 and recrystallized from ether. The above procedure yields 6-(12-hydroxydodecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (1.37 g), m.p. 63° C.
Reaction SMILES: C(O[C:4](=[N:6][C:7](=O)[C:8]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=1)[CH3:5])C.Cl.[CH3:17][S:18][C:19]1[CH:24]=[CH:23][C:22]([NH:25][NH2:26])=[CH:21][CH:20]=1.C(N(CC)CC)C.O>ClCCl.CO>[F:14][C:11]1[CH:10]=[CH:9][C:8]([C:7]2[N:25]([C:22]3[CH:23]=[CH:24][C:19]([S:18][CH3:17])=[CH:20][CH:21]=3)[N:26]=[C:4]([CH3:5])[N:6]=2)=[CH:13][CH:12]=1
Reactant: CCOC(C)=NC(=O)c1ccc(F)cc1
Reactant: CSc1ccc(NN)cc1
Agent: Cl
Solvent: CO
Solvent: CCN(CC)CC
Solvent: O
Product: CSc1ccc(-n2nc(C)nc2-c2ccc(F)cc2)cc1
Reaction time: 8 h

Procedure:
N-(1-ethoxy-ethylidene)-4-fluoro benzamide 438 mg (2.09 mmol) was dissolved in a mixed solvent of dichloromethane 20 ml and methanol 10 ml, and (4-methylsulfanyl-phenyl)-hydrazine hydrochloride 439 mg (2.23 mmol) was added to the solution. Then, triethylamine 0.35 ml (2.51 mmol) was slowly added dropwise at room temperature for 10 minutes and stirred for 8 hours. After completing the reaction, water 20 ml was added to the reacting solution and extracted two times with dichloromethane, and then, the collected organic layer was washed with saturated brine. The organic layer was dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure, and the resulting product was purified through a flash column chromatography (ethyl acetate:normal hexane=1:1). As a result, 5-(4-fluoro-phenyl)-3-mehtyl-1.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:33]=[CH:32][C:9]2[N:10]=[C:11]([C:13]3[CH:14]=[N:15][C:16]([N:19]4[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]4)=[CH:17][CH:18]=3)[S:12][C:8]=2[CH:7]=1)=[O:5])[CH3:2].[C:34]([OH:40])([C:36]([F:39])([F:38])[F:37])=[O:35].C(=O)([O-])O.[Na+]>C(Cl)Cl>[F:37][C:36]([F:39])([F:38])[C:34]([OH:40])=[O:35].[N:19]1([C:16]2[N:15]=[CH:14][C:13]([C:11]3[S:12][C:8]4[CH:7]=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH:33]=[CH:32][C:9]=4[N:10]=3)=[CH:18][CH:17]=2)[CH2:20][CH2:21][NH:22][CH2:23][CH2:24]1
Reactant: CCOC(=O)c1ccc2nc(-c3ccc(N4CCN(C(=O)OC(C)(C)C)CC4)nc3)sc2c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCOC(=O)c1ccc2nc(-c3ccc(N4CCNCC4)nc3)sc2c1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
2-[6-[4-[(1,1-Dimethylethoxy)carbonyl]-1-piperazinyl]-3-pyridinyl]-6-benzothiazolecarboxylic acid ethyl ester (0.42 g, 0.90 mmol) was dissolved in DCM (35 mL) and TFA (2 mL) was added. The reaction was stirred at r.t. for 3 days. Sat. sodium hydrogencarbonate was added to the mixture. The precipitate was collected, followed by washing with DCM and water, before drying in vacuo over P2O5 to give the title compound (0.34 g) as a yellow solid. 1H NMR δ 8.82-8.93 (m, 3H) 8.76 (s, 1H) 8.27 (dd, 1H) 8.07 (d, 2H) 7.11 (d, 1H) 4.37 (q, 2H) 3.84-3.95 (m, 4H) 3.23 (br. s., 4H) 1.36 (t, 3H); MS m/z (M+H) 369.