Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4]([N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)=[CH:5][C:6]([CH3:12])=[N:7]2.[F:19][C:20]1[CH:25]=[CH:24][C:23]([N:26]=[C:27]=[O:28])=[CH:22][CH:21]=1.CCCCCC.CCOC(C)=O>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4]([N:13]1[CH2:18][CH2:17][N:16]([C:27]([NH:26][C:23]3[CH:24]=[CH:25][C:20]([F:19])=[CH:21][CH:22]=3)=[O:28])[CH2:15][CH2:14]1)=[CH:5][C:6]([CH3:12])=[N:7]2
Reactant: O=C=Nc1ccc(F)cc1
Reactant: Cc1cc(N2CCNCC2)c2c(Cl)cccc2n1
Agent: CN(C)c1ccncc1
Solvent: CCCCCC
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: Cc1cc(N2CCN(C(=O)Nc3ccc(F)cc3)CC2)c2c(Cl)cccc2n1

Procedure:
5-Chloro-2-methyl-4-(piperazin-1-yl)quinoline (0.18 g, 0.7 mmol), 4-fluorophenyl isocyanate (91 μL, 0.8 mmol), and DMAP (5 mg) in CH2Cl2 (10 mL) are reacted according to method C yielding the product as a colorless solid after column chromatography with hexane-EtOAc.
Reaction SMILES: [Mg:1].II.[Br:4][C:5]1[CH:10]=[CH:9][C:8](OC)=[CH:7][CH:6]=1.[O:13]1[CH2:17]CCC1>>[CH3:17][O:13][Mg:1][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1.[Br-:4]
Reactant: COc1ccc(Br)cc1
Reactant: C1CCOC1
Reactant: [Mg]
Agent: II
Product: CO[Mg]c1ccccc1
Product: [Br-]
Temperature: 65 °C
Reaction time: 1 h

Procedure:
A suspension of magnesium turnings (268 g; 11.02 moles--Janssen) in tetrahydrofuran (2695 g) was heated at 65° C. under stirring and under nitrogen. Then, iodine (2.7 g) and, after 30 minutes, 4-bromoanisole (2000 g; 10.69 moles), in 1 hour, were added to the reaction mixture. At the end of the addition, the reaction mixture was kept at 75° C. for 1 hour and, then, decanted obtaining a solution of methoxyphenylmagnesiumbromide (solution A).
Reaction SMILES: [Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]Br.C1([P:15](C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>>[Br-:1].[Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][PH3+:15]
Reactant: BrCCCCCCBr
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: [Br-]
Product: [PH3+]CCCCCCBr
Yield: 120.2 %

Procedure:
9.3 g of 1,6-dibromohexane and 5 g of triphenylphosphine were stirred under argon at 100° for 1 hour. The reaction mixture was subsequently cooled and chromatographed on 90 g of silica gel with methylene chloride/methanol 95:5. The 6-bromohexyl-phosphonium bromide (6.37 g, 65%) obtained was treated with 35 ml of a 33 percent solution of dimethylamine in ethanol and stirred at room temperature for 24 hours under argon. The solution was evaporated and the residue was dried carefully in a high vacuum. The 6-(dimethylamino)hexyl-triphenylphosphonium bromide hydrobromide obtained was suspended in 50 ml of tetrahydrofuran, whereupon the suspension was treated portionwise at 0° with 2.09 g of potassium t-butylate. The mixture was stirred at 0° for 15 minutes. Subsequently, a solution of 1.86 g of 4-benzoyl-benzaldehyde [Tetrahed. Lett. 24, 4287 (1983)] in 10 ml of tetrahydrofuran was added thereto at 0° and the mixture was stirred at room temperature for 18 hours. The reaction mixture was evaporated. The residue was taken up in 100 ml of 1N hydrochloric acid and extracted three times with 100 ml of ether. The aqueous phase was made basic with 2N sodium hydroxide solution while cooling with ice and extracted three times with methylene chloride. The organic phases were dried over magnesium sulphate and evaporated. The crude product obtained was chromatographed on 100 g of neutral aluminium oxide (activity grade III) with methylene chloride/ethyl acetate 95:5. After evaporation there were obtained 1.98 g (31%) of 4-[(Z)-7-(dimethylamino)-1-heptenyl]benzophenone as a colourless oil.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:10].[CH2:17]([C:19]1[CH:24]=[CH:23][C:22]([S:25](Cl)(=[O:27])=[O:26])=[CH:21][CH:20]=1)[CH3:18]>>[C:9]([C:3]1[CH:4]=[C:5]([Cl:8])[CH:6]=[CH:7][C:2]=1[NH:1][S:25]([C:22]1[CH:23]=[CH:24][C:19]([CH2:17][CH3:18])=[CH:20][CH:21]=1)(=[O:27])=[O:26])(=[O:10])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: Nc1ccc(Cl)cc1C(=O)c1ccccc1
Reactant: CCc1ccc(S(=O)(=O)Cl)cc1
Product: CCc1ccc(S(=O)(=O)Nc2ccc(Cl)cc2C(=O)c2ccccc2)cc1

Procedure:
The title compound was prepared according to the general procedure for the synthesis of N-Aryl-benzenesulfonamides previously described using 115 mg of (2-amino-5-chloro-phenyl)-phenyl-methanone and 102 mg of 4-ethyl-benzenesulfonyl chloride. 1H-NMR (400 MHz, CDCl3): δ 1.13 (t, 3H, J=8.0 Hz), 2.53 (q, 2H, J-15.3 Hz, 7.6 Hz), 7.07 (d, 2H, J=8.4 Hz), 7.32 (d, 1H, J=2.8 Hz), 7.34-7.42 (m, 4H), 7.48 (dd, 1H, J=8.8 Hz, 2.4 Hz), 7.56 (m, 3H), 7.76 (d, 1H, J=8.8 Hz), 9.75 (s, 1H). MS: m/z 400.8 (M++1).
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.Cl.Cl.[N:13]1[CH:18]=[CH:17][N:16]=[CH:15][C:14]=1[CH2:19][NH2:20].CN(C)C(=O)C.C(=O)([O-])[O-].[Na+].[Na+]>CC(C)CC(=O)C.O>[N+:8]([C:7]1[C:2]([NH:20][CH2:19][C:14]2[CH:15]=[N:16][CH:17]=[CH:18][N:13]=2)=[N:3][CH:4]=[CH:5][CH:6]=1)([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1cccnc1Cl
Reactant: NCc1cnccn1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Solvent: CC(=O)CC(C)C
Solvent: O
Product: O=[N+]([O-])c1cccnc1NCc1cnccn1
Temperature: 100 °C
Reaction time: 1.5 h
Yield: 10 %

Procedure:
To a stirred solution of 25.4 parts of 2-chloro-3-nitropyridine, 29.5 parts of 2-pyrazinemethanamine dihydrochloride and 235 parts of N,N-dimethylacetamide were added 67.8 parts of sodium carbonate. The reaction mixture was stirred for 1.5 hours at 100° C. The reaction mixture was poured into water and 4-methyl-2-pentanone. The whole was filtered twice over diatomaceous earth and the layers were separated. The organic layer was dried, filtered and evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 3.6 parts (10%) of N-(3-nitro-2-pyridinyl)-2-pyrazinemethanamine (int. 27).
Reaction SMILES: N[C:2]1[CH:3]=[CH:4][C:5]([C:9]#[N:10])=[N:6][C:7]=1[CH3:8].[ClH:11]>CC#N.Cl[Cu]>[Cl:11][C:2]1[CH:3]=[CH:4][C:5]([C:9]#[N:10])=[N:6][C:7]=1[CH3:8]
Reactant: Cl
Reactant: Cc1nc(C#N)ccc1N
Agent: Cl[Cu]
Solvent: CC#N
Product: Cc1nc(C#N)ccc1Cl
Temperature: 60 °C
Reaction time: 2 h

Procedure:
A solution of 5-amino-6-methylpicolinonitrile (2) (260 mg, 1.95 mmol), CuCl (290 mg, 2.93 mmol) and t-BuONO (456 mg, 3.9 mmol) in CH3CN (10 mL) was stirred at room temperature under N2 for 2 h, and then warmed to 60° C. After 2 h, 10 mL 6N HCl was added and extracted with EA (3×10 mL). The organic phase was dried with anhydrous Na2SO4, filtered and concentrated. The residue was purified by Prep-TLC using PE/EtOAc=1/1 to give title compound as oil.
Reaction SMILES: C(B(CC)[C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1)C.Br[C:13]1[CH:14]=[C:15]([CH:17]=[CH:18][CH:19]=1)[NH2:16].C(=O)([O-])[O-].[K+].[K+]>O.C(COC)OC.C(OCC)(=O)C.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>[N:6]1[CH:7]=[CH:8][CH:9]=[C:4]([C:13]2[CH:14]=[C:15]([CH:17]=[CH:18][CH:19]=2)[NH2:16])[CH:5]=1
Reactant: Nc1cccc(Br)c1
Reactant: CCB(CC)c1cccnc1
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: [K+]
Solvent: COCCOC
Solvent: CCOC(C)=O
Solvent: O
Product: Nc1cccc(-c2cccnc2)c1
Temperature: 80 °C
Yield: 87.1 %

Procedure:
A mixture of diethyl 3-pyridylborane (16.3 g, 0.11 mol), 3-bromoaniline (12.2 ml, 0.11 mol), potassium carbonate (45.8 g, 0.33 mol) and tetrakis(triphenylphosphine)palladium(0) (80 mg) in a mixture of water (40 ml) and dimethoxyethane (80 ml) is heated to 80° C. under a stream of nitrogen over night. After cooling the mixture is diluted with water and ethyl acetate and filtered through a fluted filterpaper. The layers are separated. The aqueous layer is extracted once with ethyl acetate. The combined organic phases are dried over sodium sulfate and concentrated under reduced pressure. The residue is dissolved in ethanol. Water is added and the mixture is evaporated to dryness. This residue crystallizes upon trituration with ice-cold water. The crystals are collected, dried and washed with petroleum ether to afford pure 2p (16.3 g, 87%). Mp 75-76° C.
Reaction SMILES: C[O:2][C:3](=[O:23])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[N:18][C:17]([CH3:20])=[CH:16][N:15]=2)=[O:12])=[C:6]([O:21][CH3:22])[CH:5]=1.CO.O.[OH-].[Li+]>O>[CH3:22][O:21][C:6]1[CH:5]=[C:4]([CH:9]=[CH:8][C:7]=1[NH:10][C:11]([NH:13][C:14]1[CH:19]=[N:18][C:17]([CH3:20])=[CH:16][N:15]=1)=[O:12])[C:3]([OH:23])=[O:2]
Reactant: COC(=O)c1ccc(NC(=O)Nc2cnc(C)cn2)c(OC)c1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: COc1cc(C(=O)O)ccc1NC(=O)Nc1cnc(C)cn1
Temperature: 65 °C
Reaction time: 8 h
Yield: 87.8 %

Procedure:
To a stirred suspension of 3-methoxy-4-[3-(5-methyl-pyrazin-2-yl)-ureido]-benzoic acid methyl ester (7.15 g, 22.6 mmol) in 3:1 MeOH:H2O (226 mL) at RT under N2 was added lithium hydroxide monohydrate (9.5 g, 226 mmol) as a solid and the mixture heated to 65 ° C. After reaching temperature, the suspension gradually became a bright yellow solution. After about 4 hours a precipitate formed but the reaction was continued overnight. After cooling to RT, MeOH was removed by rotovap and the aqueous suspension diluted with 100 mL H2O and neutralized to pH=5 with concentrated HCl. As pH=5 was approached, the suspension turned from yellow to white. The suspension was then filtered through paper on a large ceramic funnel. The filtration went very slowly, taking several hours. The filter cake was washed twice with H2O. When most of the H2O was removed, the residue was dried under high vacuum in a dessicator overnight to give the free acid as a white solid (6 g, 88%). 1H-NMR (400 MHz, d6-DMSO) δ 8.79 (br s, 1H), 8.36 (d, 1H), 8.22 (s, 1H), 7.57 (d, 1H), 7.51 (s, 1H), 3.97 (s, 3H), 242 (s, 3H).
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[C:5]([I:13])[CH:6]=[C:7]([CH:12]=1)[C:8]([O:10][CH3:11])=[O:9])=O.C(O)(=O)[CH2:15][C:16]([OH:18])=[O:17].N1CCCCC1.Cl>N1C=CC=CC=1.O>[C:16](/[CH:15]=[CH:1]/[C:3]1[CH:4]=[C:5]([I:13])[CH:6]=[C:7]([CH:12]=1)[C:8]([O:10][CH3:11])=[O:9])([OH:18])=[O:17]
Reactant: O=C(O)CC(=O)O
Reactant: COC(=O)c1cc(I)cc(C=O)c1
Agent: Cl
Solvent: O
Solvent: c1ccncc1
Solvent: C1CCNCC1
Product: COC(=O)c1cc(I)cc(/C=C/C(=O)O)c1
Temperature: 100 °C
Reaction time: 3 h
Yield: 83.8 %

Procedure:
The mixture of methyl 5-formyl-3-iodobenzoate (2.5 g), malonic acid (1.8 g) and piperidine (0.2 ml) in pyridine (25 ml) was stirred for 3 hours at 100° C. The mixture was added to water and adjusted to pH 2 with 6N-hydrochloric acid. The isolated precipitate was collected by filtration to give methyl 5-[(E)-2-carboxyethenyl]-3-iodobenzoate (2.4 g)
Reaction SMILES: C([O:3][C:4]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][C:11]([Cl:18])=[C:12]([Br:17])[CH:13]=2)[NH:8][CH:7]=1)=[O:5])C.C(=O)([O-])[O-].[CH2:23](I)[CH3:24]>CN(C=O)C>[Br:17][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][C:11]=1[Cl:18])[N:8]([CH2:23][CH3:24])[CH:7]=[C:6]([C:4]([OH:3])=[O:5])[C:15]2=[O:16]
Reactant: CCOC(=O)c1c[nH]c2cc(Cl)c(Br)cc2c1=O
Reactant: CCI
Agent: O=C([O-])[O-]
Solvent: CN(C)C=O
Product: CCn1cc(C(=O)O)c(=O)c2cc(Br)c(Cl)cc21
Reaction time: 10 h

Procedure:
A mixture of the above ester (7.5 g), pottasium carbonate (7.8 g), ethyl iodide (9.0 ml) and DMF (100 ml was stirred at 90°-110° C. for 10 hours and evaporated. The residue was extracted with chloroform, the chloroform layer was washed with water, and dried. The solvent was evaporated. The residue was added to a solution of sodium hydroxide (4.2 g) and water (100 ml) and refluxed for 30 minutes. The alkaline solution was acidified with concentrated hydrochloric acid and the precipitate was filtered. The precipitate was washed with water, dried, and recrystallized from DMF to give 6-bromo-7-chloro-1-ethyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (6.9 g).
Reaction SMILES: [C:1]([O:5][C:6](=[O:20])[CH2:7][CH2:8][S:9][CH2:10][C:11]1[CH:12]=[C:13]([CH:17]=[CH:18][CH:19]=1)[C:14]([OH:16])=O)([CH3:4])([CH3:3])[CH3:2].CCN=C=NCCCN(C)C.Cl.[F:33][C:34]([F:68])([F:67])[C:35]1[CH:36]=[C:37]([CH:64]=[CH:65][CH:66]=1)[CH2:38][NH:39][C:40](=[O:63])[C:41]1[CH:46]=[CH:45][N:44]=[C:43]([C:47]2[CH:52]=[C:51]([N:53]([CH2:58][CH2:59][O:60][CH3:61])[CH2:54][CH2:55][O:56][CH3:57])[CH:50]=[CH:49][C:48]=2[NH2:62])[CH:42]=1>ClCCl.CN(C)C1C=CN=CC=1>[F:67][C:34]([F:33])([F:68])[C:35]1[CH:36]=[C:37]([CH:64]=[CH:65][CH:66]=1)[CH2:38][NH:39][C:40]([C:41]1[CH:46]=[CH:45][N:44]=[C:43]([C:47]2[CH:52]=[C:51]([N:53]([CH2:54][CH2:55][O:56][CH3:57])[CH2:58][CH2:59][O:60][CH3:61])[CH:50]=[CH:49][C:48]=2[NH:62][C:14]([C:13]2[CH:12]=[C:11]([CH:19]=[CH:18][CH:17]=2)[CH2:10][S:9][CH2:8][CH2:7][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:20])=[O:16])[CH:42]=1)=[O:63]
Reactant: CC(C)(C)OC(=O)CCSCc1cccc(C(=O)O)c1
Reactant: COCCN(CCOC)c1ccc(N)c(-c2cc(C(=O)NCc3cccc(C(F)(F)F)c3)ccn2)c1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Product: COCCN(CCOC)c1ccc(NC(=O)c2cccc(CSCCC(=O)OC(C)(C)C)c2)c(-c2cc(C(=O)NCc3cccc(C(F)(F)F)c3)ccn2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 64 %

Procedure:
Into a 10-mL vial, was placed a solution of 3-((3-tert-butoxy-3-oxopropylthio)methyl)benzoic acid (188.64 mg, 0.64 mmol, 2.00 equiv) in dichloromethane (5 mL), EDC.HCl (120.8 mg, 0.63 mmol, 1.98 equiv), 4-dimethylaminopyridine (77.6 mg, 0.64 mmol, 2.00 equiv), and N-(3-(trifluoromethyl)benzyl)-2-(2-amino-5-(bis(2-methoxyethyl)amino)phenyl)-isonicotinamide (160 mg, 0.32 mmol, 1.00 equiv). The resulting solution was stirred for 2 h at 25° C. in an oil bath. The reaction progress was monitored by LCMS. The resulting solution was diluted with 50 mL of dichloromethane, and washed with 3×50 mL of aqueous NH4Cl. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1:5˜1). The product was obtained as 160 mg (64%) of a yellow solid.
Reaction SMILES: [Br-:1].[OH:2][CH2:3][CH2:4][N+:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([CH3:15])=[CH:7][CH:6]=1.C1(N(C2C=CC=CC=2)C=N)C=CC=CC=1.[Br-].[OH:32][CH2:33][CH2:34][N+:35]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:38]([CH:45]=[CH:46]NC2C=CC=CC=2)=[CH:37][CH:36]=1>C(O)C>[Br-:1].[OH:2][CH2:3][CH2:4][N+:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([CH:15]=[CH:46][CH:45]=[C:38]2[C:39]3[C:44](=[CH:43][CH:42]=[CH:41][CH:40]=3)[N:35]([CH2:34][CH2:33][OH:32])[CH:36]=[CH:37]2)=[CH:7][CH:6]=1
Reactant: Cc1cc[n+](CCO)c2ccccc12
Reactant: OCC[n+]1ccc(C=CNc2ccccc2)c2ccccc21
Agent: N=CN(c1ccccc1)c1ccccc1
Agent: [Br-]
Solvent: CCO
Product: OCCN1C=CC(=CC=Cc2cc[n+](CCO)c3ccccc23)c2ccccc21

Procedure:
On an oil bath, 2.7 g of 1-(2-hydroxyethyl)-4-methylquinolinium bromide and diphenylformamidine were heated for 5 minutes to melt them. Thereto was added 150 ml of ethanol, and the resulting mixture was boiled, upon which 1-(2-hydroxyethyl)-4-(2-anilinovinyl)-quinolinium bromide was crystallized. Then, 2.5 g of 1-hydroxyethyl-4-methylquinolinium bromide and 10 ml of triethylamine were added thereto and subjected to reaction under reflux for one hour. After completion of the reaction, the reaction product was cooled and the crude crystals thus obtained were recrystallized from methanol to obtain 2 g of the objective compound (melting point 262° C.) which was dark green. Its maximum absorption wavelength as measured in methanol was 707 nm.
Reaction SMILES: ClC1C=CC2SC=C(CN3CCN(C4SC(C(O)=O)=C(C)N=4)C3=O)C=2C=1.[CH3:27][C:28]1[N:29]=[C:30]([N:36]2[CH2:40][CH2:39][N:38]([CH2:41][C:42]3[CH:43]=[CH:44][CH:45]=[C:46]4[C:51]=3[N:50]=[CH:49][CH:48]=[CH:47]4)[C:37]2=[O:52])[S:31][C:32]=1[C:33](O)=[O:34].[NH2:53][CH2:54][C:55]1[CH:56]=[N:57][CH:58]=[CH:59][CH:60]=1>>[CH3:27][C:28]1[N:29]=[C:30]([N:36]2[CH2:40][CH2:39][N:38]([CH2:41][C:42]3[CH:43]=[CH:44][CH:45]=[C:46]4[C:51]=3[N:50]=[CH:49][CH:48]=[CH:47]4)[C:37]2=[O:52])[S:31][C:32]=1[C:33]([NH:53][CH2:54][C:55]1[CH:56]=[N:57][CH:58]=[CH:59][CH:60]=1)=[O:34]
Reactant: Cc1nc(N2CCN(Cc3cccc4cccnc34)C2=O)sc1C(=O)O
Reactant: NCc1cccnc1
Agent: Cc1nc(N2CCN(Cc3csc4ccc(Cl)cc34)C2=O)sc1C(=O)O
Product: Cc1nc(N2CCN(Cc3cccc4cccnc34)C2=O)sc1C(=O)NCc1cccnc1
Yield: 44 %

Procedure:
Following the procedure as described in Example 32, making variations as required to replace 2-(3-((5-chlorobenzo[b]thiophen-3-yl)methyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid with 4-methyl-2-(2-oxo-3-(quinolin-8-ylmethyl)imidazolidin-1-yl)thiazole-5-carboxylic acid to react with 3-(aminomethyl)pyridine, the title compound was obtained as a colorless solid in 44% yield: mp 225-228° C. (methanol); 1H NMR (300 MHz, DMSO-d6) δ 8.98-8.96 (m, 1H), 8.59-8.53 (m, 2H), 8.46-8.39 (m, 2H), 7.96-7.93 (m, 1H), 7.72-7.70 (m, 2H), 7.63-7.58 (m, 2H), 7.38-7.33 (m, 1H), 5.09 (s, 2H), 4.40 (d, J=5.8 Hz, 2H), 4.07-4.01 (m, 2H), 3.63-3.58 (m, 2H), 2.48 (s, 3H); MS (ES+) m/z 459.3 (M+1).
Reaction SMILES: [NH2:1][C:2]1[CH:15]=[CH:14][CH:13]=[CH:12][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5].[CH3:16][S:17][CH2:18][C:19](OCC)=[O:20].C(OCl)(C)(C)C.C(N(CC)CC)C>C(Cl)Cl>[C:4]([C:3]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:2]=1[NH:1][C:19](=[O:20])[CH:18]2[S:17][CH3:16])(=[O:5])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: Nc1ccccc1C(=O)c1ccccc1
Reactant: CCOC(=O)CSC
Agent: CC(C)(C)OCl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CSC1C(=O)Nc2c(C(=O)c3ccccc3)cccc21
Temperature: -65 °C
Reaction time: 2 h

Procedure:
A solution of 300 g. (1.52 mole) of 2-aminobenzophenone in 4 liters of methylene chloride was chilled to -40° C. and then treated with 204 g. (1.52 mole) of the ethyl α-(methylthio)acetate dissolved in 5 liters of methylene chloride. The reaction mixture was then cooled to -65° C. and treated dropwise with 500 ml. of a methylene chloride solution containing 164 g. (1.52 mole) of t-butylhypochlorite. After addition was complete, stirring was continued for 2 hr. at -70° C. The solution was then treated with 182 g. (1.8 mole) of triethylamine and allowed to come to room temperature overnight. The methylene chloride solution was washed twice with 3 liters of ice water followed by drying over sodium sulfate and concentrating the dried solution to a yellow oil under reduced pressure. The oil was taken into 1.5 liters of methanol treated with 1 liter of 1 N hydrochloric acid and refluxed for 2 hrs. After cooling in an ice bath 343 g. (79.9%) of crude produce was recovered after filtering and drying. Two recrystallizations from toluene gave creamy white flakes; m.p. 130° C.
Reaction SMILES: CS[C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[CH2:5][Br:6].O[O:12][S:13]([O-:15])=O.[K+].[CH3:17]O>O>[CH3:17][S:13]([C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[CH2:5][Br:6])(=[O:15])=[O:12]
Reactant: CSc1ccccc1CBr
Reactant: O=S([O-])OO
Reactant: CO
Agent: [K+]
Solvent: O
Product: CS(=O)(=O)c1ccccc1CBr
Reaction time: 4.5 h

Procedure:
To a solution of 124 mg (0.57 mmol) of 2-(methylthio)-benzylbromide in 8.0 mL of methanol was added a solution of 702 mg of oxone in 7.0 mL of water. The solution was stirred for 4.5 h, concentrated in vacuo and purified by silica gel flash chromatography, eluting with 10% ethyl acetate/hexane to give 105 mg of the title compound. mass spec 249(M+). NMR (CDCl3): δ 3.25 (s, 3H), 5.07 (s, 2H), 7.50 (m, 1H), 7.60 (m, 2H), 8.05 (d, 1H).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[C:12](=[O:13])[C:11]2[C:6](=[CH:7][C:8]([Cl:14])=[CH:9][CH:10]=2)[N:5]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:4]=1.[CH2:21]([N:28]1[CH:33]=[CH:32][C:31]([C:34](O)=[O:35])=[CH:30][C:29]1=[O:37])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[Cl:14][C:8]1[CH:7]=[C:6]2[C:11]([C:12](=[O:13])[C:3]([CH2:2][NH:1][C:34]([C:31]3[CH:32]=[CH:33][N:28]([CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:29](=[O:37])[CH:30]=3)=[O:35])=[CH:4][N:5]2[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)=[CH:10][CH:9]=1
Reactant: NCc1cn(-c2ccccc2)c2cc(Cl)ccc2c1=O
Reactant: O=C(O)c1ccn(Cc2ccccc2)c(=O)c1
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: O=C(NCc1cn(-c2ccccc2)c2cc(Cl)ccc2c1=O)c1ccn(Cc2ccccc2)c(=O)c1
Temperature: 25 °C

Procedure:
In a 20 mL round-bottomed flask, 3-(aminomethyl)-7-chloro-1-phenylquinolin-4(1H)-one (intermediate D) (50 mg, 0.176 mmol), 1-benzyl-2-oxo-1,2-dihydropyridine-4-carboxylic acid (40.3 mg, 0.176 mmol), bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBrOP) (81.8 mg, 176 mmol) and N,N-diisopropylethylamine (0.092 mL, 0.527 mmol) were combined with CH2Cl2 (5.00 mL). The reaction mixture was stirred at room temperature, and the crude product was purified using preparative reverse-phase HPLC. MS calcd. for C29H23ClN3O3 [(M+H)+] 496.1, obsd. 496.0.
Reaction SMILES: [CH3:1][C:2]1[CH:16]=[CH:15][C:5]2[N:6]=[C:7]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[S:8][C:4]=2[CH:3]=1.C1C(=O)N([Br:24])C(=O)C1.CC(N=NC(C#N)(C)C)(C#N)C.C(Cl)(Cl)(Cl)Cl>C(Cl)(Cl)Cl>[Br:24][CH2:1][C:2]1[CH:16]=[CH:15][C:5]2[N:6]=[C:7]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[S:8][C:4]=2[CH:3]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1ccc2nc(-c3ccccc3)sc2c1
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Solvent: ClC(Cl)Cl
Product: BrCc1ccc2nc(-c3ccccc3)sc2c1
Temperature: 25 °C
Yield: 67.1 %

Procedure:
Combine 6-methyl-2-phenyl-benzothiazole (0.2 g, 0.98 mmol), NBS (0.2 g, 1.02 mmol), AIBN (20 mg, 0.10 mmol), carbon tetrachloride (5 mL) and reflux for 3 h. Cool the reaction mixture to ambient temperature, dilute with chloroform and wash with water. Dry the organic extracts over anhydrous Na2SO4, concentrate and purify by chromatography on silica gel eluting with hexane/EtOAc (1:0, 9:1, 8:2 and 7:3) to obtain the title compound as a white solid (0.2 g, 69%).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4](=[O:41])[C:5]([CH3:40])=[C:6]([CH2:12][C:13]2[CH:14]=[CH:15][C:16]([O:36]C(=O)C)=[C:17]([CH:35]=2)[C:18]([NH:20][C:21]2[CH:26]=[CH:25][C:24]([NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=[CH:23][CH:22]=2)=[O:19])[C:7](=[O:11])[C:8]=1[O:9][CH3:10].C(=O)([O-])O.[Na+]>CO.O>[CH3:1][O:2][C:3]1[C:4](=[O:41])[C:5]([CH3:40])=[C:6]([CH2:12][C:13]2[CH:14]=[CH:15][C:16]([OH:36])=[C:17]([CH:35]=2)[C:18]([NH:20][C:21]2[CH:26]=[CH:25][C:24]([NH:27][C:28]([O:30][C:31]([CH3:32])([CH3:33])[CH3:34])=[O:29])=[CH:23][CH:22]=2)=[O:19])[C:7](=[O:11])[C:8]=1[O:9][CH3:10]
Reactant: COC1=C(OC)C(=O)C(Cc2ccc(OC(C)=O)c(C(=O)Nc3ccc(NC(=O)OC(C)(C)C)cc3)c2)=C(C)C1=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: O
Product: COC1=C(OC)C(=O)C(Cc2ccc(O)c(C(=O)Nc3ccc(NC(=O)OC(C)(C)C)cc3)c2)=C(C)C1=O
Yield: 73.4 %

Procedure:
N-[5-(5,6-Dimethoxy-3-methyl-1,4-benzoquinon-2-yl)methyl-2-acetoxybenzoyl]-4-(tert-butoxycarbonyl)aminoaniline (0.140 g, 0.248 mmol) was dissolved in methanol (6 ml) and after adding thereto an aqueous saturated sodium hydrogencarbonate solution (2 ml), the solution was stirred at room temperature for 3 hours. After the completion of reaction, the reaction solution was diluted with water and extracted with ethyl acetate. The extract was washed with water and then dried, and the solvent was removed by distillation. The obtained residue was purified by preparative thin-layer chromatography (chloroform:methanol=10:1) and then recrystallized from a mixed solvent of ether and hexane (3:1) to obtain the titled compound (0.095 g, 0.182 mmol, 73%).