Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CCN=C=NCCCN(C)C.[CH2:12]([N:14]1[C:18]([C:19]2[CH:20]=[C:21]([C:32](O)=[O:33])[CH:22]=[C:23]([C:25]3[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=3)[CH:24]=2)=[N:17][N:16]=[N:15]1)[CH3:13].C1C=CC2N(O)N=NC=2C=1.CN1C(=O)CCC1.[CH3:52][O:53][CH2:54][CH:55]([NH2:57])[CH3:56]>C(Cl)Cl>[CH3:52][O:53][CH2:54][CH:55]([NH:57][C:32]([C:21]1[CH:22]=[C:23]([C:25]2[CH:26]=[CH:27][C:28]([CH3:31])=[CH:29][CH:30]=2)[CH:24]=[C:19]([C:18]2[N:14]([CH2:12][CH3:13])[N:15]=[N:16][N:17]=2)[CH:20]=1)=[O:33])[CH3:56]
Reactant: COCC(C)N
Reactant: CCn1nnnc1-c1cc(C(=O)O)cc(-c2ccc(C)cc2)c1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CN1CCCC1=O
Solvent: ClCCl
Product: CCn1nnnc1-c1cc(C(=O)NC(C)COC)cc(-c2ccc(C)cc2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 46 %

Procedure:
EDCI (54.0 mg, 0.282 mmol) was added in one portion to a solution of 5-(1-ethyl-1H-tetrazol-5-yl)-4′-methyl-biphenyl-3-carboxylic acid (70.0 mg, 0.229 mmol), HOBt (40.0 mg, 0.296 mmol) and NMP (101.5 mg, 1.000 mmol) in CH2Cl2 (5 mL) at 0° C. After the reaction stirred at the same temperature for 1 hour, 2-methoxy-1-methyl-ethylamine (64.3 mg, 0.72 mmol) was added. The mixture was allowed to warm to room temperature and was stirred overnight. Solvent was removed under reduced pressure and the residue was purified by column chromatography to afford 5-(1-ethyl-1H-tetrazol-5-yl)-4′-methyl-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide as white solid (40 mg, 46%). MS (M+H)=380.
Reaction SMILES: [CH:1]1[CH:6]=[C:5]([NH2:7])[C:4]([NH:8][C:9](C2C=CC(N)=CC=2)=O)=[CH:3][CH:2]=1.BrC#[N:20]>CO>[NH2:20][C:9]1[NH:8][C:4]2[CH:3]=[CH:2][CH:1]=[CH:6][C:5]=2[N:7]=1
Reactant: Nc1ccc(C(=O)Nc2ccccc2N)cc1
Reactant: N#CBr
Solvent: CO
Product: Nc1nc2ccccc2[nH]1
Temperature: 25 °C

Procedure:
Alternatively, 6.0 mmol of dianiline was treated with 6.3 mmol BrCN in 15 mL CH3OH at reflux for 3 h. The reaction mixture was cooled to ambient temperature and precipitate was filtered off to give the corresponding 2-aminobenzimidazole.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][C:9]([OH:11])=[O:10].[OH-].[Na+].[CH2:14]([O:21][C:22](Cl)=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C1COCC1.O>[CH2:14]([O:21][C:22]([NH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][C:9]([OH:11])=[O:10])=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: NCCOCCOCC(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)COCCOCCNC(=O)OCc1ccccc1
Reaction time: 2.5 h

Procedure:
A suspension of 6.7 g (12.5 mmol) of 2-[2-(aminoethoxy)ethoxy]-acetic acid in 30 ml of THF and 10 ml of water is adjusted to pH 10 with 2N NaOH, and reacted dropwise with 1.95 ml of chloroformic acid benzyl ester (Fluka, Buchs, Switzerland). While the mixture is being stirred for 2.5 h, the pH is maintained between 9 and 9.5 by 2N NaOH. After concentration of the reaction mixture under reduced pressure, the resulting aqueous phase is washed twice with ethyl acetate, adjusted to pH 1.8 with 2N sulfuric acid and extracted 3 times with ethyl acetate. The combined organic phases are then washed with water and brine, dried and concentrated under reduced pressure. The title compound so obtained is further used without being further purified. TLC Rf (ethyl acetate/acetic acid: 9/1)=0.39.
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1.[CH:15]([S:18]([C:21]1[CH:29]=[CH:28][C:24]([C:25](O)=[O:26])=[CH:23][CH:22]=1)(=[O:20])=[O:19])([CH3:17])[CH3:16]>>[Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:25](=[O:26])[C:24]2[CH:23]=[CH:22][C:21]([S:18]([CH:15]([CH3:16])[CH3:17])(=[O:20])=[O:19])=[CH:29][CH:28]=2)=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1
Reactant: CC(C)S(=O)(=O)c1ccc(C(=O)O)cc1
Reactant: Nc1ccc(Cl)c(-c2ccccn2)c1
Product: CC(C)S(=O)(=O)c1ccc(C(=O)Nc2ccc(Cl)c(-c3ccccn3)c2)cc1

Procedure:
2 g of 4-fluorobenzonitrile was used in Procedure Q with 2-propanethiol to afford 4-(isopropylthio)benzonitrile. 900 mg of 4-(isopropythio)benzonitrile was reacted via Procedure T to give 4-(isopropylthio)benzoic acid. 730 mg of 4-(isopropylthio)benzoic acid was reacted via Procedure R to give 4-(isopropylsulfonyl)benzoic acid. 75 mg of 4-chloro-3-(pyridin-2-yl)aniline was coupled to 4-(isopropylsulfonyl)benzoic acid via Procedure G. The product was purified on reverse phase HPLC to yield N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(isopropylsulfonyl)benzamide. MS (Q1) 415.0 (M)
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[SH:8].[H-].[Na+].[CH2:11]([O:13][C:14]([C@@H:16]1[CH2:20][CH:19](OS(C)(=O)=O)[CH2:18][C@H:17]1[CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=1)=[O:15])[CH3:12].Cl>O1CCCC1>[CH2:11]([O:13][C:14]([C@@H:16]1[CH2:20][CH:19]([S:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])[CH2:18][C@H:17]1[CH2:26][O:27][C:28]1[CH:29]=[CH:30][C:31]([Cl:34])=[CH:32][CH:33]=1)=[O:15])[CH3:12]
Reactant: Sc1ccccc1Cl
Reactant: CCOC(=O)[C@@H]1CC(OS(C)(=O)=O)C[C@H]1COc1ccc(Cl)cc1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)[C@@H]1CC(Sc2ccccc2Cl)C[C@H]1COc1ccc(Cl)cc1
Temperature: 0 °C
Reaction time: 96 h
Yield: 52.9 %

Procedure:
To a solution of 2-chlorobenzenthiol (306 mg) in tetrahydrofuran (4 mL) was added a suspension of sodium hydride in oil (55% w/w, 107 mg). The white suspension was cooled down to 0° C. then a solution of (1R,2R)-2-(4-Chloro-phenoxymethyl)-4-methanesulfonyloxy-cyclopentanecarboxylic acid ethyl ester (epimeric mixture, 343 mg) in tetrahydrofuran (5 mL) was slowly added. The reaction mixture was stirred at room temperature for 4 days. Hydrochloric acid (1N) was added and the mixture was extracted with ethyl acetate. The combined organic layers were washed with an aqueous saturated solution of sodiumcarbonate and brine then dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel with a gradient of cyclohexane/ethylacetate (19:1 to 3:1 v/v) as eluant to afford the title compound (0.205 g, 53%) as light yellow oil. MS (EI): 424.0 (M+H)+.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21](=O)[CH2:22][CH2:23][C:24]([O:26]CC)=O)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[NH2:31][NH2:32]>CC(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH2:22][CH2:23][C:24](=[O:26])[NH:32][N:31]=3)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: NN
Reactant: CCOC(=O)CCC(=O)c1ccc(OC2CCN(C(=O)OC(C)(C)C)CC2)cc1
Solvent: CC(C)O
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC(Oc2ccc(C3=NNC(=O)CC3)cc2)CC1
Temperature: 120 °C
Reaction time: 8 h
Yield: 88.3 %

Procedure:
To 4-[4-(3-ethoxycarbonyl-propionyl)-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester (2.68 g, 6.61 mmol) in 2-propanol (25 mL) was added hydrazine monohydrate (0.662 g, 13.2 mmol). After overnight stirring at 120° C., the reaction was concentrated down, partitioned between dichloromethane/water, washed with brine, dried over sodium sulfate, and concentrated under vacuum to obtain 2.18 g product (88%); MS m/z 374 (M+H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH3:13])[CH:6]=[C:7]2[C:11]=1[C:10](=O)[CH2:9][CH2:8]2.Cl.[NH2:15][OH:16].C([O-])(=O)C.[Na+].O>C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH3:13])[CH:6]=[C:7]2[C:11]=1[C:10](=[N:15][OH:16])[CH2:9][CH2:8]2
Reactant: COc1cc(C)cc2c1C(=O)CC2
Reactant: NO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: COc1cc(C)cc2c1C(=NO)CC2
Yield: 98 %

Procedure:
7-Methoxy-5-methyl-1-indanon (CAS no: 62358-78-5) (7.70 g, 0.044 mol) was dissolved in ethanol (40 mL) and hydroxylamine hydrochloride (6.23 g, 0.09 mol) and sodium acetate (7.38 g, 0.09 mol) were added. The reaction mixture was heated to reflux for 3 h. Then water (100 mL) was added and a precipitation formed which was filtered. The precipitate was washed with water, isolated and dried under high vacuum to yield 7-methoxy-5-methyl-indan-1-one oxime (8.20 g, 98%) as a white solid; MS: m/e=192.4 (M+H+).
Reaction SMILES: C(N(CC)CC)C.[C:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[C:16]1[CH:21]=[CH:20][C:19]([CH2:22][NH:23][CH2:24][CH2:25][CH3:26])=[CH:18][CH:17]=1)#[N:9].[Cl-].[CH3:28][O:29][C:30](=[O:39])[CH2:31][C:32]([CH3:38])([CH3:37])[CH2:33][C:34]([OH:36])=O>C(Cl)Cl>[C:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[C:16]1[CH:17]=[CH:18][C:19]([CH2:22][N:23]([CH2:24][CH2:25][CH3:26])[C:34](=[O:36])[CH2:33][C:32]([CH3:38])([CH3:37])[CH2:31][C:30]([O:29][CH3:28])=[O:39])=[CH:20][CH:21]=1)#[N:9]
Reactant: CCCNCc1ccc(-c2ccccc2C#N)cc1
Reactant: COC(=O)CC(C)(C)CC(=O)O
Agent: [Cl-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCN(Cc1ccc(-c2ccccc2C#N)cc1)C(=O)CC(C)(C)CC(=O)OC
Temperature: 25 °C
Reaction time: 2 h

Procedure:
1.83 ml of triethylamine are added to a solution of 2.19 g of N-(2'-cyanobiphenyl-4-ylmethyl)-N-propyl-amine and 2.37 g of 3,3-dimethylglutaric acid monomethyl ester monochloride in 100 ml of CH2Cl2 and the mixture is stirred at room temperature for 2 hours. Extraction twice with 50 ml of water each time and extraction of the aqueous phase with 40 ml of CH2Cl2 produces an organic phase which, after being concentrated by evaporation, yields by the customary procedure 3,3-dimethyl-4-methoxycarbonyl-butanoic acid N-(2'-cyanobiphenyl-4-ylmethyl)-N-propyl-amide that has an Rf value of 0.66 [CH2Cl2 /CH3OH (95:5)].
Reaction SMILES: [C:1]([C@H:5]1[NH:8][C:7](=[O:9])[CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[C:10]1([C@H:16]([N:19]=[C:20]=[O:21])[CH2:17][CH3:18])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>>[C:10]1([C@H:16]([NH:19][C:20]([N:8]2[C@H:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:6][C:7]2=[O:9])=[O:21])[CH2:17][CH3:18])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: CC[C@@H](N=C=O)c1ccccc1
Reactant: CC(C)(C)[C@@H]1CC(=O)N1
Product: CC[C@@H](NC(=O)N1C(=O)C[C@H]1C(C)(C)C)c1ccccc1

Procedure:
Following the same procedure as in example 1, step F, but using 4(S)-tert-butylazetidine-2-one as starting material and 1(R)-phenylpropyl isocyanate as reactant, 4(S)-tert-butyl-2-oxoazetidine-1-carboxylic acid (1(R)-phenylpropyl)amide was obtained as a waxy solid.
Reaction SMILES: [O:1]=[C:2]1[C:7]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[C:16]([C:21]#[N:22])=[CH:17][CH:18]=[CH:19][CH:20]=3)=[CH:11][CH:10]=2)=[C:6]([CH2:23][CH2:24][CH3:25])[N:5]2[N:26]=[CH:27][N:28]=[C:4]2[NH:3]1.Br[CH2:30][C:31]([C:33]1[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=1)=[O:32].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>C(OCC)(=O)C>[F:39][C:36]1[CH:37]=[CH:38][C:33]([C:31](=[O:32])[CH2:30][N:3]2[C:2](=[O:1])[C:7]([CH2:8][C:9]3[CH:10]=[CH:11][C:12]([C:15]4[C:16]([C:21]#[N:22])=[CH:17][CH:18]=[CH:19][CH:20]=4)=[CH:13][CH:14]=3)=[C:6]([CH2:23][CH2:24][CH3:25])[N:5]3[N:26]=[CH:27][N:28]=[C:4]23)=[CH:34][CH:35]=1
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)[nH]c2ncnn12
Reactant: O=C(CBr)c1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n(CC(=O)c2ccc(F)cc2)c2ncnn12
Temperature: 25 °C
Reaction time: 3 h
Yield: 57 %

Procedure:
A mixture of 4′-[(5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)methyl]biphenyl-2-carbonitrile (1 g), 2-bromo-1-(4-fluorophenyl)ethanone (0.65 mL), potassium carbonate (0.75 g) and N,N-dimethylformamide (15 mL) was stirred at room temperature for 3 hr. The reaction mixture was diluted with ethyl acetate, washed with 5% aqueous potassium hydrogensulfate 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 (0.78 g, 57%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][CH2:15][O:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([Cl:31])=[C:24]([CH2:27][CH2:28][CH2:29][OH:30])[CH:25]=2)[NH:20][C:19](=[O:32])[C:18]=1[C:33]1[CH:38]=[C:37]([CH3:39])[CH:36]=[C:35]([CH3:40])[CH:34]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[N+]1([O-])CC[O:45]CC1>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][CH2:15][O:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([Cl:31])=[C:24]([CH2:27][CH2:28][C:29]([OH:45])=[O:30])[CH:25]=2)[NH:20][C:19](=[O:32])[C:18]=1[C:33]1[CH:34]=[C:35]([CH3:40])[CH:36]=[C:37]([CH3:39])[CH:38]=1)=[O:7])([CH3:2])([CH3:4])[CH3:3]
Reactant: Cc1cc(C)cc(-c2c(OCCC3CCCCN3C(=O)OC(C)(C)C)c3cc(CCCO)c(Cl)cc3[nH]c2=O)c1
Reactant: C[N+]1([O-])CCOCC1
Product: Cc1cc(C)cc(-c2c(OCCC3CCCCN3C(=O)OC(C)(C)C)c3cc(CCC(=O)O)c(Cl)cc3[nH]c2=O)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 59.3 %

Procedure:
To a solution of 2-{2-[7-chloro-3-(3,5-dimethylphenyl)-6-(3-hydroxy-propyl)-2-oxo-1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester (176 mg in 3.0 mL methylene chloride) was added 20 mg powdered 4 Å sieves, 73 mg of 4-methylmorpholine-N-oxide, followed by 11 mg tetrapropylammonium perruthenate(VII) and the mixture stirred at room temperature. After 3 hours, the solvent was removed in vacuo and the crude aldehyde product resolvated in a mixture of tert-butanol (2 mL) and sodium phosphate (1 mL of a 1.25M solution). To this was added 1.86 mL of a 1M aqueous solution of potassium permanganate. After 30 minutes, the mixture was extracted with ethyl acetate, dried over sodium sulfate and purified by flash chromatography on silica gel (hexane:ethyl acetate, 1:1; then methylene chloride:methanol, 90:10) to give the title compound (107 mg).
Reaction SMILES: C([Li])CCC.CCCCCC.[C:12](#[N:14])[CH3:13].[Cl:15][C:16]1[CH:17]=[C:18]([C:23](=[O:27])[CH2:24][O:25][CH3:26])[CH:19]=[CH:20][C:21]=1[Cl:22]>C1COCC1>[Cl:15][C:16]1[CH:17]=[C:18]([C:23]([OH:27])([CH2:24][O:25][CH3:26])[CH2:13][C:12]#[N:14])[CH:19]=[CH:20][C:21]=1[Cl:22]
Reactant: COCC(=O)c1ccc(Cl)c(Cl)c1
Reactant: CC#N
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: COCC(O)(CC#N)c1ccc(Cl)c(Cl)c1
Reaction time: 0.25 h
Yield: 94.8 %

Procedure:
To a solution of 1.6 M n-butyllithium/hexane solution (20 ml) in THF (50 mL) was added dropwise a solution of acetonitrile (1.23 g) in THF (5 mL) at −78° C., and the mixture was stirred for 15 min, and at −40° C. for 15 min. A solution of 1-(3,4-dichlorophenyl)-2-methoxyethanone (5.00 g) in THF (30 mL) was added dropwise at −78° C., and the mixture was gradually warmed with stirring to room temperature, and stirred for 20 min. The reaction mixture was quenched with water, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated. The residue was purified by silica gel column chromatography (eluent; hexane:ethyl acetate (0%-100%)) to give the title compound (5.63 g).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[O:9][CH:10]=[CH:11][CH:12]=2)[C:5]([C:13]#[N:14])=[C:4]([S:15]([CH3:18])(=O)=O)[N:3]=1.[C:19]1(S)[CH:24]=[CH:23]C=[CH:21][CH:20]=1.C1CCN2C(=NCCC2)CC1>COCCOC>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[O:9][CH:10]=[CH:11][CH:12]=2)[C:5]([C:13]#[N:14])=[C:4]([S:15][C:18]2[CH:23]=[CH:24][CH:19]=[CH:20][CH:21]=2)[N:3]=1
Reactant: Sc1ccccc1
Reactant: CS(=O)(=O)c1nc(N)nc(-c2ccco2)c1C#N
Solvent: COCCOC
Solvent: C1CCC2=NCCCN2CC1
Product: N#Cc1c(Sc2ccccc2)nc(N)nc1-c1ccco1

Procedure:
From 2-amino-4-furan-2-yl-6-methanesulfonyl-pyrimidine-5-carbonitrile, thiophenol and DBU in DME. ES-MS m/e (%): 295 (M+H+, 100).
Reaction SMILES: [OH-].[Na+].[N+:3]([C:6]1[CH:7]=[C:8]([OH:12])[CH:9]=[CH:10][CH:11]=1)([O-:5])=[O:4].[CH3:13][O:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19]Cl)=[CH:17][CH:16]=1>CN(C)C=O>[CH3:13][O:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][O:12][C:8]2[CH:9]=[CH:10][CH:11]=[C:6]([N+:3]([O-:5])=[O:4])[CH:7]=2)=[CH:17][CH:16]=1
Reactant: O=[N+]([O-])c1cccc(O)c1
Reactant: COc1ccc(CCl)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Product: COc1ccc(COc2cccc([N+](=O)[O-])c2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 90.6 %

Procedure:
NaOH (0.54 g, 13.36 mmol) was added into 10 ml of degassed dimethylformamide at 0° C., then 3-nitrophenol (1.69 g, 12.14 mmol) dissolved in 7 ml of dimethylformamide was dropped slowly, and then para-methoxybenzylchloride (1.81 ml, 13.36 mmol) was added slowly. After stirred for 2 hours at the increased reaction temperature to room temperature, the reaction mixture was extracted using saturated ammonium chloride (100 ml) and ethylacetate (100 ml). The organic layer was washed twice using 100 ml of water, and dried using anhydrous sodium sulfate, then concentrated under vacuum. The resultant solid was solidified using n-hexane to obtain pale yellowish solid of 1-(4-methoxybenzyloxy)-3-nitrobenzene (2.85 g, 90%) finally.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11](=O)[C:12]([CH3:18])([CH3:17])[C:13](OC)=[O:14])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].O.[NH2:21][NH2:22]>C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[C:12]([CH3:18])([CH3:17])[C:13](=[O:14])[NH:21][N:22]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: COC(=O)C(C)(C)C(=O)c1ccc(OC)c(OC)c1
Reactant: NN
Solvent: CCO
Solvent: O
Product: COc1ccc(C2=NNC(=O)C2(C)C)cc1OC
Temperature: 25 °C

Procedure:
192 g of methyl 3-(3,4-dimethoxyphenyl)-2,2-dimethyl-3-oxopropanoate (compound D1) is dissolved in 600 ml of ethanol, 145 ml hydrazine hydrate is added and the mixture is heated under reflux for 17 h. The mixture is concentrated in vacuo, resuspended in 400 ml of ethanol and concentrated again. The solids are refluxed for 60 min in 400 ml of ethanol, cooled to RT and filtered. The product is washed with 50 ml of ethanol followed by 100 ml of diethyl ether and dried in vacuo at 50° C.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8]([CH2:10][O:11][C:12]3[C:13]([F:22])=[C:14]([C:18]([F:21])=[CH:19][CH:20]=3)[C:15]([NH2:17])=[O:16])=[N:7][C:6]=2[CH:23]=1.[CH2:24]([Sn](CCCC)(CCCC)CCCC)[CH:25]=[CH2:26]>CN(C=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>[CH2:26]([C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8]([CH2:10][O:11][C:12]3[C:13]([F:22])=[C:14]([C:18]([F:21])=[CH:19][CH:20]=3)[C:15]([NH2:17])=[O:16])=[N:7][C:6]=2[CH:23]=1)[CH:25]=[CH2:24]
Reactant: C=CC[Sn](CCCC)(CCCC)CCCC
Reactant: NC(=O)c1c(F)ccc(OCc2nc3cc(Br)ccc3s2)c1F
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Product: C=CCc1ccc2sc(COc3ccc(F)c(C(N)=O)c3F)nc2c1
Temperature: 120 °C
Yield: 0.6 %

Procedure:
To a solution of 3-(5-bromo-benzothiazol-2-ylmethoxy)-2,6-difluoro-benzamide (0.1 g, 0.025 mol) in 5 ml of anhydrous DMF was added Allyl tributyltin (0.083 g, 0.025 mol) and degassed the reaction mixture for the 10 minutes. Tetrakis(triphenylphosphine)Palladium (0) (0.029 g, 0.0025 mol) was added and again degassed for 10 min. The reaction mixture was heated at 120° C. for 1 h under the nitrogen atmosphere, then cooled to r.t. Water was added to the reaction mixture and extracted with ethyl acetate, The combined organic layers were dried over anhydrous Na2SO4, and evaporated to dryness under reduced pressure. The compound was crystallized with ethyl acetate/hexane to give the title compound as brown solid (0.050 g, 55%). 1H NMR (DMSO-d6, 400 MHz): δ 3.52 (d, 2H, J=6.4 Hz), 5.07-5.13 (m, 1H) 5.68 (s, 2H) 5.98-6.05 (m, 1H), 7.10 (dt, 1H, J=8.4 Hz (o-coupling), 7.31 (d, 1H, J=8.4 Hz (o-coupling), 7.38 (dt, 1H, J=9.2 Hz (o-coupling), J=5.2 Hz), 7.83 (s, 1H), 7.89 (broad s, 1H), 8.05 (d, 1H, J=8.4 Hz (o-coupling), 8.17 (broad s, 1H) MS ES+ (361.05), HPLC (method 5) Rt=16.74 min.
Reaction SMILES: [C:1]1([C:7]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]([C:21]3[CH:22]=[C:23]4[C:27](=[CH:28][CH:29]=3)[NH:26][C:25]3[N:30]=[CH:31][CH:32]=[CH:33][C:24]4=3)=[C:13]3[C:8]=2[CH:9]=[CH:10][CH:11]=[CH:12]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[I:34][C:35]1[CH:40]=[CH:39][C:38](I)=[CH:37][CH:36]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.[Cu]I>[I:34][C:35]1[CH:40]=[CH:39][C:38]([N:26]2[C:27]3[C:23](=[CH:22][C:21]([C:14]4[C:13]5[C:8]([C:7]([C:1]6[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=6)=[C:20]6[C:15]=4[CH:16]=[CH:17][CH:18]=[CH:19]6)=[CH:9][CH:10]=[CH:11][CH:12]=5)=[CH:29][CH:28]=3)[C:24]3[CH:33]=[CH:32][CH:31]=[N:30][C:25]2=3)=[CH:37][CH:36]=1
Reactant: c1ccc(-c2c3ccccc3c(-c3ccc4[nH]c5ncccc5c4c3)c3ccccc23)cc1
Reactant: Ic1ccc(I)cc1
Agent: [Cu]I
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Product: Ic1ccc(-n2c3ccc(-c4c5ccccc5c(-c5ccccc5)c5ccccc45)cc3c3cccnc32)cc1
Temperature: 120 °C
Reaction time: 12 h
Yield: 64 %

Procedure:
6-(10-phenylanthracen-9-yl)-9H-pyrido[2,3-b]indole (1.76 g, 4.19 mmol), 1,4-diiodobenzene (2.76 g, 8.37 mmol), CuI (319 mg, 1.67 mmol), K3PO4 (1.78 g, 8.37 mmol), trans-1,2-dicyclohexanediamine (0.2 mL, 1.67 mmol) were put in a 250 mL two-neck flask and dissolved in 1,4-dioxane. The solution was refluxed and stirred at 120° C. for 12 hours. After completion of the reaction, the solution was extracted with methylenechloride/H2O and distilled under reduced pressure to remove the solvent. The resultant was columned with a solution of n-hexane and methylenechloride (1:5) and was re-crystallized in a solution of methylene chloride and petroleum ether such that the solid compound was obtained, (1.67 g, yield: 64%).
Reaction SMILES: C[O:2][C:3](=O)[CH2:4][CH2:5][C:6]1[CH2:10][CH:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])O[N:7]=1.C[OH:20]>O=[Pt]=O>[C:14]([O:13][C:11](=[O:12])[CH2:9][CH2:10][CH:6]1[CH2:5][CH:4]([OH:20])[C:3](=[O:2])[NH:7]1)([CH3:17])([CH3:16])[CH3:15]
Reactant: CO
Reactant: COC(=O)CCC1=NOC(C(=O)OC(C)(C)C)C1
Agent: O=[Pt]=O
Product: CC(C)(C)OC(=O)CCC1CC(O)C(=O)N1

Procedure:
A suspension of 40 g of 4,5-dihydro-5-t-butoxycarbonyl-3-isoxazole-propanoic acid methyl ester and 2.0 g of PtO2 /C in 400 ml of methanol is placed under a hydrogen atmosphere with agitation. After H2 absorption is complete, the solution is filtered and the solvent removed under reduced pressure to give an oil. The oil is triturated with anhydrous diethyl ether to yield 4-hydroxy-5-oxo-2-pyrrolidinepropanoic acid t-butyl ester as a white solid with mp 94°-95° C. NMR (CDCl3) and 6.83 (s, 1H), 4.42 (m, 1H), 3.93 (s, 1H), 3.70 (m, 1H), 2.78-1.66 (m, 6H), 1.47 (s, 9H). IR (KBr) 3320, 2980, 1732, 1705, 1456, 1417, 1353, 1368, 1295, 1260, 1214.
Reaction SMILES: [CH:1]1[C:6]2[C:7](=[O:16])[NH:8][C:9]3[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=3[S:11][C:5]=2[CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Br[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27]>CN(C=O)C>[O:16]=[C:7]1[C:6]2[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=2[S:11][C:10]2[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=2[N:8]1[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27]
Reactant: CCOC(=O)CCCCCCBr
Reactant: O=C1Nc2ccccc2Sc2ccccc21
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)CCCCCCN1C(=O)c2ccccc2Sc2ccccc21
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 69.2 %

Procedure:
Title compound 409 (0.403 g, 1.77 mmol) was dissolved in DMF (5.0 mL) and sodium hydride (60% in oil, 0.0.086 g, 2.13 mmol) was added. The reaction mixture was stirred at 50° C. for 30 minutes. Ethyl 7-bromoheptanoate (0.631 g, 2.66 mmol) was added and the reaction mixture was stirred at 50° C. for 16 hours. The mixture was cooled down to room temperature and quenched with water. The aqueous layer was extrated 3 times with at mixture of 75% ethyl acetate in hexanes. The combined organic extracts were washed with water and brine, dried over sodium sulfate, filtered and evaporated. The residue was purified by flash chromatography (30% ethyl acetate in hexanes) to afford title compound 410 (470 mg, 69%). MS (m/z): 384.4 (M+H).