Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([S:8][CH3:9])[N:5]=[C:4]([NH:10][C:11]2[NH:15][N:14]=[C:13]([CH3:16])[CH:12]=2)[CH:3]=1.Cl.[CH:18]1([C:21]2([F:25])[CH2:24][NH:23][CH2:22]2)[CH2:20][CH2:19]1.C(N(C(C)C)CC)(C)C.C(O)(C)C>CCCCCC>[CH:18]1([C:21]2([F:25])[CH2:24][N:23]([C:2]3[N:7]=[C:6]([S:8][CH3:9])[N:5]=[C:4]([NH:10][C:11]4[NH:15][N:14]=[C:13]([CH3:16])[CH:12]=4)[CH:3]=3)[CH2:22]2)[CH2:20][CH2:19]1
Reactant: CSc1nc(Cl)cc(Nc2cc(C)n[nH]2)n1
Reactant: FC1(C2CC2)CNC1
Agent: Cl
Solvent: CCCCCC
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(C)O
Product: CSc1nc(Nc2cc(C)n[nH]2)cc(N2CC(F)(C3CC3)C2)n1
Temperature: 85 °C
Yield: 80 %

Procedure:
To a mixture of 6-chloro-N-(3-methyl-1H-pyrazol-5-yl)-2-(methylthio)pyrimidin-4-amine (150 g, 0.58 mol), 3-cyclopropyl-3-fluoroazetidine hydrochloride (132.2 g, 0.87 mol) was added diisopropylethylamine (208 g, 1.61 mol) and isopropanol (1.125 L) and then heated to reflux for 23 hours. The reaction was cooled to slightly hazy solution to 85° C. and filtered and the homogeneous solution concentrated to a minimal volume. EtOAc was added (1 L) and concentrated to minimal volume. EtOAc (1 L) and H2O (1 L) were added and the layers separated (organic started to crystallize product during the extraction). The aqueous layer was further extracted with EtOAc (500 ml). Concentrated the 1st organic to dryness to give a white solid. Hexane (750 ml) was added to the 2nd organic extract and the slurry was stirred at ambient temperature, then cooled to 0° C. for 30 min. Filtered and washed with copious Heptane. The filter cake was dried under vacuum. The filter cake and the white solid from the 1st extraction were combined to afford 155.1 g of the desired product. (155.1 g, 77%). 1H NMR (DMSO, 400 MHz) 0.44 (2H, m), 0.60 (2H, m), 1.38-1.43 (1H, m), 2.18 (3H, s), 2.42 (3H, s), 3.89-3.97 (4H, m), 5.92 (1H, br s), 6.04 (1H, br s), 9.23 (1H, s), 11.86 (1H, s). ES+ 335
Reaction SMILES: C([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[C:10]([N:23]1[CH2:27][C:26](=[O:28])[NH:25][S:24]1(=[O:30])=[O:29])[CH:9]=2)=[O:5])C.[OH-].[K+]>O>[CH2:16]([O:15][C:11]1[CH:12]=[C:13]2[C:8](=[CH:9][C:10]=1[N:23]1[CH2:27][C:26](=[O:28])[NH:25][S:24]1(=[O:30])=[O:29])[NH:7][C:6]([C:4]([OH:5])=[O:3])=[CH:14]2)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: CCOC(=O)c1cc2cc(OCc3ccccc3)c(N3CC(=O)NS3(=O)=O)cc2[nH]1
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: O=C1CN(c2cc3[nH]c(C(=O)O)cc3cc2OCc2ccccc2)S(=O)(=O)N1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 5-benzyloxy-6-(1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl)-1H-indole-2-carboxylic acid ethyl ester (from Example 65) (0.135 g, 0.398 mmol) in water (8 mL) is added 1M KOH (0.29 mL). The solution is stirred at room temperature for 1 h. The reaction product is lyophilized to yield 5-benzyloxy-6-(1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl)-1H-indole-2-carboxylic acid.
Reaction SMILES: [Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH3:14])[C:8]=1[O:15][CH3:16].[Cl:17]Cl>C(Cl)Cl>[Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]1[C:12]([Cl:17])=[CH:11][CH:10]=[C:9]([O:13][CH3:14])[C:8]=1[O:15][CH3:16]
Reactant: COc1cccc(CCCCCBr)c1OC
Reactant: ClCl
Solvent: ClCCl
Product: COc1ccc(Cl)c(CCCCCBr)c1OC
Reaction time: 3 h
Yield: 58 %

Procedure:
To 4.0 g of 1-(5-bromopentyl)-2,3-dimethoxybenzene in 50 mL of methylene chloride cooled in an ice bath was added 18 mL of 0.8M chlorine in methylene chloride. The reaction mixture was kept at 0° for 3 hours and then was concentrated under reduced pressure to yield an oil. Purification by HPLC using 30% toluene-hexane gave 2.60 g (58% yield) of 1-(5-bromopentyl)-6-chloro-2,3-dimethoxybenzene. The nmr spectrum was consistent with the structure and the mass spectrum gave a molecular ion at m/z 320 (C13H18BrClO2).
Reaction SMILES: Cl[CH2:2][CH2:3][S:4](Cl)(=[O:6])=[O:5].Cl.Cl.[CH3:10][O:11][C:12]1[CH:17]=[C:16]([O:18][CH:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[CH:15]=[CH:14][C:13]=1[CH2:25][C:26]([N:28]1[CH2:33][CH2:32][N:31]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[CH3:40])[CH2:30][CH:29]1[C:41]([NH2:43])=[O:42])=[O:27].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[CH3:10][O:11][C:12]1[CH:17]=[C:16]([O:18][CH:19]2[CH2:24][CH2:23][N:22]([S:4]([CH:3]=[CH2:2])(=[O:6])=[O:5])[CH2:21][CH2:20]2)[CH:15]=[CH:14][C:13]=1[CH2:25][C:26]([N:28]1[CH2:33][CH2:32][N:31]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[CH3:40])[CH2:30][CH:29]1[C:41]([NH2:43])=[O:42])=[O:27]
Reactant: COc1cc(OC2CCNCC2)ccc1CC(=O)N1CCN(c2ccccc2C)CC1C(N)=O
Reactant: O=S(=O)(Cl)CCCl
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: C=CS(=O)(=O)N1CCC(Oc2ccc(CC(=O)N3CCN(c4ccccc4C)CC3C(N)=O)c(OC)c2)CC1
Reaction time: 18 h

Procedure:
2-Chloroethanesulfonyl chloride (0.035 ml, 54.6 mg, 0.33 mmol) in methylene chloride (3 ml) was cooled in an ice bath under nitrogen. A solution of 1-(2-methoxy-4-(4-piperidyloxy)phenylacetyl)-4-(2-methylphenyl)-piperazine-2-carboxamide dihydrochloride (149 mg, 0.28 mmol) and diisopropylethylamine (0.243 ml, 0.18 g, 1.4 mmol) in methylene chloride (3 ml) was added dropwise and the mixture was stirred in the cold for 18 hours. The mixture was concentrated in vacuo and the residue chromatographed on silica gel eluted with 3% methanol in methylene chloride. The combined product fractions were evaporated to dryness in vacuo to give 1-(2-methoxy-4(1-ethenylsulfonyl-4-piperidyloxy)phenylacetyl)-4-(2-methylphenyl)piperazine-2-carboxamide.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[CH:9][S:10][C:3]=12.C(=O)([O-])[O-].[K+].[K+].[F:17][C:18]1[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[CH:21]=[CH:20][C:19]=1[OH:27]>C1(OC2C=CC=CC=2)C=CC=CC=1.CCOC(C)=O>[F:17][C:18]1[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[CH:21]=[CH:20][C:19]=1[O:27][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[CH:9][S:10][C:3]=12
Reactant: Clc1ccnc2ccsc12
Reactant: O=[N+]([O-])c1ccc(O)c(F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: c1ccc(Oc2ccccc2)cc1
Solvent: CCOC(C)=O
Product: O=[N+]([O-])c1ccc(Oc2ccnc3ccsc23)c(F)c1
Temperature: 25 °C
Yield: 77.1 %

Procedure:
A mixture of 2 (500 mg, 2.95 mmol), potassium carbonate (1.62 g, 11.8 mmol) and 2-fluoro-4-nitrophenol (603 mg, 3.85 mmol) were heated to 170° C. in diphenyl ether (10 ml) for 5 hrs. The mixture was cooled to room temperature, diluted with EtOAc and washed with water. The organic phase was collected, dried over anhydrous sodium sulfate and the solvents were removed under reduced pressure. The residue was purified by column chromatography, eluent gradient EtOAc-hexane (9:1) to EtOAc, to afford the title compound 3 (660 mg, 76% yield). 1H NMR (400 MHz, CDCl3) 6 (Ppm) 8.60 (d, J=5.54 Hz, 1H), 8.14 (m, 3H), 7.80 (d, J=5.47 Hz, 1H), 7.61 (d, J=5.48 Hz, 1H), 7.36 (t, J=7.63 Hz), 6.65 (m, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([C:18]2[CH:23]=[CH:22][C:21]3[O:24][CH2:25][O:26][C:20]=3[CH:19]=2)=[C:10]1[C:27]([O:29]CC)=[O:28]>CCO.[Pd]>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]([C:18]2[CH:23]=[CH:22][C:21]3[O:24][CH2:25][O:26][C:20]=3[CH:19]=2)[CH:10]1[C:27]([OH:29])=[O:28]
Reactant: CCOC(=O)C1=C(c2ccc3c(c2)OCO3)c2ccccc2C1c1ccccc1OC
Agent: [Pd]
Solvent: CCO
Product: COc1ccccc1C1c2ccccc2C(c2ccc3c(c2)OCO3)C1C(=O)O
Reaction time: 8 h
Yield: 105.3 %

Procedure:
To a solution of ethyl (RS)-1-(2-methoxyphenyl)-3-(3,4-methylenedioxyphenyl)indene-2-carboxylate (90 mg, 0.22 mmol) in EtOH (10 ml) was added 10% palladium on activated carbon (90 mg). The resulting suspension was shaken on a Parr hydrogenator at 60 psi H2 overnight, then was filtered through a pad of Celite. The filtrate was concentrated under reduced pressure to afford the title compound (90 mg, 100%), which was used without further purification.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]([N:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)=[N:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:24]([O:26][CH3:27])=[O:25])[CH:14]=3)[N:9]=2)=[CH:4][CH:3]=1.CCN(CC)CC.[C:35](Cl)(=[O:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>ClCCl>[C:35]([N:21]1[CH2:22][CH2:23][N:18]([C:17]2[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)=[N:9][C:10]3[C:15]([N:16]=2)=[CH:14][C:13]([C:24]([O:26][CH3:27])=[O:25])=[CH:12][CH:11]=3)[CH2:19][CH2:20]1)(=[O:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: COC(=O)c1ccc2nc(-c3ccc(F)cc3)c(N3CCNCC3)nc2c1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)c1ccc2nc(-c3ccc(F)cc3)c(N3CCN(C(=O)c4ccccc4)CC3)nc2c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 56.4 %

Procedure:
To a solution of methyl 2-(4-fluorophenyl)-3-(piperazin-1-yl)quinoxaline-6-carboxylate (180 mg, 0.49 mmol) in dichloromethane (10 ml) was added Et3N (200 mg, 2 mmol) followed by benzoyl chloride (170 mg, 1.18 mmol) dropwise. The resulting solution was stirred for 1 hour at room temperature and then quenched by the addition of ice-water (150 ml) and extracted with dichloromethane (3×30 ml). The organic layers were combined, dried over anhydrous magnesium sulfate and concentrated in vacuo to afford methyl 3-(4-benzoylpiperazin-1-yl)-2-(4-fluorophenyl)quinoxaline-6-carboxylate as a yellow solid (130 mg, 56%).
Reaction SMILES: C([NH:20][C:21]1[CH:22]=[C:23]([CH2:27][CH2:28]OS(C2C=CC([N+]([O-])=O)=CC=2)(=O)=O)[CH:24]=[CH:25][CH:26]=1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[CH2:42]([NH:49][CH2:50][C@@H:51]([C:60]1[CH:69]=[CH:68][C:67]([O:70][CH2:71][C:72]2[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=2)=[C:66]2[C:61]=1[CH:62]=[CH:63][C:64](=[O:78])[NH:65]2)[O:52][Si:53]([C:56]([CH3:59])([CH3:58])[CH3:57])([CH3:55])[CH3:54])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.C(=O)(O)[O-].[Na+].Cl>C(#N)C.CCOC(C)=O.O>[NH2:20][C:21]1[CH:22]=[C:23]([CH2:27][CH2:28][N:49]([CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH2:50][C@@H:51]([C:60]2[CH:69]=[CH:68][C:67]([O:70][CH2:71][C:72]3[CH:73]=[CH:74][CH:75]=[CH:76][CH:77]=3)=[C:66]3[C:61]=2[CH:62]=[CH:63][C:64](=[O:78])[NH:65]3)[O:52][Si:53]([C:56]([CH3:59])([CH3:58])[CH3:57])([CH3:55])[CH3:54])[CH:24]=[CH:25][CH:26]=1
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)OCCc2cccc(NC(c3ccccc3)(c3ccccc3)c3ccccc3)c2)cc1
Reactant: CC(C)(C)[Si](C)(C)O[C@@H](CNCc1ccccc1)c1ccc(OCc2ccccc2)c2[nH]c(=O)ccc12
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CC(C)(C)[Si](C)(C)O[C@@H](CN(CCc1cccc(N)c1)Cc1ccccc1)c1ccc(OCc2ccccc2)c2[nH]c(=O)ccc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 85.6 %

Procedure:
A stirred mixture of 4-nitrobenzenesulfonic acid 2-[3-(tritylamino)phenyl]ethyl ester (7.44 g, 13.2 mmol); 5-[(R)-2-benzylamino-1-(tert-butyldimethylsilanyloxy)ethyl]-8-benzyloxy-1H-quinolin-2-one (5.42 g, 10.5 mmol) (see, e.g., U.S. Patent Publication No. 2006/0035931 A1, published Feb. 16, 2006) and sodium bicarbonate (3.32 g, 39.5 mmol) in acetonitrile (26.4 mL) was heated at 75° C. under nitrogen for 18 h. The mixture was cooled to room temperature and the pH was adjusted to pH<2 with aqueous hydrochloric acid (1 N, ˜40 mL). The mixture was stirred at room temperature for 1 h and then the pH of the mixture was adjusted to pH 7-8 with saturated aqueous sodium bicarbonate solution (˜30 mL). Water (˜50 mL) and EtOAc (˜50 mL) were added and the layers were separated (a small amount of dilute aqueous sodium chloride solution was added to improve separation). The aqueous layer was extracted with EtOAc (2×30 mL) and the combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (30-60% of EtOAc in hexanes) to give the title compound (5.7 g, 68% yield) as a light yellow foamy solid.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[N:18]3[C:19]4[C:24]([N:25]=[C:26]([NH:27][CH2:28][CH2:29][CH2:30][OH:31])[C:17]3=[N:16][CH:15]=2)=[CH:23][C:22]([C:32]([F:35])([F:34])[F:33])=[CH:21][CH:20]=4)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[NH:8]1[CH2:9][CH:10]=[C:11]([C:14]2[N:18]3[C:19]4[C:24]([N:25]=[C:26]([NH:27][CH2:28][CH2:29][CH2:30][OH:31])[C:17]3=[N:16][CH:15]=2)=[CH:23][C:22]([C:32]([F:34])([F:33])[F:35])=[CH:21][CH:20]=4)[CH2:12][CH2:13]1
Reactant: CC(C)(C)OC(=O)N1CC=C(c2cnc3c(NCCCO)nc4cc(C(F)(F)F)ccc4n23)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: OCCCNc1nc2cc(C(F)(F)F)ccc2n2c(C3=CCNCC3)cnc12
Temperature: 25 °C
Reaction time: 6 h

Procedure:
To a solution of 4-[4-(3-hydroxy-propylamino)-7-trifluoromethyl-imidazo[1,2-a]quinoxalin-1-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (1.10 g; 2.30 mmol; 1 eq) in anhydrous dichloromethane (12 mL) is slowly added trifluoroacetic acid (1.77 mL; 23.0 mmol; 10 eq). The solution is allowed to stir for 6 hours at room temperature until completion of the reaction. The reaction mixture is concentrated and the residual traces of trifluoroacetic acid are removed by co-distillation with toluene (2×10 mL). The red gum is taken up in water (73 mL) and the resulting aqueous solution is washed with ethyl acetate (375 mL) before adjusting the pH to 8 by addition of sodium bicarbonate in powder. This basic aqueous layer is then extracted with ethyl acetate (5×100 mL). The organic extracts are combined, dried over sodium sulfate and concentrated in vacuum. The resulting crude residue is then passed through a silica gel column (ethyl acetate/methanol 8:2 then ethyl acetate/methanol/triethylamine 8:2:0.3) to afford the title compound still contaminated with minor impurities. The powder is then washed with ether to afford the title compound as an off-white solid (170 mg; 0.44 mmol; 19%)
Reaction SMILES: [CH:1]1([C:4]2[C:13](I)=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([CH3:15])[CH:5]=2)[CH2:3][CH2:2]1.[CH3:16][N:17](C=O)C>[C-]#N.[C-]#N.[Zn+2].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>[C:16]([C:13]1[C:4]([CH:1]2[CH2:3][CH2:2]2)=[CH:5][C:6]([CH3:15])=[C:7]([CH:12]=1)[C:8]([O:10][CH3:11])=[O:9])#[N:17]
Reactant: CN(C)C=O
Reactant: COC(=O)c1cc(I)c(C2CC2)cc1C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C-]#N
Agent: [Zn+2]
Product: COC(=O)c1cc(C#N)c(C2CC2)cc1C
Temperature: 100 °C
Reaction time: 8 h
Yield: 81 %

Procedure:
To a solution of methyl 4-cyclopropyl-5-iodo-2-methylbenzoate (compound 142.2, 2.00 g, 6.01 mmol, 1.00 equiv, 95%) in DMF (16 mL) was added Zn(CN)2 (890 mg, 7.58 mmol, 1.27 equiv) and Pd(PPh3)4 (731 mg, 0.630 mmol, 0.11 equiv). The resulting solution was stirred at 100° C. under nitrogen overnight. After cooling to ambient temperature, the reaction was then quenched by the addition of 100 mL of FeSO4 (aq., sat.) and diluted with ethyl acetate. The resulting mixture was stirred vigorously then filtered through celite and washed with 1 M FeSO4, water, and ethyl acetate. The layers were separated and the aqueous phase was extracted with 2×100 mL of ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified via silica gel column chromatography with ethyl acetate/petroleum ether (1/50) as eluent to yield 1.10 g (81%) of methyl 5-cyano-4-cyclopropyl-2-methylbenzoate as a light yellow oil.
Reaction SMILES: C([N:4]1[C:16]2[CH:15]=[CH:14][C:13](I)=[CH:12][C:11]=2[C:10]2[C:5]1=[CH:6][CH:7]=[C:8](I)[CH:9]=2)(=O)C.[CH:19]1[C:31]2[NH:30][C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:23]=2[CH:22]=[CH:21][CH:20]=1>[Cu]=O>[C:28]1([C:13]2[CH:14]=[CH:15][C:16]3[NH:4][C:5]4[C:10]([C:11]=3[CH:12]=2)=[CH:9][C:8]([C:6]2[C:5]3[NH:4][C:16]5[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=5)[C:10]=3[CH:9]=[CH:8][CH:7]=2)=[CH:7][CH:6]=4)[C:29]2[NH:30][C:31]3[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:24]=2[CH:25]=[CH:26][CH:27]=1
Reactant: c1ccc2c(c1)[nH]c1ccccc12
Reactant: CC(=O)n1c2ccc(I)cc2c2cc(I)ccc21
Agent: O=[Cu]
Product: c1ccc2c(c1)[nH]c1c(-c3ccc4[nH]c5ccc(-c6cccc7c6[nH]c6ccccc67)cc5c4c3)cccc12
Temperature: 170 °C
Yield: 139 %

Procedure:
A mixture of 2.0 g of 9-acetyl-3,6-diiodocarbazole and 1.1 g of carbazole were stirred together in 20 ml N,N′-dimethylacetamide. To this was added 0.8 g of copper oxide and heated to 170° C. for 24 h. The reaction was quenched with water and the solid was filtered, washed with methanol, and dried under vacuum. The solid (3 g) was then taken up for further deprotection using 0.6 g KOH with THF (3 ml), methanol (6 ml) and water (6 ml) at reflux temperature. The reaction mixture was then extracted using ethyl acetate; and the organic layer was dried over anhydrous sodium sulfate and evaporated to dryness under vacuum. Subsequent silica gel column chromatography using toluene:hexane (1:2) as eluent, yielded 1.5 g of 3,6-dicarbazolylcarbazole.
Reaction SMILES: [CH2:1]([C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[N+:14]([O-])([OH:16])=[O:15].O>C1C=CC=CC=1.C(O)(=O)C>[N+:14]([C:11]1[CH:12]=[C:7]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[CH:8]=[CH:9][C:10]=1[OH:13])([O-:16])=[O:15]
Reactant: O=[N+]([O-])O
Reactant: CCCCCCc1ccc(O)cc1
Solvent: CC(=O)O
Solvent: c1ccccc1
Solvent: O
Product: CCCCCCc1ccc(O)c([N+](=O)[O-])c1
Yield: 92.6 %

Procedure:
1.00 g (5.61 mM) of 4-hexylphenol was dissolved in a mixture solvent of 2.0 ml of benzene and 1.3 ml of acetic acid. To the solution, 0.62 ml (8.15 mM) of nitric acid (60%, density=1.38) was gradually added dropwise under cooling with iced water and stirring below 8° C. After the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried with anhydrous sodium sulfate and subjected to reduced-pressure distillation into a solid. The solid was purified by silica gel column chromatography (eluent: toluene/hexane=1/2) to obtain 1.16 g of oily yellow 2-nitro-4-hexylphenol (Yield: 92.6%).
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.II.C(N(CC)CC)C.[C:29]([NH:34][NH:35][C:36](=[O:47])[CH2:37][CH2:38][NH:39][C:40](=[O:46])[O:41][C:42]([CH3:45])([CH3:44])[CH3:43])(=O)[CH:30]([CH3:32])[CH3:31]>ClCCl>[CH:30]([C:29]1[O:47][C:36]([CH2:37][CH2:38][NH:39][C:40](=[O:46])[O:41][C:42]([CH3:43])([CH3:44])[CH3:45])=[N:35][N:34]=1)([CH3:31])[CH3:32]
Reactant: CC(C)C(=O)NNC(=O)CCNC(=O)OC(C)(C)C
Agent: II
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)c1nnc(CCNC(=O)OC(C)(C)C)o1
Temperature: 25 °C
Reaction time: 0.1 h

Procedure:
20.00 g (43.00 mmol) PS-triphenylphosphine are placed in 240 ml dichloromethane, 10.88 g (42.87 mmol) iodine are added. The mixture is stirred for 0.1 hours at ambient temperature, then 12.10 ml (87.29 mmol) triethylamine are added dropwise. 5.83 g (21.33 mmol) tert-butyl [3-(N′-isobutyryl-hydrazino)-3-oxo-propyl]-carbamate dissolved in 150 ml dichloromethane are added. The reaction mixture is stirred for 24 hours at ambient temperature, then the precipitate is filtered off. The filtrate is evaporated down and purified by chromatography.
Reaction SMILES: [OH:1][C:2]([C:15]1[CH:16]2[C:21](=[C:22]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=3)[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:19]([CH:20]=1)[CH:18]1[C:35]([N:37]([CH2:40][CH2:41]OC(=O)C=CC3C=CC(C(C)C)=CC=3)[C:38](=[O:39])[CH:17]21)=[O:36])([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:56]([NH:59][C:60]1[CH:70]=[CH:69][C:63]([CH:64]=[CH:65][C:66]([OH:68])=[O:67])=[CH:62][CH:61]=1)(=[O:58])[CH3:57].C(N=C=NCCCN(C)C)C.C(N(CC)CC)C.CN(C1C=CC=CN=1)C>ClCCl>[C:56]([NH:59][C:60]1[CH:70]=[CH:69][C:63]([CH:64]=[CH:65][C:66]([O:68][CH2:41][CH2:40][N:37]2[C:38](=[O:39])[CH:17]3[CH:18]([CH:19]4[C:21](=[C:22]([C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=5)[C:23]5[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=5)[CH:16]3[C:15]([C:2]([OH:1])([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=3)[C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=3)=[CH:20]4)[C:35]2=[O:36])=[O:67])=[CH:62][CH:61]=1)(=[O:58])[CH3:57]
Reactant: CC(=O)Nc1ccc(C=CC(=O)O)cc1
Reactant: CC(C)c1ccc(C=CC(=O)OCCN2C(=O)C3C4C=C(C(O)(c5ccccc5)c5ccccn5)C(C4=C(c4ccccc4)c4ccccn4)C3C2=O)cc1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccccn1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)Nc1ccc(C=CC(=O)OCCN2C(=O)C3C4C=C(C(O)(c5ccccc5)c5ccccn5)C(C4=C(c4ccccc4)c4ccccn4)C3C2=O)cc1
Reaction time: 72 h
Yield: 99 %

Procedure:
A similar procedure (Schwartz, E. et al. Macromolecules 2011, 44, 4735-4741) to that previously described for the preparation of 347 was followed using 2 (1.50 g, 2.70 mmol), 4-acetamidocinnamic acid (0.50 g, 2.46 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (1.04 g, 5.60 mmol), triethylamine (1.24 mL, 8.91 mmol) and dimethylaminopyridine (60 mg, 0.49 mmol) in dichloromethane (25 mL), at room temperature for 72 h. Purification by flash chromatography (hexane/ethyl acetate 1:4) afforded 337 as a white solid (2.0 g, 2.69 mmol, 99%). mp 125-130° C.; 1H NMR (300 MHz, CDCl3) δ 2.17 (3H, s, NHAc), 3.35-3.90 (4.16H, m, NCH2CH2O, H-2, H-3, W/H-4), 3.83-3.95 (0.84H, m, U/H-1, V/H-1, Y/H-4), 4.14 (0.14H, m, U/H-4), 4.28-4.38 (2.32H, m, NCH2CH2O, V/H-4), 4.43-4.47 (0.54H, m, W/H-1, Y/H-1), 5.53 (0.32H, dd, J=3.4 and 1.2 Hz, V/H-6), 5.55 (0.38H, dd, J=3.4 and 1.2 Hz, Y/H-6), 5.59 (s, OH), 5.60 (s, OH), 5.63 (s, OH), 5.69 (s, OH), 6.06 (0.14H, dd, J=3.4 and 1.2 Hz, U/H-6), 6.06 (0.16H, dd, J=3.4 and 1.2 Hz, W/H-6), 6.17 (0.30H, d, J=15.8 Hz, COCH═CH), 6.26 (0.70H, d, J=15.8 Hz, COCH═CH), 6.74-7.61 (21H, m, Ar and COCH═CH), 8.40-8.63 (2H, m, αPyr); m/z (ESI, 70 eV) 765 (MNa+, 100%); (Found MNa+ 765.2684, C46H38N4NaO6 requires 765.2687).
Reaction SMILES: C([Li])CCC.BrC1C=CC=C[C:8]=1[CH:9]=[O:10].Br[C:16]1[CH:23]=[CH:22][CH:21]=[CH:20][C:17]=1[CH:18]=[CH2:19].[Mg].[Br-].C(OC(=O)C)(=O)C.C(=O)=O.C(O)(C)C>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[CH:18]([C:17]1[CH:20]=[CH:21][CH:22]=[CH:23][C:16]=1[C:9](=[O:10])[CH3:8])=[CH2:19]
Reactant: O=Cc1ccccc1Br
Reactant: C=Cc1ccccc1Br
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C=O
Agent: [Br-]
Solvent: CC(C)O
Solvent: CC(=O)OC(C)=O
Solvent: C1CCOC1
Product: C=Cc1ccccc1C(C)=O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Into a 3 necked 500 mL round bottom flask, equipped with a cooling condenser, a self equalizing addition funnel and a rubber septum, methyl triphenyl phosphonium bromide (54.5 g, 0.153 moles, Aldrich) was suspended in THF (120 mL). After flashing with nitrogen for 30 minutes, the flask was cooled to 0° C. n-Butyl lithium (61 mL, 2.5 M in hexane, 153 mmole) was added via a syringe. After stirring for 1.5 hours, a solution of 2-bromobenzaldehyde (25.0 g, 135.1 mmole) in THF (100 mL) was dripped into the flask slowly (2 hours). After stirred for 48 hours, the reaction mixture was quenched with brine (250 mL). The aqueous layer was extracted with toluene (100 mL×2). The toluene layer was diluted with hexane to precipitate triphenylphosphine oxide. After rotary evaporating off the solvent, the crude product was purified by column chromatography (silica gel 60-200 mesh), with 100% hexane as eluding solvent. First fraction, yield 11.5 g (41%). 8.8 Grams (48 mmole) of o-bromostyrene was used for the next reaction. Into a 3-necked round bottom flask fitted with condenser, self-equalizing funnel, a stopper and charged with magnesium (10 g, pre-activated), o-bromostyrene in 30 mL THF was added to cover Mg. After initiation of the reaction, the rest of bromide solution was added slowly and the mixture was refluxed for 1.5 hours. Into another 3-necked flask, acetic anhydride (10 g, 98 mmole) was dissolved in THF (30 mL) and the flask was cooled with dry ice/isopropanol. The Grignard reagent was transferred slowly (circa 1 hour) via a cannula needle and the mixture was stirred for 2.5 hours at −70° C. After allowing to warm to room temperature, the mixture was then quenched with aqueous ammonium chloride and extracted with ethyl acetate (100 mL×2). After washing with water, dried over sodium sulfate and removal of the solvent, yellow oil was obtained. Yield: 6.5 gram (93%). 1H-NMR (CDCl3, δ): 5.3 (d, 1H), 5.6 (d, 1H); 7.2 (q, 1H), 7.3 (t, 1H), 7.4 (t, 1H); 7.55 (d, 1H); 7.6 (d, 1H). 13C-NMR: 30, 116, 127, 128, 130, 132, 136, 137.5, 138, 201. Epoxidation using a method similar to that described above did not provide a clean product.