Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[C:4]([CH3:12])[N:3]=1.[Br:13][C:14]1[CH:20]=[C:19]([CH:21]([CH3:23])[CH3:22])[CH:18]=[CH:17][C:15]=1[NH2:16].C(OCC)(=O)C>O1CCOCC1>[Br:13][C:14]1[CH:20]=[C:19]([CH:21]([CH3:22])[CH3:23])[CH:18]=[CH:17][C:15]=1[NH:16][C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[C:4]([CH3:12])[N:3]=1
Reactant: CC(C)c1ccc(N)c(Br)c1
Reactant: COC(=O)c1cc(C)nc(Cl)n1
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: COC(=O)c1cc(C)nc(Nc2ccc(C(C)C)cc2Br)n1
Temperature: 25 °C

Procedure:
A mixture of 2-chloro-4-carbomethoxy-6-methylpyrimidine (47 g, 252 mmol) and 2-bromo-4-(2-propyl)aniline (54.0 g, 252 mmol) in dioxane (400 mL) was stirred at reflux temperature for 20 h under a nitrogen atmosphere. The reaction mixture was cooled to ambient temperature and concentrated on a rotary evaporator. The residue was treated with a saturated sodium bicarbonate solution and extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to provide a red oil. Column chromatography (ethyl acetate:hexanes::1:1) gave the title product as a crude oil. Recrystallization from ether-hexanes, collection by filtration and drying in vacuo afforded the title compound as a solid (42.8 g, 47% yield): mp 75-76° C.; NMR (CDCl3, 300 MHz): 8.4 (d, 1H, J=8); 7.65 (br s, 1H), 7.4 (d, 1H, J=1), 7.3 (s, 1H), 7.2 (dd, 1H, J=8,1), 4.0 (s, 3H), 2.85 (septet, 1H, J=7), 2.5 (br s, 3H), 1.25 (d, 6H, J=7); Anal.(C16H18BrN3O2): C, 52.76, H, 4.98, N, 11.54, Br, 21.94; Found: C, 52.71, H, 4.99, N, 11.38, Br, 21.83.
Reaction SMILES: [C:1]([C:9]1[N:13]2[CH2:14][CH2:15][CH:16]([C:17]([O:19]C(C)C)=[O:18])[C:12]2=[C:11]([Br:23])[CH:10]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO.C(=O)([O-])[O-].[K+].[K+]>O>[C:1]([C:9]1[N:13]2[CH2:14][CH2:15][CH:16]([C:17]([OH:19])=[O:18])[C:12]2=[C:11]([Br:23])[CH:10]=1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)OC(=O)C1CCn2c(C(=O)c3ccccc3)cc(Br)c21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: O=C(c1ccccc1)c1cc(Br)c2n1CCC2C(=O)O

Procedure:
A solution of 336 mg. of isopropyl 5-benzoyl-7-bromo-1,2-dihydro-3H-pyrrolo[1,2-a]-pyrrole-1-carboxylate in 10 ml. of methanol is treated with a solution of 690 mg. of potassium carbonate in 5 ml. of water. The reaction mixture is refluxed under nitrogen atmosphere for 30 minitres, cooled, and evaporated to dryness. The residue is taken up in 10 ml. of 10% aqueous hydrochloric acid and 50 ml. of water and the resultant mixture extracted with ethyl acetate (2×50 ml.). The combined extracts are dried over magnesium sulfate and evaporated to dryness under reduced pressure. Crystallization of the residue from ethyl acetate-hexane affords 5-benzoyl-7-bromo-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.
Reaction SMILES: C(OC(=O)C)(=O)C.[C:8]([O:12][C:13]([C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:17]([CH2:24][CH:25]([OH:42])[CH2:26][O:27][C:28]2[CH:33]=[CH:32][C:31]([CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])=[CH:30][CH:29]=2)[CH:16]=1)=[O:14])([CH3:11])([CH3:10])[CH3:9].C(=O)([O-])O.[Na+].[Na+].[Cl-]>CS(C)=O>[C:8]([O:12][C:13]([C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:17]([CH2:24][C:25](=[O:42])[CH2:26][O:27][C:28]2[CH:33]=[CH:32][C:31]([CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])=[CH:30][CH:29]=2)[CH:16]=1)=[O:14])([CH3:11])([CH3:10])[CH3:9]
Reactant: CCCCCCCCc1ccc(OCC(O)Cn2cc(C(=O)OC(C)(C)C)c3ccccc32)cc1
Agent: O=C([O-])O
Agent: [Cl-]
Agent: [Na+]
Solvent: CC(=O)OC(C)=O
Solvent: CS(C)=O
Product: CCCCCCCCc1ccc(OCC(=O)Cn2cc(C(=O)OC(C)(C)C)c3ccccc32)cc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
2.02 g (19.8 mmol) acetic anhydride are mixed with 10 ml absolute DMSO, stirred at room temperature for 10 min and added drop-wise to a solution of 0.237 g (0.494 mmol) tert-butyl-1-[2-hydroxy-3-(4-octylphenoxy)propyl]indole-3-carboxylate in 10 ml absolute DMSO. Having stirred for 2 hours, the solution is poured into a mixture of 5% sodium hydrogen carbonate and saturated NaCl solution (1:1, v/v) and hydrolyzed for 10 min. Four extractions with diethyl ether, combination of the organic phases, concentration to half the volume on the rotary evaporator, three wash steps with saturated NaCl solution, drying on sodium sulfate, filtration and reconcentration on the rotary evaporator leave as a crude product a yellow oil which is purified on silica gel by means of flash column chromatography (flow agent: petroleum ether/ethyl acetate 95:5) and yields the product as a yellowish oil.
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]([CH:12]=[O:13])[C:9]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.[CH3:21][N:22](C)C=O>[C-]#N.[Zn+2].[C-]#N.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>[F:20][C:16]1[CH:15]=[C:14]([C:9]2[C:8]3[N:7]=[CH:6][CH:5]=[CH:4][C:3]=3[C:2]([C:21]#[N:22])=[CH:11][C:10]=2[CH:12]=[O:13])[CH:19]=[CH:18][CH:17]=1
Reactant: CN(C)C=O
Reactant: O=Cc1cc(Br)c2cccnc2c1-c1cccc(F)c1
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: N#Cc1cc(C=O)c(-c2cccc(F)c2)c2ncccc12
Temperature: 130 °C
Reaction time: 8 h
Yield: 50 %

Procedure:
A mixture of 5-bromo-8-(3-fluorophenyl)quinoline-7-carbaldehyde (0.049 g, 0.15 mmol), zinc cyanide (0.035 g, 0.30 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.034 g, 0.030 mmol) in dry N,N-dimethylformamide (0.50 mL) was stirred at 130° C. overnight. The mixture was filtered, diluted with water, extracted with ethyl acetate. The combined extracts were dried over MgSO4, concentrated and purified on silica gel (eluting with 0 to 60% ethyl acetate in hexane) to give the desired product (20 mg, 50%). LCMS calculated for C17H10FN2O (M+H)+: m/z=277.1; Found: 277.0.
Reaction SMILES: [OH:1][C:2]([CH3:12])([CH3:11])[CH2:3][C:4]1[CH:5]=[C:6]([OH:10])[CH:7]=[CH:8][CH:9]=1.[Br:13]N1C(=O)CCC1=O.O>CN(C=O)C>[Br:13][C:9]1[CH:8]=[CH:7][C:6]([OH:10])=[CH:5][C:4]=1[CH2:3][C:2]([OH:1])([CH3:12])[CH3:11]
Reactant: CC(C)(O)Cc1cccc(O)c1
Reactant: O=C1CCC(=O)N1Br
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(O)Cc1cc(O)ccc1Br
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
Alcohol 29 (12.3 g, 74.2 mmol) is dissolved in dry DMF and cooled to 0° C. under N2. Solid N-bromosuccinimide (NBS, 14.77 g, 83.0 mmol) is added in small portions (the yellow color is allowed to dissipate between additions) over 1.5 h. After the addition is complete, stirring at 0° C. is continued for 30 min. The mixture is then poured into water and extracted with EtOAc (3×). The organic phase is washed with water (1×) and brine (1×), dried (MgSO4), filtered, and evaporated. The residue is dissolved in EtOAc/CH2Cl2 and diluted with hexane to afford 30 as white crystals, mp 139-141° C. (12.7 g, 70%). Concentration of the mother liquor gives two more crops (1.2 and 1.0 g) of crystals, bringing the total to 14.9 g (82%). 1H NMR (acetone-d6, 2.05 ppm) 8.43 (S,1), 7.34 (d, 1, J=8.7), 7.01 (d, 1, J=2.7), 6.64 (dd, 1, J=8.7, 2.8), 2.89 (s,2), 1.21 (s,6); 13C NMR (acetone-d6, 20.83 ppm) 147.90, 130.98, 124.56, 111.34, 107.05, 106.19, 62.35, 39.59, 20.76; MS (EI, eE=70 eV) m/z 246/244 (M+), 231/229, 201, 188/186, 163, 150, 131, 108, 107, 91, 77, 63, 59 (base peak), 51, 43; Anal. Calcd for C10H13BrO2 (MW=245.1) : C,49.00 H,5.35. Found: C,49.03 H,5.20.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[CH:12]=2)=[CH:4][CH:3]=1.[CH2:19]=O.Cl>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:9][CH2:10][C:11]3[C:16](=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[CH:12]=3)[CH2:19]2)=[CH:6][CH:7]=1
Reactant: COc1cccc(CCNc2ccc(Cl)cc2)c1
Reactant: C=O
Agent: Cl
Solvent: CO
Product: COc1ccc2c(c1)CCN(c1ccc(Cl)cc1)C2

Procedure:
14.4 g of the product described under (a), 6 ml of 35% strength aqueous formaldehyde solution and 10 ml of concentrated hydrochloric acid in 20 ml of methanol are heated under reflux for 1 day. On distilling off the methanol, the product crystallizes out. After cooling, it is filtered off with suction and the resulting product (13.5 g, 91% of theory) is reacted further under (c) without further purification.
Reaction SMILES: [NH2:1][N:2]1[C:7](SC)=[N:6][C:5](=[O:10])[C:4]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)=[N:3]1.[CH3:18][NH:19][CH3:20]>C(#N)C>[NH2:1][N:2]1[C:7]([N:19]([CH3:20])[CH3:18])=[N:6][C:5](=[O:10])[C:4]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)=[N:3]1
Reactant: CSc1nc(=O)c(-c2ccc(F)cc2)nn1N
Reactant: CNC
Solvent: CC#N
Product: CN(C)c1nc(=O)c(-c2ccc(F)cc2)nn1N
Yield: 53 %

Procedure:
2-Amino-3-methylthio-6-(p-fluorophenyl)-5-oxo-2,5-dihydro-1,2,4-triazine (1.0 g) was added to a mixture of an aqueous solution of 40% dimethylamine (5 ml) and acetonitrile (10 ml), and the resultant mixture was heated under reflux for 1 hour. After completion of the reaction, the resultant mixture was evaporated to dryness under reduced pressure to give a crude product. Recrystallization of the crude product from acetone gave 0.7 g of 2-amino-3-dimethylamino-6-(p-fluorophenyl)-5-oxo-2,5-dihydro-1,2,4-triazine in 53% yield. M.P., 212° C.
Reaction SMILES: Cl.[NH2:2][C@H:3]1[C@@H:7]([CH3:8])[CH2:6][N:5]([C:9]([C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]([CH3:20])[N:12]=2)=[O:10])[CH2:4]1.C(N(CC)CC)C.[C:28](O)(=[O:31])[CH2:29][CH3:30].C1N=CN(C(N2C=NC=C2)=O)C=1>CN(C=O)C>[C:28]([NH:2][C@H:3]1[C@@H:7]([CH3:8])[CH2:6][N:5]([C:9]([C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]([CH3:20])[N:12]=2)=[O:10])[CH2:4]1)(=[O:31])[CH2:29][CH3:30]
Reactant: C[C@H]1CN(C(=O)c2nn(C)c3ccccc23)C[C@H]1N
Reactant: CCC(=O)O
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CCC(=O)N[C@@H]1CN(C(=O)c2nn(C)c3ccccc23)C[C@@H]1C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 17.3 %

Procedure:
Into 2 ml of DMF were dissolved 200 mg (0.68 mmol) of cis-3-amino-4-methyl-1-(l-methylindazol-3-ylcarbonyl)pyrrolidine hydrochloride and 0.09 ml (0.68 mmol) of triethylamine, and the solution was stirred for 0.5 hours at room temperature. This solution was added to another solution which was separately prepared by dissolving 0.05 ml (0.68 mmol) of propionic acid and 112 mg (0.68 mmol) of CDI into 2 ml of DMF, followed by stirring for 2 hours at room temperature. Resultant mixture was stirred overnight at room temperature. After DMF was distilled off, to the residue was added water and the solution was made alkaline with sodium bicarbonate, which was then extracted with methylene chloride. After washed with saturated saline solution and dried over anhydrous magnesium sulfate, the solution was concentrated under reduced pressure to obtain crude oil. This was subjected to silica gel column chromatographic purification (methylene chloride:acetone=5:1) to obtain 37 mg (17.3%) of aimed compound. m.p. 139°-141° C.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([O:14][C:15]2[CH:16]=[N:17][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:19][CH:20]=2)[CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([NH2:13])=O)=[CH:7]2.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:34])=CC=1>O1CCCC1>[CH3:1][C:2]1[CH:3]=[C:4]([O:14][C:15]2[CH:16]=[N:17][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:19][CH:20]=2)[CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11](=[S:34])[NH2:13])=[CH:7]2
Reactant: Cc1cc(Oc2ccc(S(C)(=O)=O)nc2)cc2cc(C(N)=O)[nH]c12
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: C1CCOC1
Product: Cc1cc(Oc2ccc(S(C)(=O)=O)nc2)cc2cc(C(N)=S)[nH]c12
Yield: 138.5 %

Procedure:
A mixture of 7-methyl-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indole-2-carboxamide (2.95 g), a Lawesson's reagent (2.1 g), and dry tetrahydrofuran (70 mL) was stirred at 55° C. for 2 hr. The reaction solution was concentrated under reduced pressure, and the obtained residue was subjected to silica gel column chromatography (ethyl acetate:hexane=40:60 to 55:45, volume ratio). The obtained yellow oil was crystallized from ethyl acetate-hexane to give the title compound (2.6 g, yield 84%) as pale-yellow crystals.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][C:8]1[CH:13]=[CH:12][C:11]([Mg]Br)=[CH:10][CH:9]=1.[CH3:16][N:17]1[C:21]([CH:22]=[O:23])=[CH:20][N:19]=[CH:18]1>C1COCC1>[CH3:16][N:17]1[C:21]([CH:22]([C:11]2[CH:12]=[CH:13][C:8]([O:7][CH:2]3[CH2:3][CH2:4][CH2:5][CH2:6][O:1]3)=[CH:9][CH:10]=2)[OH:23])=[CH:20][N:19]=[CH:18]1
Reactant: Cn1cncc1C=O
Reactant: Br[Mg]c1ccc(OC2CCCCO2)cc1
Solvent: C1CCOC1
Product: Cn1cncc1C(O)c1ccc(OC2CCCCO2)cc1
Temperature: -78 °C
Reaction time: 2 h
Yield: 97.1 %

Procedure:
4-(2-Tetrahydro-3H-pyranoxy)phenylmagnesium bromide (110 mL, 0.5 M in THF, 55 mmol) was added dropwise to a solution of 1-methyl-1H-imidazole-5-carbaldehyde (4.7 g, 50 mmol) in THF (790 mL) at −78° C. After stirring −78° C. for 2 hours, the reaction was quenched with saturated NH4Cl (aq) and warmed to room temperature. The mixture was extracted with EtOAc (500 mL), and the organic phase was washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give 14 g of the crude product 4.1, which was used in the next reaction without further purification.
Reaction SMILES: S(C1C=CC(C)=CC=1)(O[CH2:5][C@H:6]1[C@@H:9]([N:10]=[N+:11]=[N-:12])[C:8](=[O:13])[NH:7]1)(=O)=O.[Na+].[I-:22]>CC(C)=O>[N:10]([C@H:9]1[C:8](=[O:13])[NH:7][C@H:6]1[CH2:5][I:22])=[N+:11]=[N-:12]
Reactant: Cc1ccc(S(=O)(=O)OC[C@@H]2NC(=O)[C@@H]2N=[N+]=[N-])cc1
Reactant: [I-]
Agent: [Na+]
Solvent: CC(C)=O
Product: [N-]=[N+]=N[C@H]1C(=O)N[C@H]1CI

Procedure:
A degassed solution of cis-3-azido-4-oxo-2-azetidinylmethyl tosylate (2.36 g) in acetone (80 ml) was refluxed with NaI (5.85 g) overnight. Reaction was cooled and the acetone was removed in vacuo. The reaction mixture was partitioned between ethyl acetate and aqueous sodium thiosulfate solution. Phases were separated and the organic layer was extracted with thiosulfate solution. The combined aqueous extracts were extracted with ethyl acetate. The combined ethyl acetate layers were washed with brine, dried and evaporated to give an off-white solid. The product was recrystallized from ethyl acetate-hexane, melting point 130°-2° (dec.), 1.5 g (75%).
Reaction SMILES: Cl[C:2]1[C:3]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:7][CH:6]=2.[CH2:22]([O:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1)[CH3:23]>>[CH2:22]([O:24][C:25]1[CH:30]=[CH:29][C:28]([C:2]2[C:3]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[N:4][C:5]3[C:10]([N:11]=2)=[CH:9][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:7][CH:6]=3)=[CH:27][CH:26]=1)[CH3:23]
Reactant: CCOc1ccc(B(O)O)cc1
Reactant: COC(=O)c1ccc2nc(-c3ccccc3)c(Cl)nc2c1
Product: CCOc1ccc(-c2nc3cc(C(=O)OC)ccc3nc2-c2ccccc2)cc1
Yield: 42.1 %

Procedure:
The ester product was obtained via a Suzuki coupling reaction using the method previously shown in Example 13, Step 6, with methyl 3-chloro-2-phenylquinoxaline-6-carboxylate (100 mg, 0.34 mmol, 1.00 equiv) and 4-ethoxyphenylboronic acid (61 mg, 0.37 mmol, 1.10 equiv) As reactants. Purification via silica gel column (ethyl acetate/petroleum ether (1:5)) yielded 55 mg (43%) of methyl 3-(4-ethoxyphenyl)-2-phenylquinoxaline-6-carboxylate as a yellow powder.
Reaction SMILES: Cl[C:2]1([CH3:10])[CH2:7][CH2:6][C:5](Cl)([CH3:8])[CH2:4][CH2:3]1.[C:11]1([OH:17])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Cl-].[Al+3].[Cl-].[Cl-]>>[CH3:10][C:2]12[CH2:7][CH2:6][C:5]([CH3:8])([CH2:4][CH2:3]1)[C:14]1[CH:15]=[CH:16][C:11]([OH:17])=[CH:12][C:13]2=1
Reactant: CC1(Cl)CCC(C)(Cl)CC1
Reactant: Oc1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Product: CC12CCC(C)(CC1)c1cc(O)ccc12
Temperature: 120 °C

Procedure:
To a solution of 1,4-dichloro-1,4-dimethylcyclohexane (Compound 1, 3 g, 16.5 mmol) and phenol (1.55 g, 16.5 mmol) under argon at 25° C. was slowly added aluminum chloride (0.22g, 0.165 mmol). The resulting mixture was heated to 120° C. for 12 hours, and then it was quenched with ice. The products were extracted with CH2Cl2, the layers separated, and the organic layer was washed with water and brine. The organic layer was dried over Na2SO4, and filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using ethyl acetate:hexane (1:9) to yield the title compound as a yellow oil.
Reaction SMILES: C([Li])CCC.CCCCCC.C(C(C1C=CC(Cl)=CC=1)=[C:20]1[C:32]2[C:24]([CH:25]=[C:26]3[C:31]=2[CH:30]=[C:29]([C:33]([CH3:36])([CH3:35])[CH3:34])[C:28]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[CH:27]3)=[C:23](C2C=CC=C2)[C:22]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)=[C:21]1[C:54]([CH3:57])([CH3:56])[CH3:55])C1C=CC=CC=1.[CH3:65][C:66]([C:72]1[CH:77]=[CH:76][C:75]([CH3:78])=[CH:74][CH:73]=1)=[C:67]1[CH:71]=[CH:70][CH:69]=[CH:68]1>O1CCCC1>[CH3:65][C:66]([C:72]1[CH:73]=[CH:74][C:75]([CH3:78])=[CH:76][CH:77]=1)([CH:67]1[CH:68]=[CH:69][CH:70]=[CH:71]1)[C:23]1[C:24]2[CH2:25][C:26]3[C:31](=[CH:30][C:29]([C:33]([CH3:34])([CH3:36])[CH3:35])=[C:28]([C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=4)[CH:27]=3)[C:32]=2[CH:20]=[C:21]([C:54]([CH3:56])([CH3:55])[CH3:57])[C:22]=1[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1
Reactant: CC(=C1C=CC=C1)c1ccc(C)cc1
Reactant: CC(C)(C)c1cc2c(cc1-c1ccccc1)=Cc1c(C3C=CC=C3)c(-c3ccccc3)c(C(C)(C)C)c(=C(Cc3ccccc3)c3ccc(Cl)cc3)c1=2
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: Cc1ccc(C(C)(c2c3c(cc(C(C)(C)C)c2-c2ccccc2)-c2cc(C(C)(C)C)c(-c4ccccc4)cc2C3)C2C=CC=C2)cc1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
Under a nitrogen atmosphere, a solution of n-butyllithium in hexane (6.3 ml, 10.2 mmol) was dropped into a solution of 2,7-diphenyl-3,6-di-tert-butylfluorene (4.0 g, 9.3 mmol) in dry tetrahydrofuran (50 ml) at −10° C., and then the product was stirred at room temperature for 20 hours. Then, 6-methyl-6-(p-tolyl)fulvene (1.9 g, 10.2 mmol) was dropped into this solution at −10° C., and the product was stirred at room temperature for 2 hours to induce a reaction. After the reaction was terminated, dilute aqueous hydrochloric acid was added thereto, the product was subjected to extraction with hexane, the organic layer was subsequently washed with water and then dehydrated with anhydrous magnesium sulfate, and then the solvent was distilled off to produce a light brown solid. The produced solid was recrystallized with methanol to obtain 5.1 g of an objective. The analytical values were as follows.
Reaction SMILES: [NH2:1][CH2:2][C@@H:3]([C:5]1[CH:14]=[CH:13][C:12]([OH:15])=[C:11]2[C:6]=1[CH:7]=[CH:8][C:9](=[O:16])[NH:10]2)[OH:4].[CH2:17]([N:19]1[C:23]2=[N:24][C:25]([CH2:47][CH3:48])=[C:26]([CH2:35][NH:36][C:37](=[O:46])[C:38]3[CH:43]=[CH:42][CH:41]=[C:40]([CH:44]=O)[CH:39]=3)[C:27]([NH:28][CH:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[C:22]2[CH:21]=[N:20]1)[CH3:18]>>[CH2:17]([N:19]1[C:23]2=[N:24][C:25]([CH2:47][CH3:48])=[C:26]([CH2:35][NH:36][C:37](=[O:46])[C:38]3[CH:43]=[CH:42][CH:41]=[C:40]([CH2:44][NH:1][CH2:2][C@H:3]([OH:4])[C:5]4[CH:14]=[CH:13][C:12]([OH:15])=[C:11]5[C:6]=4[CH:7]=[CH:8][C:9](=[O:16])[NH:10]5)[CH:39]=3)[C:27]([NH:28][CH:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[C:22]2[CH:21]=[N:20]1)[CH3:18]
Reactant: NC[C@H](O)c1ccc(O)c2[nH]c(=O)ccc12
Reactant: CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CNC(=O)c1cccc(C=O)c1
Product: CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CNC(=O)c1cccc(CNC[C@H](O)c2ccc(O)c3[nH]c(=O)ccc23)c1

Procedure:
The title compound was synthesized in a manner analogous to that described for Intermediate 43, using Intermediate 4 in place of Intermediate 8 and Intermediate 30 in place of Intermediate 29.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[CH:15]=[C:14]([NH:16][C:17](=[O:22])[O:18][CH2:19][CH:20]=[CH2:21])[O:13][N:12]=3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.[N+:23]([C:26]1[CH:31]=[CH:30][C:29]([S:32]([N@:35]2[CH2:37][CH:36]2[CH2:38][C:39]2[C:47]3[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=3)[NH:41][CH:40]=2)(=[O:34])=[O:33])=[CH:28][CH:27]=1)([O-:25])=[O:24].O>CN(C=O)C>[NH:41]1[C:42]2[C:47](=[CH:46][CH:45]=[CH:44][CH:43]=2)[C:39]([CH2:38][C@H:36]([NH:35][S:32]([C:29]2[CH:28]=[CH:27][C:26]([N+:23]([O-:25])=[O:24])=[CH:31][CH:30]=2)(=[O:33])=[O:34])[CH2:37][N:16]([C:14]2[O:13][N:12]=[C:11]([C:7]3[CH:6]=[C:5]4[C:10](=[CH:9][CH:8]=3)[CH:1]=[N:2][CH:3]=[CH:4]4)[CH:15]=2)[C:17](=[O:22])[O:18][CH2:19][CH:20]=[CH2:21])=[CH:40]1
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)[N@]2CC2Cc2c[nH]c3ccccc23)cc1
Reactant: C=CCOC(=O)Nc1cc(-c2ccc3cnccc3c2)no1
Solvent: CN(C)C=O
Solvent: O
Product: C=CCOC(=O)N(C[C@H](Cc1c[nH]c2ccccc12)NS(=O)(=O)c1ccc([N+](=O)[O-])cc1)c1cc(-c2ccc3cnccc3c2)no1
Reaction time: 3 h
Yield: 86.6 %

Procedure:
To a 25 mL of round-bottom flask was added allyl 3-(isoquinolin-6-yl)isoxazol-5-ylcarbamate (68 mg, 230 μmol) (prepared as shown for Example 11), 1,8-diazabicyclo(5.4.0)-7-undecene (6.8 μl, 46 μmol) and 2 mL of DMF at room temperature. (S)-3-((1-(4-Nitrophenylsulfonyl)aziridin-2-yl)methyl)-1H-indole (98 mg, 276 μmol) (prepared as described in US Patent Publication No. US 2007/0173506 which is hereby incorporated by reference in its entirety and for all purposes as if specifically set forth herein) in 1 mL of DMF was added to the reaction mixture dropwise. After 3 hours, 10 mL of water was added, and then the reaction mixture was extracted twice with 20 mL of EtOAc. The extracts were combined, concentrated under reduced pressure, and purified by flash chromatography on silica gel (65% EtOAc/hexane) to give allyl(S)-3-(1H-indol-3-yl)-2-(4-nitrophenylsulfonamido)propyl(3-(isoquinolin-6-yl)isoxazol-5-yl)carbamate (130 mg, 86% yield). MS m/z: 653 (M+1).
Reaction SMILES: [NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3]([C:10]([NH:12][NH2:13])=[O:11])=[CH:2]1.[C:14]1([N:20]=[C:21]=[S:22])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>ClC(Cl)C>[NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3]([C:10]([NH:12][NH:13][C:21]([NH:20][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[S:22])=[O:11])=[CH:2]1
Reactant: S=C=Nc1ccccc1
Reactant: NNC(=O)c1c[nH]c2ncccc12
Solvent: CC(Cl)Cl
Product: O=C(NNC(=S)Nc1ccccc1)c1c[nH]c2ncccc12
Reaction time: 20 h
Yield: 98.6 %

Procedure:
350 mg of (1H-pyrrolo[2,3-b]pyridine-3-carbohydrazide and 261 μl of phenyl isothiocyanate in 10 ml of dichloroethane are stirred at 60° C. for 15 hours in a screw-lid vial. A further 78 μl of phenyl isothiocyanate are added, and the mixture is stirred at the same temperature for 20 hours. After cooling in the refrigerator, the precipitate is filtered off with suction and dried, giving 610 mg of 1-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-4-phenylthiosemicarbazide as colourless powder; (yield 98.6%); MS-FAB (M+H+)=312.3; Rf (polar method): 1.43 min.