Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[Li+].CC([N-]C(C)C)C.[Cl:21][C:22]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:23]=1[C:24]([O:26][CH3:27])=[O:25].CN(C)[CH:35]=[O:36]>C1COCC1>[Cl:21][C:22]1[C:23]([C:24]([O:26][CH3:27])=[O:25])=[C:28]([F:32])[C:29]([CH:35]=[O:36])=[CH:30][CH:31]=1
Reactant: COC(=O)c1c(F)cccc1Cl
Reactant: CN(C)C=O
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: COC(=O)c1c(Cl)ccc(C=O)c1F
Temperature: -78 °C
Reaction time: 2.5 h

Procedure:
An oven-dried round bottom flask successively purged and evacuated with N2 was charged with anhydrous THF (13.3 ml), and diisopropyl amine (6.6 ml, 46 mmol). The mixture was placed in a −78° C. dry ice/acetone bath before n-butyllithium (2.5 M in hexanes) (17 ml, 43 mmol) was added. The LDA solution was then placed in a 0° C. bath for 10 minutes before recooling to −78° C. Then, a solution of methyl 2-chloro-6-fluorobenzoate (3.50 g, 19 mmol) in THF (56 ml) was added dropwise over 30 minutes. The resulting mixture was stirred at −78° C. for 2.5 hrs, warmed to −50° C. over 30 min, and stirred for 30 minutes at −50° C. The mixture was then recooled to −78° C. before adding anhydrous dimethylformamide (14 ml, 186 mmol). The resulting mixture was stirred for 30 minutes at −78° C. and then gradually warmed to RT over 1 h. The reaction was quenched with 10% aqueous acetic acid, diluted with EtOAc and the layers were separated. The aqueous layer was extracted three times with EtOAc. The combined organics were washed with water, brine, and dried over Na2SO4, filtered and concentrated to a yellow oil, which was purified by chromatography using 12:1 hexanes/EtOAc to give the title compound as a light yellow oil, which solidified upon exposure to reduced pressure.
Reaction SMILES: Cl.[F:2][C:3]([F:29])([F:28])[C:4]1[CH:5]=[C:6]([CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=1)[CH2:7][O:8][C@H:9]1[CH2:14][CH2:13][NH:12][CH2:11][C@H:10]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[C:30](O)(=[O:33])[CH2:31][CH3:32].CCN(CC)CC.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.O>[F:29][C:3]([F:2])([F:28])[C:4]1[CH:5]=[C:6]([CH:21]=[C:22]([C:24]([F:27])([F:25])[F:26])[CH:23]=1)[CH2:7][O:8][C@H:9]1[CH2:14][CH2:13][N:12]([C:30](=[O:33])[CH2:31][CH3:32])[CH2:11][C@H:10]1[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: CCC(=O)O
Reactant: FC(F)(F)c1cc(CO[C@H]2CCNC[C@H]2c2ccccc2)cc(C(F)(F)F)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: O
Product: CCC(=O)N1CC[C@H](OCc2cc(C(F)(F)F)cc(C(F)(F)F)c2)[C@H](c2ccccc2)C1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a solution of the compound (132 mg) obtained in Example 1, propionic acid (32 mg) and Et3N (0.083 ml) in DMF (5 ml), WSC.HCl (0.15 g) and HoBt.H2O (0.092 g) were added, and the reaction mixture was stirred at room temperature for 24 hours. The reaction mixture was poured into water, and then the product was extracted with ethyl acetate. The organic layer was washed with an aqueous saturated sodium hydrogen carbonate solution and saturated brine, dried, and then the solvent was evaporated under reduced pressure. The obtained residue was purified by preparative HPLC to obtain the title compound as colorless amorphous.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH2:17][C:16](=[O:18])[C:15]2[C:10](=[C:11]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:12]=[CH:13][CH:14]=2)[N:9]=1.Cl>CO>[ClH:1].[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:17]=[C:16]([OH:18])[C:15]2[C:10](=[C:11]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:12]=[CH:13][CH:14]=2)[N:9]=1
Reactant: CCOC(=O)c1cccc2c1N=C(c1ccccc1Cl)CC2=O
Agent: Cl
Solvent: CO
Product: CCOC(=O)c1cccc2c(O)cc(-c3ccccc3Cl)nc12
Yield: 172.7 %

Procedure:
Ethyl 2-(2-chlorophenyl)-4-quinolone-8-carboxylate (1.98 gram) is dissolved in 50 ml of methanol, and stirred at room temperature for 0.5 hour with 10 ml of 40% ethanolic hydrochloric acid. The solvent is evaporated from the solution, and the residue is recrystallized from ethanol to give 1.9 grams of ethyl 2-(2-chlorophenyl)-4-hydroxyquinoline-8-carboxylate hydrochloride, colorless prisms, melting point 196° to 198° C.
Reaction SMILES: [C:1]([OH:4])(=[S:3])[CH3:2].[CH:5]1([S:11]N2C(=O)C3=CC=CC=C3C2=O)[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1>C1C=CC=CC=1>[C:1]([S:3][S:11][CH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1)(=[O:4])[CH3:2]
Reactant: CC(O)=S
Reactant: O=C1c2ccccc2C(=O)N1SC1CCCCC1
Solvent: c1ccccc1
Product: CC(=O)SSC1CCCCC1
Yield: 98 %

Procedure:
Thioacetic acid, 0.044 moles, 3.35 grams, is reacted with N-(cyclohexylthio)phthalimide in 100 ml of benzene and the product recovered following a procedure similar to Example 11. Acetylcyclohexyl disulfide, an amber oil, is recovered in 98% yield (7.5 grams). Analysis gives 51.27%C, 7.41%H and 31.78%S compared to 50.6%C, 7.38%H and 33.7%S calculated for C8H14OS2.
Reaction SMILES: [C:1]([OH:10])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[NH2:4].[OH-].[Na+].[Ni:13](Cl)Cl>O>[Ni:13].[C:1]([OH:10])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[NH2:4]
Reactant: Cl[Ni]Cl
Agent: Nc1ccccc1C(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: [Ni]
Temperature: 80 °C
Reaction time: 1 h

Procedure:
54.8 g (0.4 mol) of anthranilic acid was completely dissolved in a solution obtained by dissolving 16 g (0.4 mol) of caustic soda in 1 liter of water. The solution was heated to 80° C., and a solution of 25.9 g (0.2 mol) of nickel chloride in 150 ml of water was gradually added dropwise to the heated solution. After the addition, the mixture was stirred for 1 hour at 80° C. and then allowed to be cooled down to room temperature under stirring. After the cooling, the resultant precipitate was filtered out and washed with water until the filtrate water reached neutrality. After washing, the precipitate was dried at 90° C. to obtain about 65 g of pale blue powder.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][C@H:6]([NH:11][S:12]([CH:15]([CH3:17])[CH3:16])(=[O:14])=[O:13])[CH2:5]2.Br[C:19]1[CH:24]=[C:23]([CH3:25])[CH:22]=[CH:21][N:20]=1.C([O-])([O-])=O.[Cs+].[Cs+].CN(C)CC(O)=O>CS(C)=O.[Cu]I>[CH3:25][C:23]1[CH:22]=[CH:21][N:20]=[C:19]([O:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[CH2:7][C@H:6]([NH:11][S:12]([CH:15]([CH3:17])[CH3:16])(=[O:14])=[O:13])[CH2:5]3)[CH:24]=1
Reactant: Cc1ccnc(Br)c1
Reactant: CC(C)S(=O)(=O)N[C@H]1Cc2ccc(O)cc2C1
Agent: [Cu]I
Agent: CN(C)CC(=O)O
Agent: O=C([O-])[O-]
Solvent: CS(C)=O
Product: Cc1ccnc(Oc2ccc3c(c2)C[C@@H](NS(=O)(=O)C(C)C)C3)c1

Procedure:
N-[(2S)-5-hydroxy-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide (50 mg, 0.196 mmol, Description 3), copper(I) iodide (41.0 mg, 0.215 mmol), 2-bromo-4-methylpyridine (0.022 ml, 0.196 mmol), Cs2CO3 (191 mg, 0.587 mmol) and N,N-dimethylglycine (24.23 mg, 0.235 mmol) in dimethyl sulfoxide (2 ml) were heated under microwave conditions for 30 minutes at 190° C. The reaction mixture was partitioned between EtOAc (10 ml) and water (10 ml). Aqueous was further extracted with DCM (10 ml). The organic solution was dried over MgSO4 and evaporated under reduced pressure to yield the impure product as a dark brown oil. The product was purified by reverse phase chromatography using the MDAP to give the title compound as a white solid (5 mg).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8](F)=[C:9]([O:12][CH2:13][CH2:14][O:15][CH3:16])[CH:10]=2)[CH:5]=[C:4]([NH:18][C:19]2[CH:23]=[C:22]([CH3:24])[NH:21][N:20]=2)[N:3]=1>C(O)C>[CH2:9]([O:12][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:15][CH2:14][CH3:13])=[C:9]([O:12][CH2:13][CH2:14][O:15][CH3:16])[CH:10]=2)[CH:5]=[C:4]([NH:18][C:19]2[CH:23]=[C:22]([CH3:24])[NH:21][N:20]=2)[N:3]=1)[CH3:8]
Reactant: COCCOc1cc2c(Cl)nc(Nc3cc(C)[nH]n3)cc2cc1F
Solvent: CCO
Product: CCOc1cc2cc(Nc3cc(C)[nH]n3)nc(OCC)c2cc1OCCOC

Procedure:
Similar procedure as described in example 10 was used, starting from [1-Chloro-6-fluoro-7-(2-methoxy-ethoxy)-isoquinolin-3-yl]-(5-methyl-1H-pyrazol-3-yl)-amine and ethanol to give [1,6-Diethoxy-7-(2-methoxy-ethoxy)-isoquinolin-3-yl]-(5-methyl-1H-pyrazol-3-yl)-amine. LC-MS m/e 387(MH+).
Reaction SMILES: [CH3:1][NH:2][C:3]([C:5]1[N:6]=[C:7]([CH2:26][CH3:27])[N:8]2[CH2:13][CH2:12][NH:11][CH:10]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=3)[C:9]=12)=[O:4].[CH3:28][NH:29][C:30]([C@@H:32](OS(C1C=CC(C)=CC=1)(=O)=O)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:31]>>[CH3:1][NH:2][C:3]([C:5]1[N:6]=[C:7]([CH2:26][CH3:27])[N:8]2[CH2:13][CH2:12][N:11]([CH:32]([C:30](=[O:31])[NH:29][CH3:28])[C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH:10]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=3)[C:9]=12)=[O:4]
Reactant: CCc1nc(C(=O)NC)c2n1CCNC2CCc1ccc(C(F)(F)F)cc1
Reactant: CNC(=O)[C@@H](OS(=O)(=O)c1ccc(C)cc1)c1ccccc1
Product: CCc1nc(C(=O)NC)c2n1CCN(C(C(=O)NC)c1ccccc1)C2CCc1ccc(C(F)(F)F)cc1

Procedure:
Prepared by reaction of 3-ethyl-8-[2-(4-trifluoromethyl-phenyl)-ethyl]-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid methylamide (22 mg; 0.057 mmol) with toluene-4-sulfonic acid (S)-methylcarbamoyl-phenyl-methyl ester. Purification by preparative HPLC afforded the mixture of 2 diastereoisomers. LC-MS: tR=0.86 min., [M+H]+=528.45 g/mol.
Reaction SMILES: N#N.[C:3]([Si:7]([CH3:17])([CH3:16])[O:8][CH:9]([C:11]1[O:12][CH:13]=[CH:14][N:15]=1)[CH3:10])([CH3:6])([CH3:5])[CH3:4].C([Li])(C)(C)C.CN([CH:26]=[O:27])C.[NH4+].[Cl-]>C1COCC1.CCCCC.CC(=O)OCC.O>[C:3]([Si:7]([CH3:17])([CH3:16])[O:8][CH:9]([C:11]1[O:12][C:13]([CH:26]=[O:27])=[CH:14][N:15]=1)[CH3:10])([CH3:6])([CH3:5])[CH3:4]
Reactant: CN(C)C=O
Reactant: CC(O[Si](C)(C)C(C)(C)C)c1ncco1
Agent: N#N
Agent: [Cl-]
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Solvent: O
Solvent: CCCCC
Product: CC(O[Si](C)(C)C(C)(C)C)c1ncc(C=O)o1
Temperature: -40 °C
Reaction time: 1 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 2-[1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-oxazole (733 mg, 3.22 mmol) in dry THF (16 mL) at −78° C. was treated with t-butyllithium (2.62 mL of a 1.6M solution in pentane, 4.19 mmol) while keeping the temperature below −70° C. The reaction mixture was then stirred for 1 h at −40° C. DMF (0.50 mL, 6.45 mmol) was added dropwise at −78° C. The reaction mixture was allowed to warm up to rt and stirred for 2 h at rt. Water (30 mL) was added followed by sat. aq. NH4Cl (20 mL) and EA (20 mL), the layers separated and the aq. layer extracted with EA (2×30 mL). The combined org. extracts were dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue by FC (1:4 EA-Hept) gave the title compound as a colorless oil. TLC:rf (1:4 EA-Hept)=0.33. LC-MS-conditions 02: tR=1.08 min, [M+H]+=256.38.
Reaction SMILES: C(OC([NH:7][C@H:8]([C:15]([NH:17][C:18]1[CH:19]=[C:20]([C@H:25]([CH3:34])[CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH:21]=[CH:22][C:23]=1[Cl:24])=[O:16])[CH:9]([C:11]([F:14])([F:13])[F:12])[CH3:10])=O)C=C.CC1(C)CC(=O)CC(=O)C1>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.C1COCC1>[Cl:24][C:23]1[CH:22]=[CH:21][C:20]([C@H:25]([CH3:34])[CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:31])[CH3:32])=[O:28])=[CH:19][C:18]=1[NH:17][C:15](=[O:16])[C@H:8]([CH:9]([C:11]([F:14])([F:13])[F:12])[CH3:10])[NH2:7]
Reactant: C=CCOC(=O)N[C@H](C(=O)Nc1cc([C@H](C)CC(=O)OC(C)(C)C)ccc1Cl)C(C)C(F)(F)F
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: CC1(C)CC(=O)CC(=O)C1
Solvent: C1CCOC1
Product: CC([C@H](N)C(=O)Nc1cc([C@H](C)CC(=O)OC(C)(C)C)ccc1Cl)C(F)(F)F
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
630 mg (1.24 mmol) of tert-butyl (3R)-3-[3-({N-[(allyloxy)carbonyl]-4,4,4-trifluorovalyl}amino)-4-chlorophenyl]butanoate (Example 40A, mixture of 4 isomers) and 1.394 g (9.94 mmol) of dimedone were initially charged in 10 ml of abs. THF. At RT, the solution was deoxygenated by passing through argon for 30 min. Subsequently 28.7 mg (0.025 mmol) of tetrakis(triphenylphosphine)palladium(0) were added and the mixture was stirred at RT overnight. After dilution with ethyl acetate, the mixture was washed twice with sat. sodium bicarbonate solution and once with sat. sodium chloride solution. The organic phase was dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 40:1→20:1) and separated. This gave 420 mg of the target compound as diastereomer mixture 1 (79.9% of theory).
Reaction SMILES: [C:1]1([CH2:7][C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[N:27]1(C(=O)CC=C)[C:31]2C=C[CH:34]=[CH:35][C:30]=2N=[N:28]1.O.NN>C1COCC1.CCO>[CH2:30]([C:31]1[NH:27][N:28]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)[C:7]=1[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH:35]=[CH2:34]
Reactant: C=CCC(=O)n1nnc2ccccc21
Reactant: Cc1ccc(C(=O)Cc2ccccc2)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: NN
Agent: [Li+]
Solvent: CCO
Solvent: O
Solvent: C1CCOC1
Product: C=CCc1[nH]nc(-c2ccc(C)cc2)c1-c1ccccc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 36 %

Procedure:
To a solution of 2-phenyl-1-p-tolylethanone (1.0 g, 4.76 mmol) in THF (10 mL) added LiHMDS (1.0 M in THF) (9.51 mL, 9.51 mmol) slowly via syringe at 0° C. After stirring for 10 min, 1-(1H-benzo[d][1,2,3]triazol-1-yl)but-3-en-1-one (1.068 g, 5.71 mmol) was added in one portion. The reaction was stirred at 0° C. for 30 min and then quenched with AcOH (2 mL). EtOH (30 mL) and hydrazine hydrate (0.714 g, 14.27 mmol) were added, and the reaction was heated to reflux for 30 min. The reaction was cooled to room temperature, concentrated and the residue was extracted with EtOAc/H2O, washed with brine, dried over MgSO4, and purified by column chromatography to give the title compound as clear oil (0.47 g). LCMS m/z=275.0 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 2.31 (s, 3H), 3.38-3.43 (m, 2H), 5.07-5.14 (m, 2H), 5.90-6.01 (m, 1H), 7.03-7.09 (m, 2H), 7.19-7.30 (m, 5H), 7.30-7.36 (m, 2H).
Reaction SMILES: [CH2:1]([NH2:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].C(N(CC)CC)C.[CH2:16]([C:20]1[CH:28]=[CH:27][C:23]([C:24](Cl)=[O:25])=[CH:22][CH:21]=1)[CH2:17][CH2:18][CH3:19]>C(Cl)Cl.O>[CH2:1]([NH:8][C:24](=[O:25])[C:23]1[CH:27]=[CH:28][C:20]([CH2:16][CH2:17][CH2:18][CH3:19])=[CH:21][CH:22]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: CCCCc1ccc(C(=O)Cl)cc1
Reactant: CCCCCCCN
Solvent: ClCCl
Solvent: O
Solvent: CCN(CC)CC
Product: CCCCCCCNC(=O)c1ccc(CCCC)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a cold solution of 16 g of n-heptylamine and 29.0 ml of triethylamine in 300 ml of methylene chloride was added dropwise a solution of 27.4 g of 4-butylbenzoylchloride in 100 ml of methylene chloride. The resulting mixture was stirred at room temperature for 41/2 hours and diluted with water. The organic layer was washed with 1N sodium hydroxide, brine, dried, and evaporated. The residual solid was recrystallized from hexane to yield N-heptyl-4-n-butylbenzamide, mp 37°-38° C.
Reaction SMILES: [CH3:1][NH:2][C:3](=O)[CH:4]([OH:22])[CH:5]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[O:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N+:13]([O-:15])=[O:14].B#B.CO.[ClH:28]>C1COCC1.C(OCC)C>[ClH:28].[CH3:1][NH:2][CH2:3][CH:4]([OH:22])[CH:5]([O:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N+:13]([O-:15])=[O:14])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: CNC(=O)C(O)C(Oc1ccccc1[N+](=O)[O-])c1ccccc1
Agent: B#B
Agent: Cl
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: CO
Product: CNCC(O)C(Oc1ccccc1[N+](=O)[O-])c1ccccc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 94 %

Procedure:
50.3 g of N-methyl-2-hydroxy-3-phenyl-3-(2-nitro-phenoxy)-propionamide dissolved in 1000 ml of anhydrous THF was reduced to amine by slowly adding at 8° C. 340 ml of a molar solution of diborane in THF. The whole was refluxed for 4 hours, cooled to room temperature, the excess of diborane was decomposed with MeOH and then, again at room temperature, dropwise addition was made of 400 ml of an ethereal solution of HCl. The whole was left to stand for 16 hours and then evaporated to dryness at reduced pressure, taken up with CH2Cl2 and washed once with an aqueous solution of sodium bicarbonate. The organic phase was then washed several times with a saturated aqueous solution of NaCl, dried with sodium sulphate and evaporated to dryness. The dark oil forming the residue was dissolved in 800 ml of ethyl ether and alcoholic hydrochloric acid (18% solution in ETOH) was added; there was obtained 50.9 g of N-methyl-2-hydroxy-3-(2-nitro-phenoxy)-3-phenyl-propylamine. hydrochloride, m.p. 197°-203° C. (yield 94%).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([N:8]2[C:20]3[CH:19]=[CH:18][C:17]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[CH:16][C:15]=3[C:14]3[C:9]2=[CH:10][CH:11]=[C:12]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:13]=3)[CH:5]=[CH:6][CH:7]=1.[CH3:33][O:34][C:35]1[CH:36]=[C:37](B(O)O)[CH:38]=[CH:39][CH:40]=1.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>O.C(Cl)Cl.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(O)C>[C:27]1([C:12]2[CH:11]=[CH:10][C:9]3[N:8]([C:4]4[CH:5]=[C:6]([C:37]5[CH:38]=[CH:39][CH:40]=[C:35]([O:34][CH3:33])[CH:36]=5)[CH:7]=[CH:2][CH:3]=4)[C:20]4[C:15]([C:14]=3[CH:13]=2)=[CH:16][C:17]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:18][CH:19]=4)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: COc1cccc(B(O)O)c1
Reactant: Brc1cccc(-n2c3ccc(-c4ccccc4)cc3c3cc(-c4ccccc4)ccc32)c1
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: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Solvent: O
Product: COc1cccc(-c2cccc(-n3c4ccc(-c5ccccc5)cc4c4cc(-c5ccccc5)ccc43)c2)c1
Temperature: 25 °C
Yield: 85.4 %

Procedure:
The obtained 9-(3-bromophenyl)-3,6-diphenylcarbazole (3.20 g, 6.75 mmol), 3-methoxyphenylboronic acid (1.54 g, 10.1 mmol) and tetrakis(triphenylphosphine)palladium (0.124 g) were added to a solvent mixture of toluene (30 mL) and ethanol (10 mL). Then, an aqueous solution of sodium carbonate (37.3 g) in distilled water (90 mL) was added the mixture. The resultant mixture was refluxed for 9 hours in a nitrogen atmosphere and then cooled to room temperature. The obtained mixture was diluted with methylene chloride and the insoluble matter was removed through filtration. The organic layer was washed with water and separated. The solvent was evaporated under reduced pressure. The residue was purified through silica gel column chromatography using as an eluent a solvent mixture of methylene chloride/hexane (2/3 by volume), to thereby obtain 2.89 g of [3′-(3,6-diphenylcarbazol-9-yl)biphenyl-3-yloxy]methane.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C@@H:12](O)[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].[NH:19]=[N+:20]=[N-:21].C(P(CCCC)CCCC)CCC.N(C(OC(C)C)=O)=NC(OC(C)C)=O.C(=O)=O>C1(C)C=CC=CC=1.C1COCC1>[N:19]([C@@H:12]([C:6]1[CH:7]=[CH:8][C:9]([O:10][CH3:11])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=1)[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])=[N+:20]=[N-:21]
Reactant: [N-]=[N+]=N
Reactant: CCOc1cc([C@@H](O)CS(C)(=O)=O)ccc1OC
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: CCCCP(CCCC)CCCC
Agent: O=C=O
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CCOc1cc([C@@H](CS(C)(=O)=O)N=[N+]=[N-])ccc1OC
Reaction time: 16 h
Yield: 81 %

Procedure:
A mixture of (R)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanol (0.94 g, 3.4 mmol) in toluene (280 mL) and THF (20 mL) was sparged with nitrogen for 15 min, and then a ˜1.1 M solution of hydrazoic acid in toluene (13.8 mL, ˜15 mmol) was added. The flask was cooled in a dry ice-acetone bath. When the internal temperature reached <−60° C., tributylphosphine (1.7 mL, 6.9 mmol), and then diisopropyl azodicarboxylate (1.6 mL, 7.9 mmol) were added. The cooling bath was charged with dry ice for the next 4 h in order to maintain the reaction temperature at <−60° C., and then the temperature was allowed to gradually rise. After 16 h, the internal temperature had climbed to −2° C. Then, silica gel (20 g) was added and the resulting slurry was evaporated. The residue was chromatographed on a silica gel column, using a hexanes-EtOAc gradient. After pooling and evaporating the appropriate fractions, the residue was triturated with heptane (25 mL) and the slurry was filtered. Solids were dried under vacuum, to provide (S)-4-(1-azido-2-(methylsulfonyl)ethyl)-2-ethoxy-1-methoxybenzene as a white solid (0.84 g, 81% yield); HPLC (Hypersil BDS C8, 5.0 μm, 250×4.6 mm, 1.5 mL/min, 278 nm, 90/10 gradient to 80/20 0.1% aqueous TFA/MeOH over 10 min then gradient to 10/90 0.1% aqueous TFA/MeOH over the next 15 min): 17.77 (99.9%); 1H NMR (DMSO-d6) δ 1.33 (t, 3H), 2.99 (s, 3H), 3.55 (dd, J=4.0, 14.7 Hz, 1H), 3.77 (s, 3H), 3.90 (dd, J=9.6, 14.7 Hz, 1H), 3.98-4.13 (m, 2H), 5.01-5.21 (m, 1H), 6.90-7.05 (m, 2H), 7.08 (s, 1H).
Reaction SMILES: [C:1]1([CH2:7][CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][C:10]2=[O:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([N-]C(C)C)(C)C.[Li+].I[CH2:24][CH:25]([CH3:27])[CH3:26]>C1COCC1>[CH3:24][CH:25]([CH3:27])[CH2:26][CH:11]1[CH2:12][CH2:13][N:9]([CH2:8][CH2:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:10]1=[O:14]
Reactant: CC(C)CI
Reactant: O=C1CCCN1CCc1ccccc1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(C)CC1CCN(CCc2ccccc2)C1=O
Temperature: -78 °C
Reaction time: 0.67 h
Yield: 99.1 %

Procedure:
A solution of 1-(2-phenylethyl)-2-pyrrolidinone (500 mg, 2.64 mmol) and THF (6 mL) is cooled to -78° C. Some precipitation occurred and 2 mL of THF is added. A solution of lithium diisopropylamide (LDA, 1.4 mL, 2.8 mmol, 2.0M in heptane/THF/ethylbenzene) is added and the mixture stirred at -78° C. for 40 minutes, giving a dark brown solution. To this solution is added 1-iodo-2-methylpropane (0.37 mL, 3.2 mmol). The solution is allowed to warm from -78° C. to 5° C. over 2.5 hours. After quenching with saturated aqueous ammonium chloride, aqueous workup (EtOAc, MgSO4) and purification by column chromatography (20% EtOAc/hexane) to give 642 mg (99%) of the title compound as a white solid (mp 69°-71° C.).
Reaction SMILES: [N+:1]([C:4]1[CH:23]=[CH:22][C:7]([CH2:8][O:9][C:10]([NH:12][CH2:13][C:14]2[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=2)[CH:17]=[O:18])=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2].CC(C)=[O:26].OS(O)(=O)=O.O=[Cr](=O)=O.CO>CC(C)=O.C(OCC)(=O)C>[N+:1]([C:4]1[CH:23]=[CH:22][C:7]([CH2:8][O:9][C:10]([NH:12][CH2:13][C:14]2[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=2)[C:17]([OH:26])=[O:18])=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: CC(C)=O
Reactant: O=Cc1cccc(CNC(=O)OCc2ccc([N+](=O)[O-])cc2)c1
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: CO
Solvent: CCOC(C)=O
Product: O=C(NCc1cccc(C(=O)O)c1)OCc1ccc([N+](=O)[O-])cc1
Reaction time: 2 h

Procedure:
To 3-(p-nitrobenzyloxycarbonyl)aminomethylbenzaldehyde (1.5 g) in acetone (30 ml) was added Jones' reagent with ice-cooling, and the mixture was stirred for 2 hours. After addition of methanol (1.5 ml), the mixture was diluted with ethyl acetate, washed with water, dried over anhydrous sodium sulfate and evaporated to give 3-(p-nitrobenzyloxycarbonyl)aminomethylbenzoic acid