Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1](=O)([O-])[O-].[Na+].[Na+].Cl[C:8]1[C:9]2[CH:19]=[CH:18][C:17](=[O:20])[N:16]([C:21]3[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=3[F:28])[C:10]=2[N:11]=[C:12]([S:14][CH3:15])[N:13]=1.F[C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1>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>[F:28][C:22]1[CH:23]=[CH:24][CH:25]=[C:26]([F:27])[C:21]=1[N:16]1[C:10]2[N:11]=[C:12]([S:14][CH3:15])[N:13]=[C:8]([C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=3[CH3:1])[C:9]=2[CH:19]=[CH:18][C:17]1=[O:20]
Reactant: O=C([O-])[O-]
Reactant: OB(O)c1ccc(F)cc1
Reactant: CSc1nc(Cl)c2ccc(=O)n(-c3c(F)cccc3F)c2n1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Na+]
Solvent: C1CCOC1
Product: CSc1nc(-c2ccccc2C)c2ccc(=O)n(-c3c(F)cccc3F)c2n1
Yield: 63 %

Procedure:
THF (10 mL) and 2M sodium carbonate (2 mL) were added to a mixture of 4-chloro-8-(2,6-difluorophenyl)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one (0.34 g, 1.0 mmol, solid-supported tetrakis(triphenylphosphine)palladium(0) (0.39 g, 0.1 mmol) and 4-fluorobenzeneboronic acid (0.21 g, 1.5 mmol). The mixture was irradiated with microwave at about 150° C. for about 20 min, then filtered and the filtrate evaporated. The crude product was redissolved in ethyl acetate (10 mL) and water (10 mL). The layers were separated and the organic layer was dried over magnesium sulphate, filtered and evaporated. The crude product was purified by flash chromatography on silica gel with cyclohexane containing ethyl acetate (0 to 50%) to give the title compound (0.25 g, 63%). LC-MS m/z 396 (M+H)+, 3.55 min (ret time).
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([O:14][CH2:15][CH2:16][CH3:17])[C:11]([C:18]([F:21])([F:20])[F:19])=[CH:10][C:9]=1[NH:22][C:23](=[O:39])[CH2:24][C:25](=O)[C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([C:32]2[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=2)[CH:27]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:15]([O:14][C:12]1[C:11]([C:18]([F:21])([F:20])[F:19])=[CH:10][C:9]2[NH:22][C:23](=[O:39])[CH2:24][C:25]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]4[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=4)[CH:27]=3)=[N:7][C:8]=2[CH:13]=1)[CH2:16][CH3:17]
Reactant: CCCOc1cc(NC(=O)OC(C)(C)C)c(NC(=O)CC(=O)c2cccc(-c3cccnc3)c2)cc1C(F)(F)F
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCCOc1cc2c(cc1C(F)(F)F)NC(=O)CC(c1cccc(-c3cccnc3)c1)=N2

Procedure:
The title compound was prepared from {2-[3-oxo-3-(3-pyridin-3-yl-phenyl)-propionylamino]-5-propoxy-4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example M195) (359 mg, 0.626 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a white solid (223 mg, 81%).
Reaction SMILES: C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)=[CH:9][C:8]=1[CH2:20][CH3:21].[B:22](OC)([O:25]C)[O:23]C.Cl>O1CCCC1>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]([C:10]2[CH:9]=[C:8]([CH2:20][CH3:21])[C:7]([B:22]([OH:25])[OH:23])=[CH:12][CH:11]=2)=[CH:14][CH:15]=1
Reactant: CCc1cc(-c2ccc(Cl)cc2)ccc1Br
Reactant: COB(OC)OC
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCc1cc(-c2ccc(Cl)cc2)ccc1B(O)O
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 42.1 %

Procedure:
A solution of n-butyl lithium in hexanes (1.6 M, 38.75 ml, 0.062 mol) is added dropwise to a solution of 4-bromo-4′-chloro-3-ethylbiphenyl (12.35 g, 0.041 mol) in tetrahydrofuran (125 ml) at −78° C., under an atmosphere of nitrogen, and the mixture is stirred at −78° C. for 30 minutes. Trimethyl borate (27.8 ml, 0.25 mol) is added slowly at −78° C. and the mixture is stirred for 1 hr. The reaction mixture is allowed to warm to room temperature over 2-3 hrs and then stirred at room temperature for 1 hr. 0.1N aqueous hydrochloric acid (343 ml) is added and the mixture is stirred at room temperature overnight. The reaction mixture is extracted with ethyl acetate (3×300 ml) and the organic extracts are combined, dried with anhydrous sodium sulfate, filtered and the filtrate is concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give 4′-chloro-3-ethylbiphen-4-ylboronic acid (4.5 g) as white solid.
Reaction SMILES: Cl[C:2]1[C:3]2[N:4]([C:14]([CH2:17][CH3:18])=[N:15][N:16]=2)[C:5]2[C:10]([N:11]=1)=[CH:9][CH:8]=[C:7]([O:12][CH3:13])[CH:6]=2.[CH2:19]([NH:21][CH2:22][CH3:23])[CH3:20]>CN(C)C=O>[CH2:19]([N:21]([CH2:22][CH3:23])[C:2]1[C:3]2[N:4]([C:14]([CH2:17][CH3:18])=[N:15][N:16]=2)[C:5]2[C:10]([N:11]=1)=[CH:9][CH:8]=[C:7]([O:12][CH3:13])[CH:6]=2)[CH3:20]
Reactant: CCc1nnc2c(Cl)nc3ccc(OC)cc3n12
Reactant: CCNCC
Solvent: CN(C)C=O
Product: CCc1nnc2c(N(CC)CC)nc3ccc(OC)cc3n12
Yield: 23 %

Procedure:
4-Chloro-1-ethyl-8-methoxy-[1,2,4]triazolo[4,3-a]quinoxaline (520 mg., 0.002 mole) and 673 mg. (0.008 mole) of diethylamine in 10 ml. of N,N-dimethylformamide were stirred at room temperature overnight. The reaction mixture was poured over ice and the precipitate was separated by filtration, washed with water and air dried. Recrystallization from diethyl ether and petroleum ether then afforded 140 mg. (23% yield) of pure 4-diethylamino-1-ethyl-8-methoxy-[1,2,4]triazolo[4,3-a]quinoxaline, m.p. 135°-138° C. Mass spectrum: m/e, 299 (P).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([CH3:19])[C:16]([OH:18])=O)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].S(Cl)(Cl)=O.[C:24]([O:28][C:29]([N:31]1[C:35]([NH2:36])=[CH:34][C:33]([CH:37]2[CH2:39][CH2:38]2)=[N:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25].C(O)C(N)(CO)CO>O1CCCC1.C(N(CC)CC)C>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[CH:11][C:12]([CH:15]([CH3:19])[C:16]([NH:36][C:35]2[N:31]([C:29]([O:28][C:24]([CH3:26])([CH3:27])[CH3:25])=[O:30])[N:32]=[C:33]([CH:37]3[CH2:39][CH2:38]3)[CH:34]=2)=[O:18])=[CH:13][CH:14]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C(=O)O)c1ccc(NC(=O)OC(C)(C)C)cc1
Reactant: CC(C)(C)OC(=O)n1nc(C2CC2)cc1N
Agent: NC(CO)(CO)CO
Solvent: CCN(CC)CC
Solvent: O=S(Cl)Cl
Solvent: C1CCOC1
Product: CC(C(=O)Nc1cc(C2CC2)nn1C(=O)OC(C)(C)C)c1ccc(NC(=O)OC(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 69.9 %

Procedure:
265 mg (1 mmol) of 2-{4-[(tert-butoxycarbonyl)amino]phenyl}propanoic acid were treated at 4° C. under nitrogen with 146 μl (2 mmol) of thionylchloride. The reaction mixture was stirred for 2.5 hours and the temperature was gradually raised to room temperature. The mixture was taken up with tetrahydrofuran and evaporated thoroughly. The resulting acyl chloride, without any further purification, was dissolved in 3 ml of dry tetrahydrofuran and added dropwise to a solution of 178 mg (0.8 mmol) of tert-butyl-5-amino-3-cyclopropyl-1H-pyrazole-1-carboxylate in 3 ml of tetrahydrofuran. 312 mg (1 mmol, loading 3.2 mmol/g) of polymer supported triethylamine were then added under stirring. After 2.5 hours 80 mg (loading 3.2 mmol/g) of polymer supported trisamine were finally added in order to quench the excess of acyl chloride. After 2 hours, the resins were filtered and washed with methanol and dichloromethane. Evaporation of the filtrate afforded 263 mg of the title compound as a foam (70% yield).
Reaction SMILES: Cl[CH:2]1[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[C:4](=[O:11])[N:3]1[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=1[F:19].[C:20]1([SH:26])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(N(CC)CC)C>ClCCl>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([N:3]2[CH:2]([S:26][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:10]3[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=3[C:4]2=[O:11])=[C:13]([F:19])[CH:14]=1
Reactant: Sc1ccccc1
Reactant: O=C1C2=C(CCCC2)C(Cl)N1c1ccc(Cl)cc1F
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C1C2=C(CCCC2)C(Sc2ccccc2)N1c1ccc(Cl)cc1F
Temperature: 25 °C
Reaction time: 2 h
Yield: 85.7 %

Procedure:
In 30 ml of dichloromethane were dissolved 3.0 g of 3-chloro-2-(4-chloro-2-fluorophenyl)-2,3,4,5,6,7-hexahydro-1H-isoindol-1-one and 1.1 g of thiophenol, and 1.0 g of triethylamine was added to the solution over a 10-minute period, followed by stirring at room temperature for 2 hours. The reaction mixture was washed with water, dried over anhydrous sodium sulfate and freed of the dichloromethane under reduced pressure. The residue was purified by means of column chromatography with the use of silica gel (developing solvent of dichloromethaneacetone), thereby producing 3.2 g (yield of 86%) of the subject compound in white crystals, m.p. 86°-87° C.
Reaction SMILES: [CH3:1][CH:2]([S:16]([NH2:19])(=[O:18])=[O:17])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15].[H-].[Na+].[CH:22]([C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([CH:31]([CH3:33])[CH3:32])[C:26]=1[N:34]=[C:35]=[O:36])([CH3:24])[CH3:23]>CN(C=O)C>[CH3:24][CH:22]([C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([CH:31]([CH3:32])[CH3:33])[C:26]=1[NH:34][C:35]([NH:19][S:16]([CH:2]([CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH3:1])(=[O:18])=[O:17])=[O:36])[CH3:23]
Reactant: CC(C)c1cccc(C(C)C)c1N=C=O
Reactant: CCCCCCCCCCCCCC(C)S(N)(=O)=O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCCC(C)S(=O)(=O)NC(=O)Nc1c(C(C)C)cccc1C(C)C
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 60.6 %

Procedure:
n-BuLi (1.6M, 32 mL) was added dropwise to a 0° C. solution of N-t-butylethanesulfonamide (4.0 g, 24 mmoles) in anhydrous THF (80 mL) under dry N2. The solution was stirred for 30 minutes at 0° C. then warmed to room temperature for 30 minutes. It was then cooled back to 0° C. and a solution of 1-bromotridecane (6.4 mL, 25 mmoles) in 10 mL anhydrous THF (distilled from Na--Ph2CO) was added dropwise. The solution was allowed to warm to room temperature overnight, quenched by addition of 1N HCl (60 mL), and partitioned between ethyl acetate and brine. The organic layer was dried, filtered, and concentrated to an oil, which was dissolved in 40 mL of CF3CO2H and stirred overnight at room temperature. It was then concentrated and the solid residue recrystallized from iPr2O to afford 4.8 g (68%) of 2-pentadecylsulfonamide as a light brown (almond) powder. (b) A solution of 2-pentadecylsulfonamide (2.91 g, 10 mmoles) in DMF (40 mL dried over 3Å sieves) was added dropwise to a stirred, 0° C. suspension of NaH (0.5 g, 21 mmoles of hexane washed) in 10 mL dry DMF. The mixture was stirred 30 minutes at 0° C., then warmed to room temperature for 3 hours. It was then cooled back to 0° C. and a solution of 2,6-diisopropylphenylisocyanate (2.14 mL, 10 mmoles) in 10 mL DMF was added dropwise. The mixture was allowed to warm to room temperature overnight, cooled to 0° C., and quenched by dropwise addition of 1N HCl (60 mL). The mixture was partitioned between EtOAc (300 mL) and H2O (100 mL). The organic layer was further washed with brine, dried, filtered, and evaporated to provide an oil which was flash chromatographed (silica gel, 4:1 hexane-EtOAc) to produce 3 g of an oil which solidified on standing (m.p. 65-75° C.).
Reaction SMILES: Br[C:2]1[CH:12]=[C:11]([CH3:13])[C:5]2[N:6]=[C:7]([NH2:10])[N:8]=[N:9][C:4]=2[CH:3]=1.Br[C:15]1[CH:28]=[CH:27][C:18]([O:19][CH2:20][CH2:21][N:22]2[CH2:26][CH2:25][CH2:24][CH2:23]2)=[CH:17][CH:16]=1.C1C=CC(P([C:42]2[C:51]([C:52]3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=[C:50]3[C:45]([CH:46]=CC=C3)=[CH:44][CH:43]=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1>[CH3:46][C:45]1[CH:44]=[CH:43][CH:42]=[C:51]([CH3:52])[C:50]=1[C:2]1[CH:12]=[C:11]([CH3:13])[C:5]2[N:6]=[C:7]([NH:10][C:15]3[CH:28]=[CH:27][C:18]([O:19][CH2:20][CH2:21][N:22]4[CH2:26][CH2:25][CH2:24][CH2:23]4)=[CH:17][CH:16]=3)[N:8]=[N:9][C:4]=2[CH:3]=1
Reactant: Cc1cc(Br)cc2nnc(N)nc12
Reactant: Brc1ccc(OCCN2CCCC2)cc1
Reactant: c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1
Solvent: Cc1ccccc1
Product: Cc1cccc(C)c1-c1cc(C)c2nc(Nc3ccc(OCCN4CCCC4)cc3)nnc2c1
Reaction time: 24 h
Yield: 36.7 %

Procedure:
About 1 g (3.78 mmol) of 7-bromo-5-methyl-benzo[1,2,4]triazin-3-ylamine and about 2.04 g (7.56 mmol) of 1-[2-(4-bromo-phenoxy)-ethyl]-pyrrolidine were dissolved in about 500 ml of toluene. About 174 mg (0.19 mmol) of Pd(dba)3, about 340 mg (0.54 mmol) of BINAP, and about 500 mg (4.46 mmol) KU-Bu were added to the solution. The mixture was kept at about 100° C. for about 24 hours under argon. The crude product was purified by preparative HPLC. About 90 mg of [7-(2,6-dimethyl-phenyl)-5-methyl-benzo[1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-amine (product having formula (IX)) was isolated. Yield: about 5.2%. ESI-MS: [M+H]+, 454.6; 1H NMR (DMSO-d6): δ 1.90-2.05 (m, 10 H), 2.64 (s, 3H), 3.15 (m, 2 H), 3.59-3.64 (m, 4 H), 4.31 (t, J=5.2 Hz, 2 H), 7.09 (d, J=9.2 Hz, 2 H), 7.18 (d, J=7.4 Hz, 2 H), 7.23 (m, 1H), 7.60 (s, 1 H), 7.91 (s, 1 H), 7.98 (d, J=9.2 Hz, 2 H).
Reaction SMILES: C(N(CC)CC)C.C(O[C@@H:12]1[C@H:18]2[C@H:19]3[C@H:28]([CH2:29][CH2:30][C@:15]2([CH2:16][CH3:17])[C:14](=[O:34])[CH2:13]1)[C@@H:27]1[C:22]([CH:23]=[C:24]([O:31][CH2:32][CH3:33])[CH2:25][CH2:26]1)=[CH:21][CH2:20]3)(=O)C.O>CN(C=O)C>[CH2:32]([O:31][C:24]1[CH2:25][CH2:26][C@H:27]2[C:22](=[CH:21][CH2:20][C@@H:19]3[C@@H:28]2[CH2:29][CH2:30][C@@:15]2([CH2:16][CH3:17])[C@H:18]3[CH:12]=[CH:13][C:14]2=[O:34])[CH:23]=1)[CH3:33]
Reactant: CCOC1=CC2=CC[C@@H]3[C@H](CC[C@]4(CC)C(=O)C[C@H](OC(C)=O)[C@@H]34)[C@H]2CC1
Solvent: CN(C)C=O
Solvent: O
Solvent: CCN(CC)CC
Product: CCOC1=CC2=CC[C@@H]3[C@H](CC[C@]4(CC)C(=O)C=C[C@@H]34)[C@H]2CC1
Temperature: 40 °C
Reaction time: 72 h
Yield: 71.1 %

Procedure:
Triethylamine (2 ml, 14.4 mmol) was added to a suspension of 15α-acetoxy-3-ethoxy-18-methyl-estr-3,5-dien-17-one (2 g, 5.4 mmol) in DMF (20 ml). The mixture was stirred at 40° C. for 3 days, cooled to 10° C. and water (15 ml) was then added. The precipitate was filtered and washed with water. The crude product was purified by flash chromatography, eluting with heptane and ethyl acetate (7:3), crystallized from heptane, and dried under vacuum to afford 3-ethoxy-18-methyl-estra-3,5,15-trien-17-one (1.2 g, yield: 66%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH:16](OC)[C:17]3[C:25]4[C:20](=[N:21][CH:22]=[CH:23][CH:24]=4)[NH:19][CH:18]=3)=[CH:12][N:11]=2)=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.C([SiH](CC)CC)C.O>C(#N)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][C:17]3[C:25]4[C:20](=[N:21][CH:22]=[CH:23][CH:24]=4)[NH:19][CH:18]=3)=[CH:12][N:11]=2)=[CH:4][CH:3]=1
Reactant: COC(c1ccc(CNc2ccc(Cl)cc2)nc1)c1c[nH]c2ncccc12
Agent: CC[SiH](CC)CC
Solvent: CC#N
Solvent: O=C(O)C(F)(F)F
Solvent: O
Product: Clc1ccc(NCc2ccc(Cc3c[nH]c4ncccc34)cn2)cc1

Procedure:
To (4-Chloro-phenyl)-5-[methoxy-(1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-pyridin-2-ylmethyl-amine (57, 20.8 mg, 0.055 mmol) in acetonitrile (10.0 mL) were added trifluoroacetic acid (0.50 mL, 6.5 mmol) and triethylsilane (1.00 mL, 6.26 mmol). The reaction was heated to reflux for 3 hours, then poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 10% methanol in dichloromethane to give compound (P-0078, 6.1 mg, 32.0%). MS (ESI) [M+H+]+=349.4.
Reaction SMILES: [CH3:1]OS(C(F)(F)F)(=O)=O.[C:10]([C:17]1NC=CN=1)([C:12]1[NH:13][CH:14]=[CH:15][N:16]=1)=[O:11].C(O)[C:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:24]>[N+](C)([O-])=O>[CH2:17]([C:10]([C:12]1[N:16]([CH3:1])[CH:15]=[CH:14][N:13]=1)=[O:11])[C:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:24]
Reactant: O=C(c1ncc[nH]1)c1ncc[nH]1
Reactant: COS(=O)(=O)C(F)(F)F
Reactant: O=C(CO)c1ccccc1
Solvent: C[N+](=O)[O-]
Product: Cn1ccnc1C(=O)CC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Methyltriflate (1 mL, 8.84 mmol) was added dropwise to a solution of (0.959 g, 5.92 mmol) carbonyl diimidazole dissolved in 20 ml nitromethane. The solution was kept at about 0° C. during the addition. The solution was then warmed to room temperature and was allowed to stir for 1 h. The solution was then transferred to a flask containing freshly azeotroped (from benzene) 0.647 g (5.303 mmol) phenacyl alcohol. The resulting mixture was allowed to stir for 2 h at room temperature to form the phenacyl carbonyl-N-methylimidazole (not isolated or characterized). Freshly azotroped isopropyl alcohol (5.92 mmol) was then added and the reaction mixture was stirred overnight. The solvent was removed by vacuum distillation and the product was purified using silica gel flash chromatography with 80% hexane and 20% ethyl acetate. Yield 1.032 g (88%) from 0.715 g phenacyl alcohol, yellow oil; 1H NMR (CDCl3, 400 MHz) δ3.87 (s, 3H), 5.37 (s, 2H), 7.46-7.62 (m, 3H), 7.92 (d, J=6, 2H); 13C NMR (CDCl3, 110 MHz) δ191.9, 154.2, 133.8, 128.7, 127.5, 72.6, 68.2, 21.5; EI-MS, m/z (rel. intensity) 222 (M+, 1), 163 (27), 118 (32), 105 (100), 91 (60), 77 (66), 65 (13), 50 (44).
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=3)=[CH:8][CH:9]=2)[C:4]([CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[C:3]1[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:36][C:37]([O:39][CH3:40])=[O:38]>CC(C)=O>[CH3:40][O:39][C:37](=[O:38])[CH2:36][O:17][C:14]1[CH:15]=[CH:16][C:11]([C:7]2[CH:6]=[C:5]3[C:10](=[CH:9][CH:8]=2)[N:2]([CH3:1])[C:3]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[C:4]3[CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[CH:12][CH:13]=1
Reactant: COC(=O)CBr
Reactant: CCCCCc1c(-c2ccccc2)n(C)c2ccc(-c3ccc(O)cc3)cc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCCCCc1c(-c2ccccc2)n(C)c2ccc(-c3ccc(OCC(=O)OC)cc3)cc12

Procedure:
The desired product was prepared using a procedure similar to step 1 of example 4. Thus, 4-(1-methyl-3-pentyl-2-phenyl-1H-indol-5-yl)-phenol (0.180 g, 0.491 mmol) was reacted with K2CO3 (0.088 g, 0.639 mmol) and methyl bromoacetate (0.098 g, 0.639 mmol) in acetone (5 ml) to give the product (0.184 g, 0.417 mmol, 85%) as a viscous oil. 1H NMR (DMSO-d6) δ 0.76 (t, J=7.2 Hz, 3H), 1.15-1.22 (m, 4H), 1.51-1.56 (m, 2H), 2.65 (t, J=7.3 Hz, 2H), 3.56 (s, 3H), 3.71 (s, 3H), 4.83 (s, 2H), 7.01 (d, J=8.6 Hz, 2H), 7.41-7.45 (m, 3H), 7.47-7.50 (m, 2H), 7.54 (t, J=7.2 Hz, 2H), 7.61 (d, J=8.6 Hz, 2H), 7.73 (s, 1H); [ESI(+)], m/z 442 (M+H)+.
Reaction SMILES: FC(F)(F)C(O)=O.[S:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[S:17]([N:20]1[CH2:25][CH2:24][NH:23][CH2:22][C:21]1=[O:26])(=[O:19])=[O:18].[CH3:27][O:28][C:29]1[CH:53]=[CH:52][C:32]([CH2:33][O:34][C:35]([NH:37][C:38]2[NH:39][C:40](=[O:51])[C:41]3[N:42]=[CH:43][N:44]([CH2:47][C:48](O)=[O:49])[C:45]=3[N:46]=2)=[O:36])=[CH:31][CH:30]=1>>[S:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[S:17]([N:20]1[CH2:25][CH2:24][N:23]([C:48](=[O:49])[CH2:47][N:44]2[CH:43]=[N:42][C:41]3[C:40](=[O:51])[NH:39][C:38]([NH:37][C:35]([O:34][CH2:33][C:32]4[CH:52]=[CH:53][C:29]([O:28][CH3:27])=[CH:30][CH:31]=4)=[O:36])=[N:46][C:45]2=3)[CH2:22][C:21]1=[O:26])(=[O:19])=[O:18]
Reactant: COc1ccc(COC(=O)Nc2nc3c(ncn3CC(=O)O)c(=O)[nH]2)cc1
Reactant: O=C1CNCCN1S(=O)(=O)c1nc2ccccc2s1
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(COC(=O)Nc2nc3c(ncn3CC(=O)N3CCN(S(=O)(=O)c4nc5ccccc5s4)C(=O)C3)c(=O)[nH]2)cc1

Procedure:
The title compound was synthesized by the reaction of 1-(benzothiazole-2-sulfonyl)-piperazin-2-one trifluoroacetic acid salt with [2-N-(4-methoxybenzyloxycarbonyl)-guanin-9-yl]-acetic acid as per the procedure of Example 52. 1H NMR (500 MHz; DMSO-d6) δ 11.38 (bs, 2H), 8.33 (m, 1H), 8.24 (m, 1H), 7.81 (d, 0.6H), 7.77 (d, 0.4H), 7.71 (m, 2H), 7.36 (d, 2H), 6.94 (d, 2H), 5.16 (s, 2H), 5.12 (s, 1.2H), 5.02 (s, 0.8H), 4.51 (s, 0.8H), 4.26 (s, 1.2H), 4.24 (t, 1.2H), 4.08 (t, 0.8H), 4.03 (t, 1.2H), 3.85 (t, 0.8H), 3.75 (s, 3H).
Reaction SMILES: [Cl-].[CH:2](=O)[C:3]1[C:4](=[CH:6][CH:7]=[CH:8][CH:9]=1)[OH:5].[C:11]1([NH2:18])[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[NH2:17]>CO>[CH:14]1[CH:13]=[C:12]([NH:17][CH:2]=[C:3]2[C:4](=[O:5])[CH:6]=[CH:7][CH:8]=[CH:9]2)[C:11]([NH:18][CH:2]=[C:3]2[C:4](=[O:5])[CH:6]=[CH:7][CH:8]=[CH:9]2)=[CH:16][CH:15]=1
Reactant: Nc1ccccc1N
Reactant: O=Cc1ccccc1O
Agent: [Cl-]
Solvent: CO
Product: O=C1C=CC=CC1=CNc1ccccc1NC=C1C=CC=CC1=O

Procedure:
chloride (compound 29). Two equivalents of salicylaldehyde (2.2 g, 18.1 mmol) was mixed with one equivalent of o-phenylenediamine (920 mg, 8.4 mmol) in methanol that resulted in light orange precipitate of salphen ligand (L8). This ligand (500 mg, 1.6 mmol) was complexed with one equivalent of Fe(III) chloride (295 mg, 1.8 mmol) to obtain compound 29 (65% yield). Observed m/z value for compound 29: 370.18 (M+, —Cl). CHN analysis: Calculated (for C20H14N2O2FeCl. 2.5H2O) C: 53.37%, H, 4.26%, N, 6.22%. Observed: C: 53.32%, H, 3.88%, N, 6.00%.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C:10]3[CH:11]=[N:12][CH:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:15]=3)[N:7]([CH:20]3[CH2:22][CH2:21]3)[C:6]=2[CH:23]=1.CC1(C)C(C)(C)OB([C:32]2[CH:36]=[CH:35][NH:34][N:33]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O.C1(C)C=CC=CC=1.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>[CH:20]1([N:7]2[C:6]3[CH:23]=[C:2]([C:32]4[CH:36]=[CH:35][NH:34][N:33]=4)[CH:3]=[CH:4][C:5]=3[N:9]=[C:8]2[C:10]2[CH:11]=[N:12][CH:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:15]=2)[CH2:22][CH2:21]1
Reactant: FC(F)(F)c1cncc(-c2nc3ccc(Br)cc3n2C2CC2)c1
Reactant: CC1(C)OB(c2cc[nH]n2)OC1(C)C
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: FC(F)(F)c1cncc(-c2nc3ccc(-c4cc[nH]n4)cc3n2C2CC2)c1
Temperature: 80 °C

Procedure:
To a solution of 6-bromo-1-cyclopropyl-2-(5-trifluoromethyl-pyridin-3-yl)-1H-benzoimidazole (0.15 g, 0.00026 mol) in ethanol toluene water (6 ml 3 ml 1.5 ml respectively) mixture in a sealed tube was added 3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.1 g, 0.00052 mol) and Na2CO3 (0.082 g, 0.000785 mol) and argon was purged for 15 min. Then Pd (PPh3)4 (0.015 g, 0.000013 mol) was added and heated at 80° C. for 5 h. The solvent was evaporated and the resulting residue was added water. The aqueous layer was extracted with ethyl acetate (3×20 ml). The combined organic layers were washed with brine dried over Na2SO4 and concentrated under vacuum to afford the crude compound which was purified by column chromatography to obtain title compound 1-cyclopropyl-6-(1H-pyrazol-3-yl)-2-[5-(trifluoromethyl)pyridin-3-yl]-1H-benzimidazole (321) as an off white solid. NMR (400 MHz, DMSO-d6), δ: 12.85 (s, 1H), 9.49 (s, 1H), 9.12 (s, 1H), 8.75 (s, 1H), 8.09 (s, 1H), 7.79-7.67 (m, 3H), 7.54-7.52 (m, 1H), 6.79 (s, 1H), 3.96 (bs, 1H), 1.15 (d, J=5.6 Hz, 2H), 0.73 (bs, 2H). MS (M+1): 370.6, Purity 99.94%.
Reaction SMILES: [I:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]Br)=[CH:4][CH:3]=1.[NH:10]1[CH2:15][CH2:14][CH:13]([C:16]([OH:19])([CH3:18])[CH3:17])[CH2:12][CH2:11]1>ClCCl.C(O)C>[I:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:10]2[CH2:15][CH2:14][CH:13]([C:16]([OH:19])([CH3:18])[CH3:17])[CH2:12][CH2:11]2)=[CH:4][CH:3]=1
Reactant: CC(C)(O)C1CCNCC1
Reactant: BrCc1ccc(I)cc1
Solvent: ClCCl
Solvent: CCO
Product: CC(C)(O)C1CCN(Cc2ccc(I)cc2)CC1

Procedure:
Prepared analogously to Example 1.1.c. from 4-iodobenzyl bromide and 2-piperidin-4-ylpropan-2-ol. Yield: 1.01 g (67% of theory); C15H22INO (M=359.25); calc.: molecular ion peak (M+H)+: 360; found: molecular ion peak (M+H)+: 360; Rf value: 0.4 (silica gel, dichloromethane/ethanol (20:1)).