Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:23]=[N:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl.[OH-].[Na+]>[N:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:22]=[CH:23][C:14]=1[CH:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1
Reactant: CC(C)(C)OC(=O)N1CCC(c2cnc3ccccc3n2)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: c1ccc2nc(C3CCNCC3)cnc2c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 41.6 %

Procedure:
A mixture of 0.47 gm (1.5 mMol) 1-tert-butoxycarbonyl-4-(quinoxalin-2-yl)piperidine and 5 mL trifluoroacetic acid in 5 mL dichloromethane was stirred at room temperature for 18 hours. The reaction mixture was diluted with 2N sodium hydroxide and the phases were separated. The aqueous phase was extracted well with dichloromethane. The organic phases were combined, washed with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. The residue was subjected to flash silica gel chromatography, eluting with dichloromethane containing from 10% to 40% methanol and a trace of ammonium hydroxide. Fractions containing product were combined and concentrated under reduced pressure to provide 0.133 gm (42%) of the title compound as a tan foam.
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4](Cl)[N:3]=1.[N+:12]([C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[NH:20][CH2:19][CH2:18]2)([O-:14])=[O:13]>C(O)CCC>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([N:20]2[C:21]3[C:17](=[CH:16][C:15]([N+:12]([O-:14])=[O:13])=[CH:23][CH:22]=3)[CH2:18][CH2:19]2)[N:3]=1
Reactant: Clc1nc(Cl)c2[nH]cnc2n1
Reactant: O=[N+]([O-])c1ccc2c(c1)CCN2
Solvent: CCCCO
Product: O=[N+]([O-])c1ccc2c(c1)CCN2c1nc(Cl)nc2[nH]cnc12
Reaction time: 72 h
Yield: 90.6 %

Procedure:
37.8 g of 2,6-dichloropurine, 700 ml of butanol and 32.8 g of 5-nitroindoline are mixed and brought to a temperature of 90° C. for approximately 3 days. The mixture is allowed to return to ambient temperature. Partial drying, washing with ethyl ether and drying under vacuum at 50° C. are carried out and 57.3 g of expected product are obtained, in the form of beige crystals.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([N:28]2[CH:32]=[N:31][CH:30]=[N:29]2)=[C:6]([C:8]2[N:12]([C:13]([CH3:16])([CH3:15])[CH3:14])[C:11]3[CH:17]=[CH:18][C:19]([C:21]4[CH:22]=[N:23][C:24]([NH2:27])=[N:25][CH:26]=4)=[CH:20][C:10]=3[N:9]=2)[CH:7]=1.[Na+].[CH3:34][S:35]([O-:37])=[O:36].CNCCNC>CS(C)=O.CCOC(C)=O.O.FC(F)(F)S([O-])(=O)=O.[Cu+2].FC(F)(F)S([O-])(=O)=O>[C:13]([N:12]1[C:11]2[CH:17]=[CH:18][C:19]([C:21]3[CH:26]=[N:25][C:24]([NH2:27])=[N:23][CH:22]=3)=[CH:20][C:10]=2[N:9]=[C:8]1[C:6]1[CH:7]=[C:2]([S:35]([CH3:34])(=[O:37])=[O:36])[CH:3]=[CH:4][C:5]=1[N:28]1[CH:32]=[N:31][CH:30]=[N:29]1)([CH3:15])([CH3:14])[CH3:16]
Reactant: CC(C)(C)n1c(-c2cc(Br)ccc2-n2cncn2)nc2cc(-c3cnc(N)nc3)ccc21
Reactant: CS(=O)[O-]
Agent: [Cu+2]
Agent: CNCCNC
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: CCOC(C)=O
Solvent: O
Solvent: CS(C)=O
Product: CC(C)(C)n1c(-c2cc(S(C)(=O)=O)ccc2-n2cncn2)nc2cc(-c3cnc(N)nc3)ccc21
Temperature: 120 °C
Yield: 99.4 %

Procedure:
To a microwave vial is added 5-[2-(5-bromo-2-[1,2,4]triazol-1-yl-phenyl)-1-tert-butyl-1H-benzoimidazol-5-yl]-pyrimidin-2-ylamine (example 6) (237 mg, 0.48 mmol) in DMSO (10 mL), followed by the addition of methanesulfinic acid sodium salt (123 mg, 0.96 mmol), copper(II) trifluoromethanesulphonate (175 mg, 0.48 mmol) and N,N′-dimethylethylenediamine (85 mg, 0.96 mmol). The reaction mixture is heated in microwave reactor at 120° C. for 1.5 hours. The reaction mixture is diluted with EtOAc (20 mL) and water (10 mL). The organic layer is separated, washed with brine (10 mL), dried under anhydrous Na2SO4 (500 mg). The mixture is filtered and concentrated. The residue is purified by silica gel flash chromatography with 0-8% MeOH/CH2Cl2 as the eluent. The product fractions are collected and concentrated to afford the title compound (233 mg, 99%). LCMS (ESMS): m/z 489.52 (M++1)
Reaction SMILES: [NH2:1]O.[OH:3][C:4]1[CH:5]=[C:6]([CH:9]=[C:10]([N+:13]([O-:15])=[O:14])[C:11]=1[OH:12])[CH:7]=O>O>[OH:3][C:4]1[CH:5]=[C:6]([CH:9]=[C:10]([N+:13]([O-:15])=[O:14])[C:11]=1[OH:12])[C:7]#[N:1]
Reactant: O=Cc1cc(O)c(O)c([N+](=O)[O-])c1
Reactant: NO
Solvent: O
Product: N#Cc1cc(O)c(O)c([N+](=O)[O-])c1
Reaction time: 3.5 h

Procedure:
A solution of 1.7 g of hydroxylamine, O-sulfonic acid in 6 ml of water is added to a solution of 1.83 g of 3,4-dihydroxy-5-nitrobenzaldehyde in 25 ml of water, subsequently stirred at 65° for 3.5 hours, cooled, the separated precipitate is filtered off under suction and taken up in ethyl acetate. The organic phase is dried over sodium sulfate and evaporated in a water-jet vacuum. The crystals obtained are recrystallized from ethyl acetate/n-hexane. There is obtained 3,4-dihydroxy-5-nitrobenzonitrile in the form of yellow crystals of m.p. 194°-195°.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:21])[CH2:4][N:5]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:6](=[O:14])[C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=1.[C:22](#[N:25])[CH:23]=[CH2:24].C1CCN2C(=NCCC2)CC1>ClCCl>[CH3:1][O:2][C:3](=[O:21])[CH2:4][N:5]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH2:24][CH2:23][C:22]#[N:25])[C:6](=[O:14])[C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=1
Reactant: C=CC#N
Reactant: COC(=O)CN(C(=O)c1ccc(Cl)cc1)c1ccccc1
Solvent: ClCCl
Solvent: C1CCC2=NCCCN2CC1
Product: COC(=O)CN(C(=O)c1ccc(Cl)cc1)c1ccccc1CCC#N
Temperature: 25 °C
Reaction time: 16 h
Yield: 82.3 %

Procedure:
To 100 ml of a solution of 6.0 g of N-(p-chlorobenzoyl)phenylglycine methyl ester in dichloromethane were added 1.6 g of acrylonitrile and 3.6 g of 1,8-diazabicyclo[5.4.0]-7-undecene followed by stirring at room temperature for 16 hours. The solvent was distilled off and 100 ml of ethyl ether were added to the resulting residue. The mixture was washed with two 100 ml portions of water, and the organic layer was separated off and dried over magnesium sulphate. The solvent was distilled off and the residue was recrystallized from diethyl ether, to give 5.8 g of the desired product as a colourless powder melting at 127°-128° C.
Reaction SMILES: [CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[C:11]1[O:12][CH2:13][C:14](=[O:21])[C:15]=1[C:16]([O:18][CH2:19][CH3:20])=[O:17].[NH:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][N:29]=2)[C:24]([CH:31]=O)=[CH:23]1.N1CCC[C@H]1C(O)=O>C(O)C>[NH:22]1[C:30]2=[N:29][CH:28]=[CH:27][CH:26]=[C:25]2[C:24]([CH:31]=[C:13]2[O:12][C:11]([N:2]3[CH2:3][CH2:4][C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[CH2:1]3)=[C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:14]2=[O:21])=[CH:23]1
Reactant: CCOC(=O)C1=C(N2CCc3ccccc3C2)OCC1=O
Reactant: O=Cc1c[nH]c2ncccc12
Agent: O=C(O)[C@@H]1CCCN1
Solvent: CCO
Product: CCOC(=O)C1=C(N2CCc3ccccc3C2)OC(=Cc2c[nH]c3ncccc23)C1=O
Temperature: 25 °C
Yield: 14.8 %

Procedure:
To a solution of ethyl 2-(3,4-dihydroisoquinolin-2(1H)-yl)-4-oxo-4,5-dihydrofuran-3-carboxylate (0.15 g, 0.60 mmol) which similarly prepared according to the procedure described in the Example 4, First step and 7-azaindole-3-carboxaldehyde (0.091 g, 0.60 mmol) in ethanol (5.0 mL), L-proline (0.0070 g, 0.060 mmol) was added at ambient temperature. The mixture was refluxed for 3 days. Cooled to ambient temperature, the precipitate was collected by filtration, washed with methanol then dried to afford the titled compound as solid (0.037 g, y. 14%).
Reaction SMILES: [C:1]12([C:11]([NH:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]OS(C3C=CC(C)=CC=3)(=O)=O)=[O:12])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[NH:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1>C(#N)C>[N:31]1([CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][NH:13][C:11]([C:1]23[CH2:8][CH:7]4[CH2:6][CH:5]([CH2:4][CH:3]([CH2:9]4)[CH2:2]2)[CH2:10]3)=[O:12])[CH2:35][CH2:34][CH2:33][CH2:32]1
Reactant: Cc1ccc(S(=O)(=O)OCCCCCCNC(=O)C23CC4CC(CC(C4)C2)C3)cc1
Reactant: C1CCNC1
Solvent: CC#N
Product: O=C(NCCCCCCN1CCCC1)C12CC3CC(CC(C3)C1)C2
Temperature: 25 °C
Reaction time: 20 h
Yield: 100 %

Procedure:
To an ice-cooled solution of the product from step b in acetonitrile (25 ml) was added pyrrolidine (6.41 ml, 76.8 mmol). The coolant was removed and the reaction mixture was stirred at ambient temperature for 20 h. The mixture was partitioned between ethyl acetate (100 ml) and water (100 ml). The aqueous phase was discarded and the organic phase extracted with aqueous 2M hydrochloric acid (100 ml). The organic phase was discarded and the aqueous phase was washed with further ethyl acetate (50 ml). The pH of the aqueous phase was adjusted to pH 11 and then extracted twice with chloroform (100 ml). The combined organic phases were washed with brine (100 ml) and dried over anhydrous magnesium sulfate. The filtrate was evaporated at reduced pressure to afford the title compound (4.34 g, 100%). 1H NMR 5.54 (1H, br s), 3.26-3.20 (2H, m), 2.50-2.40 (6H, m), 2.05 (3H, s), 1.85-1.73 (14H, m), 1.52-1.50 (4H, m), 1.36-1.33 (4H, m).
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][CH2:15][CH2:16][NH:17][CH:18]1[CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:19]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.CC(C)([O-])C.[K+].CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C>C1(C)C=CC=CC=1.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][CH2:15][CH2:16][N:17]([CH:18]1[CH2:19][C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:26]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: c1ccc(CN2CCCCC2CCCNC2Cc3ccccc3C2)cc1
Reactant: Brc1ccccc1
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: CN(C)c1ccccc1-c1ccccc1P(C1CCCCC1)C1CCCCC1
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: c1ccc(CN2CCCCC2CCCN(c2ccccc2)C2Cc3ccccc3C2)cc1
Temperature: 110 °C

Procedure:
To a stirred solution of compound 24 (400 mg, 1.15 mmol) in dry toluene (12 mL) was added bromo-benzene (0.12 mL, 1.15 mmol) and potassium tertiary butoxide (322 mg, 2.87 mmol). The reaction mixture was purged with nitrogen for 30 minutes. Finally, DavePhos (90 mg, 0.23 mmol) and Pd2(dba)3 (136 mg, 0.15 mmol) were added and the reaction mixture was heated to 110° C. for 16 hour. Thin layer chromatography (TLC) showed that the reaction was completed. The reaction mixture was then diluted with ethyl acetate, washed with water and brine, dried over Na2SO4 and concentrated. The crude reaction mixture was purified by 230-400 silica gel column chromatography using 5-20% EtOAc-hexane as eluent yield compound 25.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][C:4]=1[C:13]1[C:18]([CH3:19])=[N:17][NH:16][C:15](=O)[CH:14]=1.C(=O)(O)[O-].[Na+].P(Cl)(Cl)([Cl:28])=O>>[Cl:28][C:15]1[N:16]=[N:17][C:18]([CH3:19])=[C:13]([C:4]2[CH:5]=[C:6]([C:9]([F:12])([F:11])[F:10])[CH:7]=[CH:8][C:3]=2[O:2][CH3:1])[CH:14]=1
Reactant: COc1ccc(C(F)(F)F)cc1-c1cc(=O)[nH]nc1C
Reactant: O=P(Cl)(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Product: COc1ccc(C(F)(F)F)cc1-c1cc(Cl)nnc1C
Temperature: 0 °C

Procedure:
5-[2-Methoxy-5-(trifluoromethyl)phenyl]-6-methylpyridazin-3(2H)-one (Preparation 41, 1.1 g, 39 mmol) and phosphorus oxychloride (20 mL) were heated to 100° C. for 3 hours. The reaction mixture was then cooled to 0° C. and poured onto ice before being neutralised with sodium bicarbonate. The mixture was extracted with dichloromethane (3×100 mL) and the combined organic layer washed with water (50 mL) then saturated aqueous sodium chloride solution (50 mL). The organics were dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by silica gel column chromatography (20% ethyl acetate in heptane elution) to afford the title compound as an off-white solid (900 mg).
Reaction SMILES: [H-].[Na+].[NH2:3][C:4]1[C:9]([C:10]([O:12]CC)=O)=[CH:8][N:7]=[C:6]([S:15][CH3:16])[N:5]=1.[Cl:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[N:24]=[C:25]=[O:26]>CN(C)C=O.[Cl-].[Na+].O.O>[Cl:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[N:24]1[C:10](=[O:12])[C:9]2[C:4](=[N:5][C:6]([S:15][CH3:16])=[N:7][CH:8]=2)[NH:3][C:25]1=[O:26]
Reactant: O=C=Nc1ccccc1Cl
Reactant: CCOC(=O)c1cnc(SC)nc1N
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CSc1ncc2c(=O)n(-c3ccccc3Cl)c(=O)[nH]c2n1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
NaH (5.26 g, 131 mmol) was added to a solution of ethyl 4-amino-2-(methylthio)pyrimidine-5-carboxylate (20.0 g, 94 mmol, US 2005/0020590) in N,N-dimethylformamide (700 mL) at 0° C. After 10 minutes, 1-chloro-2-isocyanatobenzene (15.9 mL, 131 mmol) was added dropwise to the mixture. The reaction was warmed to room temperature and stirred for 6 hours. The reaction mixture was diluted with brine (200 mL) and water (1000 mL) and extracted with ether (700 mL 2×). The aqueous layer was acidified with 5% citric acid (until pH=4-5), treated with brine, and extracted with ethyl acetate (2×). The combined organic layers were washed with water (2×), dried over MgSO4, filtered, and concentrated to remove most of the solvent. The mixture was filtered, and the solid was washed with cold ethyl acetate, and oven dried to provide the title compound.
Reaction SMILES: [CH3:1][C:2]1[C:8](=[O:9])[NH:7][C:5](=O)[N:4]([C@@H:10]2[O:14][C@H:13]([CH2:15][OH:16])[C@@H:12]([OH:17])[C@H:11]2O)[CH:3]=1.C(=O)(OC1C=CC=CC=1)OC1C=CC=CC=1.C(OCC)C>CN(C=O)C.CO.C(=O)(O)[O-].[Na+]>[CH3:1][C:2]1[C:8](=[O:9])[N:7]=[C:5]2[N:4]([C@@H:10]3[O:14][C@H:13]([CH2:15][OH:16])[C@H:12]([O:17]2)[CH2:11]3)[CH:3]=1
Reactant: Cc1cn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c(=O)[nH]c1=O
Agent: O=C(Oc1ccccc1)Oc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOCC
Solvent: CN(C)C=O
Solvent: CO
Product: Cc1cn2c(nc1=O)O[C@@H]1C[C@H]2O[C@@H]1CO
Temperature: 150 °C
Yield: 101.4 %

Procedure:
A 100 mL round bottom flask equipped with magnetic stir bar, reflux condensor, and nitrogen inlet was charged with 5 g of ribothymidine, 4.7 g (1.2 eq) of diphenyl carbonate and 150 mg of sodium bicarbonate in 10 mL of DMF. The mixture was heated to 150° C. for 35 minutes. The black solution was diluted with 10 mL of MeOH and slowly added to 200 mL of diethyl ether. The tan product was filtered and dried to yield 4.4 g (96%) of anhydrothymidine.
Reaction SMILES: FC(F)(F)C(O)=O.[F:8][C:9]1[CH:14]=[C:13]([N:15]2[CH:19]=[N:18][N:17]=[N:16]2)[CH:12]=[CH:11][C:10]=1[C:20]1[CH:21]=[CH:22][C:23]2[O:27][C:26]([CH:28]3[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)=[N:25][C:24]=2[CH:34]=1.[C:35](O)(=[O:39])[CH:36]([CH3:38])[CH3:37].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.CCOC(C)=O.O>[F:8][C:9]1[CH:14]=[C:13]([N:15]2[CH:19]=[N:18][N:17]=[N:16]2)[CH:12]=[CH:11][C:10]=1[C:20]1[CH:21]=[CH:22][C:23]2[O:27][C:26]([CH:28]3[CH2:29][CH2:30][N:31]([C:35](=[O:39])[CH:36]([CH3:38])[CH3:37])[CH2:32][CH2:33]3)=[N:25][C:24]=2[CH:34]=1
Reactant: Fc1cc(-n2cnnn2)ccc1-c1ccc2oc(C3CCNCC3)nc2c1
Reactant: CC(C)C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOC(C)=O
Product: CC(C)C(=O)N1CCC(c2nc3cc(-c4ccc(-n5cnnn5)cc4F)ccc3o2)CC1
Yield: 21.9 %

Procedure:
Tert-butyl 4-{5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate (100 mg, 0.22 mmol) dissolved in DCM (25 ml) and added trifluoroacetic acid (0.4 ml). This mixture stirred at rt for 3 h. After completion of the reaction, DCM removed on rotavapour and residue was co-distilled with ether to obtain 5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate (100 mg). 5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate (100 mg, 0.21 mmol) was dissolved in DMF (3 ml) and added isobutyric acid (202 mg, 0.23 mmol), EDC.HCl (99 mg, 0.52 mmol), HOBt (33 mg, 0.25 mmol) and TEA (0.23 ml, 1.7 mmol). After completion of the reaction, work up (EtOAc/H2O) followed by purification on combiflash using the gradient mixture of EtOAc and Petether (65:35) as eluent afforded the titled compound (20 mg) as a brown solid. M.P.: 190-194° C. 1H-NMR (δ ppm, CDCl3, 400 MHz): 9.04 (s, 1H), 7.88 (s, 1H), 7.68 (t, J 8.2, 1H), 7.67-7.59 (m, 2H), 7.52 (td, J 1.6, 8.4, 1H), 4.58 (d, J 12.1, 1H), 4.04 (d, J 13.2, 1H), 3.35-3.22 (m, 2H), 2.96 (t, J 12, 1H), 2.85 (septet, J 6.8, 1H), 2.30-2.18 (m, 2H), 2.05-1.72 (m, 2H), 1.16 (d, J 6.8, 6H).
Reaction SMILES: [O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH2:13][CH2:14][CH2:15][N:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([C:25]([C:27]3[S:28][C:29]([C:38]4[CH:43]=[CH:42][CH:41]=[C:40]([OH:44])[CH:39]=4)=[C:30]([CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH:31]=3)=[O:26])[CH:23]=2)[CH:18]=[C:17]1[C:45]1[CH:60]=[CH:59][C:48]([C:49]([O:51]CC2C=CC=CC=2)=[O:50])=[CH:47][CH:46]=1>CO.CCOC(C)=O.[Pd]>[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH2:13][CH2:14][CH2:15][N:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([C:25]([C:27]3[S:28][C:29]([C:38]4[CH:43]=[CH:42][CH:41]=[C:40]([OH:44])[CH:39]=4)=[C:30]([CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH:31]=3)=[O:26])[CH:23]=2)[CH:18]=[C:17]1[C:45]1[CH:46]=[CH:47][C:48]([C:49]([OH:51])=[O:50])=[CH:59][CH:60]=1
Reactant: CCOC(=O)Cc1cc(C(=O)c2ccc3cc(-c4ccc(C(=O)OCc5ccccc5)cc4)n(CCCCN4C(=O)c5ccccc5C4=O)c3c2)sc1-c1cccc(O)c1
Agent: [Pd]
Solvent: CO
Solvent: CCOC(C)=O
Product: CCOC(=O)Cc1cc(C(=O)c2ccc3cc(-c4ccc(C(=O)O)cc4)n(CCCCN4C(=O)c5ccccc5C4=O)c3c2)sc1-c1cccc(O)c1
Yield: 88 %

Procedure:
A mixture of 6 (50 mg, 0.061 mmol) and 10% Pd—C (20 mg) in MeOH (8 mL) and EtOAc (3 mL) was stirred under 1 atm H2 atmosphere until 6 was no longer detected by TLC. The resulting solution was filtered and concentrated in vacuo to give 7 as a yellow amorphous solid (39 mg, 88%). 1H NMR (400 MHz, CDCl3) δ 8.16 (d, J=8.4 Hz, 2H), 8.06 (s, 1H), 7.77-7.65 (m, 7H), 7.59 (d, J=8.0 Hz, 2H), 7.29 (t, J=8.0 Hz, 2H), 7.11 (s, 1H), 7.03 (d, J=7.6 Hz, 1H), 6.93 (d, J=8.0 Hz, 1H), 6.66 (s, 1H), 4.34 (brt, 2H), 4.15 (q, J=7.2 Hz, 2H), 3.72 (s, 2H), 3.52 (brt, 2H), 1.72-1.65 (m, 2H), 1.51-1.47 (m, 2H), and 1.24 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 188.63, 171.67, 170.53, 168.73, 157.13, 149.52, 143.65, 141.52, 137.98, 137.73, 137.34, 134.34, 134.25, 131.97, 131.89, 131.84, 130.82, 130.56, 130.40, 129.55, 129.37, 123.54, 121.93, 121.17, 120.89, 116.52, 116.44, 112.83, 104.34, 61.59, 43.97, 37.38, 34.90, 27.46, 25.84, and 14.40.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([NH:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:3]=1.[Cl:16][C:17]1[CH:18]=[CH:19][C:20]([N+:27]([O-:29])=[O:28])=[C:21]([CH:26]=1)[C:22](=[O:25])[CH2:23]Br>>[NH2:7][C:6]1[C:5]2[C:4](=[CH:3][C:2]([Cl:1])=[CH:9][CH:8]=2)[N:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:23]=1[C:22](=[O:25])[C:21]1[CH:26]=[C:17]([Cl:16])[CH:18]=[CH:19][C:20]=1[N+:27]([O-:29])=[O:28]
Reactant: O=C(CBr)c1cc(Cl)ccc1[N+](=O)[O-]
Reactant: CCOC(=O)Nc1cc(Cl)ccc1C#N
Product: CCOC(=O)n1c(C(=O)c2cc(Cl)ccc2[N+](=O)[O-])c(N)c2ccc(Cl)cc21

Procedure:
The title compound was prepared according to the procedure described in step 2 of Example 1 from 4-chloro-2-(ethoxycarbonylamino)benzonitrile (Example 1, step 1) and 5-chloro-2-nitrophenacyl bromide (Schofield, K.; and Simpson, J. C. E.; J. Chem. Soc., 1947, 1170-1174.). 1H-NMR (CDCl3) δ: 8.12 (1 H, d, J=1.8 Hz), 7.95 (1 H, d, J=8.4 Hz), 7.56-7.48 (3 H, m), 7.31 (1 H, dd, J=1.6, 8.4 Hz), 6.32 (2 H, br s), 3.99 (2 H, q, J=7.1 Hz), 1.09 (3 H, t, J=7.1 Hz).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[S:6]([NH:9][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]2[C:18]=1[NH:17][C:16]([C:19]([OH:21])=O)=[CH:15]2)(=[O:8])=[O:7].[NH2:22][C:23]1[S:24][CH:25]=[CH:26][N:27]=1.C(N(C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(OCC)(=O)C.CN(C)C=O>[S:24]1[CH:25]=[CH:26][N:27]=[C:23]1[NH:22][C:19]([C:16]1[NH:17][C:18]2[C:14]([CH:15]=1)=[CH:13][CH:12]=[CH:11][C:10]=2[NH:9][S:6]([C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)(=[O:7])=[O:8])=[O:21]
Reactant: Nc1nccs1
Reactant: O=C(O)c1cc2cccc(NS(=O)(=O)c3cccs3)c2[nH]1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: O=C(Nc1nccs1)c1cc2cccc(NS(=O)(=O)c3cccs3)c2[nH]1
Temperature: 60 °C
Reaction time: 18 h
Yield: 78.5 %

Procedure:
A mixture of 7-[(2-thienylsulfonyl)amino]-1H-indole-2-carboxylic acid (200 mg), 2-aminothiazole (75 mg), ethyldiisopropylamine (0.16 mL), 0-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (354 mg) and N,N-dimethylformamide (8 mL) was stirred at 60° C. for 18 hr. The reaction mixture was diluted with ethyl acetate, washed with aqueous citric acid solution, aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography (ethyl acetate), and the obtained crystals were washed with ethyl acetate-hexane to give the title compound (197 mg, yield 78%) as pale-yellow crystals. melting point 300-302° C. (decomposition).
Reaction SMILES: [CH:1]1[CH:6]=[CH:5][C:4]([CH2:7][CH:8]([OH:12])[C:9]([OH:11])=[O:10])=[CH:3][CH:2]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH2:19](Br)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CN(C=O)C.CCOC(C)=O>[CH2:19]([O:10][C:9](=[O:11])[CH:8]([OH:12])[CH2:7][C:4]1[CH:3]=[CH:2][CH:1]=[CH:6][CH:5]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: O=C(O)C(O)Cc1ccccc1
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=C(OCc1ccccc1)C(O)Cc1ccccc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 93.4 %

Procedure:
To a solution of DL-Phenyllactic acid (5.0 g, 30.09 mmol) in DMF (30 mL) was added Cs2CO3 (10.79 g, 33.11 mmol) in portions during 10 minutes period at room temperature. The resulting mixture was stirred for 15 min at room temperature, followed by the addition of benzyl bromide (3.57 mL, 30.09 mmol). The resulting mixture was stirred at room temperature overnight. The reaction mixture was diluted with EtOAc (300 mL), washed with saturated NaHCO3, water (100×2) and brine, dried (Na2SO4) and filtered. The filtrate was concentrated to give 7.20 g (89%) of the title compound.
Reaction SMILES: [CH2:1]1[CH:5]2[CH:6]3[CH:10]=[CH:9][CH:8]([CH:4]2[CH:3]=[CH:2]1)[CH2:7]3.[Br:11][C:12]([F:19])([F:18])[C:13]([F:17])([F:16])[CH:14]=[CH2:15]>C1(C)C=CC=CC=1.COC1C=CC(O)=CC=1>[Br:11][C:12]([F:19])([F:18])[C:13]([F:17])([F:16])[CH:14]1[CH2:15][CH:1]2[CH2:2][CH:3]1[CH:4]1[CH:5]2[CH:6]2[CH2:7][CH:8]1[CH:9]=[CH:10]2
Reactant: C=CC(F)(F)C(F)(F)Br
Reactant: C1=CC2C3C=CC(C3)C2C1
Agent: COc1ccc(O)cc1
Solvent: Cc1ccccc1
Product: FC(F)(Br)C(F)(F)C1CC2CC1C1C3C=CC(C3)C21
Temperature: 170 °C
Reaction time: 5 h
Yield: 81.2 %

Procedure:
An autoclave was charged with 108.5 g of dicyclopentadiene and 322.4 g of 1-bromo-1,1,2,2-tetrafluoro-3-butene. A solution of 0.3 g of 4-methoxyphenol dissolved in 5 ml of toluene was added to the autoclave as a polymerization inhibitor and the mixture was stirred for 5 hours at 170° C. The reaction product was purified by distillation under reduced pressure at 85° C. and 0.1 mmHg to obtain 226 g of 1-bromo-1,1,2,2-tetrafluoro-2-(tetracyclo[4.4.0.12,5.17,10]dodec-3-en-8-yl)ethane as a clear liquid (hereinafter referred to as “compound (5-a)”).