Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: FC(F)(F)C1C=C(C=CC=1)O[C:7]([O:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=1)=[CH:8][CH:9]=O.[F:27][C:28]([F:39])([F:38])[C:29]1[CH:37]=[CH:36][C:32]([C:33]([NH2:35])=[NH:34])=[CH:31][CH:30]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[F:21][C:18]([F:19])([F:20])[C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][CH:15]=1)[O:11][C:7]1[CH:8]=[CH:9][N:35]=[C:33]([C:32]2[CH:31]=[CH:30][C:29]([C:28]([F:27])([F:38])[F:39])=[CH:37][CH:36]=2)[N:34]=1
Reactant: O=CC=C(Oc1cccc(C(F)(F)F)c1)Oc1cccc(C(F)(F)F)c1
Reactant: N=C(N)c1ccc(C(F)(F)F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: FC(F)(F)c1ccc(-c2nccc(Oc3cccc(C(F)(F)F)c3)n2)cc1
Temperature: 80 °C
Reaction time: 4 h
Yield: 79.6 %

Procedure:
A mixture of 3,3-bis-(3-trifluoromethylphenoxy)-acrolein (10 mmoles), 4-trifluoromethylbenzamidine (10 mmoles), potassium carbonate (10 mmoles) and acetonitril (100 ml), is stirred at 80° C. for four hours. The reaction mixture is cooled down to ambient temperature and filtered through silica. The organic phase is washed with ethyl acetate and concentrated in vacuo. The residue is purified by chromatography on Al2O3 (petrol ethers/ethyl acetate: 2/1) to yield 3.06 g (80%) of the pure product having a melting point of 66° C.
Reaction SMILES: [C:1]([CH2:3][C:4](O)=[O:5])#[N:2].C(Cl)(=O)C(Cl)=O.[CH2:13]([O:15][C:16](=[O:32])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[NH:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)[CH3:14]>ClCCl.CN(C)C=O.O.C(=O)(O)[O-].[Na+]>[CH2:13]([O:15][C:16](=[O:32])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[N:23]([C:4](=[O:5])[CH2:3][C:1]#[N:2])[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)[CH3:14]
Reactant: N#CCC(=O)O
Reactant: CCOC(=O)c1ccccc1NCc1ccc(F)cc1
Agent: O=C(Cl)C(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CCOC(=O)c1ccccc1N(Cc1ccc(F)cc1)C(=O)CC#N
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a stirred mixture of commercially available cyanoacetic acid (1 eq, 0.170 g, 2.0 mmole) in dichloromethane was added oxalylchloride (0.253 g, 2.0 mmole, 0.169 mL) and 2 drops dimethylformamide. The reaction was stirred for 2 hours at RT until homogenous solution developed. 2-(4-Fluoro-benzylamino)-benzoic acid ethyl ester (1 eq, 0.500 g, 1.82 mmole) was added and the resulting solution, was allowed to stir at RT overnight. Reaction mixture was diluted with saturated sodium bicarbonate water (20 mL) and extracted with ethyl acetate (25 mL×3). Combined organic phase was washed consecutively with water, brine before drying over sodium sulfate. Organic phase was evaporated and the residue was purified by flash chromatography to afford 2-[(2-Cyano-acetyl)-(4-fluoro-benzyl)-amino]-benzoic acid ethyl ester as an off white solid (0.423 g, 68%, LCMS calc M+H 341, obs M+H 341).
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[O:3]1.N(/C(OC(C)C)=O)=N\C(OC(C)C)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[CH2:49][CH2:50][N:51]([CH3:59])[C:52](=[O:58])[O:53][C:54]([CH3:57])([CH3:56])[CH3:55]>C1COCC1>[CH3:59][N:51]([CH2:50][CH2:49][N:12]1[CH:13]=[C:9]([B:4]2[O:5][C:6]([CH3:7])([CH3:8])[C:2]([CH3:14])([CH3:1])[O:3]2)[CH:10]=[N:11]1)[C:52](=[O:58])[O:53][C:54]([CH3:55])([CH3:57])[CH3:56]
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Reactant: CN(CCO)C(=O)OC(C)(C)C
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CN(CCn1cc(B2OC(C)(C)C(C)(C)O2)cn1)C(=O)OC(C)(C)C
Reaction time: 4 h
Yield: 53.5 %

Procedure:
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (5 g, 25.8 mmol), bis(1-methylethyl) (E)-1,2-diazenedicarboxylate (5.73 g, 28.3 mmol), triphenylphosphine (7.43 g, 28.3 mmol) and 1,1-dimethylethyl (2-hydroxyethyl)methylcarbamate (4.52 g, 25.8 mmol) were dissolved in THF at 0° C. under nitrogen and the resulting mixture was stirred at this temperature for 4 h, then evaporated in vacuo and the residue triturated with MTBE. The precipitated solid was removed by filtration and the filtrate evaporated in vacuo, then purified by chromatography on silica gel (gradient:0-100% EtOAc in Hexanes) to give 1,1-dimethylethyl methyl{2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]ethyl}carbamate (4.85 g, 13.81 mmol, 53.6% yield) as a colourless oil.
Reaction SMILES: FC(F)(F)C(O)=O.[CH3:8][N:9]([CH3:38])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[NH:16][C:17]1[CH:29]=[C:28]([CH2:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:27]=[CH:26][C:18]=1[C:19]([O:21]C(C)(C)C)=[O:20]>>[CH3:38][N:9]([CH3:8])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[NH:16][C:17]1[CH:29]=[C:28]([CH2:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:27]=[CH:26][C:18]=1[C:19]([OH:21])=[O:20]
Reactant: CN(C)c1ccccc1Nc1cc(CCc2ccccc2)ccc1C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Product: CN(C)c1ccccc1Nc1cc(CCc2ccccc2)ccc1C(=O)O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Trifluoroacetic acid 5.0 mL was added to the obtained tert-butyl 2-((2-(dimethylamino)phenyl)amino)-4-phenethylbenzoate, and it was stirred at room temperature for 3 hours. The solvent was removed under reduced pressure, the obtained residue was refined by reversed-phase silica gel column chromatography [eluent; 50-85% acetonitrile/0.1% trifluoroacetic acid aqueous solution], and ethyl acetate, water and saturated sodium hydrogen carbonate aqueous solution were added to it, and it was adjusted to pH6.5. The organic layer was separated and collected,dried over anhydrous magnesium sulfate after washing with saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. Hexane was added to the obtained residue, and solid matter was filtrated to give 2-((2-(dimethylamino)phenyl)amino)-4-phenethylbenzoic acid 7.0 mg of a yellow solid.
Reaction SMILES: S(Cl)(Cl)(=O)=O.[CH:6]([C:9]1[CH:14]=[C:13]([CH:15]([CH3:17])[CH3:16])[CH:12]=[CH:11][C:10]=1[SH:18])([CH3:8])[CH3:7].[Cl:19][C:20]1[CH:25]=[C:24]([S:26]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])(=[O:28])=[O:27])[CH:23]=[CH:22][C:21]=1[N:41]([C:45]1[CH2:49][C:48](=[O:50])[N:47]([C:51]2[C:56]([Cl:57])=[CH:55][C:54]([Cl:58])=[CH:53][C:52]=2[Cl:59])[N:46]=1)[C:42](=[O:44])[CH3:43].Cl>ClCCl.CN(C)C=O>[Cl:19][C:20]1[CH:25]=[C:24]([S:26]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])(=[O:27])=[O:28])[CH:23]=[CH:22][C:21]=1[N:41]([C:45]1[CH:49]([S:18][C:10]2[CH:11]=[CH:12][C:13]([CH:15]([CH3:17])[CH3:16])=[CH:14][C:9]=2[CH:6]([CH3:8])[CH3:7])[C:48](=[O:50])[N:47]([C:51]2[C:56]([Cl:57])=[CH:55][C:54]([Cl:58])=[CH:53][C:52]=2[Cl:59])[N:46]=1)[C:42](=[O:44])[CH3:43]
Reactant: CCCCCCCCCCCCS(=O)(=O)c1ccc(N(C(C)=O)C2=NN(c3c(Cl)cc(Cl)cc3Cl)C(=O)C2)c(Cl)c1
Reactant: CC(C)c1ccc(S)c(C(C)C)c1
Agent: Cl
Solvent: O=S(=O)(Cl)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCS(=O)(=O)c1ccc(N(C(C)=O)C2=NN(c3c(Cl)cc(Cl)cc3Cl)C(=O)C2Sc2ccc(C(C)C)cc2C(C)C)c(Cl)c1
Reaction time: 2 h

Procedure:
Sulfuryl chloride (6.2 g, 46 mmol) was added dropwise to a stirred solution of 2,4-diisopropylthiophenol (8.9 g, 46 mmol) in dichloromethane (50 ml) and stirring was continued at room temperature for 2 hrs. Volatiles were removed by rotary evaporation to give an oil. A solution of N-(2-chloro-4-dodecylsulfonylphenyl)-N-[4,5-dihydro-5-oxo-1-(2,4,6-trichlorophenyl)-1H-pyrazol-3-yl]acetamide (29.0 g, 44 mmol) in N,N-dimethylformamide (75 ml) was added to the oil and the mixture was stirred at room temperature for 26 hrs. The solution was poured into 3N hydrochloric acid (750 ml) and the resulting sticky solid was collected by filtration. The solid was dissolved in ethyl acetate (200 ml) and the organic solution was washed with brine (100 ml), dried (MgSO4) and evaporated to an orange glass. The crude material was purified by column chromatography on 63-200 mesh silica gel eluting with 1:4 ethyl acetate/60-80 petroleum ether. Pure product was obtained as a cream colored glass, 11.7 g, 31%. C41H51Cl4N3O4S2Req: C 57.5%,H 6.0%,Cl 16.6%,N 4.9%,S 7.5%; Fd: C 57.1%,H 6.1%,Cl 16.4%,N 4.8%,S 7.2%
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9]O)=[CH:4][CH:3]=1.[Br:11]C(Br)(Br)Br.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][Br:11])=[CH:4][CH:3]=1
Reactant: OCCc1ccc(Br)cc1
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: BrCCc1ccc(Br)cc1
Reaction time: 1 h
Yield: 157.7 %

Procedure:
To a solution of 2-(4-bromophenyl)ethanol (1.00 g) and tetrabromomethane (3.96 g) in tetrahydrofuran (10 ml) was added triphenylphosphine (2.87 g) at room temperature and the mixture was stirred at the same temperature for 1 hour under nitrogen. The mixture was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to give 1-bromo-4-(2-bromoethyl)benzene (2.07 g).
Reaction SMILES: [OH-].[Na+].[CH:3]([C:6]1([C:12]([O:14][CH3:15])=[O:13])[CH2:10][CH2:9][CH2:8][C:7]1=[O:11])([CH3:5])[CH3:4].[Cl:16][C:17]1[CH:24]=[CH:23][C:20]([CH:21]=O)=[CH:19][CH:18]=1.Cl>O.CO>[Cl:16][C:17]1[CH:24]=[CH:23][C:20]([CH:21]=[C:8]2[CH2:9][CH2:10][C:6]([CH:3]([CH3:5])[CH3:4])([C:12]([O:14][CH3:15])=[O:13])[C:7]2=[O:11])=[CH:19][CH:18]=1
Reactant: O=Cc1ccc(Cl)cc1
Reactant: COC(=O)C1(C(C)C)CCCC1=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: COC(=O)C1(C(C)C)CCC(=Cc2ccc(Cl)cc2)C1=O

Procedure:
To a solution of 4 g of sodium hydroxide in 1000 ml of water were added 21 g of methyl 1-isopropyl-2-oxocylopentanecarboxylate (prepared in Reference Example 2 hereinafter) and a solution of 16 g of 4-chlorobenzaldehyde in 1000 ml of methanol, and the mixture was stirred for 5 hours at room temperature. The reaction mixture was neutralized with diluted hydrochloric acid and the precipitate was collected by filtration. Product 33.6 g (yield, 96.2%)
Reaction SMILES: [NH2:1][C@H:2]1[C:11]([CH3:13])([CH3:12])[C:10]2[CH:9]=[C:8]([C:14]([NH2:16])=[O:15])[CH:7]=[CH:6][C:5]=2[CH2:4][C@@H:3]1[O:17][CH3:18].[CH3:19][C:20]([CH3:30])([CH3:29])[CH2:21][C:22]([NH:24][CH2:25][CH2:26][CH:27]=O)=[O:23].C(O)(C(F)(F)F)=O>>[CH3:19][C:20]([CH3:29])([CH3:30])[CH2:21][C:22]([NH:24][CH2:25][CH2:26][CH2:27][NH:1][C@H:2]1[C:11]([CH3:13])([CH3:12])[C:10]2[CH:9]=[C:8]([C:14]([NH2:16])=[O:15])[CH:7]=[CH:6][C:5]=2[CH2:4][C@@H:3]1[O:17][CH3:18])=[O:23]
Reactant: CC(C)(C)CC(=O)NCCC=O
Reactant: CO[C@H]1Cc2ccc(C(N)=O)cc2C(C)(C)[C@@H]1N
Solvent: O=C(O)C(F)(F)F
Product: CO[C@H]1Cc2ccc(C(N)=O)cc2C(C)(C)[C@@H]1NCCCNC(=O)CC(C)(C)C

Procedure:
Following the process of Example 11(c) using (6S,7S)-7-amino-6-methoxy-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid amide and 3,3-dimethyl-N-(3-oxo-propyl)-butyramide the TFA salt of the title compound was prepared. (m/z): [M+H]+ calcd for C23H37N3O3, 404.28; found, 404.4.
Reaction SMILES: C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.FC(F)(F)S([O:24][C:25]1[CH:38]=[CH:37][C:28]2[C@H:29]([CH2:32][C:33]([O:35]C)=[O:34])[CH2:30][O:31][C:27]=2[CH:26]=1)(=O)=O.[CH3:41][C:42]1[CH:47]=[C:46]([O:48][CH2:49][CH2:50][CH2:51][S:52]([CH3:55])(=[O:54])=[O:53])[CH:45]=[C:44]([CH3:56])[C:43]=1[C:57]1[CH:62]=[CH:61][CH:60]=[C:59]([CH2:63]O)[CH:58]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.COCCOC.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]>[CH3:56][C:44]1[CH:45]=[C:46]([O:48][CH2:49][CH2:50][CH2:51][S:52]([CH3:55])(=[O:53])=[O:54])[CH:47]=[C:42]([CH3:41])[C:43]=1[C:57]1[CH:62]=[CH:61][CH:60]=[C:59]([CH2:63][O:24][C:25]2[CH:38]=[CH:37][C:28]3[C:29]([CH2:32][C:33]([OH:35])=[O:34])=[CH:30][O:31][C:27]=3[CH:26]=2)[CH:58]=1
Reactant: COC(=O)C[C@@H]1COc2cc(OS(=O)(=O)C(F)(F)F)ccc21
Reactant: Cc1cc(OCCCS(C)(=O)=O)cc(C)c1-c1cccc(CO)c1
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: O=C(C=Cc1ccccc1)C=Cc1ccccc1
Solvent: COCCOC
Solvent: Cc1ccccc1
Product: Cc1cc(OCCCS(C)(=O)=O)cc(C)c1-c1cccc(COc2ccc3c(CC(=O)O)coc3c2)c1
Temperature: 25 °C
Reaction time: 6 h
Yield: 53.2 %

Procedure:
A solution of tris(dibenzylideneacetone)dipalladium (0). dibenzylideneacetone solvate (42.5 mg) and 2-(dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl) (76.18 mg) in toluene (4 ml) and 1,2-dimethoxyethane (4 ml) was stirred at 70° C. for 1 hr. After allowing to cool to room temperature, methyl(S)-2-(6-(((trifluoromethyl)sulfonyl)oxy)-2,3-dihydrobenzofuran-3-yl)acetate (864.3 mg), (2′,6′-dimethyl-4′-(3-(methylsulfonyl)propoxy)-[1,1′-biphenyl]-3-yl)methanol (1.15 g) and cesium carbonate (2.60 g) were added, and the mixture was stirred at 85° C. for 6 hr. The mixture was allowed to cool to room temperature and concentrated, toluene (30 mL) and water (30 mL) were added, and an extraction operation was performed. The organic layer was washed with water (30 mL) and 10% brine (30 mL), and concentrated. The obtained oil was dissolved in dimethyl sulfoxide (15 mL), and 2N sodium hydroxide (4 mL) was added at room temperature. The mixture was stirred at 70° C. for 1 hr, and allowed to cool to room temperature. Ethyl acetate (30 mL) and water (30 mL) were added, and the mixture was partitioned. The aqueous layer was acidified with 6N hydrochloric acid to pH 1, ethyl acetate (30 mL) was added, and an extraction operation was performed. The organic layer was washed with water (30 mL), and concentrated. The crude product was recrystallized from acetone (15 mL)-water (30 mL), and the obtained solid was dried at 60° C. under reduced pressure to give the title compound (706 mg) as white crystals. Yield 53%.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:8])=[CH:6][CH:7]=1.[Br:9]Br>[Fe]>[Br:9][C:3]1[CH:4]=[C:5]([CH3:8])[CH:6]=[CH:7][C:2]=1[CH3:1]
Reactant: BrBr
Reactant: Cc1ccc(C)cc1
Agent: [Fe]
Product: Cc1ccc(C)c(Br)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
p-Xylene (934.4 g; 8.8 mol) and Fe powder (16 g) were placed in the reaction vessel and about 20 ml of bromine were slowly added dropwise. The commencement of the reaction (after about 10 minutes) could be recognized by gas evolution. After the reaction had begun, the remaining bromine (total: 1278.4 g; 8.0 mol) was added dropwise at RT, with water bath cooling (4 hours). The mixture was stirred further for 2 hours at RT. The slightly brownish reaction solution was filtered off and stirred first with water, and then with 480 ml of saturated aqueous Na2SO3 solution, subsequently shaken once with dilute aqueous NaOH and twice with H2O; the organic phase (clear and colorless) was dried over MgSO4, filtered and purified by being vacuum-distilled twice (diaphragm pump/oil bath, about 100-120° C./60 cm column).
Reaction SMILES: [CH3:1][C:2]([Si:5]([CH3:30])([CH3:29])[O:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[CH:16][C:15]=2[F:22])=[C:10]([CH:23](O)[C:24]([CH3:27])([CH3:26])[CH3:25])[CH:9]=1)([CH3:4])[CH3:3].CS([Cl:35])(=O)=O>C(Cl)Cl.O>[Cl:35][CH:23]([C:10]1[CH:9]=[C:8]([CH2:7][O:6][Si:5]([C:2]([CH3:4])([CH3:3])[CH3:1])([CH3:30])[CH3:29])[CH:13]=[CH:12][C:11]=1[C:14]1[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[CH:16][C:15]=1[F:22])[C:24]([CH3:27])([CH3:26])[CH3:25]
Reactant: CS(=O)(=O)Cl
Reactant: COc1ccc(F)c(-c2ccc(CO[Si](C)(C)C(C)(C)C)cc2C(O)C(C)(C)C)c1
Solvent: O
Solvent: ClCCl
Product: COc1ccc(F)c(-c2ccc(CO[Si](C)(C)C(C)(C)C)cc2C(Cl)C(C)(C)C)c1
Reaction time: 22 h
Yield: 43.4 %

Procedure:
To a stirred solution of 69.16A (0.200 g, 0.46 mmol) in DCM (5.00 mL) at 0° C. was added TEA (0.077 mL, 0.55 mmol), followed by methanesulfonyl chloride (0.043 mL, 0.55 mmol). The reaction was then stirred for 22 hours, diluted with water, and extracted three times with EtOAc. After drying over anhydrous magnesium sulfate and filtering, the organic solvent was removed under reduced pressure and the product was purified on silica gel (0-10% EtOAc in hexanes) to yield 69.16B as a colorless oil (0.090 g, 43% yield) and a further product 69.16C as a clear oil (0.050 g, 21% yield).
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.CC1(C)C(C)(C)OB([C:20]2[CH:21]=[CH:22][C:23]([C:26]#[N:27])=[N:24][CH:25]=2)O1>>[N:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH:10]=[CH:11][C:2]=1[C:20]1[CH:21]=[CH:22][C:23]([C:26]#[N:27])=[N:24][CH:25]=1
Reactant: Clc1ccc2ccccc2n1
Reactant: CC1(C)OB(c2ccc(C#N)nc2)OC1(C)C
Product: N#Cc1ccc(-c2ccc3ccccc3n2)cn1
Yield: 2.6 %

Procedure:
A from 2-chloroquinoline (82 mg, 0.5 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinonitrile (115 mg, 0.5 mmol). The product was obtained as yellow solid (3 mg, 3%). 1H NMR (400 MHz, CDCl3): δ 9.48 (dd, J=2.4, 0.8 Hz, 1H), 8.69 (dd, J=8.0, 2.0 Hz, 1H), 8.33 (d, J=8.8 Hz, 1H), 8.19 (d, J=8.4 Hz, 1H), 7.93 (d, J=8.4 Hz, 1H), 7.90 (dd, J=8.4, 1.2 Hz, 1H), 7.87 (dd, J=8.4, 0.8 Hz, 1H), 7.81 (m, 1H), 7.63 (m, 1H); MS (ESI):232 (M+H+).
Reaction SMILES: [H-].[Na+].[C:3]([NH:6][C:7]1[C:8]2[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[C:9]=2[O:10][C:11]=1[CH3:12])(=[O:5])[CH3:4].I[CH2:21][CH3:22].O>CN(C)C=O>[C:3]([N:6]([C:7]1[C:8]2[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[C:9]=2[O:10][C:11]=1[CH3:12])[CH2:21][CH3:22])(=[O:5])[CH3:4]
Reactant: CC(=O)Nc1c(C)oc2c([N+](=O)[O-])cccc12
Reactant: CCI
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCN(C(C)=O)c1c(C)oc2c([N+](=O)[O-])cccc12
Reaction time: 0.5 h
Yield: 98.9 %

Procedure:
Sodium hydride (60%, 54 mg) was added to a solution of 3-acetylamino-2-methyl-7-nitrobenzo[b]furan (280 mg) in N,N-dimethylformamide (3 ml) at 4° C. The mixture was stirred for 30 minutes and to the mixture was added iodoethane (240 mg). The mixture was stirred at ambient temperature for 2 hours. The reaction mixture was poured into cold water and the separated oil was extracted with ethyl acetate. The extract was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel to give 3-(N-acetyl-N-ethylamino)-2-methyl-7-nitrobenzo[b]furan as a crystalline solid (310 mg).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[H-].[Na+].[CH2:10]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH2:23][CH:22]([CH2:26]I)[CH2:21]1)=[O:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>CN(C=O)C>[CH2:10]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH2:23][CH:22]([CH2:26][N:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]2=[O:1])[CH2:21]1)=[O:19])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: O=C(OCc1ccccc1)N1CCCC(CI)C1
Reactant: Oc1ccccn1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C(OCc1ccccc1)N1CCCC(Cn2ccccc2=O)C1
Temperature: 80 °C
Reaction time: 2 h
Yield: 72.8 %

Procedure:
To a stirred solution of 2-hydroxypyridine (200 mg, 2 mmol) in DMF (5 mL) was added NaH (60% mixture in mineral oil, 100 mg, 2.5 mmol). The mixture was stirred at 80° C. under N2 for 2 h, and then 3-iodomethylpiperidine-1-carboxylic acid benzyl ester (720 mg, 2 mmol) was added. The mixture was stirred at 80° C. for 10 h, cooled to room temperature, quenched with water, and extracted with EtOAc. The combined organic layers were washed with brine, dried, and concentrated. The residue was purified by chromatography with CH2Cl2-EtOAc-MeOH (10:10:1) to give a viscous oil (475 mg, 73%). 1H NMR (CDCl3) δ 7.30 (m, 7H), 6.55 (d, 1H, J=9.0 Hz), 6.12 (m, 1H), 5.11 (s, 2H), 4.10-3.50 (m, 4H), 3.09 (t, 1H, J=10.2 Hz), 2.92 (dd, 1H, J=13.2, 9.0 Hz), 2.10 (m, 1H), 1.85-1.20 (m, 4H).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][C:10](=[O:13])[CH2:9]2)=[CH:4][CH:3]=1.CO.[BH4-].[Na+]>C(Cl)Cl.O>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][CH:10]([OH:13])[CH2:9]2)=[CH:4][CH:3]=1
Reactant: O=C1CCC(c2ccc(Cl)nc2)C1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Solvent: O
Product: OC1CCC(c2ccc(Cl)nc2)C1
Temperature: 25 °C
Yield: 101.2 %

Procedure:
3-(6-Chloropyridin-3-yl)cyclopentanone (0.27 g, 1.4 mmol) was dissolved in CH2Cl2 (10 mL) and MeOH (1 mL) in a 100 mL round bottomed flask and treated with NaBH4 (0.05 g, 1.4 mmol) with stirring at room temperature. After 15 min. the reaction was diluted with water, the layers separated, the aqueous phase extracted with CH2Cl2, and the combined organic layers dried (Na2SO4), filtered and concentrated to give 3-(6-chloropyridin-3-yl)cyclopentanol (0.28 g, 100%) as an oily mixture of cis and trans isomers: LC/MS (ESI) m/z 197, 1H NMR (300 MHz, CDCl3) δ 8.27 (m, 2H), 7.65-7.48 (m, 2H), 7.26 (m, 2H), 4.52 (m, 2H), 3.49-2.99 (m, 2H), 2.51-2.01 (m, 4H), 1.99-1.40 m, 10H).
Reaction SMILES: [Br:1][C:2]1[S:6][C:5]([C@:7]2([CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[S:13](=[O:15])(=[O:14])[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)=[CH:4][CH:3]=1.[C@@]12(CS([O-])(=O)=O)C(C)(C)C(CC1)CC2=O.[CH3:39][N:40]([CH3:45])[S:41](Cl)(=[O:43])=[O:42].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1>[Br:1][C:2]1[S:6][C:5]([C@:7]2([CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[S:13](=[O:15])(=[O:14])[CH2:12][CH2:11][N:10]([S:41]([N:40]([CH3:45])[CH3:39])(=[O:43])=[O:42])[CH2:9][CH2:8]2)=[CH:4][CH:3]=1
Reactant: CN(C)S(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)C[C@]1(c2ccc(Br)s2)CCNCCS1(=O)=O
Agent: CC1(C)C2CC[C@]1(CS(=O)(=O)[O-])C(=O)C2
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Product: CN(C)S(=O)(=O)N1CC[C@](CC(=O)OC(C)(C)C)(c2ccc(Br)s2)S(=O)(=O)CC1
Temperature: 25 °C
Reaction time: 60 h
Yield: 89.4 %

Procedure:
A mixture of tert-butyl 2-[(S)-7-(5-bromo-2-thienyl)-1,1-dioxoperhydro-1,4-thiazepin-7-yl]acetate•(1R)-10 -camphorsulfonate (2.00 g), dimethylaminosulfonyl chloride (569 mg) and 2M aqueous sodium carbonate (10.6 ml) in dioxane (40 ml) was stirred for 2.5 days at room temperature. After the reaction solution was concentrated in vacuo, the mixture was diluted with water. The obtained suspension was stirred for 30 minutes under ice-cooling. The resulting solid was collected, washed with water and dried in vacuo to give tert-butyl 2-[(S)-7-(5-bromo-2-thienyl)-4-dimethylaminosulfonyl-1,1-dioxoperhydro-1,4-thiazepin-7-yl]acetate (1.449 g) as a white solid.
Reaction SMILES: [NH2:1][C:2]1[CH:47]=[CH:46][C:5]([CH2:6][C:7]2[N:12]3[CH:13]=[C:14]([C:16]4[C:24]5[C:19](=[N:20][CH:21]=[CH:22][CH:23]=5)[N:18](S(C5C=CC=CC=5)(=O)=O)[CH:17]=4)[CH:15]=[C:11]3[C:10](=[O:34])[N:9]([CH2:35][C:36]3[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][C:37]=3[O:44][CH3:45])[CH:8]=2)=[CH:4][CH:3]=1.[OH-].[Na+]>O1CCOCC1>[NH2:1][C:2]1[CH:47]=[CH:46][C:5]([CH2:6][C:7]2[N:12]3[CH:13]=[C:14]([C:16]4[C:24]5[C:19](=[N:20][CH:21]=[CH:22][CH:23]=5)[NH:18][CH:17]=4)[CH:15]=[C:11]3[C:10](=[O:34])[N:9]([CH2:35][C:36]3[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][C:37]=3[O:44][CH3:45])[CH:8]=2)=[CH:4][CH:3]=1
Reactant: COc1ccc(Cn2cc(Cc3ccc(N)cc3)n3cc(-c4cn(S(=O)(=O)c5ccccc5)c5ncccc45)cc3c2=O)c(OC)c1
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: COc1ccc(Cn2cc(Cc3ccc(N)cc3)n3cc(-c4c[nH]c5ncccc45)cc3c2=O)c(OC)c1

Procedure:
A mixture of EXAMPLE 23I (1.7 g, 2.63 mmol) in dioxane (150 ml) was heated with NaOH (0.53 g, 13.2 mmol) at 50° C. for 4 hours. After cooling, the reaction mixture was partitioned between ethyl acetate (300 mL) and brine (200 mL). The organic phase was washed with brine (200 mL), dried over anhydrous Na2SO4, filtered and concentrated. The crude material was purified by flash chromatography (2% methanol in CH2Cl2) to afford the title compound. LC-MS (ESI): m/z 506 (M+H), RT: 1.53 min; 1H NMR (400 MHz, dimethylsulfoxide-d6): δ 3.75 (s, 3H), 3.77 (s, 3H), 3.92 (s, 2H), 4.88 (s, 1H), 4.99 (s, 1H), 6.46 (s, 1H), 6.50 (s, 1H), 6.56 (d, J=8.0 Hz, 3H), 7.07 (d, J=8.4 Hz, 1H), 7.06 (d, J=8 Hz, 2H), 7.14 (d, J=3.2 Hz, 1H), 7.31 (s, 1H), 7.71 (s, 1H), 7.85 (d, J=1.2 Hz, 1H), 8.22 (d, J=8.0 Hz, 1H), 8.26 (d, J=4.8 Hz, 1H), 11.75 (br s, 1H).