Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:10]2[N:9]([CH2:11][C:12](OCC)=[O:13])[C:8]3[CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:20][CH2:21][C:7]=3[C:6]=2[C:5]([Cl:29])=[CH:4][CH:3]=1.[Li+].[BH4-].[OH-].[Na+].CCOC(C)=O>C1COCC1.O>[Cl:1][C:2]1[C:10]2[N:9]([CH2:11][CH2:12][OH:13])[C:8]3[CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:27])([CH3:26])[CH3:28])=[O:23])[CH2:20][CH2:21][C:7]=3[C:6]=2[C:5]([Cl:29])=[CH:4][CH:3]=1
Reactant: CCOC(=O)Cn1c2c(c3c(Cl)ccc(Cl)c31)CCN(C(=O)OC(C)(C)C)CC2
Agent: [BH4-]
Agent: [Li+]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1CCc2c(n(CCO)c3c(Cl)ccc(Cl)c23)CC1
Temperature: 25 °C
Reaction time: 7 h
Yield: 66.3 %

Procedure:
A solution of tert-butyl 7,10-dichloro-6-(2-ethoxy-2-oxoethyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (3.0 g, 6.8 mmol) in dry THF (30 mL) was cooled to 0° C. Then, LiBH4 (0.74 g, 34 mmol) was added and the reaction was allowed to warm slowly to rt. Additional LiBH4 (0.30 g, 14 mmol) was added after 24 h. After another 7 h, the reaction was diluted with H2O (75 mL) followed by addition of 10% aqueous NaOH and extraction with EtOAc (3×100 mL). The combined organic extracts were washed with brine, dried over Na2SO4, decanted, and concentrated. The crude product was purified by column chromatography (Biotage, 40M, SIM) with heptane/EtOAc (1:1) followed by crystallization from EtOAc/heptane gave 1.8 g (65%) of a white solid: mp 156.0-158.5° C.; IR (diffuse reflectance) 1686, 1652, 1476, 1433, 1414, 1400, 1364, 1353, 1319, 1302, 1229, 1178, 1156, 1063, 972 cm−1; MS (EI) m/z 398 (M+), 398, 342, 270, 268, 263, 258, 256, 212, 57, 56; Anal. Calcd for C19H24Cl2N2O3: C, 57.15; H, 6.06; N, 7.01; found: C, 57.23; H, 6.10; N, 7.00.
Reaction SMILES: C(O[C:4]([C:6]1[C:7]([N:18]([CH:26]2[CH2:28][CH2:27]2)[CH2:19][CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[N:8][C:9]2[C:14]([CH:15]=1)=[CH:13][C:12]([F:16])=[C:11]([F:17])[CH:10]=2)=[O:5])C.CC[O-].[Na+].C(O)(=O)C.O>C(O)C>[CH2:24]([O:23][C:21]([CH:20]1[CH2:19][N:18]([CH:26]2[CH2:28][CH2:27]2)[C:7]2[N:8]=[C:9]3[CH:10]=[C:11]([F:17])[C:12]([F:16])=[CH:13][C:14]3=[CH:15][C:6]=2[C:4]1=[O:5])=[O:22])[CH3:25]
Reactant: CCOC(=O)CCN(c1nc2cc(F)c(F)cc2cc1C(=O)OCC)C1CC1
Agent: CC[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Solvent: CCO
Product: CCOC(=O)C1CN(C2CC2)c2nc3cc(F)c(F)cc3cc2C1=O
Temperature: 20 °C

Procedure:
A solution of 3-ethoxycarbonyl-6,7-difluoro-2-[N-cyclopropyl-N-(β-ethoxycarbonylethyl)amino]quinoline in 20 cm3 of absolute ethanol is added in the course of 60 minutes to a solution of 1.6 g of sodium ethylate brought to reflux in 40 cm3 of absolute ethanol. The solution obtained is stirred under reflux for a further 60 minutes. 2.6 cm3 of glacial acetic acid are then introduced in the course of 10 minutes. The reaction mixture is stirred for a further 15 minutes and, with the mixture still refluxing, 26 cm3 of water are then introduced in the course of 5 minutes. The suspension obtained is cooled to approximately 20° C. The precipitate is drained at approximately 20° C. and washed with twice 10 cm3 of water. The wet product is dried under reduced pressure (20 kPa) at approximately 60° C. 1.25 g of crude 3-ethoxycarbonyl-7,8-difluoro-1-cyclopropyl-4-oxo-1,2,3,4-tetrahydrobenzo[b][1,8]naphthyridine are isolated in the form of a yellow solid, melting point 172° C.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:7]2=[N:8][S:9][N:10]=[C:6]2[CH:5]=1)([O-])=O.Cl[Sn]Cl.O>O1CCOCC1.C(O)C>[NH2:1][C:4]1[CH:12]=[CH:11][C:7]2=[N:8][S:9][N:10]=[C:6]2[CH:5]=1
Reactant: O=[N+]([O-])c1ccc2nsnc2c1
Agent: Cl[Sn]Cl
Solvent: C1COCCO1
Solvent: O
Solvent: CCO
Product: Nc1ccc2nsnc2c1
Temperature: 50 °C
Reaction time: 0.17 h
Yield: 88 %

Procedure:
To a solution of 5-nitrobenzo-2,1,3-thiadiazole in a mixture of dioxane (22 mL) and ethanol (22 mL) at RT added solid SnCl2 followed by addition of water (1 mL). The reaction mixture was warmed up to 50° C. and stirred for 10 min, cooled to RT, concentrated and partitioned between ethyl acetate/1N NaOH. The organic layer was washed with 1N NaOH, water, brine, dried over MgSO4 and charcoal. Evaporation of the solvent gave 5-aminobenzo-2,1,3-thiadiazole as a yellow powder (3.0 g, 88%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:13])([CH3:12])[C:9]([OH:11])=O)=[CH:4][CH:3]=1.[NH2:14][CH2:15][CH2:16][CH2:17][N:18]1[CH2:23][CH2:22][CH:21]([C:24]2[CH:25]=[C:26]([NH:30][C:31](=[O:35])[CH2:32][CH2:33][CH3:34])[CH:27]=[CH:28][CH:29]=2)[CH2:20][CH2:19]1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([CH3:13])([CH3:12])[C:9]([NH:14][CH2:15][CH2:16][CH2:17][N:18]2[CH2:23][CH2:22][CH:21]([C:24]3[CH:25]=[C:26]([NH:30][C:31](=[O:35])[CH2:32][CH2:33][CH3:34])[CH:27]=[CH:28][CH:29]=3)[CH2:20][CH2:19]2)=[O:11])=[CH:6][CH:7]=1
Reactant: CC(C)(C(=O)O)c1ccc(Cl)cc1
Reactant: CCCC(=O)Nc1cccc(C2CCN(CCCN)CC2)c1
Product: CCCC(=O)Nc1cccc(C2CCN(CCCNC(=O)C(C)(C)c3ccc(Cl)cc3)CC2)c1

Procedure:
Example 80 was prepared from 2-(4-chlorophenyl)-2-methylpropanoic acid and N-{3-[1-(3-aminopropyl)-4-piperidinyl]phenyl}butanamide according to the procedures described in Scheme 9: ESMS m/e: 484.3 (M+H)+.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][CH:12]=1)[C:6](=[N:8][OH:9])[NH2:7])#[N:2].[Br:13][C:14]1[CH:15]=[N:16][CH:17]=[C:18]([CH:22]=1)[C:19](Cl)=O.N>>[Br:13][C:14]1[CH:22]=[C:18]([C:19]2[O:9][N:8]=[C:6]([C:5]3[CH:4]=[C:3]([CH:12]=[CH:11][CH:10]=3)[C:1]#[N:2])[N:7]=2)[CH:17]=[N:16][CH:15]=1
Reactant: N#Cc1cccc(C(N)=NO)c1
Reactant: O=C(Cl)c1cncc(Br)c1
Agent: N
Product: N#Cc1cccc(-c2noc(-c3cncc(Br)c3)n2)c1

Procedure:
The title compound was prepared according to the procedure of Example 4B using 3-cyano-N′-hydroxybenzimidamide and 5-bromonicotinoyl chloride (Alfa). 1H NMR (300 MHz, DMSO-d6) δ 7.67 (m, 1 H), 7.74 (m, 1 H), 8.41 (m, 1 H), 8.49 (m, 1 H), 8.64 (s, 1 H), 8.93 (s, 1 H), 9.4 (s, 1 H) ppm; MS (DCI/NH3) m/z 327 (M+H)+.
Reaction SMILES: C([N:3](C(=O)C1C=CC(O)=CC=1)[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[C@@H:12]1[CH2:21][CH2:20][C:19]2[CH:18]=[C:17]([O:22]C(=O)C(C)(C)C)[CH:16]=[CH:15][C:14]=2[CH2:13]1)C.Br[CH2:39][C:40]([N:42]1[CH2:47][CH2:46][CH2:45][C:44]([CH3:49])([CH3:48])[CH2:43]1)=O>>[CH3:48][C:44]1([CH3:49])[CH2:45][CH2:46][CH2:47][N:42]([CH2:40][CH2:39][O:10][C:8]2[CH:9]=[CH:4][C:5]([CH2:12][CH2:13][CH2:14][NH:3][C:4]3[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=3[C@@H:12]3[CH2:21][CH2:20][C:19]4[CH:18]=[C:17]([OH:22])[CH:16]=[CH:15][C:14]=4[CH2:13]3)=[CH:6][CH:7]=2)[CH2:43]1
Reactant: CCN(C(=O)c1ccc(O)cc1)c1cc(OC)ccc1[C@@H]1CCc2cc(OC(=O)C(C)(C)C)ccc2C1
Reactant: CC1(C)CCCN(C(=O)CBr)C1
Product: COc1ccc([C@@H]2CCc3cc(O)ccc3C2)c(NCCCc2ccc(OCCN3CCCC(C)(C)C3)cc2)c1
Yield: 92.4 %

Procedure:
Synthesized from pivalic acid (R)-6-{2-[ethyl(4-hydroxybenzoyl)amino]-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-yl ester (20 mg) and 2-bromo-1-(3,3-dimethylpiperidin-1-yl)ethanone (19 mg) according to an analogous synthetic method to Example 404 and purified by LC-MS, the title compound (10 mg) was obtained.
Reaction SMILES: [C:1]([S:14]([N:17]([CH2:21][CH2:22][CH2:23][C:24]([O:26]C)=[O:25])[CH2:18][CH2:19][CH3:20])(=[O:16])=[O:15])([C:4]([C:7]([C:10]([F:13])([F:12])[F:11])([F:9])[F:8])([F:6])[F:5])([F:3])[F:2].[OH-].[K+:29].C(O)(C)C>O>[C:1]([S:14]([N:17]([CH2:21][CH2:22][CH2:23][C:24]([O:26][K:29])=[O:25])[CH2:18][CH2:19][CH3:20])(=[O:16])=[O:15])([C:4]([C:7]([C:10]([F:13])([F:12])[F:11])([F:9])[F:8])([F:6])[F:5])([F:3])[F:2]
Reactant: [K+]
Reactant: CCCN(CCCC(=O)OC)S(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Agent: [OH-]
Solvent: O
Solvent: CC(C)O
Product: CCCN(CCCC(=O)O[K])S(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Temperature: 25 °C
Yield: 163.2 %

Procedure:
A round bottom flask fitted with a heating mantle and an overhead stirrer was charged with C4F9SO2N(C3H7)CH2CH2CH2COOCH3 (63.0 g; 0.143 mole), KOH (11.0 g; 0.196 mole; pellets) isopropanol (22 ml.) and deionized water (18 mL). The ensuing mixture was refluxed overnight, cooled to room temperature, yielding a solution of C4F9SO2N(C3H7)CH2CH2CH2COOK (108.6 g; 53.4% solids).
Reaction SMILES: [Cl:1][C:2]1[C:3]([O:9][C:10]2[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[C:12]([N+:19]([O-:21])=O)[CH:11]=2)=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.[CH3:22]NO.C([O-])([O-])=O.[K+].[K+]>C1COCC1>[CH3:22][N:19]([OH:21])[C:12]1[CH:11]=[C:10]([O:9][C:3]2[C:2]([Cl:1])=[CH:7][C:6]([Cl:8])=[CH:5][N:4]=2)[CH:15]=[CH:14][C:13]=1[N+:16]([O-:18])=[O:17]
Reactant: O=[N+]([O-])c1ccc(Oc2ncc(Cl)cc2Cl)cc1[N+](=O)[O-]
Reactant: CNO
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CN(O)c1cc(Oc2ncc(Cl)cc2Cl)ccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 48 h

Procedure:
A mixture of 4-(3,5-dichloro-2-pyridyloxy)-1,2-dinitrobenzene (800 mg, 2.42 mmol), N-methylhydroxyamine (472 mg, 4.84 mmol), K2CO3 (400 mg, 2.90 mmol) and THF (10 ml) is stirred at RT for 48 hours. The reaction mixture is filtered, and the filtrate is concentrated and then taken up in methylene chloride, washed, dried and evaporated to give N-methyl-N-[2-nitro-5-(3,5-dichloro-2-pyridyloxy)phenyl]-hydroxyamine, a crystalline solid.
Reaction SMILES: [CH3:1][C:2]1[NH:6][N:5]=[C:4]([C:7]2[S:8][CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([O:18][C:19]([F:22])([F:21])[F:20])=[CH:14][CH:13]=3)[N:11]=2)[N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[Cl:29][C:30]1[CH:35]=[C:34]([CH2:36]Cl)[CH:33]=[CH:32][N:31]=1>CN(C=O)C.O>[Cl:29][C:30]1[CH:35]=[C:34]([CH2:36][N:6]2[C:2]([CH3:1])=[N:3][C:4]([C:7]3[S:8][CH:9]=[C:10]([C:12]4[CH:13]=[CH:14][C:15]([O:18][C:19]([F:22])([F:20])[F:21])=[CH:16][CH:17]=4)[N:11]=3)=[N:5]2)[CH:33]=[CH:32][N:31]=1
Reactant: Cc1nc(-c2nc(-c3ccc(OC(F)(F)F)cc3)cs2)n[nH]1
Reactant: ClCc1ccnc(Cl)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1nc(-c2nc(-c3ccc(OC(F)(F)F)cc3)cs2)nn1Cc1ccnc(Cl)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 50.5 %

Procedure:
To a stirred mixture of 2-(5-methyl-1H-1,2,4-triazol-3-yl)-4-(4-(trifluoromethoxy)phenyl)thiazole (3 g, 9.2 mmol) and Cs2CO3 (4.8 g, 13 mmol) in DMF (20 mL) was added 2-chloro-4-(chloromethyl)pyridine (2.1 g, 13 mmol). The mixture was stirred at RT for 16 h, then diluted with H2O (20 mL) and extracted with EtOAc (3×30 mL). The combined organic layers were washed with H2O (20 mL), concentrated under reduced pressure and the residue was purified by silica gel column chromatography (Petroleum ether:EtOAc=4:1) to afford the title compound as an oil (2.1 g, 50.6%).
Reaction SMILES: [CH3:1][N:2]1[C:6]([N+]([O-])=O)=[C:5]([N+:10]([O-:12])=[O:11])[N:4]=[CH:3]1.[C:13]1([OH:19])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[OH-].[Na+]>O>[CH3:1][N:2]1[C:6]([O:19][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:5]([N+:10]([O-:12])=[O:11])[N:4]=[CH:3]1
Reactant: Cn1cnc([N+](=O)[O-])c1[N+](=O)[O-]
Reactant: Oc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: Cn1cnc([N+](=O)[O-])c1Oc1ccccc1
Temperature: 50 °C
Reaction time: 1 h
Yield: 95.8 %

Procedure:
A mixture of 17.2 g (0.1 mole) of 1-methyl-4,5-dinitroimidazole, 11.2 g (0.12 mole) of phenol and 4.4 g (0.11 mole) of NaOH in 200 ml of water was stirred for 1 hour at 50° C. Thereafter, the solution was diluted with a further 300 ml of water and was cooled. The precipitated crystals were filtered off under suction and recrystallized from water. 21.0 g (96%) of 1-methyl-4-nitro-5-phenoxyimidazole of melting point 116°-118° C. were obtained.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[N:5][C:6](Cl)=[CH:7][CH:8]=2)[N:3]=1.[OH:13][C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1.[OH-].[K+]>O>[NH2:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[N:5][C:6]([O:13][C:14]3[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=3)=[CH:7][CH:8]=2)[N:3]=1
Reactant: Oc1cccnc1
Reactant: Nc1ccc2ccc(Cl)nc2n1
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: Nc1ccc2ccc(Oc3cccnc3)nc2n1
Temperature: 4 °C
Yield: 8.8 %

Procedure:
The procedure is similar to that described in Example 4, but starting with 2-amino-7-chloro-1,8-naphthyridine (17.9 g), 3-hydroxypyridine (38 g) and potassium hydroxide pellets (11,2 g; 85% purity). The product produced by precipitation in water and extraction with ethyl acetate (4.7 g) is dissolved in boiling ethyl acetate (80 cc). After 3 hours' cooling at 4° C., the crystallised solid is separated by filtration, washed with ethyl ether (2×5 cc) and dried in the air at 20° C. 2-Amino-7-(3-pyridyl)oxy-1,8-naphthyridine (2.1 g) is produced, m.p. 178° C.
Reaction SMILES: C([O:3][C:4]([C:6]1([CH2:23][S:24][C:25]2[NH:29][C:28]3[CH:30]=[CH:31][CH:32]=[CH:33][C:27]=3[N:26]=2)[C:10]([S:11][C:12]2[NH:16][C:15]3[CH:17]=[CH:18][CH:19]=[CH:20][C:14]=3[N:13]=2)=[C:9]([OH:21])[C:8](=[O:22])[O:7]1)=[O:5])C.C(=O)(O)[O-].[Na+]>O.C(O)C>[NH:13]1[C:14]2[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=2[N:16]=[C:12]1[S:11][C:10]1[C:6]([CH2:23][S:24][C:25]2[NH:26][C:27]3[CH:33]=[CH:32][CH:31]=[CH:30][C:28]=3[N:29]=2)([C:4]([OH:5])=[O:3])[O:7][C:8](=[O:22])[C:9]=1[OH:21]
Reactant: CCOC(=O)C1(CSc2nc3ccccc3[nH]2)OC(=O)C(O)=C1Sc1nc2ccccc2[nH]1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: O=C1OC(CSc2nc3ccccc3[nH]2)(C(=O)O)C(Sc2nc3ccccc3[nH]2)=C1O
Yield: 54.7 %

Procedure:
3-(1H-benzoimidazol-2-ylsulfanyl)-2-(1H-benzoimidazol-2-ylsulfanylmethyl)-4-hydroxy-5-oxo-2,5-dihydro-furan-2-carboxylic acid ethyl ester (32 g) prepared as described in Example 1 was suspended in water (400 mL) and ethanol (300 mL). The suspension was stirred continuously and aqueous sodium bicarbonate solution (23 g in 350 mL of water) was added dropwise during about 5 hours to maintain pH of around 7.5 to 8. The resulting mixture was stirred at 20° C. for 2 days. The milky mixture was put on a rotary evaporator to remove ethanol at a temperature below 40° C. under reduced pressure. The suspension became a clear solution soon after the evaporation started. During the evaporation process 400 mL of water were added to ensure complete removal of ethanol. The solution was adjusted to pH8 and allowed to stir at 40° C. for 18 hours. The product was precipitated out by acidifying the solution to pH 5-6 using acetic acid water solution (12 mL of acetic acid in 230 mL of water). The solid was filtered, washed with water (40 mL) and acetonitrile (40 mL), and dried under vacuum, giving 3-(1H-benzoimidazol-2-ylsulfanyl)-2-(1H-benzoimidazol-2-ylsulfanylmethyl)-4-hydroxy-5-oxo-2,5-dihydro-furan-2-carboxylic acid as a pale grey solid (16.5 g). 1HNMR (300 MHz, D2O) δ=7.10-6.70 (m, 8H), 3.80 (d, 1H), 3.60 (d, 1H) ppm. 13CNMR (75 MHz, D2O) δ=173.7, 173.2, 160.5, 156.6, 149.8, 149.3, 137.9, 122.2, 122.0, 113.7, 113.4, 104.5, 87.5, 37.4 ppm.
Reaction SMILES: [CH2:1]([N:4]1[C:10]2[N:11]=[CH:12][CH:13]=[CH:14][C:9]=2[C:8](=[O:15])[NH:7][C:6]2[CH:16]=[CH:17][C:18](OS(C(F)(F)F)(=O)=O)=[N:19][C:5]1=2)[CH2:2][CH3:3].C([Sn](CCCC)(CCCC)[C:33]1[CH:34]=[N:35][NH:36][CH:37]=1)CCC>>[CH2:1]([N:4]1[C:10]2[N:11]=[CH:12][CH:13]=[CH:14][C:9]=2[C:8](=[O:15])[NH:7][C:6]2[CH:16]=[CH:17][C:18]([C:33]3[CH:34]=[N:35][NH:36][CH:37]=3)=[N:19][C:5]1=2)[CH2:2][CH3:3]
Reactant: CCCN1c2nc(OS(=O)(=O)C(F)(F)F)ccc2NC(=O)c2cccnc21
Reactant: CCCC[Sn](CCCC)(CCCC)c1cn[nH]c1
Product: CCCN1c2nc(-c3cn[nH]c3)ccc2NC(=O)c2cccnc21

Procedure:
The title compound (mp 291°-292° C.) was prepared from 5,11-dihydro-11-n-propyl-2-trifluoromethanesulfonyloxy-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one and 4-(tributylstannyl)pyrazole in a manner analogous to that described in Example 1.
Reaction SMILES: [C:1]1([CH:7]=[CH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[N+:15]([O-])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[Sn]>>[C:1]1([CH:7]=[CH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[NH2:15])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=[N+]([O-])c1ccccc1C=Cc1ccccc1
Agent: Cl
Agent: [Sn]
Product: Nc1ccccc1C=Cc1ccccc1
Temperature: 25 °C
Yield: 76.4 %

Procedure:
At room temperature, a mixture of 12.9 g (0.057 mol) of 1-phenyl-2-(2-nitro-phenyl)-ethene and 210 ml of 17% strength aqueous hydrochloric acid is admixed with 38.7 g of tin powder and slowly heated to reflux temperature. The mixture is boiled under reflux for 2 hours and then cooled to room temperature and extracted repeatedly with diethyl ether. The organic phase is concentrated under reduced pressure. The residue that remains is admixed with water, and the resulting mixture is neutralized by addition of dilute aqueous sodium hydroxide solution and then extracted repeatedly with methylene chloride. The combined organic phases are dried over sodium sulphate and subsequently concentrated under reduced pressure. The residue that remains is chromatographed over silica gel using cyclohexane: ethyl acetate=3:1. Concentration of the eluate gives 8.5 g (76.4% of theory) of 2-(2-phenylethen-1-yl)-aniline in the form of a solid substance of melting point 80° C.
Reaction SMILES: Br[C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[F:9][C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][C:11]=1B1OC(C)(C)C(C)(C)O1.[F-].[K+].O>O1CCCC1.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]>[F:8][C:7]1[C:2]([C:11]2[CH:12]=[C:13]([N+:16]([O-:18])=[O:17])[CH:14]=[CH:15][C:10]=2[F:9])=[N:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC1(C)OB(c2cc([N+](=O)[O-])ccc2F)OC1(C)C
Reactant: Fc1cccnc1Br
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: [F-]
Solvent: C1CCOC1
Solvent: O
Product: O=[N+]([O-])c1ccc(F)c(-c2ncccc2F)c1
Temperature: 35 °C
Reaction time: 18 h
Yield: 92.4 %

Procedure:
To 2-bromo-3-fluoropyridine (1.198 g, 6.807 mmol), prepared according to the procedure of Queguiner et al. (Tetrahedron, 1983, 39, 2009-21), and 2-(2-fluoro-5-nitrophenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (2.72 g, 10.2 mmol), in dry tetrahydrofuran (20 ml) under an atmosphere of nitrogen, was added potassium fluoride (2.0 g), water (1.0 ml) and tris(dibenzylideneacetone)dipalladium(0) (0.139 g). The mixture was thoroughly degassed, then a solution of tri-tert-butylphosphine (3.05 ml of a 0.1 M solution in 1,4-dioxane) was added. The mixture was stirred at 35° C. for 18 h. The reaction was partitioned between dichloromethane and water, the organic phase separated, evaporated, and the residue chromatographed (silica gel; CH2Cl2) to afford 3-fluoro-2-(2-fluoro-5-nitrophenyl)pyridine as a white solid (1.485 g): MS (ES+) m/z 236 M+H]+.
Reaction SMILES: [N+:1]([C:4]1[CH:14]=[CH:13][CH:12]=[C:6]2[C:7]([O:9][C:10](=[O:11])[C:5]=12)=O)([O-:3])=[O:2].[NH2:15][CH2:16][CH2:17][CH2:18][C:19]([OH:21])=[O:20]>>[N+:1]([C:4]1[CH:14]=[CH:13][CH:12]=[C:6]2[C:7]([N:15]([CH2:16][CH2:17][CH2:18][C:19]([OH:21])=[O:20])[C:10](=[O:11])[C:5]=12)=[O:9])([O-:3])=[O:2]
Reactant: O=C1OC(=O)c2c1cccc2[N+](=O)[O-]
Reactant: NCCCC(=O)O
Product: O=C(O)CCCN1C(=O)c2cccc([N+](=O)[O-])c2C1=O
Yield: 78.8 %

Procedure:
3-nitrophthalic anhydride (0.5 g, 0.0026 mol) and 4-aminobutyric acid (0.268 g, 0.0026 mol) were refluxed as above overnight. The clear solution was purified as per 120 to yield 0.57 g (79%) 122 as a very pale orange powder: mp=144–146° C.; Rf 0.62 (A): Rf 0.87 (C): Rf 0.78(D): IR (cm−1): 3000–3250 (OH), 3219 (C═CH), 2953 (C—H), 1778 (C═O), 1716 (C═O), 1667 (C═O), 1615 (C═C), 1548 (N═O), 1442 (C═C), 1395 (C—O), 1355 (N═O), 1189 (C—O), 723 (C═CH); MS m/z (rel intensity) 313 (100), 278 (65), 277 (42), 191 (71).
Reaction SMILES: COC(=O)C(N1C=CC=C1)[CH2:5][C:6]#[C:7][CH2:8][CH2:9][CH2:10][C:11]1[N:12]=[C:13]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:14][C:15]=1[CH3:16].[CH3:29][CH2:30][O:31][C:32]([CH2:34][C:35]1[S:39][CH:38]=[CH:37][CH:36]=1)=[O:33]>>[CH2:30]([O:31][C:32](=[O:33])[CH:34]([C:35]1[S:39][CH:38]=[CH:37][CH:36]=1)[CH2:5][C:6]#[C:7][CH2:8][CH2:9][CH2:10][C:11]1[N:12]=[C:13]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[O:14][C:15]=1[CH3:16])[CH3:29]
Reactant: COC(=O)C(CC#CCCCc1nc(-c2ccccc2)oc1C)n1cccc1
Reactant: CCOC(=O)Cc1cccs1
Product: CCOC(=O)C(CC#CCCCc1nc(-c2ccccc2)oc1C)c1cccs1
Yield: 38 %

Procedure:
Prepared in a manner similar to ester 1-10 with the exception that Ethyl 2-thiophene acetate was used instead of Methyl 2-pyrrolo-acetate. Chromatography gave 206 mg of the ethyl ester 1-12 (38% yield) as a yellow oil. NMR CDCl3 (δ): 7.99 (2H, m); 7.43 (3H, m); 7.21 (1H, dd, J=1.0, 5.1 Hz); 6.98 (1H, m); 6.94 (1H, m); 4.22 (2H, m); 4.03 (1H, t, J=7.0, 8.0 Hz), 2.92 (1H, m); 2.71 (1H, m); 2.54 (2H, t, J=7.3, 7.3 Hz); 2.31 (3H, s); 2.14 (2H, m); 1.81 (2H, m); 1.25 (3H, t, J=7.1, 7.1 Hz). M+1=408.2.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:18]=[CH:17][C:9]2[O:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[C:8]=2[CH:7]=1.[CH2:19]([O:21][C:22](=[O:34])[C@@H:23]([O:32][CH3:33])[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][CH:26]=1)[CH3:20]>>[CH2:19]([O:21][C:22](=[O:34])[CH:23]([O:32][CH3:33])[CH2:24][C:25]1[CH:26]=[CH:27][C:28]([O:31][CH2:2][CH2:3][CH2:4][O:5][C:6]2[CH:18]=[CH:17][C:9]3[O:10][C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=4[C:8]=3[CH:7]=2)=[CH:29][CH:30]=1)[CH3:20]
Reactant: BrCCCOc1ccc2oc3ccccc3c2c1
Reactant: CCOC(=O)[C@H](Cc1ccc(O)cc1)OC
Product: CCOC(=O)C(Cc1ccc(OCCCOc2ccc3oc4ccccc4c3c2)cc1)OC

Procedure:
A mixture of 2-(3-Bromo-propoxy)-dibenzofuran and (2S)-3-(4-hydroxy-phenyl)-2-methoxy propionic acid ethyl ester were allowed to react under the Standard Procedure I to give the title compound.
Reaction SMILES: [NH:1]([C:5]1[CH:57]=[CH:56][C:8]([C:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([CH:18]3[CH2:23][CH2:22][N:21]([C:24](=[O:34])[CH2:25][CH2:26][C:27]([O:29]C(C)(C)C)=[O:28])[CH2:20][CH2:19]3)=[C:14]([C:35]3[CH2:39][C:38]([CH2:48][C:49]([O:51]C(C)(C)C)=[O:50])([CH2:40][C:41](=[O:47])[O:42]C(C)(C)C)[O:37][N:36]=3)[CH:13]=2)=[O:10])=[CH:7][CH:6]=1)[C:2]([NH2:4])=[NH:3].[C:58]([OH:64])([C:60]([F:63])([F:62])[F:61])=[O:59]>>[F:61][C:60]([F:63])([F:62])[C:58]([OH:64])=[O:59].[C:49]([CH2:48][C:38]1([CH2:40][C:41]([OH:47])=[O:42])[O:37][N:36]=[C:35]([C:14]2[CH:13]=[C:12]([O:11][C:9](=[O:10])[C:8]3[CH:7]=[CH:6][C:5]([NH:1][C:2]([NH2:4])=[NH:3])=[CH:57][CH:56]=3)[CH:17]=[CH:16][C:15]=2[CH:18]2[CH2:19][CH2:20][N:21]([C:24](=[O:34])[CH2:25][CH2:26][C:27]([OH:29])=[O:28])[CH2:22][CH2:23]2)[CH2:39]1)([OH:51])=[O:50]
Reactant: CC(C)(C)OC(=O)CCC(=O)N1CCC(c2ccc(OC(=O)c3ccc(NC(=N)N)cc3)cc2C2=NOC(CC(=O)OC(C)(C)C)(CC(=O)OC(C)(C)C)C2)CC1
Solvent: O=C(O)C(F)(F)F
Product: N=C(N)Nc1ccc(C(=O)Oc2ccc(C3CCN(C(=O)CCC(=O)O)CC3)c(C3=NOC(CC(=O)O)(CC(=O)O)C3)c2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of 3-(5,5-bis(2-tert-butoxy-2-oxoethyl)-4,5-dihydro-1,2-oxazol-3-yl)-4-(1-(4-tert-butoxy-4-oxobutanoyl)piperidin-4-yl)phenyl 4-carbamimidamidobenzoate (29.2 mg) and TFA (1 mL) was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and then, the residue was washed with diethyl ether to obtain the title compound (25.4 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([O:12][C:13]3[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=3)[CH:8]=[N:9]2)=[CH:4][CH:3]=1.Br[C:21]([CH3:28])([CH3:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23]>>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([O:12][C:13]3[CH:14]=[CH:15][C:16]([O:19][C:21]([CH3:28])([CH3:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:17][CH:18]=3)[CH:8]=[N:9]2)=[CH:4][CH:3]=1
Reactant: CCOC(=O)C(C)(C)Br
Reactant: Oc1ccc(Oc2cnc3cc(Cl)ccc3c2)cc1
Product: CCOC(=O)C(C)(C)Oc1ccc(Oc2cnc3cc(Cl)ccc3c2)cc1

Procedure:
Ethyl 2-{4-[(7-chloroquinolin-3-yl)oxy]phenoxy}-2-methylpropionate (15) was prepared from 4-[(7-chloroquinolin-3-yl)oxy]phenol and ethyl 2-bromo-2-methylpropionate following essentially the same procedure as that described in Example 1 part (c). The product, a pale yellow oil was characterised by proton magnetic resonance spectroscopy. Pmr spectrum (CDCl3 ; δ in ppm): 8.65 (1H, d); 7.95 (1H, bs); 7.35 (3H, m); 6.9 (4H, s); 4.2 (2H, q); 1.6 (6H, s); 1.2 (3H, t).