Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:4][C:5]1[CH:6]=[C:7]([CH:15]([CH3:21])[C:16]([O:18]CC)=O)[CH:8]=[CH:9][C:10]=1[O:11]C(=O)C)(=O)C.[CH2:22]([NH2:26])[CH2:23][CH2:24][CH3:25]>>[CH2:22]([NH:26][C:16](=[O:18])[CH:15]([C:7]1[CH:8]=[CH:9][C:10]([OH:11])=[C:5]([OH:4])[CH:6]=1)[CH3:21])[CH2:23][CH2:24][CH3:25]
Reactant: CCOC(=O)C(C)c1ccc(OC(C)=O)c(OC(C)=O)c1
Reactant: CCCCN
Product: CCCCNC(=O)C(C)c1ccc(O)c(O)c1
Temperature: 150 °C
Reaction time: 2 h

Procedure:
A mixture of 5 g of ethyl 3,4-diacetoxyphenylpropionate and 3.5 g of n-butylamine was heated to 150° C. with stirring for 2 hours in an autoclave. After cooling, the reaction mixture was concentrated and the residue was purified by silica gel chromatography. A solvent mixture of chloroform:methanol=20:1 was used as eluent. Pure N-n-butyl-3,4-dihydroxyphenylpropionamide was obtained as colorless viscous oil. The yield was 5.45 g.
Reaction SMILES: [C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([C:13](=[O:15])[CH3:14])=[CH:10][CH:11]=2)[CH2:6][C:5]1=[O:16])(=[O:3])[CH3:2].[Cl:17][C:18]1[CH:19]=[C:20]([CH:24]=[C:25]([Cl:27])[CH:26]=1)[C:21](O)=[O:22]>>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([C:13](=[O:15])[CH3:14])=[CH:10][CH:11]=2)[C:6](=[C:21]([C:20]2[CH:19]=[C:18]([Cl:17])[CH:26]=[C:25]([Cl:27])[CH:24]=2)[OH:22])[C:5]1=[O:16])(=[O:3])[CH3:2]
Reactant: O=C(O)c1cc(Cl)cc(Cl)c1
Reactant: CC(=O)c1ccc2c(c1)CC(=O)N2C(C)=O
Product: CC(=O)c1ccc2c(c1)C(=C(O)c1cc(Cl)cc(Cl)c1)C(=O)N2C(C)=O

Procedure:
Prepared from 1,5-diacetyl-2-indolinone and 3,5-dichlorobenzoic acid
Reaction SMILES: [F:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[C:4]([F:9])[C:3]=1[NH:10][C:11](=O)[C:12]1[CH:17]=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=2)[CH:15]=[C:14]([CH3:25])[C:13]=1[O:26][CH3:27]>C1COCC1>[F:1][C:2]1[C:3]([NH:10][CH2:11][C:12]2[CH:17]=[C:16]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=3)[CH:15]=[C:14]([CH3:25])[C:13]=2[O:26][CH3:27])=[C:4]([F:9])[CH:5]=[CH:6][C:7]=1[OH:8]
Reactant: COc1c(C)cc(-c2cccc(F)c2)cc1C(=O)Nc1c(F)ccc(O)c1F
Solvent: C1CCOC1
Product: COc1c(C)cc(-c2cccc(F)c2)cc1CNc1c(F)ccc(O)c1F
Temperature: 60 °C
Yield: 32.3 %

Procedure:
To a solution of N-(2,6-difluoro-3-hydroxy-phenyl)-5-(3-fluorophenyl)-2-methoxy-3-methyl-benzamide (150 mg, 0.39 mmol, 1.0 eq) in THF (3 mL) at 0° C. was added a solution of BH3 (1M in THF, 2.32 mL, 2.32 mmol, 5.9 eq). The reaction was heated at 60° C. overnight, then quenched by addition of water. The aqueous layer was extracted with EtOAc and the organic extract was washed with 5% Na2CO3, water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The crude residue was purified by column chromatography (petroleum ether:EtOAc, 1:0 to 10:1) to give the title compound as an oil (47 mg, 33%).
Reaction SMILES: [O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH2:9]([NH2:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.I[C:18]1[CH:26]=[CH:25][CH:24]=[CH:23][C:19]=1[C:20]([OH:22])=[O:21].C(O)CO>[Cu]I.CC(O)C>[CH2:9]([NH:16][C:18]1[CH:26]=[CH:25][CH:24]=[CH:23][C:19]=1[C:20]([OH:22])=[O:21])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: O=C(O)c1ccccc1I
Reactant: NCc1ccccc1
Agent: [Cu]I
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CC(C)O
Solvent: OCCO
Product: O=C(O)c1ccccc1NCc1ccccc1
Temperature: 80 °C
Yield: 70.8 %

Procedure:
Copper(I) iodide (10 mg, 0.05 mmol), K3PO4 (636 mg, 3.00 mmol), benzylamine (131 μL, 1.20 mmol), 2-iodobenzoic acid (248 mg, 1.00 mmol), ethylene glycol (111 μL, 2.00 mmol) and 2-propanol (1.0 mL) were used and heated at 80° C. for 18 hours. The above workup procedure was followed and gave 2-(N-benzyl)aminobenzoic acid (161 mg, 71% isolated yield) as a light yellow solid.
Reaction SMILES: ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl.[CH2:15]([O:17][C:18](=[O:42])[CH:19]([C:26]1[N:27]([C:35]2[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=2)[N:28]=[C:29]2[C:34]=1[CH2:33][CH2:32][CH2:31][CH2:30]2)[CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1)[CH3:16]>O1CCOCC1>[CH2:15]([O:17][C:18](=[O:42])[CH:19]([C:26]1[N:27]([C:35]2[CH:36]=[CH:37][C:38]([Cl:41])=[CH:39][CH:40]=2)[N:28]=[C:29]2[C:34]=1[CH:33]=[CH:32][CH:31]=[CH:30]2)[CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1)[CH3:16]
Reactant: CCOC(=O)C(c1c2c(nn1-c1ccc(Cl)cc1)CCCC2)C1CCCCC1
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Solvent: C1COCCO1
Product: CCOC(=O)C(c1c2ccccc2nn1-c1ccc(Cl)cc1)C1CCCCC1
Yield: 19 %

Procedure:
2,3-Dichloro-5,6-dicyanobenzoquinone (136 mg, 600 μmol) was added to a solution of [2-(4-chloro-phenyl)-4,5,6,7-tetrahydro-2H-indazol-3-yl]-cyclohexyl-acetic acid ethyl ester (60 mg, 150 μmol in dioxane (3.3 ml) under an argon atmosphere. The reaction mixture was heated under reflux conditions for 4 d. The solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel, iPrOAc/heptane) to give the title compound (11 mg, 28 μmol; 19%) as colorless solid. MS: m/e=397.0 [M+H+].
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([NH:7][N:8]=[C:9]([C:12]#[N:13])[C:10]#[N:11])[CH:2]=1.NC1C=NC=CC=1.C(#N)CC#N.O.[NH2:27][NH2:28]>C(O)C>[NH2:13][C:12]1[C:9](=[N:8][NH:7][C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[C:10]([NH2:11])=[N:28][N:27]=1
Reactant: N#CC(C#N)=NNc1cccnc1
Reactant: NN
Agent: Nc1cccnc1
Solvent: O
Solvent: N#CCC#N
Solvent: CCO
Product: NC1=NN=C(N)C1=NNc1cccnc1
Temperature: 25 °C

Procedure:
This compound was prepared using 2-[(pyridin-3-yl)hydrazono]malononitrile (342 mg, 2 mmole), which was derived from 3-aminopyridine (940 mg, 10 mmole)) and malononitrile (858 mg, 13 mmol) as described in Example 8, and hydrazine hydrate (110 mg, 2.2 mmole) in ethanol. Solids had not formed after heating the reaction at 80° C. for 40 minutes, however, analysis of the reaction solution by TLC indicated that no starting material remained. The solution was allowed to cool to room temperature and the solvent was evaporated. The product was obtained after upon re-crystallization from ethanol as a yellow solid (150 mg). 1H NMR (ppm, DMSO-d6): 6.18 (br., s, 4H), 7.20 (dd, 1H), 8.00 (dd, 1H), 8.38 (d, 1H), 8.85 (s, 1H), 10.77 (br., s, 1H).
Reaction SMILES: N[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[C:3]=1[OH:9].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:17][C:18](Cl)=[O:19].C[N:22](C=O)C>C(OCC)(=O)C>[Br:8][C:4]1[C:3]2[O:9][NH:22][C:18](=[O:19])[CH2:17][C:2]=2[CH:7]=[CH:6][CH:5]=1
Reactant: Nc1cccc(Br)c1O
Reactant: O=C(Cl)CCl
Reactant: CN(C)C=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Product: O=C1Cc2cccc(Br)c2ON1
Temperature: 25 °C
Reaction time: 8 h
Yield: 91 %

Procedure:
2-Amino-6-bromophenol (1.0 g, 5.32 mmol) was dissolved in DMF (20 mL), and potassium carbonate (1.6 g, 11.7 mmol) and chloroacetyl chloride (0.466 mL, 5.85 mmol) were added thereto, and stirred at room temperature overnight. After diluted with ethyl acetate, the resultant was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled away, and the residue washed with an ethyl acetate-hexane mixture solvent to thus obtain the title compound.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][C:15](Br)=[CH:16][CH:17]=3)[CH:12]=[C:11]2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Li])CCC.CN(C)[CH:33]=[O:34].[Cl-].[NH4+]>O1CCCC1.O>[C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][C:15]([CH:33]=[O:34])=[CH:16][CH:17]=3)[CH:12]=[C:11]2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=S(=O)(c1ccccc1)n1c(-c2ccccc2)cc2cc(Br)ccc21
Reactant: CN(C)C=O
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: O
Product: O=Cc1ccc2c(c1)cc(-c1ccccc1)n2S(=O)(=O)c1ccccc1
Reaction time: 0.5 h

Procedure:
To a solution of 1-benzenesulfonyl-5-bromo-2-phenylindole (958 mg) in tetrahydrofuran (11.6 mL) was added dropwise n-butyllithium (2.76 mol/L hexane solution, 0.84 mL) at −78° C. under an argon atmosphere, and the mixture was stirred for 30 minutes. Then N,N-dimethylformamide (0.535 mL) was added dropwise, and the mixture was stirred at −78° C. for 30 minutes and at room temperature for 2 hours. A saturated aqueous ammonium chloride solution and water were added to the reaction mixture and this resulting mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (225 mg).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH3:28])[C:15](=[O:27])[C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([SH:26])[CH:17]=2)=[C:4]([O:29][CH3:30])[CH:3]=1.Br[CH2:32][CH2:33][CH2:34][C:35]([OH:37])=[O:36].CCN(C(C)C)C(C)C.[NH4+].[Cl-]>C(#N)C.CCOC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH3:28])[C:15]([C:16]2[CH:17]=[C:18]([S:26][CH2:32][CH2:33][CH2:34][C:35]([OH:37])=[O:36])[CH:19]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:21]=2)=[O:27])=[C:4]([O:29][CH3:30])[CH:3]=1
Reactant: COc1cc(F)ccc1-c1ccncc1N(C)C(=O)c1cc(S)cc(C(F)(F)F)c1
Reactant: O=C(O)CCCBr
Agent: [Cl-]
Agent: [NH4+]
Solvent: CC#N
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc(F)ccc1-c1ccncc1N(C)C(=O)c1cc(SCCCC(=O)O)cc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
To a suspension of N-(4-(4-fluoro-2-methoxyphenyl)pyridin-3-yl)-3-mercapto-N-methyl-5-(trifluoromethyl)benzamide (0.05 g, 115 μmol, Example 216, intermediate a) in acetonitrile (1 mL) were added 4-bromobutanoic acid (36.4 mg, 218 μmol) and DIPEA (29.6 mg, 40.0 μL, 229 μmol). After the addition of DIPEA the white suspension turned to a light yellow solution, which was stirred at room temperature for 24 hours before another batch of DIPEA (29.6 mg, 40.0 μL, 229 μmol) was added (white suspension turned into light yellow solution). The reaction mixture was stirred at room temperature for another 20 hours and then poured on saturated aqueous NH4Cl solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were dried over MgSO4, filtered and evaporated. The product was purified by preparative HPLC (Gemini NX column) using a gradient of MeOH:water (containing 0.1% formic acid) (20:80 to 98:2). Colorless solid (0.01 g; 16%). MS (ESI): m/z=523.13 [M+H]+.
Reaction SMILES: Br[C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[CH:5]=[CH:4][CH:3]=1.[Li]CCCC.N1([CH:25]=[O:26])CCCCC1.[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[N:7]1[C:2]([CH:25]=[O:26])=[CH:3][CH:4]=[CH:5][C:6]=1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=1
Reactant: Brc1cccc(-c2ccccn2)n1
Reactant: O=CN1CCCCC1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: O=Cc1cccc(-c2ccccn2)n1
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
A cooled (−78° C.) solution of commercially available 6-bromo-2,2′-bipyridine (600 mg; 2.55 mmol) in anh. THF (10 ml) was treated dropwise with a solution of 1.6 M n-BuLi in hexanes (1.60 ml; 2.56 mmol), and the resulting mixture was further stirred at −78° C., under nitrogen, for 30 min. Piperidine-1-carbaldehyde (577 mg; 5.10 mmol) was added dropwise to the cooled (−78° C.) reaction mixture, and stirring was continued at −78° C. for 30 min. Aq. sat. NH4Cl (25 ml) and AcOEt (50 ml) were added, and the separated organic layer was further washed with brine (20 ml), dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (toluene/AcOEt=8/2) afforded [2,2′-bipyridine]-6-carbaldehyde as a dark-purple solid. LC-MS (conditions C): tR=0.75 min.; [M+H]+: 185.24 g/mol.
Reaction SMILES: [C:1]([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C:7](=[CH:8][C@H:9]([OH:29])[C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[C@@H:12]3[CH2:28][C@@H:13]3[C:14]32[O:27][CH2:26][CH2:25][O:24]3)[CH2:6]1)(=[O:3])[CH3:2].C([O:34]O)(C)(C)C>C1(C)C=CC=CC=1.C(OCC)C>[C:1]([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C@@:7]3([O:34][C@@H:8]3[C@H:9]([OH:29])[C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[C@@H:12]3[CH2:28][C@@H:13]3[C:14]32[O:27][CH2:26][CH2:25][O:24]3)[CH2:6]1)(=[O:3])[CH3:2]
Reactant: CC(C)(C)OO
Reactant: CC(=O)O[C@H]1CC[C@@]2(C)C(=C[C@H](O)[C@H]3[C@@H]4[C@@H]5C[C@@H]5C5(OCCO5)[C@@]4(C)CC[C@@H]32)C1
Solvent: Cc1ccccc1
Solvent: CCOCC
Product: CC(=O)O[C@H]1CC[C@]2(C)[C@H]3CC[C@@]4(C)[C@@H]([C@@H]5C[C@@H]5C45OCCO5)[C@@H]3[C@@H](O)[C@H]3O[C@]32C1
Temperature: 80 °C

Procedure:
A solution of 23.3 g of 3β-acetoxy-17,17-ethylenedioxy-15β,16β-methylene-5-androsten-7β-ol in 350 ml of toluene was combined dropwise, after adding vanadium(IV) oxide acetylacetonate, within 35 minutes with 23.3 ml of 80% tert.-butyl hydroperoxide, dissolved in 115 ml of toluene. The reaction solution was maintained at 80° C. for another 30 minutes, then cooled, diluted with diethyl ether, washed with sodium bisulfite solution, sodium bicarbonate solution, and water, and dried and evaporated, thus obtaining 24.5 g of 3β-acetoxy-5,6β-epoxy-17,17-ethylenedioxy-15β,16β-methylene-5β-androstan-7β-ol, mp 162°-163° C. (diisopropyl ether).
Reaction SMILES: Cl[CH:2]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:3]1[CH:16]=[CH:15][C:6]2[NH:7][C:8]([NH:10][C:11](=[O:14])[O:12][CH3:13])=[N:9][C:5]=2[CH:4]=1.[OH-].[NH4+:24]>O1CCCC1>[NH2:24][CH:2]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:3]1[CH:16]=[CH:15][C:6]2[NH:7][C:8]([NH:10][C:11](=[O:14])[O:12][CH3:13])=[N:9][C:5]=2[CH:4]=1
Reactant: [NH4+]
Reactant: COC(=O)Nc1nc2cc(C(Cl)c3ccccc3)ccc2[nH]1
Agent: [OH-]
Solvent: C1CCOC1
Product: COC(=O)Nc1nc2cc(C(N)c3ccccc3)ccc2[nH]1
Temperature: 25 °C
Reaction time: 12 h
Yield: 22 %

Procedure:
The above hydrochloride salt of methyl (±)-[5- [chloro (phenyl)methyl]-1H-benzimidazol-2-yl]carbamate was then suspended in dry tetrahydrofuran (30 mL) and excess ammonium hydroxide was added to this suspension. The resulting reaction mixture was stirred at room temperature for 12 hours. The solvent was then removed and the residue was chromatographed on silica gel 60F254 (40 g, 70-230 mesh, column size 1'×1") using CHCl3 :CH3OH (95:5) as eluant. Fractions 3 through 12 (20 mL each) upon concentrating on a steam bath under vacuum afforded the title product, yield 22%; mp>232° C.; IR (KBr): 3340, 1718, 1630, 1600, 870, 750, 721, 695 cm-1. 1H-NMR (DMSO-d6): δ 3.75 (2, 3H, --OCH3); 5.23 (2, 1H, CH--N), 5.60-6.87 (m, 2H, NH2 [exchangeable with D2O]), 6.90-7.83 (m, 9H, Ar--H and NHCO [exchangeable with D2O]). Analysis calculated for C16H16N4O2 : C, 64.85; H, 5.44; N, 18.91 and found: C, 65.03; H, 5.53; N, 18.67.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH2:15][C:16]([O:18][CH2:19]C)=[O:17])[CH:5]=[C:6]([Br:14])[C:7]=1[S:8]C(=O)N(C)C.C(O)C>[OH-].[Na+]>[Br:1][C:2]1[CH:3]=[C:4]([CH2:15][C:16]([O:18][CH3:19])=[O:17])[CH:5]=[C:6]([Br:14])[C:7]=1[SH:8]
Reactant: CCOC(=O)Cc1cc(Br)c(SC(=O)N(C)C)c(Br)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: COC(=O)Cc1cc(Br)c(S)c(Br)c1
Yield: 55.6 %

Procedure:
A solution of ethyl 3,5-dibromo-4-(N,N-dimethylcarbamoylthio)phenylacetate (8 g, 0.018 mol), from Preparation D, in 100 mL of 10% aqueous sodium hydroxide and 10 mL ethanol was heated at reflux for 20 hrs under a nitrogen atmosphere. The reaction mixture was cooled and neutral impurities extracted with ethyl acetate. The aqueous phase was acidified with 6N HCl and extracted twice with ethyl acetate. The combined extracts were washed with water and saturated sodium chloride solution, dried (Na2SO4), and the solvent removed on a rotary evaporator. The residue was dissolved in methanol and treated with 3 mL of concentrated sulfuric acid and heated at reflux temperature for 3 hrs. The reaction mixture was cooled and concentrated. The residue was diluted with ethyl acetate, washed with water and brine, dried (Na2SO4), and the solvent removed on a rotary evaporator. The residue was purified by flash chromatography (silica gel, 5% acetone/hexane) to obtain methyl 3,5-dibromo-4-mercaptophenylacetate (3.5 g, 0.01 mol, 57% yield), MP: 63.5°-65° C.
Reaction SMILES: C([CH:3]([N:7]([CH:21](CC)[C:22]([O-:24])=O)[CH:8]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:4]([O-])=[O:5])C.O.[NH2:28][NH2:29]>CO>[C:9]1([CH:8]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:7]2[CH2:21][C:22](=[O:24])[NH:29][NH:28][C:4](=[O:5])[CH2:3]2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: CCC(C(=O)[O-])N(C(CC)C(=O)[O-])C(c1ccccc1)c1ccccc1
Reactant: NN
Solvent: O
Solvent: CO
Product: O=C1CN(C(c2ccccc2)c2ccccc2)CC(=O)NN1

Procedure:
Reacting diethyl-N-benzhydryliminodiacetate with hydrazine hydrate in the presence of methanol at reflux temperature and a reaction time of 20 hours to afford 5-diphenylmethyl-3,7-diketo-1,2-dihydro-1,2,5-triazepine.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:17]1[C:25]([N+:26]([O-:28])=[O:27])=[CH:24][CH:23]=[CH:22][C:18]=1[C:19]([OH:21])=[O:20].CN(C)C1C=CC=CC=1.C(N(CC)C(C)C)(C)C.[OH-].[Na+]>C(Cl)(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([NH:13][C:17]2[C:25]([N+:26]([O-:28])=[O:27])=[CH:24][CH:23]=[CH:22][C:18]=2[C:19]([OH:21])=[O:20])=[CH:14][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Nc1ccc(OCc2ccccc2)cc1
Reactant: O=C(O)c1cccc([N+](=O)[O-])c1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)c1ccccc1
Solvent: ClC(Cl)Cl
Product: O=C(O)c1cccc([N+](=O)[O-])c1Nc1ccc(OCc2ccccc2)cc1
Yield: 90.6 %

Procedure:
A mixture comprising 2.2 g (11 mmol.) of 4-benzyloxyaniline, 2.0 g (10 mmol) of 2-chloro-3-nitrobenzoic acid, 6 ml of N,N-dimethylaniline and 1.6 ml of N,N-diisopropylethylamine was heated at 100° C. for 12 hours under stirring. After cooling, 30 ml, of chloroform and 30 ml of 1N sodium hydroxide were added thereto. The precipitate thus formed was separated by filtration, stirred together with 5% hydrochloric acid and washed with water to thereby give 3.3 g of 2-((4-benzyloxyphenyl)amino)-3-nitrobenzoic acid. This product was added to 40 ml of chloroform and 0.3 ml of N,N-dimethylaniline and 6 ml of phosphorus oxychloride were further added thereto. After heating under reflux for 30 minutes and then cooling, the crystals thus precipitated were separated by filtration. Thus 2.1 g of the title compound was obtained.
Reaction SMILES: [C:1]1(=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[CH:3]=[CH:2]1>C(O)C.Cl>[CH:7]1[CH:6]=[C:5]2[C:4]([OH:11])=[CH:3][CH:2]=[C:1]([OH:12])[C:10]2=[CH:9][CH:8]=1
Reactant: O=C1C=CC(=O)c2ccccc21
Agent: Cl
Solvent: CCO
Product: Oc1ccc(O)c2ccccc12
Yield: 71.9 %

Procedure:
To 1,4-naphthoquinone (25 g) suspended in ethanol (100 ml) was added a solution (150 ml) of stannous chloride (368 g) in concentrated hydrochloric acid gradually at room temperature. After the evolution of heat had ceased and a homogeneous state was established, the reaction mixture was brought back to room temperature and the resulting crystals were collected by filtration, rinsed with water, and dried to provide the title compound (18.2 g).
Reaction SMILES: [C:1]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:24]=[C:23]3[C:19]([CH2:20][N:21]([C@@H:26]([CH:31]([CH3:33])[CH3:32])[C:27]([O:29][CH3:30])=[O:28])[C:22]3=[O:25])=[CH:18][CH:17]=2)=[CH:12][CH:11]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N[C:35]1[CH:40]=[CH:39][C:38]([C:41]2C=C3C(CN([C@@H](C(C)C)C(OC)=O)C3=O)=C[CH:42]=2)=[CH:37][CH:36]=1.C(C1C=CC(C(Cl)=O)=CC=1)CCCCCCC>>[CH3:32][CH:31]([CH3:33])[C@H:26]([N:21]1[CH2:20][C:19]2[C:23](=[CH:24][C:16]([C:13]3[CH:12]=[CH:11][C:10]([NH:9][C:1](=[O:8])[C:2]4[CH:3]=[CH:4][C:5]([CH2:39][CH2:40][CH2:35][CH2:36][CH2:37][CH2:38][CH2:41][CH3:42])=[CH:6][CH:7]=4)=[CH:15][CH:14]=3)=[CH:17][CH:18]=2)[C:22]1=[O:25])[C:27]([O:29][CH3:30])=[O:28]
Reactant: COC(=O)[C@H](C(C)C)N1Cc2ccc(-c3ccc(N)cc3)cc2C1=O
Reactant: COC(=O)[C@H](C(C)C)N1Cc2ccc(-c3ccc(NC(=O)c4ccccc4)cc3)cc2C1=O
Agent: CCCCCCCCc1ccc(C(=O)Cl)cc1
Product: CCCCCCCCc1ccc(C(=O)Nc2ccc(-c3ccc4c(c3)C(=O)N([C@H](C(=O)OC)C(C)C)C4)cc2)cc1
Yield: 98 %

Procedure:
The compound of example 171 was prepared analogous to compound of example 97 by reaction of compound of example 6 with 4-(n-octyl)benzoyl chloride.
Reaction SMILES: [CH3:1][C:2]1[N:3]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:4]2[C:9]([C:10]=1[C:11](O)=[O:12])=[CH:8][CH:7]=[CH:6][CH:5]=2.N1(O)C2C=CC=CC=2N=N1.C(N(CC)CC)C.[NH2:37][CH2:38][C:39]1[C:40]([OH:47])=[N:41][C:42]([CH3:46])=[CH:43][C:44]=1[CH3:45]>ClCCl.O>[OH:47][C:40]1[C:39]([CH2:38][NH:37][C:11]([C:10]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:2]=2[CH3:1])=[O:12])=[C:44]([CH3:45])[CH:43]=[C:42]([CH3:46])[N:41]=1
Reactant: Cc1c(C(=O)O)c2ccccc2n1-c1ccccc1
Reactant: Cc1cc(C)c(CN)c(O)n1
Agent: On1nnc2ccccc21
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1cc(C)c(CNC(=O)c2c(C)n(-c3ccccc3)c3ccccc23)c(O)n1
Temperature: 25 °C
Yield: 50 %

Procedure:
To a solution of 2-methyl-1-phenyl-1H-indole-3-carboxylic acid (115 mg, 0.46 mmol) in anhydrous dichloromethane (3 mL) was added 1H-benzo[d][1,2,3]triazol-1-ol (75 mg, 0.55 mmol), 1-Ethyl-3-(3-dimethyllaminopropyl)carbodiimide hydrochloride (106 mg, 0.55 mmol) and triethylamine (0.16 mL, 1.15 mmol). The mixture was stirred at room temperature for half an hour, 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (70 mg, 0.46 mmol) was added and stirred at room temperature for 3 hours. The reaction mixture was added water (20 mL), extracted with dichloromethane (20 mL×2), combined and concentrated the organic layers to give the residue, which was purified by column chromatography (silica gel, dichloromethane/methanol=25:1) to afford N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-2-methyl-1-phenyl-1H-indole-3-carboxamide (12 mg, 50% yield. LRMS (M+H+) m/z: calcd for 385.18. found 385. 1H NMR (300 MHz, CDCl3) δ 12.62 (s, 1H), 7.89 (d, J=8.0 Hz, 1H), 7.77-7.40 (m, 3H), 7.43-7.18 (m, 3H), 7.22-7.00 (m, 2H), 5.98 (s, 1H), 4.65 (s, 2H), 2.60-2.52 (m, 3H), 2.45 (s, 3H), 2.25 (s, 3H).
Reaction SMILES: [CH:1]1([C:4]#[C:5][C:6]2[CH:7]=[CH:8][C:9]([C:12]([O:14]C)=[O:13])=[N:10][CH:11]=2)[CH2:3][CH2:2]1.[OH-].[K+].O.Cl>CO>[CH:1]1([C:4]#[C:5][C:6]2[CH:7]=[CH:8][C:9]([C:12]([OH:14])=[O:13])=[N:10][CH:11]=2)[CH2:3][CH2:2]1
Reactant: COC(=O)c1ccc(C#CC2CC2)cn1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: O=C(O)c1ccc(C#CC2CC2)cn1
Temperature: 50 °C
Reaction time: 0.33 h
Yield: 73 %

Procedure:
To a small flask were added methyl 5-(cyclopropylethynyl)picolinate (240 mg, 1.193 mmol) and potassium hydroxide (147 mg, 2.62 mmol) in MeOH (4 ml). The mixture was stirred at 50° C. for 20 min. It was cooled to RT and the solvent was reduced. The white solid was treated with small amount of water (˜1.5 mL), and acidified by 6N HCl to pH 2. The light brown precipitate was formed and the resulting mixture was cooled to 0° C. by ice bath. The brown precipitate was collected by filtration to yield 5-(cyclopropylethynyl)picolinic acid (163 mg, 0.871 mmol, 73.0% yield) as light yellow solid. It was dried in high vacuum for overnight and was used directly for next step. MS m/z=188.1 (M+H).