Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:12][CH2:11][CH2:10][C@H:9]2[NH:13][S:14]([CH:17]([CH3:19])[CH3:18])(=[O:16])=[O:15])=[CH:4][CH:3]=1.[C:20]([C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1)#[N:21].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1>[C:20]([C:22]1[CH:27]=[CH:26][C:25]([C:2]2[CH:7]=[CH:6][C:5]([C@H:8]3[CH2:12][CH2:11][CH2:10][C@H:9]3[NH:13][S:14]([CH:17]([CH3:19])[CH3:18])(=[O:16])=[O:15])=[CH:4][CH:3]=2)=[CH:24][CH:23]=1)#[N:21]
Reactant: N#Cc1ccc(B(O)O)cc1
Reactant: CC(C)S(=O)(=O)N[C@@H]1CCC[C@@H]1c1ccc(I)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1COCCO1
Product: CC(C)S(=O)(=O)N[C@@H]1CCC[C@@H]1c1ccc(-c2ccc(C#N)cc2)cc1
Temperature: 85 °C
Reaction time: 8 h
Yield: 8.6 %

Procedure:
(+,−) Cis propane-2-sulfonic acid [2-(4-iodo-phenyl)-cyclopentyl]-amide (150 mg, 0.38 mmol, prepared in example 17) was treated with 4-cyanophenyl boronic acid (56 mg, 0.38 mmol), palladium tetrakis triphenylphosphine (22 mg, 0.02 mmol) and cesium carbonate (150 mg, 0.46) under nitrogen in 10 mL of degassed dioxane. The reaction was heated to 85° C. and stirred overnight. The reaction was concentrated in vacuo and purified by radial chromatography eluting with 30:70 ethyl acetate:hexanes to give 12 mg (9%) of the title compound as a white solid. The NMR was consistent with the assigned structure.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]2=[N:13][CH:14]=[N:15][C:16]([O:17][C@@H:18]([CH2:29][O:30][CH3:31])[C:19]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][N:23]=3)=[O:20])=[C:11]2[CH:10]=[N:9]1>CO.[Pd]>[CH3:31][O:30][CH2:29][C@H:18]([O:17][C:16]1[N:15]=[CH:14][N:13]=[C:12]2[N:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][CH:2]=3)[N:9]=[CH:10][C:11]=12)[C:19]([NH:21][C:22]1[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][N:23]=1)=[O:20]
Reactant: COC[C@H](Oc1ncnc2c1cnn2-c1ccccc1Cl)C(=O)Nc1ccc(C)cn1
Agent: [Pd]
Solvent: CO
Product: COC[C@H](Oc1ncnc2c1cnn2-c1ccccc1)C(=O)Nc1ccc(C)cn1
Temperature: 25 °C
Reaction time: 24 h
Yield: 20.6 %

Procedure:
Palladium (10% on Carbon) (25.5 mg, 0.24 mmol) was added to (2S)-2-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-methoxy-N-(5-methylpyridin-2-yl)propanamide (Example 3) (105 mg, 0.24 mmol) in methanol (2.5 mL) at ambient temperature under nitrogen. This was then purged with hydrogen and the resulting solution was stirred at ambient temperature for 24 hours. The mixture was filtered through celite and evaporated. The residue was purified by flash silica chromatography eluting with 0 to 100% EtOAc in isohexane to afford (S)-3-methoxy-N-(5-methylpyridin-2-yl)-2-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide (20.0 mg, 20.7%).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:18])[O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:26]1[CH:27]=[CH:28][C:29]([N+:32]([O-:34])=[O:33])=[N:30][CH:31]=1.O>CN(C)C=O>[N+:32]([C:29]1[N:30]=[CH:31][C:26]([O:1][C:2]2[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:18])[O:10][CH2:11][C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)=[CH:4][CH:3]=2)=[CH:27][CH:28]=1)([O-:34])=[O:33]
Reactant: O=C(Nc1ccc(O)cc1)OCc1ccccc1
Reactant: O=[N+]([O-])c1ccc(Br)cn1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C(Nc1ccc(Oc2ccc([N+](=O)[O-])nc2)cc1)OCc1ccccc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 56.1 %

Procedure:
To a solution of benzyl (4-hydroxyphenyl)carbamate (1.44 g, 5.91 mmol) in N,N-dimethylformamide (10 mL) were added cesium carbonate (2.41 g, 7.39 mmol) and 5-bromo-2-nitropyridine (1.0 g, 4.93 mmol), and the mixture was stirred at room temperature for 16 hr. Water (40 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate/tetrahydrofuran (=2/1, 120 mL). The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (NH silica gel, hexane/ethyl acetate=3/1→1/3) to give the title compound (1.01 g, 56%).
Reaction SMILES: [CH3:1][C@@:2]1([OH:22])[C@H:6]([OH:7])[C@@H:5]([CH2:8][OH:9])[O:4][C@H:3]1[N:10]1[C:14]2[N:15]=[CH:16][N:17]=[C:18]([NH2:19])[C:13]=2[C:12]([C:20]#[CH:21])=[CH:11]1.[H][H]>C1COCC1.[Pd].CC([O-])=O.CC([O-])=O.[Pb+2]>[CH3:1][C@@:2]1([OH:22])[C@H:6]([OH:7])[C@@H:5]([CH2:8][OH:9])[O:4][C@H:3]1[N:10]1[C:14]2[N:15]=[CH:16][N:17]=[C:18]([NH2:19])[C:13]=2[C:12]([CH:20]=[CH2:21])=[CH:11]1
Reactant: [H][H]
Reactant: C#Cc1cn([C@@H]2O[C@H](CO)[C@@H](O)[C@@]2(C)O)c2ncnc(N)c12
Agent: [Pd]
Agent: CC(=O)[O-]
Agent: [Pb+2]
Solvent: C1CCOC1
Product: C=Cc1cn([C@@H]2O[C@H](CO)[C@@H](O)[C@@]2(C)O)c2ncnc(N)c12
Reaction time: 168 h
Yield: 75 %

Procedure:
The acetylene product prepared above was dissolved in 3 mL THF and 22 mg of Lindlar's catalyst was added. The solution was stirred at ambient temperature under 1 atm of hydrogen (via balloon) for 7 days. The balloon was recharged with hydrogen at the beginning of each day. After 7 days, the reaction was filtered through celite to remove catalyst, concentrated in vacuo, and purified by reverse phase HPLC on Phenominex column (250×20 mm) using a gradient of acetonitrile in water from 0 to 30% over 30 min at 10 mL/min to yield 30 mg (75% yield) of the title compound;
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[CH2:13]([O:20][N:21]1[C:30](=[O:31])[C:29]2[CH:32]=[C:33]([C:36]#[N:37])[C:34](Cl)=[C:27]3[C:28]=2[C:23](=[CH:24][CH:25]=[CH:26]3)[C:22]1=[O:38])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C(#N)C>[CH2:13]([O:20][N:21]1[C:30](=[O:31])[C:29]2[CH:32]=[C:33]([C:36]#[N:37])[C:34]([N:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)=[C:27]3[C:28]=2[C:23](=[CH:24][CH:25]=[CH:26]3)[C:22]1=[O:38])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: N#Cc1cc2c3c(cccc3c1Cl)C(=O)N(OCc1ccccc1)C2=O
Reactant: C1CCNC1
Solvent: CCN(CC)CC
Solvent: CC#N
Product: N#Cc1cc2c3c(cccc3c1N1CCCC1)C(=O)N(OCc1ccccc1)C2=O
Temperature: 0 °C
Yield: 68.6 %

Procedure:
To a solution of pyrrolidine (0.070 g, 0.98 mmol) and triethyl amine (0.11 g, 1.1 mmol) in acetonitrile (5 mL) at reflux was added 2-benzyloxy-6-chloro-5-cyano-benzo[de]isoquinoline-1,3-dione (0.20 g, 0.55 mmol, from Example A2). The reaction was heated at reflux for 20 minutes, then cooled to 0° C. The resulting precipitate was removed by filtration, washed with cold acetonitrile, and dried to give 0.15 g of the title compound.
Reaction SMILES: [C:1]([O:5][C@@H:6]([C:11]1[C:26]([CH3:27])=[CH:25][C:14]2[N:15]=[C:16]([C:18]3[CH:23]=[CH:22][N:21]=[C:20](Cl)[N:19]=3)[S:17][C:13]=2[C:12]=1[C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=1)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2].[CH3:35][N:36]([CH3:45])[C:37]([N:39]1[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1)=[O:38]>O1CCOCC1>[C:1]([O:5][C@@H:6]([C:11]1[C:26]([CH3:27])=[CH:25][C:14]2[N:15]=[C:16]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]([N:42]4[CH2:41][CH2:40][N:39]([C:37](=[O:38])[N:36]([CH3:35])[CH3:45])[CH2:44][CH2:43]4)[N:19]=3)[S:17][C:13]=2[C:12]=1[C:28]1[CH:29]=[CH:30][C:31]([Cl:34])=[CH:32][CH:33]=1)[C:7]([O:9][CH3:10])=[O:8])([CH3:2])([CH3:3])[CH3:4]
Reactant: COC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(-c3ccnc(Cl)n3)sc2c1-c1ccc(Cl)cc1
Reactant: CN(C)C(=O)N1CCNCC1
Solvent: C1COCCO1
Product: COC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(-c3ccnc(N4CCN(C(=O)N(C)C)CC4)n3)sc2c1-c1ccc(Cl)cc1
Temperature: 40 °C
Reaction time: 4 h

Procedure:
To (S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(2-chloropyrimidin-4-yl)-5-methylbenzo[d]thiazol-6-yl)acetate (30.0 mg, 0.058 mmol) was added piperazine-1-carboxylic acid dimethylamide (36.6 mg, 0.232 mmol) in 1,4-dioxane (1 mL). The reaction mixture was stirred at 40° C. for 4 h, then at room temperature overnight. The reaction mixture was filtered through Celite (ethyl acetate eluent), concentrated, and used without further purification. LCMS-ESI+ calc'd for C32H38ClN6O4S (M+H+): 637.2; Found: 637.2 (M+H+).
Reaction SMILES: [O:1]=[C:2]1[C:11]2[CH:10]=[CH:9][CH:8]=[C:7]3[NH:12][CH:13]([C:21]4[CH:28]=[CH:27][C:24]([CH:25]=O)=[CH:23][CH:22]=4)[CH:14]([C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)[C:5]([C:6]=23)=[N:4][NH:3]1.[BH4-].[Na+].[CH3:31][NH2:32]>>[CH3:31][NH:32][CH2:25][C:24]1[CH:23]=[CH:22][C:21]([CH:13]2[NH:12][C:7]3[C:6]4[C:5](=[N:4][NH:3][C:2](=[O:1])[C:11]=4[CH:10]=[CH:9][CH:8]=3)[CH:14]2[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:28][CH:27]=1
Reactant: CN
Reactant: O=Cc1ccc(C2Nc3cccc4c(=O)[nH]nc(c34)C2c2ccccc2)cc1
Agent: [BH4-]
Agent: [Na+]
Product: CNCc1ccc(C2Nc3cccc4c(=O)[nH]nc(c34)C2c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 19 %

Procedure:
To 4-(3-oxo-9-phenyl-3,7,8,9-tetrahydro-2H-pyrido[4,3,2-de]phthalazin-8-yl)benzaldehyde (59 mg, 0.16 mmol) was added methanamine (20 ml) and the mixture was stirred at room temperature for 2 h. Then 30 mg of sodium borohydride was added and stirred for another 2 h. The resulting mixture was evaporated under reduced pressure and purified by prep-HPLC. 11.5 mg of 8-(4-((methylamino)methyl)phenyl)-9-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one was obtained (yield: 19%). 1H-NMR (400 MHz, CD3OD) δ: 2.66 (s, 3H), 4.33-4.35 (d, J=8 Hz, 1H), 4.83-4.85 (d, J=7.6 Hz, 1H), 7.10-7.12 (m, 2H), 7.15-7.22 (m, 4H), 7.34-7.42 (m, 4H), 7.55-7.57 (m, 1H), 7.63-7.67 (m, 1H). LC-MS (ESI) m/z: 383 (M+1)+.
Reaction SMILES: [C:1]([C:4]1[CH:36]=[CH:35][C:7]([O:8][CH2:9][CH:10]([OH:34])[CH2:11][O:12][C:13]2[CH:30]=[CH:29][C:16]3[C:17](=[O:28])[CH:18]=[C:19]([CH2:21][CH2:22][C:23]([O:25]CC)=[O:24])[O:20][C:15]=3[C:14]=2[CH2:31][CH2:32][CH3:33])=[C:6]([CH2:37][CH2:38][CH3:39])[C:5]=1[OH:40])(=[O:3])[CH3:2].C(=O)([O-])[O-].[Na+].[Na+].CCOCC>C(O)C>[C:1]([C:4]1[CH:36]=[CH:35][C:7]([O:8][CH2:9][CH:10]([OH:34])[CH2:11][O:12][C:13]2[CH:30]=[CH:29][C:16]3[C:17](=[O:28])[CH:18]=[C:19]([CH2:21][CH2:22][C:23]([OH:25])=[O:24])[O:20][C:15]=3[C:14]=2[CH2:31][CH2:32][CH3:33])=[C:6]([CH2:37][CH2:38][CH3:39])[C:5]=1[OH:40])(=[O:3])[CH3:2]
Reactant: CCCc1c(OCC(O)COc2ccc3c(=O)cc(CCC(=O)OCC)oc3c2CCC)ccc(C(C)=O)c1O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOCC
Solvent: CCO
Product: CCCc1c(OCC(O)COc2ccc3c(=O)cc(CCC(=O)O)oc3c2CCC)ccc(C(C)=O)c1O
Yield: 70.7 %

Procedure:
A solution of ethyl 3-[7-[3-(4-acetyl-3-hydroxy-2-n-propylphenoxy)-2-hydroxypropyloxy]-4-oxo-8-n-propyl-4H-1-benzopyran-2-yl]propionate (0.79 g) and sodium carbonate (0.79 g) in aqueous ethanol was refluxed for 1 hour. Ethanol was removed by distillation and the residual aqueous solution cooled. Acidification afforded a gum which solidified on prolonged treatment with refluxing ether. Crystallisation from acetone-ether yielded 3-[7-[3-(4-acetyl-3-hydroxy-2-n-propylphenoxy)-2-hydroxypropyloxy]-4-oxo-8-n-propyl-4H-1-benzo pyran-2-yl]propionic acid (0.53 g) mp 79°-80° C. The sodium salt was prepared therefrom by the method of Example 1(h).
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[OH:12][CH2:13][CH:14]([CH2:16][OH:17])[OH:15].Cl>N1C=CC=CC=1>[S:7]([O:12][CH2:13][CH:14]([CH2:16][O:17][S:7]([C:4]1[CH:5]=[CH:6][C:1]([CH3:11])=[CH:2][CH:3]=1)(=[O:9])=[O:8])[OH:15])([C:4]1[CH:5]=[CH:6][C:1]([CH3:11])=[CH:2][CH:3]=1)(=[O:9])=[O:8]
Reactant: OCC(O)CO
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: Cl
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OCC(O)COS(=O)(=O)c2ccc(C)cc2)cc1

Procedure:
Compound 2 was synthesized according to the previous reported method with modifications (Benbouzid et al., 1988). p-Toluenesulfonyl chloride (10.29 g, 54 mmol) dissolved in dry pyridine was added to a stirred solution of anhydrous glycerol (2.48 g, 27 mmol) in dry pyridine (30 ml at 0° C.). The solution was added slowly and left to react for 44 hours in the refrigerator (0°-3° C.). The pink mixture was poured over crushed ice and acidified with concentrated HCl. The organic layer was separated and the aqueous layer was washed with methylene chloride (2×50 ml). The combined organic extracts were washed successively with 2N HCl (2×10 ml) and distilled water (2×10 ml) and dried over anhydrous Na2SO4. The filtrate was evaporated and the residual crude product was purified by column chromatography on silica gel to afford Compound 2 as an oil: 9.72 g (24.3 mmol) yield 90%. 1H NMR [Chemical shift (d), multiplicity, coupling constant (Hz), number of protons, atom]: 7.75 (d; J=8.2 Hz; 4H, Har.); 7.35 (d; J=8.2 Hz; 4H; Har.); 4.1 (bs; 4H; H1,3); 3.35 (bs; 1H; H2); 2.4 (s; 6H; 2CH3). 13C NMR (ppm): 145 (C ar.); 131.7 (C ar.); 129.7 (CH ar.); 127.6 (CH ar.); 69.3 (C1,3); 66.7 (C2); 21.2 (CH3) Satisfactory 1H and 13C NMR data as well as mass spectral data were recorded for this compound. These spectra were consistent with the structures shown in FIG. 1.
Reaction SMILES: O.[OH-].[Li+].C[O:5][C:6]([C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[N:20]=[C:19]([C:27]([F:30])([F:29])[F:28])[CH:18]=2)[CH:9]=1)=[O:7]>O1CCCC1.O>[C:6]([C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[N:20]=[C:19]([C:27]([F:30])([F:28])[F:29])[CH:18]=2)[CH:9]=1)([OH:7])=[O:5]
Reactant: COC(=O)c1cn(-c2cc(C(F)(F)F)nc3ccccc23)c2ccccc12
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)c1cn(-c2cc(C(F)(F)F)nc3ccccc23)c2ccccc12

Procedure:
0.204 g (4.9 mmol) of lithium hydroxide monohydrate and 8 cm3 of water are added to 0.6 g (1.62 mmol) of 3-methoxycarbonyl-1-(2-(trifluoromethyl)quinol-4-yl)-1H-indole dissolved in 8 cm3 of tetrahydrofuran. After stirring at reflux for 15 hours, the reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa) to give a residue which is taken up in 20 cm3 of water (pH=10). The resulting aqueous solution is washed with 30 cm3 of ethyl acetate, adjusted to pH 6 with N hydrochloric acid and extracted with 50 cm3 of ethyl acetate. The organic phase is dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The solid obtained is triturated in 20 cm3 of isopropyl ether and filtered off, resulting in 0.3 g of 3-carboxy-1-(2-(trifluoromethyl)quinol-4-yl)-1H-indole in the form of a yellow powder. Mass spectrum (EI): m/e 356 (M+•), m/e 311.
Reaction SMILES: [Cl:1][C:2]1[C:7]([C:8]([C:10]2[NH:14][CH:13]=[C:12]([S:15](Cl)(=[O:17])=[O:16])[CH:11]=2)=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[NH2:19][CH2:20][CH2:21][N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.C(N(CC)CC)C>C(Cl)Cl>[N:22]1([CH2:21][CH2:20][NH:19][S:15]([C:12]2[CH:11]=[C:10]([C:8]([C:7]3[C:2]([Cl:1])=[N:3][CH:4]=[CH:5][CH:6]=3)=[O:9])[NH:14][CH:13]=2)(=[O:17])=[O:16])[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1
Reactant: NCCN1CCOCC1
Reactant: O=C(c1cc(S(=O)(=O)Cl)c[nH]1)c1cccnc1Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(c1cc(S(=O)(=O)NCCN2CCOCC2)c[nH]1)c1cccnc1Cl
Temperature: 25 °C
Reaction time: 4 h
Yield: 68.8 %

Procedure:
To a solution of 5-(2-chloro-pyridine-3-carbonyl)-1H-pyrrole-3-sulfonyl chloride (500 mg, 1.64 mmol) in DCM (5 mL) was added 4-(2-aminoethyl)morpholine (427 mg, 3.28 mmol) and triethylamine (0.5 mL). The mixture was stirred at room temperature for 4 hours. The reaction was extracted with DCM, the combined DCM was washed with water and brine, dried and concentrated. The residue was purified on a silica gel column to give 450 mg (69%) of 5-(2-chloro-pyridine-3-carbonyl)-1H-pyrrole-3-sulfonic acid (2-morpholin-4-yl-ethyl)-amide as a white solid.
Reaction SMILES: C[C:2]1[CH:6]=C(C)[N:4]([C:8](=[NH:20])[NH:9][S:10]([C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)(=[O:12])=[O:11])[N:3]=1.CS(O)(=O)=O.N[N:27]1[CH2:32]CN(C)[CH2:29][CH2:28]1>>[NH2:20][C:8]([NH:4][N:3]1[CH2:2][CH2:6][N:27]([CH3:32])[CH2:28][CH2:29]1)=[N:9][S:10]([C:13]1[CH:14]=[CH:15][C:16]([CH3:19])=[CH:17][CH:18]=1)(=[O:11])=[O:12]
Reactant: CN1CCN(N)CC1
Reactant: Cc1ccc(S(=O)(=O)NC(=N)n2nc(C)cc2C)cc1
Agent: CS(=O)(=O)O
Product: Cc1ccc(S(=O)(=O)N=C(N)NN2CCN(C)CC2)cc1

Procedure:
The compound of Example 8 was prepared according to the accompanying synthesis procedure from 0.5 ml of N-[(3,5-dimethylpyrazol-1-yl)-iminomethyl]-4-methylbenzene-sulfonamide solution (0.2 M, acetonitrile) with 19 mg of methanesulfonic acid and 0.5 ml of N-amino-4-methylpiperazine solution (1.0 M, acetonitrile) and filed in a substance databank. Calculated mol. wt. 311.40; found mol. wt. (M+H) 312.2; 623.0 (Dimer)
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:11]([O-:13])=[O:12])=[C:6]([CH:10]=1)[C:7](O)=[O:8].S(Cl)(Cl)=O.[NH4+:18].[OH-]>O1CCOCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:11]([O-:13])=[O:12])=[C:6]([CH:10]=1)[C:7]([NH2:18])=[O:8]
Reactant: [NH4+]
Reactant: O=C(O)c1cc(F)ccc1[N+](=O)[O-]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O=S(Cl)Cl
Product: NC(=O)c1cc(F)ccc1[N+](=O)[O-]
Temperature: 25 °C

Procedure:
5-Fluoro-2-nitro-benzoic acid (17.9 g, 96.8 mmol) was heated in thionyl chloride (35 mL, 5 mol eq.) for two hours at 85° C. (oil bath temperature). The reaction mixture was evaporated, taken up and evaporated twice with dry toluene. The resulting acid chloride was dissolved in dry dioxane (180 mL) and added to an ice-water bath cooled solution of 33% NH4OH (23.5 mL, 2 mol eq.) in dioxane (180 mL). The reaction was allowed to warm up gradually to room temperature and then evaporated to dryness. The crystalline residue was triturated in water (50 mL), collected by filtration, washed with a small amount of water and dried in vacuo at 80° C. to constant weight (17.56 g, 98.5%).
Reaction SMILES: [CH:1]1[C:11]2[CH:10]=[CH:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[C:6](=[C:16]3[CH2:21][CH2:20][N:19]([C:22](=[O:36])[CH2:23][N:24]([CH2:32][CH:33]([CH3:35])[CH3:34])C(=O)OC(C)(C)C)[CH2:18][CH2:17]3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[ClH:37].O1CCOCC1.C(=O)([O-])O.[Na+]>O1CCOCC1>[ClH:37].[CH:12]1[C:8]2[CH:9]=[CH:10][C:11]3[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=3[C:6](=[C:16]3[CH2:17][CH2:18][N:19]([C:22](=[O:36])[CH2:23][NH:24][CH2:32][CH:33]([CH3:34])[CH3:35])[CH2:20][CH2:21]3)[C:7]=2[CH:15]=[CH:14][CH:13]=1
Reactant: CC(C)CN(CC(=O)N1CCC(=C2c3ccccc3C=Cc3ccccc32)CC1)C(=O)OC(C)(C)C
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1COCCO1
Product: CC(C)CNCC(=O)N1CCC(=C2c3ccccc3C=Cc3ccccc32)CC1
Reaction time: 8 h

Procedure:
128.5 mg (0.264 mmol) of t-butyl 2-[4-(5H-dibenzo[a,d][7]annulen-5-ylidene)-1-piperidinyl]-2-oxoethyl(isobutyl)carbamate was dissolved in 1 ml of 1,4-dioxane. 0.5 ml of 4 N hydrochloric acid/1,4-dioxane solution was added to the obtained solution, and they were stirred overnight. Saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture. After the extraction with ethyl acetate 3 times, the extract was dried over anhydrous sodium sulfate and then the solvent was evaporated under reduced pressure. The residue was purified by the silica gel chromatography (hexane:ethyl acetate=89:11 to 65:35). The solvent was evaporated under reduced pressure, and the residue was dissolved in 2 ml of diethyl ether. 4 N hydrochloric acid/ethyl acetate solution was added to the obtained solution. The precipitates thus formed were taken by the filtration and then washed with diethyl ether. After drying under reduced pressure, the title compound was obtained.
Reaction SMILES: [H][H].[C:3]([NH:6][C:7](=[CH:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:8]([OH:10])=[O:9])(=[O:5])[CH3:4]>CO>[C:3]([NH:6][C@H:7]([C:8]([OH:10])=[O:9])[CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)(=[O:5])[CH3:4]
Reactant: CC(=O)NC(=Cc1ccccc1)C(=O)O
Reactant: [H][H]
Solvent: CO
Product: CC(=O)N[C@@H](Cc1ccccc1)C(=O)O
Reaction time: 0.5 h

Procedure:
The organic inorganic composite material 2-13 (50 mg) and 2 mg (4.9 mmol) of bis(cyclooctadiene)rhodium (I) tetrafluoroborate were stirred in 3 ml of methanol at room temperature for 30 minutes in a hydrogen atmosphere of 1 atm. 105 mg (0.51 mmol) of α-(acetoamido)cinnamic acid was added to the resulting mixture, and reaction was conducted at room temperature for 30 minutes. Thus, N-acetyl-phenylalanine was obtained. An enantiomer excess of D-form determined by HPLC analysis (Chirace AD-H, manufactured by Daicel) was 97% e.e.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([CH:8](OC(=O)C)[O:9]C(=O)C)[C:5]([Br:17])=[CH:4][C:3]=1[CH:18](OC(=O)C)[O:19]C(=O)C.S(=O)(=O)(O)O>C(O)C.O>[Br:1][C:2]1[CH:7]=[C:6]([CH:8]=[O:9])[C:5]([Br:17])=[CH:4][C:3]=1[CH:18]=[O:19]
Reactant: CC(=O)OC(OC(C)=O)c1cc(Br)c(C(OC(C)=O)OC(C)=O)cc1Br
Agent: O=S(=O)(O)O
Solvent: CCO
Solvent: O
Product: O=Cc1cc(Br)c(C=O)cc1Br
Temperature: -10 °C
Yield: 86.8 %

Procedure:
Unpurified 2,5-dibromo-α,α,α',α'-tetraacetoxy-1,4-xylene (60.5 g, 0.122 mole) was dissolved with stirring in three liters of hot ethanol. Then 450 ml of water was added followed by 75 ml of concentrated sulfuric acid which was added very slowly. After being allowed to reflux for an hour, the reaction mixture was diluted with 900 ml of hot water. Cooling overnight at -10° C. resulted in the recrystallization of 30.9 g (87% yield) of 2,5-dibromoterephthalaldehyde, mp 184°-189° C. (lit 189°-190.5° C.) which was isolated by filtration.
Reaction SMILES: [NH2:1][C:2]1([C:13]2[CH:18]=[CH:17][C:16]([CH:19]([CH3:21])[CH3:20])=[CH:15][C:14]=2[O:22][CH3:23])[C:10](=[O:11])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=[O:12].[C:24](Cl)(=[O:26])[CH3:25].C(N(CC)CC)C>C(Cl)Cl>[CH:19]([C:16]1[CH:17]=[CH:18][C:13]([C:2]2([NH:1][C:24](=[O:26])[CH3:25])[C:10](=[O:11])[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3]2=[O:12])=[C:14]([O:22][CH3:23])[CH:15]=1)([CH3:21])[CH3:20]
Reactant: COc1cc(C(C)C)ccc1C1(N)C(=O)c2ccccc2C1=O
Reactant: CC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1cc(C(C)C)ccc1C1(NC(C)=O)C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 62251.7 %

Procedure:
2-Amino-2-(4-isopropyl-2-methoxyphenyl)-2H-inden-1,3-dione (0.10 g, 0.32 mmol) was dissolved in methylene chloride (4 ml). This solution was added with acetyl chloride (0.05 ml, 0.70 mmol), followed by stirring at room temperature for 15 min, and added with triethylamine (0.12 ml, 0.86 mmol), and stirred for 6 hrs. After the reaction mixture was extracted with methylene chloride (50 ml×3), the organic layer was purified using column chromatography (45% ethylacetate in hexane) to afford the title compound (70 g, 62%).
Reaction SMILES: [CH:1]([C:4]1[C:5](=[O:20])[NH:6][C:7](=[O:19])[NH:8][C:9]=1[O:10][C:11]1[CH:16]=[C:15]([CH3:17])[CH:14]=[C:13]([CH3:18])[CH:12]=1)([CH3:3])[CH3:2].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27]Cl)[CH:22]=1>>[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27][N:8]2[C:9]([O:10][C:11]3[CH:12]=[C:13]([CH3:18])[CH:14]=[C:15]([CH3:17])[CH:16]=3)=[C:4]([CH:1]([CH3:3])[CH3:2])[C:5](=[O:20])[NH:6][C:7]2=[O:19])[CH:22]=1
Reactant: ClCc1cccnc1
Reactant: Cc1cc(C)cc(Oc2[nH]c(=O)[nH]c(=O)c2C(C)C)c1
Product: Cc1cc(C)cc(Oc2c(C(C)C)c(=O)[nH]c(=O)n2Cc2cccnc2)c1
Yield: 33.4 %

Procedure:
5-Isopropyl-6-(3,5-dimethylphenoxy)-2,4-pyrimidinedione and 3-picolyl chloride were reacted by the same way with the example 1 to obtain the titled compound (122 mg, yield: 33.4%).
Reaction SMILES: [N:1]1([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[Cl:14][C:15]1[CH:20]=[N:19][CH:18]=[C:17](Cl)[N:16]=1.C([O-])([O-])=O.[K+].[K+].CCOCC>C(#N)C>[Cl:14][C:15]1[N:16]=[C:17]([N:4]2[CH2:5][CH2:6][N:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:2][CH2:3]2)[CH:18]=[N:19][CH:20]=1
Reactant: Clc1cncc(Cl)n1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOCC
Solvent: CC#N
Product: CC(C)(C)OC(=O)N1CCN(c2cncc(Cl)n2)CC1
Temperature: 65 °C
Reaction time: 15 h
Yield: 89.9 %

Procedure:
A mixture of tert-butyl 1-piperazinecarboxylate (5.07 g, 27.2 mmol), 2,6-dichloropyrazine (3.38 g, 22.7 mmol), and K2CO3 (4.09 g, 30.0 mmol) in acetonitrile (20 mL) was stirred at 65° C. for 12.5 h and for a further 15 h at room temperature. Ether was added and the suspension was filtered. Concentration in vacuo fumished the crude product as an oil that crystallized upon standing. Purification by chromatography on silica gel using ethyl acetate/n-hexane (6:4) as eluent gave 6.1 g (90%) of the title compound as a solid. HRMS m/z calcd for C13H19ClN4O2 (M)+ 298.1197, found 298.1211. Anal. (C13H19ClN4O2) C, H, N.