Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([N:8]1[CH2:12][CH2:11][CH:10]([NH:13][C:14]([C:16]2[S:17][CH:18]=[CH:19][C:20]=2[NH:21][C:22]2[CH:27]=[CH:26][N:25]=[C:24]3[NH:28][CH:29]=[CH:30][C:23]=23)=[O:15])[CH2:9]1)=O)(C)(C)C.C(NCCN)[C:32]1[CH:37]=[CH:36]C=[CH:34][CH:33]=1>>[CH2:12]([NH:8][CH2:9][CH2:10][NH:13][C:14]([C:16]1[S:17][CH:18]=[CH:19][C:20]=1[NH:21][C:22]1[CH:27]=[CH:26][N:25]=[C:24]2[NH:28][CH:29]=[CH:30][C:23]=12)=[O:15])[C:11]1[CH:36]=[CH:37][CH:32]=[CH:33][CH:34]=1
Reactant: NCCNCc1ccccc1
Reactant: CC(C)(C)OC(=O)N1CCC(NC(=O)c2sccc2Nc2ccnc3[nH]ccc23)C1
Product: O=C(NCCNCc1ccccc1)c1sccc1Nc1ccnc2[nH]ccc12

Procedure:
This compound was prepared in an analogous manner as 3-{[3-(1H-Pyrrolo[2,3-b]pyridin-4-ylamino)-thiophene-2-carbonyl]-amino}-pyrrolidine-1-carboxylic acid tert-butyl ester using N-benzylethylenediamine instead of 1-BOC-3-aminopyrrolidine. LCMS (ESI) 392 (M+H) 1H NMR (400 MHz, DMSO-d6) δ ppm 11.52 (1H, br. s.) 10.27 (1H, s) 8.05 (1H, t, J=5.47 Hz) 8.01 (1H, d, J=5.37 Hz) 7.77 (1H, d, J=5.37 Hz) 7.46 (1H, d, J=5.47 Hz) 7.14-7.33 (7H, m) 6.80 (1H, d, J=5.56 Hz) 6.43 (1H, dd, J=3.42, 1.85 Hz) 3.69 (2H, s) 3.35 (2H, d, J=6.05 Hz) 2.65 (2H, t, J=6.59 Hz)
Reaction SMILES: [CH3:1][N:2]([CH3:16])[S:3]([C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10](=[O:15])[CH2:9]2)(=[O:5])=[O:4].[N:17]1([CH2:23][CH2:24][O:25][C:26]2[CH:27]=[C:28]3[C:32](=[CH:33][CH:34]=2)[NH:31][C:30]([CH:35]=O)=[CH:29]3)[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1>>[CH3:1][N:2]([CH3:16])[S:3]([C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10](=[O:15])[C:9]2=[CH:35][C:30]1[NH:31][C:32]2[C:28]([CH:29]=1)=[CH:27][C:26]([O:25][CH2:24][CH2:23][N:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1)=[CH:34][CH:33]=2)(=[O:5])=[O:4]
Reactant: O=Cc1cc2cc(OCCN3CCOCC3)ccc2[nH]1
Reactant: CN(C)S(=O)(=O)c1ccc2c(c1)CC(=O)N2
Product: CN(C)S(=O)(=O)c1ccc2c(c1)C(=Cc1cc3cc(OCCN4CCOCC4)ccc3[nH]1)C(=O)N2

Procedure:
2-Oxo-2,3-dihydro-1H-indole-5-sulfonic acid dimethylamide was condensed with 5-(2-morpholin-4-yl-ethoxy)-1H-indole-2-carbaldehyde to give the title compound.
Reaction SMILES: Br[C:2]1([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:14]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2.[C:21]([O:25][CH3:26])(=[O:24])[CH2:22][SH:23]>C1(C)C=CC=CC=1>[C:15]1([C:2]2([S:23][CH2:22][C:21]([O:25][CH3:26])=[O:24])[C:14]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=3[C:8]3[C:3]2=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: COC(=O)CS
Reactant: BrC1(c2ccccc2)c2ccccc2-c2ccccc21
Solvent: Cc1ccccc1
Product: COC(=O)CSC1(c2ccccc2)c2ccccc2-c2ccccc21
Yield: 78.3 %

Procedure:
A solution of 9-bromo-9-phenylfluorene (Aldrich) (1.9 g, 5.9 mmol) and methyl thioglycolate (0.70 mL, 7.8 mmol) in 50 mL of toluene is heated at reflux for 4 hours. The reaction is cooled and concentrated in vacuo. The resulting oil is chromatographed on silica gel eluting with a gradient of ethyl acetate/toluene/hexane (3:20:77 to 5:40:55). The purified product is co-evaporated with hexane 2 times and dried under vacuum for 3 days to give 1.6 g (77%) of methyl (9-phenylfluoren-9-yl-thio)acetate as an oil.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][C:2]=1[CH2:11][N:12]1[CH2:20][CH2:19][C:15]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)([C:16]([NH2:18])=[O:17])[CH2:14][CH2:13]1.[CH:28](N)=O.C(OCC)(=O)C>O>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][C:2]=1[CH2:11][N:12]1[CH2:20][CH2:19][C:15]2([N:21]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:28][NH:18][C:16]2=[O:17])[CH2:14][CH2:13]1
Reactant: NC(=O)C1(Nc2ccccc2)CCN(CC2=Cc3ccccc3CC2)CC1
Reactant: NC=O
Solvent: O
Solvent: CCOC(C)=O
Product: O=C1NCN(c2ccccc2)C12CCN(CC1=Cc3ccccc3CC1)CC2
Temperature: 170 °C

Procedure:
A mixture of 1-[(3,4-dihydro-2-naphthalenyl)methyl]-4-anilino isonipecotamide (5.0 g) and formamide (18 g) is heated for 12 hours at 170° C. The reaction mixture is cooled, diluted with water (100 ml), and extracted with chloroform. The chloroform solution is dried over sodium sulfate and concentrated to give crude product. Trituration with ethyl acetate produces the title compound.
Reaction SMILES: [Cl:1][C:2]1[S:6][C:5]([C:7]([OH:9])=O)=[CH:4][C:3]=1[C:10]1[N:14]([CH3:15])[N:13]=[CH:12][C:11]=1[CH3:16].[NH2:17][C@@H:18]([CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=1)[CH2:19][N:20]1[C:28](=[O:29])[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]1=[O:30].C(N(CC)C(C)C)(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>ClCCl>[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:17][C@@H:18]([CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=2)[CH2:19][N:20]2[C:28](=[O:29])[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21]2=[O:30])=[O:9])=[CH:4][C:3]=1[C:10]1[N:14]([CH3:15])[N:13]=[CH:12][C:11]=1[CH3:16]
Reactant: N[C@@H](Cc1cccc(F)c1)CN1C(=O)c2ccccc2C1=O
Reactant: Cc1cnn(C)c1-c1cc(C(=O)O)sc1Cl
Agent: Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cc1cnn(C)c1-c1cc(C(=O)N[C@@H](Cc2cccc(F)c2)CN2C(=O)c3ccccc3C2=O)sc1Cl
Temperature: 25 °C
Reaction time: 1 h
Yield: 42.9 %

Procedure:
To a 500 mL round-bottomed flask was added 5-chloro-4-(1,4-dimethyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic acid (6.8 g, 26.5 mmol), 2-[(2S)-2-amino-3-(3-fluorophenyl)propyl]-1H-isoindole-1,3(2H)-dione (8.69 g, 29.1 mmol), N,N-diisopropyl ethylamine (14 mL, 80 mmol) and Pybrop (18.52 g, 39.7 mmol) in dichloromethane (DCM) (100 mL). After stirring at RT for 1 h, the reaction solution was washed with H2O (2×100 mL) and the organic layer was dried Na2SO4, filtered and concentrated. The crude product was added to a silica gel column and was eluted with (EtOAc/hexanes, 1:1) to give the title compound (6.1 g, 42.9%) as a white solid: LCMS (ES) m/z 537 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:19]=[CH:18][C:17]([N:20]2[C:24](=[O:25])[NH:23][CH:22]=[N:21]2)=[CH:16][C:3]=1[C:4]([NH:6][CH2:7][C:8]1([OH:15])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:5].C([O-])([O-])=O.[Cs+].[Cs+].[CH3:32][O:33][CH2:34][CH2:35]Br>CS(C)=O.O>[Cl:1][C:2]1[CH:19]=[CH:18][C:17]([N:20]2[C:24](=[O:25])[N:23]([CH2:35][CH2:34][O:33][CH3:32])[CH:22]=[N:21]2)=[CH:16][C:3]=1[C:4]([NH:6][CH2:7][C:8]1([OH:15])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]1)=[O:5]
Reactant: COCCBr
Reactant: O=C(NCC1(O)CCCCCC1)c1cc(-n2nc[nH]c2=O)ccc1Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CS(C)=O
Solvent: O
Product: COCCn1cnn(-c2ccc(Cl)c(C(=O)NCC3(O)CCCCCC3)c2)c1=O
Temperature: 25 °C
Reaction time: 48 h
Yield: 34.9 %

Procedure:
A slurry of 2-Chloro-N-(1-hydroxy-cycloheptylmethyl)-5-(5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)-benzamide (44.4 mg, 0.122 mmol) and Cs2CO3 (66.0 mg, 0.202 mmol) were stirred in DMSO (0.813 mL) at ambient temperature for 20 minutes. 2-Bromoethyl methyl ether (17.0 mg, 0.122 mmol) was added and the reaction stirred at ambient temperature for 48 hours. The reaction was diluted with water (15-fold) and the aqueous extracted with CH2Cl2 (3×). The organics were dried over sodium sulfate, and concentrated in vacuo. The crude was purified by reverse phase HPLC reverse phase HPLC using a (25–65% gradient of 0.1% formic acid in acetonitrile and 0.1% formic acid in water) (to give the title compound (18 mg). LCMS (m/z) 423.5 M+1.
Reaction SMILES: O[CH2:2][CH2:3][CH2:4][C:5]1[N:6]=[C:7]([C:26]2[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][CH:27]=2)[S:8][C:9]=1[CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[NH:22][C:21](=[O:23])[O:20][N:19]=2)=[C:14]([O:24][CH3:25])[CH:13]=1.C(N(CC)CC)C.[CH3:43][S:44](Cl)(=O)=O>CN(C)C=O>[CH3:25][O:24][C:14]1[CH:13]=[C:12]([O:11][CH2:10][C:9]2[S:8][C:7]([C:26]3[CH:27]=[CH:28][C:29]([C:32]([F:34])([F:33])[F:35])=[CH:30][CH:31]=3)=[N:6][C:5]=2[CH2:4][CH2:3][CH2:2][S:44][CH3:43])[CH:17]=[CH:16][C:15]=1[C:18]1[NH:22][C:21](=[O:23])[O:20][N:19]=1
Reactant: CS(=O)(=O)Cl
Reactant: COc1cc(OCc2sc(-c3ccc(C(F)(F)F)cc3)nc2CCCO)ccc1-c1noc(=O)[nH]1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COc1cc(OCc2sc(-c3ccc(C(F)(F)F)cc3)nc2CCCSC)ccc1-c1noc(=O)[nH]1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a solution of 100 mg of 3-{4-[4-(3-hydroxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-methoxy-phenyl}-4H-[1,2,4]oxadiazol-5-one in 1 mL of dimethylformamide at 0° C. were added 0.077 mL of triethylamine and 0.015 mL of methanesulfonyl chloride. The resulting mixture was stirred at 0° C. for 30 minutes and then concentrated under reduced pressure. The product was dissolved in 3 mL of dimethylformamide. To the resulting solution were added 5.5 mg of sodium methanethiolate and 13 mg of potassium iodide. The reaction mixture was heated for 10 minutes to 90° C. under microwave irradiation in a sealed tube. It was then concentrated under reduced pressure, taken into dichloromethane, washed with water, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to give 20 mg of 3-{2-methoxy-4-[4-(3-methylsulfanyl-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-phenyl}-4H-1,2,4-oxadiazol-5-one.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8]([C:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([C:19]4[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=4[O:27][CH2:28][CH:29]4[CH2:31][CH2:30]4)[C:13]=3[NH:12][CH:11]=2)=[O:9])[CH2:3][CH2:2]1.Cl[C:33]([CH2:35][O:36]C(=O)C)=[O:34]>>[OH:36][CH2:35][C:33]([N:1]1[CH2:2][CH2:3][CH:4]([NH:7][C:8]([C:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([C:19]4[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=4[O:27][CH2:28][CH:29]4[CH2:30][CH2:31]4)[C:13]=3[NH:12][CH:11]=2)=[O:9])[CH2:5][CH2:6]1)=[O:34]
Reactant: COc1ccc(-c2ncnc3c(C(=O)NC4CCNCC4)c[nH]c23)c(OCC2CC2)c1
Reactant: CC(=O)OCC(=O)Cl
Product: COc1ccc(-c2ncnc3c(C(=O)NC4CCN(C(=O)CO)CC4)c[nH]c23)c(OCC2CC2)c1

Procedure:
Starting from 4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid piperidin-4-ylamide (example A152) and acetic acid chlorocarbonyl-methyl ester the title compound is obtained as colorless solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[O:19][CH3:20])[C:5]([C:7]1[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=1[C:9](O)=[O:10])=O.C1(C)C=CC=CC=1.[CH3:28][NH:29][NH2:30]>O>[CH3:28][N:29]1[N:30]=[C:5]([C:4]2[CH:16]=[CH:17][C:18]([O:19][CH3:20])=[C:2]([Cl:1])[CH:3]=2)[C:7]2[C:8](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:9]1=[O:10]
Reactant: CNN
Reactant: COc1ccc(C(=O)c2ccccc2C(=O)O)cc1Cl
Solvent: O
Solvent: Cc1ccccc1
Product: COc1ccc(-c2nn(C)c(=O)c3ccccc23)cc1Cl
Yield: 68.7 %

Procedure:
A mixture of 2-(3-chloro-4-methoxybenzoyl)benzoic acid (10.46 g, 0,036 mol), toluene (50 mL) and methyl hydrazine (2.1 mL) was refluxed in the presence of a Dean Stark trap until the theoretical amount of water had been collected. The reaction mixture was cooled, and the product was collected by filtration to afford 7.42 g (68.7%) of 2-methyl-4-(3-chloro-4-methoxyphenyl)-1-(2H)-phthalazinone, m.p. 195°-195° C. An additional 1.89 g of product was also collected from the filtrate for a total of 9.31 g (86.2%).
Reaction SMILES: [C:1]([O:6][C:7](=[O:11])[C:8]([CH3:10])=C)(=O)[C:2](C)=C.O[CH2:13][CH2:14][N:15](CC)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>N1C=CC=CC=1>[C:7]([O:6][CH2:1][CH2:2][N:15]([CH2:14][CH3:13])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)(=[O:11])[CH:8]=[CH2:10]
Reactant: C=C(C)C(=O)OC(=O)C(=C)C
Reactant: CCN(CCO)c1ccccc1
Solvent: c1ccncc1
Product: C=CC(=O)OCCN(CC)c1ccccc1
Temperature: 55 °C
Reaction time: 2 h

Procedure:
Methacrylic anhydride (7.7 g, 0.05 mol) is added to a solution of N-(2-hydroxyethyl)-N-ethylaniline (6.6 g, 0.04 mol) in pyridine (25 ml) and the mixture is stirred at 55° C. for 2 hours. On cooling the mixture is passed through silica gel to give N-(2-acryloyloxyethyl)-N-ethylaniline as a pale yellow oil. 5.3 g, 65%
Reaction SMILES: C[O:2][C:3](=O)[C:4]1[C:5](=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=1)[NH:6][C:7](=[O:18])[CH2:8][S:9]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:10].[H-].[Na+].O.Cl>O1CCCC1>[Cl:23][C:20]1[CH:19]=[C:5]2[C:4]([C:3]([OH:2])=[C:8]([S:9]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[O:10])[C:7](=[O:18])[NH:6]2)=[CH:22][CH:21]=1
Reactant: COC(=O)c1ccc(Cl)cc1NC(=O)CS(=O)Cc1ccccc1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: O=c1[nH]c2cc(Cl)ccc2c(O)c1S(=O)Cc1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
1.0 g (2.73 mmol) of N-(benzylsulfinyl)acetyl-4-chloro-anthranilic acid methyl ester is placed in 10 ml of tetrahydrofuran at 0°, and 0.13 g (3 mmol) of sodium hydride dispersion in oil (55%) is added thereto. The mixture is then stirred for 15 minutes at 0° and for 2 hours at room temperature. Water is added and the reaction mixture is then adjusted to pH 2-3 with 1N hydrochloric acid and extracted with ethyl acetate. The organic phases are washed with water and brine, combined, dried with sodium sulfate, filtered and concentrated. Crystallisation of the crude product from ethyl acetate/petroleum ether yields 7-chloro-3-(benzylsulfinyl)-4-hydroxy-2(1H)-quinolone in the form of colourless crystals having a melting point of 234° (decomp.).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]([C:10](OCC)=[O:11])[CH2:2]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].C1COCC1.O>C1COCC1>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]([CH2:10][OH:11])[CH2:2]1
Reactant: CCOC(=O)C1CNc2ccccc21
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: OCC1CNc2ccccc21

Procedure:
0.79 g (3.5 mmol) ethyl 2,3-dihydro-1H-indole-3-carboxylate were added batchwise at RT to 7.8 mL (7.8 mmol) of a 1 molar lithium aluminium hydride-THF solution in 40 mL THF and the mixture was refluxed for 1 h. Then the reaction mixture was decomposed with water, while cooling, the precipitate formed was filtered off and the filtrate was evaporated down.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[CH:16]=[CH:15][C:14]([CH:17](O)[C:18]3[C:26]4[C:21](=[N:22][CH:23]=[CH:24][CH:25]=4)[N:20]([Si](C(C)C)(C(C)C)C(C)C)[CH:19]=3)=[CH:13][N:12]=2)=[O:10])=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.C([SiH](CC)CC)C>C(#N)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[CH:16]=[CH:15][C:14]([CH2:17][C:18]3[C:26]4[C:21](=[N:22][CH:23]=[CH:24][CH:25]=4)[NH:20][CH:19]=3)=[CH:13][N:12]=2)=[O:10])=[CH:4][CH:3]=1
Reactant: CC(C)[Si](C(C)C)(C(C)C)n1cc(C(O)c2ccc(C(=O)Nc3ccc(Cl)cc3)nc2)c2cccnc21
Agent: CC[SiH](CC)CC
Solvent: CC#N
Solvent: O=C(O)C(F)(F)F
Product: O=C(Nc1ccc(Cl)cc1)c1ccc(Cc2c[nH]c3ncccc23)cn1
Temperature: 80 °C
Reaction time: 2 h

Procedure:
To 5-[Hydroxy-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-pyridine-2-carboxylic acid (4-chloro-phenyl)-amide (71, 100.0 mg, 0.19 mmol) in acetonitrile (10.0 mL) were added trifluoroacetic acid (0.20 mL, 2.6 mmol) and triethylsilane (0.40 mL, 2.5 mmol). The reaction was stirred at 80° C. for 2 hours. The reaction was concentrated and purified by silica gel column chromatography eluting with 20% ethyl acetate in hexane to give a yellow solid compound (P-0076, 5.5 mg, 8.1%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1.Cl[C:13]1[CH:14]=[C:15]([CH:21]=[CH:22][N:23]=1)[C:16]([O:18][CH2:19][CH3:20])=[O:17]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[CH:14]=[C:15]([CH:21]=[CH:22][N:23]=2)[C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:6]=[CH:7][CH:8]=1
Reactant: CCOC(=O)c1ccnc(Cl)c1
Reactant: COc1cccc(B(O)O)c1
Product: CCOC(=O)c1ccnc(-c2cccc(OC)c2)c1

Procedure:
3-Methoxyphenylboronic acid (1.00 g) and ethyl 2-chloroisonicotinate (1.20 g) were treated in the same manner as in Preparation Example 1 to obtain the title compound.
Reaction SMILES: [CH:1]1([CH2:4][N:5]2[C:10](=[O:11])[C:9]([CH3:12])=[CH:8][NH:7][C:6]2=[O:13])[CH2:3][CH2:2]1.[CH2:14]([N:20]=[C:21]=[O:22])[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]>>[CH:1]1([CH2:4][N:5]2[C:10](=[O:11])[C:9]([CH3:12])=[CH:8][N:7]([C:21]([NH:20][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])=[O:22])[C:6]2=[O:13])[CH2:2][CH2:3]1
Reactant: CCCCCCN=C=O
Reactant: Cc1c[nH]c(=O)n(CC2CC2)c1=O
Product: CCCCCCNC(=O)n1cc(C)c(=O)n(CC2CC2)c1=O
Yield: 23 %

Procedure:
The title compound was obtained according to the procedure described for the synthesis of Example 1, starting from 3-(cyclopropylmethyl)-5-methyl-1H-pyrimidine-2,4-dione (0.05 g, 0.30 mmol); 1.8 equivalents of hexyl isocyanate were used herein. The crude product was purified by preparative HPLC-MS to afford the title compound (0.02 g, 23%) as colorless oil. 1H NMR (400 MHz, CDCl3): δ 0.36-0.44 (m, 2H), 0.44-0.53 (m, 2H), 0.89 (t, J=6.7 Hz, 3H), 1.17-1.48 (m, 6H), 1.50-1.77 (m, 3H), 2.00 (d, J=1.3 Hz, 3H), 3.38 (td, J=7.1, 5.5 Hz, 2H), 3.86 (d, J=7.2 Hz, 2H), 8.23 (q, J=1.3 Hz, 1H), 9.37 (t, J=5.5 Hz, 1H). 13C NMR (101 MHz, CDCl3): δ 4.02, 9.76, 13.47, 14.15, 22.66, 26.70, 29.35, 31.55, 41.34, 46.25, 111.81, 132.62, 150.77, 152.71, 163.16. MS (ESI) m/z: 308 [M-H]+.
Reaction SMILES: [C:1]1([CH:7]2[CH2:12][N:11]([C:13](=[O:15])[CH3:14])[CH2:10][C:9]3[S:16][CH:17]=[CH:18][C:8]2=3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1CCCCC1.C(OCC)(=[O:27])C>>[C:1]1([CH:7]2[CH2:12][N:11]([C:13](=[O:15])[CH3:14])[C:10](=[O:27])[C:9]3[S:16][CH:17]=[CH:18][C:8]2=3)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC(=O)N1Cc2sccc2C(c2ccccc2)C1
Reactant: CCOC(C)=O
Solvent: C1CCCCC1
Product: CC(=O)N1CC(c2ccccc2)c2ccsc2C1=O
Yield: 20 %

Procedure:
The compound is prepared according to the procedure of Example 1, from 4-phenyl-6-acetyl-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine, to give white crystals, M.p.=132° C. (cyclohexane-ethyl acetate), Yield: 20%.
Reaction SMILES: [CH3:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][N:7]2[CH:11]=[C:10]([CH2:12][CH2:13][O:14]S(C3C=CC(C)=CC=3)(=O)=O)[N:9]([CH2:25][CH2:26][CH3:27])[C:8]2=[O:28])=[CH:4][CH:3]=1.[CH2:31]([O:33][C:34](=[O:47])[C:35]([O:45][CH3:46])([CH3:44])[CH2:36][C:37]1[CH:42]=[CH:41][C:40](O)=[CH:39][CH:38]=1)[CH3:32].C([O-])([O-])=O.[K+].[K+]>CCO.O>[CH2:31]([O:33][C:34](=[O:47])[C:35]([O:45][CH3:46])([CH3:44])[CH2:36][C:37]1[CH:42]=[CH:41][C:40]([O:14][CH2:13][CH2:12][C:10]2[N:9]([CH2:25][CH2:26][CH3:27])[C:8](=[O:28])[N:7]([CH2:6][C:5]3[CH:4]=[CH:3][C:2]([CH3:1])=[CH:30][CH:29]=3)[CH:11]=2)=[CH:39][CH:38]=1)[CH3:32]
Reactant: CCCn1c(CCOS(=O)(=O)c2ccc(C)cc2)cn(Cc2ccc(C)cc2)c1=O
Reactant: CCOC(=O)C(C)(Cc1ccc(O)cc1)OC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: O
Product: CCCn1c(CCOc2ccc(CC(C)(OC)C(=O)OCC)cc2)cn(Cc2ccc(C)cc2)c1=O
Temperature: 75 °C
Yield: 43.1 %

Procedure:
A mixture of toluene-4-sulfonic acid 2-[1-(4-methyl-benzyl)-2-oxo-3-propyl-2,3-dihydro-1H-imidazol-4-yl]-ethyl ester (0.079 g, 0.184 mmol), 3-(4-hydroxy-phenyl)-2-methoxy-2-methyl-propionic acid ethyl ester (0.038 g, 0.169 mmol) and K2CO3 (0.047 g, 0.340 mmol) in EtOH (8 mL) was heated at 75° C. under N2 for 16 h. The reaction mixture was cooled to room temperature and quenched with aqueous 1 N HCl (1 mL). The solvent was removed in vacuo to give a residue that was diluted with water and extracted with EtOAc. The organic layer was dried (MgSO4) and the solvent removed in vacuo to afford crude product that was purified by flash chromatography using a 2:1 hexanes:acetone to afford 0.036 g (44%) 2-methoxy-2-methyl-3-(4-{2-[1-(4-methyl-benzyl)-2-oxo-3-propyl-2,3-dihydro-1H-imidazol-4-yl]-ethoxy}-phenyl)-propionic acid ethyl ester.
Reaction SMILES: [CH2:1]([N:3]([CH2:6][C:7]1[S:11][C:10]([C:12]([OH:14])=O)=[CH:9][C:8]=1[CH3:15])[CH2:4][CH3:5])[CH3:2].[OH:16][CH2:17][C:18]([NH:20][CH2:21][C@H:22]([OH:38])[CH2:23][O:24][C:25]1[C:30]([CH3:31])=[CH:29][C:28]([C:32](=[NH:35])[NH:33]O)=[CH:27][C:26]=1[O:36][CH3:37])=[O:19]>>[CH2:4]([N:3]([CH2:6][C:7]1[S:11][C:10]([C:12]2[O:14][N:33]=[C:32]([C:28]3[CH:29]=[C:30]([CH3:31])[C:25]([O:24][CH2:23][C@@H:22]([OH:38])[CH2:21][NH:20][C:18](=[O:19])[CH2:17][OH:16])=[C:26]([O:36][CH3:37])[CH:27]=3)[N:35]=2)=[CH:9][C:8]=1[CH3:15])[CH2:1][CH3:2])[CH3:5]
Reactant: CCN(CC)Cc1sc(C(=O)O)cc1C
Reactant: COc1cc(C(=N)NO)cc(C)c1OC[C@@H](O)CNC(=O)CO
Product: CCN(CC)Cc1sc(-c2nc(-c3cc(C)c(OC[C@@H](O)CNC(=O)CO)c(OC)c3)no2)cc1C
Yield: 9.9 %

Procedure:
The title compound (6 mg) is prepared starting from 5-diethylaminomethyl-4-methyl-thiophene-2-carboxylic acid (30 mg, 130 μmol) and (S)-2-hydroxy-N-(2-hydroxy-3-[4-(N-hydroxycarbamimidoyl)-2-methoxy-6-methyl-phenoxy]-propyl)-acetamide (38 mg, 117 μmol) according to Method A; LC-MS: tR=0.51 min; [M+1]+=519.17.
Reaction SMILES: [Cl:1][C:2]1[C:7]([O:8][CH2:9][C:10]#[CH:11])=[CH:6][C:5]([N:12]2[C:17](=[O:18])[N:16]([CH3:19])[C:15](=[O:20])[CH:14]=[N:13]2)=[C:4]([F:21])[CH:3]=1>C(O)(=O)C.O.[Zn]>[Cl:1][C:2]1[C:7]([O:8][CH2:9][C:10]#[CH:11])=[CH:6][C:5]([N:12]2[C:17](=[O:18])[N:16]([CH3:19])[C:15](=[O:20])[CH2:14][NH:13]2)=[C:4]([F:21])[CH:3]=1
Reactant: C#CCOc1cc(-n2ncc(=O)n(C)c2=O)c(F)cc1Cl
Agent: [Zn]
Solvent: O
Solvent: CC(=O)O
Product: C#CCOc1cc(N2NCC(=O)N(C)C2=O)c(F)cc1Cl
Temperature: 60 °C
Yield: 74 %

Procedure:
A solution of 1.6 g (0.0052 mole) of 2-(4-chloro-2-fluoro-5-(2-propynyloxy)phenyl]-4-methyl-1,2,4-triazine-3.5(2H,4H)-dione (compound 21) dissolved in 5 mL of glacial acetic acid was added dropwise to a stirred suspension of 1.5 g (0.023 mole) of zinc dust in 10 mL of glacial acetic acid and 5 mL of water. After complete addition the mixture was heated at 60° C. for 1.5 hours. The mixture was filtered and the filtrate was partitioned between 50 mL of water and 50 mL of diethyl ether. The organic phase was washed first with water followed by a saturated aqueous sodium bicarbonate solution. The washed organic phase was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure to yield 1.2 g of 2-[4-chloro-2-fluoro-5-(2-propynyloxy)phenyl]-1,6-dihydro-4-methyl-1,2,4-triazine-3,5(2H,4H)-dione as an oil, compound A-3 of Table A-1.
Reaction SMILES: C([O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17]Br)=[CH:11][CH:10]=1)C1C=CC=CC=1.[N:19]1[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2[NH:21][CH:20]=1>>[N:19]1([CH2:17][CH2:16][O:15][C:12]2[CH:11]=[CH:10][C:9]([OH:8])=[CH:14][CH:13]=2)[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2[N:21]=[CH:20]1
Reactant: c1ccc2[nH]cnc2c1
Reactant: BrCCOc1ccc(OCc2ccccc2)cc1
Product: Oc1ccc(OCCn2cnc3ccccc32)cc1

Procedure:
In a manner analogous to that described in Example 1(b), from 1-benzyloxy-4-(2-bromoethoxy)benzene and benzimidazole, 4-[2-(1-benzimidazolyl)ethoxy]phenol was obtained.
Reaction SMILES: [C:1]1([N:7]2[C:11](=[O:12])[CH:10]([CH2:13][CH2:14][S:15][CH3:16])[NH:9][C:8]2=[O:17])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S([O-])(O[CH3:22])(=O)=O.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH3:22][N:9]1[CH:10]([CH2:13][CH2:14][S:15][CH3:16])[C:11](=[O:12])[N:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:8]1=[O:17]
Reactant: COS(=O)(=O)[O-]
Reactant: CSCCC1NC(=O)N(c2ccccc2)C1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CSCCC1C(=O)N(c2ccccc2)C(=O)N1C

Procedure:
A solution in acetone of 250 g (1 mole) of 3-phenyl-5-methylthioethyl hydantoin (compound no. 27) and 126 g (1 mole) of methyl sulphate is heated under reflux for 8 hours, accompanied by the addition with stirring of 138 g (1 mole) of potassium carbonate. The concentration of the acetone solution is between 0.5 and 1 mole per liter. On completion of the reaction, the potassium salts are separated by filtration and the acetone eliminated by evaporation. The residue crystallises on cooling. It can be recrystallised from methanol.