Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]=[CH:7]1.[C:15]([C:17]1[CH:18]=[C:19]([N:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[CH:20]=[CH:21][CH:22]=1)#[N:16].C(N(C(C)C)CC)(C)C.[I-].[K+]>C(#N)C>[C:15]([C:17]1[CH:18]=[C:19]([N:23]2[CH2:28][CH2:27][N:26]([CH2:2][CH2:3][CH2:4][CH2:5][N:6]3[C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=4[N:8]=[CH:7]3)[CH2:25][CH2:24]2)[CH:20]=[CH:21][CH:22]=1)#[N:16]
Reactant: ClCCCCn1cnc2ccccc21
Reactant: N#Cc1cccc(N2CCNCC2)c1
Agent: [I-]
Agent: [K+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: N#Cc1cccc(N2CCN(CCCCn3cnc4ccccc43)CC2)c1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 62.1 %

Procedure:
1-(4-chlorobutyl)-1H-benzimidazole (7.51 g, 0.036 mol) was dissolved into 100 ml of acetonitrile, 3-cyanophenyl piperazine (5.6 g, 0.03 mol), diisopropylethylamine (15.5 g, 0.12 mol) and potassium iodide (5.0 g, 0.03 mol) were respectively added. The mixture was stirred for 10 min at ambient temperature, and then heated and refluxed to react for 10-15 hours. The mixture was cooled down to ambient temperature and filtered. The filtrate was concentrated to produce oily products, and treated by chromatography with neutral Al2O3, eluted with dichloromethane/methanol mixture to produce 6.7 g compound (I-10) with a yield of 62.4%. ESI-MS [M+H]+: m/z 360.2.
Reaction SMILES: Cl[C:2]1[NH:7][C:6]2[CH:8]=[CH:9][C:10]([Cl:12])=[CH:11][C:5]=2[S:4](=[O:14])(=[O:13])[N:3]=1.[C:15]1([CH:21]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:22][CH2:23][NH2:24])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>>[Cl:12][C:10]1[CH:9]=[CH:8][C:6]2[NH:7][C:2]([NH:24][CH2:23][CH2:22][CH:21]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[N:3][S:4](=[O:14])(=[O:13])[C:5]=2[CH:11]=1
Reactant: O=S1(=O)N=C(Cl)Nc2ccc(Cl)cc21
Reactant: NCCC(c1ccccc1)c1ccccc1
Product: O=S1(=O)N=C(NCCC(c2ccccc2)c2ccccc2)Nc2ccc(Cl)cc21

Procedure:
Starting from 3,7-dichloro-4H-1,2,4-benzothiadiazine 1,1-dioxide (300 mg; 1.19 mmol) and 3,3-diphenylpropylamine (1.5 g; 7.1 mmol) with the use of same procedure as in example 21 300 mg (59%) of the title compound was prepared; 1H-NMR (DMSO-d6) ppm; 10.7 (s, 1H, NH), 7.68 (d, 1H, H-8), 7.60 (dd, 1H, H-5), 7.25 (m, 11H, ), 4.1 (t, 1H, CH), 3.11 (q, 2H, CH2), 2.35 (q, 2H, CH2); MS:EI/70eV: 425 (M+), 245, 193, 180, 165, 152, 115.
Reaction SMILES: [O:1]([CH2:8][CH2:9][OH:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Na].[H-].[Na+].[N+]([C:17]1[CH:24]=[CH:23][CH:22]=[C:21]([N+:25]([O-:27])=[O:26])[C:18]=1[C:19]#[N:20])([O-])=O>CS(C)=O>[N+:25]([C:21]1[CH:22]=[CH:23][CH:24]=[C:17]([O:10][CH2:9][CH2:8][O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:18]=1[C:19]#[N:20])([O-:27])=[O:26]
Reactant: OCCOc1ccccc1
Reactant: N#Cc1c([N+](=O)[O-])cccc1[N+](=O)[O-]
Agent: [H-]
Agent: [Na+]
Agent: [Na]
Solvent: CS(C)=O
Product: N#Cc1c(OCCOc2ccccc2)cccc1[N+](=O)[O-]
Temperature: 25 °C
Yield: 99.7 %

Procedure:
2-Phenoxyethanol (4.15 ml, 0.033 mole) is added to dimethylsulfoxyl sodium prepared from 1.39 g of 57 per cent sodium hydride and 40 ml dimethylsulfoxide, giving a mixture of the solid salt of the alcohol after about 20 minutes. This mixture is added to a solution of 5.8 g (0.030 mole) 2,6-dinitrobenzonitrile in 20 ml of dimethylsulfoxide at 30°-40°C., and the resulting purple solution is stirred over night at room temperature. The solvent is removed at 70°C. on a rotary evaporator, and the residue is triturated with water. A solid is filtered off and it is dissolved in ethylacetate. The ethylacetate solution is washed twice with H2O, brine, and dried with calcium sulfate. Evaporation of the ethylacetate, gives 8.5 g of 2-nitro-6(2-phenoxyethoxy)-benzonitrile, which is crystallized from 200 ml ethyl alcohol, giving 6 g, m.p. 129°-137.5°C.
Reaction SMILES: CC1C=C(N2CCN(CCOC3C=CC=CC=3)C2=O)SC=1C(O)=O.[F:25][C:26]1[CH:47]=[CH:46][C:29]([CH2:30][N:31]2[CH2:35][CH2:34][N:33]([C:36]3[S:40][C:39]([C:41](O)=[O:42])=[C:38]([CH3:44])[CH:37]=3)[C:32]2=[O:45])=[CH:28][CH:27]=1.[CH3:48][C:49]1[CH:53]=[CH:52][S:51][C:50]=1[CH2:54][NH2:55]>>[F:25][C:26]1[CH:27]=[CH:28][C:29]([CH2:30][N:31]2[CH2:35][CH2:34][N:33]([C:36]3[S:40][C:39]([C:41]([NH:55][CH2:54][C:50]4[S:51][CH:52]=[CH:53][C:49]=4[CH3:48])=[O:42])=[C:38]([CH3:44])[CH:37]=3)[C:32]2=[O:45])=[CH:46][CH:47]=1
Reactant: Cc1cc(N2CCN(Cc3ccc(F)cc3)C2=O)sc1C(=O)O
Reactant: Cc1ccsc1CN
Agent: Cc1cc(N2CCN(CCOc3ccccc3)C2=O)sc1C(=O)O
Product: Cc1ccsc1CNC(=O)c1sc(N2CCN(Cc3ccc(F)cc3)C2=O)cc1C
Yield: 73 %

Procedure:
Following the procedures as described in Example 55, making variations as required to replace 3-methyl-5-(2-oxo-3-(2-phenoxyethyl)imidazolidin-1-yl)thiophene-2-carboxylic acid with 5-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)-3-methylthiophene-2-carboxylic acid to react with (3-methylthiophen-2-yl)methanamine, the title compound was obtained as a colorless solid in 73% yield: 1H NMR (300 MHz, CDCl3) δ 7.30-7.23 (m, 2H), 7.13 (d, J=5.0 Hz, 1H), 7.08-6.99 (m, 2H), 6.82 (d, J=5.0 Hz, 1H), 6.08 (s, 1H), 5.83 (br s, 1H), 4.65 (d, J=5.0 Hz, 2H), 4.42 (s, 2H), 3.83-3.74 (m, 2H), 3.47-3.39 (m, 2H), 2.49 (5, 3H), 2.24 (s, 3H): MS (ES+) m/z 444.2 (M+1).
Reaction SMILES: Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([NH:8][C:9]([C:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([C:20]4[C:28]5[O:27][CH2:26][O:25][C:24]=5[CH:23]=[CH:22][C:21]=4[O:29][CH2:30][CH:31]4[CH2:34][CH2:33][CH2:32]4)[C:14]=3[NH:13][CH:12]=2)=[O:10])[CH2:4][CH2:3]1.[CH:35]1([C:38](Cl)=[O:39])[CH2:37][CH2:36]1>>[CH:35]1([C:38]([N:2]2[CH2:7][CH2:6][CH:5]([NH:8][C:9]([C:11]3[C:15]4[N:16]=[CH:17][N:18]=[C:19]([C:20]5[C:28]6[O:27][CH2:26][O:25][C:24]=6[CH:23]=[CH:22][C:21]=5[O:29][CH2:30][CH:31]5[CH2:32][CH2:33][CH2:34]5)[C:14]=4[NH:13][CH:12]=3)=[O:10])[CH2:4][CH2:3]2)=[O:39])[CH2:37][CH2:36]1
Reactant: O=C(Cl)C1CC1
Reactant: O=C(NC1CCNCC1)c1c[nH]c2c(-c3c(OCC4CCC4)ccc4c3OCO4)ncnc12
Agent: Cl
Product: O=C(NC1CCN(C(=O)C2CC2)CC1)c1c[nH]c2c(-c3c(OCC4CCC4)ccc4c3OCO4)ncnc12

Procedure:
Starting from 4-(5-cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid piperidin-4-ylamide hydrochloride (example A174) and cyclopropanecarbonyl chloride the title compound is obtained as colorless solid.
Reaction SMILES: Br[CH:2]([CH:6]([C:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:18][CH3:19])[CH:14]=2)[CH:9]=1)[CH3:7])[C:3](Br)=[O:4].[C:20]([NH2:28])(=[S:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.N1C=CC=CC=1>C1(C)C=CC=CC=1>[CH3:19][O:18][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([CH:6]([C:2]1[S:27][C:20]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[N:28][C:3]=1[OH:4])[CH3:7])[CH:17]=[CH:16]2
Reactant: COc1ccc2cc(C(C)C(Br)C(=O)Br)ccc2c1
Reactant: NC(=S)c1ccccc1
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: COc1ccc2cc(C(C)c3sc(-c4ccccc4)nc3O)ccc2c1
Temperature: 100 °C
Yield: 35.4 %

Procedure:
To a solution of 2-bromo-3-(6-methoxy-2-naphthyl) butyrylbromide (386 mg, 1 mmol) in toluene (20 mL) was added thiobenzamide (137 mg, 1 mmol) and pyridine (0.16 mL, 2 mmol) in toluene (60 mL) at 23° C. The reaction mixture was heated at 100° C. for 4 hours and then cooled and the solvent removed in vacuo. Recrystallization of the residue from ethanol/ether provided the desired product (128 mg). mp 224°-226° C., 1H NMR (60 MHz, DMSO-d6) 1.30 (3H, d, J=7 Hz), 3.82 (3H, s), 3.92 (1H, g, J=7 Hz), 7.1-8.0 (11H, m), 10.55 (1H, s); Mass Spectrum: 361 (M+).
Reaction SMILES: [C:1]([O:5][CH2:6][CH:7]=[CH2:8])(=[O:4])[NH:2][NH2:3].[CH3:9][C:10]1([CH3:26])[CH2:15][CH:14]([NH:16][C:17](=[O:23])[C:18](OCC)=[O:19])[CH2:13][C:12]([CH3:25])([CH3:24])[NH:11]1>CO>[CH3:9][C:10]1([CH3:26])[CH2:15][CH:14]([NH:16][C:17](=[O:23])[C:18]([NH:3][NH:2][C:1]([O:5][CH2:6][CH:7]=[CH2:8])=[O:4])=[O:19])[CH2:13][C:12]([CH3:25])([CH3:24])[NH:11]1
Reactant: CCOC(=O)C(=O)NC1CC(C)(C)NC(C)(C)C1
Reactant: C=CCOC(=O)NN
Solvent: CO
Product: C=CCOC(=O)NNC(=O)C(=O)NC1CC(C)(C)NC(C)(C)C1
Temperature: 50 °C
Reaction time: 1.33 h
Yield: 85.7 %

Procedure:
Into a 250 ml 3-neck flask was added 9.2 grams (0.079 mole) of allyl carbazate from (A), 34.2 grams (0.08 mole) of a 60% solution of ethyl N-(2,2,6,6-tetramethyl-4-piperidinyl)oxamate and 50 ml of methanol. The flask was equipped with a magnetic stirrer, thermometer and a Dean Stark trap with a reflux The reaction was heated in an oil bath and the methanol was distilled off through the Dean Stark trap. After the methanol distillation ceased, a vacuum was applied to the system to remove any residual methanol and the reaction was cooked for 80 minutes at 90° C. The reaction was cooled to 50° C. and 50 ml of methanol was added and the reaction heated back up to reflux to dissolve the residue. The methanol solution was cooled and concentrated to 25 ml. Upon addition of 25 ml of methyl t-butyl ether, a white solid formed. The solid was filtered off and dried in a vacuum oven over night. The dry powder weighed 22.1 grams (85.7% yield) and assayed 100% by liquid chromatography. The infrared scan of the product contained a weak carbonyl at 1750 cm-1 and a strong carbonyl at 1680 cm-1.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[CH3:12][N:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16](=[O:23])[C:15]([S:24]([CH3:26])=[O:25])=[N:14]1.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl>[CH3:12][N:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16](=[O:23])[C:15]([S:24]([CH3:26])(=[O:9])=[O:25])=[N:14]1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: Cn1nc(S(C)=O)c(=O)c2ccccc21
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: Cn1nc(S(C)(=O)=O)c(=O)c2ccccc21
Reaction time: 0.08 h
Yield: 104.1 %

Procedure:
A quantity of 6.16 g (0.027 mole) of 85% m-chloroperbenzoic acid was added to a solution of 6.6 g (0.03 mole) of 1-methyl-3-(methylsulfinyl)-4(1H)-cinnolinone in 100 ml of chloroform. The temperature rose to 45° C. After 5 minutes the solution was brought to reflux for 5 minutes, cooled, mixed with 200 ml of 5% sodium bicarbonate and stirred for 10 minutes. Additional chloroform (300 ml) was added to dissolve the separated product. The organic layer was separated, dried over anhydrous potassium carbonate and concentrated to give 6.7 g (94.4%) of white product melting at 202°-204°. Recrystallization from chloroform-methanol gave pure product melting at 204°-206° C.
Reaction SMILES: [CH3:1][CH:2]([S:5][C:6]1[CH:11]=[CH:10][C:9]([SH:12])=[CH:8][CH:7]=1)[CH2:3][CH3:4].C(=O)([O-])[O-].[K+].[K+].Br[CH2:20][CH2:21][N:22]1[C:26](=[O:27])[C:25]2=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]2[C:23]1=[O:32].O>CN(C=O)C>[CH3:1][CH:2]([S:5][C:6]1[CH:7]=[CH:8][C:9]([S:12][CH2:20][CH2:21][N:22]2[C:26](=[O:27])[C:25]3=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]3[C:23]2=[O:32])=[CH:10][CH:11]=1)[CH2:3][CH3:4]
Reactant: CCC(C)Sc1ccc(S)cc1
Reactant: O=C1c2ccccc2C(=O)N1CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCC(C)Sc1ccc(SCCN2C(=O)c3ccccc3C2=O)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To 4-(1-methylpropylthio)benzenethiol (8.79 g, 44.3 mmol) in 25 ml of DMF is added, under N2, potassium carbonate (7.05 g, 51.0 mmol) followed by dropwise addition of N-(bromoethyl)phthalimide (12.94 g, 51.0 mmol) in 30 ml of DMF. The mixture is stirred at RT overnight. Water is then added and the aqueous phase is extracted with ether. The combined organic layers are washed with 5% sodium hydroxide, with water and with brine, dried and the solvent removed to give N-{2-[4-(1-methylpropylthio)phenylthio]ethyl)phthalimide. Following the procedures of Example 13, the above phthalimide (2.12 g, 5.7 mmol) is reacted with hydrazine hydrate (0.28 ml, 5.7 mmol) to give 2-[4-(1-methylpropylthio)phenylthio]ethylamine.
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[CH:31]=[CH:30][C:9]([CH2:10][O:11][C:12]3[CH:20]=[CH:19][C:18]4[NH:17][C:16]5[CH:21]([CH2:24][C:25]([O:27]CC)=[O:26])[CH2:22][CH2:23][C:15]=5[C:14]=4[CH:13]=3)=[CH:8][C:7]=2[C:32]([F:35])([F:34])[F:33])[CH2:3][CH2:2]1.[Li+].[OH-]>O1CCOCC1.CCOC(C)=O>[CH:1]1([CH2:4][O:5][C:6]2[CH:31]=[CH:30][C:9]([CH2:10][O:11][C:12]3[CH:20]=[CH:19][C:18]4[NH:17][C:16]5[CH:21]([CH2:24][C:25]([OH:27])=[O:26])[CH2:22][CH2:23][C:15]=5[C:14]=4[CH:13]=3)=[CH:8][C:7]=2[C:32]([F:35])([F:33])[F:34])[CH2:3][CH2:2]1
Reactant: CCOC(=O)CC1CCc2c1[nH]c1ccc(OCc3ccc(OCC4CC4)c(C(F)(F)F)c3)cc21
Agent: [Li+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: O=C(O)CC1CCc2c1[nH]c1ccc(OCc3ccc(OCC4CC4)c(C(F)(F)F)c3)cc21
Reaction time: 3 h

Procedure:
To a solution of ethyl 2-(7-(4-(cyclopropylmethoxy)-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate (22.9 mg, 0.047 mmol) in dioxane was added 1M LiOH (0.188 mL, 0.188 mmol). The reaction mixture was stirred 3 h, taken up in EtOAc and washed with 1 M HCl. The EtOAc extract was dried over MgSO4 and concentrated. The residue was purified by preparative HPLC/MS to give the title compound as a solid. LCMS m/z=460.3 [M±H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.30-0.38 (m, 2H), 0.52-0.59 (m, 2H), 1.17-1.27 (m, 1H), 2.03-2.13 (m, 1H), 2.35 (dd, J=15.98, 8.91 Hz, 1H), 2.59-2.76 (m, 4H), 3.99 (d, J=6.69 Hz, 2H), 5.05 (s, 2H), 6.69 (dd, J=8.84, 2.40 Hz, 1H), 6.91 (d, J=2.53 Hz, 1H), 7.19 (d, J=8.72 Hz, 1H), 7.24 (d, J=8.46 Hz, 1H), 7.62-7.71 (m, 2H), 10.45 (s, 1H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.S([O-])([O-])(=O)=O.[Mg+2].[Cl-].[C:18]([O:22][C:23](=[O:26])[CH2:24][Zn+])([CH3:21])([CH3:20])[CH3:19]>O1CCCC1.C(OCC)(=O)C>[CH2:18]([O:22][C:23](=[O:26])[CH:24]([NH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2)[CH2:24][C:23]([O:22][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:26])[CH3:19]
Reactant: Nc1ccc2[nH]ncc2c1
Reactant: CC(C)(C)OC(=O)C[Zn+]
Agent: O=S(=O)([O-])[O-]
Agent: [Cl-]
Agent: [Mg+2]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCOC(=O)C(CC(=O)OC(C)(C)C)Nc1ccc2[nH]ncc2c1
Temperature: 25 °C
Reaction time: 23 h
Yield: 65 %

Procedure:
To a solution/suspension of 5-aminoindazole (1.01 g, 7.6 mmol) in tetrahydrofuran (20 mL) was added ethyl glyoxlate solution (ca. 50% in toluene, 1.7 mL, 1.1 equiv) in one portion followed by magnesium sulfate (4.6 g). The mixture was stirred at room temperature overnight (23 h) and then filtered and concentrated in vacuo. The resulting crude imine intermediate (1.3 g, 6 mmol) was dried by azeotroping with anhydrous benzene and further dried under high vacuum. The residue was then dissolved in tetrahydrofuran (20 mL) and cooled at 0° C. A solution of 2-tert-butoxy-2-oxoethylzinc chloride (0.5 M in ether, 24 mL, 2 equiv) was then slowly added. After stirring at 0° C. for 1 h, the mixture was stored at 4° C. overnight. The mixture was then diluted with ethyl acetate and quenched with half-saturated ammonium chloride solution along with a minimum amount of 0.5 N HCl to dissolve the precipitated solids. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water and saturated sodium bicarbonate solution. The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel, eluting with 10% methanol in methylene chloride, to afford the desired product (1.3 g, 65%) as a tan oil. 1H-NMR (400 MHz, CDCl3) δ 7.89 (1H, s), 7.40–7.27 (1H, m), 6.98–6.77 (2H, m), 4.42–4.35 (1H, m), 4.30–4.12 (3H, m), 2.80 (2H, d, J=4.4 Hz ), 1.43 (9H, s), 1.27–1.17 (4H, m). Mass spec.: 356.24 (M+Na)+, 278.23 (M−tBu)+, tR=1.287 min.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:24])[C@@H:5]1[CH2:9][CH2:8][CH2:7][N:6]1[C:10](=[O:23])[C@H:11]([CH3:22])[NH:12][C:13]([C:15]1[CH:20]=[CH:19][N:18]=[C:17](Cl)[CH:16]=1)=[O:14])[CH3:2].C(O)C(O)C.[S:30]([O-])([O-])(=O)=S.[Na+].[Na+]>O>[CH2:1]([O:3][C:4](=[O:24])[C@@H:5]1[CH2:9][CH2:8][CH2:7][N:6]1[C:10](=[O:23])[C@H:11]([CH3:22])[NH:12][C:13]([C:15]1[CH:20]=[CH:19][NH:18][C:17](=[S:30])[CH:16]=1)=[O:14])[CH3:2]
Reactant: O=S([O-])([O-])=S
Reactant: CCOC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)c1ccnc(Cl)c1
Agent: [Na+]
Solvent: CC(O)CO
Solvent: O
Product: CCOC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)c1cc[nH]c(=S)c1
Yield: 85 %

Procedure:
To a solution of 4.5 g (0.013 mol) of N-[(2-Chloro-4-pyridinyl)carbonyl]-L-alanyl-L-proline ethyl ester (Compound No. 3) in 45 ml of a 10:1 mixture of 1,2-propyleneglycol:water, 15.2 g of sodium thiosulfate are added, and the mixture is heated under reflux for 15 hours. The resulting reaction mixture is diluted with 100 ml of water and extracted with four 100 ml portions of methylene chloride. The organic layer is washed three times with 100 ml of water, dried over anhydrous magnesium sulfate, and the solvent is distilled off at reduced pressure. The residue obtained is purified by crystallisation from a mixture of acetone:petroleum ether, to give the title product as a yellow solid (yield: 85%).
Reaction SMILES: Br[C:2]1[CH:19]=[CH:18][C:17]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[C:4]=2[CH:3]=1.[CH:20]1[C:28]2[C:27]3[CH:29]=[CH:30][CH:31]=[CH:32][C:26]=3[S:25][C:24]=2[C:23](B(O)O)=[CH:22][CH:21]=1.C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH:3]1[C:4]2[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[C:11]3[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:17]=2[CH:18]=[CH:19][C:2]=1[C:32]1[C:26]2[S:25][C:24]3[CH:23]=[CH:22][CH:21]=[CH:20][C:28]=3[C:27]=2[CH:29]=[CH:30][CH:31]=1
Reactant: Brc1ccc2c3ccccc3c3ccccc3c2c1
Reactant: OB(O)c1cccc2c1sc1ccccc12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: O
Product: c1ccc2c(c1)sc1c(-c3ccc4c5ccccc5c5ccccc5c4c3)cccc12
Yield: 85.1 %

Procedure:
4.4 g (14.6 mmol) of 2-bromotriphenylene, 4.0 g (17.5 mmol) of 4-dibenzothiopheneboronic acid, 0.51 g (0.44 mmol) of tetrakistriphenylphosphinepalladium, and 4.0 g (43.4 mmol) of potassium carbonate were charged in a 250 mL round bottom flask with solvent 90 mL of toluene and 10 mL of water. The reaction mixture was purged with nitrogen for 30 min and then was heated up to reflux for overnight under nitrogen with stirring. The reaction mixture was cooled and the organic extracts were purified by column chromatography and recrystallization with toluene. 5.1 g (86%) of white solid was obtained as the product which was confirmed by proton NMR.
Reaction SMILES: [C:1]1([C:7]2[C:15]([CH:16]=O)=[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][N:9]3[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[NH2:19][NH:20][C:21]([NH2:23])=[O:22]>C(O)C>[C:1]1([C:7]2[C:15]([CH:16]=[N:19][NH:20][C:21]([NH2:23])=[O:22])=[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][N:9]3[N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=Cc1c(-c2ccccc2)nn2ccccc12
Reactant: NNC(N)=O
Agent: Cl
Solvent: CCO
Product: NC(=O)NN=Cc1c(-c2ccccc2)nn2ccccc12
Yield: 41.5 %

Procedure:
A mixture of 2-phenylpyrazolo[1,5-a]pyridine-3-carbaldehyde (0.5 g) and semicarbazide hydrochloride (0.25 g) in ethanol (7ml) was refluxed for 1 hour and then cooled. The resulting precipitates were filtered and recrystallized from a mixture of water and ethanol to give 2-phenylpyrazolo[1,5-a]pyridine-3-carbaldehyde semicarbazone (0.26 g).
Reaction SMILES: CC(C)([O-])C.[K+].[Cl:7][C:8]1[CH:9]=[CH:10][C:11]2[NH:17][C:16](=O)[CH2:15][N:14]=[C:13]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[F:25])[C:12]=2[CH:26]=1.P(Cl)(OCC)(OCC)=O.[N+:36]([CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])#[C-:37]>O1CCCC1>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]2[N:17]3[CH:37]=[N:36][C:38]([C:39]([O:41][CH2:42][CH3:43])=[O:40])=[C:16]3[CH2:15][N:14]=[C:13]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[F:25])[C:12]=2[CH:26]=1
Reactant: [C-]#[N+]CC(=O)OCC
Reactant: O=C1CN=C(c2ccccc2F)c2cc(Cl)ccc2N1
Agent: CC(C)(C)[O-]
Agent: CCOP(=O)(Cl)OCC
Agent: [K+]
Solvent: C1CCOC1
Product: CCOC(=O)c1ncn2c1CN=C(c1ccccc1F)c1cc(Cl)ccc1-2
Reaction time: 0.08 h

Procedure:
Potassium t-butoxide, 1.29 g (0.0115 mol) was added to a stirred solution of 2.88 g (0.01 mol) of 7-chloro-1,3-dihydro-5-(2-fluorophenyl)-2H-1,4-benzodiazepine-2-one in 50 ml of tetrahydrofuran, that had been cooled in an ice bath and covered with a nitrogen atmosphere. After stirring for 5 minutes, 2.59 g (0.015 mol) diethyl chlorophosphate was added. After stirring for 5 minutes, a mixture of 2.26 g (0.02 mol) of ethyl isocyanoacetate in 50 ml of tetrahydrofuran that had been treated with 2.24 g (0.02 mol) of potassium t-butoxide just prior to the addition, was added. After 5 minutes, the ice bath was removed and the stirring was continued for 15 minutes. The mixture was acidified with 2 ml of glacial acetic acid, diluted with 200 ml of saturated sodium bicarbonate solution and extracted twice with 125 ml portions of toluene. The extracts were dried and evaporated and the residue was crystallized from ether to give the product with mp 195°-197°. For analysis, the material was recrystallized from methylene chloride/ether/hexane to give colorless crystals with mp 195°-196°.
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5]1[CH:20]=[C:19]([O:21][CH3:22])[CH:18]=[CH:17][C:6]=1[CH2:7][N:8]1[CH2:12][C@H:11]([CH:13]([CH3:15])[CH3:14])[NH:10][C:9]1=[O:16].Br[CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26]>CN(C=O)C>[CH2:28]([O:27][C:25](=[O:26])[CH2:24][N:10]1[C@@H:11]([CH:13]([CH3:15])[CH3:14])[CH2:12][N:8]([CH2:7][C:6]2[CH:17]=[CH:18][C:19]([O:21][CH3:22])=[CH:20][C:5]=2[O:4][CH3:3])[C:9]1=[O:16])[CH3:29]
Reactant: CCOC(=O)CBr
Reactant: COc1ccc(CN2C[C@H](C(C)C)NC2=O)c(OC)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)CN1C(=O)N(Cc2ccc(OC)cc2OC)C[C@@H]1C(C)C
Reaction time: 0.33 h

Procedure:
Sodium hydride (60%, 380 mg) was added to a solution of (4S)-1-(2,4-dimethoxybenzyl)-4-(propan-2-yl)imidazolidin-2-one (2.4 g) in DMF (35 mL), and the mixture was stirred for 20 min. Ethyl bromoacetate (1.14 mL) was added thereto, and the mixture was stirred at 90° C. for 1 hr. Additional ethyl bromoacetate (1.14 g) and sodium hydride (60%, 380 mg) were added thereto, and the resulting mixture was further stirred at 90° C. for 1 hr. After the solvent was distilled off under reduced pressure, the residue was purified by column chromatography (silica gel cartridge, hexane/ethyl acetate) to afford ethyl[(55)-3-(2,4-dimethoxybenzyl)-2-oxo-5-(propan-2-yl)imidazolidin-1-yl]acetate (1.5 g).
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]([S:8][CH:9]2[N:12]([C:13](=[C:22](N3CCCCC3)[CH2:23][Br:24])[C:14]([O:16][CH2:17][C:18]([Cl:21])([Cl:20])[Cl:19])=[O:15])[C:11](=[O:31])[CH:10]2[NH:32][C:33](=[O:42])[CH2:34][O:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[O:7])[CH2:3][CH2:2]1.Cl.C[OH:45]>>[CH:1]1([CH2:4][O:5][C:6]([S:8][CH:9]2[N:12]([C:13](=[C:22]([OH:45])[CH2:23][Br:24])[C:14]([O:16][CH2:17][C:18]([Cl:19])([Cl:20])[Cl:21])=[O:15])[C:11](=[O:31])[CH:10]2[NH:32][C:33](=[O:42])[CH2:34][O:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[O:7])[CH2:3][CH2:2]1
Reactant: O=C(COc1ccccc1)NC1C(=O)N(C(C(=O)OCC(Cl)(Cl)Cl)=C(CBr)N2CCCCC2)C1SC(=O)OCC1CC1
Reactant: CO
Agent: Cl
Product: O=C(COc1ccccc1)NC1C(=O)N(C(C(=O)OCC(Cl)(Cl)Cl)=C(O)CBr)C1SC(=O)OCC1CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 83.5 %

Procedure:
To a solution of 2,2,2-trichloroethyl α-[4-cyclopropylmethoxycarbonylthio-3-phenoxyacetamido-2-oxoazetidin-1-yl]-α-[2-bromo-1-(piperidin-1-yl)ethylidene]acetate (573 mg) in methanol (30 ml) is added 10% hydrochloric acid (7 ml), and the mixture is stirred at room temperature or at 40° to 45° C. After 30 minutes, the reaction mixture is poured into ice water, and is extracted with benzene. The extract solution is washed with water, dried, and evaporated to give 2,2,2-trichloroethyl α-[4-cyclopropylmethoxycarbonylthio-3-phenoxyacetamido-2-oxoazetidin-1-yl]-α-(2-bromo-1-hydroxyethylidene)-acetate (434 mg). Yield: 83.5%. IR: νmaxCHCl3 3450, 1790, 1720, 1720 (sh), 1700 cm-1. NMR: δCDCl3 0.1-1.4m7H, 3.98d(7 Hz)2H, 4.27d(5 Hz)2H, 4.57s2H, 4.82d(3 Hz)2H, 5.27d(6;8 Hz)1H, 5.93d(5 Hz)1H, 6.8-7.5m6H, 11.67bra1H.