Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][N:15]([CH2:17][CH2:18][O:19][CH3:20])[CH3:16])=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][C:29](Cl)=[S:30])=[CH:24][CH:23]=1.C([O-])(O)=O.[Na+]>O1CCOCC1.O.CCOCC>[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][C:29]([N:1]2[C:9]3[C:4](=[CH:5][C:6]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][N:15]([CH2:17][CH2:18][O:19][CH3:20])[CH3:16])=[CH:7][CH:8]=3)[CH2:3][CH2:2]2)=[S:30])=[CH:24][CH:23]=1
Reactant: S=C(Cl)Oc1ccc(Cl)cc1
Reactant: COCCN(C)CCCCOc1ccc2c(c1)CCN2
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOCC
Solvent: C1COCCO1
Solvent: O
Product: COCCN(C)CCCCOc1ccc2c(c1)CCN2C(=S)Oc1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 64 %

Procedure:
220 mg (0.8 mmol) [4-(2,3-Dihydro-1H-indol-5-yloxy)-butyl]-(2-methoxy-ethyl)-methyl-amine in 0.5 ml dioxane were treated with 186 mg (0.9 mmol) chloro-thioformic acid (4-chloro-phenyl)ester in 0.5 ml dioxane at 0° C. The solution was stirred at RT for 3 h, was diluted with water and ether and a saturated aqueous solution of NaHCO3 was added. The inorganic layer was extracted with ether, washed with water and dried over Na2SO4. Column chromatography with CH2Cl2/MeOH 19:1 yielded 230 mg (64%) 5-{4-[(2-Methoxy-ethyl)-methyl-amino]-butoxy}-2,3-dihydro-indole-1-carbothioic acid O-(4-chloro-phenyl)ester as yellow viscous oil, MS: 449 (MH+, 1Cl).
Reaction SMILES: [H-].[Na+].[CH2:3](I)[CH3:4].[N+:6]([C:9]1[CH:10]=[C:11]([CH:16]=[C:17]([N+:19]([O-:21])=[O:20])[CH:18]=1)[NH:12][C:13](=[O:15])[CH3:14])([O-:8])=[O:7].O>CN(C)C=O>[N+:6]([C:9]1[CH:10]=[C:11]([CH:16]=[C:17]([N+:19]([O-:21])=[O:20])[CH:18]=1)[N:12]([CH2:3][CH3:4])[C:13](=[O:15])[CH3:14])([O-:8])=[O:7]
Reactant: CC(=O)Nc1cc([N+](=O)[O-])cc([N+](=O)[O-])c1
Reactant: CCI
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCN(C(C)=O)c1cc([N+](=O)[O-])cc([N+](=O)[O-])c1

Procedure:
Sodium hydride (50% in mineral oil; 1.44 g.), followed by ethyl iodide (3.6 ml.), were added, in small portions during 2 minutes, to a warm stirred solution of 3',5'-dinitroacetanilide (6.75 g.) in dimethylformamide (20 ml.). The mixture was heated on the steam bath for 150 minutes, then cooled, poured into water (400 ml.) and extracted with ethyl acetate (3 × 100 ml.). The combined organic extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated to dryness. The residue was purified by chromatography on alumina (150 g.) using benzene as the eluant. The fractions containing the required product were combined, evaporated to dryness and the residue crystallised from ethanol, to give 3',5'-dinitro-N-ethylacetanilide (4.2 g.), m.p. 126°-127°C.
Reaction SMILES: O[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19]1[CH:27]=[CH:26][C:22]([C:23]([OH:25])=[O:24])=[CH:21][CH:20]=1.[BrH:28].S(=O)(=O)(O)O>C(O)(=O)C>[Br:28][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19]1[CH:27]=[CH:26][C:22]([C:23]([OH:25])=[O:24])=[CH:21][CH:20]=1
Reactant: Br
Reactant: O=C(O)c1ccc(NCCCCCCCCCCCCCCCCO)cc1
Agent: O=S(=O)(O)O
Solvent: CC(=O)O
Product: O=C(O)c1ccc(NCCCCCCCCCCCCCCCCBr)cc1
Temperature: 0 °C

Procedure:
A mixture of 16 g. of 4-(16-hydroxyhexadecylamino)benzoic acid and 150 g. of 30-32% hydrogen bromide in acetic acid is treated with 30 ml. of concentrated sulfuric acid, stirred under reflux for 8 hours, poured into ice-water, and filtered. The product is washed with water, dried and recrystallized from ether-petroleum ether to yield 4-(16-bromohexadecylamino)benzoic acid as a white, crystalline solid.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:3]=1[NH2:15].[C:16](Cl)(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CN(C)C(=O)C>[Cl:1][C:2]1[C:3]([NH:15][C:16](=[O:23])[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:5]=[CH:6][N:7]=1
Reactant: Nc1c(Cl)ncnc1Nc1ccccc1
Reactant: O=C(Cl)c1ccccc1
Solvent: CC(=O)N(C)C
Product: O=C(Nc1c(Cl)ncnc1Nc1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 97.3 %

Procedure:
6-chloro-N4-phenylpyrimidine-4,5-diamine obtained in step 1 (35 g, 158.6 mmol) was dissolved in N,N-dimethylacetamide (265 ml) at 0° C. Benzoyl chloride (20.5 mL, 174.5 mmol) was added slowly to the resulting solution at 0° C. and warmed to room temperature. The reaction mixture thus obtained was stirred for 4 hours at room temperature and filtered with NaHCO3(aq)/H2O. The collected solid was dried under reduced pressure to obtain the title compound (50.1 g, 97%) as white solid.
Reaction SMILES: Cl[C:2]1[N:3]=[N:4][C:5](Cl)=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=1.[OH:19][C:20]1[CH:29]=[C:28]2[C:23]([CH:24]=[CH:25][CH:26]=[N:27]2)=[CH:22][CH:21]=1.[H-].[Na+]>CN(C=O)C>[N:27]1[C:28]2[C:23](=[CH:22][CH:21]=[C:20]([O:19][C:5]3[N:4]=[N:3][C:2]([O:19][C:20]4[CH:29]=[C:28]5[C:23]([CH:24]=[CH:25][CH:26]=[N:27]5)=[CH:22][CH:21]=4)=[C:7]([C:8]4[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=4)[CH:6]=3)[CH:29]=2)[CH:24]=[CH:25][CH:26]=1
Reactant: FC(F)(F)c1ccc(-c2cc(Cl)nnc2Cl)cc1
Reactant: Oc1ccc2cccnc2c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: FC(F)(F)c1ccc(-c2cc(Oc3ccc4cccnc4c3)nnc2Oc2ccc3cccnc3c2)cc1
Temperature: 80 °C

Procedure:
To a solution of 3,6-dichloro-4-(4-trifluoromethyl-phenyl)-pyridazine, (Example 45(d)), (441 mg, 1.5 mmol) and 7-hydroxyquinoline (441 mg, 3.0 mmol, Acros) in DMF (10 mL) was added 60% NaH (150 mg, 3.8 mmol) and the mixture was heated at 80° C. for 14 h. The solvent was removed in vacuum, the residue was partitioned between EtOAc/H2O and the aqueous layer was extracted with EtOAc. The combined organic layers were evaporated onto SiO2 and purified by flash silica gel chromatography with EtOAc/hexanes (0:1→1:0) as eluant to give the title compound as an off-white amorphous solid. Mp: 158–162° C. MS (ESI, pos ion.) m/z: 511 (M+1).
Reaction SMILES: C([N:8]([CH2:30][C@@H:31]([C:33]1[CH:42]=[CH:41][C:40]([O:43]CC2C=CC=CC=2)=[C:39]2[C:34]=1[CH:35]=[CH:36][C:37](=[O:51])[NH:38]2)[OH:32])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18][CH2:19][C:20]1[CH:21]=[C:22]([S:26]([NH2:29])(=[O:28])=[O:27])[CH:23]=[CH:24][CH:25]=1)C1C=CC=CC=1.[C:52]([O:55]CC)(=[O:54])[CH3:53].C(O)(=O)C>C(O)C.[Pd].[OH-].[OH-].[Pd+2]>[C:52]([OH:55])(=[O:54])[CH3:53].[OH:32][C@H:31]([C:33]1[CH:42]=[CH:41][C:40]([OH:43])=[C:39]2[C:34]=1[CH:35]=[CH:36][C:37](=[O:51])[NH:38]2)[CH2:30][NH:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18][CH2:19][C:20]1[CH:21]=[C:22]([S:26]([NH2:29])(=[O:27])=[O:28])[CH:23]=[CH:24][CH:25]=1
Reactant: NS(=O)(=O)c1cccc(CCCOCCCCCCCN(Cc2ccccc2)C[C@H](O)c2ccc(OCc3ccccc3)c3[nH]c(=O)ccc23)c1
Reactant: CCOC(C)=O
Agent: [Pd+2]
Agent: [Pd]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CCO
Product: NS(=O)(=O)c1cccc(CCCOCCCCCCCNC[C@H](O)c2ccc(O)c3[nH]c(=O)ccc23)c1

Procedure:
A solution of 3-(3-{[7-(benzyl{(2R)-2-[8-(benzyloxy)-2-oxo-1,2-dihydroquinolin-5-yl]-2-hydroxyethyl}amino)heptyl]oxy}propyl)benzenesulfonamide (36 mg) in ethanol (10 ml) with ethyl acetate (2 ml) and glacial acetic acid (1 ml) was hydrogenated using 10% palladium on carbon (50% water by weight, 10 mg) and 20% palladium hydroxide on carbon (10 mg) for 19 h. The catalyst was removed by filtration and the filtrate was evaporated in vacuo. The residue was purified on an aminopropyl SPE cartridge (2 g), eluting with methanol-dichloromethane mixtures. Evaporation of the appropriate fractions with glacial acetic acid gave the title compound (15 mg). LCMS RT=2.26 min ES+ve m/z 532 (MH)+
Reaction SMILES: C(OC([N:8]1[C:16]2[C:11](=[C:12]([C:20]([C:23]3[O:24][C:25]4[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][C:26]=4[N:27]=3)([OH:22])[CH3:21])[C:13]([O:18][CH3:19])=[CH:14][C:15]=2[CH3:17])[CH:10]=[CH:9]1)=O)(C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+]>CO>[OH:22][C:20]([C:23]1[O:24][C:25]2[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][C:26]=2[N:27]=1)([C:12]1[C:13]([O:18][CH3:19])=[CH:14][C:15]([CH3:17])=[C:16]2[C:11]=1[CH:10]=[CH:9][NH:8]2)[CH3:21]
Reactant: COc1cc(C)c2c(ccn2C(=O)OC(C)(C)C)c1C(C)(O)c1nc2cc(C#N)ccc2o1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CO
Product: COc1cc(C)c2[nH]ccc2c1C(C)(O)c1nc2cc(C#N)ccc2o1
Temperature: 60 °C
Reaction time: 0.5 h

Procedure:
A suspension of (±)-tert-butyl-4-(1-(5-cyanobenzo[d]oxazol-2-yl)-1-hydroxyethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (6.5 mg, 0.019 mmol) and Cs2CO3 (146 mg, 0.447 mmol) in MeOH (0.5 mL) was heated at 60° C. and stirred for 30 min. The reaction mixture was cooled to rt, quenched with a saturated aq. solution of ammonium chloride, diluted with AcOEt and water. The layers were separated and the aq. layer was extracted with AcOEt. The combined organic layers were dried over MgSO4, filtered and evaporated to dryness. The resulting residue was purified by flash chromatography (0-50% EtOAc:heptanes) to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.88 (br. s., 1H) 8.36 (dd, J=1.39, 0.76 Hz, 1H) 7.65-8.00 (m, 2H) 7.28 (t, J=2.84 Hz, 1H) 6.95 (dd, J=3.03, 2.02 Hz, 1H) 6.62 (s, 1H) 6.31 (s, 1H) 3.19 (s, 3H) 2.44 (d, J=0.51 Hz, 3H) 1.95-2.02 (m, 3H). MS (ESI+) m/z 348.1 (M+H).
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:15][C:14](=[O:16])[N:13]=[C:12]1[NH2:17])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:18][C:19]1[CH:26]=[C:25]([CH3:27])[CH:24]=[CH:23][C:20]=1[CH2:21]Br.C([O-])([O-])=O.[K+].[K+]>C(#N)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][C:14](=[O:16])[N:13]=[C:12]1[NH:17][CH2:21][C:20]1[CH:23]=[CH:24][C:25]([CH3:27])=[CH:26][C:19]=1[CH3:18])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NC1=NC(=O)CN1C(=O)OCc1ccccc1
Reactant: Cc1ccc(CBr)c(C)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: Cc1ccc(CNC2=NC(=O)CN2C(=O)OCc2ccccc2)c(C)c1
Yield: 24.9 %

Procedure:
A suspension of 2-amino-4-oxo-4,5-dihydro-imidazole-1-carboxylic acid benzyl ester (93.2 mg, 0.40 mmol), 2,4-dimethylbenzylbromide (79.64 mg, 0.40 mmol) and K2CO3 (83.01 mg, 0.60 mmol) in acetonitrile (8 mL) was heated to reflux under argon for 45 min. Partition between EtOAc and water to give a suspension. Filter off the solid to give 2-(2,4-dimethyl-benzylamino)-4-oxo-4,5-dihydro-imidazole-1-carboxylic acid benzyl ester (35.0 mg). The filtrate was separated, dried to give an oil which was purified by preparative TLC, eluted with 50% nHex/EtOAc to give 60.0 mg of 2-(2, 4-dimethyl-benzylamino)-4-oxo-4,5-dihydro-imidazole-1-carboxylic acid benzyl ester as a white solid (total yield: 95.0 mg, 67.7%).
Reaction SMILES: [Na+].[I-].C[Si](Cl)(C)C.[F:8][C:9]1[CH:10]=[C:11]([C:16]2(O)[C:24]3[O:23][N:22]=[C:21]([C:25]4[CH:30]=[CH:29][C:28]([N:31]5[CH:35]=[C:34]([CH3:36])[N:33]=[CH:32]5)=[C:27]([O:37][CH3:38])[CH:26]=4)[C:20]=3[CH2:19][CH2:18][CH2:17]2)[CH:12]=[C:13]([F:15])[CH:14]=1>CC#N>[F:8][C:9]1[CH:10]=[C:11]([CH:16]2[C:24]3[O:23][N:22]=[C:21]([C:25]4[CH:30]=[CH:29][C:28]([N:31]5[CH:35]=[C:34]([CH3:36])[N:33]=[CH:32]5)=[C:27]([O:37][CH3:38])[CH:26]=4)[C:20]=3[CH2:19][CH2:18][CH2:17]2)[CH:12]=[C:13]([F:15])[CH:14]=1
Reactant: COc1cc(-c2noc3c2CCCC3(O)c2cc(F)cc(F)c2)ccc1-n1cnc(C)c1
Agent: C[Si](C)(C)Cl
Agent: [I-]
Agent: [Na+]
Solvent: CC#N
Product: COc1cc(-c2noc3c2CCCC3c2cc(F)cc(F)c2)ccc1-n1cnc(C)c1
Yield: 66 %

Procedure:
To a suspension of NaI (1.54 g, 10.3 mmol) in CH3CN (20 mL) was added TMSCl (1.12 g, 10.27 mmol) and a solution of 7-(3,5-difluorophenyl)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-4,5,6,7-tetrahydrobenzo[d]isoxazol-7-ol (691 mg, 1.6 mmol) in CH3CN (1.0 mL) The reaction mixture was stirred at 60° C. overnight, cooled, and partitioned between water and DCM. The organic phase was washed with 10% aq. Na2S2O3, water, and brine, dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography using 0-5% MeOH in DCM as solvent to afford 445 mg of the title product.
Reaction SMILES: [CH2:1]([OH:7])[CH2:2][CH2:3][CH2:4][C:5]#[CH:6].[C:8]1([C:14](Cl)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.N1C=CC=CC=1>O>[C:8]1([C:14]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[O:7][CH2:1][CH2:2][CH2:3][CH2:4][C:5]#[CH:6])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: C#CCCCCO
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: O
Solvent: c1ccncc1
Product: C#CCCCCOC(c1ccccc1)(c1ccccc1)c1ccccc1

Procedure:
A stirred mixture of 9.81 g. (0.10 moles) of 5-hexyn-1-ol, 33.5 g. (0.12 moles) of triphenylmethyl chloride, and 200 ml. of dry pyridine is refluxed for 60 minutes. The cooled mixture is poured into water and extracted with ether. The extract is washed successively with water, ice-cold N hydrochloric acid, water, saturated sodium bicarbonate solution, and saturated sodium chloride solution. The extract is dried with magnesium sulfate. The crude product obtained after evaporation of the solvent is purified by chromatography on Florisil to give an oil, νmax. 3290 (acetylenic hydrogen), 1600, 1072, and 705 cm-1 (triphenylmethoxy group).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([C:9]2[NH:10][C:11]3[C:16]([C:17]=2[CH2:18][CH2:19][N:20]2C(=O)C4C(=CC=CC=4)C2=O)=[CH:15][C:14]([OH:31])=[CH:13][CH:12]=3)[CH:5]=[C:6]([CH3:8])[CH:7]=1.NN>C(O)C.O1CCCC1>[NH2:20][CH2:19][CH2:18][C:17]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([OH:31])[CH:15]=2)[NH:10][C:9]=1[C:4]1[CH:3]=[C:2]([CH3:1])[CH:7]=[C:6]([CH3:8])[CH:5]=1
Reactant: Cc1cc(C)cc(-c2[nH]c3ccc(O)cc3c2CCN2C(=O)c3ccccc3C2=O)c1
Agent: NN
Solvent: C1CCOC1
Solvent: CCO
Product: Cc1cc(C)cc(-c2[nH]c3ccc(O)cc3c2CCN)c1
Temperature: 25 °C

Procedure:
To a solution of 2-[2-[2-(3,5-dimethylphenyl)-5-hydroxy-1H-indol-3-yl]ethyl]isoindole-1,3-dione (418 mg in a mixture of 7 mL ethanol and 7 mL tetrahydrofuran) was added 2.5 mL of 95% aqueous hydrazine and the reaction stirred at room temperature. After 12 hours the mixture was concentrated in vacuo and purified by flash chromatography on silica gel (methylene chloride:methanol:ammonium hydroxide, 89:11:1) to provide the title compound (228 mg).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][CH3:9].[Mg].[Br:11][C:12]1[CH:20]=[CH:19][CH:18]=[CH:17][C:13]=1[C:14](Cl)=[O:15]>>[Br:11][C:12]1[CH:20]=[CH:19][CH:18]=[CH:17][C:13]=1[C:14]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][CH3:9])=[O:15]
Reactant: O=C(Cl)c1ccccc1Br
Reactant: COc1ccccc1Br
Agent: [Mg]
Product: COc1ccccc1C(=O)c1ccccc1Br
Yield: 65.9 %

Procedure:
Following the Procedure described in Preparation VIa and starting from 9.4 g (0.050 mol) of 2-bromoanisole, 1.7 g (0.069 mol) of magnesium and 11 g (0.050 mol) of 2-bromobenzoyl chloride, 9.6 g of the expected product (yield: 66%) are obtained after crystallization from ether.
Reaction SMILES: Cl[C:2]1[N:10]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[N:3]=1.[N+:17]([C:20]1[CH:26]=[CH:25][C:23]([NH2:24])=[CH:22][CH:21]=1)([O-:19])=[O:18]>>[N+:17]([C:20]1[CH:26]=[CH:25][C:23]([NH:24][C:2]2[N:10]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:5]3=[N:6][CH:7]=[CH:8][CH:9]=[C:4]3[N:3]=2)=[CH:22][CH:21]=1)([O-:19])=[O:18]
Reactant: Nc1ccc([N+](=O)[O-])cc1
Reactant: CCOC(=O)Cn1c(Cl)nc2cccnc21
Product: CCOC(=O)Cn1c(Nc2ccc([N+](=O)[O-])cc2)nc2cccnc21
Temperature: 150 °C
Reaction time: 1 h
Yield: 101.2 %

Procedure:
A mixture of ethyl (2-chloro-3H-imidazo[4,5-b]pyridin-3-yl)acetate (2.8 g) and 4-nitroaniline (1.6 g) was stirred at 150° C. for 1 h to give the title compound (4.0 g).
Reaction SMILES: [C:1]([CH2:4][CH2:5][CH2:6][O:7][C:8]1[C:9]([Se:22][C:23]2[CH:33]=[CH:32][C:26]([C:27]([O:29]CC)=[O:28])=[CH:25][CH:24]=2)=[CH:10][C:11]2[C:12]([CH3:21])([CH3:20])[CH2:13][CH2:14][C:15]([CH3:19])([CH3:18])[C:16]=2[CH:17]=1)([OH:3])=[O:2].[OH-].[Na+]>C1COCC1.C(O)C>[C:1]([CH2:4][CH2:5][CH2:6][O:7][C:8]1[C:9]([Se:22][C:23]2[CH:24]=[CH:25][C:26]([C:27]([OH:29])=[O:28])=[CH:32][CH:33]=2)=[CH:10][C:11]2[C:12]([CH3:21])([CH3:20])[CH2:13][CH2:14][C:15]([CH3:19])([CH3:18])[C:16]=2[CH:17]=1)([OH:3])=[O:2]
Reactant: CCOC(=O)c1ccc([Se]c2cc3c(cc2OCCCC(=O)O)C(C)(C)CCC3(C)C)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: CC1(C)CCC(C)(C)c2cc([Se]c3ccc(C(=O)O)cc3)c(OCCCC(=O)O)cc21

Procedure:
In manner similar to that of Example 2, by reaction of 250 mg (0.46 mmol) of ethyl 4-[3-(3-carboxypropoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl]benzoate with 183 mg (4.6 mmol) of sodium hydroxide in a THF/ethanol mixture (5 ml/5 ml), 172 mg (76%) of a white powder are obtained. m.p.: 230° C.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([O:10][CH3:11])[N:3]=1.[OH:12][C:13]1[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][C:14]=1[C:15]([O:17][CH3:18])=[O:16].CS([O-])=O.[Na+].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:11][O:10][C:4]1[CH:5]=[C:6]([O:8][CH3:9])[N:7]=[C:2]([O:12][C:13]2[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][C:14]=2[C:15]([O:17][CH3:18])=[O:16])[N:3]=1
Reactant: COC(=O)c1cccc(C)c1O
Reactant: COc1cc(OC)nc(Cl)n1
Agent: CS(=O)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1cccc(C)c1Oc1nc(OC)cc(OC)n1
Reaction time: 8 h

Procedure:
4.38 g (25 mmol) of 2-chloro-4,6-dimethoxypyrimidine, 4.17 g (25.0 mmol) of methyl 2-hydroxy-3-methylbenzoate and 0.66 g (6.3 mmol) of sodium methanesulfinate were heated in the presence of 5.17 g (37.5 mmol) of potassium carbonate in 25 ml of N,N-dimethylformamide to 120° C. with stirring. After 8 hours, the solvent was removed in a rotary evaporator at 60° C./20 mbar. The residue was taken up in 30 ml of water and 30 ml of dichloromethane. After the organic phase had been separated off, the aqueous phase was again extracted with 20 ml of dichloromethane. The combined organic phases was washed with water, dried over magnesium sulfate and evaporated. The residue was purified by chromatography on a silica gel column (eluent hexane/ethyl acetate 4:1). The title product was obtained from the product fraction in a yield of 5.23 g (65.8 percent of theory) (GC content 96 percent). The melting point of the compound was 73.8° to 79.1° C. Other data concerning the title compound was:
Reaction SMILES: [C:1]1([CH2:10][C:11]([OH:13])=O)[O:2][CH:3]=[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.[OH:14][C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[O:18][C:17](=[O:25])[CH:16]=1.C1CCC(N=C=NC2CCCCC2)CC1.[Na].C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.CN(C1C=CN=CC=1)C.C(O)C>[O:2]1[C:3]2[CH:4]=[CH:9][CH:8]=[CH:7][C:6]=2[CH:5]=[C:1]1[CH2:10][C:11]([C:16]1[C:17](=[O:25])[O:18][C:19]2[C:24]([C:15]=1[OH:14])=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:13]
Reactant: O=c1cc(O)c2ccccc2o1
Reactant: O=C(O)Cc1occ2ccccc12
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Agent: O=C([O-])O
Solvent: ClC(Cl)Cl
Solvent: CCO
Product: O=C(Cc1cc2ccccc2o1)c1c(O)c2ccccc2oc1=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
1.76 g (10.0 mmol) of 2-benzofuranacetic acid, 1.62 g (10.0 mmol) of 4-hydroxy-coumarin and 2.27 g (11.1 mmol) of DCC were suspended in 50 ml of chloroform, then 130 mg (1.06 mmol) of DMAP added and stirring carried out overnight at 60° C. The reaction liquid was then cooled to room temperature and the insoluble material filtered off. The mother liquor was concentrated and the residue purified by column chromatography. The solid obtained was recrystallized from ethanol and Compound 16 (460 mg, 1.43 mmol, 14%) obtained. This was converted to the sodium salt with an equivalent quantity of sodium hydrogen carbonate.
Reaction SMILES: [Mg].BrCCBr.[F:6][C:7]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:8]=1[CH2:9]Br.[O:16]=[C:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1.Cl.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+]>C(OCC)C.C1COCC1>[F:6][C:7]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:8]=1[CH2:9][C:17]1([OH:16])[CH2:18][CH2:19][N:20]([C:23]([O:25][C:26]([CH3:28])([CH3:27])[CH3:29])=[O:24])[CH2:21][CH2:22]1
Reactant: Fc1ccc(CBr)c(F)c1
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Agent: Cl
Agent: O=C([O-])C(O)C(O)C(=O)[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: BrCCBr
Solvent: CCOCC
Product: CC(C)(C)OC(=O)N1CCC(O)(Cc2ccc(F)cc2F)CC1
Temperature: -78 °C
Reaction time: 1 h
Yield: 47.5 %

Procedure:
To a suspension of magnesium (1.2 g) and 1,2-dibromoethane (0.11 mL) in diethyl ether (30 mL) was added a solution of 2,4-difluorobenzyl bromide (10 g) in diethyl ether (10 mL) at room temperature under a nitrogen atmosphere, and the mixture was stirred at the same temperature for 1 hr. The reaction mixture was diluted with THF (30 mL), and cooled to −78° C., and a solution of tert-butyl 4-oxopiperidine-1-carboxylate (5.0 g) in THF (10 mL) was added thereto. The mixture was allowed to warm to room temperature, and stirred overnight. To the reaction mixture was added a small amount of 1N hydrochloric acid at 0° C. to quench the reaction. Saturated aqueous potassium sodium tartrate solution was added thereto, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane), and recrystallized from ethyl acetate/hexane to give the title compound (3.9 g).
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][N:20]([C:23]1[S:24][C:25]([I:32])=[C:26]([C:28]([O:30][CH3:31])=[O:29])[N:27]=1)[CH2:19][CH2:18]2)=[O:12].Cl[CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39].C(N(CC)CC)C>ClCCl>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[N:10]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[C:11]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][N:20]([C:23]1[S:24][C:25]([I:32])=[C:26]([C:28]([O:30][CH3:31])=[O:29])[N:27]=1)[CH2:19][CH2:18]2)=[O:12]
Reactant: C[Si](C)(C)CCOCCl
Reactant: COC(=O)c1nc(N2CCc3cccc(C(=O)Nc4nc5ccccc5s4)c3C2)sc1I
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)c1nc(N2CCc3cccc(C(=O)N(COCC[Si](C)(C)C)c4nc5ccccc5s4)c3C2)sc1I
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of Example 15A (2.0 g) and (2-(chloromethoxy)ethyl)trimethylsilane (1.2 g) in dichloromethane (20 mL) was added triethylamine (1.55 g). The mixture was stirred at room temperature overnight and concentrated. The residue was purified by flash chromatography, eluting with 20% ethyl acetate in hexane, to give the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:9]([C:11]3[C:15]4=[N:16][C:17]([O:22][CH3:23])=[C:18]([O:20][CH3:21])[CH:19]=[C:14]4[N:13]([CH3:24])[CH:12]=3)=[CH:10][C:3]=12.CO>[OH-].[K+]>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[NH:8][C:9]([C:11]3[C:15]4=[N:16][C:17]([O:22][CH3:23])=[C:18]([O:20][CH3:21])[CH:19]=[C:14]4[N:13]([CH3:24])[CH:12]=3)=[CH:10][C:3]=12
Reactant: COc1cc2c(nc1OC)c(-c1cc3c(Cl)ccnc3n1S(=O)(=O)c1ccc(C)cc1)cn2C
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: COc1cc2c(nc1OC)c(-c1cc3c(Cl)ccnc3[nH]1)cn2C

Procedure:
Reflux bisazaindole 29 (40 mg, 0.081 mmol) in KOH at 4%/MeOH (10 mL) for 5.5 h and then concentrate the reaction under vacuum. Purification on SiO2 (MeOH at 2-4%/CH2Cl2) leads to 30 (13 mg, 47.3%) as a white solid: 1H NMR (CDCl3) δ 10.92 (s broad, 1H), 8.07 (d, 1H, J=5.3 Hz), 7.49 (s, 1H), 7.05 (s apparent overlapping d, 2H, J=5.2 Hz), 6.62 (s, 1H), 4.22 (s, 3H), 3.96 (s, 3H), 3.81 (s, 3H), TLC (EtOAc at 40%/heptane), Rf=0.40, m/z obs.=343.3 (M+1), 345.3.
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][NH2:9])=[CH:4][CH:3]=1.[C:10]([C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1)(=O)[CH3:11]>>[I:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][N:9]=[C:10]([C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)[CH3:11])=[CH:4][CH:3]=1
Reactant: NNc1ccc(I)cc1
Reactant: CC(=O)c1cccnc1
Product: CC(=NNc1ccc(I)cc1)c1cccnc1

Procedure:
Analogously to the process described in Example 1A, 5.0 g (21.36 mmol) of 4-iodophenylhydrazine and 3-acetylpyridine give 5.15 g (71% of theory) of the title compound.