Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[C:6]([N+:11]([O-])=O)[CH:5]=1>C(O)C.[Pt](=O)=O>[NH2:11][C:6]1[CH:5]=[C:4]([CH2:3][O:2][CH3:1])[CH:9]=[CH:8][C:7]=1[OH:10]
Reactant: COCc1ccc(O)c([N+](=O)[O-])c1
Agent: O=[Pt]=O
Solvent: CCO
Product: COCc1ccc(O)c(N)c1
Reaction time: 16 h
Yield: 85 %

Procedure:
A mixture of 4-[(methyloxy)methyl]-2-nitrophenol D119 (0.72 g, 3.93 mmol) and platinum (IV) oxide (0.089 g, 0.393 mmol) in ethanol (15 mL) was stirred under an atmosphere of hydrogen for 16 hr. The catalyst was removed by filtration through celite and the filtrate concentrated to dryness in vacuo to afford the title compound as a green/brown solid 0.51 g, 85%.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:14]1[CH2:19][CH2:18][S:17](=[O:21])(=[O:20])[CH2:16][CH2:15]1.[CH3:22][C:23]([O:41][Si:42]([CH2:47][CH3:48])([CH2:45][CH3:46])[CH2:43][CH3:44])([CH3:40])[CH2:24][CH2:25][C:26]1[S:27][C:28](B2OC(C)(C)C(C)(C)O2)=[CH:29][CH:30]=1.C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1>[O:20]=[S:17]1(=[O:21])[CH2:18][CH2:19][CH:14]([C:5]2[C:4]3[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=[C:2]([C:28]4[S:27][C:26]([CH2:25][CH2:24][C:23]([CH3:40])([O:41][Si:42]([CH2:47][CH3:48])([CH2:43][CH3:44])[CH2:45][CH3:46])[CH3:22])=[CH:30][CH:29]=4)[CH:3]=3)[NH:7][CH:6]=2)[CH2:15][CH2:16]1
Reactant: CC[Si](CC)(CC)OC(C)(C)CCc1ccc(B2OC(C)(C)C(C)(C)O2)s1
Reactant: NC(=O)c1cc(Br)cc2c(C3CCS(=O)(=O)CC3)c[nH]c12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: CC[Si](CC)(CC)OC(C)(C)CCc1ccc(-c2cc(C(N)=O)c3[nH]cc(C4CCS(=O)(=O)CC4)c3c2)s1
Temperature: 150 °C

Procedure:
5-bromo-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide (90 mg, 0.24 mmol), ({1,1-dimethyl-3-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-thienyl]propyl}oxy)(triethyl)silane (149 mg, 0.36 mmol, 1.5 eq), potassium carbonate (200 mg, 1.4 mmol, 6 eq), and palladium tetrakistriphenylphosphine (28 mg, 0.024 mmol, 0.1 eq) were diluted in dioxane (1.5 mL) and water (0.5 mL) in a 2-5 mL microwave vial. The mixture was degassed by bubbling argon through for 5 minutes, then heated in a microwave oven at 150° C. under high absorption for 40 minutes. The mixture was filtered through a thiol SPE cartridge, then concentrated to give the crude product as a brown oil. This material was purified by Isco Combiflash, 40 gram column, eluting with 0-15% methanol in dichloromethane. The desired product was obtained as a brownish tarry substance and was re-purified by ammonium hydroxide Gilson eluting with 20-95% acetonitrile in water. The product fractions were concentrated in a Genevac EZ2 evaporator to give the title compound as a light yellow solid (55 mg, 40%).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.N1C=CC=CC=1.[N:16]1([C:22](Cl)=[O:23])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[N:16]1([C:22]([O:1][C:2]2[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=2)=[O:23])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1
Reactant: O=Cc1ccc(O)cc1
Reactant: O=C(Cl)N1CCOCC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=Cc1ccc(OC(=O)N2CCOCC2)cc1
Temperature: 25 °C
Yield: 74.8 %

Procedure:
To a 250 mL dry round bottom flask were added 4-hydroxybenzaldehyde (6.11 g, 50.0 mmol), anhydrous CH2Cl2 (80 mL) and pyridine (4.86 mL, 60.0 mmol). The mixture was stirred in an ice-water, then 4-morpholinecarbonyl chloride (6.12 mL, 52.5 mmol) was added. The mixture was stirred and warmed slowly to room temperature, then stirred at room temperature overnight. An aqueous solution of 5% NaHCO3 (100 mL) was added to the reaction mixture. The CH2Cl2 layer was separated, and the aqueous layer was extracted continually with CH2Cl2 (50 mL×2). The combined CH2Cl2 solution was dried over Na2SO4. Removal of the solvent gave 4-formylphenyl morpholine-4-carboxylate (8.80 g) as white solid. Yield: 75%. 1H NMR (CDCl3, 300 MHz): δ=9.97 (s, 1H), 7.90 (d, J=9.0 Hz, 2H), 7.30 (d, J=9.0 Hz, 2H), 3.77-3.57 (m, 6H). 13C NMR (CDCl3, 75.5 MHz, mixture of two isomers): δ=191.0, 156.0, 152.6, 133.6, 131.1, 122.3, 66.5, 66.4, 45.0, 44.2.
Reaction SMILES: [CH2:1]([C@H:8]1[C@@H:13]([O:14][CH2:15][C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:17]=2)[CH2:12][CH2:11][NH:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C[O:33][CH2:32][CH2:31]1>C(Cl)(=O)C.CCN(CC)CC>[C:32]([N:10]1[CH2:11][CH2:12][C@H:13]([O:14][CH2:15][C:16]2[CH:17]=[C:18]([C:26]([F:29])([F:27])[F:28])[CH:19]=[C:20]([C:22]([F:23])([F:24])[F:25])[CH:21]=2)[C@H:8]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:9]1)(=[O:33])[CH3:31]
Reactant: FC(F)(F)c1cc(CO[C@H]2CCNC[C@H]2Cc2ccccc2)cc(C(F)(F)F)c1
Reactant: C1CCOC1
Solvent: CCN(CC)CC
Solvent: CC(=O)Cl
Product: CC(=O)N1CC[C@H](OCc2cc(C(F)(F)F)cc(C(F)(F)F)c2)[C@H](Cc2ccccc2)C1
Reaction time: 1 h
Yield: 79 %

Procedure:
To a solution of the compound (0.40 g) obtained in Example 404 in THF (4 ml), acetyl chloride (0.075 ml) and Et3N (0.147 ml) were added at room temperature, and the reaction mixture was stirred at the same temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and then the residue was dissolved in ethyl acetate. The organic layer was washed with 1 N hydrogen chloride and brine, dried, and then the solvent was evaporated under reduced pressure. The obtained residue was purified by preparative thin layer chromatography to obtain the title compound as pale yellow oil (0.275 g, 79%).
Reaction SMILES: [C:1]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])(=[O:4])[CH:2]=[CH2:3].Cl.[CH2:11]([O:18][C:19](=[O:25])[C@@H:20]1[CH2:24][CH2:23][CH2:22][NH:21]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CCN(CC)CC>C(O)(C)(C)C>[CH2:11]([O:18][C:19]([C@@H:20]1[CH2:24][CH2:23][CH2:22][N:21]1[CH2:3][CH2:2][C:1]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4])=[O:25])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: C=CC(=O)OC(C)(C)C
Reactant: O=C(OCc1ccccc1)[C@@H]1CCCN1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CC(C)(C)O
Product: CC(C)(C)OC(=O)CCN1CCC[C@H]1C(=O)OCc1ccccc1
Temperature: 80 °C
Yield: 79 %

Procedure:
Tert-butyl acrylate (5.00 mL) was added to a solution of L-proline benzyl ester hydrochloride salt (1.10 g, 4.54 mmol) and Et3N (632 μL, 4.54 mmol) in tert-butanol (5.00 mL). The reaction was heated to 80° C. for 3 h then and evaporated in vacuo. The residue was purified by FCC, using 0-50% EtOAc in cyclohexane, to give the title compound (1.20 g, 79%). 1H NMR (300 MHz, CDCl3): 1.43 (9H, s), 1.72-2.00 (3H, m), 2.08 (1H, m), 2.39-2.48 (3H, m), 2.72 (1H, ddd, J 12.2, 8.4, 6.7), 3.00 (1H, dt, J 12.3, 7.8), 3.13 (1H, m), 3.28 (1H, dd, J 8.6, 5.4), 5.13 (1H, d, J 12.3), 5.18 (1H, d, J 12.3), 7.29-7.39 (5H, m).
Reaction SMILES: [C:1]([NH:9][C:10]1[CH:32]=[CH:31][N:13]([C@@H:14]2[O:28][C@H:17]([CH2:18][O:19][C:20](=[O:27])[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C@@H:16]([NH2:29])[C@H:15]2[F:30])[C:12](=[O:33])[N:11]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:34][O:35][C:36]1[CH:55]=[CH:54][C:39]([C:40](Cl)([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)=[CH:38][CH:37]=1>N1C=CC=CC=1>[C:1]([NH:9][C:10]1[CH:32]=[CH:31][N:13]([C@@H:14]2[O:28][C@H:17]([CH2:18][O:19][C:20](=[O:27])[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C@@H:16]([NH:29][C:40]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:39]3[CH:38]=[CH:37][C:36]([O:35][CH3:34])=[CH:55][CH:54]=3)[C@H:15]2[F:30])[C:12](=[O:33])[N:11]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COc1ccc(C(Cl)(c2ccccc2)c2ccccc2)cc1
Reactant: N[C@H]1[C@@H](F)[C@H](n2ccc(NC(=O)c3ccccc3)nc2=O)O[C@@H]1COC(=O)c1ccccc1
Solvent: c1ccncc1
Product: COc1ccc(C(N[C@H]2[C@@H](F)[C@H](n3ccc(NC(=O)c4ccccc4)nc3=O)O[C@@H]2COC(=O)c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Reaction time: 8 h

Procedure:
N4,5'-O-dibenzoyl-2'-fluoro-3'-(4-methoxytrityl)amino-2',3'-dideoxycytidine 14 was prepared as follows: To 0.9 g (2.0 mmol) of 13 in 25 mL anhydrous pyridine was added 0.86 g (2.8 mmol) 4-methoxytrityl chloride, and the mixture stirred overnight. The reaction was quenched with 0.5 mL H2O and concentrated in vacuo. CH2Cl2 (50 mL) was added and washed with 50 mL saturated aqueous NaHCO3 and with water (2×50 mL). The solvent was removed in vacuo, replaced with 10 mL CH2Cl2, and pipetted into 80 mL rapidly stirred 1/1 hexane/ether. After further stirring for 2 h, the product was collected by filtration and dried under vacuum, giving 1.3 g (88% yield) of product as a white powder. Mass-spectrometry, FAB+, M+H+, calculated: 725.2775, observed: 725.2761. 1H NMR δ 8.59 (br s, 1H), 8.07 (br d, J=5.7 Hz, 1H), 7.89 (br d, J=7 Hz, 2H), 7.83 (dd, J=1.3, 6.7 Hz, 2H), 7.68 (dd, J=7.4, 7.4 Hz, 2H), 7.5-7.6 (m, 8H), 7.43 (dd, J=2.1, 6.9 Hz, 2H), 7.1-7.3 (mm, 7H), 6.71 (d, J=8.9 Hz, 2H), 5.80 (d, J=15.4 Hz, 1H), 5.03 (dd, J=2.0, 13.0 Hz, 1H), 4.98 (dd, J=2.3;, 13.1 Hz, 1H),4.41 (brd,J=10.5 Hz, 1H),3.63 (s,3H),3.36(dddd,J=3.1, 11.1, 11.1, 25.7 Hz, 1H), 2.84 (dd, J=3.1, 49.9 Hz, 1H), 2.52 (dd, J=2.7, 11.5 Hz, 1H); 19F NMR δ -196.3 (m).
Reaction SMILES: [OH:1][CH:2]1[CH2:6][CH2:5][CH2:4][C:3]1([CH2:12][CH2:13][CH3:14])[C:7]([O:9][CH2:10][CH3:11])=[O:8].C(Cl)Cl.[CH3:18][C:19]1[CH:27]=[CH:26][C:22]([C:23](Cl)=[O:24])=[CH:21][CH:20]=1>N1C=CC=CC=1>[CH2:12]([C:3]1([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:4][CH2:5][CH2:6][CH:2]1[O:1][C:23](=[O:24])[C:22]1[CH:26]=[CH:27][C:19]([CH3:18])=[CH:20][CH:21]=1)[CH2:13][CH3:14]
Reactant: CCCC1(C(=O)OCC)CCCC1O
Reactant: Cc1ccc(C(=O)Cl)cc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCCC1(C(=O)OCC)CCCC1OC(=O)c1ccc(C)cc1
Reaction time: 12 h

Procedure:
Ethyl 2-hydroxy-1-n-propyl-cyclopentane carboxylate (6.00 g) was diluted using 60 ml of methylene chloride. At room temperature and with magnetic stirring, pyridine (3.66 ml) was slowly added, then 4-methyl-benzoyl chloride (6.12 ml) was dropwise added. Upon the completion of the addition, the reaction was continued for 12 hours. Then solvent was removed, and the residue was extracted using ethyl acetate and water. Organic layer was washed, in turn, using 10% hydrochloric acid aqueous solution to pH of about 2, using saline solution to neutrality, using 10% aqueous solution of sodium carbonate for three times, and then using saline solution to neutrality. The organic layer was dried, and removing solvent gave 10.41 g of yellow liquid. MS: m/e 319(M+′+1), 318(M+′), 317(M+′−1), 259, 230, 199, 182, 153, 105(base), 77.
Reaction SMILES: P(Br)(Br)[Br:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][C:7]=1[C:14]1[CH:15]=[CH:16][C:17]([CH2:25]O)=[N:18][C:19]=1[CH2:20][C:21]([CH3:24])([CH3:23])[CH3:22].C(=O)([O-])O.[Na+]>CN(C=O)C>[Br:2][CH2:25][C:17]1[N:18]=[C:19]([CH2:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C:14]([C:7]2[CH:8]=[C:9]([O:12][CH3:13])[CH:10]=[CH:11][C:6]=2[F:5])=[CH:15][CH:16]=1
Reactant: BrP(Br)Br
Reactant: COc1ccc(F)c(-c2ccc(CO)nc2CC(C)(C)C)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc(F)c(-c2ccc(CBr)nc2CC(C)(C)C)c1
Temperature: 0 °C
Reaction time: 0.33 h

Procedure:
Phosphorus tribromide (112 μL) was added to DMF (3.0 mL) at 0° C., and the mixture was stirred at 0° C. for 20 min. To the obtained white suspension was added a solution of (5-(2-fluoro-5-methoxyphenyl)-6-neopentylpyridin-2-yl)methanol (300 mg) in DMF (1.0 mL), and the mixture was stirred at room temperature for 1 hr. Saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture at 0° C., and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (255 mg) as a pale-yellow oil.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1Cl)=[CH:13][CH:12]=[CH:11][C:10]=2[N+:17]([O-])=O)=[O:5])[CH3:2].[CH3:20][O:21][C:22]1[CH:23]=[C:24]([CH:27]=[C:28]([O:30][CH3:31])[CH:29]=1)[CH2:25][NH2:26]>>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[NH:26][CH2:25][C:24]1[CH:27]=[C:28]([O:30][CH3:31])[CH:29]=[C:22]([O:21][CH3:20])[CH:23]=1)=[CH:13][CH:12]=[CH:11][C:10]=2[NH2:17])=[O:5])[CH3:2]
Reactant: COc1cc(CN)cc(OC)c1
Reactant: CCOC(=O)c1cnc2c([N+](=O)[O-])cccc2c1Cl
Product: CCOC(=O)c1cnc2c(N)cccc2c1NCc1cc(OC)cc(OC)c1
Yield: 87 %

Procedure:
The compound prepared in Example 3 was reacted with 3,5-dimethoxy-benzylamine according to the method as described in Example 4 and the obtained compound was treated as described in Example 14 to prepare the title compound (yield 87%).
Reaction SMILES: [C:1]([N:5]1[C:9]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)=[CH:8][C:7]([CH2:17][CH2:18][CH:19]=O)=[N:6]1)([CH3:4])([CH3:3])[CH3:2].[CH3:21][O:22][C:23]1[CH:28]=[CH:27][C:26]([N:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)=[CH:25][CH:24]=1.CCN(C(C)C)C(C)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[C:1]([N:5]1[C:9]([C:10]2[CH:11]=[CH:12][C:13]([F:16])=[CH:14][CH:15]=2)=[CH:8][C:7]([CH2:17][CH2:18][CH2:19][N:32]2[CH2:33][CH2:34][N:29]([C:26]3[CH:25]=[CH:24][C:23]([O:22][CH3:21])=[CH:28][CH:27]=3)[CH2:30][CH2:31]2)=[N:6]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: COc1ccc(N2CCNCC2)cc1
Reactant: CC(C)(C)n1nc(CCC=O)cc1-c1ccc(F)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc(N2CCN(CCCc3cc(-c4ccc(F)cc4)n(C(C)(C)C)n3)CC2)cc1

Procedure:
102 mg (58%) of target compound was obtained by using a method same as in Example 1 by using 3-(1-tert-butyl-5-(4-fluorophenyl)-1H-pyrazol-3-yl)propanal (100 mg, 0.365 mmol), 1-(4-methoxyphenyl)piperazine (71 mg, 0.365 mmol), DIPEA (0.1 mL, 0.548 mmol) and NaBH(OAc)3 (232 mg, 1.095 mmol).
Reaction SMILES: Br[CH2:2][C:3]1[S:4][C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=1>CC(C)=O>[S:4]1[C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=[C:3]1[CH2:2][O:25][C:22]1[CH:23]=[CH:24][C:19]([NH2:18])=[CH:20][CH:21]=1
Reactant: Nc1ccc(O)cc1
Reactant: BrCc1nc2ccccc2s1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC(C)=O
Product: Nc1ccc(OCc2nc3ccccc3s2)cc1
Temperature: 25 °C
Reaction time: 8.5 h
Yield: 52.4 %

Procedure:
4.56 g of 2-bromomethylbenzothiazole and 3.25 g of cesium carbonate were added to a solution of 2.17 g of 4-aminophenol in 70 ml of acetone, and the resulting mixture was stirred at room temperature for 8.5 hours, after which a further 3.25 g of cesium carbonate were added and the reaction mixture was stirred at room temperature for a further 4 hours. The reaction mixture was then filtered and the filtrate was concentrated by evaporation under reduced pressure. The resulting crude crystalline solid was purified by column chromatography through silica gel using a mixture of hexane and ethyl acetate as the eluent, initially using a gradient of the two solvents starting with a 1: 1 by volume mixture and changing to a final 3:2 by volume mixture to give 2.67 g (yield 52%) of the title compound as a solid having a melting point of 87° to 89° C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1F)[CH:5]=[O:6].[CH3:11][S-:12].[Na+].Cl>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[S:12][CH3:11])[CH:5]=[O:6]
Reactant: C[S-]
Reactant: O=Cc1ccc(F)c(F)c1
Agent: Cl
Agent: [Na+]
Solvent: CN(C)C=O
Product: CSc1ccc(C=O)cc1F
Temperature: 90 °C
Yield: 60.7 %

Procedure:
A mixture of 3,4-difluorobenzaldehyde (4.26 g, 30 mmol) and sodium thiomethoxide (2.1 g, 30 mmol) in DMF (40 mL) was heated at 90° C. for 1 hour. After cooling, 2N aqueous HCl was added to the mixture. The whole was extracted with Et2O (70 mL×3), the combined organic layer washed with water, brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with ethyl acetate/hexane (1/10) to provide the subtitle compound (3.1 g, 61% yield) as a colorless oil.
Reaction SMILES: CCN([CH2:6][CH2:7][NH:8][C:9]([C:11]1[CH:16]=[CH:15][C:14]([I:17])=[CH:13][CH:12]=1)=[O:10])CC.[CH:18]1C=C[C:21]([CH2:24][O:25][C@H:26]([C:32]([OH:34])=[O:33])[C@H:27]([NH2:31])[C:28]([OH:30])=[O:29])=[CH:20][CH:19]=1.C(O)(C(F)(F)F)=O>C(Cl)(Cl)Cl>[I:17][C:14]1[CH:13]=[CH:12][C:11]([C:9]([NH:8][C:7]2[CH:6]=[C:21]([CH:20]=[CH:19][CH:18]=2)[CH2:24][O:25][C@H:26]([C:32]([OH:34])=[O:33])[C@@H:27]([C:28]([OH:30])=[O:29])[NH2:31])=[O:10])=[CH:16][CH:15]=1
Reactant: CCN(CC)CCNC(=O)c1ccc(I)cc1
Reactant: N[C@H](C(=O)O)[C@H](OCc1ccccc1)C(=O)O
Solvent: ClC(Cl)Cl
Solvent: O=C(O)C(F)(F)F
Product: N[C@H](C(=O)O)[C@H](OCc1cccc(NC(=O)c2ccc(I)cc2)c1)C(=O)O
Reaction time: 24 h
Yield: 94.8 %

Procedure:
Protected I-BzA-TBOA (120 mg, 0.17 mmol) was dissolved in 1 ml of chloroform. After adding 1 ml of TFA, the obtained mixture was stirred for 24 hours. Then the solvent was distilled off and water was added to the residue followed by repeated freeze-drying. Thus, 78 mg (76%) of the title compound was obtained. Amorphous product; [α]D −37.7° (c 0.34, CHCl3); 1H NMR (CDCl3, 400 MHz); ™4.30 (d, 1 H, J=5.0 Hz), 4.45 (d, 1 H, J=11.0 Hz), 4.68 (d, 1 H, J=11.0 Hz), 7.14 (d, 1 H, J=7.5 Hz), 7.30 (t, 1 H, J=8.0 Hz), 7.59 (s, 1 H), 7.64 (d, 1 H, J=8.5 Hz), 7.67 (d, 2 H, J=7.5 Hz), 7.86 (d, 2 H, J=7.5 Hz).
Reaction SMILES: [Li+].CC([N-]C(C)C)C.[CH2:9]1[CH2:13][O:12][CH2:11][CH2:10]1.[Se:14]1[CH:18]=[CH:17][CH:16]=[C:15]1[C:19]1[Se:20][C:21]([C:24]2[Se:25]C=CC=2)=[CH:22][CH:23]=1.CN(C=O)C>C(OCC)(=O)C>[CH:11]([C:10]1[Se:25][C:24]([C:21]2[Se:20][C:19]([C:15]3[Se:14][CH:18]=[CH:17][CH:16]=3)=[CH:23][CH:22]=2)=[CH:13][CH:9]=1)=[O:12]
Reactant: C1CCOC1
Reactant: c1c[se]c(-c2ccc(-c3ccc[se]3)[se]2)c1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: O=Cc1ccc(-c2ccc(-c3ccc[se]3)[se]2)[se]1
Temperature: -78 °C
Reaction time: 3 h
Yield: 75 %

Procedure:
LDA (1.0 M solution in THF, 310 mL) was added to an anhydrous THF solution (4 mL) containing 2,2′:5′,2″-terselenophene (100 mg) under N2 at −78° C. The solution was stirred at −78° C. for 3 h, anhydrous DMF (1 mL) was added, stirred at −78° C. for 1 h, and slowly warmed to room temperature. The reaction solution was diluted with ethyl acetate (100 mL) and washed with H2O (4×100 mL). The organic layer was separated, dried over MgSO4, filtered, and the solvent was removed under vacuum. The residue was chromatographed over silica gel using CH2Cl2 to afford 2-formyl-5,2′:5′,2″-terselenophene in 75% yield.
Reaction SMILES: [H-].[Na+].[CH2:3]([O:5][C:6]([C:8]1([NH:17][C:18](=[O:30])[C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([CH3:25])[C:20]=2[O:26][CH:27]([CH3:29])[CH3:28])[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])[CH3:4].[CH3:31]I>C1COCC1>[CH2:3]([O:5][C:6]([C:8]1([N:17]([C:18](=[O:30])[C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([CH3:25])[C:20]=2[O:26][CH:27]([CH3:29])[CH3:28])[CH3:31])[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])[CH3:4]
Reactant: CI
Reactant: CCOC(=O)C1(NC(=O)c2cccc(C)c2OC(C)C)Cc2ccccc2C1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)C1(N(C)C(=O)c2cccc(C)c2OC(C)C)Cc2ccccc2C1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 56.7 %

Procedure:
To a solution of NaH (sodium hydride, 60% dispersion, 86.0 mg, 2.15 mmol)) in anhydrous THF (20 mL) is added dropwise the solution of 2-(2-isopropoxy-3-methyl-benzoylamino)-indan-2-carboxylic acid ethyl ester (6) (410 mg, 1.07 mmol) in THF (5 mL) at 0° C. After stirring for 20 min, methyl iodide (452 μL, 7.26 mmol) is added dropwise and the resulting suspension is warmed up to RT and continued stirring overnight. After being quenched by saturated aqueous solution of ammonium chloride (5 mL), the reaction mixture is diluted in EtOAc (50 mL). The organic layer is separated, washed with water (1×5 mL) and brine (2×5 mL), dried over anhydrous Na2SO4 and concentrated in in vacuo. The residue is purified by flash column chromatography (115 g silica gel, gradient elution: 0%-30% EtOAc in heptane) to give the pure product (118) as a colorless oil (240 mg, 57%).
Reaction SMILES: [OH:1][CH:2]([C:15]1[CH:20]=[CH:19][C:18]2[O:21][CH2:22][O:23][C:17]=2[CH:16]=1)[C:3]#[C:4][C:5]([O:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][O:13][CH3:14])=[O:6]>C(Cl)Cl.[O-2].[O-2].[Mn+4]>[CH2:22]1[O:21][C:18]2[CH:19]=[CH:20][C:15]([C:2]([C:3]#[C:4][C:5]([O:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][O:13][CH3:14])=[O:6])=[O:1])=[CH:16][C:17]=2[O:23]1
Reactant: COCCOCCOC(=O)C#CC(O)c1ccc2c(c1)OCO2
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClCCl
Product: COCCOCCOC(=O)C#CC(=O)c1ccc2c(c1)OCO2
Reaction time: 2 h

Procedure:
A solution of 7.9 g (24.5 mmol) of 2-(2-methoxyethoxy)ethyl 4-hydroxy-4-[3,4-(methylenedioxy)phenyl]-2butynoate in 100 ml of methylene chloride was added dropwise at 0° to a suspension of 64 g (0.74 mol) of manganese dioxide in 150 ml of methylene chloride. The reaction mixture was stirred at 0° for 2 hours, filtered over magnesium sulphate and concentrated. The residue was purified by flash chromatography on 800 g of silica gel (elution agent methylene chloride/ether 4:1). There was obtained 2-(2-methoxyethoxy)ethyl 3-[3,4-(methylenedioxy)-benzoyl]propiolate as a yellow oil.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:16][CH2:17][CH2:18][O:19][CH3:20])=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[NH2:21][C:22]1[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][C:23]=1[Cl:29].[H-].[Na+].CN(C)C=O>O>[NH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:16][CH2:17][CH2:18][O:19][CH3:20])=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:10]=3)[N:5]=[CH:4][CH:3]=2)=[CH:24][C:23]=1[Cl:29]
Reactant: Nc1ccc(O)cc1Cl
Reactant: COCCOc1cc2nccc(Cl)c2cc1C(=O)OC
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COCCOc1cc2nccc(Oc3ccc(N)c(Cl)c3)c2cc1C(=O)OC

Procedure:
Methyl 4-chloro-7-(2-methoxyethoxy)-6-quinolinecarboxylate (4.9 g), 4-amino-3-chlorophenol (2.0 g), sodium hydride (550 mg) and dimethylformamide (20 ml) were stirred together at 100° C. for 2 hours. The mixture was returned to room temperature, water was added, and extraction was performed with ethyl acetate. Silica gel was added to the extract solution and the solvent was distilled off under reduced pressure. The silica gel was charged into a dry column packed with silica gel, and purification was performed by column chromatography (hexane:ethyl acetate=1:1, followed by ethyl acetate) to obtain 3.2 g of the target substance as a violet solid.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[N+:11]([O-:13])=[O:12])[C:5]([OH:7])=O.[CH3:14][N:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1>>[CH3:1][C:2]1[CH:3]=[C:4]([C:5]([N:18]2[CH2:19][CH2:20][N:15]([CH3:14])[CH2:16][CH2:17]2)=[O:7])[CH:8]=[CH:9][C:10]=1[N+:11]([O-:13])=[O:12]
Reactant: CN1CCNCC1
Reactant: Cc1cc(C(=O)O)ccc1[N+](=O)[O-]
Product: Cc1cc(C(=O)N2CCN(C)CC2)ccc1[N+](=O)[O-]

Procedure:
Prepared from 3-methyl-4-nitrobenzoic acid and 1-methylpiperazine following the method used to prepare Intermediate 27. δH (DMSO-d6) 8.03 (d, J=8.3 Hz, 1H), 7.52 (d, J=1.9 Hz, 1H), 7.44 (dd, J8.4, 1.9 Hz, 1H), 3.66 (m, 2H), 3.26 (s, 2H), 2.53 (s, 3H), 2.37 (s, 2H), 2.25 (s, 2H), 2.19 (s, 3H).