Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].CN(C)C=O.CS(O[CH:15]1[CH2:20][CH2:19][CH:18]([O:21][CH2:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:17]([F:30])[CH2:16]1)(=O)=O.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.CCCCCC>[C:24]1([CH2:23][CH2:22][O:21][CH:18]2[CH2:19][CH2:20][CH:15]([N:1]=[N+:2]=[N-:3])[CH2:16][CH:17]2[F:30])[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: [N-]=[N+]=[N-]
Reactant: CS(=O)(=O)OC1CCC(OCCc2ccccc2)C(F)C1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: [N-]=[N+]=NC1CCC(OCCc2ccccc2)C(F)C1
Temperature: 50 °C
Yield: 71.3 %

Procedure:
Sodium azide (0.500 g, 7.69 mmol) was added to a N,N-dimethylformamide (10 mL) solution of 3-Fluoro-4-(2-phenylethoxy)cyclohexyl methanesulfonate (0.597 g, 1.89 mmol) under nitrogen. The resulting mixture was heated at 50° C. for 24 h, then cooled and poured into saturated sodium bicarbonate. The aqueous mixture was extracted with ethyl acetate (3×) and the combined organic extracts were washed with brine, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Flash column chromatography (hexane:ethyl acetate, e 90:10) gave 4-Azido-2-fluorocyclohexyl 2-phenylethyl ether as a colorless oil (0.355 g, 71% yield).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:22])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([S:10][C:11]2[C:19]3[C:14](=[CH:15][C:16](Br)=[CH:17][CH:18]=3)[NH:13][C:12]=2[CH3:21])[CH:5]=1.[CH3:23][S:24]([O-:26])=[O:25].[Na+]>CN1C(=O)CCC1.[Cu]I>[CH3:1][O:2][C:3](=[O:22])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([S:10][C:11]2[C:19]3[C:14](=[CH:15][C:16]([S:24]([CH3:23])(=[O:26])=[O:25])=[CH:17][CH:18]=3)[NH:13][C:12]=2[CH3:21])[CH:5]=1
Reactant: CS(=O)[O-]
Reactant: COC(=O)c1cccc(Sc2c(C)[nH]c3cc(Br)ccc23)c1
Agent: [Cu]I
Agent: [Na+]
Solvent: CN1CCCC1=O
Product: COC(=O)c1cccc(Sc2c(C)[nH]c3cc(S(C)(=O)=O)ccc23)c1
Temperature: 140 °C
Reaction time: 8 h

Procedure:
3-(6-Bromo-2-methyl-1H-indol-3-ylsulfanyl)-benzoic acid methyl ester (0.113 g, 0.3 mmol), sodium methanesulfinate (0.138 g, 1.35 mmol), and copper(I) iodide (0.257 g, 1.35 mmol) were combined in NMP (3 mL) in a sealed reaction vessel and stirred at 140° C. for overnight. The resulting mixture was cooled to room temperature, and subjected to standard aqueous workup. The crude residue was purified by silica gel chromatography (10-100% EtOAc in hexanes) to afford the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:21]=[CH:22][C:23]=1[O:24][CH3:25])[CH2:6][CH:7]1[C:16]2[C:11](=[CH:12][C:13]([O:19][CH3:20])=[C:14]([O:17][CH3:18])[CH:15]=2)[CH2:10][CH2:9][NH:8]1.Br[CH2:27][C:28](Br)=[O:29].[NH2:31][CH:32]1[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([CH3:41])[CH:39]=2)[CH2:34][CH2:33]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:21]=[CH:22][C:23]=1[O:24][CH3:25])[CH2:6][CH:7]1[C:16]2[C:11](=[CH:12][C:13]([O:19][CH3:20])=[C:14]([O:17][CH3:18])[CH:15]=2)[CH2:10][CH2:9][N:8]1[CH2:27][C:28]([NH:31][CH:32]1[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([CH3:41])[CH:39]=2)[CH2:34][CH2:33]1)=[O:29]
Reactant: COc1ccc(CC2NCCc3cc(OC)c(OC)cc32)cc1OC
Reactant: Cc1ccc2c(c1)C(N)CC2
Reactant: O=C(Br)CBr
Product: COc1ccc(CC2c3cc(OC)c(OC)cc3CCN2CC(=O)NC2CCc3ccc(C)cc32)cc1OC

Procedure:
prepared by reaction of 1-(3,4-Dimethoxy-benzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline and 2-bromoacetyl bromide with 1-amino-6-methyl-indane
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:4]=1[CH:5]=O.[C:13]([O:19][CH2:20][CH3:21])(=[O:18])[CH2:14][C:15]([CH3:17])=[O:16].C1C=CC=CC=1.N1CCCCC1>C(O)(=O)C>[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:4]=1[CH2:5][CH:14]([C:15]([CH3:17])=[O:16])[C:13]([O:19][CH2:20][CH3:21])=[O:18]
Reactant: COc1ccc(OC)c(C=O)c1
Reactant: CCOC(=O)CC(C)=O
Solvent: c1ccccc1
Solvent: CC(=O)O
Solvent: C1CCNCC1
Product: CCOC(=O)C(Cc1cc(OC)ccc1OC)C(C)=O

Procedure:
A mixture of 2,5-dimethoxybenzaldehyde (100 g), ethyl acetoacetate (84.5 g) and anhydrous benzene (200 ml), piperidine (6 ml) and acetic acid (12 ml) was heated at reflux for 3 hours in an apparatus fitted with a Dean-Stark trap to collect the azeotropically distilled water. The reaction mixture was cooled, benzene (300 ml) added, and the solution was washed successively with water (100 ml), cold 0.1N hydrochloric acid (200 ml), 5% aqueous sodium bicarbonate (200 ml) and dilute acetic acid (100 ml) and dried over anhydrous magnesium sulfate. The solvent was then removed under reduced pressure and the residual oil distilled, b.p. 169°-170° C./0.3 mm Hg. The product, ethyl α-(2,5-dimethoxybenzylidene)acetoacetate, solidified on standing (104 g, m.p. 68°-69° C.) and was recrystallized from ethanol-pentane (m.p. 72°-73° C.). A portion (38 g) of the product was reduced catalytically in the presence of palladium on charcoal catalyst (Pd/C) in ethyl acetate (150 ml). The product, after removal of solvent, was purified by distillation under reduced pressure to give ethyl α-(2,5-dimethoxybenzyl)acetoacetate, b.p. 146°-148° C./0.3 mm Hg.
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[NH:10][CH:9]=[C:8]2[C:16]1[N:24]([S:25]([C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=2)(=[O:27])=[O:26])[C:19]2=[N:20][CH:21]=[CH:22][CH:23]=[C:18]2[CH:17]=1.[CH3:35][O:36][CH2:37][CH2:38]Br.O>CN(C)C=O.C(OCC)(=O)C>[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[N:10]([CH2:38][CH2:37][O:36][CH3:35])[CH:9]=[C:8]2[C:16]1[N:24]([S:25]([C:28]2[CH:29]=[CH:30][C:31]([CH3:34])=[CH:32][CH:33]=2)(=[O:27])=[O:26])[C:19]2=[N:20][CH:21]=[CH:22][CH:23]=[C:18]2[CH:17]=1
Reactant: COc1cc2[nH]cc(-c3cc4cccnc4n3S(=O)(=O)c3ccc(C)cc3)c2cc1OC
Reactant: COCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: O
Product: COCCn1cc(-c2cc3cccnc3n2S(=O)(=O)c2ccc(C)cc2)c2cc(OC)c(OC)cc21
Reaction time: 16 h

Procedure:
0.01 g of sodium hydride (60%) is added to a solution of 0.1 g of 2-[5,6-dimethoxy-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine in 2.5 ml of anhydrous dimethylformamide, under an inert argon atmosphere at a temperature in the region of 20° C. Agitation is maintained at this temperature for 30 minutes. 0.023 ml of bromoethyl methyl ether is added. The reaction medium is agitated at the same temperature for 16 hours. 3 ml of water and 3 ml of ethyl acetate are added. After separation by settling out, the organic phase is dried over sodium sulfate, filtered, and then concentrated under reduced pressure. The residue obtained is purified on a flash-pack chromatography cartridge (silica, dichloromethane as eluent). The fractions containing the product are concentrated under reduced pressure. 0.082 g of 2-[5,6-dimethoxy-1-(2-methoxyethyl)-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine is thus obtained, the characteristics of which are as follows:
Reaction SMILES: C(N(CC)CC)C.[F:8][C:9]1[CH:17]=[CH:16][C:12]([C:13](Cl)=[O:14])=[CH:11][CH:10]=1.[CH2:18]([O:20][C:21](=[O:31])[CH2:22][NH:23][C:24]1[C:29]([NH2:30])=[CH:28][CH:27]=[CH:26][N:25]=1)[CH3:19].C(OC(=O)CNC1C([N+]([O-])=O)=CC=CN=1)C>O1CCCC1.[Pd]>[CH2:18]([O:20][C:21](=[O:31])[CH2:22][NH:23][C:24]1[C:29]([NH:30][C:13](=[O:14])[C:12]2[CH:16]=[CH:17][C:9]([F:8])=[CH:10][CH:11]=2)=[CH:28][CH:27]=[CH:26][N:25]=1)[CH3:19]
Reactant: CCOC(=O)CNc1ncccc1N
Reactant: O=C(Cl)c1ccc(F)cc1
Agent: [Pd]
Agent: CCOC(=O)CNc1ncccc1[N+](=O)[O-]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCOC(=O)CNc1ncccc1NC(=O)c1ccc(F)cc1
Yield: 5.6 %

Procedure:
Under a nitrogen atmosphere, triethylamine (31.8 g, 0.315 mole) and 4-fluorobenzoyl chloride (50 g, 0.315 mole) were added simultaneously, dropwise, to a stirred and chilled solution of freshly prepared N-[[3-amino]-2-pyridinyl]glycine ethyl ester (0.33 mole) by palladium/carbon reduction of N-[[3-nitro]-2-pyridinyl]glycine ethyl ester, (75.3 g, 0.33 mole) in dry tetrahydrofuran (~800 ml). The reaction mixture was stirred at room temperature overnight and the solvent was evaporated under reduced pressure. The residue was partitioned between ethyl acetate (300 ml) and water (300 ml), the insoluble material was filtered off, the layers were separated and the aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed three times with water, dried over magnesium sulfate, treated with charcoal, filtered and evaporated to give 76.8 g of crude solid (77% yield). A 6.8-g portion of the solid was recrystallized from isopropyl alcohol and water to give 5.63 g of title compound, mp 127° -128.5° C.
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]#[N:13])=[CH:9][CH:10]=2)[C:5](Cl)=[N:4][N:3]=1.Cl.[CH2:16]([C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][C:25]=1[O:26][CH3:27])[CH2:21][NH2:22])[CH3:17].C1CCN2C(=NCCC2)CC1>CN1CCCC1=O>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]#[N:13])=[CH:9][CH:10]=2)[C:5]([NH:22][CH2:21][C:20]2[CH:23]=[CH:24][C:25]([O:26][CH3:27])=[C:18]([CH2:16][CH3:17])[CH:19]=2)=[N:4][N:3]=1
Reactant: N#Cc1ccc2c(Cl)nnc(Cl)c2c1
Reactant: CCc1cc(CN)ccc1OC
Agent: Cl
Solvent: C1CCC2=NCCCN2CC1
Solvent: CN1CCCC1=O
Product: CCc1cc(CNc2nnc(Cl)c3ccc(C#N)cc23)ccc1OC

Procedure:
1,4-Dichlorophthalazine-6-carbonitrile and 3-ethyl-4-methoxybenzylamine hydrochloride were stirred at room temperature in 1-methyl-2-pyrrolidinone in the presence of DBU, whereby 1-chloro-4-[(3-ethyl-4-methoxybenzyl)amino]-6-phthalazine carbonitrile was obtained as a less polar compound.
Reaction SMILES: [CH2:1]([NH:8][C:9](=[N:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[S:10][CH2:11][CH3:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[C:21]([N:25]=[C:26]=[O:27])([CH3:24])([CH3:23])[CH3:22]>C(N(CC)CC)C.C(Cl)Cl>[CH2:14]([N:13]([C:26](=[O:27])[NH:25][C:21]([CH3:24])([CH3:23])[CH3:22])[C:9](=[N:8][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7])[S:10][CH2:11][CH3:12])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]
Reactant: CCCCCCCN=C(NCCCCCCC)SCC
Reactant: CC(C)(C)N=C=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCCCCN=C(SCC)N(CCCCCCC)C(=O)NC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
The equipment was the same as used in Example 26. 3.0 g (0.01 mole) 1,3-di-n-heptyl-2-S-ethyl isothiourea was mixed with 30 ml of methylene chloride. Two drops of triethylamine and 1 drop of dibutyltindilaurate were added to the mixture followed by 1.0 g (0.01 mole) tert-butyl isocyanate. The temperature rose from 24° to 39° C. The reaction mixture was stirred overnight at ambient temperature and then heated for one-half hour at 35° to 40° C. to complete the reaction. The reaction mixture was vacuum evaporated to produce 3.83 g (96 weight percent of theory yield) of a clear liquid having a nD30 of 1.4750. The product was identified as the title product by IR and NMR spectra analyses. Compound No. 40 in Table I.
Reaction SMILES: [OH-].[Na+].[C:3]1([C:5](=[CH:7][CH:8]=[CH:9][CH:10]=1)O)[OH:4].[CH3:11][O:12][C:13]1(C)C=CC(S([O-])(=O)=O)=C[CH:14]1[CH2:23]CC.CS(C)=[O:29]>O>[CH3:11][O:12][CH2:13][CH:14]([O:29][O:4][C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:5]=1)[CH3:23]
Reactant: CS(C)=O
Reactant: Oc1ccccc1O
Reactant: CCCC1C=C(S(=O)(=O)[O-])C=CC1(C)OC
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: COCC(C)OOc1ccccc1
Temperature: 25 °C
Reaction time: 14 h

Procedure:
90 parts of 44.5% strength sodium hydroxide solution are added drop by drop under nitrogen to a solution of 110 parts of pyrocatechol and 244 parts of 1-methoxy-2-propyl-p-toluenesulphonate in 500 parts by volume of dimethylsulphoxide. During the addition, the temperature rises to 42°C. The mixture is stirred for 14 hours at room temperature, poured into 2000 parts of water, and extracted three times each time with 250 parts by volume of toluene. The toluene solution is washed twice each time with 200 parts of water, and evaporated. The residue is distilled in a high vacuum. Boiling point 70°-82°C/0.04 mm Hg.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=O)[CH3:10])=[CH:5][CH:4]=1.C(OC(=O)[NH:16][NH2:17])C.O=[S:20](Cl)Cl>>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:17]=[N:16][S:20][CH:10]=2)=[CH:5][CH:4]=1
Reactant: O=S(Cl)Cl
Reactant: CCOC(=O)NN
Reactant: COc1ccc(C(C)=O)cc1
Product: COc1ccc(-c2csnn2)cc1
Temperature: 25 °C

Procedure:
The hydrazone (16.0 g, 68 mmol) derived from p-methoxyacetophenone and ethylcarbazate was added to 50 ml of SOCl2 and cooled in an ice bath. The reaction was warmed to room temperature and then heated at 60° C. for 1 hour. The reaction was cooled, and the solvent was removed under vacuum, affording a crude solid. The solid was recrystallized from ether affording 4 (9.95 g, 76%), m.p. 91°-93.5° C.
Reaction SMILES: N1([CH:6]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14](=O)[CH:15]=[C:16]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)C3C=CC=CC=3)=[CH:9][CH:8]=2)C=CN=C1.[Cl-].[Al+3].[Cl-].[Cl-].[NH4+:40].[OH-:41]>ClC1C=CC=CC=1>[N:40]1([CH:6]([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:7]2[CH:12]=[C:11]3[C:10](=[CH:9][CH:8]=2)[NH:13][C:14](=[O:41])[CH:15]=[C:16]3[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:9]=[CH:10][N:13]=[CH:14]1
Reactant: [NH4+]
Reactant: [OH-]
Reactant: O=C(C=C(c1ccccc1)c1ccccc1)Nc1ccc(C(c2ccccc2)n2ccnc2)cc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: Clc1ccccc1
Product: O=c1cc(-c2ccccc2)c2cc(C(c3ccccc3)n3ccnc3)ccc2[nH]1
Temperature: 95 °C
Reaction time: 8 h
Yield: 16 %

Procedure:
A mixture of intermediate (1-c) (22.85 g) and aluminium chloride (48 g) in chlorobenzene (200 ml) was heated at 95° C. overnight. The mixture was cooled, poured into ice water, basified with NH4OH and evaporated till dryness. The residue was taken up in DCM and ethanol. The residue was filtered and evaporated. The residue was taken up in DCM and stirred with HCl 3N overnight. The mixture was extracted, the aqueous layer was washed with ethyl acetate, basified with NH4OAc and then extracted with ethyl acetate and the organic layer was dried (MgSO4) and evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /CH3OH/NH4OH 95/5/0.05) (35-70 μm). The pure fractions were collected and evaporated, yielding 2.13 g (16%) of (±)-6-[(1H-imidazol-1-yl)phenylmethyl]-4-phenyl-2(1H)-quinolinone; mp. 253.0° C. (comp. 1).
Reaction SMILES: [OH:1][C:2]12[CH2:35][CH2:34][C@:33]3([CH3:36])[C:28](=[C:29]([CH3:37])[CH2:30][CH2:31][CH2:32]3)[C@@H:3]1[O:4][C:5](=[O:27])[CH:6]2[CH2:7][N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[C:19]([O:21][CH3:22])[CH:18]=[C:17]([O:23][CH3:24])[C:16]=2[CH2:25][OH:26])[CH2:10][CH2:9]1.[C:38](OC(=O)C)(=[O:40])[CH3:39].N1C=CC=CC=1>C(Cl)Cl.CN(C1C=CN=CC=1)C.O>[C:38]([O:26][CH2:25][C:16]1[C:17]([O:23][CH3:24])=[CH:18][C:19]([O:21][CH3:22])=[CH:20][C:15]=1[CH2:14][N:11]1[CH2:12][CH2:13][N:8]([CH2:7][CH:6]2[C:5](=[O:27])[O:4][C@H:3]3[C:28]4[C@@:33]([CH3:36])([CH2:34][CH2:35][C:2]23[OH:1])[CH2:32][CH2:31][CH2:30][C:29]=4[CH3:37])[CH2:9][CH2:10]1)(=[O:40])[CH3:39]
Reactant: COc1cc(CN2CCN(CC3C(=O)O[C@H]4C5=C(C)CCC[C@]5(C)CCC34O)CC2)c(CO)c(OC)c1
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Solvent: O
Solvent: ClCCl
Product: COc1cc(CN2CCN(CC3C(=O)O[C@H]4C5=C(C)CCC[C@]5(C)CCC34O)CC2)c(COC(C)=O)c(OC)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Compound of example 38 (200.0 mg, 0.39 mmol) was dissolved in DCM (10 mL). To it was added acetic anhydride (43.86 mg, 0.43 mmol), pyridine (61.70 mg, 0.78 mmol) and DMAP (2 mg) and reaction mixture was stirred at room temperature (25° C.) for 2 hours. Reaction mixture was diluted with water and extracted with DCM (3×50 mL). The crude product was purified by column chromatography (silica gel, 40% ethyl acetate in petroleum ether) to obtain the title compound.
Reaction SMILES: Cl[CH2:2][O:3][C:4](=[O:31])[N:5]([C:28](=[O:30])[CH3:29])[CH2:6][C@@H:7]1[O:11][C:10](=[O:12])[N:9]([C:13]2[CH:18]=[CH:17][C:16]([CH:19]3[CH2:24][CH2:23][S:22](=[O:26])(=[O:25])[CH2:21][CH2:20]3)=[C:15]([F:27])[CH:14]=2)[CH2:8]1.[C:32]1([C@H:38]([CH3:42])[C:39]([O-:41])=[O:40])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.[Cs+].[I-].[Na+].O>C(#N)C>[C:28]([N:5]([CH2:6][C@@H:7]1[O:11][C:10](=[O:12])[N:9]([C:13]2[CH:18]=[CH:17][C:16]([CH:19]3[CH2:24][CH2:23][S:22](=[O:26])(=[O:25])[CH2:21][CH2:20]3)=[C:15]([F:27])[CH:14]=2)[CH2:8]1)[C:4]([O:3][CH2:2][O:41][C:39](=[O:40])[C@H:38]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH3:42])=[O:31])(=[O:30])[CH3:29]
Reactant: CC(=O)N(C[C@H]1CN(c2ccc(C3CCS(=O)(=O)CC3)c(F)c2)C(=O)O1)C(=O)OCCl
Reactant: C[C@H](C(=O)[O-])c1ccccc1
Agent: [Cs+]
Agent: [I-]
Agent: [Na+]
Solvent: O
Solvent: CC#N
Product: CC(=O)N(C[C@H]1CN(c2ccc(C3CCS(=O)(=O)CC3)c(F)c2)C(=O)O1)C(=O)OCOC(=O)[C@@H](C)c1ccccc1
Temperature: 25 °C
Yield: 75 %

Procedure:
(R)-acetyl-{3-[4-(1,1-dioxo-hexahydro-1λ6-thiopyran-4-yl)-3-fluoro-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-carbamic acid chloromethyl ester (10) (0.40 g, 0.84 mmol), cesium 2(S)-phenyl-propionate (0.37 g, 1.31 mmol) and sodium iodide (0.13 g, 0.86 mmol) in acetonitrile (25 mL) are heated to reflux overnight. After cooling to RT, water is added and the reaction mixture is extracted with EtOAc and then with dichloromethane. The organic phases are washed separately with brine and then the organic layers are combined, dried over MgSO4, filtered, and conc in vacuo. The isolated residue is subjected to silica gel flash chromatography, eluting with MeOH/CH2Cl2 gradient (0-5% MeOH over 1 hour and 20 minutes) to afford the title compound. Isolated yield: 75%. 1H NMR (400 MHz, DMSO-d6): δ 7.43-7.39 (m, 1H), 7.33 (t, 1H), 7.27-7.15 (m, 6H), 5.78-5.72 (m, 2H), 4.63-4.57 (m, 1H0, 4.02-3.95 (m, 2H), 3.84 (q, 1H), 3.76-3.69 (m, 2H), 3.36-3.26 (m, partially obscured by water, 2H), 3.18-3.12 (m, 1H), 3.07-3.04 (m, 2H), 2.30 (d, 3H), 2.11 (q, 2H), 2.01-1.97 (m, 2H), 1.35 (d, 3H); MS-APCI (m/z+): 341, 385, 517, 591.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14](Br)[CH:15]=2)[CH:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:18]1(B(O)O)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>O.C(O)C.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>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:15]=2)[CH:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OB(O)c1ccccc1
Reactant: Brc1ccc2ccn(Cc3ccccc3)c2c1
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: [Na+]
Solvent: O
Solvent: CCO
Solvent: Cc1ccccc1
Product: c1ccc(Cn2ccc3ccc(-c4ccccc4)cc32)cc1
Yield: 58.4 %

Procedure:
1-Benzyl-6-phenyl-1H-indole was prepared by coupling 1-benzyl-6-bromo-1H-indole (3.48 g , 12.2 mmol), and phenylboronic acid (1.63 g, 13.4 mmol), using tetrakis(triphenylphosphine)palladium (0.976 g, 0.846 mmol), and sodium carbonate (5.2 g, 49 mmol) in water (25 mL), ethanol (5 mL), and toluene (55 mL), according to the procedure described in Step 2 of Example 2. Purification by flash chromatography using 0-2.5% ethyl acetate in hexane as an eluant afforded the title compound as a light green solid (2.02 g, 58%), mp: 109-110° C. Mass spectrum (+ES, [M+H]+) m/z 284; 1HNMR (500 MHz, DMSO-d6): δ 7.75 (s, 1H), 7.6-7.65 (m, 3H), 7.55 (d, 1H, J=3.1 Hz), 7.45 (t, 2H, J=7.5 Hz), 7.3-7.35 (m, 4H), 7.2-7.25 (m, 3H), 6.5 (d, 1H, J=3.0 Hz), and 5.5 ppm (s, 2H).
Reaction SMILES: [C:1]([C@@:3]1([OH:23])[CH2:8][CH2:7][C@H:6]2[C@H:9]3[C:19](=[CH:20][CH2:21][C@:4]12[CH3:5])[C@:17]1([CH3:18])[C:12](=[CH:13][C:14](=[O:22])[CH2:15][CH2:16]1)[CH2:11][CH2:10]3)#N.[Cl:24][CH2:25][Si](C)(C)Cl.[Li+].CC([N-]C(C)C)C.C1C[O:41]CC1>CN(C)C1C=CN=CC=1>[Cl:24][CH2:25][C:1](=[O:41])[C@:3]1([OH:23])[C@:4]2([CH3:5])[C@H:6]([C@H:9]3[C:19](=[CH:20][CH2:21]2)[C@:17]2([CH3:18])[C:12](=[CH:13][C:14](=[O:22])[CH2:15][CH2:16]2)[CH2:11][CH2:10]3)[CH2:7][CH2:8]1
Reactant: C1CCOC1
Reactant: C[Si](C)(Cl)CCl
Reactant: C[C@]12CCC(=O)C=C1CC[C@@H]1C2=CC[C@@]2(C)[C@H]1CC[C@]2(O)C#N
Agent: CC(C)[N-]C(C)C
Agent: CN(C)c1ccncc1
Agent: [Li+]
Product: C[C@]12CCC(=O)C=C1CC[C@@H]1C2=CC[C@@]2(C)[C@H]1CC[C@]2(O)C(=O)CCl
Reaction time: 1 h

Procedure:
17β-Cyano-17α-hydroxyandrosta-4,9(11)-dien-3-one (I, 3.316 gm) and 4-dimethylaminopyridine (63 mg) are slurried in dry THF (5 ml), treated with TEA (1.9 ml) and immediately cooled in an ice-acetone bath. With rapid stirring chloromethyldimethylchlorosilane (1.54 ml) is added dropwise. After 1 hr, the mixture is allowed to warm to 20°-25° over the course of 2 hrs, giving a mixture containing 17β-cyano-17α-hydroxyandrosta-4,9(11)-dien-3-one 17-(chloromethyl)dimethylsilyl ether (II). This mixture is transferred dropwise (10 min) to a solution of LDA (which is prepared from diisopropyl amine [7.0 ml] and 7-butyllithium-hexanes [1.6 molar, 26.6 ml, 42.6 mmol]) in dry THF (75 ml), stirring rapidly in a dry ice-acetone bath. After stirring 1 hr, the mixture is quenched with aqueous hydrochloric acid (6M, 25 ml), allowing the exotherm to carry the temperature to about 0° . Water (~50 ml) and methanol (~50 ml) are added, and the mixture is allowed to stir vigorously for 20 hrs at 20°-25°. The product is recovered by filtration and washed successively with water and methanol to give the title compound. A second crop is obtained on concentrating the mother liquors.
Reaction SMILES: Br[CH2:2][CH2:3][NH:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].[OH:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1[I:21])[C:16]#[N:17].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C=O)C>[C:7]([O:6][C:5]([NH:4][CH2:3][CH2:2][O:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1[I:21])[C:16]#[N:17])=[O:11])([CH3:10])([CH3:9])[CH3:8]
Reactant: N#Cc1ccc(I)c(O)c1
Reactant: CC(C)(C)OC(=O)NCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)NCCOc1cc(C#N)ccc1I
Temperature: 75 °C
Reaction time: 3 h

Procedure:
18.5 g (82.6 mmol) of t-butyl (2-bromoethyl)carbamate was dissolved in 200 ml of DMF. 10.1 g (41.3 mmol) of 3-hydroxy-4-iodobenzonitrile and 5.7 g (41.3 mmol) of potassium carbonate were added to the obtained solution, and they were stirred at 75° C. for 3 hours. After the treatment with ethyl acetate as the extracting solvent by an ordinary method, the title compound was obtained.
Reaction SMILES: [N+](C1C=CC(O[C:9]([O:11][C:12]2[CH:13]=[N:14][CH:15]=[C:16]([CH:21]=2)[C:17]([O:19][CH3:20])=[O:18])=[O:10])=CC=1)([O-])=O.C(#N)C.Cl.[NH:28]1[CH2:33][CH2:32][CH:31]([CH2:34][CH2:35][C:36]2[CH:37]=[C:38]([NH:42][C:43]([NH2:45])=[O:44])[CH:39]=[CH:40][CH:41]=2)[CH2:30][CH2:29]1>CCOC(C)=O>[NH2:45][C:43]([NH:42][C:38]1[CH:37]=[C:36]([CH2:35][CH2:34][CH:31]2[CH2:32][CH2:33][N:28]([C:9]([O:11][C:12]3[CH:13]=[N:14][CH:15]=[C:16]([CH:21]=3)[C:17]([O:19][CH3:20])=[O:18])=[O:10])[CH2:29][CH2:30]2)[CH:41]=[CH:40][CH:39]=1)=[O:44]
Reactant: NC(=O)Nc1cccc(CCC2CCNCC2)c1
Reactant: COC(=O)c1cncc(OC(=O)Oc2ccc([N+](=O)[O-])cc2)c1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CC#N
Product: COC(=O)c1cncc(OC(=O)N2CCC(CCc3cccc(NC(N)=O)c3)CC2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 65.8 %

Procedure:
Methyl 5-{[(4-nitrophenoxy)carbonyl]oxy}nicotinate (228 mg) was added to an acetonitrile (5 ml) solution of 1-{3-[2-(4-piperidinyl)ethyl]phenyl}urea hydrochloride (185 mg) and TEA (0.2 ml), followed by stirring overnight at room temperature. The reaction liquid was diluted with EtOAc, washed with aqueous saturated sodium hydrogencarbonate solution and saturated brine in that order, and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the resulting residue was purified by silica gel column chromatography (eluent: chloroform:methanol=10:1 (v/v)) to obtain methyl 5-({[4-(2-{3-[(aminocarbonyl)amino]phenyl}ethyl)-1-piperidyl]carbonyl}oxy)nicotinate (183 mg).