Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][CH2:2][CH2:3][C:4]1[C:10]2[C:11]3[O:25][C:24]([CH3:27])([CH3:26])[CH2:23][CH2:22][C:12]=3[C:13]3[O:18][C@@H:17]([CH3:19])[C@H:16]([CH3:20])[C@H:15]([OH:21])[C:14]=3[C:9]=2[O:8][C:6](=[O:7])[CH:5]=1.[CH3:28][CH2:29][CH2:30]C1C2C3OC(C)(C)C=CC=3C3OC(C)C(C)C(O)C=3C=2OC(=O)C=1>CO.O=[Pt]=O>[CH3:20][C@@H:16]1[C@H:15]([OH:21])[C:14]2[C:9]3[O:8][C:6]([CH:5]=[C:4]([C:3]4[CH:28]=[CH:29][CH:30]=[CH:1][CH:2]=4)[C:10]=3[C:11]3[O:25][C:24]([CH3:27])([CH3:26])[CH:23]=[CH:22][C:12]=3[C:13]=2[O:18][C@H:17]1[CH3:19])=[O:7]
Reactant: CCCc1cc(=O)oc2c3c(c4c(c12)OC(C)(C)CC4)O[C@@H](C)[C@H](C)[C@@H]3O
Reactant: CCCc1cc(=O)oc2c3c(c4c(c12)OC(C)(C)C=C4)OC(C)C(C)C3O
Agent: O=[Pt]=O
Solvent: CO
Product: C[C@H]1[C@H](C)Oc2c3c(c4c(-c5ccccc5)cc(=O)oc4c2[C@H]1O)OC(C)(C)C=C3

Procedure:
This example illustrates the preparation of antiviral 7,8-dihydro compounds (FIG. 6) of series 2, specifically 7,8-dihydrocalanolide A (FIG. 6A), 7,8-dihydrocalanolide B (FIG. 6B), 7,8-dihydrocostatolide (FIG. 6), and 7,8-dihydrosoulattrolide (FIG. 6D) from the corresponding 7,8-unsaturated compounds of series 1. Of these six compounds, only one structure (7,8-dihydrocostatolide (FIG. 6C); Stout, G. H., et al., J. Org. Chem., 29, 3604-3609 (1964)) had been previously reported, however none of the six were known heretofore to have antiviral activity. The 7,8-dihydro compounds were made by catalytic hydrogenation of the selected appropriate 7,8-unsaturated precursors. In a typical procedure, 10 mg of calanolide A was stirred with 2.5 mg PtO2 (Aldrich) in 4 ml MeOH under an atmosphere of H2 (a balloon filled with H2 was attached to the reaction vessel to provide a slightly positive pressure of H2) for 30 min. The mixture was filtered, and the solvent removed in vacuo to provide a light yellow oil which was purified by SiO2HPLC (21.1×300 mm, Dynamax column) eluted with 25 ml/min hexane/EtOAc (7:3) to give 9.0 mg of 7,8-dihydrocalanolide A (EIMS m/z 372, appropriate for C22H28O5 ; 1H NMR, see Table 5). In an exactly analogous fashion, 6 mg of calanolide B with 3 mg PtO2 in 4 ml MeOH was converted to 3.6 mg of 7,8-dihydrocalanolide B (EIMS m/z 372, appropriate for C22H28O5 ; 1H NMR, see Table 5); 100 mg of costatolide with 15 mg PtO2 in 20 ml MeOH was converted to 89.9 mg 7,8-dihydrocostatolide (EIMS m/z 372, appropriate for C22H28O5 ; 1H NMR, see Table 5); and 12 mg of soulattrolide with 3 mg PtO2 in 4 ml MeOH was converted to 8.9 mg 7,8-dihydrosoulattrolide (EIMS m/z 406, appropriate for C25H26O5 ; 1H NMR, see Table 5).
Reaction SMILES: [CH3:1][C:2]([C:9]([CH3:20])=[CH:10][CH2:11][CH:12]([CH3:19])[CH2:13][CH2:14][CH:15]=[C:16]([CH3:18])[CH3:17])=[CH:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[CH3:21][OH:22]>>[CH3:21][O:22][C:16]([CH3:18])([CH3:17])[CH2:15][CH2:14][CH2:13][CH:12]([CH3:19])[CH2:11][CH:10]=[C:9]([CH3:20])[C:2]([CH3:1])=[CH:3][C:4]([O:6][CH2:7][CH3:8])=[O:5]
Reactant: CCOC(=O)C=C(C)C(C)=CCC(C)CCC=C(C)C
Reactant: CO
Product: CCOC(=O)C=C(C)C(C)=CCC(C)CCCC(C)(C)OC

Procedure:
Methanol is added to the terminal bond of ethyl 3,4,7,11-tetramethyldodeca-2,4,10-trienoate using the process of Example 23 or 29 to give ethyl 11-methoxy-3,4,7,11 -tetramethyldodeca- 2,4 -dienoate. In the same manner, water is added to give ethyl 11-hydroxy-3,4,7,11-tetramethyldodeca-2,4-dienoate. Similarly, there is prepared ethyl 11-methoxy-3,5,7,11-tetramethyldodeca-2,4-dienoate and ethyl 11-hydroxy-3,5,7,11-tetramethyldodeca-2,4-dienoate from ethyl 3,5,7,11-tetramethyldodeca-2,4,10-trienoate. The hydrochloride, ethyl 11-chloro-3,4,7,11-tetramethyldodeca-2,4-dienoate and ethyl 11-chloro-3,5,7,11-tetramethyldodeca-2,4-dienoate are prepared from the trienoate using the process of Example 39.
Reaction SMILES: I[C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[CH2:5][C:6]1[O:10][C:9]([C:11]2[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][CH:12]=2)=[N:8][N:7]=1.C1CCN2C(=NCCC2)CC1.[O:33]1[CH2:37]CC[CH2:34]1.C[OH:39]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:34][O:33][C:37](=[O:39])[C:2]1[CH:21]=[CH:20][CH:19]=[C:4]([CH2:5][C:6]2[O:10][C:9]([C:11]3[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][CH:12]=3)=[N:8][N:7]=2)[CH:3]=1
Reactant: C1CCOC1
Reactant: CO
Reactant: N#Cc1ccc(-c2nnc(Cc3cccc(I)c3)o2)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Solvent: C1CCC2=NCCCN2CC1
Product: COC(=O)c1cccc(Cc2nnc(-c3ccc(C#N)cc3)o2)c1
Temperature: 100 °C
Yield: 48 %

Procedure:
Add molybedinum hexacarbonyl (0.07 g, 0.26 mmol) to 4-[5-(3-iodo-benzyl)-[1,3,4]oxadiazol-2-yl]-benzonitrile (0.10 g (0.26 mmol) in 2 mL of a 1:1 mixture of tetrahydrofuran MeOH in a microwave pressure tube. Add DBU (0.11 mL, 0.74 mmol) causing the solution to darken. Add palladium acetate (0.006 g, 0.030 mmol) to the mixture, seal the tube and heat at 100° C. in a microwave reactor for 10 minutes. Cool the mixture to room temperature and purify by flash silica gel chromatography to give 0.04 g 48% yield of 3-[5-(4-cyano-phenyl)-[1,3,4]oxadiazol-2-ylmethyl]-benzoic acid methyl ester a solid.
Reaction SMILES: [C:1]1(=[O:22])[N:5]([CH2:6][CH2:7][O:8][CH2:9][C:10](=[O:16])[CH2:11][C:12]([O:14][CH3:15])=[O:13])[C:4](=[O:17])[C:3]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:2]12.[Cl:23][C:24]1[CH:31]=[CH:30][CH:29]=[CH:28][C:25]=1[CH:26]=O.N1CCCCC1.C(O)(=O)C>CC(O)C>[Cl:23][C:24]1[CH:31]=[CH:30][CH:29]=[CH:28][C:25]=1[CH:26]=[C:11]([C:10]([CH2:9][O:8][CH2:7][CH2:6][N:5]1[C:4](=[O:17])[C:3]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:2]2[C:1]1=[O:22])=[O:16])[C:12]([O:14][CH3:15])=[O:13]
Reactant: COC(=O)CC(=O)COCCN1C(=O)c2ccccc2C1=O
Reactant: O=Cc1ccccc1Cl
Solvent: C1CCNCC1
Solvent: CC(C)O
Solvent: CC(=O)O
Product: COC(=O)C(=Cc1ccccc1Cl)C(=O)COCCN1C(=O)c2ccccc2C1=O
Temperature: 37.5 °C
Reaction time: 2 h

Procedure:
85 g of methyl 4-(2-(phthalimido)ethoxy)acetoacetate was agitated with 31.7 ml of 2-chlorobenzaldehyde and 37 ml of 2-propanol at 20-25° C. The solution of 1.1 ml of piperidine in 14 ml of 2-propanol was added dropwise during 1.5 hour. The mixture was than agitated for 2 hours at the same temperature and for 2 hours at 35-40° C. The mixture was acidified with 1.5 ml of acetic acid, 140 ml of 2-propanol was added and the solution was cooled to 0-5° C. The isopropanolic layer was separated and the organic layer was again washed with 53 ml of 2-propanol. The organic layer, containing the desired product, was evaporated to dryness in order to remove the residual solvent.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]([CH3:14])=[CH:12][S:11][C:10]1=[S:15].[CH3:16][I:17]>CC(C)=O>[I-:17].[NH2:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N+:9]1[C:13]([CH3:14])=[CH:12][S:11][C:10]=1[S:15][CH3:16]
Reactant: CI
Reactant: Cc1csc(=S)n1-c1ccc(F)cc1N
Solvent: CC(C)=O
Product: CSc1scc(C)[n+]1-c1ccc(F)cc1N
Product: [I-]
Temperature: 25 °C
Reaction time: 12 h

Procedure:
3 g (12.5 mmol) of 3-(2-amino-4-fluorophenyl)-4-methyl-1,3-thiazole-2(3H)-thione 2b obtained in stage A were solubilised in acetone (100 mL), then CH3I (10 eq, 7.8 mL) was added and the solution stirred at r.t. for 12 h. 3-(2-Amino-4-fluorophenyl)-4-methyl-2-(methylsulfanyl)-1,3-thiazol-3-ium iodide (3b) was recovered by filtration (pale yellow powder, 4.7 g, 98%). Mp=206° C.; 1H NMR (300 MHz, CD3OD) δ=2.26 (3H, d, J=1.1, CH3), 2.94 (3H, s, SCH3), 6.51-7.27 (3H, m, Ar), 7.82 (1H, q, J=1.1, H5); 13C NMR (75 MHz, CD3OD) δ=13.79, 17.97, 104.17 (d, J=27), 105.83 (d, J=25), 115.66 (d, J=2), 117.98, 130.83 (d, J=12), 147.65 (d, J=1), 148.28, 166.95 (d, J=248), 182.41; HRMS m/z C11H12N2FS2 [M−I]+ calcd: 255.0420, found: 255.0417.
Reaction SMILES: [C:1]([CH2:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[C:9]([CH3:14])[CH:8]=1)=[O:5])#[N:2].CO/[CH:17]=[CH:18]/[C:19](=O)[CH3:20].N12CCN(CC1)CC2.C(OCC)(=O)C>COCCOCCO.O>[F:13][C:10]1[CH:11]=[CH:12][C:7]([N:6]2[C:19]([CH3:20])=[CH:18][CH:17]=[C:3]([C:1]#[N:2])[C:4]2=[O:5])=[CH:8][C:9]=1[CH3:14]
Reactant: Cc1cc(NC(=O)CC#N)ccc1F
Reactant: CO/C=C/C(C)=O
Agent: C1CN2CCN1CC2
Solvent: COCCOCCO
Solvent: CCOC(C)=O
Solvent: O
Product: Cc1cc(-n2c(C)ccc(C#N)c2=O)ccc1F
Temperature: 25 °C
Yield: 34.8 %

Procedure:
A solution (30 mL) of 2-cyano-N-(4-fluoro-3-methylphenyl)acetamide (3.60 g, 19.0 mmol), (3E)-4-methoxybut-3-en-2-one (2.80 g, 28.0 mmol) and 1,4-diazabicyclo[2.2.2]octane (3.20 g, 28.0 mmol) in 2-(2-methoxyethoxy)ethanol was stirred at 120° C. for 12 hr. After cooling to room temperature, the reaction solution was divided into two layers with ethyl acetate and water and subjected to extraction (3 times) with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure, and the obtained residue was washed with ethyl acetate and collected by filtration to give the title compound (1.60 g, 34%) as a brown solid.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([OH:12])=[O:11])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:19](Br)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CN(C)C=O.C1(C)C=CC=CC=1.O>[OH:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][C:10]([O:12][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:11])=[CH:6][CH:7]=1
Reactant: BrCc1ccccc1
Reactant: O=C(O)CCc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Solvent: O
Product: O=C(CCc1ccc(O)cc1)OCc1ccccc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 94.1 %

Procedure:
To a solution of 3-(4-hydroxyphenyl)propionic acid (1.49 g, 8.96 mmol) in dimethylformamide (21.5 mL) were added potassium carbonate (1.30 g, 9.41 mmol) and benzyl bromide (1.69 g, 9.86 mmol), and the mixture was stirred at room temperature for 12 h. The reaction mixture was diluted with toluene and water to separate the phases. The residue obtained by concentrating the organic layer under reduced pressure was subjected to silica gel column chromatography (hexane-ethyl acetate 5:1→3:1) to give 2.16 g of benzyl 3-(4-hydroxyphenyl)propionate as oil (yield: 94%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[Cl:11])[C:5](Cl)=[O:6].[CH3:12][NH:13][CH2:14][C:15]([CH3:23])([N:20]([CH3:22])[CH3:21])[CH2:16][CH2:17][CH2:18][CH3:19]>C1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[Cl:11])[C:5]([N:13]([CH3:12])[CH2:14][C:15]([CH3:23])([N:20]([CH3:21])[CH3:22])[CH2:16][CH2:17][CH2:18][CH3:19])=[O:6]
Reactant: CCCCC(C)(CNC)N(C)C
Reactant: O=C(Cl)c1ccc(Cl)c(Cl)c1
Solvent: c1ccccc1
Product: CCCCC(C)(CN(C)C(=O)c1ccc(Cl)c(Cl)c1)N(C)C

Procedure:
A solution of 3,4-dichlorobenzoyl chloride (1.048 g., 5 mmole) in dry benzene (25 ml.) was added to a solution of N-methyl-2-methyl-2-dimethylamino hexylamine (0.754 g., 4.4 mmole) in dry benzene (25 ml.) and the solution heated under reflux for 1 hr. The cooled solution was washed with 2N sodium hydroxide solution (4 × 100 ml.), water (4 × 100 ml.), dried (Na2SO4) and evaporated to a colourless oil (1.612 g.). The oil was dissolved in benzene, chromatographed on a column of alumina (25 × 3.0 cm.) eluting with benzene/ether 1:1, and fractions (9 × 100 ml.) were collected. Fractions 2-8 were combined and, on evaporation, afforded 3,4-dichloro-N-methyl-N-[2-methyl-2-dimethylamino-hexyl]benzamide as a colourless oil (1.282 g., 84%).
Reaction SMILES: [C:1]([C@H:5]([NH:9][NH:10][C:11](=[O:21])[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[C:13]=1[CH3:20])[CH2:6][CH2:7][CH3:8])([CH3:4])([CH3:3])[CH3:2].[CH3:22][O:23][C:24]1[CH:25]=[C:26]([CH:30]=[C:31]([O:34][CH3:35])[C:32]=1[CH3:33])[C:27](Cl)=[O:28].C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[C:1]([C@H:5]([N:9]([C:27](=[O:28])[C:26]1[CH:30]=[C:31]([O:34][CH3:35])[C:32]([CH3:33])=[C:24]([O:23][CH3:22])[CH:25]=1)[NH:10][C:11](=[O:21])[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[C:13]=1[CH3:20])[CH2:6][CH2:7][CH3:8])([CH3:2])([CH3:3])[CH3:4]
Reactant: CCC[C@@H](NNC(=O)c1cccc(OC)c1C)C(C)(C)C
Reactant: COc1cc(C(=O)Cl)cc(OC)c1C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: CCC[C@@H](N(NC(=O)c1cccc(OC)c1C)C(=O)c1cc(OC)c(C)c(OC)c1)C(C)(C)C
Temperature: 25 °C

Procedure:
(R)-3-methoxy-2-methyl-benzoic acid N′-(1-tert-butyl-butyl)-hydrazide (100 mg, 0.34 mmol) and 3,5-dimethoxy-4-methyl-benzoyl chloride (90 mg, 0.41 mmol) were dissolved in 1 mL methylene chloride. 1.5 eq. of ca. 25% K2CO3 was added, and the reaction mixture was stirred at room temperature and monitored by TLC. Upon completion, the phases were separated, adding additional CH2Cl2 and/or water as needed to aid manipulation. The CH2Cl2 phase was dried over MgSO4 or Na2SO4, and solvent was removed in vacuo to provide an oily solid. This was triturated with 1:1 hexane:ether and allowed to dry in air to yield (R)-3,5-Dimethoxy-4-methyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(3-methoxy-2-methyl-benzoyl)-hydrazide. Rf=0.29 (2:1 hexanes:ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 7.1 (t, 1H), 7.0 (s, NH 1H), 6.9 (d, 1H), 6.7 (s, 2H), 6.3 (d, 1H), 4.78 (m, 1H), 3.95 (s, 3H), 3.85 (2s, 6H), 2.2 (s, 3H), 2.05 (m, 1H), 1.95 (s, 3H), 1.8 (m, 1H), 1.6 (m, 2H), 1.2+1.1+1.05 (3s, 9H), 1.05 (m, 3H); HRMS (ESI) m/z calcd for C27H39N2O5 [M+H]+ 471.2859. found 471.2850, calcd for C27H38NaN2O5 [M+Na]+ 493.2670. found 493.2678.
Reaction SMILES: [CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:12]1[N:17]=[CH:16][C:15]([C:18]2[N:23]3[N:24]=[C:25]([NH:27][C:28]([CH:30]4[CH2:32][CH2:31]4)=[O:29])[N:26]=[C:22]3[CH:21]=[CH:20][CH:19]=2)=[CH:14][CH:13]=1>C1COCC1>[CH2:1]([O:8][C:12]1[N:17]=[CH:16][C:15]([C:18]2[N:23]3[N:24]=[C:25]([NH:27][C:28]([CH:30]4[CH2:31][CH2:32]4)=[O:29])[N:26]=[C:22]3[CH:21]=[CH:20][CH:19]=2)=[CH:14][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Nc1nc2cccc(-c3ccc(Cl)nc3)n2n1)C1CC1
Reactant: OCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=C(Nc1nc2cccc(-c3ccc(OCc4ccccc4)nc3)n2n1)C1CC1
Temperature: 70 °C
Reaction time: 3 h

Procedure:
At 0° C. and under N2 atmosphere, Benzyl alcohol (2 eq) in a solution of THF was treated with NaH 60% in mineral oil (4 eq) for 30 min. Then cyclopropanecarboxylic acid [5-(6-chloro-pyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-amide prepared by method A was added to the solution and the mixture was stirred at 70° C. for 3 hours. The reaction was completed. The reaction mixture was quenched with water and the compound was extracted with EtOAc. The compound was washed with brine, dried on MgSO4, filtrated and concentrated. Compound was purified on Prep HPLC.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:20](=[O:21])[C:11]2=[CH:12][NH:13][C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=3[C:10]2=[N:9]1.I[CH2:23][CH3:24].C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[CH2:23]([N:13]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=2[C:10]2=[N:9][N:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[F:1])[C:20](=[O:21])[C:11]2=[CH:12]1)[CH3:24]
Reactant: O=c1c2c[nH]c3ccccc3c-2nn1-c1ccccc1F
Reactant: CCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: CCn1cc2c(=O)n(-c3ccccc3F)nc-2c2ccccc21
Temperature: 25 °C
Reaction time: 14 h

Procedure:
2-(2-Fluorophenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (51 mg, 0.18 mmol) was dissolved in dimethylsulfoxide (1 mL) and treated with iodoethane (0.018 mL, 0.22 mmol, 1.2 equiv) and potassium carbonate (30 mg, 0.22 mmol, 1.2 equiv). The mixture was stirred at ambient temperature for 14 hours, filtered and purified by preparative reverse phase HPLC (82:20 to 5:95; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.78 (1H, s), 8.48 (1H, dd, J=8.0, 1.5 Hz), 7.74-7.58 (4H, m), 7.42-7.36 (1H, m), 7.29-7.23 (2H, m), 4.44 (1H, q, J=7.4 Hz), 1.64 (3H, t, J=7.2 Hz) ppm; low resolution mass spectrometry (ES+) m/z 308.0 [(M+H)+; calculated for C18H15FN3O: 308.1].
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6](=[CH:11][CH:12]=1)[N:7]=[C:8](C)[N:9]=2.[C:13]1(OC)C=CC=CC=1.[F:21][C:22]([F:29])([F:28])[S:23]([O:26]C)(=[O:25])=[O:24]>C(OCC)(=O)C>[F:21][C:22]([F:29])([F:28])[S:23]([O-:26])(=[O:25])=[O:24].[CH3:13][N:7]1[C:6]2=[CH:11][CH:12]=[C:2]([CH3:1])[CH:3]=[CH:4][C:5]2=[NH+:9][CH:8]1[S:23][CH3:22]
Reactant: Cc1ccc2nc(C)nc-2cc1
Reactant: COS(=O)(=O)C(F)(F)F
Reactant: COc1ccccc1
Solvent: CCOC(C)=O
Product: CSC1[NH+]=C2C=CC(C)=CC=C2N1C
Product: O=S(=O)([O-])C(F)(F)F

Procedure:
27 g of 6-methyl-2-methylcycloheptimidazole was added to 100 ml of anisole and stirred under cooling with ice. Next, 28 g of methyl trifluoromethanesulfonate was dropwise added and further everything was stirred under cooling with ice. After everything was stirred for 1 hour at room temperature, 200 ml of ethyl acetate was added, and the crystals precipitated were separated by filtration and dried.
Reaction SMILES: [SH:1][C:2]([SH:7])=[CH:3][C:4](=[O:6])[CH3:5].[N+:8]([CH2:11][CH2:12]OC(=O)C)([O-])=[O:9]>C(O)C>[O:6]=[C:4]([CH3:5])[CH:3]=[C:2]1[S:7][C:11](=[N:8][OH:9])[CH2:12][S:1]1
Reactant: CC(=O)OCC[N+](=O)[O-]
Reactant: CC(=O)C=C(S)S
Solvent: CCO
Product: CC(=O)C=C1SCC(=NO)S1

Procedure:
To a solution of 6.8 grams (0.5m) of 4,4-dimercapto-3-buten-2-one in ethanol cooled to 10° C. was added 2.0 grams (0.5m) of sodium hydroxide dissolved in 30 ml of ethanol followed by dropwise addition at 0°-10° C. of 6.7 grams (0.5m) of nitroethylacetate dissolved in ethanol.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[O:11][C:12]2[CH:18]=[CH:17][CH:16]=[CH:15][C:13]=2[N:14]=1)([O-])=O.NC1C=CC=C[C:21]=1[C:26]1[O:27]C2C=CC=CC=2N=1>C(Cl)Cl.C(O)C.O=[Pt]=O>[O:11]1[C:12]2[CH:18]=[CH:17][CH:16]=[CH:15][C:13]=2[N:14]=[C:10]1[C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[NH:1][C:26](=[O:27])[CH3:21]
Reactant: Nc1ccccc1-c1nc2ccccc2o1
Reactant: O=[N+]([O-])c1ccccc1-c1nc2ccccc2o1
Agent: O=[Pt]=O
Solvent: ClCCl
Solvent: CCO
Product: CC(=O)Nc1ccccc1-c1nc2ccccc2o1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
The compound was prepared in a multistep synthesis employing Scheme 3, as described: A suspension of 2-aminophenol (5.0 g, 45.81 mmol) and 2-nitrobenzaldehyde (6.92 g, 45.81 mmol) in cyclohexane (200 mL) was heated to reflux using a Dean-Stark apparatus to remove water for 5 h. The reaction mixture was concentrated in vacuo to yield bright yellow crystals of the corresponding imine (10.71 g, 97% yield). To a solution of this imine (7.88 g, 32.56 mmol) in CH2Cl2 (200 mL) was added Ag2O (9.05 g, 39.07 mmol) and the reaction mixture was allowed to stir at RT overnight. The solvent was removed in vacuo to yield a solid shown to be the 2-(2-nitrophenyl) benzoxazole. This product was then suspended in ethanol (200 mL) with PtO2 (0.3 g) and charged with H2 (60 psi). The reaction mixture was allowed to shake on a Parr apparatus for 3 h. This was filtered through celite and the filtrate was removed in vacuo to yield a yellow solid. 1H NMR showed this to be the desired 2-(2-aminophenyl) benzoxazole, 3.85 g. This was acetylated according to General Procedure A and purified by recrystallization from cyclohexane/ethyl acetate, m.p. 125°-128° C.; 1H NMR (300 MHz, DMSO-d6) δ11.48 (s, 1H), 8.54 (d, J=9 Hz, 1H), 8.13 (dd, J=1.5, 9 Hz, 1H), 7.80-7.75 (m, 2H), 7.57 (m, 1H), 7.45 (m, 2H), 7.25 (t, J=9 Hz, 1H), 2.23 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ5 168.79, 161.46, 148.92, 140.39, 138.59, 132.89, 128.62, 126.18, 125.28, 123.37, 120.29, 119.83, 113.05, 111.07, 25.15; IR (KBr) 3270, 1685, 1540, 1240, 750 cm-1 ; MS (DCI) m/e MH+ =253; Analysis calc' d for C15H12N2O2 : C, 71.42; H, 4.79; N, 11.10; found: C, 71.24; H, 5.14;N, 10.76.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C@@H:9]([C@H:13]2[CH2:17][O:16][C:15](=[O:18])[NH:14]2)[CH2:10][CH:11]=[CH2:12])[CH:5]=[CH:6][C:7]=1[Cl:8].[H-].[Na+].[CH3:21]I>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:9]([C@H:13]2[CH2:17][O:16][C:15](=[O:18])[N:14]2[CH3:21])[CH2:10][CH:11]=[CH2:12])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: C=CC[C@@H](c1ccc(Cl)c(Cl)c1)[C@H]1COC(=O)N1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: C=CC[C@@H](c1ccc(Cl)c(Cl)c1)[C@H]1COC(=O)N1C
Temperature: 70 °C
Reaction time: 14 h
Yield: 85.6 %

Procedure:
To a solution of 4(S)-(1(S)-(3,4-dichlorophenyl)-3-butenyl)-2-oxazolidinone (3.25 g, 11.4 mmol) in DMF (25 mL) at room temp was added NaH (573 mg, 95%, 22.7 mmol). The mixture was stirred for 20 min whereupon MeI (3.54 mL, 57.0 mmol) freshly filtered through basic alumina was added and the resultant reaction mixture was stirred at 70° C. for 14 h. The cooled reaction mixture was diluted with H2O (250 mL) and extracted with EtOAc (3×125 mL). The combined organic extracts were washed with H2O (3×100 mL), brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by column chromatography (silica gel 60, 1-5% MeOH/CH2Cl2) to afford the title compound (2.93 g, 86%) as a colorless solid and recovered starting material (382 mg, 11%).
Reaction SMILES: [C:1]1([CH2:7][CH:8]2[CH2:12][O:11][C:10](=[O:13])[N:9]2[C:14](=[O:34])[CH2:15][CH:16]2[CH2:21][CH2:20][CH:19]([CH2:22][O:23][Si:24]([CH:31]([CH3:33])[CH3:32])([CH:28]([CH3:30])[CH3:29])[CH:25]([CH3:27])[CH3:26])[CH2:18][CH2:17]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(C1C=C(C(C)C)C(S([N:50]=[N+:51]=[N-:52])(=O)=O)=C(C(C)C)C=1)C.C(O)(=O)C>C1COCC1.C1(C)C=CC=CC=1>[C:1]1([CH2:7][CH:8]2[CH2:12][O:11][C:10](=[O:13])[N:9]2[C:14](=[O:34])[CH:15]([N:50]=[N+:51]=[N-:52])[CH:16]2[CH2:21][CH2:20][CH:19]([CH2:22][O:23][Si:24]([CH:25]([CH3:27])[CH3:26])([CH:28]([CH3:30])[CH3:29])[CH:31]([CH3:33])[CH3:32])[CH2:18][CH2:17]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC(C)c1cc(C(C)C)c(S(=O)(=O)N=[N+]=[N-])c(C(C)C)c1
Reactant: CC(C)[Si](OCC1CCC(CC(=O)N2C(=O)OCC2Cc2ccccc2)CC1)(C(C)C)C(C)C
Solvent: CC(=O)O
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CC(C)[Si](OCC1CCC(C(N=[N+]=[N-])C(=O)N2C(=O)OCC2Cc2ccccc2)CC1)(C(C)C)C(C)C
Yield: 52 %

Procedure:
Acyl oxazolidinone (1.28 g, 2.62 mmol) from Step G in 30 mL of THF at −78° C. was treated with 5.8 mL (2.89 mmol) of a 1.5 M solution of potassium hexamethyldisilylamide in toluene followed by 973 mg (3.14 mmol) of trisyl azide in 6 mL of THF and quenched by the addition of 634 mg (10.5 mmol) of acetic acid according to the procedure of D. A. Evans et al., J. Amer. Chem. Soc. 1990, 10, 4011. Purification by Biotage chromatography on silica gel (25% ether/hexane) provided 720 mg (52%) of the title compound. 1H NMR (500 MHz, CDCl3) δ 7.39–7.24 9 (m, 5H), 5.12 (d, 0.3H, J=8.7 Hz), 4.97 (d, 0.7H, J=7.5 Hz), 4.72 (m, 1H), 4.25 (m, 2H), 3.61 (d, 0.6H, J=7 Hz), 3.51 (d, 1.4H, J=5.9 Hz), 3.33 (dd, 1H, J=3 and 4 Hz), 2.87 (dt, 1H, J=3 and 10 Hz), 2.0–1.4 (m, 8H), 1.07–0.9 (m and d, 24H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](/[CH:9]=[CH:10]/[C:11]2[CH:16]=[CH:15][C:14]([N:17]3[C:21](=[O:22])[CH2:20][CH:19]([C:23]([OH:25])=[O:24])[CH2:18]3)=[CH:13][CH:12]=2)=[CH:5][CH:4]=1.Cl[CH2:27]Cl>CO.S(=O)(=O)(O)O>[CH3:27][O:24][C:23]([CH:19]1[CH2:20][C:21](=[O:22])[N:17]([C:14]2[CH:15]=[CH:16][C:11](/[CH:10]=[CH:9]/[C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)=[CH:12][CH:13]=2)[CH2:18]1)=[O:25]
Reactant: COc1ccc(/C=C/c2ccc(N3CC(C(=O)O)CC3=O)cc2)cc1
Reactant: ClCCl
Agent: O=S(=O)(O)O
Solvent: CO
Product: COC(=O)C1CC(=O)N(c2ccc(/C=C/c3ccc(OC)cc3)cc2)C1
Temperature: 40 °C

Procedure:
A solution of 700 mg (2.1 mmol) of (RS)-(E)-1-{4-[2-(4-methoxy-phenyl)-vinyl]-phenyl}-5-oxo-pyrrolidine-3-carboxylic acid in 7 ml of dichloromethane and 0.7 ml of methanol is treated with 1drop of sulfuric acid and heated at 40° C. for 20 hours. For the working-up, the solvent is evaporated, thereafter, the residue is treated with water and ethyl acetate. The organic layer is separated, dried over magnesium sulfate, and evaporated under reduced pressure. After crystallization from ether of the crude ester, 584 mg (80% of theory) of (RS)-(E)-1-{4-[2-(4-methoxy-phenyl)-vinyl]-phenyl}-5-oxo-pyrrolidine-3-carboxylic acid methyl ester are obtained as a light brown solid; MS: m/e=352 (M+H)+.