Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:15]2[C:6](=[CH:7][C:8]3[C:13]([CH:14]=2)=[C:12]([Cl:16])[CH:11]=[CH:10][CH:9]=3)[CH:5]=[CH:4][CH:3]=1.N#N.Cl[Sn](Cl)(Cl)Cl.ClC[CH:26]([O:29]C(CCl)CCl)CCl.Cl>O.C(Cl)Cl>[Cl:1][C:2]1[C:15]2[C:6](=[C:7]([CH:26]=[O:29])[C:8]3[C:13]([CH:14]=2)=[C:12]([Cl:16])[CH:11]=[CH:10][CH:9]=3)[CH:5]=[CH:4][CH:3]=1
Reactant: ClCC(CCl)OC(CCl)CCl
Reactant: Clc1cccc2cc3cccc(Cl)c3cc12
Agent: Cl
Agent: Cl[Sn](Cl)(Cl)Cl
Agent: N#N
Solvent: ClCCl
Solvent: O
Product: O=Cc1c2cccc(Cl)c2cc2c(Cl)cccc12
Yield: 21 %

Procedure:
1,8-Dichloroanthracene prepared by the method of H. O. House et. al. (J. Org. Chem. 38 1167 (1973)). A 3 L 3-neck flask fitted with overhead mechanical stirrer, thermometer, condenser, and N2 line was charged with 1,8-dichloroanthracene (17.3 g, 70 mmol) and CH2Cl2 (1500 mL). After further cooling with salt-ice bath to 5°, SnCl4 (Aldrich, 98%, 36.5 g, 0.14 mol, 16.4 mL), was added in one portion to the reaction. No temperature change occurred. The pot temperature was kept below 5°, and 1,1-dichloromethylmethylether (Aldrich, 16.09 g, 0.14 mol, 12.60 mL) was added dropwise over 1 h. The resulting suspension was warmed slowly to reflux (37°). Considerable HCl gas evolution occurred during the warming and the early part of the reaction at 37°. The reaction mixture was then cooled to 10° and hydrolysed by careful addition of 1 L of cold H2O. After 4 h the layers were separated and the organic layer filtered, dried with anhydrous Na2SO4 (Mallinckrodt, 100 g) and filtered again and the volume reduced to 100 mL. The clear yellow solution was passed through a 1000 g plug of SiO2 using PhCH3 as the eluting solvent with 500 mL fractions. This chromatography separated unreacted 1,8-dichloroanthracene (11 g, 63%) from the aldehyde and a more polar product. Fractions containing the aldehyde were combined and the PhCH3 removed, to give 5.83 g (21%) of 4,5-dichloro-9-anthracenecarbaldehyde mp 218°-220°, (PhCH3 /CH3OH), (C, H, Cl), (lit. 224°-226°, E. L. Stogryn, J. Med. Chem. 17 563 (1974)).
Reaction SMILES: C(O[CH2:5][CH2:6][CH2:7][CH2:8][CH:9]=[CH:10][CH2:11][CH2:12][CH2:13][CH3:14])(=O)C.[Cl:15]C=CCCCC.C=CCCCC>Cl[Ru](=CC1C=CC=CC=1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)Cl>[Cl:15][CH2:5][CH2:6][CH2:7][CH2:8][CH:9]=[CH:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: CCCCC=CCCCCOC(C)=O
Reactant: CCCCC=CCl
Agent: Cl[Ru](Cl)(=Cc1ccccc1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1
Solvent: C=CCCCC
Product: CCCCC=CCCCCCl

Procedure:
FIG. 1B is a reaction diagram showing the second step of the synthesis of 5-decenyl acetate, in which 1-chloro-hexene is reacted with 1-hexene in the presence of Grubbs' catalyst to yield 1-chloro-5-decene.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([Cl:10])[C:3]=1[C:4]#[N:5].[CH3:11][C:12]([C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=1)=[O:13].C([O-])(=O)C.C([O-])(=O)C.C1([I+2])C=CC=CC=1.FC(S(O)(=O)=O)(F)F>>[Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([Cl:10])[C:3]=1[C:4]1[O:13][C:12]([C:14]2[CH:15]=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[CH:11][N:5]=1
Reactant: CC(=O)c1ccc([N+](=O)[O-])cc1
Reactant: N#Cc1c(Cl)cccc1Cl
Agent: CC(=O)[O-]
Agent: O=S(=O)(O)C(F)(F)F
Agent: [I+2]c1ccccc1
Product: O=[N+]([O-])c1ccc(-c2cnc(-c3c(Cl)cccc3Cl)o2)cc1

Procedure:
2,6-Dichlorobenzonitrile and 4-nitrophenyl methyl ketone can be reacted with phenyliodine (III) diacetate and trifluoromethylsulfonic acid by the method of R. S. Varma, et al, J. Heterocyclic Chem., 1998, 35(6), 1533–1534 to give 2-(2,6-dichlorophenyl)-5-(4-nitrophenyl)-1,3-oxazole. The nitrophenyl group can be reduced to the corresponding aniline with tin (II) dichloride or iron powder and ammonium chloride. Reaction of this aniline with 2,2-dichloroacetyl chloride and triethylamine can then give 2,2-dichloro-N-[4-[2-(2,6-dichlorophenyl)-5-(1,3-oxazolyl)]phenyl]acetamide.
Reaction SMILES: [NH2:1][CH2:2][C:3]([NH:5][C@H:6]([C:8]([NH:10][CH2:11][C:12]([NH:14][C@@H:15]([C:17]([NH:19][CH2:20][C:21]([OH:23])=O)=[O:18])[CH3:16])=[O:13])=[O:9])[CH3:7])=[O:4].Cl.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1>CN(C=O)C.O>[NH:1]1[C:21](=[O:23])[CH2:20][NH:19][C:17](=[O:18])[C@@H:15]([CH3:16])[NH:14][C:12](=[O:13])[CH2:11][NH:10][C:8](=[O:9])[C@H:6]([CH3:7])[NH:5][C:3](=[O:4])[CH2:2]1
Reactant: C[C@H](NC(=O)CN)C(=O)NCC(=O)N[C@H](C)C(=O)NCC(=O)O
Agent: Cl
Agent: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Solvent: O
Solvent: CN(C)C=O
Product: C[C@@H]1NC(=O)CNC(=O)CNC(=O)[C@@H](C)NC(=O)CNC1=O
Temperature: -40 °C
Reaction time: 48 h
Yield: 67 %

Procedure:
This compound was synthesized by the method of Veber, D. F. et al, J. Org. Chem. 44, 3101-5 (1979). To a solution of Gly-Ala-Gly-DAla-Gly.HCl prepared as in Example 34D (9.70 g, 26.4 mmol) in anhydrous DMF (3200 ml) was added enough TEA to adjust the pH to ~8 (measured by spotting the reaction mixture on moistened Hydrion paper) and the resulting mixture was cooled to -40° C. To this mixture was added DPPA (8.86 g, 32.2 mmol) dropwise over 5 min. The temperature was maintained at ~-35° C. for a period of 5 h and then the reaction mixture was stored at -25° C. (internal temperature) for 48 h thereafter. During this time the pH was monitored periodically (as described above) and maintained at ~8 by the addition of TEA. After this time the reaction mixture was allowed to stand at 0° C. for 48 h. Again the pH was monitored periodically and maintained at ~8 by the addition of TEA. After this time the reaction was diluted with water (3200ml) and stirred with Bio-Rad AG 501-X8 (mixed-bed) resin (1500 g) for 6 h. The resin was separated by filtration and the solution was concentrated to dryness. Trituration of the residue with refluxing THF for 12 h, filtration of the hot THF and drying at high vacuum afforded 5.50 g (67% yield) of the product as a white powder: mp >300° C. (dec); 1H NMR (DMSO-d6) δ 1.16-1.25 (m, 6 H), 3.38-4.23 (m, 8 H), 7.55 (t, J=5.6 Hz, 1 H), 7.60 (t, J=5.4 Hz, 1 H), 8.20-8.25 (m, 1 H), 8.40 (d, J=7.6 Hz, 1 H); FAB mass spectrum (NBA+Li+) m/z 320 (M+Li)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[CH:4][CH:3]=1.Cl[CH2:12][CH2:13][N:14]([CH2:22][CH2:23]Cl)[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18].[H-].[Na+]>CN(C)C=O>[C:9]([C:8]1([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[CH2:23][CH2:22][N:14]([C:15]([O:16][C:17]([CH3:19])([CH3:18])[CH3:20])=[O:21])[CH2:13][CH2:12]1)#[N:10]
Reactant: CC(C)(C)OC(=O)N(CCCl)CCCl
Reactant: N#CCc1ccc(F)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCC(C#N)(c2ccc(F)cc2)CC1
Temperature: 0 °C

Procedure:
2-(4-Fluorophenyl)acetonitrile (1.35 g, 10.0 mmol) and tert-butyl bis(2-chloroethyl)carbamate (2.42 g, 10.0 mmol) were combined in dimethylformamide (30 mL) and cooled to 0° C. The reaction was treated with sodium hydride (760 mg, 30.0 mmol) in several portions. The ice bath was removed and the reaction heated at 60° C. for 24 h. After cooling to room temperature, the mixture was poured into ice water and extracted with ethyl acetate (2×). The organic layers were pooled together, washed with brine (2×), dried over sodium sulfate, and concentrated. Column chromatography on silica gel (15% ethyl acetate/hexanes) gave 1.65 g (54%). 1H-NMR (CDCl3, 500 MHz) δ 7.39-7.44 (m, 2H), 7.04-7.10 (m, 2H), 4.23-4.27 (m, 2H), 3.12-3.21 (m, 2H), 2.03-2.07 (m, 2H), 1.82-1.92 (m, 2H), 1.45 (s, 9H). Mass spec.: 327.11 (MNa)+.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:18](=[O:19])[N:17]2[C:12]([C:13]([CH3:21])([CH3:20])[O:14][CH2:15][CH2:16]2)=[N:11][C:10]=1[C:22]([OH:24])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][C:28]=1[NH:34][CH2:35][CH3:36]>>[CH2:35]([NH:34][C:28]1[CH:29]=[C:30]([F:33])[CH:31]=[CH:32][C:27]=1[CH2:26][NH:25][C:22]([C:10]1[N:11]=[C:12]2[N:17]([C:18](=[O:19])[C:9]=1[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH2:16][CH2:15][O:14][C:13]2([CH3:21])[CH3:20])=[O:24])[CH3:36]
Reactant: CCNc1cc(F)ccc1CN
Reactant: CC1(C)OCCn2c1nc(C(=O)O)c(OCc1ccccc1)c2=O
Product: CCNc1cc(F)ccc1CNC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2(C)C

Procedure:
The title compound can be prepared from intermediate 27, 3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido-[2,1-c][1,4]oxazine-2-carboxylic acid and 2-(aminomethyl)-N-ethyl-5-fluorobenzenamine. 1HNMR 400 MHz (CDCl3) δ (ppm): 1.27 (3H, t, J=7.1 Hz, CH3), 1.63 (6H, s, 2×CH3), 3.10 (2H, q, J=7.1 Hz, CH2), 4.04 (4H, m, 2×CH2), 4.45 (2H, d, J=6.6 Hz, NCH2), 5.27 (2H, s, OCH2), 6.28 (1H, broad s, aromatic), 6.31 (1H, m, aromatic), 6.98 (1H, m, aromatic), 7.3-7.38 (3H, m, aromatics), 7.49 (2H, m, aromatics), 7.54 (1H, broad t, NH). HRMS (ESI+) calculated for C26H30FN4O4 [M+H+]: 481.2251: found: 481.2254.
Reaction SMILES: C[O:2][C:3]([CH:5]1[CH2:9][C:8](=[CH2:10])[CH2:7][CH:6]1[NH:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:4].O[Li].O>CO.O>[C:15]([O:14][C:12]([NH:11][CH:6]1[CH2:7][C:8](=[CH2:10])[CH2:9][CH:5]1[C:3]([OH:4])=[O:2])=[O:13])([CH3:18])([CH3:16])[CH3:17]
Reactant: C=C1CC(NC(=O)OC(C)(C)C)C(C(=O)OC)C1
Agent: [Li]O
Solvent: O
Solvent: CO
Product: C=C1CC(NC(=O)OC(C)(C)C)C(C(=O)O)C1
Reaction time: 1 h
Yield: 93.4 %

Procedure:
To a solution of 1.28 g of 35a in 30 ml of MeOH was added a solution of 0.42 g of LiOH.H2O in 10 ml of H2O and stirring was continued at 50° C. for 1 h. The solution was evaporated to approximately half of the volume, the aqueous layer was washed with Et2O, acidified with HCl, the suspension was filtered and the residue dried to give 1.13 g (93%) of the title compound 35b. MS: 242.4 (M+H)+.
Reaction SMILES: [CH2:1]1[CH2:6][CH2:5][CH:4]([N:7]=[C:8]=[N:9][CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[CH2:3][CH2:2]1.C1C=CC2N([OH:25])N=NC=2C=1.O.CN1CCOCC1>CN(C=O)C>[CH:10]1([NH:9][C:8](=[O:25])[NH:7][CH:4]2[CH2:3][CH2:2][CH2:1][CH2:6][CH2:5]2)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Reactant: On1nnc2ccccc21
Solvent: CN1CCOCC1
Solvent: CN(C)C=O
Solvent: O
Product: O=C(NC1CCCCC1)NC1CCCCC1
Temperature: 25 °C
Reaction time: 17 h

Procedure:
DCys(O3Bu4N)-Pro-DThg-Leu-resin prepared in the same manner described in Example 5, was acylated with Boc-DTrp(CHO) by the standard protocol described in Example 5. The resulting resin was washed successively with DMF, methanol, and dichloromethane and dried in vacuo to give Boc-DTrp(CHO)-DCys(O3Bu4N)-Pro-nThg-Leu-resin. The resin was added to TFA/water(95/5, 20 ml) and the mixture was stirred at room temperature for 1.5 h and filtered. The collected resin was washed with TFA and the combined filtrate and washings were concentrated under reduced pressure. The residue was precipitated with ether to give DTrp(CHO)-DCys(O3Bu4N)-Pro-DThg-Leu. A solution of the pentapeptide(28 mg) in DMF(1.4 ml) was added dropwise to a solution of DCC(9 mg), HOBT H2O(7 mg) and N-methylmorpholine(1.6 μl) in DMF(1.4 ml) under ice cooling over a period of 1 h. The reaction mixture was stirred under ice cooling for 1 h and at room temperature for 17 h. Acetic acid(10 μl) was added to the reaction mixture. The resulting mixture was stirred and concentrated under reduced pressure. The residue was triturated with water to give colorless dicyclohexyl urea which was collected by filtration and thoroughly washed with water. The combined filtrate and washings were lyophilized to give a colorless solid which was purified by thin layer chromatography on silica gel (Analtichem International, Empore sheet) with butanol/acetic acid/water(8/1/1) for development to give an ammonium salt of the title compound. A water solution of the ammonium salt was passed through a column of ion exchange resin(AMBERLITE IR-120B, H+ -form) and lyophilized. The resulting solid(12.93 mg) was dissolved in water(0.6 ml) and the equimolar amount of NaHCO3 was added. The solution was directly purified by reverse-phase short column chromatography(Waters, SEP-PAK C18 cartridge) with water and methanol for elution. The combined methanolic layers were concentrated under reduced pressure to give the title compound(10.74 mg) as a colorless powder.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[O:15][C:16]1[CH:26]=[CH:25][C:19]([O:20][CH2:21][C:22]([OH:24])=O)=[CH:18][CH:17]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[CH3:49][O:50][C:51]1[CH:52]=[C:53]([CH:56]=[CH:57][CH:58]=1)[CH2:54][NH2:55].C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.O>[CH3:49][O:50][C:51]1[CH:52]=[C:53]([CH:56]=[CH:57][CH:58]=1)[CH2:54][NH:55][C:22](=[O:24])[CH2:21][O:20][C:19]1[CH:18]=[CH:17][C:16]([O:15][C:6]2[C:5]3[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=3)[N:9]=[CH:8][N:7]=2)=[CH:26][CH:25]=1
Reactant: COc1cc2ncnc(Oc3ccc(OCC(=O)O)cc3)c2cc1OC
Reactant: COc1cccc(CN)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=C([O-])O
Solvent: O
Solvent: ClC(Cl)Cl
Product: COc1cccc(CNC(=O)COc2ccc(Oc3ncnc4cc(OC)c(OC)cc34)cc2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 15.5 %

Procedure:
2-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]phenoxy}-acetic acid (150 mg), WSC.HCl (122 mg), and HOBT.H2O (86 mg) were dissolved in chloroform (5 ml) to prepare a solution. 3-Methoxybenzylamine (70 mg) was then added to the solution, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was washed with 1 N hydrochloric acid, water, and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (31 mg, yield 16%).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[N:3][C:2]=1[S:7][CH2:8][CH:9]1[CH:13]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:24][C@H:23]([CH2:25][NH:26][C:27](=[O:29])[CH3:28])[O:22][C:21]3=[O:30])=[CH:16][CH:15]=2)[CH2:11][NH:10]1.C(Cl)(Cl)Cl.ClCCl.[CH:38](OCC)=[O:39]>>[CH:38]([N:10]1[CH2:11][C:12]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:24][C@H:23]([CH2:25][NH:26][C:27](=[O:29])[CH3:28])[O:22][C:21]3=[O:30])=[CH:16][CH:15]=2)=[CH:13][CH:9]1[CH2:8][S:7][C:2]1[N:3]=[CH:4][CH:5]=[CH:6][N:1]=1)=[O:39]
Reactant: CC(=O)NC[C@H]1CN(c2ccc(C3=CC(CSc4ncccn4)NC3)cc2)C(=O)O1
Reactant: CCOC=O
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Product: CC(=O)NC[C@H]1CN(c2ccc(C3=CC(CSc4ncccn4)N(C=O)C3)cc2)C(=O)O1
Reaction time: 2 h
Yield: 20 %

Procedure:
The amine (Reference Example 7, 0.048 g, 0.11 mM) was refluxed in ethyl formate (3 ml). After 2 hours, chloroform (1 ml) and dichloromethane (1 ml) was added to solublise the precipitate. After 70 hours the solution was evaporated and the residue dissolved in acetonitrile/EtOAc (1:1) and the precipitate removed by filtration. The mother liquor was purified by Isolute chromatography (using as eluant a mixture increasing in polarity from 50% to 70% MeCN in EtOAc) to give after trituration with diethyl ether the title product (0.010 g, 20%).
Reaction SMILES: [OH-].[K+].[C:3]([O:7][OH:8])([CH3:6])([CH3:5])[CH3:4].[C:9]([N:14]=[N:15][C:16](Cl)([CH2:18][CH:19]([CH3:21])[CH3:20])[CH3:17])([CH2:12][CH3:13])([CH3:11])[CH3:10].[OH-].[Na+]>>[C:9]([N:14]=[N:15][C:16]([O:8][O:7][C:3]([CH3:6])([CH3:5])[CH3:4])([CH2:18][CH:19]([CH3:20])[CH3:21])[CH3:17])([CH2:12][CH3:13])([CH3:11])[CH3:10]
Reactant: CC(C)(C)OO
Reactant: CCC(C)(C)N=NC(C)(Cl)CC(C)C
Agent: [K+]
Agent: [Na+]
Agent: [OH-]
Product: CCC(C)(C)N=NC(C)(CC(C)C)OOC(C)(C)C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 82.3 %

Procedure:
To a cooled solution of 9.1 grams (.0407 moles) of 25% potassium hydroxide solution in a 100 ml. reaction flask equipped with a magnetic stirrer, thermometer and addition funnel was added 5.2 grams (.052 moles) of 90% t-butyl hydroperoxide. The reaction mixture was stirred for 30 minutes at 25° C and then cooled to 18° C. To the above solution was added 8.06 grams (0.037 moles) of 2-t-amylazo-2-chloro-4-methylpentane dropwise over 15 minutes holding the temperature at 18°-22° C with a cold water bath. After the addition was complete, the reaction was stirred for 10 minutes at 20° C, cooled to 5° C and stirred an additional 40 minutes. A small portion of 50% sodium hydroxide was then added to react with the excess t-butyl hydroperoxide and the reaction stirred for an additional 15 minutes, poured into 150 ml. of ice cold water and the product extracted with pentane. The pentane solution was washed with ice cold water, saturated NaHCO3 solution and water. The pentane solution was dried over anhydrous sodium sulfate, filtered and the pentane evaporated under reduced pressure to leave 8.3 grams (83% yield) of crude 2-t-amylazo-2-(t-butylperoxy)-4-methylpentane.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)/[C:7](=[CH:11]\[C:12]1[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=1)/[C:6]([CH3:20])=[C:5]2[CH2:21][CH2:22][O:23][NH2:24].[O:25]=[CH:26][CH2:27][C:28](O)=[O:29]>>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)/[C:7](=[CH:11]\[C:12]1[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=1)/[C:6]([CH3:20])=[C:5]2[CH2:21][CH2:22][O:23][N:24]=[C:28]([OH:29])[CH2:27][CH:26]=[O:25]
Reactant: O=CCC(=O)O
Reactant: CSc1ccc(/C=C2/C(C)=C(CCON)c3cc(F)ccc32)cc1
Product: CSc1ccc(/C=C2/C(C)=C(CCON=C(O)CC=O)c3cc(F)ccc32)cc1

Procedure:
The title compound is prepared by reaction of O-2-[Z-5-fluoro-2-methyl-1-(4-methylthiophenyl)methylene-1H-inden-3-yl]ethyl hydroxylamine with 3-oxopropionic acid by the method of Example 1.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:25]([F:28])([F:27])[F:26])[O:13][N:12]=[C:11]([C:14]3[CH:23]=[CH:22][C:17]([C:18]([NH:20][CH3:21])=[O:19])=[C:16]([CH3:24])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.C(N(CC)CC)C.[S:36]1(=O)[CH2:40][CH2:39][CH2:38][CH2:37]1>C1(C)C=CC=CC=1.[I-].[Zn+2].[I-]>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:25]([F:27])([F:26])[F:28])[O:13][N:12]=[C:11]([C:14]3[CH:23]=[CH:22][C:17]([C:18]([N:20]([CH3:21])[CH:37]4[CH2:38][CH2:39][CH2:40][S:36]4)=[O:19])=[C:16]([CH3:24])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: O=S1CCCC1
Reactant: CNC(=O)c1ccc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)cc1C
Agent: [I-]
Agent: [Zn+2]
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: Cc1cc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)ccc1C(=O)N(C)C1CCCS1
Temperature: 0 °C
Yield: 18.1 %

Procedure:
In a solution of 0.43 g of 4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazole-3-yl]-2-methyl-N-methyl benzoic acid amide synthesized similarly to Synthetic Example 29 and 0.20 g of triethylamine in 5 ml of toluene, 0.45 g of trimethyl silyl trifurate was added and stirred vigorously. 10 minutes after the stirring, the reaction mixture was cooled to 0° C., 0.10 g of tetrahydrothiophene-1-oxide and 0.06 g of zinc iodide were added with stirring, and continued to stir at room temperature further for 4 days. After the completion of the reaction, 10 ml of ice water was added in the reaction mixture, and extracted with ethyl acetate (20 ml×2), the organic phase was dehydrated and dried with saturated sodium chloride aqueous solution and anhydrous sodium sulfate in that order, and the solvent was distilled under reduced pressure. The residue was purified with silica gel column chromatography that was eluated with ethyl acetate-hexane (1:2) to obtain 0.09 g of the aimed product as white crystal.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:12]([O:13][CH3:14])=[C:11]([OH:15])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]=1[OH:16].Cl[C:18]([O:20][CH3:21])=[O:19].C(N(CC)CC)C>O1CCCC1>[CH3:14][O:13][C:12]1[C:3]([O:2][CH3:1])=[C:4]([O:16][C:18]([O:20][CH3:21])=[O:19])[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:11]=1[O:15][C:18]([O:20][CH3:21])=[O:19]
Reactant: COc1c(OC)c(O)c2ccccc2c1O
Reactant: COC(=O)Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COC(=O)Oc1c(OC)c(OC)c(OC(=O)OC)c2ccccc12
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of 1.0 g of 2,3-dimethoxy-1,4-dihydroxynaphthalene, prepared as shown in Preparation 5, in 50 ml of tetrahydrofuran was added 1.40 g of methyl chloroformate followed by 1.50 g of triethylamine. The mixture was stirred at room temperature for 16 hours, filtered, then the solvent removed under reduced pressure. The residue was dissolved in diethyl ether, washed with dilute hydrochloric acid and dried over anhydrous sodium sulfate. The ether was removed under reduced pressure and the residue chromatographed on silica gel, eluting with a 1:1 mixture of methylene chloride and hexane, to give 2,3-dimethoxy-1,4-di(methoxycarbonyloxy)naphthalene, m.p. 53°-54° C.
Reaction SMILES: O([C@H]1[C@H](O)[C@@H](CO)OC(O)[C@@H]1NC(C)=O)[C@@H]1O[C@@H](C)[C@@H](O)[C@@H](O)[C@@H]1O.[CH3:26][C@@H:27]1[O:32][C@@H:31]([O:33][C@@H:34]([C@H:42]([O:47][C@@H:48]2[O:53][C@H:52]([CH2:54][OH:55])[C@H:51]([OH:56])[C@H:50]([O:57][C@@:58]3([C:75]([OH:77])=[O:76])[O:63][C@@H:62]([C@H:64]([OH:69])[C@H:65]([OH:68])[CH2:66][OH:67])[C@H:61]([NH:70][C:71]([CH3:73])=[O:72])[C@@H:60]([OH:74])[CH2:59]3)[C@H:49]2[OH:78])[C@H:43]([OH:46])[CH2:44][OH:45])[C@@H:35]([NH:38][C:39]([CH3:41])=[O:40])[CH:36]=[O:37])[C@@H:30]([OH:79])[C@H:29]([OH:80])[C@@H:28]1[OH:81]>>[OH:76][C:75]([C@@:58]1([O:63][C@@H:62]([C@@H:64]([C@@H:65]([CH2:66][OH:67])[OH:68])[OH:69])[C@H:61]([NH:70][C:71]([CH3:73])=[O:72])[C@@H:60]([OH:74])[CH2:59]1)[O:57][C@H:50]1[C@@H:51]([OH:56])[C@@H:52]([CH2:54][OH:55])[O:53][C@@H:48]([O:47][C@@H:42]2[C@@H:43]([CH2:44][OH:45])[O:46][C@@H:36]([OH:37])[C@H:35]([NH:38][C:39]([CH3:41])=[O:40])[C@H:34]2[O:33][C@@H:31]2[O:32][C@@H:27]([CH3:26])[C@@H:28]([OH:81])[C@@H:29]([OH:80])[C@@H:30]2[OH:79])[C@@H:49]1[OH:78])=[O:77]
Reactant: CC(=O)N[C@H]1[C@H]([C@H](O)[C@H](O)CO)O[C@@](O[C@H]2[C@@H](O)[C@@H](CO)O[C@@H](O[C@@H]([C@H](O[C@@H]3O[C@@H](C)[C@@H](O)[C@@H](O)[C@@H]3O)[C@H](C=O)NC(C)=O)[C@H](O)CO)[C@@H]2O)(C(=O)O)C[C@@H]1O
Agent: CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@@H]1O[C@@H](C)[C@@H](O)[C@@H](O)[C@@H]1O
Product: CC(=O)N[C@@H]1[C@@H](O[C@@H]2O[C@@H](C)[C@@H](O)[C@@H](O)[C@@H]2O)[C@H](O[C@@H]2O[C@H](CO)[C@H](O)[C@H](O[C@]3(C(=O)O)C[C@H](O)[C@@H](NC(C)=O)[C@H]([C@H](O)[C@H](O)CO)O3)[C@H]2O)[C@@H](CO)O[C@H]1O

Procedure:
NeuAcα2→3Galβ1→4(Fucα1→3GlcNAc=Slex.
Reaction SMILES: BrCCOC1C=CC(CO)=CC=1.[Cl:13][CH2:14][CH2:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][OH:24])=[CH:19][CH:18]=1.[Cl:25][C:26]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29](O)=[CH:28][CH:27]=1.C(P(CCCC)CCCC)CCC>C1COCC1>[Cl:13][CH2:14][CH2:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][O:24][C:29]2[C:30]3[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:26]([Cl:25])=[CH:27][CH:28]=2)=[CH:19][CH:18]=1
Reactant: OCc1ccc(OCCCl)cc1
Reactant: Oc1ccc(Cl)c2ccccc12
Agent: CCCCP(CCCC)CCCC
Agent: OCc1ccc(OCCBr)cc1
Solvent: C1CCOC1
Product: ClCCOc1ccc(COc2ccc(Cl)c3ccccc23)cc1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
A stirred solution of 8.4 grams (0.045 mole) of the mixture of (4-(2-bromoethoxy)phenyl)methan-1-ol and (4-(2-chloroethoxy)phenyl)methan-1-ol, 8.1 grams (0.045 mole) of 4-chloronaphthol, and 13.7 mL (0.054 mole) of tributylphosphine in 500 mL of THF was cooled in an ice bath and 12.6 grams (0.049 mole) of 1-1′-(azodicarbomyl)dipiperidine was added. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature where it stirred for 24 hours. After this time, the solvent was reduced under reduce pressure, yielding a solid. The solid was purified by column chromatography on silica gel, yielding 15 grams of crude product. The crude product was further purified by column chromatography on silca gel, yielding 6.7 grams of title compound.