Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:3][C:4](=O)[CH2:5][C:6]([C@H:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][CH3:17])=[O:15])[C@@H:10]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=2)[CH2:9]1)=[O:7])C.[OH-].[Na+].Cl.[NH2:33]O.Cl>CO.CO.O.O.C(OCC)(=O)C>[O:3]=[C:4]1[CH:5]=[C:6]([C@H:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][CH3:17])=[O:15])[C@@H:10]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=3)[CH2:9]2)[O:7][NH:33]1
Reactant: NO
Reactant: CCOC(=O)CC(=O)[C@H]1CCN(C(=O)OC)[C@@H](Cc2cccc(C(F)(F)F)c2)C1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: CCOC(C)=O
Solvent: O
Product: COC(=O)N1CC[C@H](c2cc(=O)[nH]o2)C[C@@H]1Cc1cccc(C(F)(F)F)c1
Reaction time: 0.5 h

Procedure:
A solution of Cis-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(3-(trifluoromethyl)benzyl)-piperidine-1-carboxylate (2.45 g, 5.90 mmol) in MeOH (7 mL) was added to a solution of NaOH (307 mg, 7.67 mmol) in MeOH/H2O (8 ml/0.5 mL) at −30° C. After 10 min hydroxylamine hydrochloride (0.82 g, 11.80 mmol) and NaOH (472 mg, 11.80 mmol) were added in MeOH (8 mL) and H2O (8 mL). Stirring was continued at −30° C. for 30 min. The reaction solution was poured into 6 M HCl 60 mL) at 80° C. and heated for 30 min. The reaction mixture was dissolved between water and ethyl acetate. The organic phase was isolated, dried with Na2SO4, filtered through celite and the solvent was evaporated. Purification using prepLC (pH=3, large column 40-55% MeCN over 20 min) Cis-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(3-(trifluoromethyl)benzyl)piperidine-1-carboxylate (1.27 g, 56%) was isolated. 1H NMR (400 MHz, cdcl3) δ 1.86-2.15 (m, 4H), 2.68 (dd, 1H), 2.86 (dd, 1H), 2.96-3.06 (m, 1H), 3.12-3.25 (m, 1H), 3.58 (s, 3H), 3.95-4.08 (m, 1H), 4.25-4.37 (m, 1H), 5.75 (s, 1H), 7.23-7.32 (m, 1H), 7.35-7.41 (m, 2H), 7.43-4.49 (m, 1H). MS m/z 385 (M+H)+
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH2:7][C:6]([CH:12]=[O:13])=[CH:5]2.I[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:15]([O:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH2:7][C:6]([CH:12]=[O:13])=[CH:5]2)[CH2:16][CH2:17][CH2:18][CH3:19]
Reactant: O=CC1=Cc2cc(O)ccc2OC1
Reactant: CCCCCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCCCCOc1ccc2c(c1)C=C(C=O)CO2
Reaction time: 1 h

Procedure:
2 g (11.4 mmol) of the hydroxyaldehyde obtained in Step A and also 2.7 g (13.6 mmol) of iodopentane are added to a suspension of 1.9 g (13.6 mmol) of potassium carbonate in 50 ml of anhydrous acetone; the medium is then heated at reflux. After one hour, 1.2 g of potassium carbonate are added to the solution, and that operation is then re-started after one hour. At the end of 12 hours of heating at reflux, the solution is allowed to cool, the salts are filtered off over Celite and the solvent is then evaporated in vacuo. Chromatography on a silica column (eluant: petroleum ether/ethyl acetate 90/10) yields the title aldehyde in the form of a yellow syrup.
Reaction SMILES: [C:1]([O:4][C:5](=[O:7])[CH3:6])(=O)[CH3:2].N1C=CC=CC=1.[CH2:14](O)[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]/[CH:22]=[CH:23]\CC>C(Cl)Cl.C(OCC)C>[C:5]([O:4][CH2:1][CH2:2][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]/[CH:17]=[CH:16]\[CH2:15][CH3:14])(=[O:7])[CH3:6]
Reactant: CC/C=C\CCCCCCCCO
Reactant: CC(=O)OC(C)=O
Solvent: ClCCl
Solvent: c1ccncc1
Solvent: CCOCC
Product: CC/C=C\CCCCCCCCOC(C)=O
Temperature: 25 °C
Reaction time: 17 h
Yield: 87 %

Procedure:
Acetic anhydride (0.17 mL, 1.8 mmol), then pyridine (90 μL, 1.1 mmol), were added sequentially to alcohol 7 (0.17 g, 0.93 mmol) in CH2Cl2 (1.8 mL), and stirred at room temperature for 17 hours. The mixture was diluted with diethyl ether, washed with saturated aqueous NaHCO3, then brine, dried with Na2SO4, and concentrated. Flash chromatography of the residue (SiO2, 5% EtOAc in hexanes) provided 8 (0.18 g, 87% yield, 74% Z as determined by 13C-NMR) as a colorless oil; 1H NMR (CDCl3): δ 5.28-5.43 (2H, m), 4.05 (2H, t, J=6.8 Hz), 2.04 (7H, m), 1.61 (2H, td, J=9.8, 8.7, 4.6 Hz), 1.29 (10H, m), 0.95 (3H, m); 13C NMR (CDCl3): δ 171.3, 131.6, 129.3, 64.7, 32.6, 29.8, 29.5, 29.3, 29.2, 28.7, 26.0, 21.1, 20.6, 14.5; HRMS (FAB): 227.2045, [C14H26O2+H]+ requires 227.2006.
Reaction SMILES: [Cl:1][C:2]1[S:3][C:4]([CH:7]=[O:8])=[CH:5][N:6]=1.[CH3:9][Mg+].[Br-]>C1COCC1.CCOCC>[Cl:1][C:2]1[S:3][C:4]([C:7](=[O:8])[CH3:9])=[CH:5][N:6]=1
Reactant: C[Mg+]
Reactant: O=Cc1cnc(Cl)s1
Agent: [Br-]
Solvent: CCOCC
Solvent: C1CCOC1
Product: CC(=O)c1cnc(Cl)s1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 73 %

Procedure:
2-Chloro-thiazole-5-carbaldehyde (1.00 g., 6.77 mmol) was dissolved in THF (10 mL) and cooled to −78° C. MeMgBr (2.26 mL of a 3.0 M solution in Et2O, 6.78 mmol) was added dropwise. The mixture was stirred at −78° C. for 30 min and then allowed to slowly warm to −20° C. over a further 30 min. The reaction was quenched by the addition of EtOAc (2 mL), allowed to warm to 20° C., and 2 M hydrochloric acid (20 mL) was added. The mixture was poured into water (200 mL) and extracted into DCM (200 mL), dried (Na2SO4) and concentrated. The residue was dissolved in reagent grade acetone (20 mL), cooled in an ice bath, and Jones' reagent (3.0 mL of a 2.67 M solution) was added dropwise. The mixture was stirred for 16 h, allowing to warm to 20° C., and then quenched with IPA (5 mL), poured into saturated aqueous NaHCO3 (200 mL) and extracted with EtOAc (2×100 mL). The EtOAc extracts were dried (Na2SO4) and concentrated to give pure product (800 mg, 73%) as a somewhat volatile white solid.
Reaction SMILES: [CH:1]1[CH:6]=[C:5](Cl)[CH:4]=[C:3]([C:8](OO)=O)[CH:2]=1.[CH2:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1>>[CH2:12]=[CH:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:1][CH:2]=1.[CH2:17]=[CH:12][CH:13]=[CH2:14].[CH2:1]=[CH:2][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: C1CCCCC1
Reactant: O=C(OO)c1cccc(Cl)c1
Product: C=CC=C
Product: C=Cc1ccccc1
Reaction time: 24 h

Procedure:
3 g SBS (the molecular weight is about 100,000; trade name is Taipol SBS-4202; manufactured by TSRC corp.) was fully dissolved in 60 ml cyclohexane. Adding a certain amount (0.7512 g) of mCPBA into the SBS solution and reacting at room temperature for 24 hrs. After reaction, the product was precipitated by 100 ml methanol for several times to be purified and isolated. According to H1-NMR determination, the transformation rate of double bond-epoxy group was about 2.1%, as shown in FIG. 1.
Reaction SMILES: [C:1]([O:20][CH3:21])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\CCCCCCCC.CCCCCCCCCCCCCC.C=C>ClCCl.C(OCC)=C>[CH2:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[CH3:21][O:20][C:1](=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH:9]=[CH2:10]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)OC
Agent: C=C
Agent: C=COCC
Agent: CCCCCCCCCCCCCC
Solvent: ClCCl
Product: C=CCCCCCCCC
Product: C=CCCCCCCCC(=O)OC
Temperature: 40 °C
Yield: 99 %

Procedure:
The ethylenolysis of methyl oleate was used as a test to determine the activity of (PCy3)Cl2Ru(3-pentafluorophenyl-6,8-diisopropoxyinden-1-ylidene). A catalyst compound stock solution (0.1379 mM) was made by dissolving the catalyst compound in anhydrous dichloromethane. Methyl oleate (0.87 g, 1.0 mL), catalyst compound stock solution (0.906 g), dichloromethane (4.12 g), and tetradecane (0.152 g) as an internal standard were placed in a Fisher-Porter bottle equipped with a stir bar. The vessel was then filled with ethylene to 150 psig and placed in an oil bath heated to 40° C. for 3 hours. The vessel was then depressurized and 5 drops ethyl vinyl ether added to stop the reaction. A sample was analyzed by gas chromatography. The cross-metathesis reaction yielded 18.5% 1-decene and methyl-9-decenoate with 99% selectivity 1-decene and methyl-9-decenoate yields corresponded to 4300 turnovers of decene per equivalent of ruthenium.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][C:10]=1[C:18]([CH3:21])([CH3:20])[CH3:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:22]([O:26][C:27](=[O:30])[CH2:28][NH2:29])([CH3:25])([CH3:24])[CH3:23].CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>CCOC(C)=O.CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([NH:29][CH2:28][C:27]([O:26][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:30])=[O:15])=[CH:11][C:10]=1[C:18]([CH3:21])([CH3:20])[CH3:19])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)CN
Reactant: CC(C)(C)c1cc(C(=O)O)ccc1OCc1ccccc1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Product: CC(C)(C)OC(=O)CNC(=O)c1ccc(OCc2ccccc2)c(C(C)(C)C)c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 102 %

Procedure:
To a solution of 4-(benzyloxy)-3-tert-butylbenzoic acid (2.36 g, 8.31 mmol) in anhyd DMF (56 mL) was added glycine t-butyl ester (1.63 g, 12.5 mmol), BOP reagent (5.51 g, 12.5 mmol), and N-methylmorpholine (2.74 mL, 24.9 mmol). The mixture was stirred at room temperature for 12 h under nitrogen atmosphere and then diluted with EtOAc (200 mL). The organic layer was washed consecutively with 1 N HCl (250 mL), satd NaHCO3 (100 mL), 5% LiCl (2×100 mL), and brine (50 mL), dried (Na2SO4), and concentrated in vacuo. tert-butyl 2-(4-(benzyloxy)-3-tert-butylbenzamido)acetate (3.37 g, quant.) was isolated as a white solid: 1H NMR (300 MHz, CDCl3) δ 7.81 (s, 1H), 7.63-7.60 (m, 1H), 7.46-7.34 (m, 5H), 6.95-6.93 (m, 1H), 6.52 (s, 1H), 5.16 (s, 2H), 4.14-4.11 (m, 2H), 1.51 (s, 9H), 1.41 (s, 9H); MS found: (M+H)+=398.
Reaction SMILES: C(O)(C(F)(F)F)=O.C(OC(C(F)(F)F)=O)(C(F)(F)F)=O.[C:21]([CH2:24][CH2:25][CH2:26][CH2:27][N:28]1[C:36]2[C:31](=[CH:32][CH:33]=[C:34]([C:37]([OH:39])=[O:38])[CH:35]=2)[C:30]([CH:40]2[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]2)=[CH:29]1)(O)=[O:22]>O>[CH:40]1([C:30]2[C:31]3[C:36](=[CH:35][C:34]([C:37]([OH:39])=[O:38])=[CH:33][CH:32]=3)[N:28]3[CH2:27][CH2:26][CH2:25][CH2:24][C:21](=[O:22])[C:29]=23)[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1
Reactant: O=C(O)CCCCn1cc(C2CCCCC2)c2ccc(C(=O)O)cc21
Solvent: O
Solvent: O=C(O)C(F)(F)F
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Product: O=C(O)c1ccc2c(C3CCCCC3)c3n(c2c1)CCCCC3=O
Temperature: 25 °C
Reaction time: 4 h
Yield: 118.5 %

Procedure:
A mixture of TFA (1.0 mL) and TFAA (469 mg, 2.232 mmol) was added dropwise to 1-(4-carboxybutyl)-3-cyclohexyl-1H-indole-6-carboxylic acid (365 mg, 1.063 mmol) at 0° C. The reaction mixture was then warmed to rt. and stirred for 4 hr. Water was then added slowly to quench the reaction and a precipitate formed. This was collected by filtration to provide the product as a yellow-greenish solid, (410 mg, >100% yield). MS m/z 326(MH+); 1H NMR (500 MHz, CD3OD) δ ppm 1.39-1.50 (m, 3 H) 1.73-2.14 (m, 11 H) 2.88 (m, 2 H) 3.45 (m, 1 H) 4.46 (m, 2 H) 7.73 (dd, J=8.54, 1.22 Hz, 1 H) 7.98 (d, J=8.55 Hz, 1 H) 8.21 (s, 1 H).
Reaction SMILES: [CH:1]([Br:4])(Br)[Br:2].[N:5]1([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[CH2:9][CH:8]=[CH:7][CH2:6]1>ClCCl.[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.O>[CH2:13]([O:12][C:10]([N:5]1[CH2:9][CH:8]2[CH:7]([C:1]2([Br:4])[Br:2])[CH2:6]1)=[O:11])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: O=C(OCc1ccccc1)N1CC=CC1
Reactant: BrC(Br)Br
Agent: CC[N+](CC)(CC)Cc1ccccc1
Agent: [Cl-]
Solvent: ClCCl
Solvent: O
Product: O=C(OCc1ccccc1)N1CC2C(C1)C2(Br)Br
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A solution of bromoform (0.94 mL, 10.8 mmol) in 5 mL of dichloromethane was added over 1.5 hours to a stirred solution of benzyl 3-pyrroline-1-carboxylate (1.77 mL, 9.8 mmol) and benzyltriethylammonium chloride (0.055 g, 0.025 mmol) in 1:1 dichloromethane-50% aqueous NaOH (60 mL). The black solution was stirred for 18 hours at room temperature and then diluted with dichloromethane and H2O. The layers were separated and the organic phase washed with satd NH4Cl, brine, and dried (MgSO4), filtered and concentrated. The crude product was purified by column chromatography (0-20% ethyl acetate-hexane) to afford 6,6-dibromo-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid benzyl ester.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][C:20]([F:23])([F:22])[F:21])[CH:14]=1)[C:7]([C:24]([OH:26])=O)=[CH:6]2)#[N:2].Cl.[NH2:28][CH2:29][C:30]1([OH:36])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1>>[OH:36][C:30]1([CH2:29][NH:28][C:24]([C:7]2[N:8]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][C:20]([F:21])([F:23])[F:22])[CH:14]=3)[C:9]3[C:5]([CH:6]=2)=[CH:4][C:3]([C:1]#[N:2])=[CH:11][CH:10]=3)=[O:26])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1
Reactant: N#Cc1ccc2c(c1)cc(C(=O)O)n2Cc1cccc(OC(F)(F)F)c1
Reactant: NCC1(O)CCCCC1
Agent: Cl
Product: N#Cc1ccc2c(c1)cc(C(=O)NCC1(O)CCCCC1)n2Cc1cccc(OC(F)(F)F)c1

Procedure:
The title compound was prepared using 5-cyano-1-(3-trifluoromethoxybenzyl)-1H-indole-2-carboxylic acid [prepared from 3-(trifluoromethoxy)benzyl bromide and ethyl 5-cyanoindole-2-carboxylate] and 1-aminomethyl-1-cyclohexanol hydrochloride in a manner similar to that described in Example 11.
Reaction SMILES: Cl.[NH2:2][OH:3].[Cl:4][C:5]1[CH:12]=[CH:11][C:8]([CH:9]=O)=[CH:7][CH:6]=1.C(O)C>O.[OH-].[Na+]>[Cl:4][C:5]1[CH:12]=[CH:11][C:8]([CH:9]=[N:2][OH:3])=[CH:7][CH:6]=1
Reactant: NO
Reactant: O=Cc1ccc(Cl)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: ON=Cc1ccc(Cl)cc1
Yield: 75.7 %

Procedure:
To a solution of 50 g of hydroxylamine hydrochloride in 300 ml of water was added a suspension of 20 g of 4-chlorobenzaldehyde in 200 ml of 10% aqueous sodium hydroxide solution. Ethanol was then added until the mixture was clear. The solution was heated on a steam bath for 25 minutes, then cooled in an ice bath. The solid which separated was collected by filtration and dried in a vacuum desiccator. A second fraction was obtained by adding water just to the cloud point. This solid was collected and dried and the two products combined to give 16.75 g of 4-chlorobenzaldoxime, m.p. 108°-109°.
Reaction SMILES: [NH2:1]/[C:2](/[N:5]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[N:31]=[C:32]([CH:35]3[CH2:37][CH2:36]3)[O:33][CH:34]=2)=[CH:26][CH:25]=1)[CH2:6][CH2:7][C:8]1[CH:22]=[CH:21][C:11]([O:12][C:13]([CH3:20])([CH3:19])[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:10][CH:9]=1)=[N:3]\[OH:4].C(N(CC)CC)C.[F:45][C:46]([F:57])([F:56])[C:47]1[CH:48]=[C:49]([CH:53]=[CH:54][CH:55]=1)[C:50](Cl)=O>C1(C)C=CC=CC=1>[CH:35]1([C:32]2[O:33][CH:34]=[C:30]([C:27]3[CH:26]=[CH:25][C:24]([CH2:23][N:5]([C:2]4[N:1]=[C:50]([C:49]5[CH:53]=[CH:54][CH:55]=[C:47]([C:46]([F:45])([F:56])[F:57])[CH:48]=5)[O:4][N:3]=4)[CH2:6][CH2:7][C:8]4[CH:22]=[CH:21][C:11]([O:12][C:13]([CH3:20])([CH3:19])[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:10][CH:9]=4)=[CH:29][CH:28]=3)[N:31]=2)[CH2:36][CH2:37]1
Reactant: CCOC(=O)C(C)(C)Oc1ccc(CCN(Cc2ccc(-c3coc(C4CC4)n3)cc2)/C(N)=N/O)cc1
Reactant: O=C(Cl)c1cccc(C(F)(F)F)c1
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: CCOC(=O)C(C)(C)Oc1ccc(CCN(Cc2ccc(-c3coc(C4CC4)n3)cc2)c2noc(-c3cccc(C(F)(F)F)c3)n2)cc1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 57.5 %

Procedure:
To a cooled solution of ethyl 2-[4-(2-{[(E)-amino(hydroxyimino)methyl][4-(2-cyclopropyl-1,3-oxazol-4-yl)benzyl]amino}ethyl)phenoxy]-2-methylpropanoate (0.108 g, 0.21 mmol) in toluene (2 ml) was added triethylamine (0.028 mL, 0.20 mmol) dropwise. After 5 min, 3-(trifluoromethyl)benzoyl chloride (0.031 ml, 0.20 mmol) in toluene (0.1 ml) was added dropwise. The mixture was allowed to warm to rt over 2 h and then heated to 110C for 2 hr. Upon cooling, the mixture was filtered, and the solid was washed with EtOAc. The filtrate was concentrated in vacuo, and the resulting residue was partitioned between EtOAc and a solution of 0.5N aqueous HCl. The organic phase was washed with 0.5N aqueous HCl (1×), 0.5N aqueous NaOH (2×), and brine (1×), dried with Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (EtOAc/hexanes, 10:90 to 20:80) to yield ethyl 2-{4-[2-([4-(2-cyclopropyl-1,3-oxazol-4-yl)benzyl]{5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}amino)ethyl]phenoxy}-2-methylpropanoate (76 mg, 58%).
Reaction SMILES: [C:1]([CH:4]([CH3:26])[CH2:5][CH2:6][N:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[C:15]([CH3:16])[C:10]=2[N:9]=[C:8]1[CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=1)(O)=[O:2].[NH2:27][CH2:28][CH2:29][CH2:30][N:31]1[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O>[N:31]1([CH2:30][CH2:29][CH2:28][NH:27][C:1]([CH:4]([CH3:26])[CH2:5][CH2:6][N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[C:15]([CH3:16])[C:10]=3[N:9]=[C:8]2[CH2:17][O:18][C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)=[O:2])[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1
Reactant: Cc1cccc2c1nc(COc1ccc(Cl)cc1)n2CCC(C)C(=O)O
Reactant: NCCCN1CCCCC1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: Cc1cccc2c1nc(COc1ccc(Cl)cc1)n2CCC(C)C(=O)NCCCN1CCCCC1
Temperature: 25 °C
Reaction time: 64 h
Yield: 125.7 %

Procedure:
To a stirring solution of 1-[3-carboxybutyl]-2-[(4-chlorophenoxy)methyl]-4-methylbenzimidazole (1.2 g, 3.2 mmol) in N,N-dimethylformamide (75 ml) were added sequentially 1-amino-3-(piperidin-1-yl)propane (500 mg, 1.1 eq), 1-hydroxybenzotriazole (475 mg, 1.1 eq), and dicyclohexylcarbodiimide (726 mg, 1.1 eq). The resulting mixture was then stirred under a nitrogen atmosphere at room temperature for 64 hours. The reaction mixture was then filtered and the resulting filtrate was concntrated under reduced pressure. This residue was taken into ethyl acetate (200 ml) and washed once with water (200 ml), dried over potassium carbonate. The solvents were removed in vacuo to yield 2.00 grams of a semi-solid material.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[CH:11]=[C:12]([C:28]#[N:29])[C:13]4[CH:14]=[N:15][N:16]([S:19]([C:22]5[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=5)(=[O:21])=[O:20])[C:17]=4[CH:18]=3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[NH:30]1[C:38]2[C:33](=[C:34]([C:39]3[CH:40]=[C:41]([C:58]#[N:59])[C:42]4[CH:43]=[N:44][N:45]([S:48]([C:51]5[CH:56]=[CH:55][C:54]([CH3:57])=[CH:53][CH:52]=5)(=[O:50])=[O:49])[C:46]=4[CH:47]=3)[CH:35]=[CH:36][CH:37]=2)[CH:32]=[CH:31]1.C[Si]([N:64]=[N+:65]=[N-:66])(C)C.C([Sn](CCCC)=O)CCC>C1(C)C=CC=CC=1>[NH:30]1[C:38]2[C:33](=[C:34]([C:39]3[CH:47]=[C:46]4[C:42]([CH:43]=[N:44][N:45]4[S:48]([C:51]4[CH:56]=[CH:55][C:54]([CH3:57])=[CH:53][CH:52]=4)(=[O:50])=[O:49])=[C:41]([C:58]4[NH:66][N:65]=[N:64][N:59]=4)[CH:40]=3)[CH:35]=[CH:36][CH:37]=2)[CH:32]=[CH:31]1.[NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[CH:18]=[C:17]4[C:13]([CH:14]=[N:15][N:16]4[S:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)(=[O:21])=[O:20])=[C:12]([C:28]4[NH:66][N:65]=[N:64][N:29]=4)[CH:11]=3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1
Reactant: C[Si](C)(C)N=[N+]=[N-]
Reactant: Cc1ccc(S(=O)(=O)n2ncc3c(C#N)cc(-c4cccc5[nH]ccc45)cc32)cc1
Reactant: N#Cc1cc(-c2cccc3[nH]ccc23)cc2c1cnn2S(=O)(=O)c1ccccc1
Agent: CCCC[Sn](=O)CCCC
Solvent: Cc1ccccc1
Product: Cc1ccc(S(=O)(=O)n2ncc3c(-c4nnn[nH]4)cc(-c4cccc5[nH]ccc45)cc32)cc1
Product: O=S(=O)(c1ccccc1)n1ncc2c(-c3nnn[nH]3)cc(-c3cccc4[nH]ccc34)cc21
Temperature: 120 °C
Yield: 141.3 %

Procedure:
6-(1H-Indol-4-yl)-1-(phenylsulfonyl)-1H-indazole-4-carbonitrile (0.669 g, 1.679 mmol) and 6-(1H-indol-4-yl)-1-[(4-methylphenyl)sulfonyl]-1H-indazole-4-carbonitrile (0.561 g, 1.360 mmol) were slurried in toluene (60 ml) and treated with trimethylsilyl azide (0.887 ml, 6.68 mmol) and dibutyl(oxo)stannane (0.151 g, 0.608 mmol). The reaction mixture was heated, under nitrogen at 120° C. for 16 h, then additional trimethylsilyl azide (0.221 ml, 1.67 mmol) was added. After heating for a further 2 h, the solution was evaporated to dryness, treated with methanol (30 ml) and absorbed onto Florisil. The Florisil was loaded onto a silica cartridge (100 g) which was eluted with 0-30% methanol+1% triethylamine/dichloromethane. The appropriate fractions were combined and concentrated to give the title compound as a brown solid (1.724 g).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH3:7].C([Li])CCC.[C:13]1(=[O:22])[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH2:14]1.Cl>O1CCCC1>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][C:13]1([OH:22])[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH2:14]1
Reactant: O=C1CCc2ccccc21
Reactant: Cc1ccccn1
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: OC1(Cc2ccccn2)CCc2ccccc21
Temperature: -20 °C

Procedure:
A mixture of 29.5 ml (0.3 mol) of alpha-picoline with 140 ml of tetrahydrofuran was cooled to −20° C. and 187.5 ml of n-butyllithium (1.6M in hexane, 0.3 mol) were subsequently added while stirring. The mixture was allowed to warm to room temperature while stirring and a solution of 39.6 g (0.3 mol) of 1-indanone in 35 ml of tetrahydrofuran was then added over a period of 25 minutes while stirring. The mixture was then stirred for a further 1.5 hours and hydrolyzed with 600 ml of dilute hydrochloric acid, the organic phase was separated off and the aqueous phase was extracted once with diethyl ether. The aqueous phase was then neutralized with aqueous ammonia solution and extracted 3 times with 150 ml each time of chloroform. The organic phases were combined and the solvent was distilled off. The 1-(2-pyridinylmethyl)-1-indanol obtained in this way was dissolved using 500 ml of 10% strength by weight hydrochloric acid and heated for 3 hours on a waterbath. The reaction mixture was cooled, washed with ether and the aqueous phase was neutralized with aqueous ammonia solution. The neutralized aqueous phase was extracted 3 times with 150 ml each time of chloroform and the combined organic phases were dried over magnesium sulfate. After the magnesium sulfate had been filtered off, the solvent was distilled off to leave 52.7 g of a mixture of 2-(1H-inden-3-ylmethyl)pyridine and 2-[(E)-2,3-dihydro-1H-inden-1-ylidenemethyl]pyridine in a ratio of 10:9 in a total yield of 95%. NMR 1H (CDCl3): 8.61 (d, 1H); 7.61 (td, 1H); 7.55 (d, 1H); 7.51 (d, 1H); 7.36 (d, 1H); 7.32-7.22 (m, 3H); 7.16 (dd, 1H); 6.31 (m, 1H); 4.17 (br s, 2H); 3.43 (br s, 2H).
Reaction SMILES: N1C=CN=C1.[C:6]([Si:10]([CH3:13])([CH3:12])Cl)([CH3:9])([CH3:8])[CH3:7].[CH2:14]([O:16][C:17]1[CH:18]=[C:19]([C:26]2[S:27][CH:28]=[C:29]([C:31]3[CH:36]=[CH:35][C:34]([OH:37])=[C:33]([C:38]([O:40][CH3:41])=[O:39])[CH:32]=3)[N:30]=2)[CH:20]=[CH:21][C:22]=1[O:23][CH2:24][CH3:25])[CH3:15].C(OCC)(=O)C>CN(C)C=O>[CH2:14]([O:16][C:17]1[CH:18]=[C:19]([C:26]2[S:27][CH:28]=[C:29]([C:31]3[CH:36]=[CH:35][C:34]([O:37][Si:10]([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:13])[CH3:12])=[C:33]([C:38]([O:40][CH3:41])=[O:39])[CH:32]=3)[N:30]=2)[CH:20]=[CH:21][C:22]=1[O:23][CH2:24][CH3:25])[CH3:15]
Reactant: CCOc1ccc(-c2nc(-c3ccc(O)c(C(=O)OC)c3)cs2)cc1OCC
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCOc1ccc(-c2nc(-c3ccc(O[Si](C)(C)C(C)(C)C)c(C(=O)OC)c3)cs2)cc1OCC
Temperature: 0 °C
Reaction time: 4 h
Yield: 99.4 %

Procedure:
5.23 g of imidazole and 4.85 g of tert-butyldimethylchlorosilane were added, in this order, to a suspension of 4.02 g of 2-(3,4-diethoxyphenyl)-4-(3-methoxycarbonyl-4-hydroxyphenyl)thiazole in 60 ml of dimethylformamide at room temperature. The mixture was stirred at the same temperature for 4 hours. To the reaction mixture were added 100 ml of ice water and 200 ml of ethyl acetate. The organic layer was separated, washed with 100 ml of water and 50 ml of a saturated aqueous sodium chloride solution in this order, dried over anhydrous magnesium sulfate and subjected to distillation to remove the solvent. The residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=10/1) to obtain 5.14 g of 2-(3,4-diethoxyphenyl)-4-(3-methoxycarbonyl-4-tert-butyldimethylsilyloxyphenyl)thiazole.