Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:30])[C:9]1[CH:14]=[C:13]([N+:15]([O-:17])=[O:16])[CH:12]=[CH:11][C:10]=1[N:18]1[C:22]([CH2:23]O)=[C:21]([CH3:25])[N:20]=[C:19]1[CH2:26][N:27]([CH3:29])[CH3:28].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:50]1(=[O:60])[NH:54][C:53](=[O:55])[C:52]2=[CH:56][CH:57]=[CH:58][CH:59]=[C:51]12.N(C(OCC)=O)=NC(OCC)=O>>[N+:15]([C:13]1[CH:12]=[CH:11][C:10]([N:18]2[C:22]([CH2:23][N:54]3[C:50](=[O:60])[C:51]4=[CH:59][CH:58]=[CH:57][CH:56]=[C:52]4[C:53]3=[O:55])=[C:21]([CH3:25])[N:20]=[C:19]2[CH2:26][N:27]([CH3:29])[CH3:28])=[C:9]([C:8](=[O:30])[C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])[CH:14]=1)([O-:17])=[O:16]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: Cc1nc(CN(C)C)n(-c2ccc([N+](=O)[O-])cc2C(=O)c2ccccc2Cl)c1CO
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: Cc1nc(CN(C)C)n(-c2ccc([N+](=O)[O-])cc2C(=O)c2ccccc2Cl)c1CN1C(=O)c2ccccc2C1=O

Procedure:
In the manner given in Example 3, 2'-chloro-5-nitro-2-[2-[(dimethylamino)methyl]-4-methyl-5-hydroxymethylimidazol-1-yl]benzophenone, triphenylphosphine, phthalimide and thereafter diethyl azodicarboxylate are reacted together to give N-[[1-[4-nitro-2-(o-chlorobenzoyl)phenyl]-2-[(dimethylamino)methyl]-4-methylimidazol-5-yl]methyl]-phthalimide.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[Br:12])[N+:8]([O-])=[C:7]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:6](=[O:19])[NH:5]2.P(Cl)(Cl)Cl>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[Br:12])[N:8]=[C:7]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:6](=[O:19])[NH:5]2
Reactant: CCOC(=O)c1c(=O)[nH]c2cc(Cl)c(Br)cc2[n+]1[O-]
Solvent: C1CCOC1
Solvent: ClP(Cl)Cl
Product: CCOC(=O)c1nc2cc(Br)c(Cl)cc2[nH]c1=O
Temperature: 0 °C

Procedure:
One gram of ethyl 6-chloro-7-bromo-3,4-dihydro-3-oxo-2-quinoxaline carboxylate N-oxide was dissolved in 50 ml. of THF. Six ml. of phosphorus trichloride were added and the resulting mixture heated gently at refluxing temperature overnight. The reaction mixture was poured into 500 ml. of an ice-water mixture. A solid, comprising ethyl 6-chloro-7-bromo-3,4-dihydro-3-oxo-2-quinoxaline carboxylate formed in the above reaction, was separated by filtration; melting point=203°-205° C.; yield=0.6 g.
Reaction SMILES: [Mg].[CH3:2]I.[CH3:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:9][CH:8]=1)=[O:6].[Cl-].[NH4+]>C(OC)(C)(C)C.O1CCCC1>[CH2:14]([O:13][C:10]1[CH:11]=[CH:12][C:7]([C:5]([OH:6])([CH3:2])[CH3:4])=[CH:8][CH:9]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: CI
Reactant: CC(=O)c1ccc(OCc2ccccc2)cc1
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: COC(C)(C)C
Solvent: C1CCOC1
Product: CC(C)(O)c1ccc(OCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 91.8 %

Procedure:
The reaction flask was charged under argon with 3.45 g of magnesium (142 mmol). A solution of 21.16 g of methyl iodide (147 mmol) in 120 mL of tert-butyl-methyl-ether was added during 45 minutes at 45° C. under stirring. Then stirring was continued for 1 hour at 45° C. and then a solution of 27.12 g of 4-benzyloxyacetophenone (120 mmol) in 100 mL of tetrahydrofuran was added during 45 minutes, while a temperature of 45° C. was again maintained. Stirring at 45° C. was continued for 1.5 hours. After cooling to room temperature, the white suspension was poured into a mixture of 100 mL of 10% aqueous ammonium chloride and of ice and extracted with 150 mL of ethyl acetate. The aqueous phase was separated and extracted with 100 mL of ethyl acetate. The organic phase was washed with 120 mL of 20% aq. sodium chloride, combined, dried (MgSO4) and evaporated under reduced pressure to give 29.9 g of crude product as an oil which partially crystallised. The crude product was taken up in 30 mL of dichloromethane. The solution was concentrated at the rotary evaporator almost to dryness. Then 6 mL of ethyl acetate was added followed by gradual addition of a total of 180 mL of hexane. The suspension was then kept at 0° C. for 30 minutes. The crystals were collected and washed with cold hexane. After drying for 2 hours at 16 mbar/45° C., 26.7 g (92%) 2-(4-benzyloxy-phenyl)-propan-2-ol was obtained.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH3:14])=[CH:10][CH:11]=2)[N:6]2[CH:15]=[C:16]([C:18]([O:20]CC)=[O:19])[N:17]=[C:5]2[CH:4]=1.C(=O)([O-])[O-].[Na+].[Na+].Cl>CO>[CH3:1][O:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH3:14])=[CH:10][CH:11]=2)[N:6]2[CH:15]=[C:16]([C:18]([OH:20])=[O:19])[N:17]=[C:5]2[CH:4]=1
Reactant: CCOC(=O)c1cn2c(cc(OC)c3ccc(OC)cc32)n1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CO
Product: COc1ccc2c(OC)cc3nc(C(=O)O)cn3c2c1

Procedure:
A mixture of 1 g of ethyl 5,8-dimethoxyimidazo-[1,2-a]-quinoline-2-carboxylate in a mixture of 10 ml of methanol and a 5% sodium carbonate solution was refluxed for 1 hour, and the resultant solution was acidified with dilute hydrochloric acid. The precipitate of 5,8-dimethoxyimidazo-[1,2-a]-quinoline-2-carboxylic acid thus formed was filtered off and was suspended in 10 ml of methanol. The mixture was acidified with HCl/methanol to obtain a clear solution from which the acid crystallized upon addition of diethyl ether to obtain the said acid melting at 248°-250° C.
Reaction SMILES: [O:1]=[C:2]1[NH:6][C:5]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=2)([CH2:7][O:8][CH2:9][CH:10]=[CH2:11])[C:4](=[O:19])[N:3]1[C:20]1[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[C:22]([C:28]([F:31])([F:30])[F:29])[CH:21]=1.[C:32](=O)([O-])[O-].[K+].[K+].CI>CN(C=O)C>[O:1]=[C:2]1[N:6]([CH3:32])[C:5]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=2)([CH2:7][O:8][CH2:9][CH:10]=[CH2:11])[C:4](=[O:19])[N:3]1[C:20]1[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[C:22]([C:28]([F:31])([F:29])[F:30])[CH:21]=1
Reactant: O=C([O-])[O-]
Reactant: C=CCOCC1(c2cccc(C)c2)NC(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C1=O
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: C=CCOCC1(c2cccc(C)c2)C(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C(=O)N1C
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 4-[2,5-dioxo-4-(3-methylphenyl)-4-[(2-propenyloxy)methyl]imidazolidin-1-yl]-2-trifluoromethylbenzonitrile (829 mg) in DMF (1.5 mL) is added potassium carbonate (320 mg) and methyliodide (480 μL). The mixture is stirred 3 hours at rt, evaporated, washed with brine, extracted with ethyl acetate, dried over MgSO4 and concentrated to give the desired compound.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH:4]([C:7]2[C:8]([O:13][C:14]3[CH:20]=[CH:19][C:17]([NH2:18])=[CH:16][CH:15]=3)=[N:9][CH:10]=[CH:11][CH:12]=2)[CH2:3][CH2:2]1.Cl[C:22]1[N:26]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)[C:25]2[CH:36]=[CH:37][CH:38]=[CH:39][C:24]=2[N:23]=1>CC(O)C>[CH3:35][O:34][C:31]1[CH:30]=[CH:29][C:28]([CH2:27][N:26]2[C:25]3[CH:36]=[CH:37][CH:38]=[CH:39][C:24]=3[N:23]=[C:22]2[NH:18][C:17]2[CH:16]=[CH:15][C:14]([O:13][C:8]3[C:7]([CH:4]4[CH2:3][CH2:2][O:1][CH2:6][CH2:5]4)=[CH:12][CH:11]=[CH:10][N:9]=3)=[CH:20][CH:19]=2)=[CH:33][CH:32]=1
Reactant: COc1ccc(Cn2c(Cl)nc3ccccc32)cc1
Reactant: Nc1ccc(Oc2ncccc2C2CCOCC2)cc1
Solvent: CC(C)O
Product: COc1ccc(Cn2c(Nc3ccc(Oc4ncccc4C4CCOCC4)cc3)nc3ccccc32)cc1
Temperature: 170 °C

Procedure:
A glass microwave reaction vessel was charged with 4-(3-(tetrahydro-2H-pyran-4-yl)pyridin-2-yloxy)aniline (0.2573 g, 0.952 mmol) and 2-chloro-1-(4-methoxybenzyl)-1H-benzo[d]imidazole (0.312 g, 1.142 mmol) in IPA. The reaction mixture was stirred and heated in a Biotage Initiator microwave reactor at 170° C. for 30 min. Solvent was evaporated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage pre-packed silica gel column (40S), eluting with a gradient of 10% to 80% EtOAc in hexane, to provide 1-(4-methoxybenzyl)-N-(4-(3-(tetrahydro-2H-pyran-4-yl)pyridin-2-yloxy)phenyl)-1H-benzo[d]imidazol-2-amine. IC50 (uM) +++++.
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[N:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.[CH3:21][S:22][C:23](SC)=[CH:24][N+:25]([O-:27])=[O:26]>C(O)C>[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[N:15]1[CH2:16][CH2:17][N:18]([C:23]([S:22][CH3:21])=[CH:24][N+:25]([O-:27])=[O:26])[CH2:19][CH2:20]1
Reactant: CSC(=C[N+](=O)[O-])SC
Reactant: COc1cc2ncnc(N3CCNCC3)c2cc1OC
Solvent: CCO
Product: COc1cc2ncnc(N3CCN(C(=C[N+](=O)[O-])SC)CC3)c2cc1OC
Yield: 31 %

Procedure:
To an ethanol solution (30 mL) of 6,7-dimethoxy-4-(1-piperazinyl)quinazoline described in South African Patent 67 06512 (1968) (Compound (i); 6.00 g, 21.9 mmol), commercially available 1,1-bis(methylthio)-2-nitroethylene (4.27 g, 25.8 mol) was added, followed by stirring under heating at 50 C for 9 hours and then heating under reflux for 2.5 hours. After the reaction solution was allowed to stand for cooling, the solvent was evaporated and then the resulting residue was purified by silica gel column chromatography to give the target compound (2.65 g, 6.78 mmol).
Reaction SMILES: C([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)C1C=CC=CC=1.ClC(Cl)C.ClC(OC(Cl)=O)C>>[CH3:21][O:20][C:17]1[CH:16]=[CH:15][C:14]([C:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH:10]=2)=[CH:19][CH:18]=1
Reactant: COc1ccc(C2=CCN(Cc3ccccc3)CC2)cc1
Agent: CC(Cl)OC(=O)Cl
Solvent: CC(Cl)Cl
Product: COc1ccc(C2=CCNCC2)cc1

Procedure:
A mixture of 1-benzyl-1,2,3,6-tetrahydro-4-(4-methoxyphenyl)pyridine (XVI, EXAMPLE 42--Step 2, 2.021 g, 7.2 mmol), dichloroethane (19 ml) and 1-chloroethylchloroformate (2.8 ml, 26.0 mmol) is refluxed overnight. The mixture is concentrated to about one third the original volume and methanol is added. The mixture is refluxed for 2 hr, then cooled and concentrated. The resulting solids are slurried in dichloromethane, ether is added, and the solids are collected and then partitioned between dichloromethane and saturated aqueous sodium bicarbonate. Some solids remained in the aqueous phase and are collected and combined with the organic fractions. Following chromatography on silica gel eluting with methanol/dichloromethane (0.5% ammonium hydroxide, 6/94), the appropriate fractions are pooled and concentrated to give 1,2,3,6-tetrahydro-4-(4-methoxypheny)pyridine (XVII).
Reaction SMILES: [Li+].[OH-].[C:3]1([CH2:9][O:10][C:11]2[CH:20]=[CH:19][C:18]([C:21]([N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[O:22])=[CH:17][C:12]=2[C:13]([O:15]C)=[O:14])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl>O.O1CCCC1>[C:3]1([CH2:9][O:10][C:11]2[CH:20]=[CH:19][C:18]([C:21]([N:23]3[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]3)=[O:22])=[CH:17][C:12]=2[C:13]([OH:15])=[O:14])[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: COC(=O)c1cc(C(=O)N2CCCCC2)ccc1OCc1ccccc1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)c1cc(C(=O)N2CCCCC2)ccc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A solution of LiOH (534 mg, 12.73 mmol) in water (8 ml) was added to a stirred solution of methyl 2-[(phenylmethyl)oxy]-5-(1-piperidinylcarbonyl)benzoate (may be prepared as described in Description 52; 450 mg, 1.27 mmol) in tetrahydrofuran (2 ml) at room temperature. The mixture was stirred at room temperature for 3 h. The mixture was then acidified by 6N HCl and the precipitate was collected and dried to yield the title compound as a white solid. 400 mg.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:23])[CH2:5][N:6]([CH:20]1[CH2:22][CH2:21]1)[C:7](=[O:19])[C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=1)[CH3:2].[CH2:24]([N:31]1[CH:35]=[C:34]([C:36](O)=[O:37])[N:33]=[N:32]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>>[CH2:1]([O:3][C:4](=[O:23])[CH:5]([N:6]([CH:20]1[CH2:22][CH2:21]1)[C:7](=[O:19])[C:8]1[CH:9]=[CH:10][C:11]([O:14][C:15]([F:16])([F:17])[F:18])=[CH:12][CH:13]=1)[C:36]([C:34]1[N:33]=[N:32][N:31]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:35]=1)=[O:37])[CH3:2]
Reactant: O=C(O)c1cn(Cc2ccccc2)nn1
Reactant: CCOC(=O)CN(C(=O)c1ccc(OC(F)(F)F)cc1)C1CC1
Product: CCOC(=O)C(C(=O)c1cn(Cc2ccccc2)nn1)N(C(=O)c1ccc(OC(F)(F)F)cc1)C1CC1

Procedure:
The title compound, a colorless oil (0.6 g, 27%), was prepared in analogy to intermediate 8A by reaction of [cyclopropyl-(4-trifluoromethoxy-benzoyl)-amino]-acetic acid ethyl ester (intermediate 7B) with 1-benzyl-1H-[1,2,3]triazole-4-carboxylic acid. MS: 517.1 (MH+).
Reaction SMILES: [O:1]([C:8]1[CH:14]=[CH:13][C:11]([NH2:12])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:16][C:17]#[N:18].C(N(CC)CC)C>O1CCCC1>[O:1]([C:8]1[CH:9]=[CH:10][C:11]([NH:12][CH2:16][C:17]#[N:18])=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Nc1ccc(Oc2ccccc2)cc1
Reactant: N#CCBr
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: N#CCNc1ccc(Oc2ccccc2)cc1
Temperature: 85 °C
Yield: 44.8 %

Procedure:
A mixture of 4-phenoxyaniline (7.0 g, 37.8 mmol), bromoacetonitrile (4.5 g, 37.8 mmol) and triethylamine (4.2 g, 41.6 mmol) in tetrahydrofuran (50 mL) was heated at 85° C. for 5.25 hours then cooled and another portion of bromoacetonitrile (6.5 g, 5.46 mmol) was added. The mixture was heated at 85° C. for 18 hours then cooled and concentrated under reduced pressure. The residue was partitioned between dichloromethane (50 mL) and water (50 mL). The aqueous layer was extracted with dichloromethane (30 mL) then the combined organic solutions were extracted with 5 N aqueous sodium hydroxide (30 mL), dried over magnesium sulfate, filtered and the filtrate concentrated under reduced pressure. The residue was then purified by flash chromatography on silica gel using dichloromethane/ethyl acetate (98:2) as an eluent to provide 3.8 g (45%) of the title compound as a dark brown solid: 1H NMR (DMSO-d6, 400 MHz) δ 7.32 (t, 2H), 7.03 (t, 1H), 6.87–6.94 (m, 4H), 6.76 (d, 2H), 6.26 (bs, 2H), 4.25 (s, 2H);RP-HPLC (Hypersil HS-C18, 5 μm, 100 A, 4.6×250 mm; 25%–100% acetonitrile-0.05 M ammonium acetate over 25 min, 1 mL/min) tr 18.4 min.; MS: MH+ 225.1.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([O:9][CH3:10])[C:5](Cl)=[N:6][CH:7]=1.BrC1C=N[CH:15]=[C:16]([O:18]C)C=1.[O-]CC.[Na+].C(O)C>O>[Br:1][C:2]1[CH:3]=[C:4]([O:9][CH3:10])[C:5]([O:18][CH2:16][CH3:15])=[N:6][CH:7]=1
Reactant: COc1cc(Br)cnc1Cl
Reactant: COc1cncc(Br)c1
Agent: CC[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CCOc1ncc(Br)cc1OC

Procedure:
As shown in step 5-i of Scheme 5, 5-bromo-2-chloro-3-methoxypyridine (1.0 g, 4.5 mmol, prepared in the same manner as Compound 1003 in Example 2 starting with 3-bromo-5-methoxypyridine) was treated with a sodium ethoxide/ethanol solution (5.05 mL, 21% w/v, 13.5 mmol) and the reaction mixture microwave irradiated at 100° C. for 20 minutes. Water was added and the ethanol evaporated under reduced pressure. The resulting aqueous solution was extracted with DCM and ether, followed by drying the combined extracts over MgSO4. After filtration, removal of the volatiles under reduced pressure provided 5-bromo-2-ethoxy-3-methoxypyridine (Compound 1016), 0.72 g, 69% yield): ESMS (M+H) 232.32/234.23. As shown in step 5-ii of Scheme 5, Compound 1017 (ESMS (M+H) 218.32/220.23) was prepared in the same manner as Compound 1016, using sodium methoxide in methanol instead of sodium ethoxide in ethanol.
Reaction SMILES: BrC1C=CC=C2C=1C(C1C(O)=CC3OCOC=3C=1)[C:5](=[O:16])N2CCCCC.[OH:27][C:28]1[C:29]([CH:37]2[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[N:39]([CH2:46][C:47]3[CH:56]=[CH:55][C:50]([C:51]([O:53][CH3:54])=[O:52])=[CH:49][CH:48]=3)[C:38]2=[O:57])=[CH:30][C:31]2[O:35][CH2:34][O:33][C:32]=2[CH:36]=1>>[OH:27][C:28]1[C:29]([C:37]2([CH2:5][OH:16])[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[N:39]([CH2:46][C:47]3[CH:56]=[CH:55][C:50]([C:51]([O:53][CH3:54])=[O:52])=[CH:49][CH:48]=3)[C:38]2=[O:57])=[CH:30][C:31]2[O:35][CH2:34][O:33][C:32]=2[CH:36]=1
Reactant: COC(=O)c1ccc(CN2C(=O)C(c3cc4c(cc3O)OCO4)c3ccccc32)cc1
Reactant: CCCCCN1C(=O)C(c2cc3c(cc2O)OCO3)c2c(Br)cccc21
Product: COC(=O)c1ccc(CN2C(=O)C(CO)(c3cc4c(cc3O)OCO4)c3ccccc32)cc1

Procedure:
Following the procedure as described in PREPARATION 1E, and making non-critical variations to replace 4-bromo-3-(6-hydroxy-1,3-benzodioxol-5-yl)-1-pentyl-1,3-dihydro-2H-indol-2-one with methyl 4-{[3-(6-hydroxy-1,3-benzodioxol-5-yl)-2-oxo-2,3-dihydro-1H-indol-1-yl]methyl}benzoate, the title compound was obtained (81%): MS (ES+) m/z 448.1 (M+1).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:17]([OH:24])=[C:18]([C:20]([CH3:23])([CH3:22])[CH3:21])[CH:19]=1)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]#[N:15])=[CH:10][C:9]=1[Cl:16])=[O:6].[S:25]1[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[CH:27]=[C:26]1B(O)O>>[S:25]1[C:26]([C:2]2[CH:19]=[C:18]([C:20]([CH3:23])([CH3:22])[CH3:21])[C:17]([OH:24])=[C:4]([CH:3]=2)[C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]#[N:15])=[CH:10][C:9]=2[Cl:16])=[O:6])=[CH:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]1=2
Reactant: OB(O)c1cc2ccccc2s1
Reactant: CC(C)(C)c1cc(Br)cc(C(=O)Nc2ccc(C#N)cc2Cl)c1O
Product: CC(C)(C)c1cc(-c2cc3ccccc3s2)cc(C(=O)Nc2ccc(C#N)cc2Cl)c1O

Procedure:
The title compound was prepared from 3-bromo-5-tert-butyl-N-(2-chloro-4-cyanophenyl)-6-hydroxy-benzamide and benzothiophen-2-boronic acid
Reaction SMILES: [F:1][C:2]([F:21])([F:20])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:14][C:13]([C:15](OCC)=[O:16])=[N:12][CH:11]=2)=[CH:6][CH:5]=1.O.[NH2:23][NH2:24]>CCO>[F:1][C:2]([F:21])([F:20])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:14][C:13]([C:15]([NH:23][NH2:24])=[O:16])=[N:12][CH:11]=2)=[CH:6][CH:5]=1
Reactant: CCOC(=O)c1ncc(-c2ccc(OC(F)(F)F)cc2)o1
Reactant: NN
Solvent: CCO
Solvent: O
Product: NNC(=O)c1ncc(-c2ccc(OC(F)(F)F)cc2)o1
Temperature: 25 °C
Reaction time: 16 h
Yield: 75 %

Procedure:
To a solution of ethyl 5-(4-(trifluoromethoxy)phenyl)oxazole-2-carboxylate (6.4 g, 21.2 mmol) in EtOH (30 mL), was added dropwise hydrazine hydrate (6 mL, 84% in H2O) while stifling at RT. The mixture was then stirred for further 16 h at RT and then concentrated under reduced pressure to half volume. Upon addition of H2O (30 mL) a yellow solid precipitated, which was filtered, washed with H2O (3×30 mL) and dried to afford the title compound as a light yellow solid (4.6 g, 75%). MS (ES+) C11H8F3N3O3 requires: 287. found: 288 [M+H]+;
Reaction SMILES: [Na].[C:2]([O:8][CH2:9][CH3:10])(=[O:7])[CH2:3][C:4]([CH3:6])=[O:5].[CH:11](=O)/[CH:12]=[CH:13]/[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.Cl>C(O)C>[CH2:9]([O:8][C:2]([CH:3]1[CH:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:12][CH:11]=[CH:6][C:4]1=[O:5])=[O:7])[CH3:10]
Reactant: CCOC(=O)CC(C)=O
Reactant: O=C/C=C/c1ccccc1
Agent: Cl
Agent: [Na]
Solvent: CCO
Product: CCOC(=O)C1C(=O)C=CCC1c1ccccc1
Temperature: 25 °C
Reaction time: 65 h

Procedure:
Under a nitrogen atmosphere, 0.1 gram (0.004 mole) of sodium metal was reacted in 40 mL of ethanol. The solution was stirred, and 13.0 grams (0.100 mole) of ethyl acetoacetate was added. The reaction mixture was cooled in an ice bath, and 13.2 grams (0.100 mole) of trans-cinnamaldehyde in 10 mL of ethanol was added dropwise during a 10 minute period. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature where it stirred for about 18 hours. After this time the reaction mixture was saturated with gaseous hydrochloric acid and then was allowed to stand for about 65 hours. The reaction mixture was concentrated under reduced pressure to yield 2-ethoxycarbonyl-3-phenylcyclohex-5-enone. A 100% yield (24.4 grams) of product was assumed.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([C:11]1[CH:12]=[C:13]([OH:19])[C:14]([OH:18])=[CH:15][C:16]=1[CH3:17])(=[O:10])=[O:9].C(=O)([O-])[O-].[K+].[K+].Br[CH:27](Br)[C:28]([OH:30])=[O:29].Cl>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([C:11]1[C:16]([CH3:17])=[CH:15][C:14]2[O:18][CH:27]([C:28]([OH:30])=[O:29])[O:19][C:13]=2[CH:12]=1)(=[O:10])=[O:9]
Reactant: Cc1cc(O)c(O)cc1S(=O)(=O)c1ccccc1Cl
Reactant: O=C(O)C(Br)Br
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1cc2c(cc1S(=O)(=O)c1ccccc1Cl)OC(C(=O)O)O2
Reaction time: 15 h

Procedure:
23 g (77 mmol) of 4-(2-chlorophenylsulphonyl)-5-methyl-1,2-benzenediol are added to a finely particulate suspension of 50.9 g (385 mmol) of freshly calcined potassium carbonate in 180 ml of dry dimethylformamide and there is added dropwise thereto, in the course of 15 minutes, a solution of 8.50 g (39 mmol) of dibromoacetic acid in 80 ml of dimethylformamide. The mixture is then stirred for 15 hours at 80°. Subsequently, the reaction mixture is poured onto ice and adjusted to pH 1-2 with concentrated hydrochloric acid. The aqueous phase is extracted once more with ethyl acetate. The combined organic phases are washed with water and saturated sodium chloride solution, dried with sodium sulphate and concentrated by evaporation. The resulting brown oil is stirred with 150 ml of ethyl acetate at 0° until crystallisation occurs. The crude 5-(2-chlorophenylsulphonyl)-6-methyl-1,3-benzodioxole-2-carboxylic acid so obtained is recrystallised twice from acetonitrile, resulting in the form of sand-coloured crystals having a melting point of 211°-213.5°.
Reaction SMILES: [C:1]([OH:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[CH2:21](O)[CH3:22]>>[C:1]([OH:20])(=[O:19])[CH2:2][CH2:3][CH2:4]/[CH:5]=[CH:6]\[CH2:7]/[CH:8]=[CH:9]\[CH2:10]/[CH:11]=[CH:12]\[CH2:13]/[CH:14]=[CH:15]\[CH2:16][CH2:17][CH2:18][CH2:21][CH3:22]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Reactant: CCO
Product: CCCCC/C=C\C/C=C\C/C=C\C/C=C\CCCC(=O)O

Procedure:
Rats receiving intragastric pretreatment with PL solution only had 3 hours after ethanol macroscopic hemorrhagic lesions involving 35.8±2% of glandular mucosal area. Treatment with oleic acid did not change significantly occurrence of mucosal hemorrhagic lesions -29.1±3%. Rats receiving pretreatment with 120 mM and 240 mM LLC had significantly decreased macroscopic hemorrhagic lesions -6.5±1% and 1.3±0.5% respectively (p<0.01) 3 hours after ethanol. Macroscopic protection rat gastric mucosa against ethanol was similar to that afforded by arachidonic acid except for the presence of marked edema in the forestomach (containing squamous, paraepidermoidal epithelium) 3 hours after ethanol in group pretreated with linoleic acid (C).
Reaction SMILES: [CH:1]1[CH2:6][CH2:5][CH:4]=[CH:3][CH:2]=1.[C:7]1([S:13](/[CH:16]=[CH:17]/[S:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)(=[O:20])=[O:19])(=[O:15])=[O:14])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>C1(C)C=CC=CC=1>[C:7]1([S:13]([CH:16]2[CH:17]([S:18]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)(=[O:20])=[O:19])[CH:3]3[CH2:4][CH2:5][CH:6]2[CH:1]=[CH:2]3)(=[O:14])=[O:15])[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1
Reactant: O=S(=O)(/C=C/S(=O)(=O)c1ccccc1)c1ccccc1
Reactant: C1=CCCC=C1
Solvent: Cc1ccccc1
Product: O=S(=O)(c1ccccc1)C1C2C=CC(CC2)C1S(=O)(=O)c1ccccc1
Yield: 104.4 %

Procedure:
A mixed solution of 3.16 g (39.5 mmol) of 1,3-cyclohexadiene, 10.5 g (34.1 mmol) of trans-1,2-bis(phenylsulfonyl)ethylene, and 200 ml of toluene was refluxed for 7 hours. After that, the solution was cooled and concentrated under reduced pressure to yield a reaction mixture. The reaction crude product was recrystallized (chloroform/hexane) to yield 5,6-bis(phenylsulfonyl)-bicyclo[2.2.2]octa-2-ene (13.8 g, 35.6 mmol, 90% yield).