Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([O:12][CH3:13])=[O:11])=[CH:4][CH:3]=1.[CH3:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[C:16]=1[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH:28]=O)[CH:23]=1.C([BH3-])#N.[Na+].C(O)(=O)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1(C)C=CC=CC=1>[CH3:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[C:16]=1[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][NH:1][C:2]2[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][C:10]([O:12][CH3:13])=[O:11])=[CH:6][CH:7]=2)[CH:23]=1
Reactant: COC(=O)CCc1ccc(N)cc1
Reactant: Cc1cccc(C)c1-c1cccc(C=O)c1
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: Cc1ccccc1
Product: COC(=O)CCc1ccc(NCc2cccc(-c3c(C)cccc3C)c2)cc1
Temperature: 25 °C
Reaction time: 55 h
Yield: 61 %

Procedure:
To a solution of methyl 3-(4-aminophenyl)propanoate (3.33 g, 18.6 mmol) and 2′,6′-dimethylbiphenyl-3-carbaldehyde (3.91 g, 18.6 mmol) in toluene (40 mL) were added molecular sieves (0.4 nm, beads, 7.2 g), and the mixture was stirred at room temperature for 55 hr. The reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The obtained residue was dissolved in tetrahydrofuran (100 mL). Sodium cyanoborohydride (2.53 g, 40.3 mmol) and acetic acid (2.31 mL, 40.3 mmol) were successively added, and the mixture was stirred under a nitrogen atmosphere at room temperature for 3 hr. Aqueous citric acid solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (10%-40% ethyl acetate/hexane) to give the title compound (4.24 g, yield 61%) as a colorless oil.
Reaction SMILES: [ClH:1].[CH2:2]1[C:14]2[C:13]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[N:7]([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:6]=2[CH2:5][CH2:4][NH:3]1.[C:21]1(NN)C=CC=CC=1>>[ClH:1].[CH3:21][C:10]1[CH:11]=[CH:12][C:13]2[C:14]3[CH2:2][NH:3][CH2:4][CH2:5][C:6]=3[N:7]([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:8]=2[CH:9]=1
Reactant: CCOC(=O)Cn1c2c(c3ccccc31)CNCC2
Reactant: NNc1ccccc1
Agent: Cl
Product: CCOC(=O)Cn1c2c(c3ccc(C)cc31)CNCC2

Procedure:
The title compound is prepared using a procedure analogous to Intermediate 1, substituting 3-methylphenylhydrazine for phenylhydrazine in Step 1a).
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4](I)[CH:3]=1.[NH2:13][C:14]1[CH:15]=[C:16]([CH:21]=[CH:22][C:23]=1[NH2:24])[C:17]([O:19][CH3:20])=[O:18].C([O-])([O-])=O.[K+].[K+]>ClC1C=CC=CC=1.C(OCC)(=O)C.[Cu]>[NH2:13][C:14]1[CH:15]=[C:16]([C:17]([O:19][CH3:20])=[O:18])[CH:21]=[CH:22][C:23]=1[NH:24][C:4]1[CH:3]=[C:2]([Cl:1])[CH:11]=[CH:10][C:5]=1[C:6]([O:8][CH3:9])=[O:7]
Reactant: COC(=O)c1ccc(Cl)cc1I
Reactant: COC(=O)c1ccc(N)c(N)c1
Agent: [Cu]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Clc1ccccc1
Solvent: CCOC(C)=O
Product: COC(=O)c1ccc(Nc2cc(Cl)ccc2C(=O)OC)c(N)c1
Temperature: 25 °C
Yield: 67.7 %

Procedure:
A mixture of methyl 4-chloro-2-iodobenzoate (0.593 g, 2 mmol), methyl 3,4-diaminobenzoate (0.332 g, 2 mmol), copper (0.126 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol) in chlorobenzene (40 mL) was heated to reflux for 20 hours, cooled to room temperature, diluted with ethyl acetate, and filtered through diatomaceous earth (Celite®). The solution was washed with water and brine, dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel with 7:3 hexanes/ethyl acetate to provide 0.453 g (68%) of the desired product. MS (DCI) m/e 334 (M+H)+, 352 (M+NH4)+; 1H NMR (300 MHz, DMSO-d6) δ 8.99 (s, 1H), 7.89 (d, J=8.5 Hz, 1H), 7.47 (d, J=1.0 Hz, 1H), 7.21 (m, 2H), 6.80 (dd, J=8.5, 2.0 Hz, 1H), 6.65 (d, J=2.1 Hz, 1H), 5.30 (s, 2H), 3.86 (s, 3H), 3.82 (s, 3H).
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]([F:13])([F:12])[F:11])[CH:3]=1>C(O)C.[Ni]>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH2:7])=[C:4]([C:10]([F:11])([F:12])[F:13])[CH:3]=1
Reactant: N#Cc1ccc(F)cc1C(F)(F)F
Agent: [Ni]
Solvent: CCO
Product: NCc1ccc(F)cc1C(F)(F)F
Reaction time: 2.5 h
Yield: 19.6 %

Procedure:
To a solution of 4-fluoro-2-(trifluoromethyl)benzonitrile (2.0 g) in ethanol (10.0 mL) was added Raney Ni (catalytic amount). The reaction mixture was subjected for hydrogenation in Parr apparatus under 50 psi for 2-3 h. The reaction mass was filtered through celite and the filtrate was concentrated to afford 0.400 g of desired product. 1HNMR (CDCl3): δ 3.98 (s, 2H), 7.24 (t, J=9.0 Hz, 1H), 7.34 (d, J=8.7 Hz, 1H), 7.54 (t, J=7.8 Hz, 1H); MS [M+H]+:194.03.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]([Cl:10])[N:3]=1.[CH:11]([Mg]Br)=[CH2:12].ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>O1CCCC1>[Cl:1][C:2]1[N:7]=[C:6]([CH:11]=[CH2:12])[C:5]([O:8][CH3:9])=[C:4]([Cl:10])[N:3]=1
Reactant: COc1cnc(Cl)nc1Cl
Reactant: C=C[Mg]Br
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Solvent: C1CCOC1
Product: C=Cc1nc(Cl)nc(Cl)c1OC
Temperature: 25 °C
Reaction time: 4 h
Yield: 60 %

Procedure:
To a solution of commercially available 2,6-dichloro-5-methoxy pyrimidine (100 grams (g), 0.55 moles (mol)) in dry tetrahydrofuran (THF) was added, dropwise, 1 molar (M) vinyl magnesium bromide in tetrahydrofuran solvent (124 g, 0.94 mol) over one hour (h) at room temperature. The mixture was then stirred for 4 h at room temperature. Excess Grignard reagent was quenched by addition of acetone (200 milliliters (mL)) while the temperature of the mixture was maintained at a temperature below 20° C. Thereafter, 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) (151 g, 0.67 mol) was added at once and stirred overnight. A yellow solid precipitated out. The solid was filtered and washed with ethyl acetate (500 mL). The filtrate was concentrated under reduced pressure and the resulting crude compound was diluted with ethyl acetate (2 liters (L)). The resulting undissolved, dark, semi-solid was separated by filtration using ethyl acetate. It was further concentrated under reduced pressure to provide a crude compound, which was purified by column chromatography. The compound was eluted with 5% to 10% ethyl acetate in hexane mixture to provide the title compound (70 g, 60%): mp 60-61° C.; 1H NMR (CDCl3) δ 3.99 (s, 3H), 5.85 (d, 1H), 6.75 (d, 1H), 6.95 (dd, 1H).
Reaction SMILES: CS(O[CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:23]=[CH:22][C:14]2[C:15]([CH3:21])([CH3:20])[O:16][C:17](=[O:19])[NH:18][C:13]=2[CH:12]=1)(=O)=O.[Cl:24][C:25]1[CH:26]=[C:27]([SH:32])[CH:28]=[CH:29][C:30]=1[Cl:31]>>[Cl:24][C:25]1[CH:26]=[C:27]([S:32][CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:23]=[CH:22][C:14]3[C:15]([CH3:20])([CH3:21])[O:16][C:17](=[O:19])[NH:18][C:13]=3[CH:12]=2)[CH:28]=[CH:29][C:30]=1[Cl:31]
Reactant: Sc1ccc(Cl)c(Cl)c1
Reactant: CC1(C)OC(=O)Nc2cc(OCCCCOS(C)(=O)=O)ccc21
Product: CC1(C)OC(=O)Nc2cc(OCCCCSc3ccc(Cl)c(Cl)c3)ccc21

Procedure:
Prepared analogously to Example 210 from 7-(4-methanesulfonyloxy-butoxy)-4,4-dimethyl-4H-3,1-benzoxazin-2-one and 3,4-dichloro-thiophenol.
Reaction SMILES: [Mg].Br[C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([O:13][CH3:14])[CH:7]=[CH:6]2.[CH2:15]([CH:18]1[CH2:23][CH2:22][C:21](=O)[CH2:20][CH2:19]1)[CH2:16][CH3:17].Cl>O1CCCC1>[CH3:14][O:13][C:8]1[CH:7]=[CH:6][C:5]2[C:10](=[CH:11][CH:12]=[C:3]([C:21]3[CH2:22][CH2:23][CH:18]([CH2:15][CH2:16][CH3:17])[CH2:19][CH:20]=3)[CH:4]=2)[CH:9]=1
Reactant: COc1ccc2cc(Br)ccc2c1
Reactant: CCCC1CCC(=O)CC1
Agent: Cl
Agent: [Mg]
Solvent: C1CCOC1
Product: CCCC1CC=C(c2ccc3cc(OC)ccc3c2)CC1
Reaction time: 1 h
Yield: 75.8 %

Procedure:
5.7 g of magnesium was suspended in 12 ml of tetrahydrofuran. To the suspension was then added dropwise a solution of 50 g of 6-bromo-2-methoxynaphthalene in 200 ml of tetrahydrofuran at a rate such that tetrahydrofuran was gently refluxed. The reaction mixture was then further stirred for 1 hour. To the reaction solution was then added dropwise a solution of 30 g of 4-propylcyclohexanone in 120 ml of tetrahydrofuran at room temperature. The reaction mixture was then further stirred for 1 hour. To the reaction solution was then added 200 ml of a 10% hydrochloric acid. The reaction mixture was extracted with 300 ml of toluene, washed with water, saturated aqueous solution of sodium bicarbonate and saturated brine, and then dried over anhydrous sodium sulfate. The solvent was then distilled off. To the residue were then added 230 ml of toluene and 4.0 g of p-toluenesulfonic acid monohydrate. The reaction mixture was then heated under reflux for 3 hour. The reaction solution was allowed to cool to root temperature, washed with water, saturated aqueous solution of sodium bicarbonate and saturated brine, and then dried over anhydrous sodium sulfate. The solvent was then distilled off. The residue was then recrystallized from ethanol to obtain 44.8 g of 2-methoxy-6-(4-propylcyclohexa-1-ene-1-yl)naphthalene.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[CH:21]([C:22]3[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][C:23]=3[CH3:29])[C:20]([C:30]([O:32][CH2:33][CH2:34][CH:35]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[O:31])=[C:19]([CH3:48])[NH:18][C:17]=2[CH3:49])=[O:15])[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C([O-])=O>ClCCl>[C:36]1([CH:35]([C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH2:34][CH2:33][O:32][C:30](=[O:31])[C:20]2[C:21]([C:22]3[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][C:23]=3[CH3:29])=[C:16]([C:14]([N:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)=[O:15])[C:17]([CH3:49])=[N:18][C:19]=2[CH3:48])[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1
Reactant: CC1=C(C(=O)OCCC(c2ccccc2)c2ccccc2)C(c2ccc(C)cc2C)C(C(=O)N2CCN(C(=O)OC(C)(C)C)CC2)=C(C)N1
Agent: O=C([O-])C(F)(F)F
Solvent: ClCCl
Product: Cc1ccc(-c2c(C(=O)OCCC(c3ccccc3)c3ccccc3)c(C)nc(C)c2C(=O)N2CCNCC2)c(C)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
274 mg (0.413 mmol) of 4-[4-(2,4-dimethylphenyl)-5-(3,3-diphenylpropoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-3-carbonyl] piperazine-1-carboxylic acid-t-butyl ester was dissolved in 10 ml of dichloromethane. 5 ml of trifluoroacetate was added and stirred at room temperature for 2 hours. After concentration under reduced pressure, saturated aqueous sodium hydrogencarbonate solution was added and the reaction mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by the silica gel chromatography (dichloromethane/methanol=100/1 to 10/1) to obtain the title compound.
Reaction SMILES: [CH2:1]([C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[C:22]([O-])(=[O:24])[CH3:23].[Cl-].[Cl-].[Cl-].[Al+3]>C(Cl)(Cl)Cl>[OH:21][C:18]1[CH:17]=[CH:16][C:15]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])=[CH:20][C:19]=1[C:22](=[O:24])[CH3:23]
Reactant: CC(=O)[O-]
Reactant: CCCCCCCCCCCCCCc1ccc(O)cc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClC(Cl)Cl
Product: CCCCCCCCCCCCCCc1ccc(O)c(C(C)=O)c1
Temperature: 120 °C

Procedure:
A 900 mg portion of 4-tetradecylphenol, acetate was heated at 70° C. under argon and 720 mg of aluminum trichloride was added portionwise. After 2 hours the temperature was raised to 120° C. and the mixture was heated at this temperature for 45 minutes. The mixture was then cooled, diluted with chloroform, washed with 50% aqueous hydrochloric acid then water and dried. The solvents were removed and the residue recrystallized from ether-methanol, giving 850 mg of the desired compound, mp 38.5°-39.5° C.
Reaction SMILES: [NH2:1]/[C:2](/[C:7]#[N:8])=[C:3](\[NH2:6])/[C:4]#[N:5].[C:9]([C:12]#[N:13])(=O)[CH3:10]>>[C:12]([C:9](=[N:6]/[C:3](=[C:2](\[NH2:1])/[C:7]#[N:8])/[C:4]#[N:5])[CH3:10])#[N:13]
Reactant: CC(=O)C#N
Reactant: N#C/C(N)=C(/N)C#N
Product: CC(C#N)=N/C(C#N)=C(\N)C#N
Reaction time: 0.17 h

Procedure:
A mixture of 16 g of diaminomaleonitrile and 12.6 g of acetyl cyanide was stirred with a glass rod whereby an exothermic reaction occurred and the resulting reaction mixture turned into a yellow-colored mixture. After allowing the mixture to stand for 10 minutes, the mixture was washed with small amount of cooled methanol and dried under reduced pressure to obtain 22.65 g (95.9% yield) of crude crystals of α-cynoethylidenediaminomaleonitrile which was found to have a purity sufficient to be used in subsequent reactions. For analysis, a sample of the above crystals was then repeatedly recrystallized from a mixture of methanol and water (3:2 by volume) to obtain α-cyanoethylidenediaminomaleonitrile having a melting point of 220°-221° C as milky white fine crystals.
Reaction SMILES: [N:1]1[NH:2][N:3]=[C:4]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH:5]=1.C(=O)([O-])[O-].[K+].[K+].I[CH:18]([CH3:20])[CH3:19]>C(#N)C>[CH3:19][CH:18]([N:3]1[C:4]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:5][N:1]=[N:2]1)[CH3:20]
Reactant: CCOC(=O)c1cn[nH]n1
Reactant: CC(C)I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCOC(=O)c1cnnn1C(C)C
Temperature: 55 °C
Reaction time: 2 h

Procedure:
A mixture of ethyl 2H-1,2,3-triazole-4-carboxylate (1.5 g), potassium carbonate (2.64 g) and 2-iodopropane (1.91 ml) in dry acetonitrile (30 ml) was stirred at 50-60° C. under nitrogen for 2 h. Further 2-iodopropane (0.955 ml) was added and the mixture was stirred at 50-60° C. under nitrogen for 1.5 h. The mixture was cooled to room temperature and allowed to stand for 4 days. The mixture was filtered through a 2 g silica SPE column eluting with ethyl acetate. The solution was concentrated in vacuo, Purification by chromatography on silica gel (100 g cartridge), eluting with a gradient of 0-100% ethyl acetate in cyclohexane over 40 min gave the title compound (315 mg) as a colourless oil.
Reaction SMILES: [CH3:1]C(C)([O-])C.[K+].C(NC(C)C)(C)C.C([Li])CCC.[Si:19]([O:26][CH:27]([C:37]([F:40])([F:39])[F:38])[CH2:28][CH:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=1)[CH3:30])([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20].CI>>[Si:19]([O:26][CH:27]([C:37]([F:38])([F:40])[F:39])[CH2:28][C:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=1)([CH3:1])[CH3:30])([C:22]([CH3:25])([CH3:23])[CH3:24])([CH3:21])[CH3:20]
Reactant: CC(C)(C)[O-]
Reactant: CC(CC(O[Si](C)(C)C(C)(C)C)C(F)(F)F)c1ccccn1
Agent: [K+]
Agent: [Li]CCCC
Solvent: CI
Solvent: CC(C)NC(C)C
Product: CC(C)(CC(O[Si](C)(C)C(C)(C)C)C(F)(F)F)c1ccccn1
Temperature: -50 °C
Reaction time: 0.5 h
Yield: 61.9 %

Procedure:
To a solution of 3.87 mL (3.87 mmol, 1.5 eq.) of potassium tert-butoxide (1.0 M solution in THF) and 542 μL (3.87 mmol, 1.5 eq.) of diisopropylamine, 1.55 mL (3.87 mmol, 1.5 eq) of n-butyl lithium (2.5 M solution in hexanes) was added dropwise at −75° C. The resulting mixture was allowed to warm to −50° C. over 15 minutes. Then the reaction mixture was treated with 860 mg (2.58 mmol) of 2-[3-(tert-butyldimethylsilanyloxy)-4,4,4-trifluoro-1-methylbutyl]pyridine at −50° C. and the resulting mixture was stirred for 30 minutes at −50° C. The reaction mixture was cooled to −75° C. and treated with 482 μL (7.74 mmol) of methyl iodide and stirred for 1 minute. The reaction mixture was quenched with saturated NH4Cl solution and the product was extracted into ether. The ethereal layer was washed with water and brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography to give 555 mg (62%) of 2-[3-(tert-butyldimethylsilanyloxy)-4,4,4-trifluoro-1,1-dimethylbutyl]pyridine as a colorless oil.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH2:9][CH2:10][CH2:11][N:12]=2)[CH:5]=[CH:6][CH:7]=1.[BH4-].[Na+]>CO>[F:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:9][CH2:10][CH2:11][NH:12]2)[CH:5]=[CH:6][CH:7]=1
Reactant: Fc1cccc(C2=NCCC2)c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: Fc1cccc(C2CCCN2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 69.2 %

Procedure:
To a stirred solution of 5-(3-fluoro-phenyl)-3,4-dihydro-2H-pyrrole (1.10 g, 6.74 mmol) in methanol (40 ml) was added at 0° C. sodium borohydride (0.51 g, 13.4 mmol) and the reaction mixture was stirred at RT for 1 h. Then additional sodium borohydride (0.25 g, 6.61 mmol) was added and stirring was continued for 1 h. The mixture was evaporated, dissolved in saturated NaHCO3-solution (70 ml) and extracted with dichloromethane (2×70 ml). The combined organic layers were washed with brine (70 ml), dried (MgSO4) and evaporated. The crude product was purified by column chromatography on silica gel (dichloromethane/MeOH/NH4OH 15:1:0.1) to give the product (0.77 g, 69%) as a colorless oil, MS: m/e=165 (M+).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([OH:12])=[O:11])=[CH:2]1.[CH2:13](O)[CH3:14]>>[CH2:13]([O:11][C:10]([C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[NH:1][CH:2]=1)=[O:12])[CH3:14]
Reactant: CCO
Reactant: O=C(O)c1c[nH]c2ccccc12
Product: CCOC(=O)c1c[nH]c2ccccc12

Procedure:
The title compound is prepared starting from indole-3-carboxylic acid (commercially available from Aldrich) by esterification with ethanol using standard methods of organic synthesis (e.g. J. March, Advanced Organic Chemistry, Reactions, Mechanisms and Structure (1992, 4th edition) 393–394 (Wiley interscience, New York).
Reaction SMILES: Br[CH2:2][C:3]1[N:4]=[C:5]([CH3:13])[O:6][C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].C(N)(=[S:16])C>C(O)C>[SH:16][CH2:2][C:3]1[N:4]=[C:5]([CH3:13])[O:6][C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9]
Reactant: CCOC(=O)c1oc(C)nc1CBr
Reactant: CC(N)=S
Solvent: CCO
Product: CCOC(=O)c1oc(C)nc1CS
Temperature: 90 °C
Yield: 95 %

Procedure:
5 mmol of ethyl 4-(bromomethyl)-2-methyl-1,3-oxazole-5-carboxylate was dissolved in 50 ml of ethanol, then 5.5 mmol of thioacetoamide was added, then heated up to 90° C. to carry out the reaction for 4 hours. The reacted liquid was cooled down to a room temperature. Ethanol is evaporated out and then the product was purified using column separation with solvents of ethyl acetate and hexane, obtaining ethyl 4-(mercaptomethyl)-2-methyl-1,3-oxazole-5-carboxylate (yield 95%).
Reaction SMILES: [CH2:1]([S:3][CH:4]([CH3:8])[CH2:5][CH2:6][OH:7])[CH3:2].[CH3:9][S:10](Cl)(=[O:12])=[O:11]>C(Cl)Cl>[CH3:9][S:10]([O:7][CH2:6][CH2:5][CH:4]([S:3][CH2:1][CH3:2])[CH3:8])(=[O:12])=[O:11]
Reactant: CCSC(C)CCO
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Product: CCSC(C)CCOS(C)(=O)=O
Reaction time: 2.5 h

Procedure:
3-(Ethylthio)-1-butanol (for example, as prepared for Intermediate 27) (247 mg, 1.84 mmol) was dissolved in DCM (10 ml), and the stirred solution was cooled in an external ice-water bath. Methanesulfonyl chloride (commercially available, for example, from Aldrich) (154 μl, 1.99 mmol) was added and stirring was continued under a nitrogen atmosphere for 2.5 h. The reaction mixture was diluted with further DCM (5 ml) and quenched with saturated aqueous sodium hydrogen carbonate. The layers were separated and the aqueous was extracted with further DCM (×2) (hydrophobic frit). The combined organic solutions were concentrated in vacuo to give the title compound as a colourless oil, which later partially solidified (360 mg, 92%): 1H NMR δ (CDCl3) 4.46-4.32 (2H, m), 3.03 (3H, s), 2.98-2.88 (1H, m), 2.57 (2H, q, J=7.5 Hz), 2.03-1.87 (2H, m), 1.35 (3H, d, J=7 Hz), 1.26 (3H, t, J=7 Hz).
Reaction SMILES: [O:1]=[C:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]1[CH2:12][C:13]([OH:15])=O.[NH2:16][C:17]1[S:18][CH:19]=[C:20]([CH3:26])[C:21]=1[C:22]([O:24][CH3:25])=[O:23]>>[CH3:26][C:20]1[C:21]([C:22]([O:24][CH3:25])=[O:23])=[C:17]([NH:16][C:13](=[O:15])[CH2:12][N:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[CH2:10][CH2:11][C:2]2=[O:1])[S:18][CH:19]=1
Reactant: COC(=O)c1c(C)csc1N
Reactant: O=C(O)CN1C(=O)CCc2ccccc21
Product: COC(=O)c1c(C)csc1NC(=O)CN1C(=O)CCc2ccccc21

Procedure:
The title compound was prepared from 2-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetic acid (0.43 g, 2.09 mmol) and methyl 2-amino-4-methylthiophene-3-carboxylate (0.358 g, 2.09 mmol) according to protocol B. Retention time (min)=6.895, method [7], MS(ESI) 359.1 (M+H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:4]=1[CH:11]([OH:18])[C:12]#[C:13][C:14]([O:16][CH3:17])=[O:15]>C(Cl)Cl.[O-2].[O-2].[Mn+4]>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:4]=1[C:11]([C:12]#[C:13][C:14]([O:16][CH3:17])=[O:15])=[O:18]
Reactant: COC(=O)C#CC(O)c1cc(OC)ccc1OC
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClCCl
Product: COC(=O)C#CC(=O)c1cc(OC)ccc1OC
Reaction time: 1 h

Procedure:
A solution of 13.8 g (55 mm ol) of methyl 4-(2,5-dimethoxyphenyl)-4-hydroxy-2-butynoate in 80 ml of methylene chloride is added dropwise at 0° to a suspension of 139 g (1.6 mol) of manganese dioxide in 350 ml of methylene chloride The reaction mixture was stirred at 0° for 1 hour, filtered over magnesium sulphate and concentrated. Crystallization of the residue from methylene chloride/ether yielded methyl 3-(2,5-dimethoxybenzoyl)propiolate of melting point 70°-71°.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:8][C:7]=1[CH2:19][CH2:20][CH3:21].[OH:22][C:23]1[CH:28]=[CH:27][C:26]([S:29]([NH2:32])(=[O:31])=[O:30])=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[O:12]([C:9]1[CH:10]=[CH:11][C:6]([O:5][CH2:4][CH2:3][CH2:2][O:22][C:23]2[CH:28]=[CH:27][C:26]([S:29]([NH2:32])(=[O:30])=[O:31])=[CH:25][CH:24]=2)=[C:7]([CH2:19][CH2:20][CH3:21])[CH:8]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: CCCc1cc(Oc2ccccc2)ccc1OCCCBr
Reactant: NS(=O)(=O)c1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CCCc1cc(Oc2ccccc2)ccc1OCCCOc1ccc(S(N)(=O)=O)cc1
Temperature: 50 °C
Reaction time: 5 h

Procedure:
To a solution of 1-(3-bromopropoxy)-4-phenoxy-2-propylbenzene (1.01 g, 2.9 mmol) and 4-hydroxybenzenesulfonamide (0.5 g, 2.9 mmol) in dry DMF (29 mL) was added cesium carbonate (1.04 g, 3.2 mmol). The resulting suspension was stirred in a 50° C. oil bath for 5 h. After cooling to room temperature, the reaction suspension was concentrated under vacuum to a residue, which was then partitioned between ethyl acetate and water. The ethyl acetate phase was dried over sodium sulfate, filtered, and concentrated to an oil. The oil was chromatographed over silica gel with hexanes/ethyl acetate (2:1) to isolate the title compound.,
Reaction SMILES: Cl[CH2:2][C:3]1[C:4](=[O:13])[O:5][C:6]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2.C(=O)([O-])[O-].[K+].[K+].C1OCCOCCOCCOCCOCCOC1.[OH:38][CH2:39][CH2:40][C:41](=[O:43])[CH3:42]>C1COCC1>[O:43]=[C:41]([CH3:42])[CH2:40][CH2:39][O:38][CH2:2][C:3]1[C:4](=[O:13])[O:5][C:6]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2
Reactant: CC(=O)CCO
Reactant: O=c1oc2ccccc2cc1CCl
Agent: C1COCCOCCOCCOCCOCCO1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CC(=O)CCOCc1cc2ccccc2oc1=O
Temperature: 25 °C

Procedure:
3-(Chloromethyl)-2H-chromen-2-one (19.461 g, 100 mmol) is dissolved into 100 mL of anhydrous THF in a three neck flask equipped with a condenser, stir bar, and argon inlet. To the mixture is added 27.6 g (200 mmol) of anhydrous potassium carbonate and 2.0 g of 18-crown-6. 4-Hydroxy-2-butanone (16.2 g, 200 mmol) is added and the system is refluxed for 16 hours, cooled to room temperature, filtered, and the organic solvents are removed by rotary evaporation. The solid organic residue is purified by column chromatography using 3:1 ethyl acetate:hexanes to yield 3-(3-oxo-butoxymethyl)-chromen-2-one.