Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br.[CH3:2][C:3]1[C:4]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:26]=2)=[N:5][C:6]2[C:11]([C:12]=1[C:13]([O:15]C)=[O:14])=[CH:10][C:9]([S:17]([CH:20]([CH3:22])[CH3:21])(=[O:19])=[O:18])=[C:8]([O:23]C)[CH:7]=2>C(O)(=O)C.O>[OH:23][C:8]1[CH:7]=[C:6]2[C:11]([C:12]([C:13]([OH:15])=[O:14])=[C:3]([CH3:2])[C:4]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:33])([F:34])[F:32])[CH:26]=3)=[N:5]2)=[CH:10][C:9]=1[S:17]([CH:20]([CH3:22])[CH3:21])(=[O:19])=[O:18]
Reactant: COC(=O)c1c(C)c(-c2cccc(C(F)(F)F)c2)nc2cc(OC)c(S(=O)(=O)C(C)C)cc12
Agent: Br
Solvent: O
Solvent: CC(=O)O
Product: Cc1c(-c2cccc(C(F)(F)F)c2)nc2cc(O)c(S(=O)(=O)C(C)C)cc2c1C(=O)O
Temperature: 25 °C
Yield: 94.1 %

Procedure:
Hydrobromic acid (80 mL, 1467 mmol) was added slowly to a solution of methyl 3-methyl-6-[(1-methylethyl)sulfonyl]-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (14.13 g, 29.3 mmol) in acetic acid (30 mL). The mixture was heated to reflux for 5 days. The mixture was cooled to room temperature and diluted with water. The solids were collected by filtration, washed with water, and dried to afford 7-hydroxy-3-methyl-6-[(1-methylethyl)sulfonyl]-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (12.5 g, 94% yield). 1H NMR (400 MHz, DMSO-d6) δ11.73 (br. s., 1H), 8.31 (s, 1H), 7.94-8.00 (m, 2H), 7.91 (d, J=7.78 Hz, 1H), 7.79 (t, J=7.65 Hz, 1H), 7.54 (s, 1H), 3.91 (dt, J=6.81, 13.74 Hz, 1H), 2.35 (s, 3H), 1.22 (s, 3H), 1.21 (s, 3H); MS (m/z) 454.1 (M+H+).
Reaction SMILES: [C:1]([O:5][C:6](=[O:47])[C@@H:7]([NH:20][C:21](=[O:46])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][C:33]1[CH:38]=[CH:37][C:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])=[CH:35][CH:34]=1)[CH2:8][CH2:9][C:10]([O:12]CC1C=CC=CC=1)=[O:11])([CH3:4])([CH3:3])[CH3:2]>C1COCC1.[Pd]>[C:1]([O:5][C:6](=[O:47])[C@@H:7]([NH:20][C:21](=[O:46])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][C:33]1[CH:34]=[CH:35][C:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])=[CH:37][CH:38]=1)[CH2:8][CH2:9][C:10]([OH:12])=[O:11])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)c1ccc(CCCCCCCCCCCC(=O)N[C@@H](CCC(=O)OCc2ccccc2)C(=O)OC(C)(C)C)cc1
Agent: [Pd]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)c1ccc(CCCCCCCCCCCC(=O)N[C@@H](CCC(=O)O)C(=O)OC(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 98.9 %

Procedure:
(S)-2-[12-(4-tert-Butoxycarbonylphenyl) dodecanoylamino]pentanedioic acid 5-benzyl ester 1-tert-butyl ester (175 mg, 0.27 mmol) was dissolved in THF and placed under nitrogen. 10% palladium on carbon (ca. 20 mg) was added, and the flask was evacuated and filled with nitrogen three times. The flask was equipped with balloon filled with hydrogen, and stirred at rt overnight. The solution was filtered through celite, washing with THF. The filtrate was concentrated under vacuum to yield an oil (0.15 g).
Reaction SMILES: [Br:1]Br.[CH:3]1[C:19]2=[C:20]3[C:10]([C:11]([C:13]4[C:18]2=[CH:17][CH:16]=[CH:15][CH:14]=4)=[O:12])=[CH:9][CH:8]=[CH:7][C:6]3=[CH:5][CH:4]=1.O>C(O)(=O)C>[Br:1][C:5]1[CH:4]=[CH:3][C:19]2[C:18]3[C:13]([C:11](=[O:12])[C:10]4[C:20]=2[C:6]=1[CH:7]=[CH:8][CH:9]=4)=[CH:14][CH:15]=[CH:16][CH:17]=3
Reactant: O=C1c2ccccc2-c2cccc3cccc1c23
Reactant: BrBr
Solvent: O
Solvent: CC(=O)O
Product: O=C1c2ccccc2-c2ccc(Br)c3cccc1c23
Yield: 68.1 %

Procedure:
A solution of 11.2 g of bromine in 20.5 g of acetic acid was added dropwise to a mixture of 11.5 g of benzanthrone, 184 g of acetic acid and 23 g of water with stirring. The total mixture was heated with stirring to 100° C for 5.5 hours. The precipitated crystals were filtered and washed with water and dried. The product was recrystallized from a mixture of 88.3 g of chlorobenzene and 6.3 g of methanol whereby 10.52 g of 3-bromobenzanthrone were obtained.
Reaction SMILES: N([O-])=O.[Na+].[NH2:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:8][CH:7]=1.[N-:18]=[N+:19]=[N-].[Na+]>C(O)(C(F)(F)F)=O>[N:5]([C:6]1[CH:7]=[CH:8][C:9]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:10][CH:11]=1)=[N+:18]=[N-:19]
Reactant: [N-]=[N+]=[N-]
Reactant: CCOC(=O)Cc1ccc(N)cc1
Agent: O=N[O-]
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Product: CCOC(=O)Cc1ccc(N=[N+]=[N-])cc1
Yield: 92.2 %

Procedure:
Following the general procedure of Marchesini (J. Org. Chem. 49, p. 4287-4290, 1984), sodium nitrite (38 g, 0.56 mol) was slowly added to a stirred and cooled (0° C.) mixture of ethyl 4-aminophenylacetate (25 g, 0.14 mol) in 700 mL of TFA. After the addition was complete, the reaction was stirred at 0° C. for another 0.5 hour and then sodium azide (27 g, 0.42 mol) was slowly added over a period of 0.5 hours. The mixture was stirred for another 2 hours at 0° C. and then quenched with ice water and the product was extracted with EtOAc. The organic phase was washed with water, dried over magnesium sulfate, filtered, concentrated to yield 26.5 g (90%) of the title compound as a white solid. 1H NMR (300 MHz, DMSO-d6) δ7.31 (d, J=8 Hz, 2H), 7.07 (d, J=7 Hz, 2H), 4.07 (q, J=7 Hz, 2H), 3.66 (s, 2H), 1.17 (t, J=7 Hz, 3H).
Reaction SMILES: [ClH:1].Cl.[NH2:3][C:4]1[S:16][C:7]2[CH2:8][CH2:9][N:10]([CH2:13][CH2:14][CH3:15])[CH2:11][CH2:12][C:6]=2[CH:5]=1.[S-:17][C:18]#[N:19].[K+].BrBr>>[ClH:1].[ClH:1].[NH2:19][C:18]1[S:17][C:5]2[C:6]3[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][CH3:15])[CH2:9][CH2:8][C:7]=3[S:16][C:4]=2[N:3]=1
Reactant: CCCN1CCc2cc(N)sc2CC1
Reactant: N#C[S-]
Agent: BrBr
Agent: Cl
Agent: [K+]
Product: CCCN1CCc2sc3nc(N)sc3c2CC1

Procedure:
This compound was prepared from 2-amino-6-propyl-5,6,7,8-tetrahydro-4H-thieno[2,3-d]azepine dihydrochloride, potassium thiocyanate and bromine analogous to Example 1.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH2:11][C:12](=[O:18])[NH:13]3)=[CH:5][CH:4]=1.[N:19]1([CH2:24][CH2:25][NH:26][C:27]([C:29]2[C:33]([CH3:34])=[C:32]([CH:35]=O)[NH:31][C:30]=2[CH3:37])=[O:28])[CH:23]=[CH:22][N:21]=[N:20]1>C(O)C.N1CCCCC1>[N:19]1([CH2:24][CH2:25][NH:26][C:27]([C:29]2[C:33]([CH3:34])=[C:32]([CH:35]=[C:11]3[C:10]4[C:14](=[CH:15][CH:16]=[CH:17][C:9]=4[C:6]4[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)[NH:13][C:12]3=[O:18])[NH:31][C:30]=2[CH3:37])=[O:28])[CH:23]=[CH:22][N:21]=[N:20]1
Reactant: Cc1[nH]c(C=O)c(C)c1C(=O)NCCn1ccnn1
Reactant: COc1ccc(-c2cccc3c2CC(=O)N3)cc1
Solvent: CCO
Solvent: C1CCNCC1
Product: COc1ccc(-c2cccc3c2C(=Cc2[nH]c(C)c(C(=O)NCCn4ccnn4)c2C)C(=O)N3)cc1
Temperature: 25 °C
Reaction time: 72 h
Yield: 44.8 %

Procedure:
To a solution of 4-(4-methoxy-phenyl)-1,3-dihydro-indol-2-one (59.8 mg, 0.25 mmol) and 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-[1,2,3]triazol-1-yl-ethyl)-amide (67.9 mg, 0.25 mmol) in ethanol (2 mL) was added piperidine (3 drops). The reaction mixture was stirred at room temperature for three days. A yellow solid product was precipitated out, filtered, washed by ethanol for three times, and dried under high vacuum to provide pure product 5-[4-(4-methoxy-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-[1,2,3]triazol-1-yl-ethyl)-amide as a yellow solid (54 mg, 45%).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[C:8]([Cl:10])[CH:7]=[CH:6][C:5]=1[N:11]=[N:12][C:13]1[CH:18]=[C:17]([CH3:19])[CH:16]=[C:15]([C:20]([CH3:23])([CH3:22])[CH3:21])[C:14]=1[OH:24])([O-])=O.[OH-].[Na+].C1C2C(=[O:40])C3C(=CC=CC=3)C=2C=CC=1.N(C1C=CC=CC=1)=NC1C=CC=CC=1.C1C(O)=CC(O)=C(C(C2C=CC(O)=CC=2O)=O)C=1.S(=O)(=O)(O)O>O.C(O)CCC>[OH:24][C:14]1[C:15]([C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:16][C:17]([CH3:19])=[CH:18][C:13]=1[N:12]1[N+:11]([O-:40])=[C:5]2[CH:6]=[CH:7][C:8]([Cl:10])=[CH:9][C:4]2=[N:1]1
Reactant: O=C1c2ccccc2-c2ccccc21
Reactant: Cc1cc(N=Nc2ccc(Cl)cc2[N+](=O)[O-])c(O)c(C(C)(C)C)c1
Agent: O=C(c1ccc(O)cc1O)c1ccc(O)cc1O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Solvent: CCCCO
Product: Cc1cc(-n2nc3cc(Cl)ccc3[n+]2[O-])c(O)c(C(C)(C)C)c1
Temperature: 65 °C
Reaction time: 5 h
Yield: 829.1 %

Procedure:
2-nitro-4-chloro-2'-hydroxy-3'-t-butyl-5'-methylazobenzene 23.2 g was added to a mixture of n-butanol 60 g, water 10.6 g and 97% sodium hydroxide 6.9 g, and the resultant mixture was stirred while raising temperature to 65° C. Thereafter, the mixture was cooled to 50° C., and 9-fluorenone 1.5 g was added to the mixture. The reaction mixture was then heated to 90° C. in one hour, and the mixture was stirred at 90°~96° C. for five hours to effect reaction, thus almost all of the azobenzene having disappeared to finish the reaction of Process (b). Thereafter, water 50 ml was added to the reaction mixture, and the mixture was neutralized to pH 8~9 with 62% sulfuric acid 10 g. The neutralized liquor was cooled to 20° C. to precipitate a crystal. The crystal thus precipitated was separated by filtration, thus producing the wet product 22.9 g of 2-(2-hydroxy-3-t-butyl-5-methylphenyl)-5-chlorobenzotriazole-N-oxide (dry product: 20.6 g, yield: 93.0%, melting point: 160°~163° C.).
Reaction SMILES: Cl[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:6]([Cl:13])[N:5]=[C:4]([S:14][CH3:15])[N:3]=1.[CH3:16][O:17][C:18]1[CH:33]=[CH:32][C:21]([CH2:22][NH:23][CH2:24][CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:20][CH:19]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:13][C:6]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:2]([N:23]([CH2:24][CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:22][C:21]2[CH:20]=[CH:19][C:18]([O:17][CH3:16])=[CH:33][CH:32]=2)[N:3]=[C:4]([S:14][CH3:15])[N:5]=1
Reactant: CCOC(=O)c1c(Cl)nc(SC)nc1Cl
Reactant: CCOC(=O)CCCNCc1ccc(OC)cc1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)CCCN(Cc1ccc(OC)cc1)c1nc(SC)nc(Cl)c1C(=O)OCC
Temperature: 80 °C
Yield: 57.3 %

Procedure:
The mixture of ethyl 4,6-dichloro-2-(methylthio)pyrimidine-5-carboxylate (7.9 g, 29.88 mmol) and ethyl 4-((4-methoxybenzyl)amino)butanoate (5 g, 19.92 mmol) in DMF (500 mL) and DIPEA (4.6 g, 35.85 mmol) was heated at 80° C. for 2 h. The reaction mixture was then cooled to room temperature and crushed ice was added. The reaction mixture was extracted with EtOAc (3×100 mL), and the combined EtOAc layer was dried over sodium sulphate, filtered and evaporated under reduced pressure to give a residue which was purified by column chromatography (silica gel, gradient 0-5% EtOAc in hexanes) to afford ethyl 4-chloro-6-((4-ethoxy-4-oxobutyl)(4-methoxybenzyl)amino)-2-(methylthio)pyrimidine-5-carboxylate (5.5 g, 40%). 1H NMR (400 MHz, CDCl3): δ 7.12 (d, J=8.4 Hz, 2H), 6.85 (d, J=8.4 Hz, 2H), 4.66 (s, 2H), 4.16 (q, J=6.8 Hz, 2H), 4.10 (q, J=7.2 Hz, 2H), 3.79 (s, 3H), 3.42 (t, J=7.6 Hz, 2H), 2.45 (s, 3H), 2.24 (t, J=6.8 Hz, 2H), 1.94 (quintet, J=7.2 Hz, 2H), 1.24 (t, J=7.2 Hz, 3H), 1.22 (t, J=7.2 Hz, 3H). LCMS [M+H]: 482
Reaction SMILES: C(O)(C(F)(F)F)=O.[C:8]([NH:11][C:12]1[CH:21]=[C:20]2[C:15]([CH:16]=[C:17]([C:23]3[C:24]([F:38])=[CH:25][C:26]([F:37])=[C:27]([NH:29]C(=O)OC(C)(C)C)[CH:28]=3)[C:18]([CH3:22])=[N:19]2)=[CH:14][N:13]=1)(=[O:10])[CH3:9]>C(Cl)Cl>[NH2:29][C:27]1[C:26]([F:37])=[CH:25][C:24]([F:38])=[C:23]([C:17]2[C:18]([CH3:22])=[N:19][C:20]3[C:15]([CH:16]=2)=[CH:14][N:13]=[C:12]([NH:11][C:8](=[O:10])[CH3:9])[CH:21]=3)[CH:28]=1
Reactant: CC(=O)Nc1cc2nc(C)c(-c3cc(NC(=O)OC(C)(C)C)c(F)cc3F)cc2cn1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC(=O)Nc1cc2nc(C)c(-c3cc(N)c(F)cc3F)cc2cn1
Temperature: 25 °C
Reaction time: 16 h
Yield: 81 %

Procedure:
Add TFA (5 mL, 64.9 mmol) to a solution of tert-butyl (5-(7-acetamido-2-methyl-1,6-naphthyridin-3-yl)-2,4-difluorophenyl)carbamate (0.63 g, 1.470 mmol) in DCM (5 mL), stir at RT for 16 h, then concentrate to dryness. Neutralize with satd. NaHCO3, extract with EtOAc/THF (1×), wash the organic layer with brine, dry over MgSO4 and concentrate to dryness. Triturate with THF/Hex, collect the solids via filtration and dry to afford the title compound (391 mg, 81%) as a tan solid. 1H NMR (400 MHz, DMSO-d6): δ 10.76 (s, 1H), 9.13 (d, J=0.84 Hz, 1H), 8.49 (s, 1H), 8.25 (s, 1H), 7.21 (dd, J=11.28, 9.65 Hz, 1H), 6.76 (dd, J=9.87, 7.72 Hz, 1H), 5.18 (s, 2H), 2.49 (s, 3H), 2.15 (s, 3H); MS (ESI) m/z: 329.1 (M+H+).
Reaction SMILES: [C:1]1([NH:7][NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:23](Cl)=[O:24])=[CH:19][CH:18]=1>CCOCC>[C:1]1([NH:7][NH:8][C:23](=[O:24])[C:20]2[CH:21]=[CH:22][C:17]([F:16])=[CH:18][CH:19]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NNc1ccccc1
Reactant: O=C(Cl)c1ccc(F)cc1
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: O=C(NNc1ccccc1)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 60111.8 %

Procedure:
A mixture of phenylhydrazine (25 ml, 0.25 mmole) and triethylamine (35 ml, 0.25 mmole) in anhydrous ether (500 ml) was cooled down to -5° to -10° C. (ice-salt bath) under nitrogen and treated dropwise, over a 30 minute period, with 4-fluorobenzene carbonyl chloride (30 ml, 0.25 mole). The reaction mixture was warmed to room temperature, stirred for 3.0 hours, then filtered, washing the solids well with ether (200 ml). The solids were dissolved in dichloromethane (600 ml), stripped to near dryness, suspended in hexane (600 ml) and filtered. The clear filtrate was evaporated to dryness, triturated with tetrahydrofuran (700 ml) and filtered, washing the solids well with tetrahydrofuran (100 ml). The filtrate was evaporated to dryness and dried in vacuo to give a crude product (34.6 g) contaminated with two other components.
Reaction SMILES: [CH:1]#[C:2][CH2:3][NH:4][C@H:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[CH2:7][CH2:6]1.[C:14]([OH:26])(=[O:25])[CH2:15][C:16]([CH2:21][C:22]([OH:24])=[O:23])([C:18]([OH:20])=[O:19])[OH:17]>CC(C)=O>[CH:1]#[C:2][CH2:3][NH:4][C@H:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[CH2:7][CH2:6]1.[C:14]([O-:26])(=[O:25])[CH2:15][C:16]([CH2:21][C:22]([O-:24])=[O:23])([C:18]([O-:20])=[O:19])[OH:17]
Reactant: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: C#CCN[C@@H]1CCc2ccccc21
Solvent: CC(C)=O
Product: O=C([O-])CC(O)(CC(=O)[O-])C(=O)[O-]
Reaction time: 6 h

Procedure:
To a solution of 100 mg (0.58 mmol) rasagiline in 1 ml acetone a solution of 117 mg (0.61 mmol, 1.05 eq) anhydrous citric acid in 1 ml warm acetone was added. The solution became turbid during addition forming a waxy precipitate. The supernatant was removed and the wax was washed with 2 ml acetone twice using sonication. On drying in high vacuum a white solid foam was obtained. Drying was continued for 6 h on high vacuum (120 mg, 0.33 mmol, 57%).
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C([O-])([O-])=O.[K+].[K+].CS(C)=O.F[C:17]1[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=1>O>[N:1]1([C:17]2[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: N#Cc1ccc(F)cc1
Reactant: c1c[nH]cn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: N#Cc1ccc(-n2ccnc2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 31.9 %

Procedure:
To a mixture of imidazole (5.13 g, 75.35 mmol) , K2CO3 (11.45 g) and DMSO (50 ml) at room temperature was added to 4-fluorobenzonitrile (10.04 g) in one portion. The reaction mixture was stirred at room temperature for 1 hour, and then was warmed on a steam for 2 hours. The reaction mixture was cooled to room temperature, and poured into cold water. A precipitate formed which was collected by filtration and washed with water and recrystallized from CHCl3 /hexane to afford 4.07 g of 4-(1-imidazolyl)benzonitrile, m.p. 146°-148° C.
Reaction SMILES: [CH:1]1[C:13]2[CH:12]([C:14](O)=[O:15])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)C(Cl)=O.CN(C=O)C.[CH2:28]([NH2:31])[CH2:29][CH3:30]>C(Cl)Cl.C1COCC1.C(OCC)(=O)C.O>[CH2:28]([NH:31][C:14]([CH:12]1[C:11]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[C:5]2[C:13]1=[CH:1][CH:2]=[CH:3][CH:4]=2)=[O:15])[CH2:29][CH3:30]
Reactant: CCCN
Reactant: O=C(O)C1c2ccccc2-c2ccccc21
Agent: O=C(Cl)C(=O)Cl
Solvent: O
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CCCNC(=O)C1c2ccccc2-c2ccccc21
Temperature: -40 °C
Reaction time: 0.75 h
Yield: 73.3 %

Procedure:
A solution of 9-fluorene carboxylic acid (20.0 g, 95 mmol) in 200 mL of CH2Cl2 was treated with oxalyl chloride (12.5 g, 105 mmol) and 0.2 mL of DMF. After 0.75 h, the mixture was concentrated under reduced pressure to give a white solid. The solid was diluted with 100 mL of THF cooled to −40° C., treated with propylamine (11.8 g, 200 mmol). The suspension was stirred for 3 h at room temperature and diluted with ethyl acetate and water. The organic fraction was dried over Na2SO4 and concentrated to a white solid. The solid purified by trituration with hot hexanes and recrystalization from hot methanol to give 17.5 g (87%) of title compound as white flakes. mp 197-199° C.
Reaction SMILES: C(O)(=O)/C=C/C(O)=O.[CH:9]1([N:15]2[CH2:19][CH2:18][CH:17]([N:20]([CH3:32])[C:21](=O)[C:22]3[CH:27]=[CH:26][C:25]([N+:28]([O-:30])=[O:29])=[CH:24][CH:23]=3)[CH2:16]2)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.[OH-].[Na+].[S-2:35].[K+].[K+]>C1C=CC=CC=1>[CH:9]1([N:15]2[CH2:19][CH2:18][CH:17]([N:20]([CH3:32])[C:21](=[S:35])[C:22]3[CH:27]=[CH:26][C:25]([N+:28]([O-:30])=[O:29])=[CH:24][CH:23]=3)[CH2:16]2)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1
Reactant: CN(C(=O)c1ccc([N+](=O)[O-])cc1)C1CCN(C2CCCCC2)C1
Reactant: [S-2]
Agent: O=C(O)/C=C/C(=O)O
Agent: [K+]
Agent: [Na+]
Solvent: c1ccccc1
Product: CN(C(=S)c1ccc([N+](=O)[O-])cc1)C1CCN(C2CCCCC2)C1

Procedure:
Twenty-five grams (0.56 mole) of N-(1-cyclohexyl-3-pyrrolidinyl)-p-nitro-N-methylbenzamide fumarate was partitioned between dil. sodium hydroxide and 400 ml. benzene. The benzene solution was dried with sodium sulfate and distilled to a volume of 250 ml. To this was added a finely ground mixture of 10 g. (0.045 mole) of phosphorous pentasulfide and 10 g. of potassium sulfide. The mixture was refluxed 4 hours and an additional 10 g. of phosphorous pentasulfide added and refluxed 2 hours. The benzene was decanted off of the hard solid. The solid was partitioned between dil. sodium hydroxide and chloroform. The chloroform was dried, concentrated and the residue crystallized twice from isopropyl ether-ethyl acetate. Yield 3.77 g. (19.5%); m.p. 108°-110°C.
Reaction SMILES: [CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][CH:2]2[NH:8][C:9]([NH2:11])=[S:10].Br[C:13]([CH3:20])([CH3:19])[C:14](OCC)=[O:15]>>[CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][CH:2]2[NH:8][C:9]1[S:10][C:13]([CH3:20])([CH3:19])[C:14](=[O:15])[N:11]=1
Reactant: NC(=S)NC1CC2CCC1C2
Reactant: CCOC(=O)C(C)(C)Br
Product: CC1(C)SC(NC2CC3CCC2C3)=NC1=O

Procedure:
Synthesis was performed from N-bicyclo[2.2.1]hept-2-ylthiourea and Ethyl 2-bromoisobutyrate according to Method C.
Reaction SMILES: [CH2:1]=[CH:2][CH3:3].[CH3:4][C:5]1[CH:6]=[C:7]([OH:12])[CH:8]=[C:9]([CH3:11])[CH:10]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>>[CH3:1][C:2]1[C:8]([CH:9]([CH3:11])[CH3:10])=[C:7]([OH:12])[CH:6]=[C:5]([CH3:4])[CH:3]=1
Reactant: C=CC
Reactant: Cc1cc(C)cc(O)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Product: Cc1cc(C)c(C(C)C)c(O)c1
Reaction time: 3 h
Yield: 23.2 %

Procedure:
63 g of propylene are introduced into 244 g of 3,5-dimethylphenol and 22 g of p-toluene sulphonic acid at 120° C. Thereupon the mixture is stirred at this temperature for 3 h. The catalyst is removed by washing with sodium hydrogen carbonate solution. Then the mixture is fractionated. At boiling point 120° C (12 mm Hg) 57 g of 3,5-dimethyl-2-isopropylphenol are obtained.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:43])[CH:5]([C:15]1[CH:20]=[C:19]([O:21][CH2:22][CH3:23])[CH:18]=[C:17]([O:24][Si](C(C)(C)C)(C2C=CC=CC=2)C2C=CC=CC=2)[C:16]=1[F:42])[NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]#[N:14])=[CH:9][CH:8]=1)[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.CCOC(C)=O>C1COCC1>[CH2:1]([O:3][C:4](=[O:43])[CH:5]([NH:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]#[N:14])=[CH:11][CH:12]=1)[C:15]1[CH:20]=[C:19]([O:21][CH2:22][CH3:23])[CH:18]=[C:17]([OH:24])[C:16]=1[F:42])[CH3:2]
Reactant: CCOC(=O)C(Nc1ccc(C#N)cc1)c1cc(OCC)cc(O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)c1F
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCOC(=O)C(Nc1ccc(C#N)cc1)c1cc(OCC)cc(O)c1F
Temperature: 0 °C
Reaction time: 4 h
Yield: 77.8 %

Procedure:
A solution of 27.6 g (RS)-[3-(tert-butyl-diphenyl-silanyloxy)-5-ethoxy-2-fluoro-phenyl]-(4-cyano-phenylamino)-acetic acid ethyl ester described in example 3.4 in 470 ml THF was cooled to 0° C. and treated with 50.9 ml 1M tetrabutylammonium fluoride solution in THF. The reaction mixture was stirred at 0° C. for 4 hrs. The crude product was isolated by extraction with EtOAc and purified by chromatography on silica gel (cyclohexane/EtOAc) to yield 12.89 g (RS)-(4-cyano-phenylamino)-(5-ethoxy-2-fluoro-3-hydroxy-phenyl)-acetic acid ethyl ester as a yellow semisolid.
Reaction SMILES: [CH3:1][CH:2]([CH2:4][CH2:5][CH2:6][C@H:7]([CH2:9][CH2:10][CH2:11][C@H:12]([CH2:14][CH2:15][CH2:16]/[C:17](=[CH:19]/[CH2:20][OH:21])/[CH3:18])[CH3:13])[CH3:8])[CH3:3].C([O:26]O)(C)(C)C.S([O-])([O-])=O.[Na+].[Na+].[OH-].[Na+]>[O-2].[O-2].[O-2].[O-2].[O-2].[V+5].[V+5]>[O:26]1[C:17]([CH3:18])([CH2:16][CH2:15][CH2:14][CH:12]([CH3:13])[CH2:11][CH2:10][CH2:9][CH:7]([CH3:8])[CH2:6][CH2:5][CH2:4][CH:2]([CH3:1])[CH3:3])[CH:19]1[CH2:20][OH:21]
Reactant: CC(C)(C)OO
Reactant: C/C(=C\CO)CCC[C@H](C)CCC[C@H](C)CCCC(C)C
Agent: [V+5]
Agent: O=S([O-])[O-]
Agent: [Na+]
Product: CC(C)CCCC(C)CCCC(C)CCCC1(C)OC1CO
Temperature: 25 °C
Reaction time: 6 h
Yield: 96 %

Procedure:
A Three-necked flask of 2-liter capacity, fitted with a stirrer, reflux-condenser and thermometer, was charged with 463.6 g (1.57 moles) of phytol, 221.8 g (1.72 moles) of a 70% (by weight) aqueous solution of t-butyl hydroperoxide and 710 mg of vanadium pentoxide and the reaction was conducted at 90° C. for 6 hours. Then, 350.4 g of a 14% (by weight) aqueous solution of sodium sulfite was added and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was transferred to a separatory funnel. The upper layer was mixed with the same volume of 1N aqueous sodium hydroxide solution and stirred at room temperature and, then, extracted with n-hexane. The extract was washed with the same volume of water 3 times and the n-hexane was distilled off to give 467.0 g (yield 96%) of 2,3-epoxy-3,7,11,15-tetramethylhexadecan-1-ol.
Reaction SMILES: [F:1][C:2](I)([F:25])[C:3]([F:24])([F:23])[C:4]([F:22])([F:21])[C:5]([F:20])([F:19])[C:6]([F:18])([F:17])[C:7]([F:16])([F:15])[C:8]([F:14])([F:13])[C:9]([F:12])([F:11])[F:10].S(S([O-])=O)([O-])=O.[Na+].[Na+].P([O-])([O-])(O)=O.[Na+].[Na+].[CH3:42][S:43]SC>CN(C)C=O.O>[F:1][C:2]([S:43][CH3:42])([F:25])[C:3]([F:24])([F:23])[C:4]([F:22])([F:21])[C:5]([F:20])([F:19])[C:6]([F:18])([F:17])[C:7]([F:16])([F:15])[C:8]([F:14])([F:13])[C:9]([F:12])([F:11])[F:10]
Reactant: FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)I
Reactant: CSSC
Agent: O=P([O-])([O-])O
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CSC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Yield: 20 %

Procedure:
Perfluorooctyl iodide (5.5 g), sodium dithionite (3 g), sodium hydrogen phosphate (3 g) and methyl disulphide (1 g) are stirred in dimethylformamide (10 cc) and water (5 cc) for 6 hours. After the usual treatment, methyl perfluorooctyl sulphide is obtained in 20% yield.