Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([O:9][C:10]2[C:15]([F:16])=[C:14]([CH3:17])[CH:13]=[CH:12][C:11]=2[Cl:18])[CH:5]=[C:6]([Cl:8])[CH:7]=1.C1C(=O)N([Br:26])C(=O)C1.CC(N=NC(C#N)(C)C)(C#N)C>C(Cl)(Cl)(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([O:9][C:10]2[C:15]([F:16])=[C:14]([CH2:17][Br:26])[CH:13]=[CH:12][C:11]=2[Cl:18])[CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1ccc(Cl)c(Oc2cc(Cl)cc(Br)c2)c1F
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Product: Fc1c(CBr)ccc(Cl)c1Oc1cc(Cl)cc(Br)c1
Temperature: 80 °C
Reaction time: 8 h
Yield: 48.7 %

Procedure:
To a solution of 2-[(3-bromo-5-chlorophenyl)oxy]-1-chloro-3-fluoro-4-methylbenzene (9.69 g, 27.7 mmol) and NBS (4.93 g, 27.7 mmol) in carbon tetrachloride (250 ml) was added AIBN (0.227 g, 1.384 mmol) and the mixture was stirred at 80° C. overnight. An additional portion of AIBN (0.227 g, 1.384 mmol) was added and the mixture was stirred for another 4 hours. The mixture was cooled to rt, the solvent was removed and the crude material was purified via silica gel chromatography to give 2-[(3-bromo-5-chlorophenyl)oxy]-4-(bromomethyl)-1-chloro-3-fluorobenzene (5.78 g, 49% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.38-7.67 (m, 3H), 7.10 (s, 1H), 6.98-7.07 (m, 1H), 4.70 (s, 2H)
Reaction SMILES: C([CH:3]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=CO[C:4]1=[O:14])#N.C1(=[O:20])CCCC1.C(C(C#N)=C1C=C(C)OC(C)=C1)#N.[N:34]1[CH:39]=[CH:38]C=[CH:36][CH:35]=1>>[CH2:35]([N:34]([C:11]1[CH:12]=[CH:13][C:8]2[CH:7]=[C:3]([CH:4]=[O:14])[O:20][C:9]=2[CH:10]=1)[CH2:39][CH3:38])[CH3:36]
Reactant: O=C1CCCC1
Reactant: c1ccncc1
Reactant: N#CC1C(=O)OC=C1c1ccccc1
Agent: CC1=CC(=C(C#N)C#N)C=C(C)O1
Product: CCN(CC)c1ccc2cc(C=O)oc2c1

Procedure:
The new dyes of this invention are prepared by condensation of the new intermediates of Examples 1 and 2 in pyridine with an active methylene compound such as 3-cyano-4-phenyl-2-furanone, cyclopentanone, 4-dicyanomethylene-2,6-dimethyl-4H-pyran, 3-acetyl-7-(N,N-dialkylamino)coumarins and the like.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1>[Rh]>[CH2:9]1[C:10]2[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=2)[CH2:6][CH2:7][CH2:8]1.[CH2:9]1[CH:10]2[CH:5]([CH2:4][CH2:3][CH2:2][CH2:1]2)[CH2:6][CH2:7][CH2:8]1
Reactant: c1ccc2ccccc2c1
Agent: [Rh]
Product: C1CCC2CCCCC2C1
Product: c1ccc2c(c1)CCCC2

Procedure:
Hydrogenation of naphthalene, a PAH, was carried out by mixing 0.1 M naphthalene in the presence of Rh/C with H2 (60 bar, 870 psi) and scCO2 (100 bar, 1450 psi) at 60° C. The percentage of tetralin and decalin formed was analyzed at 30 minutes, 1 hour, 2 hours, 3 hours and 4 hours. FIG. 3 is a graph showing the hydrogenation of naphthalene as a function of time, in which the amount of naphthalene is indicated by diamonds, the amount of tetralin is indicated by squares, and the amount of decalin is indicated by triangles. The vertical axis represents relative concentration of hydrocarbon in percent total hydrocarbon, and the horizontal axis represents duration of the reaction process in units of hours.
Reaction SMILES: [CH2:1]([C:5]([CH2:10][CH3:11])([CH2:8][OH:9])[CH2:6][OH:7])[CH2:2][CH2:3][CH3:4].[C:12]1([CH3:18])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(C1C=CC(S(O)(=O)=O)=CC=1)C.[CH2:31]([O:33][C:34](OCC)(OCC)[O:35][CH2:36]C)C>[Cl-].[Na+].O.C(N(CC)CC)C>[CH2:1]([C:5]1([CH2:10][CH3:11])[CH2:6][O:7][C:34]2([O:35][CH2:36][C:17]([CH2:16][CH2:15][CH2:14][CH3:13])([CH2:12][CH3:18])[CH2:31][O:33]2)[O:9][CH2:8]1)[CH2:2][CH2:3][CH3:4]
Reactant: CCOC(OCC)(OCC)OCC
Reactant: CCCCC(CC)(CO)CO
Reactant: Cc1ccccc1
Agent: CCc1ccc(S(=O)(=O)O)cc1
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CCN(CC)CC
Product: CCCCC1(CC)COC2(OC1)OCC(CC)(CCCC)CO2
Temperature: 25 °C

Procedure:
See also U.S. Pat. No. 5,808,108. In a three neck 500 mL RB flask equipped with a reflux condenser, a Dean-Stark trap and under nitrogen, 2-butyl-2-ethyl-1,3-propanediol (35.33 g, 0.22 mol) and toluene (350 mL) were added. The resulting mixture was heated to reflux for 2 h. The resulting solution was cooled to RT and 4-ethylbenzenesulfonic acid (0.35 g) and tetraethylorthocarbonate (21.3 g, 0.11 mol) were added. The reaction mixture was heated to reflux and the azeotropic solution collected in the Dean-Stark trap. The azeotropic mixture was measured and removed from the trap and poured into brine. The toluene phase was separated giving ˜22 mL of ethanol, via shaking with brine. TLC of the reaction mixture showed the complete conversion of the starting diol. To the cooled reaction mixture was added triethylamine (3.0 mL). The reaction mixture was then concentrated at reduced pressure (rotovap) and then dried under vacuum. This crude material was then fractionally vacuum distilled and the fraction boiling at 175–181° C. at 240 Pa and collected (24.72 g) as a water white clear liquid. 13C NMR (CDCl3): 4.59, 11.30, 20.72, 21.20, 22.29, 28.08, 31.78, 67.13, 112.20 (Corthocarbonate).
Reaction SMILES: [CH2:1]([C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].[OH-:17].[Na+].[CH2:19]=O>>[OH:17][CH2:19][C:14]1[CH:15]=[C:10]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9])[CH:11]=[CH:12][C:13]=1[OH:16]
Reactant: C=O
Reactant: [OH-]
Reactant: CCCCCCCCCc1ccc(O)cc1
Agent: [Na+]
Product: CCCCCCCCCc1ccc(O)c(CO)c1

Procedure:
The general procedure of Example 35 was repeated except that 50 grams of p-nonyl phenol (0.227 mole) was used, along with 9.73 grams (0.238 mole) of 98% sodium hydroxide and 23.0 grams (0.284 mole) of the formaldehyde solution to obtain the intermediate 2-hydroxymethyl-4-nonyl phenol. The desired product, 2-(2-hydroxyethyl) thiomethyl-4-nonyl phenol, was obtained from 23.85 grams (0.095 mole) of the intermediate and 7.4 grams of the 2-mercaptoethanol (0.095 mole) in 50 ml of toluene, along with 0.10 gram of the catalyst. Structural formula 27 for the product was confirmed by 1H and 13C NMR.
Reaction SMILES: C(O[C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=O)(C)(C)C.ClC[C:16](Cl)=[O:17].[C:19]([CH2:21][CH2:22][NH:23][CH3:24])#[N:20]>>[C:19]([CH2:21][CH2:22][N:23]([CH3:24])[C:16](=[O:17])[CH2:6][N:8]1[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]1)#[N:20]
Reactant: CNCCC#N
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: O=C(Cl)CCl
Product: CN(CCC#N)C(=O)CN1CCNCC1

Procedure:
The title compound was prepared from 1-tert-butyloxycarbonyl-piperazine, chloroacetylchloride and N-(2-cyanoethyl)-N-methylamine in an analogous manner as described in example 21.
Reaction SMILES: [NH2:1][C:2]1[C:34]([C:35]#[N:36])=[N:33][C:5]2[CH:6]=[C:7]3[C:16](=[N:17][C:4]=2[CH:3]=1)[C:15]1[N:14]=[C:13]2[C:18](=CC4C=CC=CC=4)[CH2:19][CH2:20][CH2:21][C:12]2=[C:11]([CH2:29][CH2:30][CH2:31][CH3:32])[C:10]=1[CH2:9][CH2:8]3.N#N.[O:39]=[O+][O-].CSC>CO>[NH2:1][C:2]1[C:34]([C:35]#[N:36])=[N:33][C:5]2[CH:6]=[C:7]3[C:16](=[N:17][C:4]=2[CH:3]=1)[C:15]1[N:14]=[C:13]2[C:18](=[O:39])[CH2:19][CH2:20][CH2:21][C:12]2=[C:11]([CH2:29][CH2:30][CH2:31][CH3:32])[C:10]=1[CH2:9][CH2:8]3
Reactant: CCCCc1c2c(nc3c1CCc1cc4nc(C#N)c(N)cc4nc1-3)C(=Cc1ccccc1)CCC2
Reactant: O=[O+][O-]
Agent: N#N
Solvent: CO
Solvent: CSC
Product: CCCCc1c2c(nc3c1CCc1cc4nc(C#N)c(N)cc4nc1-3)C(=O)CCC2
Temperature: -78 °C
Yield: 35 %

Procedure:
To a 250 mL round bottomed flask were added 0.305 g (0.147 mmol) of crude 2-amino-12-benzylidene-8-n-butyl-3-cyano-6,7,9,10,11,12hexahydrobenzo[b]pyrido[2,3-j][1,10]phenanthroline, 40 mL of CH2CL2 and 115 mL of CH3OH. The solution was cooled to approximately -78° C. by means of a dry ice/acetone bath and N2 was passed through the solution for 5 min. A stream of O3 was passed through the solution until the color turned from dark orange-brown to dark green-brown. N2 was passed through the solution for an additional 5 min. then 0.6 mL of dimethyl sulfide was added via syringe. The solution was allowed to warm to room temperature overnight and the solvents removed by rotary evaporation. The crude product was washed with ether (3×50 mL) then recrystallized from CHCL3 /EtOH. Vacuum filtration gave 0.09 g (35%) of product as a yellow solid after drying at 0.5 mm Hg pressure and 61° C. for 48 hr. (mp>300° C.).
Reaction SMILES: [N:1]1([C:6]2[CH:7]=[C:8]([CH:13]=[CH:14][CH:15]=2)[C:9]([O:11]C)=O)[CH:5]=[CH:4][N:3]=[CH:2]1.N1(C2C=C(C=CC=2)C(O)=O)C=CN=C1.[C:30]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])(=[O:32])[CH3:31].[Li]>OS(O)(=O)=O.CO>[C:34]([O:33][C:30](=[O:32])[CH2:31][C:9]([C:8]1[CH:13]=[CH:14][CH:15]=[C:6]([N:1]2[CH:5]=[CH:4][N:3]=[CH:2]2)[CH:7]=1)=[O:11])([CH3:37])([CH3:36])[CH3:35]
Reactant: COC(=O)c1cccc(-n2ccnc2)c1
Reactant: CC(=O)OC(C)(C)C
Agent: O=C(O)c1cccc(-n2ccnc2)c1
Agent: O=S(=O)(O)O
Agent: [Li]
Solvent: CO
Product: CC(C)(C)OC(=O)CC(=O)c1cccc(-n2ccnc2)c1

Procedure:
Prepared from methyl 3-(1H-imidazol-1-yl)benzoate [prepared from 3-(1H-imidazol-1-yl)benzoic acid (J. Med. Chem. 1987, 30, 1342; CAS-No. [108035-47-8] by refluxing in conc. H2SO4/MeOH] by treatment with lithium tert.-butyl acetate according to general procedure H (method b). Obtained as an orange-brown oil.
Reaction SMILES: [N:1]1([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Cl[C:15]1[N:20]=[C:19](CC)[CH:18]=[CH:17][N:16]=1.[CH2:23](N(CC)CC)[CH3:24]>C(O)C>[CH2:23]([C:18]1[CH:19]=[N:20][C:15]([N:4]2[CH2:5][CH2:6][N:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:2][CH2:3]2)=[N:16][CH:17]=1)[CH3:24]
Reactant: CCc1ccnc(Cl)n1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: CCN(CC)CC
Solvent: CCO
Product: CCc1cnc(N2CCN(C(=O)OC(C)(C)C)CC2)nc1
Temperature: 0 °C
Yield: 90 %

Procedure:
A mixture of tert-butyl piperazine-1-carboxylate (6.5 gm, 35.2 mmol), 2-chloro-4-ethylpyrimidine (5 gm, 35.2 mmol), triethylamine (3.55 gm, 35.2 mmol), and absolute ethanol (60 ml) were refluxed for 12 h and then cooled. Ice water was added and the resulting precipitate was filtered, washed with cold water, and finally dried to afford the desired crude intermediate, tert-butyl 4-(5-ethylpyrimidin-2-yl)piperazine-1-carboxylate, as white flakes (9.24 gm, 90% yield); mp: 67-68° C. 1H-NMR (DMSO-d6): δ 1.19 (t, J=7.56 Hz, 3H), 1.46 (s, 9H), 2.47 (q, J=7.56 Hz, 2H), 3.49 (t, J=4.8 Hz, 4H), 3.76 (t, J=4.8 Hz, 4H), 8.19 (s, 2H). 13C-NMR (DMSO-d6): δ 15.59, 22.66, 28.4, 43.76, 43.77, 79.8, 124.95, 154.84, 157.08, 160.05. MS: calcd 292.19 for C15H24N4O2 [M]+. found, 293.19 [M+1]+. b) HCl/MeOH mixture was prepared by adding 10 ml acetyl chloride dropwise to 100 ml methanol at 0° C. The resulting mixture was warmed to room temperature. The intermediate from step a (9 gm, 30.8 mmol) was then added to the HCl/MeOH and stirred for 12 h at room temperature. Methanol was removed using a row; evaporator. The residue was dissolved in water; the solution was neutralized using solid NaHCO3. The mixture was extracted with CHCl3 (3×200 mL). The combined organic layers was washed successively with saturated NaHCO3, and saturated brine and then dried with anhydrous Na2SO4. Concentration of the organic layer afforded the desired crude product 1 as a white solid (4.8 gm, 81% yield); mp: 115-116° C. 1H-NMR (DMSO-d6): δ 1.20 (t, J=7.56 Hz, 3H), 2.48 (q, J=7.56 Hz, 2H), 3.09 (t, J=5.16 Hz, 4H), 3.94 (t, J=5.16 Hz, 4H), 8.19 (s, 2H). 13C-NMR (DMSO-d6): δ 15.53, 22.67, 42.76, 44.30, 125.52, 157.15, 160.09.
Reaction SMILES: C([O:9][C@@H:10]1[C@H:14]([O:15]C(=O)C2C=CC=CC=2)[C@@H:13]([CH2:24][O:25]C(=O)C2C=CC=CC=2)[O:12][C@H:11]1[N:34]1[C:38]2[N:39]=[CH:40][NH:41][C:42](=[O:43])[C:37]=2[S:36][C:35]1=[O:44])(=O)C1C=CC=CC=1>N>[C@@H:11]1([N:34]2[C:38]3[N:39]=[CH:40][NH:41][C:42](=[O:43])[C:37]=3[S:36][C:35]2=[O:44])[O:12][C@H:13]([CH2:24][OH:25])[C@@H:14]([OH:15])[C@H:10]1[OH:9]
Reactant: O=C(OC[C@H]1O[C@@H](n2c(=O)sc3c(=O)[nH]cnc32)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1)c1ccccc1
Agent: N
Product: O=c1[nH]cnc2c1sc(=O)n2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Yield: 57 %

Procedure:
Compound 9 (1.0 g, 1.63 mmol) was combined with methanolic ammonia (saturated at 0° C., 50 mL) and heated at 90° C. for 14 h in a steel bomb. The solvent was evaporated and the residue was treated with hot benzene which was decanted off. The resulting solid was purified by silica gel flash chromatography using chloroform and then CHCl3 -MeOH (6:1) to yield 280 mg (57%) of 10 after crystallization from water: mp 216°-218° C.: UV λmax (pH 1) 217 nm (ε 25,300), 259 (9700), 286 (6300): 1H NMR (DMSO-d6) δ 5.85 (d, J=5.1 Hz, 1H, C1, H), 8.30 (s, 1H, C5H), 13.09 (b, 1H, N6H, exchanges with D2O), and other sugar protons. Anal. Calcd. for C10H11N3O6S: C, 39.87: H, 3.68: N, 13.95: S, 10.64. 3.61: N, 14.06: S, 10.43.
Reaction SMILES: C([N:20]1[CH:24]=[C:23]([CH2:25][CH2:26][OH:27])[N:22]=[CH:21]1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(#N)C.Br[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[C:39]1[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=1>C(Cl)Cl>[F:45][C:42]1[CH:43]=[CH:44][C:39]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=2[CH2:32][N:22]2[C:23]([CH2:25][CH2:26][OH:27])=[CH:24][N:20]=[CH:21]2)=[CH:40][CH:41]=1
Reactant: OCCc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Reactant: Fc1ccc(-c2ccccc2CBr)cc1
Solvent: CC#N
Solvent: ClCCl
Product: OCCc1cncn1Cc1ccccc1-c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a suspension of 2-(1-trityl-1H-imidazol-4-yl)ethanol (0.65 g, 1.80 mmol), acetonitrile (9 mL) and CH2Cl2 (12 mL) is added a solution of 2-bromomethyl-4′-fluorobiphenyl (0.478 g, 1.80 mmol) in CH2Cl2 (2 mL). The resulting mixture is stirred at room temperature overnight. The solution is concentrated and the residue is taken up in MeOH and heated to 75° C. for 3.5 h. The solution is then concentrated and the residue is partitioned between CH2Cl2 and aqueous 5% NaHCO3. The aqueous layer is then extracted with CH2Cl2 (3×). The combined organic layers are then washed with brine and dried over Na2SO4. The residue is then purified by flash chromatography (CH2Cl2/MeOH) give 2-[3-(4′-fluorobiphenyl-2-ylmethyl)-3H-imidazol-4-yl]ethanol. MS (ESI) m/z 297.1 (M+H).
Reaction SMILES: C(N(CC)CC)C.Cl[S:9]([C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[O:18][C:17](=[O:22])[C:16](=[N+:23]=[N-:24])[C:15]2=[O:25])(=[O:11])=[O:10].Cl.C1C[O:30]CC1>>[CH2:16]=[CH:15][C:14]1[CH:19]=[CH:20][C:21]([OH:30])=[CH:12][CH:13]=1.[N+:23](=[C:16]1[C:15](=[O:25])[C:14]2[C:19](=[CH:20][CH:21]=[C:12]([S:9]([O-:30])(=[O:11])=[O:10])[CH:13]=2)[O:18][C:17]1=[O:22])=[N-:24]
Reactant: C1CCOC1
Reactant: [N-]=[N+]=C1C(=O)Oc2ccc(S(=O)(=O)Cl)cc2C1=O
Agent: Cl
Solvent: CCN(CC)CC
Product: C=Cc1ccc(O)cc1
Product: [N-]=[N+]=C1C(=O)Oc2ccc(S(=O)(=O)[O-])cc2C1=O
Temperature: 12 °C
Reaction time: 0.07 h
Yield: 1032.7 %

Procedure:
Example 8 illustrates the preparation of a partially substituted polymeric product with a photoactive compound. Example 3 was substantially repeated in Example 8 with the exception of modifications in procedure as set forth below. A 500 mL three-necked round-bottom flask equipped with a magnetic stirrer, water bath, thermometer, nitrogen inlet and bubbler was charged with a solution of PHS (13.3 g, 110 mmol based on monomer repeat units) in THF (170 g). Triethylamine (6.8 g) was added dropwise and the reaction mixture was allowed to stir for an additional 3-5 minutes. A solution of 6-chlorosulfonyl-3-diazo-4-oxo-3,4-dihydrocoumarin (1.6 g, 5.6 mmol) in THF (124 g) was added dropwise and the reaction was allowed to stir at room temperature. After one hour, HPLC analysis showed no residual starting material. The reaction mixture was cooled in an ice bath and neutralized by dropwise addition of conc. HCl (8 g) while maintaining the reaction temperature around 12° C. The reaction mixture was filtered to remove any insoluble impurities. The filtrate was precipitated, with stirring, into ten times its weight of hexane. The resulting slurry was filtered, dried in a vacuum oven overnight at 60° C.; yield 11.2 g of white solids (77% yield). The product was characterized by UV-Vis as follows: the UV-Vis absorption spectrum of the product in THF solvent was determined at a dilution factor, DF=46,948.36 yielding, λ1 max=230 mn, ε1 max=91,245.78 liters/mole cm; and λ2 max=282 nm, ε2 max=29,969.20 liters/mole cm (based on a repeat unit MW=2633.2).
Reaction SMILES: [CH2:1]([N:8]1[C:13]([CH3:14])=[CH:12][C:11]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:10][C:9]1=[O:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(=O)C.C([O-])(=O)C.[Na+].[Br:33]Br>O>[CH2:1]([N:8]1[C:13]([CH3:14])=[CH:12][C:11]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:10]([Br:33])[C:9]1=[O:23])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1cc(OCc2ccccc2)cc(=O)n1Cc1ccccc1
Reactant: BrBr
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: Cc1cc(OCc2ccccc2)c(Br)c(=O)n1Cc1ccccc1
Reaction time: 0.5 h

Procedure:
The product from example 35, 1-benzyl-4-(benzyloxy)-6-methylpyridin-2(1H)-one (4.2 mmol, 1.3 g), acetic acid (50 mL), and sodium acetate (5.0 mmol, 0.41 g) were stirred at room temperature. Bromine (4.2 mmol, 0.67 g) was added drop wise with stirring. After ½ hour, water (100 mL) was added and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic extracts were washed with saturated aqueous sodium bicarbonate solution and brine. After drying over magnesium sulfate and concentrating, the mixture was purified by flash column chromatography eluting with ethyl acetate:hexanes (1:2). The appropriate fractions were concentrated to yield a light oil. (1.0 g, 62%): 1H NMR (DMSO-d6/300 MHz) 7.4-7.0 (m, 10H), 6.5 (s, 1H), 5.29 (s, 2H), 5.27 (s, 2H), 2.2 (s, 3H). ESHRMS m/z 384.057 (M+H, C20H18NO2Br requires 384.060).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4](=[O:40])[CH:5]=[C:6]([O:38][CH3:39])[C:7](=[O:37])[C:8]=1[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]/[CH:16]=[CH:17]\[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]1[C:30](=[O:31])[C:29]([O:32][CH3:33])=[CH:28][C:27](=[O:34])[C:26]=1[O:35][CH3:36].ClC1C=C(C=CC=1)C(O)=[O:46]>C(Cl)Cl>[CH3:1][O:2][C:3]1[C:4](=[O:40])[CH:5]=[C:6]([O:38][CH3:39])[C:7](=[O:37])[C:8]=1[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH:16]1[O:46][CH:17]1[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]1[C:30](=[O:31])[C:29]([O:32][CH3:33])=[CH:28][C:27](=[O:34])[C:26]=1[O:35][CH3:36]
Reactant: O=C(O)c1cccc(Cl)c1
Reactant: COC1=CC(=O)C(OC)=C(CCCCCCC/C=C\CCCCCCCC2=C(OC)C(=O)C=C(OC)C2=O)C1=O
Solvent: ClCCl
Product: COC1=CC(=O)C(OC)=C(CCCCCCCC2OC2CCCCCCCC2=C(OC)C(=O)C=C(OC)C2=O)C1=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
9 Milligrams of 1,16-bis(2,5-dimethoxy-1,4-benzoquinon-3-yl)-cis-8-hexadecene was dissolved in 1 ml of methylene chloride, then to this solution was added 8 mg of m-chlorobenzoic acid and the mixture was stirred at room temperature for 1 hour. After the completion of the reaction, the solvent was removed by evaporation under reduced pressure, and the residue obtained was purified by means of a preparative thin layer chromatography [adsrobent: "Silica gel 60 F254 " manufactured by E. Merck A. G., developing solvent: benzene-ethyl acetate (5:1 mixture by volume/volume)] to obtain 3 mg of 1,16-bis(2,5-dimethoxy-1,4-benzoquinon-3-yl)-8,9-epoxyhexadecane. Yellow oily substance.
Reaction SMILES: O[C:2]1([C:18]2[O:19][C:20]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[N:22]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[C:23]1([C:21]2[N:22]=[C:18]([C:2]3[CH:3]([CH2:9][C:10]4[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=4)[CH2:4][CH2:5][CH2:6][CH2:7][CH:8]=3)[O:19][C:20]=2[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: COc1cccc(CC2CCCCCC2(O)c2nc(-c3ccccc3)c(-c3ccccc3)o2)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: COc1cccc(CC2CCCCC=C2c2nc(-c3ccccc3)c(-c3ccccc3)o2)c1
Yield: 94.1 %

Procedure:
A mixture of 1-hydroxy-1-(4,5-diphenyloxazol-2-yl)-2-(3-methoxybenzyl)cycloheptane (5.2 g) and p-toluenesulfonic acid (500 mg) in toluene (50 ml) was stirred under reflux for 4 hours. The solution was washed with water, sat. NaHCO3 and brine, dried over MgSO4, and evaporated in vacuo. The residue was purified by chromatography on silica gel to afford 1-(4,5-diphenyloxazol-2-yl)-7-(3-methoxybenzyl)-1-cycloheptene (4.7 g).
Reaction SMILES: [NH2:1][C:2]1[C:11]2[N:10]=[CH:9][C:8]([CH2:12][CH2:13][C:14]3[CH:19]=[CH:18][C:17]([C:20](=O)[CH3:21])=[CH:16][CH:15]=3)=[CH:7][C:6]=2[C:5]2[CH:23]=[CH:24][C:25]([CH3:27])=[CH:26][C:4]=2[N:3]=1.[NH:28]1[CH2:32][CH2:31][CH2:30][C@H:29]1[CH2:33][OH:34].C(O)(C(F)(F)F)=O>>[NH2:1][C:2]1[C:11]2[N:10]=[CH:9][C:8]([CH2:12][CH2:13][C:14]3[CH:19]=[CH:18][C:17]([CH:20]([N:28]4[CH2:32][CH2:31][CH2:30][C@H:29]4[CH2:33][OH:34])[CH3:21])=[CH:16][CH:15]=3)=[CH:7][C:6]=2[C:5]2[CH:23]=[CH:24][C:25]([CH3:27])=[CH:26][C:4]=2[N:3]=1
Reactant: OC[C@@H]1CCCN1
Reactant: CC(=O)c1ccc(CCc2cnc3c(N)nc4cc(C)ccc4c3c2)cc1
Solvent: O=C(O)C(F)(F)F
Product: Cc1ccc2c(c1)nc(N)c1ncc(CCc3ccc(C(C)N4CCC[C@H]4CO)cc3)cc12

Procedure:
((2S)-1-(1-(4-(2-(5-Amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)phenyl)ethyl)pyrrolidin-2-yl)methanol was prepared from 1-(4-(2-(5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)phenyl)ethanone (from Example 171) and (S)-pyrrolidin-2-ylmethanol (commercially available) following the procedures described for Example 182, 1H NMR (Acetone-d6) TFA Salt: δ 8.83 (s, 1H), 8.80 (s, 1H), 8.43 (d, 1H), 7.36-7.53 (m, 6H), 4.68 (m, 1H), 3.69 (m, 2H), 3.19-3.21 (m, 4H), 2.55 (m, 4H), 1.75-1.78 (m, 6H), 1.74 (d, 3H). LRMS [M+H]=441.2
Reaction SMILES: [CH:1]([O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[CH:7][C:6]=1[C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=2)[CH2:18][CH2:17]1)=[O:15])([CH3:3])[CH3:2].[CH:32]1N=CN(C(N2C=NC=C2)=O)C=1.CO>CN(C=O)C>[CH3:32][O:10][C:9](=[O:11])[C:8]1[CH:12]=[CH:13][C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[C:6]([C:14]([N:16]2[CH2:21][CH2:20][N:19]([C:22]3[CH:23]=[CH:24][C:25]([C:28]([F:30])([F:31])[F:29])=[CH:26][CH:27]=3)[CH2:18][CH2:17]2)=[O:15])[CH:7]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: CC(C)Oc1ccc(C(=O)O)cc1C(=O)N1CCN(c2ccc(C(F)(F)F)cc2)CC1
Solvent: CN(C)C=O
Solvent: CO
Product: COC(=O)c1ccc(OC(C)C)c(C(=O)N2CCN(c3ccc(C(F)(F)F)cc3)CC2)c1
Temperature: 50 °C
Reaction time: 16 h

Procedure:
To 0.3 mmol 4-isopropoxy-3-[4-(4-trifluoromethyl-phenyl)-piperazine-1-carbonyl]-benzoic acid in 2 ml DMF was added 0.4 mmol CDI, and the mixture heated at 50° C. for 30 min. 5.2 mmol methanol was then added, and the mixture was stirred at RT for 16 h. The mixture was then cooled to room temperature, concentrated in vacuo, and the residue chromatographed on silica gel (eluant: ethyl acetate/heptane 1:4) to afford the title compound. MS (m/e): 451.2 (M+H+, 100%)
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:11]([OH:13])=O)=[CH:3]1.[NH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][C:22]([O:24][CH3:25])=[O:23])=[CH:17][C:16]=1O.B(O)(O)O>C1(C)C(C)=CC=CC=1>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:11]2[O:13][C:16]3[CH:17]=[C:18]([CH2:21][C:22]([O:24][CH3:25])=[O:23])[CH:19]=[CH:20][C:15]=3[N:14]=2)=[CH:3]1
Reactant: Cn1cc(C(=O)O)c2ccccc21
Reactant: COC(=O)Cc1ccc(N)c(O)c1
Agent: OB(O)O
Solvent: Cc1ccccc1C
Product: COC(=O)Cc1ccc2nc(-c3cn(C)c4ccccc34)oc2c1
Temperature: 25 °C
Yield: 10.9 %

Procedure:
In xylene (20 mL), a mixture of 1-methyl-3-indolecarboxylic acid (1.00 g, 5.71 mmol), methyl 4-amino-3-hydroxyphenylacetate (1.03 g, 5.71 mmol) and boric acid (1.05 g, 17.1 mmol) was heated and refluxed for 24 hours by using a Dean-Stark trap. After the reaction mixture was cooled down to room temperature, the solvent was distilled off under reduced pressure. The residue was purified by chromatography on a silica gel column, whereby from chloroform-ethyl acetate (4:1, v/v) eluate fractions, methyl 2-(1-methyl-3-indolyl)-6-benzoxazolylacetate (0.20 g, 11%) was obtained as a yellow oil.