Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:12]=[CH:11][C:10]([Cl:13])=[CH:9][C:3]=1[C:4]([O:6]CC)=[O:5].[F:14][C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[OH-].[Li+]>O.O1CCCC1.O1CCOCC1>[Cl:13][C:10]1[CH:11]=[N:12][C:2]([O:21][C:18]2[CH:19]=[CH:20][C:15]([F:14])=[CH:16][CH:17]=2)=[C:3]([CH:9]=1)[C:4]([OH:6])=[O:5]
Reactant: CCOC(=O)c1cc(Cl)cnc1Cl
Reactant: Oc1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Agent: [Li+]
Solvent: O
Solvent: C1COCCO1
Solvent: C1CCOC1
Product: O=C(O)c1cc(Cl)cnc1Oc1ccc(F)cc1
Temperature: 25 °C
Reaction time: 5 h
Yield: 89.1 %

Procedure:
Ethyl 2,5-dichloronicotinate (2.50 g) was combined with 4-fluorophenol (1.49 g) in a sealable tube containing anhydrous 1,4-dioxane (7 mL). Anhydrous cesium carbonate (4.52 g) was added, and the reaction mixture immersed in a heated oil bath (105° C.) overnight. After cooling to ambient temperature, the resulting suspension was filtered and the solids washed with 1,4-dioxane (2×10 mL). The filtrate was collected and concentrated in vacuo to yield a crude solid (3.89 g). Tetrahydrofuran (12 mL) was added to the crude solid, followed by water (20 mL), and finely ground lithium hydroxide (1.36 g). The solution was allowed to stir 5 hours at room temperature. The organics were then removed in vacuo and the pH of the solution was then adjusted from 14 to 2 with 3N aq. hydrochloric acid. The resulting mixture was then extracted with ethyl acetate (5×50 mL). The combined organics were dried over magnesium sulfate, filtered and concentrated to dryness in vacuo to yield the crude title compound (2.71 g).
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][CH2:12][C:13]3[CH:14]=[N:15][C:16]([CH3:19])=[CH:17][CH:18]=3)[C:6]3[CH2:20][CH2:21][NH:22][CH2:23][C:5]=3[C:4]=2[CH:3]=1.[C:24](#[N:27])[CH:25]=[CH2:26].N([O-])=O.[NH4+].C([O-])(O)=O.[Na+]>O>[CH3:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][CH2:12][C:13]3[CH:14]=[N:15][C:16]([CH3:19])=[CH:17][CH:18]=3)[C:6]3[CH2:20][CH2:21][N:22]([CH2:26][CH2:25][C:24]#[N:27])[CH2:23][C:5]=3[C:4]=2[CH:3]=1
Reactant: C=CC#N
Reactant: Cc1ccc2c(c1)c1c(n2CCc2ccc(C)nc2)CCNC1
Agent: O=C([O-])O
Agent: O=N[O-]
Agent: [NH4+]
Solvent: O
Product: Cc1ccc2c(c1)c1c(n2CCc2ccc(C)nc2)CCN(CCC#N)C1
Reaction time: 0.17 h
Yield: 51.1 %

Procedure:
8-Methyl-5-(2-(6-methylpyridin-3-yl)ethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (250 mg, 8.19 mmol) was taken into water (3 mL) along with acrylonitrile (0.065 mL, 0.982 mmol) and stirred for 10 min. Ceric ammonium nitrite (133 mg, 0.245 mmol) was added to it at once and the reaction mixture was stirred for 2 h. Product was detected by LCMS and TLC. The reaction mixture was basified with sat. NaHCO3 solution and extracted into EtOAc. The organic layer was dried over anhydrous sodium sulfate, concentrated and the crude product purified by column chromatography (Silica gel, 2-4% MeOH in DCM) to get product 180 mg (61.43%). This was converted into the oxalate salt (143 mg). 1HNMR (CD3OD, Oxalate salt) d (ppm): 7.88 (s, 1H), 7.68-7.64 (d, 1H), 7.38-7.34 (d, 1H), 7.22 (s, 1H), 7.18-7.15 (d, 1H), 7.02-6.97 (d, 1H), 4.42 (s, 2H), 4.40-4.36 (t, 2H), 3.58-3.38 (m, 4H), 3.19-3.08 (m, 4H), 2.88-2.80 (t, 2H), 2.53 (s, 3H), 2.40 (s, 3H).
Reaction SMILES: [O:1]=[C:2]1[CH2:7][O:6][C:5]2[N:8]=[C:9]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:27][CH2:26][CH2:25]4)=[CH:20][CH:19]=3)[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[CH:11][C:4]=2[NH:3]1.[H-].[Na+].I[CH2:39][CH3:40]>CN(C)C=O>[CH2:39]([N:3]1[C:2](=[O:1])[CH2:7][O:6][C:5]2[N:8]=[C:9]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:32])([CH3:34])[CH3:33])[CH2:25][CH2:26][CH2:27]4)=[CH:20][CH:19]=3)[C:10]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)=[CH:11][C:4]1=2)[CH3:40]
Reactant: CCI
Reactant: CC(C)(C)OC(=O)NC1(c2ccc(-c3nc4c(cc3-c3ccccc3)NC(=O)CO4)cc2)CCC1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCN1C(=O)COc2nc(-c3ccc(C4(NC(=O)OC(C)(C)C)CCC4)cc3)c(-c3ccccc3)cc21
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 13.2 %

Procedure:
In a 15 mL reaction tube was added tert-butyl 1-(4-(2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutylcarbamate (50 mg, 0.106 mmol) in anhydrous N,N-dimethylformamide (1 mL) to give a yellow solution, then cooled to 0° C. under a nitrogen atmosphere. Sodium hydride, 60% in oil (10 mg, 0.254 mmol) was added and the mixture stirred at 0° C. for 15 minutes. Iodoethane (10 μl, 0.127 mmol) was added and the mixture stirred at 0° C. for 30 minutes, allowed to warm to room temperature then stirred for one hour. Further sodium hydride, 60% in oil (10.18 mg, 0.254 mmol) was added and the reaction mixture was heated to 40° C. under a nitrogen atmosphere for one hour. Further iodoethane (10 μl, 0.127 mmol) was added and the mixture stirred at room temperature for 30 minutes. The reaction mixture was quenched by the addition of saturated sodium bicarbonate solution (5 mL) and extracted into ethyl acetate (3×5 mL). The organic phase was washed with 50:50 water:brine (2×10 mL) then brine (10 mL), dried over Na2SO4, filtered and concentrated to dryness under reduced pressure. The residue was purified by Biotage chromatography (cyclohexane:ethyl acetate, gradient elution from 88:12 to 0:100) to give the desired product as a pale yellow solid (7 mg, 13% yield). 1H-NMR (500 MHz, CDCl3) δ 7.10-7.28 (10H, m), 4.93 (1H, br s), 4.81 (2H, s), 3.94 (2H, q), 2.10-2.55 (4H, m), 1.90-2.08 (1H, m), 1.65-1.80 (1H, m), 1.00-1.40 (9H, br m), 1.14 (3H, t). LCMS (Method A) RT=7.29 min, M+H+=500.12.
Reaction SMILES: [CH3:1][C:2]1[C:3]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[N:4][C:5]2[C:10]([C:11]=1[C:12]([OH:14])=[O:13])=[CH:9][CH:8]=[CH:7][CH:6]=2.[Br:21]N1C(=O)CCC1=O.S([O-])([O-])(=O)=S.[Na+].[Na+].Cl.[OH-].[Na+]>C(Cl)(Cl)(Cl)Cl.O.C(OCC)(=O)C.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[Br:21][CH2:1][C:2]1[C:3]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[N:4][C:5]2[C:10]([C:11]=1[C:12]([OH:14])=[O:13])=[CH:9][CH:8]=[CH:7][CH:6]=2
Reactant: Cc1c(-c2ccccc2)nc2ccccc2c1C(=O)O
Reactant: O=C1CCC(=O)N1Br
Agent: Cl
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Agent: O=S([O-])([O-])=S
Solvent: CCOC(C)=O
Solvent: ClC(Cl)(Cl)Cl
Solvent: O
Product: O=C(O)c1c(CBr)c(-c2ccccc2)nc2ccccc12
Reaction time: 4 h
Yield: 108.8 %

Procedure:
To a solution of 3-methyl-2-phenylquinoline-4-carboxylic acid (1.5 g, 5.7 mmol) and N-bromosuccinimide (1.52 g, 8.5 mmol) in carbon tetrachloride (25 mL) was added benzoyl peroxide (approximately 10 mg) and heated under reflux with illumination using a long wavelength ultraviolet lamp (Blak-ray model B100-AP, Upland, Calif.). After 4 h, additional portions of N-bromosuccinimide (750 mg, 4.2 mmol) and benzoyl peroxide (approximately 10 mg) were added. After an additional 2 h, the cooled mixture was diluted with water. Sodium thiosulfate (1 g) was added, then the pH was adjusted to approximately 4.0 by addition of dilute HCl and NaOH. The mixture was further diluted with ethyl acetate, extracted, and dried (MgSO4) to afford the product as a light brown powder (1.62 g, 6.2 mmol). 1H NMR (300 MHz, DMSO) δ 8.09 (d, J=8.4 Hz, 1H), 7.96-7.86 (m, 2H), 7.76 (d, J=8.2 Hz, 1H), 7.68-7.64 (m, 2H), 7.61-7.55 (m, 3H), 4.75 (s, 2H). LRMS m/z 342.0.
Reaction SMILES: [CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[CH2:11][CH2:12][NH2:13].Br[CH2:15][C:16]1[C:26]([N+:27]([O-:29])=[O:28])=[CH:25][CH:24]=[CH:23][C:17]=1[C:18](OCC)=[O:19].C([O-])(O)=O.[Na+]>ClCCl>[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[CH2:11][CH2:12][N:13]1[CH2:15][C:16]2[C:17](=[CH:23][CH:24]=[CH:25][C:26]=2[N+:27]([O-:29])=[O:28])[C:18]1=[O:19]
Reactant: NCCN1CCc2ccccc2C1
Reactant: CCOC(=O)c1cccc([N+](=O)[O-])c1CBr
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: O=C1c2cccc([N+](=O)[O-])c2CN1CCN1CCc2ccccc2C1
Temperature: 25 °C
Reaction time: 16 h
Yield: 57.8 %

Procedure:
To a solution of 2-(3,4-dihydro-1H-isoquinolin-2-yl)ethylamine (36) (0.36 g, 2.0 mmol) in dichloromethane (4 mL) was added the bromide 35 (0.75 g, 2.6 mmol) in dichloromethane (5 mL) at 0° C. The mixture was allowed to warm to room temperature and stirred for 16 hours before it was poured into saturated NaHCO3 (aq. 50 mL) and extracted with dichloromethane (2×50 mL). The combined organic layers were washed with water (70 mL), brine (70 mL), dried over MgSO4, and concentrated on a rotavap. The residue was chromatographed on silica gel eluting with 3:1 to 1:1 hexanes/EtOAc to give 37 (0.39 g, 57%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[CH:6]=[CH:5][CH:4]=1.OO.[Br:12]Br>C(O)(=O)C>[Br:12][C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][C:7]=1[CH3:9]
Reactant: COc1cccc(C)c1
Reactant: BrBr
Agent: OO
Solvent: CC(=O)O
Product: COc1ccc(Br)c(C)c1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
36.65 g (0.3 mol) of m-cresol methyl ether and 39.8 g (0.35 mol) of 30% hydrogen peroxide in 40 ml of acetic acid (98%) are initially introduced into a flask which has a volume of 250 ml and ground-glass joints and is fitted with an internal thermometer, stirrer and dropping funnel. The mixture is stirred vigorously and cooled to 0° C. Subsequently, bromine dissolved in 40 ml of 98% acetic acid is slowly added dropwise over 3 hours. The reaction is highly exothermic. During the period of dropwise addition, the reaction temperature is held constant at about 0° to 5° C. Following the end of dropwise addition, the temperature is raised to 20° C. and stirring is continued for one hour. The stirrer is then switched off and the mixture is left to stand at 20° C. Two phases immediately form. The lower organic, halogenated phase is separated off from the upper acetic acid phase and concentrated, to give 2-bromo-5-methoxytoluene of the formula ##STR11## as a yellow oil.
Reaction SMILES: [CH3:1][C:2]1[O:3][C:4]2[CH:13]=[C:12]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[CH:22][S:23][C:16]=34)[CH:11]=[CH:10][C:5]=2[C:6]=1[C:7](Cl)=[O:8].[CH3:24][C:25]1[NH:29][N:28]=[C:27]([NH2:30])[CH:26]=1>>[CH3:24][C:25]1[NH:29][N:28]=[C:27]([NH:30][C:7]([C:6]2[C:5]3[CH:10]=[CH:11][C:12]([O:14][C:15]4[CH:20]=[CH:19][N:18]=[C:17]5[CH:21]=[CH:22][S:23][C:16]=45)=[CH:13][C:4]=3[O:3][C:2]=2[CH3:1])=[O:8])[CH:26]=1
Reactant: Cc1cc(N)n[nH]1
Reactant: Cc1oc2cc(Oc3ccnc4ccsc34)ccc2c1C(=O)Cl
Product: Cc1cc(NC(=O)c2c(C)oc3cc(Oc4ccnc5ccsc45)ccc23)n[nH]1

Procedure:
This material was prepared from 2-methyl-6-[thieno[3,2-b]pyridin-7-yloxy]benzofuran-3-carbonyl chloride 101 and (5-methyl-1H-pyrazol-3-yl)amine in a similar manner as that described for example 108. 1H NMR (DMSO-d6) δ 12.09 (1H, bs), 10.45 (1H, s), 8.50 (1H, d, J=5.6 Hz), 8.14 (1H, d, J=5.6 Hz), 7.77 (1H, d, J=8.6 Hz), 7.65 (1H, d, J=2.3 Hz), 7.59 (1H, d, J=5.3 Hz), 7.24 (1H, dd, J=8.3, 2.0 Hz), 6.64 (1H, d, J=5.6 Hz), 6.39 (1H, bs), 2.64 (3H, s), 2.23 (3H, s).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7]([NH:9][C:10]1([O:38][CH3:39])[C:36](=[O:37])[N:12]2[CH:13]([C:20]([O:22][CH:23]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[O:21])[C:14]([CH:17]([OH:19])[CH3:18])=[CH:15][S:16][C@H:11]12)=[O:8].CC(C)=O.[Cr](O)(O)(=O)=O>C(O)(C)C>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7]([NH:9][C:10]1([O:38][CH3:39])[C:36](=[O:37])[N:12]2[CH:13]([C:20]([O:22][CH:23]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)=[O:21])[C:14]([C:17](=[O:19])[CH3:18])=[CH:15][S:16][C@H:11]12)=[O:8]
Reactant: COC1(NC(=O)Cc2cccs2)C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)C(C(C)O)=CS[C@@H]21
Agent: O=[Cr](=O)(O)O
Solvent: CC(C)=O
Solvent: CC(C)O
Product: COC1(NC(=O)Cc2cccs2)C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)C(C(C)=O)=CS[C@@H]21
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 47.8 %

Procedure:
To a solution of 0.154 g. of benzhydryl 7-(2-thienylacetamido)-7-methoxy-3-(1-hydroxyethyl)-2-cephem-4-carboxylate in 40 ml. of acetone was added 1.5 eq. of chromic acid. After stirring the mixture at room temperature for 10 minutes, 2 ml. of isopropanol was added. After stirring for an additional 5 minutes, the reaction mixture was evaporated in vacuo to dryness. The residue was dissolved in an ethyl acetate/water slurry. The organic layer was separated, washed successively with water (2X), aqueous sodium bicarbonate solution, 1N.HCl, and brine and dried over anhydrous sodium sulfate. Evaporation in vacuo to dryness provided product which was chromatographed on 5.0 g. of silica gel using a toluene-ethyl acetate gradient to give 0.073 g. (47.8 percent) of the title product as a white froth:
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][CH:12]1[C:16]2[N:17]=[CH:18][N:19]=[C:20]([N:21]3[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]3)[C:15]=2[C@H:14]([CH3:34])[CH2:13]1.O>C(Cl)Cl.CCOC(C)=O>[CH3:34][C@H:14]1[C:15]2[C:20]([N:21]3[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]3)=[N:19][CH:18]=[N:17][C:16]=2[C:12](=[O:11])[CH2:13]1
Reactant: C[C@@H]1CC(O)c2ncnc(N3CCN(C(=O)OC(C)(C)C)CC3)c21
Agent: O=C(Cl)C(=O)Cl
Solvent: O
Solvent: CS(C)=O
Solvent: ClCCl
Product: C[C@@H]1CC(=O)c2ncnc(N3CCN(C(=O)OC(C)(C)C)CC3)c21
Temperature: 25 °C
Reaction time: 0.58 h
Yield: 79.7 %

Procedure:
To a −78° C. solution of oxalyl chloride (0.203 mL, 2.33 mmol) in 10 mL DCM was added dropwise by syringe a solution of DMSO (0.330 mL, 4.66 mmol) in 3 mL DCM. The reaction mixture was stirred 35 minutes, then a solution of (R)-tert-butyl 4-(7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (0.556 g, 1.66 mmol) in 5 mL DCM was added slowly by syringe. The reaction mixture was stirred another 1 hour at −78° C., after which neat TEA (1.09 mL, 7.81 mmol) was added. The reaction mixture was then allowed to warm to room temperature, stirred 30 minutes, and H2O was added. The mixture was extracted with 3×75 mL DCM, and the combined extracts were dried (Na2SO4), filtered, and concentrated in vacuo. The crude was purified on silica gel (Biotage 40M): the column was flushed with about 300 mL 4:1 DCM:EtOAc, then gradient to 1:4 DCM: EtOAc to give (R)-tert-butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (0.440 g, 79.6% yield) as a brown foam. MS (APCI+) m/z 333 [M+H]+. 1H NMR (CDCl3, 400 MHz) δ 8.73 (s, 1H), 3.93-3.82 (m, 2H), 3.74-3.48 (m, 7H), 2.96 (dd, J=19.6, 7.3 Hz, 1H), 2.34 (dd, J=19.6, 1.5 Hz, 1H), 1.50 (s, 9H), 1.32 (d, J=6.8 Hz, 3H).
Reaction SMILES: [C:1]([OH:5])(=O)[CH:2]=[CH2:3].[CH2:6]([N:13]1[CH2:18][CH2:17][CH:16]([NH:19][C:20]2[CH2:25][CH2:24][CH2:23][C:22](=[O:26])[CH:21]=2)[CH2:15][CH2:14]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>C(Cl)(Cl)Cl>[CH2:6]([N:13]1[CH2:18][CH2:17][CH:16]([N:19]2[C:20]3[CH2:21][CH2:3][CH2:2][C:1](=[O:5])[C:25]=3[CH2:24][CH2:23][C:22]2=[O:26])[CH2:15][CH2:14]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: C=CC(=O)O
Reactant: O=C1C=C(NC2CCN(Cc3ccccc3)CC2)CCC1
Solvent: ClC(Cl)Cl
Product: O=C1CCCC2=C1CCC(=O)N2C1CCN(Cc2ccccc2)CC1
Reaction time: 6 h

Procedure:
Acrylic acid (28.9 ml) is added to 1-(1-benzyl-4-piperidinylamino)-1-cyclohexen-3-on (100 g) and the mixture is refluxed with stirring for 6 hours. After cooling, the reaction mixture is dissolved in chloroform containing 10% methanol and purified by silica gel column chromatography (solvent; dichloromethane:methanol=40:1). The resultant is recrystallized from ethanol/water to give 1-(1-benzyl-4-piperidinyl)-5-oxo-3,4,5,6,7,8-hexahydrocarbostyril (23.98 g) as colorless needles, m.p.: 102°-103° C.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]2[C:15]([O:16][CH3:17])=[CH:14][NH:13][C:12](=[O:18])[CH:11]=2)[CH:3]=1.[H-].[Na+].[CH3:21][CH:22]([CH3:37])[CH:23](OS(C(F)(F)F)(=O)=O)[C:24]([O:26][CH2:27][CH3:28])=[O:25]>>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]2[C:15]([O:16][CH3:17])=[CH:14][N:13]([CH:23]([CH:22]([CH3:37])[CH3:21])[C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:12](=[O:18])[CH:11]=2)[CH:3]=1
Reactant: COc1c[nH]c(=O)cc1-c1cc(Cl)ccc1C#N
Reactant: CCOC(=O)C(OS(=O)(=O)C(F)(F)F)C(C)C
Agent: [H-]
Agent: [Na+]
Product: CCOC(=O)C(C(C)C)n1cc(OC)c(-c2cc(Cl)ccc2C#N)cc1=O

Procedure:
3.50 g (13.4 mmol) of 4-chloro-2-(5-methoxy-2-oxo-1,2-dihydropyridin-4-yl)benzonitrile in the presence of 1.5 eq. of sodium hydride and 5.60 g (20.1 mmol, 1.5 eq.) of ethyl 3-methyl-2-{[(trifluoromethyl)sulphonyl]oxy}butanoate (racemate) were reacted at RT according to General Method 4E. The crude product was purified by flash chromatography (silica gel 50, cyclohexane/ethyl acetate mixtures). Yield: 3.70 g (66% of theory)
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([Cl:12])[N:10]=2)[N:5]=[CH:4][C:3]=1[C:13](=[O:15])[CH3:14].[CH3:16][N:17]([CH3:27])[CH2:18][CH2:19][C:20]1[CH:26]=[CH:25][C:23]([NH2:24])=[CH:22][CH:21]=1>>[Cl:12][C:9]1[N:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][C:3]([C:13](=[O:15])[CH3:14])=[C:2]2[NH:24][C:23]1[CH:22]=[CH:21][C:20]([CH2:19][CH2:18][N:17]([CH3:16])[CH3:27])=[CH:26][CH:25]=1
Reactant: CC(=O)c1cnc2ccc(Cl)nc2c1Cl
Reactant: CN(C)CCc1ccc(N)cc1
Product: CC(=O)c1cnc2ccc(Cl)nc2c1Nc1ccc(CCN(C)C)cc1
Yield: 60.6 %

Procedure:
Following general procedure I, 1-(4,6-dichloro-1,5-naphthyridin-3-yl)ethanone (150 mg, 0.64 mmol) was reacted with 4-[2-(dimethylamino)ethyl)aniline (110 mg, 0.64 mmol) to afford the desired product (143 mg, 60%) as a yellow solid: 1H NMR (500 MHz, CDCl3) δ 10.86 (br s, 1H), 8.99 (s, 1H), 8.14 (d, J=8.8 Hz, 1H), 7.50 (d, J=8.8 Hz, 1H), 7.22-7.15 (m, 2H), 7.11-7.04 (m, 2H), 2.87 (t, J=8.1 Hz, 2H), 2.70-2.60 (m, 2H), 2.55 (s, 3H), 2.39 (s, 6H); ESI MS m/z 369 [M+H]+
Reaction SMILES: [C:1]([C:3]1[C:4]([CH3:13])=[C:5]([C:9]([CH3:12])=[CH:10][CH:11]=1)[C:6](O)=[O:7])#[N:2].B.O.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1>[C:1]([C:3]1[C:4]([CH3:13])=[C:5]([CH2:6][OH:7])[C:9]([CH3:12])=[CH:10][CH:11]=1)#[N:2]
Reactant: Cc1ccc(C#N)c(C)c1C(=O)O
Agent: B
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: Cc1ccc(C#N)c(C)c1CO
Yield: 37.1 %

Procedure:
A solution of 3-cyano-2,6-dimethylbenzoic acid (8.11 grams, 0.049 mole) in tetrahydrofuran (100 ml) was cooled to 0°. Borane (48.7 grams, 0.049 mole) in tetrahydrofuran was added dropwise over a 20 minute period. The mixture was allowed to come to room temperature, and water was added. Potassium carbonate was added to separate the layers. The aqueous layer was extracted with diethyl ether. The extract was added to the organic phase, which was dried over magnesium sulfate, filtered, and the solvent evaporated to give (3-cyano-2,6-dimethylphenyl)methanol (2.93 grams).
Reaction SMILES: [F:1][C:2]1[CH:25]=[CH:24][C:5]([C:6]([NH:8][CH:9]([C:15](=[O:23])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[CH3:22])[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[O:7])=[C:4]([C:26]([F:29])([F:28])[F:27])[CH:3]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C(Cl)Cl.C(O)C.CC1C=CC(C(C)C)=CC=1.CC1C=CC(C(C)C)=CC=1.Cl[Ru]Cl.Cl[Ru]Cl>[F:1][C:2]1[CH:25]=[CH:24][C:5]([C:6]([NH:8][C@@H:9]([C@H:15]([OH:23])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[CH3:22])[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[O:7])=[C:4]([C:26]([F:27])([F:28])[F:29])[CH:3]=1
Reactant: CCOC(=O)C(NC(=O)c1ccc(F)cc1C(F)(F)F)C(=O)c1ccccc1C
Agent: Cl[Ru]Cl
Agent: c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1
Solvent: Cc1ccc(C(C)C)cc1
Solvent: ClCCl
Solvent: CCO
Product: CCOC(=O)[C@@H](NC(=O)c1ccc(F)cc1C(F)(F)F)[C@H](O)c1ccccc1C

Procedure:
4.7 g (0.0114 mol) of ethyl 2-(4-fluoro-2-trifluoromethylbenzoylamino)-3-oxo-3-o-tolylpropionate were dissolved in methylene chloride, the solution was degassed in an ultrasonic bath and 200 mg of catalyst mix were added. The catalyst mix had been prepared beforehand by heating 78 mg of dichloro(p-cymene)ruthenium(II) dimer (RuCl2Cy) and 138 mg of BINAP in methylene chloride and ethanol at 50° C. for 1 h, followed by removal of the solvents.
Reaction SMILES: Cl.[Cl:2][C:3]1[C:8]([C:9]([NH2:11])=[NH:10])=[CH:7][N:6]=[C:5]([O:12][CH3:13])[CH:4]=1.C(=O)(O)[O-].[K+].Br[CH2:20][C:21]([C:23]1[N:24]([CH:29]([CH3:31])[CH3:30])[N:25]=[C:26]([CH3:28])[N:27]=1)=O>C1COCC1.O>[Cl:2][C:3]1[C:8]([C:9]2[NH:11][CH:20]=[C:21]([C:23]3[N:24]([CH:29]([CH3:31])[CH3:30])[N:25]=[C:26]([CH3:28])[N:27]=3)[N:10]=2)=[CH:7][N:6]=[C:5]([O:12][CH3:13])[CH:4]=1
Reactant: COc1cc(Cl)c(C(=N)N)cn1
Reactant: Cc1nc(C(=O)CBr)n(C(C)C)n1
Agent: Cl
Agent: O=C([O-])O
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: COc1cc(Cl)c(-c2nc(-c3nc(C)nn3C(C)C)c[nH]2)cn1
Yield: 96.5 %

Procedure:
A suspension of 4-chloro-6-methoxy-nicotinamidine hydrochloride (18.4 mmol) and potassium bicarbonate (7.37 g, 73.6 mmol) in THF (42 mL) and water (8.5 mL) was heated to reflux and treated with a solution of 2-bromo-1-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-ethanone (4.53 g, 18.4 mmol) in THF (14 mL) added dropwise. The reaction mixture was heated at reflux for 18 h before removal of volatile solvent in vacuo. The resultant suspension was filtered and the residue washed with water then dried to give the title compound as a brown solid (5.91 g, 97%). LCMS: RT=2.68 min, [M+H]+=333/335. 1H NMR 400 MHz (CDCl3) δ: 10.41 (1 H, s), 9.02 (1 H, s), 7.81 (1 H, s), 6.87 (1H, s), 5.91 (1 H, m), 4.00 (3 H, s), 2.41 (3 H, s), 1.55 (6 H, d, J=6.71 Hz).
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[C:7]([O:9][CH3:10])[C:6](B(O)O)=[CH:5][N:4]=1.Br[C:15]1[CH:16]=[C:17]([CH:19]=[CH:20][CH:21]=1)[NH2:18].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]1[N:8]=[C:7]([O:9][CH3:10])[C:6]([C:15]2[CH:16]=[C:17]([NH2:18])[CH:19]=[CH:20][CH:21]=2)=[CH:5][N:4]=1
Reactant: COc1ncc(B(O)O)c(OC)n1
Reactant: Nc1cccc(Br)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: COc1ncc(-c2cccc(N)c2)c(OC)n1
Temperature: 25 °C
Yield: 55 %

Procedure:
2,4-dimethoxypyrimidine-5-boronic acid (0.160 g, 0.872 mmol) and 3-bromoaniline (0.063 mL, 0.581 mmol) were combined in DME (3 mL) in a flame-dried, round-bottom flask. Na2CO3 (2M, 0.610 mL, 1.22 mmol) and Pd(PPh3)4 (0.02 g, 0.017 mmol) were added to the stirred solution. The reaction was refluxed overnight under argon flow, and subsequently cooled to room temperature. The solvent was removed under vacuum and the resulting residue was resuspended in CH2Cl2. The organic phase was dried over MgSO4, filtered, and concentrated under vacuum. The crude product was purified by flash silica column chromatography (10-100% EtOAc/hexanes). The purification was monitored by TLC. The solvent was removed under vacuum from fractions containing product, resulting in 0.074 g in 55% yield.
Reaction SMILES: [C:1]1([CH:8]=[CH:7][C:5]([OH:6])=[CH:4][CH:3]=1)[OH:2].[OH-].[K+].[I-].[K+].C1(C)C=CC=CC=1S(O[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH:32]=[CH2:33])(=O)=O.Cl>O.C(O)C.CO>[CH2:33]([O:2][C:1]1[CH:8]=[CH:7][C:5]([OH:6])=[CH:4][CH:3]=1)[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH:24]=[CH2:23]
Reactant: C=CCCCCCCCCCOS(=O)(=O)c1ccccc1C
Reactant: Oc1ccc(O)cc1
Agent: Cl
Agent: [I-]
Agent: [K+]
Solvent: CCO
Solvent: CO
Solvent: O
Product: C=CCCCCCCCCCOc1ccc(O)cc1

Procedure:
FIG. 2 is a flow diagram showing the steps of synthesizing a representative monomer 1M according to the present invention. In a 50 ml of bi-neck bottle, 3.28 g of hydroquinone, 1.96 g of potassium hydroxide, 0.50 g of potassium iodide, 10.0 ml of methanol and 20.0 ml of ethanol are introduced and mixed. 3.00 g of 11-tolylsulfonyloxy-1-undecene is dropped slowly into the bottle and the resulting mixture is subsequently heated to the boiling point thereof. After the solvent is distillated off, 100.0 ml of cold water is added and 6N HCl is dropped until the mixture becomes acidic. Then the resulting mixture is subjected to extraction using ether. The organic layer is subjected to dehydration using magnesium sulfate, filtration, concentration and further purification with silica gel column chromatography, thereby obtaining a white solid product, 4-(10-undecenoxy)phenol.