Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([CH:8]=[CH:7][CH:6]=[C:4]([OH:5])[CH:3]=1)[OH:2].[CH:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=[CH:11][C:10]=1[C:19]([CH2:21][C:22](OCC)=[O:23])=O.O>S(=O)(=O)(O)O>[OH:2][C:1]1[CH:3]=[C:4]2[C:6]([C:19]([C:10]3[CH:11]=[CH:12][C:13]4[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=4)[CH:9]=3)=[CH:21][C:22](=[O:23])[O:5]2)=[CH:7][CH:8]=1
Reactant: Oc1cccc(O)c1
Reactant: CCOC(=O)CC(=O)c1ccc2ccccc2c1
Agent: O=S(=O)(O)O
Solvent: O
Product: O=c1cc(-c2ccc3ccccc3c2)c2ccc(O)cc2o1
Temperature: 25 °C
Reaction time: 120 h
Yield: 26 %

Procedure:
A mixture of resorcinol (11.0 g, 0.1 mole) and ethyl 2-naphthoylacetate (24.2 g, 0.1 mole) in concentrated sulphuric acid (50 ml) was stirred at room temperature for 5 days then poured into water to give a yellow gum. The gum was washed several times with water then dissolved in ethanol and diluted with water to give 7-hydroxy-4-(2-naphthyl)coumarin as a fine pale brown precipitate in 26% yield.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2=[C:6]([CH:26]=1)[O:7][CH2:8][C:9]1[N:25]=[CH:24][CH:23]=[CH:22][C:10]=1/[C:11]/2=[C:12](\[C:15]1[CH:16]=[C:17]([NH2:21])[CH:18]=[CH:19][CH:20]=1)/[CH2:13][CH3:14].N1C=CC=CC=1.[CH3:33][S:34](Cl)(=[O:36])=[O:35].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl.C(O)(C)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2=[C:6]([CH:26]=1)[O:7][CH2:8][C:9]1[N:25]=[CH:24][CH:23]=[CH:22][C:10]=1/[C:11]/2=[C:12](\[C:15]1[CH:16]=[C:17]([NH:21][S:34]([CH3:33])(=[O:36])=[O:35])[CH:18]=[CH:19][CH:20]=1)/[CH2:13][CH3:14]
Reactant: CC/C(=C1\c2ccc(Cl)cc2OCc2ncccc21)c1cccc(N)c1
Reactant: CS(=O)(=O)Cl
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Solvent: ClCCl
Solvent: CC(C)O
Solvent: c1ccncc1
Product: CC/C(=C1\c2ccc(Cl)cc2OCc2ncccc21)c1cccc(NS(C)(=O)=O)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 71.5 %

Procedure:
Under a nitrogen atmosphere, solid (E)-3-[1-(8-chloro-11H-10-oxa-1-aza-dibenzo[a,d]cyclohepten-5-ylidene)-propyl]-phenylamine (198 g, 545 mmol), pyridine (67.0 mL, 828 mmol) and dichloromethane (1.6 L) are charged to a 5 liter 4 neck round bottom flask equipped with a mechanical stirrer and thermocouple. To the dark green reaction mixture, a solution of methanesulfonyl chloride (51.0 mL, 658 mmol) in dichloromethane (400 mL) is added dropwise over 20 min from an addition funnel. An exotherm of 6.9° C. is observed over the course of the addition. Upon completion of addition the reaction is stirred for 16 h at ambient temperature. The mixture is charged to a 22 L bottom outlet flask containing 10% citric acid solution (2 L). The mixture is stirred for 15 min and the layers separated upon standing. The organic layer is washed with a 15% NaCl solution. The organic layer is charged to a 5 L 4 neck flask, equipped with a mechanical stirrer under a nitrogen atmosphere. The deep red solution is treated with DARCO® activated charcoal (200 g), Na2SO4 (200 g) and TMT (trithiocyanuric acid trisodium salt hydrate) (50 g). The mixture is stirred for 18 h at ambient temperature and then filtered over a 2 in (about 5 cm) pad of diatomaceous earth (Hy-flo Supercel®). The filtrate is concentrated in vacuo yielding a hard white foam. Isopropyl alcohol (1 L, 5 volumes) is added to the foam and the slurry is stirred at 40° C. for one hour. The thick mixture is cooled to ambient temperature. The solids are vacuum filtered over a polypropylene pad in a buchner funnel The material is dried at 70° C. for 16 h under house vacuum yielding 171.85 g (71.4%) of white crystalline product. LC-ES/MS m/e 441.2 [M+H]+, 439.1 [M−H]−. Anal. Calcd for C23H21N2ClO3S: C, 62.65; H, 4.80; N, 6.35. Found: C, 62.81; H, 4.82; N, 6.20.
Reaction SMILES: [Si:1]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23](Br)=[CH:22][CH:21]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:27][Si:28]([C:31]#[CH:32])([CH3:30])[CH3:29].C(N(CC)CC)C.O>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I.CCOCC>[Si:1]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:32]#[C:31][Si:28]([CH3:30])([CH3:29])[CH3:27])=[CH:22][CH:21]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C#C[Si](C)(C)C
Reactant: CC(C)(C)[Si](OCc1ccc(Br)cc1)(c1ccccc1)c1ccccc1
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: CC(C)(C)[Si](OCc1ccc(C#C[Si](C)(C)C)cc1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
A 25 mL round bottom flask was flame-dried under high vacuum. The vacuum was broken by the addition of dry argon, and the flask was allowed to cool to room temperature. The flask was charged with 2.0 g (4.70 mmol) of 4-bromobenzyl tert-butyldiphenylsilyl ether (Compound 1), 2.0 mL (14.1 mmol) of (trimethylsilyl)acetylene, and 16.5 mL of triethylamine. The solution was purged with argon for 15 minutes and bis(triphenylphosphine)palladium (II) chloride (83 mg, 0.12 mmol) and copper (I) iodide (22 mg, 0.12 mmol) were added and the solution stirred at ambient temperature for 3 days. The solution was poured into a separatory funnel containing water and ether. The layers were separated and the aqueous layer was extracted 3 times with ether. The combined ether layers were washed once with brine, and dried over magnesium sulfate, and the solvents were removed under reduced pressure. The residue was purified by distillation (bp=180° B 185° C., 1 torr) to give the title compound.
Reaction SMILES: [C:1]([CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])#[N:2].C([Sn]([N:24]=[N+:25]=[N-:26])(CCCC)CCCC)CCC.Cl>COCCOC.CO>[NH:24]1[C:1]([CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])=[N:2][N:26]=[N:25]1
Reactant: CCCC[Sn](CCCC)(CCCC)N=[N+]=[N-]
Reactant: CCOC(=O)CCCC#N
Agent: Cl
Solvent: COCCOC
Solvent: CO
Product: CCOC(=O)CCCc1nnn[nH]1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Ethyl 4-cyanobutyrate (approximately 15 g) was dissolved in DME. Tris(n-butyl)tin azide (5 ml) was added and the reaction solution was heated to 85° overnight then cooled to room temperature. The cooled solution was diluted with methanol (20 ml) then 1N hydrochloric acid (20 ml) was added. The solution was stirred for one hour then partitioned between ethyl acetate and water. The organic layer was separated, dried over magnesium sulfate and evaporated under reduced pressure. The residue was chromatographed by preparatory-scale HPLC (silcia column) eluted with a gradient of 30 to 70% ethyl acetate in hexane plus 1% acetic and to yield 3.39 g of the title product: n.m.r.(300 MHz, CDCl3) δ: 4.2 (q, 2H); 2.95 (t, 2H); 2.5 (t, 2H); 2.1 (t, 2H); 1.3 (t, 3H).
Reaction SMILES: COCO[C:5]1[CH:10]=[C:9]([O:11][CH2:12][O:13][CH3:14])[CH:8]=[CH:7][C:6]=1[C:15](=[O:17])C>C(O)C>[CH3:14][O:13][CH2:12][O:11][C:9]1[CH:10]=[CH:5][C:6]([CH:15]=[O:17])=[CH:7][CH:8]=1
Reactant: COCOc1ccc(C(C)=O)c(OCOC)c1
Solvent: CCO
Product: COCOc1ccc(C=O)cc1
Yield: 91.7 %

Procedure:
In 50 ml of ethanol were dissolved 6.31 g of the 2',4'-bis(methoxymethoxy)acetophenone obtained in Production Example 10 and 4.00 g of the p-methoxymethoxybenzaldehyde obtained in Production Example 25, and the solution was cooled to 0° C. and 30 ml of a saturated solution of potassium hydroxide in ethanol was added to the solution. The temperature of the reaction liquid was elevated to room temperature and the liquid was stirred for 2 days. The reaction liquid was diluted with water, neutralized with 6N hydrochloric acid and extracted with ethyl acetate, and the organic layer was dried with sodium sulfate and concentrated under reduced pressure to obtain a reaction mixture in the form of a syrup. The syrup was subjected to the column chromatography (320 g of 270-400 mesh Kieselgel 60; 0.5 kg/cm2 ; eluting solvent: hexane/ethyl acetate=1). Fractions of 50 ml were collected and the 66th to 87th fractions were combined to obtain 5.64 g (yield=55.9 %) of 2',4,4'-tris(methoxymethoxy)chalcone.
Reaction SMILES: C([Li])CCC.CCCCCC.Br[C:13]1[C:18]([CH3:19])=[C:17]([O:20][CH3:21])[C:16]([CH3:22])=[C:15]([CH3:23])[C:14]=1[O:24][CH3:25].[CH2:26](Br)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>O1CCCC1>[CH2:26]([C:13]1[C:18]([CH3:19])=[C:17]([O:20][CH3:21])[C:16]([CH3:22])=[C:15]([CH3:23])[C:14]=1[O:24][CH3:25])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: COc1c(C)c(C)c(OC)c(Br)c1C
Reactant: BrCc1ccccc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: COc1c(C)c(C)c(OC)c(Cc2ccccc2)c1C
Reaction time: 0.33 h
Yield: 82.6 %

Procedure:
A 24.1 ml (38.6 mmole) of n-butyllithium.hexane solution was added dropwise to 10.0 g (38.6 mmole) of 1-bromo-2,5-dimethoxy-3,4,6-trimethylbenzene dissolved in anhydrous tetrahydrofuran (100 ml), under an atmosphere of argon at -40° C. over the period of 10 minutes, followed by stirring for another 20 minutes. Then, 3.32 g (38.6×0.6 mmole) of cuprous bromide was added, followed by stirring at -40° to -20° C. for 1 hour. After addition of a solution of 6.60 g (38.6 mmole) of benzyl bromide in tetrahydrofuran (15 ml), the cooling bath was removed, the reaction solution was stirred at 70° C. for 1 hour and cooled with ice, followed by addition of 1N hydrochloric acid (50 ml) and stirring. The tetrahydrofuran was distilled off under reduced pressure, and isopropyl ether was added to the residue. The insoluble matter was filtered through a bed of Hyflo Supercell, and the isopropyl ether layer was separated out, washed with water and aqueous sodium chloride solution successively, dried (magnesium sulfate) and evaporated. The residual solution was distilled under reduced pressure to give 8.62 g (83%) of 1-benzyl-2,5-dimethoxy-3,4,6-trimethylbenzene, b.p. 140°-142° C. (0.3 torr) and m.p. 70° to 71° C.
Reaction SMILES: C[O-].[Na+].[OH:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11]([C:15]([OH:17])=[O:16])=[N:10][CH:9]=[CH:8]2.[Cl:18][C:19]1[CH:24]=[C:23](Cl)[N:22]=[CH:21][N:20]=1>CO.CN(C=O)C>[Cl:18][C:19]1[N:20]=[CH:21][N:22]=[C:23]([O:4][C:5]2[CH:6]=[C:7]3[C:12](=[CH:13][CH:14]=2)[C:11]([C:15]([OH:17])=[O:16])=[N:10][CH:9]=[CH:8]3)[CH:24]=1
Reactant: O=C(O)c1nccc2cc(O)ccc12
Reactant: Clc1cc(Cl)ncn1
Agent: C[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CO
Product: O=C(O)c1nccc2cc(Oc3cc(Cl)ncn3)ccc12
Temperature: 10 °C
Reaction time: 14 h

Procedure:
40 ml (20 mMol) of a 0.5 M solution of sodium methylate in MeOH are added to a suspension of 1.9 g (10 mMol) 6-hydroxy-isoquinoline-1-carboxylic acid (CAS 174299-07-1) in 50 ml MeOH and sonicated until a solution is obtained. The solvent is then evaporated off. The residue is dried in high vacuum for 4 h and 100 ml DMF are added. The suspension is cooled to 10° C. and a solution of 1.55 g (10 mMol) 4,6-dichloropyrimidine in 25 ml DMF is added. The reaction mixture is stirred at room temperature for 14 h. The solvent is evaporated off and the mixture is partitioned between H2O/EtOAc. After extraction, the aqueous phase is neutralized with a 1 N solution of HCl. The suspension is extracted with EtOAc, washed with H20 and brine, dried (MgSO4) and concentrated to give a beige powder: 1H-NMR (DMSO-d6): δ ppm 7.60 (s, 1H), 7.68 (dd, J=9.4, 2.3 Hz, 1H), 7.98 (d, J=2.3 Hz, 1H), 8.04 (d, J=5.5 Hz, 1H), 8.59 (d, J=5.9 Hz, 1H), 8.66 (s, 1H), 8.68 (s, 1H).
Reaction SMILES: O.[NH2:2][NH2:3].[Br:4][C:5]1[CH:6]=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:8](F)=[N:9][CH:10]=1>C(O)(C)C>[Br:4][C:5]1[CH:6]=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:8]([NH:2][NH2:3])=[N:9][CH:10]=1
Reactant: Fc1ncc(Br)cc1-c1ccccc1
Reactant: NN
Solvent: O
Solvent: CC(C)O
Product: NNc1ncc(Br)cc1-c1ccccc1
Temperature: 82 °C

Procedure:
Hydrazine monohydrate (1.76 mL, 13 mmol) was added into a solution of 5-bromo-2-fluoro-3-phenylpyridine (326 mg, 1.29 mmol) in isopropanol (12 mL) at room temperature. The reaction mixture was heated gradually to 82° C. over 5 h and continued to heat overnight, cooled to room temperature and concentrated to give 1-(5-bromo-3-phenylpyridin-2-yl)hydrazine which was used directly in next step.
Reaction SMILES: C([O:5][C:6](=[O:40])[C:7]([S:10][C:11]1[S:12][CH:13]=[C:14]([CH2:16][CH2:17][O:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)=[CH:21][C:20]=2[C:32]([N:34]2[CH2:39][CH2:38][O:37][CH2:36][CH2:35]2)=[O:33])[N:15]=1)([CH3:9])[CH3:8])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[F:31][C:28]1[CH:27]=[CH:26][C:25]([C:22]2[CH:23]=[CH:24][C:19]([O:18][CH2:17][CH2:16][C:14]3[N:15]=[C:11]([S:10][C:7]([CH3:8])([CH3:9])[C:6]([OH:40])=[O:5])[S:12][CH:13]=3)=[C:20]([C:32]([N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[O:33])[CH:21]=2)=[CH:30][CH:29]=1
Reactant: CC(C)(C)OC(=O)C(C)(C)Sc1nc(CCOc2ccc(-c3ccc(F)cc3)cc2C(=O)N2CCOCC2)cs1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC(C)(Sc1nc(CCOc2ccc(-c3ccc(F)cc3)cc2C(=O)N2CCOCC2)cs1)C(=O)O
Temperature: 25 °C
Reaction time: 12 h
Yield: 73.7 %

Procedure:
2-{[4-(2-{[4′-Fluoro-3-(morpholin-4-ylcarbonyl)biphenyl-4-yl]oxy}ethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid tert-butyl ester (180 mg) obtained in Example 93-2 was dissolved in dichloromethane (2 mL), trifluoroacetic acid (2 mL) was added, and the mixture was stirred at room temperature for 12 hr. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=1:1 to 0:1) to give the title compound (120 mg) as a colorless oil.
Reaction SMILES: [Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH3:10])=[CH:5][CH:4]=1.[Br:11][C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][C:19]=1[O:20][CH2:21][CH3:22])[CH:15]=[O:16].[Cl-].[NH4+]>C1COCC1>[Br:11][C:12]1[CH:13]=[C:14]([CH:15]([C:3]2[CH:8]=[CH:7][C:6]([CH2:9][CH3:10])=[CH:5][CH:4]=2)[OH:16])[CH:17]=[CH:18][C:19]=1[O:20][CH2:21][CH3:22]
Reactant: CCOc1ccc(C=O)cc1Br
Reactant: CCc1ccc(Br)cc1
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CCOc1ccc(C(O)c2ccc(CC)cc2)cc1Br
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 87.2 %

Procedure:
THF (10 mL) was added to magnesium (353 mg, 14.5 mmol), and furthermore 1-bromo-4-ethylbenzene (2 mL, 14.5 mmol) was added dropwise thereto and the mixture was heated to reflux for one hour. The reaction mixture was cooled to 0° C., and a solution of 3-bromo-4-ethoxybenzaldehyde (2.21 g, 9.68 mmol) in THF (5 mL) was added thereto and the reaction mixture was stirred at the same temperature for 1.5 hours. To the reaction mixture, a saturated ammonium chloride aqueous solution was added and the resulting mixture was extracted with ethyl acetate. The extract was washed with a saturated sodium chloride aqueous solution and dried over magnesium sulfate. The residue obtained by distilling the solvent under reduced pressure was purified by silica gel column chromatography [developing solution=n-hexane to n-hexane:ethyl acetate (3:1)] to obtain the title compound (2.83 g, 88%).
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([C:16](=[O:18])[CH3:17])[CH:8]=[C:9]([N+:13]([O-])=O)[C:10]=1[O:11][CH3:12])([CH3:4])([CH3:3])[CH3:2].[Cl-].[NH4+].C(O)C.O>[Fe].C(OCC)(=O)C>[NH2:13][C:9]1[CH:8]=[C:7]([C:16](=[O:18])[CH3:17])[CH:6]=[C:5]([C:1]([CH3:2])([CH3:3])[CH3:4])[C:10]=1[O:11][CH3:12]
Reactant: COc1c([N+](=O)[O-])cc(C(C)=O)cc1C(C)(C)C
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CCO
Product: COc1c(N)cc(C(C)=O)cc1C(C)(C)C
Temperature: 25 °C
Yield: 48.4 %

Procedure:
Iron powder (365 g) was added to a mixture of 1-[3-(tert-butyl)-4-methoxy-5-nitrophenyl]-1-ethanone (850 g), ammonium chloride (723 g), ethanol (4 l) and water (1 l) at 70° C. to 80° C. over a period of 1 hour. The reaction mixture was cooled to room temperature and then poured into a mixture of ice water and ethyl acetate and filtered through celite. The organic layer of the mother liquor was washed with brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the resulting crystals were filtered off to yield the title compound (362 g) as white crystals.
Reaction SMILES: C(OC([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:19]([CH2:20][CH2:21][O:22][CH:23]([CH3:25])[CH3:24])[C:18]3[CH:26]=[CH:27][CH:28]=[CH:29][C:17]=3[N:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[IH:30].C(O)C>C(OCC)C>[IH:30].[CH:23]([O:22][CH2:21][CH2:20][N:19]1[C:18]2[CH:26]=[CH:27][CH:28]=[CH:29][C:17]=2[N:16]=[C:15]1[N:11]1[CH2:12][CH2:13][CH2:14][NH:8][CH2:9][CH2:10]1)([CH3:25])[CH3:24]
Reactant: CC(C)OCCn1c(N2CCCN(C(=O)OC(C)(C)C)CC2)nc2ccccc21
Agent: I
Solvent: CCOCC
Solvent: CCO
Product: CC(C)OCCn1c(N2CCCNCC2)nc2ccccc21
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Combine 1-(t-butoxycarbonyl)-4-(1-(2-(isopropoxy)ethyl)-1H-benzimidazol-2-yl)[1,4]diazepane (0.63 g, 1.57 mmol), aqueous hydriodic acid (5 mL, 57%), and ethanol (10 mL). Heat to reflux. After 1 hour, cool to ambient temperature and pour the reaction mixture into diethyl ether (350 mL) and stir to give a solid. After 1 hour, collect the solid by filtration, rinse with diethyl ether, and dry in vacuo to give the title compound.
Reaction SMILES: [C:1]([O:21]C)(=O)[C:2]1[CH:7]=[CH:6][C:5]([S:8][S:9][C:10]2[CH:19]=[CH:18][C:13]([C:14]([O:16]C)=O)=[CH:12][CH:11]=2)=[CH:4][CH:3]=1.[CH2:23]([CH2:25][NH2:26])[OH:24]>>[OH:24][CH2:23][CH2:25][NH:26][C:14](=[O:16])[C:13]1[CH:12]=[CH:11][C:10]([S:9][S:8][C:5]2[CH:4]=[CH:3][C:2]([C:1]([NH:26][CH2:25][CH2:23][OH:24])=[O:21])=[CH:7][CH:6]=2)=[CH:19][CH:18]=1
Reactant: NCCO
Reactant: COC(=O)c1ccc(SSc2ccc(C(=O)OC)cc2)cc1
Product: O=C(NCCO)c1ccc(SSc2ccc(C(=O)NCCO)cc2)cc1
Temperature: 140 °C
Yield: 68.7 %

Procedure:
A mixture of 16.5 g of dimethyl 4,4'-dithiobis[benzoate] [Werbel et al., J. Heterocycl. Chem. 17, 497 (1980)] and 13.0 g of ethanolamine was heated at 140° C. while collecting the methanol which distilled from the reaction. After evolution of methanol had ceased, the reaction mixture was cooled and acidified with dilute hydrochloric acid. The solid product which formed was collected and dried to give 13.3 g of N,N'-bis(2-hydroxyethyl)-4,4'-dithiobis[benzamide], used directly in the next reaction.
Reaction SMILES: [CH2:1]([O:3][CH:4]([O:19][CH2:20][CH3:21])[C:5]1[N:6]=[C:7]2[C:12]([C:13](OCC)=[O:14])=[CH:11][CH:10]=[CH:9][N:8]2[CH:18]=1)[CH3:2].[K+].[Br-]>>[CH2:1]([O:3][CH:4]([O:19][CH2:20][CH3:21])[C:5]1[N:6]=[C:7]2[C:12]([CH2:13][OH:14])=[CH:11][CH:10]=[CH:9][N:8]2[CH:18]=1)[CH3:2]
Reactant: CCOC(=O)c1cccn2cc(C(OCC)OCC)nc12
Agent: [Br-]
Agent: [K+]
Product: CCOC(OCC)c1cn2cccc(CO)c2n1

Procedure:
From 2i (yield: 60%); mp 87-89° C.; IR (KBr) 2977, 1148 cm−1; 1H NMR (400 MHz, CDCl3) δ 1.25 (t, 6H, J=7 Hz), 3.68 (m, 4H), 4.52 (brs, 1H), 5.02 (s, 2H), 5.71 (s, 1H), 6.75 (t, 1H, J=7 Hz), 7.12 (d, 1H, J=7 Hz), 7.65 (s, 1H), 8.00 (d, 1H, J=7 Hz); 13C NMR (100 MHz, CDCl3) δ 15.3, 61.7, 61.9, 98.6, 106.1, 110.7, 112.5, 121.5, 124.8, 130.2, 143.9; MS m/z 250 (M+, 4), 206 (33), 177 (100), 175 (38), 159 (91), 78 (15).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=O)=[C:4]([O:11][CH3:12])[CH:3]=1.[F:13][C:14]1[CH:15]=[C:16]([NH2:22])[C:17]([NH2:21])=[CH:18][C:19]=1[F:20]>>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]2[NH:21][C:17]3[CH:18]=[C:19]([F:20])[C:14]([F:13])=[CH:15][C:16]=3[N:22]=2)=[C:4]([O:11][CH3:12])[CH:3]=1
Reactant: COc1cc(Cl)ccc1C(=O)O
Reactant: Nc1cc(F)c(F)cc1N
Product: COc1cc(Cl)ccc1-c1nc2cc(F)c(F)cc2[nH]1
Temperature: 180 °C
Yield: 77 %

Procedure:
To a suspension of 4-chloro-2-methoxy-benzoic acid (5 g, 0.026 mol; CAS Reg. No. 78955-90-5) in polyphosphoric acid (50 g) was added compound 4,5-difluoro-benzene-1,2-diamine (3.86 g, 0.026 mol; CAS Reg. No. 76179-40-3) and the resulting mixture was heated to 180° C. for 1 h. The reaction mixture was then cooled and neutralized with ice cold 10% aqueous sodium carbonate solution, and then extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and evaporated under reduced pressure. The residue was purified by column chromatography over silica gel (25% ethyl acetate/n-hexane) to give the desired compound as a brown solid (77%). MS (Turbo Spray): m/z=295.1 (M+H).
Reaction SMILES: O1CCCC1.Br[C:7]1[CH:16]=[N:15][C:10]2[O:11][CH2:12][CH2:13][NH:14][C:9]=2[CH:8]=1.[CH3:17][O:18][C:19]1[CH:20]=[N:21][CH:22]=[C:23](B2OC(C)(C)C(C)(C)O2)[CH:24]=1.C(=O)([O-])[O-].[K+].[K+]>O>[CH3:17][O:18][C:19]1[CH:24]=[C:23]([C:7]2[CH:16]=[N:15][C:10]3[O:11][CH2:12][CH2:13][NH:14][C:9]=3[CH:8]=2)[CH:22]=[N:21][CH:20]=1
Reactant: COc1cncc(B2OC(C)(C)C(C)(C)O2)c1
Reactant: Brc1cnc2c(c1)NCCO2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: COc1cncc(-c2cnc3c(c2)NCCO3)c1
Temperature: 80 °C
Reaction time: 4 h
Yield: 80 %

Procedure:
To 3 ml of tetrahydrofuran/0.5 ml of distilled water, 7-bromo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine (80.0 mg, 0.37 mmol), 3-methoxy-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolane-2-yl)-pyridine (105 mg, 0.45 mmol), potassium carbonate (103 mg, 0.74 mmol) and tetrakis triphenylphosphine palladium (129 mg, 0.11 mmol) were added and stirred at 80° C. for 4 hours. After completion of the reaction, the mixture was extracted with ethyl acetate, and the combined organic layer was dried over anhydrous sodium sulfate (Na2SO4), filtered and evaporated under reduced pressure. The residue was purified by column chromatography on amine silica eluting with a solvent of dichloromethane:methanol=40:1. The fractions containing the product were collected and evaporated to obtain 7-(5-methoxy-pyridin-3-yl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine as white solid (72 mg, 80%).
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[S:3]([O:6]S(C(F)(F)F)(=O)=O)(=[O:5])=[O:4].[C:16]([C:20]1[CH:21]=[C:22](O)[CH:23]=[C:24]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:25]=1)([CH3:19])([CH3:18])[CH3:17]>N1C=CC=CC=1>[O:6]([C:22]1[CH:21]=[C:20]([C:16]([CH3:18])([CH3:17])[CH3:19])[CH:25]=[C:24]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:23]=1)[S:3]([C:2]([F:15])([F:14])[F:1])(=[O:5])=[O:4]
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Reactant: CC(C)(C)c1cc(O)cc(C(C)(C)C)c1
Solvent: c1ccncc1
Product: CC(C)(C)c1cc(OS(=O)(=O)C(F)(F)F)cc(C(C)(C)C)c1
Temperature: 25 °C

Procedure:
Molecules of the present invention can be synthesized using well-known organic synthesis methods. FIG. 8 shows a method for synthesizing a molecule belonging to the subclass shown in FIG. 6 according to one embodiment of the present invention. A detailed description of the organic synthesis is described below in an experimental subsection called “Synthesis of 1,4-bis[3′,5′-di-tert-butylphenylethynyl]-5-methyl-2-methoxycarbonylbenzene.” The organic synthesis includes adding nitric acid and water to a solution of 2,5-dibromo-p-xylene 802, which is refluxed to obtain in solution 2,5-dibromo-4-methylbenzoic acid 804. Methanol and concentrated sulfuric acid are added to the solution of 2,5-dibromo-4-methylbenzoic acid 804, which is refluxed to obtain a solution of methyl 2,5-dibromo-4-methylbenzoate 806. In a separate part of the synthesis, trifluoromethanesulfonic anhydride and pyridine are added to a solution of 3,5-di-tert-butylphenol 808 and the solution is warmed to room temperature to obtain 3,5-di-tert-butylphenyl triflate 810. A solution of 3,5-di-tert-butylphenyl triflate 810, PdCl2, (PPH3)2, CuI, tetrabutylammonium iodide, and trimethylsilylacetylene are stirred to obtain 1-[3′,5′-di-tert-butylphenyl-2-trimethylsilylacetylene 812. Combining 1-[3′,5′-di-tert-butylphenyl-2-trimethylsilylacetylene 812, methyl 2,5-dibromo-4-methylbenzoate 806, PdCl2, (PPH3)2, CuI, triethylamine, tetrahydrofuran, and tetrabutylammonium fluoride and stirring at room temperature yields the desired molecule 1,4-bis[3′,5′-di-tert-butylphenylethynyl]-5-methyl-2-methoxycarbonylbenzene 814.