Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([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.[OH-].[K+].Cl[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][OH:36]>CS(C)=O>[C:1]([C:20]1[CH:21]=[CH:22][C:23]([O:26][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][OH:36])=[CH:24][CH:25]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Oc1ccc(C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Reactant: OCCCCCCCl
Agent: [K+]
Agent: [OH-]
Solvent: CS(C)=O
Product: OCCCCCCOc1ccc(C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Temperature: 100 °C
Reaction time: 2 h

Procedure:
A 25 mL 3-neck flask was equipped with a magnetic stirrer, a reflux condenser with nitrogen blanket, and a heating mantle with a temperature controller and a thermocouple. The flask was charged with 1.12 grams (0.0033 moles) of 4-tritylphenol, 0.22 grams (0.0033 moles, 85 wt. %) of potassium hydroxide pellets, and with 5 mL of dimethylsulfoxide. The mixture was stirred under nitrogen while heating to 100° C. After about 2 hours, all of the potassium hydroxide had dissolved, and the mixture was cooled to 70° C. 6-Chlorohexanol (0.45 grams, 0.0033 moles) was then added in one portion. The reaction mixture was maintained at 100° C. for about 0.5 hours, then it was stirred at room temperature overnight. A sample withdrawn for GC analysis at this point showed no remaining starting materials, indicating that the reaction was completed. The reaction mixture was poured into 100 mL of water. Solids precipitated. The mixture was filtered. The beige solids were washed on the filter with several portions of water, then they were air-dried. The yield of product was 1.2 grams (83%). The structure was confirmed by IR, 1H- and 13C-NMR, and GC/MS analyses.
Reaction SMILES: [Li]CCCC.CCCCCC.CC1(C)CCCC(C)(C)N1.[Cl:22][C:23]1[CH:28]=[N:27][CH:26]=[CH:25][N:24]=1.[CH2:29]([Sn:33](Cl)([CH2:38][CH2:39][CH2:40][CH3:41])[CH2:34][CH2:35][CH2:36][CH3:37])[CH2:30][CH2:31][CH3:32].[Li]>C1COCC1>[Cl:22][C:23]1[CH:28]=[N:27][CH:26]=[C:25]([Sn:33]([CH2:34][CH2:35][CH2:36][CH3:37])([CH2:38][CH2:39][CH2:40][CH3:41])[CH2:29][CH2:30][CH2:31][CH3:32])[N:24]=1
Reactant: Clc1cnccn1
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Agent: CC1(C)CCCC(C)(C)N1
Agent: [Li]
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCCC[Sn](CCCC)(CCCC)c1cncc(Cl)n1
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 71.6 %

Procedure:
To a solution of nBuLi, 1.6 m in hexane (21.49 mL, 34.4 mmol) in THF (80 mL) at −50° C. was added 2,2,6,6-tetramethylpiperidine (5.80 mL, 34.4 mmol). The mixture was warmed to 0° C. and stirred for 20 min. The mixture was then cooled to −78° C. In another flask, 2-chloropyrazine (0.974 mL, 10.91 mmol) and tributyltin chloride (2.96 mL, 10.91 mmol) were dissolved in THF (50 mL) and cooled to −78° C. The cooled solution was transferred to lithium solution through cannula and the resulting orange mixture was slowly warmed up to −40° C. in 3 h, and was quenched with sat. HCl:EtOH:THF (1:4:5, 50 mL) and warmed to RT. The mixture was neutralized with sat. NaHCO3 and the volatiles were removed. The residue was diluted in H2O and extracted with DCM. The combined organic layers were dried, filtered and concentrated. The residue was purified with silica gel chromatography (eluting with 0-30% DCM in Hex) to give 2-chloro-6-(tributylstannyl)pyrazine (3.15 g, 7.81 mmol, 71.5%) as a clear oil. MS (ESI, pos. ion) m/z: 405 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 8.42 (1H, s), 8.38 (1H, s), 1.50-1.62 (6H, m), 1.27-1.41 (6H, m), 1.14-1.22 (6H, m), 0.89 (9H, t, J=7.3 Hz)
Reaction SMILES: [CH2:1]([NH:8][CH:9]([CH3:16])[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:18][C:19]([O:21][CH3:22])=[O:20].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:1]([N:8]([CH2:18][C:19]([O:21][CH3:22])=[O:20])[CH:9]([CH3:16])[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC(=O)CBr
Reactant: CCOC(=O)CC(C)NCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCOC(=O)CC(C)N(CC(=O)OC)Cc1ccccc1
Temperature: 25 °C
Yield: 82.3 %

Procedure:
A suspension of ethyl 3-(benzylamino)butanoate (5.9 g, 26.7 mmol), methyl bromoacetate (3.0 ml, 31.7 mmol) and potassium carbonate (7.4 g, 53.5 mmol) in acetonitrile (100 ml), was stirred at room temperature for 18 hs. The reaction was filtered through celite and concentrated to give ethyl 3-[benzyl(2-methoxy-2-oxoethyl)amino]butanoate (6.45 g, 82%) as a clear oil, MS (M+H)+=294.
Reaction SMILES: [C:1]([O:5][C:6](=[O:33])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15](=[O:32])[C:16]2[CH:21]=[C:20]([OH:22])[CH:19]=[C:18]([O:23][C:24]3[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[CH:26][CH:25]=3)[CH:17]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[Br:34][C:35]1[CH:40]=[CH:39][C:38]([CH2:41]Br)=[CH:37][CH:36]=1>>[C:1]([O:5][C:6](=[O:33])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15](=[O:32])[C:16]2[CH:17]=[C:18]([O:23][C:24]3[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[CH:26][CH:25]=3)[CH:19]=[C:20]([O:22][CH2:41][C:38]3[CH:39]=[CH:40][C:35]([Br:34])=[CH:36][CH:37]=3)[CH:21]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: BrCc1ccc(Br)cc1
Reactant: CC(C)(C)OC(=O)NC1CCC(NC(=O)c2cc(O)cc(Oc3ccc(C#N)cc3)c2)CC1
Product: CC(C)(C)OC(=O)NC1CCC(NC(=O)c2cc(OCc3ccc(Br)cc3)cc(Oc3ccc(C#N)cc3)c2)CC1
Yield: 83.9 %

Procedure:
Using 1.3 g (2.88 mmol) of {4-[3-(4-cyanophenoxy)-5-hydroxybenzoylamino]cyclohexyl}carbamic acid tert-butyl ester and 1-bromo-4-bromomethyl-benzene (0.72 g, 2.88 mmol) and following the procedure of Example 42(b) afforded 1.5 g of the required product. 1H NMR (DMSO-d6): δ 1.20 (4H, m), 1.4 (9H, s), 1.8 (4H, m), 3.2 (1H, m), 3.7 (1H, m), 5.2 (2H, s), 6.78 (1H, d), 6.88 (1H, s), 7.12 (2H, d), 7.2 (1H, s), 7.4 (3H, s), 7.6 (2H, d), 7.86 (2H, d), 8.28 (1H, d).
Reaction SMILES: [Cl:1][C:2]1[C:3]([OH:24])=[CH:4][C:5]([OH:23])=[C:6]([C:8](=[O:22])[CH2:9][C:10]2[CH:21]=[CH:20][C:13]([O:14][CH2:15][CH2:16][CH2:17][C:18]#[N:19])=[CH:12][CH:11]=2)[CH:7]=1.[C:25](OC(=O)C)(=O)[CH3:26].C(=O)([O-])[O-].[K+].[K+]>CCCCCC.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]2[C:5](=[CH:4][C:3]=1[OH:24])[O:23][C:25]([CH3:26])=[C:9]([C:10]1[CH:21]=[CH:20][C:13]([O:14][CH2:15][CH2:16][CH2:17][C:18]#[N:19])=[CH:12][CH:11]=1)[C:8]2=[O:22]
Reactant: N#CCCCOc1ccc(CC(=O)c2cc(Cl)c(O)cc2O)cc1
Reactant: CC(=O)OC(C)=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: Cc1oc2cc(O)c(Cl)cc2c(=O)c1-c1ccc(OCCCC#N)cc1

Procedure:
This compounds was synthesised in the same manner as described above. 4-{4-[2-(5-Chloro-2,4-dihydroxy-phenyl)-2-oxo-ethyl]-phenoxy}-butyronitrile (0.62 g, 1.8 mmol), acetic anhydride (1.0 ml), potassium carbonate (1 g, 7.2 mmol). 4-[4-(6-Chloro-7-hydroxy-2-methyl-4-oxo-4H-chromen-3-yl)-phenoxy]-butyronitrile was obtained as a white solid (0.55 g, 82.7%) Rf 0.6 ethyl acetate/hexane (70/30).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[O:23][C:17]3=[CH:18][N:19]=[C:20](Cl)[CH:21]=[C:16]3[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC1(C)C(C)(C)OB([C:32]2[O:36][C:35]([Si:37]([CH:44]([CH3:46])[CH3:45])([CH:41]([CH3:43])[CH3:42])[CH:38]([CH3:40])[CH3:39])=[N:34][CH:33]=2)O1>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[O:23][C:17]3=[CH:18][N:19]=[C:20]([C:32]4[O:36][C:35]([Si:37]([CH:41]([CH3:43])[CH3:42])([CH:44]([CH3:46])[CH3:45])[CH:38]([CH3:39])[CH3:40])=[N:34][CH:33]=4)[CH:21]=[C:16]3[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CCC(C2Cc3cc(Cl)ncc3O2)CC1
Reactant: CC(C)[Si](c1ncc(B2OC(C)(C)C(C)(C)O2)o1)(C(C)C)C(C)C
Product: CC(C)[Si](c1ncc(-c2cc3c(cn2)OC(C2CCN(C(=O)OC(C)(C)C)CC2)C3)o1)(C(C)C)C(C)C

Procedure:
The title compound is prepared from 4-(5-chloro-2,3-dihydro-furo[2,3-c]pyridin-2-yl)-piperidine-1-carboxylic acid tert-butyl ester and 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2-triisopropylsilanyl-oxazole following a procedure analogous to that described for Intermediate 15. LC (method 10): tR=2.02 min; Mass spectrum (ESI+): m/z=528 [M+H]+.
Reaction SMILES: [C:1]1([CH:7]=[C:8]([C:13](=O)[CH3:14])[C:9]([O:11][CH3:12])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[SH:23]>CN(C)C=O.CCOCC>[CH3:14][C:13]1[NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[S:23][CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:8]=1[C:9]([O:11][CH3:12])=[O:10]
Reactant: Nc1ccccc1S
Reactant: COC(=O)C(=Cc1ccccc1)C(C)=O
Solvent: CN(C)C=O
Solvent: CCOCC
Product: COC(=O)C1=C(C)Nc2ccccc2SC1c1ccccc1
Temperature: 25 °C
Reaction time: 6 h

Procedure:
A solution of 2-[(phenyl)methylene]-3-oxobutanoic acid, methyl ester (13.0 g., 63.7 mmole) in dry dimethylformamide (20 ml.) is treated dropwise with 2-aminothiophenol (8.85 g. of 90%, 63.7 mmole). A slight release of heat is noted. The reaction is stirred at room temperature for 6 hours and then heated at 65° for 72 hours. It is cooled to room temperature and diluted with ether. The resulting solution is thoroughly washed with water, sodium bicarbonate and brine. After drying over anydrous magnesium sulfate, the solvent is stripped off to give a yellow solid. It is triturated with isopropyl ether and filtered off to provide 6.93 g. of light yellow crystals. Recrystallization from isopropyl ether-dichloromethane gives an analytically pure sample of 2,5-dihydro-4-methyl-2-phenyl-1,5-benzothiazepine-3-carboxylic acid, methyl ester; m.p. 154°-156°. TLC(silica gel, hexane:acetone, 70:30) Rf =0.35.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][Si:10]([CH3:13])([CH3:12])[CH3:11])=[CH:4][N:3]=1.[CH3:14][N:15]1[CH:19]2[CH2:20][CH2:21][CH2:22][CH:18]2[NH:17][C:16]1=[O:23]>>[CH3:14][N:15]1[CH:19]2[CH2:20][CH2:21][CH2:22][CH:18]2[N:17]([C:2]2[CH:7]=[CH:6][C:5]([C:8]#[C:9][Si:10]([CH3:13])([CH3:12])[CH3:11])=[CH:4][N:3]=2)[C:16]1=[O:23]
Reactant: C[Si](C)(C)C#Cc1ccc(Br)nc1
Reactant: CN1C(=O)NC2CCCC21
Product: CN1C(=O)N(c2ccc(C#C[Si](C)(C)C)cn2)C2CCCC21

Procedure:
The title compound, an off-white solid, MS: m/e=314.1 (M+H+), was prepared in accordance with the general method of example 106, step 4 starting from 2-bromo-5-((trimethylsilyl)ethynyl)-pyridine (Example 37, step 1) and (3aRS,6aSR)-1-methylhexahydrocyclopenta[d]imidazol-2(1H)-one (Example 106, step 3).
Reaction SMILES: [CH3:1][N:2]([CH3:21])[S:3]([C:6]1[C:11]([N:12]2[CH:17]=[CH:16][C:15](=[O:18])[CH:14]=[CH:13]2)=[CH:10][C:9]([NH2:19])=[C:8]([NH2:20])[CH:7]=1)(=[O:5])=[O:4].[C:22](O)(=[O:26])[C:23](O)=[O:24].N>Cl>[CH3:1][N:2]([CH3:21])[S:3]([C:6]1[CH:7]=[C:8]2[C:9](=[CH:10][C:11]=1[N:12]1[CH:13]=[CH:14][C:15](=[O:18])[CH:16]=[CH:17]1)[NH:19][C:23](=[O:24])[C:22](=[O:26])[NH:20]2)(=[O:5])=[O:4]
Reactant: CN(C)S(=O)(=O)c1cc(N)c(N)cc1-n1ccc(=O)cc1
Reactant: O=C(O)C(=O)O
Agent: Cl
Agent: N
Product: CN(C)S(=O)(=O)c1cc2[nH]c(=O)c(=O)[nH]c2cc1-n1ccc(=O)cc1
Yield: 34.2 %

Procedure:
First, a mixture containing 500 mg of 4-dimethylsulfamoyl-5-(4-oxo-4H-pyridin-1-yl)-1,2-phenylenediamine, 438 mg of oxalic acid, and 10 ml of 2N hydrochloric acid was refluxed by heating in an oil bath for 3 hours. The mixture was cooled and made basic with aqueous ammonia. Precipitated crystals were filtered. Then, 534 mg of the crude crystals thus obtained were further recrystallized with dimethylformaldehyde and water to give 201 mg of 6-dimethylsulfamoyl-7-(4-oxo-4H-pyridin-1-yl)-1,4-dihydroquinoxaline-2,3-dione.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([C:8]2[N:9]=[C:10](S)[NH:11][CH:12]=2)[CH:5]=[CH:4][N:3]=1.CN(C)C=O>[Ni].C(Cl)(Cl)Cl.CO>[NH2:1][C:2]1[CH:7]=[C:6]([C:8]2[N:9]=[CH:10][NH:11][CH:12]=2)[CH:5]=[CH:4][N:3]=1
Reactant: Nc1cc(-c2c[nH]c(S)n2)ccn1
Agent: [Ni]
Solvent: ClC(Cl)Cl
Solvent: CO
Solvent: CN(C)C=O
Product: Nc1cc(-c2c[nH]cn2)ccn1

Procedure:
To a solution of 2.3 g. (12 mmoles) of 4-(2-amino-4-pyridyl)imidazole-2-thiol in 60 ml. of dimethylformamide was added 8 g. of Raney nickel and the mixture heated at 115° C. for 3 hours. The mixture was filtered and the filtrate concentrated to a brown solid. After trituration with boiling chloroform, the solid was taken up in 50 ml. of absolute ethanol, treated with charcoal and the filtered solution concentrated to a small volume. The precipitate was filtered and dried, 1.12 g. (60%), m.p. 193°-196° C. The analytical sample was prepared by chromatographing on Florisil TM using chloroform-methanol (9:1, v:v) as the eluent, m.p. 196°-198° C.
Reaction SMILES: [Cl:1][C:2]1[C:7]([N+:8]([O-])=O)=[C:6]([Cl:11])[CH:5]=[C:4]([CH3:12])[N:3]=1>C(O)C.[Ni]>[NH2:8][C:7]1[C:2]([Cl:1])=[N:3][C:4]([CH3:12])=[CH:5][C:6]=1[Cl:11]
Reactant: Cc1cc(Cl)c([N+](=O)[O-])c(Cl)n1
Agent: [Ni]
Solvent: CCO
Product: Cc1cc(Cl)c(N)c(Cl)n1
Temperature: 60 °C
Reaction time: 7 h
Yield: 96 %

Procedure:
2,4-Dichloro-6-methyl-3-nitropyridine (30 g, 144.9 mmol) was dissolved in ethanol (300 mL), and Raney nickel (1.50 g, 25.6 mmol) was added to the solution, followed by stirring for 7 hours at 60° C. under hydrogen atmosphere (0.15 MPa). Raney nickel was removed through filtration, and the filtrate was concentrated under reduced pressure. The residue was dissolved in chloroform (60 mL), and the solution was left to stand for one hour. Subsequently, the formed insoluble substance was removed through filtration, and the filtrate was concentrated under reduced pressure, to thereby yield 24.62 g of 3-amino-2,4-dichloro-6-methylpyridine (yield: 96%) as a colorless solid. The product was recrystallized from hexane, to thereby yield colorless crystals.
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([C:12]([OH:14])=O)[CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2.C([N:17](CC)CC)C.COC(Cl)=O.O>CC(C)=O.CC1C=CC(CCN)=CC=1>[N:8]1[C:9]2[C:4](=[CH:3][CH:2]=[CH:11][C:10]=2[C:12]([NH2:17])=[O:14])[CH:5]=[CH:6][CH:7]=1
Reactant: CCN(CC)CC
Reactant: O=C(O)c1cc(Cl)cc2cccnc12
Agent: COC(=O)Cl
Agent: Cc1ccc(CCN)cc1
Solvent: CC(C)=O
Solvent: O
Product: NC(=O)c1cccc2cccnc12

Procedure:
5.2 g of 6-chloro-quinoline-8-carboxylic acid in 150 ml of acetone were combined, while stirring and cooling with ice, with 2.8 g of triethylamine and 2.6 g of chloroformic acid methyl ester. The whole was stirred for about 10 minutes, a solution of 3.4 g of 2-(4-methylphenyl)-ethylamine in 50 ml of 2-(4-methylphenyl)-ethyl-amine in 50 ml of acetone was added and the mixture was again stirred for 1 hour at room temperature. Then, water was added, the precipitate was filtered off with suction, treated with a dilute ammonia solution, undissolved matter was filtered off and recrystallized from dilute methanol. The 6-chloro-N-(2-<4-methylphenyl>-ethyl)-quinoline-8-carboxylic acid amide so obtained was found to melt at 102°-104° C.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[CH:5]=[C:4]([NH:14][C:15]2[CH:19]=[C:18]([CH3:20])[NH:17][N:16]=2)[N:3]=1>CC(O)C>[CH:9]([O:12][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[CH:5]=[C:4]([NH:14][C:15]2[CH:19]=[C:18]([CH3:20])[NH:17][N:16]=2)[N:3]=1)([CH3:10])[CH3:8]
Reactant: COc1ccc2cc(Nc3cc(C)[nH]n3)nc(Cl)c2c1
Solvent: CC(C)O
Product: COc1ccc2cc(Nc3cc(C)[nH]n3)nc(OC(C)C)c2c1

Procedure:
Similar procedure as described in example 10 was used, starting from propan-2-ol and (1-chloro-7-methoxy-isoquinolin-3-yl)-(5-methyl-1H-pyrazol-3-yl)-amine to give (1-isopropoxy-7-methoxy-isoquinolin-3-yl)-(5-methyl-1H-pyrazol-3-yl)-amine. LC-MS m/e 313(MH+).
Reaction SMILES: [CH2:1]([C:13]1[CH:14]=[C:15]([C:18]2[C:23]3=[N:24][S:25][N:26]=[C:22]3[C:21](Br)=[C:20]([Cl:28])[C:19]=2[Cl:29])[S:16][CH:17]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[CH2:30]([C:42]1[CH:43]=[C:44]([Sn](C)(C)C)[S:45][CH:46]=1)[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.ClC1C=CC=CC=1>[CH2:1]([C:13]1[CH:14]=[C:15]([C:18]2[C:23]3=[N:24][S:25][N:26]=[C:22]3[C:21]([C:44]3[S:45][CH:46]=[C:42]([CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])[CH:43]=3)=[C:20]([Cl:28])[C:19]=2[Cl:29])[S:16][CH:17]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCCCCc1csc([Sn](C)(C)C)c1
Reactant: CCCCCCCCCCCCc1csc(-c2c(Cl)c(Cl)c(Br)c3nsnc23)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: Clc1ccccc1
Product: CCCCCCCCCCCCc1csc(-c2c(Cl)c(Cl)c(-c3cc(CCCCCCCCCCCC)cs3)c3nsnc23)c1
Temperature: 120 °C
Yield: 93 %

Procedure:
4-(4-Dodecyl-thiophen-2-yl)-5,6-dichloro-7-bromo-benzo[1,2,5]thiadiazole (0.530 g, 0.99 mmol), (4-dodecyl-thiophen-2-yl)-trimethyl-stannane (0.577 g, 1.39 mmol), and Pd(PPh3)2Cl2 (34.8 mg) were placed in a 100-mL Schlenk flask. The system was subjected to three quick vacuum-nitrogen cycles and 40 mL of anhydrous chlorobenzene was added. The mixture was heated at 120° C. for 17 hours. After the reaction was cooled down, the solvent was removed by rotary evaporation. The product was purified by silica gel column with chloroform/hexane (v/v, 1/1) as the eluent. The final product (650 mg, 92.8% yield) was obtained as an orange solid after being dried in vacuo. 1H NMR (CDCl3, 500 MHz): δ 7.49 (d, 2H, J=1.0 Hz), 7.22 (d, 2H, J=1.0 Hz), 2.72 (t, 4H, J=8.0 Hz), 1.71 (m, 4H), 1.27 (m, 36H), 0.89 (t, 6H, 7.0 Hz). 13C NMR (CDCl3, 500 MHz): δ 152.71, 143.12, 134.32, 134.23, 132.64, 126.42, 123.09, 31.97, 30.53, 30.46, 29.74, 29.72, 29.70, 29.67, 29.54, 29.42, 22.75, 14.19. Anal. calcd. for (C38H54Cl2N2S3): C, 64.65; H, 7.71; N, 3.97. Found: C, 64.72; H, 7.65; N, 3.98. m.p: 79-80° C.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[C:20]([CH:21](O)[CH3:22])=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][N:17]=2)[N:12]=1)(=[O:4])=[O:3].[C:24]1(=[O:34])[NH:28][C:27](=[O:29])[C:26]2=[CH:30][CH:31]=[CH:32][CH:33]=[C:25]12.N(C(OC(C)C)=O)=NC(OC(C)C)=O.O>C1COCC1>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[C:20]([CH:21]([N:28]2[C:24](=[O:34])[C:25]3[C:26](=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:27]2=[O:29])[CH3:22])=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][N:17]=2)[N:12]=1)(=[O:3])=[O:4]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: CC(O)c1cc2ncccc2nc1-c1ccccc1S(C)(=O)=O
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Solvent: O
Solvent: C1CCOC1
Product: CC(c1cc2ncccc2nc1-c1ccccc1S(C)(=O)=O)N1C(=O)c2ccccc2C1=O
Reaction time: 0.17 h

Procedure:
To a mixture of crude of 1-(2-(2-(methylsulfonyl)phenyl)-1,5-naphthyridin-3-yl)ethanol (700 mg, 2.13 mmol) and phthalimide (627 mg, 4.26 mmol) in THF (21 mL) was added triphenylphosphene (1.12 g, 4.26 mmol) at 0° C. The reaction mixture was stirred for 10 min at same temperature. Diisopropyl azodicarboxylate (0.9 mL, 4.26 mmol) was added to mixture at 0° C. The reaction mixture was stirred for overnight at 0° C. Water was added to reaction mixture and extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated in vacuo to give 2-(1-(2-(2-(methylsulfonyl)phenyl)-1,5-naphthyridin-3-yl)ethyl)isoindoline-1,3-dione: LC-MS (ESI) m/z 458.1 [M+H]+. It was carried on crude for next step.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]([Br:12])[C:9]([OH:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.Br[CH:15]([CH3:17])[CH3:16]>>[Br:1][C:2]1[CH:11]=[C:10]([Br:12])[C:9]([O:13][CH:15]([CH3:17])[CH3:16])=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2
Reactant: CC(C)Br
Reactant: Oc1c(Br)cc(Br)c2cccnc12
Product: CC(C)Oc1c(Br)cc(Br)c2cccnc12
Yield: 97 %

Procedure:
Reaction of 5,7-dibromo-quinolin-8-ol with 2-bromopropane following the method described in Example 8 gave 5,7-dibromo-8-isopropoxy-quinoline 6 (97%): 1H NMR (CDCl3): δ 8.94 (dd, J=1.5 and 4.2, 1 H), 8.48 (dd, J=1.5 and 8.4, 1 H), 8.00 (s, 1 H), 7.52 (dd, J=4.2 and 8.4, 1 H), 5.22 (m, 1 H), 1.43 (d, J=6.1, 6 H); mass spectrum: m/z 344, 346, 348 (M++1, 50, 100 and 50%, respectively). Reaction of 6 with aryl boronic acids, and cleavage of the isopropoxy group following the method outlined in Example 8 gave compounds L1 and L2 (data in Table 4).
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[O:8]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:12][CH2:11][C:9]1=[O:10]>>[OH:8][C:18]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH2:12][CH2:11][C:9]([N:5]1[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]1)=[O:10]
Reactant: O=C1CCc2ccccc2O1
Reactant: CN1CCNCC1
Product: CN1CCN(C(=O)CCc2ccccc2O)CC1
Temperature: 80 °C
Reaction time: 2 h
Yield: 103.4 %

Procedure:
N-Methylpiperazine (1.23 g) was added to 3,4-dihydrocoumarine (1.80 g) and stirred for 2 hours at 80° C., thereby yielding the entitled compound (3.12 g) as pale brown solid.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][N:8]([Si](C(C)C)(C(C)C)C(C)C)[C:5]2=[N:6][CH:7]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O>O1CCCC1>[CH3:1][C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1
Reactant: Cc1cnc2c(ccn2[Si](C(C)C)(C(C)C)C(C)C)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: O
Product: Cc1cnc2[nH]ccc2c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To 5-Methyl-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (12, 0.160 g, 0.55 mmol) in tetrahydrofuran (3.0 mL) was added tetra-n-butylammonium fluoride (0.145 g, 0.55 mmol). The reaction was stirred for 1 hour at room temperature. The reaction was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 3% methanol in dichloromethane to provide light yellow solid (13, 0.07 g, 95%).
Reaction SMILES: C(OC([N:8]1[CH2:13][C:12]([C:14](=[O:16])[NH2:15])=[CH:11][CH2:10][CH2:9]1)=O)(C)(C)C.[F:17][C:18]([F:23])([F:22])[C:19]([OH:21])=[O:20]>C(Cl)(Cl)Cl>[F:17][C:18]([F:23])([F:22])[C:19]([OH:21])=[O:20].[C:14]([C:12]1[CH2:13][NH:8][CH2:9][CH2:10][CH:11]=1)(=[O:16])[NH2:15]
Reactant: CC(C)(C)OC(=O)N1CCC=C(C(N)=O)C1
Solvent: ClC(Cl)Cl
Solvent: O=C(O)C(F)(F)F
Product: NC(=O)C1=CCCNC1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
In 4.0 ml of chloroform, 1.1 g of 1-tert-butoxycarbonyl-5-carbamoyl-1,2,3,6-tetrahydropyridine was dissolved, and 4.0 ml of trifluoroacetic acid was added thereto. The reaction mixture was stirred for 30 minutes at room temperature, and was subsequently concentrated under reduced pressure to yield 1.4 g of crude 5-carbamoyl-1,2,3,6-tetrahydropyridine trifluoroacetate in the form of amorphous.
Reaction SMILES: N1CCCCC1.[CH:7](=O)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[C:16]([CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C(OC)(C)(C)C>[CH2:28]([O:27][C:25](=[O:26])[C:24]([C:16](=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[CH:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])[CH3:29]
Reactant: CCOC(=O)CC(=O)c1ccccc1
Reactant: CCCCCCCC=O
Solvent: COC(C)(C)C
Solvent: C1CCNCC1
Product: CCCCCCCC=C(C(=O)OCC)C(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
Piperidine (0.10 ml, 0.5 mol %) is added to a mixture of octanal (25.6 g, 0.20 mol) and ethyl benzoylacetate (38.4 g, 0.20 mol) at 5° C. The resulting solution is warmed to room temperature and stirred for 24 h, during which a fine emulsion is formed. The mixture is diluted with methyl t-butyl ether and the organic layer washed with 2 N aq. HCl-solution, water and brine, then dried over MgSO4.