Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:4]1[C:5](Br)=[N:6][CH:7]=[CH:8][CH:9]=1)(=[O:3])[CH3:2].[C:11]1([C:17]#[CH:18])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.CCN(C(C)C)C(C)C.[Cl-]>CN(C=O)C.C(Cl)Cl>[C:11]1([C:17]#[C:18][C:5]2[C:4]([C:1](=[O:3])[CH3:2])=[CH:9][CH:8]=[CH:7][N:6]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: C#Cc1ccccc1
Reactant: CC(=O)c1cccnc1Br
Agent: [Cl-]
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(=O)c1cccnc1C#Cc1ccccc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
66 mg 3-Acetyl-2-bromopyridine, 56 μL phenylacetylene, 170 μL DIPEA, 22.5 mg triphenylphosphinpalladium(II) chlorid, 3 mg Cu(I)I were suspended in 1 mL DMF under argon atmosphere and stirred for 16 h at 25° C. The mixture was diluted with DCM and extracted with diluted aq. NH3 and brine. The organic phase was concentrated and the mixture separated via flash chromatography (10 g SiO2, cyclohexane→cyclohexane/ethylacetate 70:30) to yield 40 mg 1-(2-(phenylethynyl)pyridin-3-yl)ethanone as solid. Analysis: HPLC-MS: Rt=1.21 min (method E), M+H=222.
Reaction SMILES: [CH3:1][CH:2]1[C:7]2(Cl)[C:8](=[O:9])[C:4]([Cl:13])([C:5]([Cl:12])=[C:6]2Cl)[CH:3]1[C:14]1[O:18][N:17]=[C:16]([CH3:19])[CH:15]=1.[CH3:20][CH2:21][O-].[Na+].C([OH:26])C>>[Cl:13][C:4]1[C:5]([Cl:12])=[CH:6][C:7]([C:8]([O:9][CH2:20][CH3:21])=[O:26])=[C:2]([CH3:1])[C:3]=1[C:14]1[O:18][N:17]=[C:16]([CH3:19])[CH:15]=1
Reactant: CC[O-]
Reactant: CCO
Reactant: Cc1cc(C2C(C)C3(Cl)C(=O)C2(Cl)C(Cl)=C3Cl)on1
Agent: [Na+]
Product: CCOC(=O)c1cc(Cl)c(Cl)c(-c2cc(C)no2)c1C
Temperature: 25 °C

Procedure:
0.11 g of 6-methyl-5-(3-methylisoxazol-5-yl)-1,2,3,4-tetrachlorobicyclo[2.2.1]hept-2en-7-one (a mixture of trans:cis=1:1) was dissolved in 1 ml of ethanol, and 0.06 g of sodium ethylate was added, while cooling with ice. The resulting solution was stirred for an hour at room temperature. The reaction solution was poured into 50 ml of ice-water, and extracted with 30 ml of ethyl acetate twice. The organic layer was washed with saturated salt water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. The obtained viscous liquid was purified on silica gel column chromatography (elution with n-hexane/ethyl acetate) to give 0.024 g of the title compound as white crystals. Melting point 86-88° C.
Reaction SMILES: [H-].[Na+].[OH:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[O:9])=[CH:6][CH:5]=1.[CH2:12]([O:14][CH:15]([O:18][CH2:19][CH3:20])[CH2:16]Br)[CH3:13]>CN(C=O)C>[CH2:12]([O:14][CH:15]([O:18][CH2:19][CH3:20])[CH2:16][O:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[O:9])=[CH:6][CH:5]=1)[CH3:13]
Reactant: O=Cc1ccc(O)cc1
Reactant: CCOC(CBr)OCC
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(COc1ccc(C=O)cc1)OCC
Temperature: 27.5 °C
Reaction time: 0.5 h
Yield: 64.7 %

Procedure:
To a stirred suspension of sodium hydride (2.5 g, 100 mmol, 98%) in DMF (100 mL) was added a solution of 4-hydroxy benzaldehyde (10.0 g, 82 mmol) in DMF (100 mL) slowly dropwise at 25-30° C. and stirred for 30 min at 25-30° C. 2,2-diethoxy-1-bromoethane (19.7 g, 100 mmol) was added to the reaction mixture. The reaction mixture was immersed in a preheated oil bath at 60° C. and stirring was continued for 48 h at 60° C. The reaction mixture was cooled to room temperatures, quenched with water (200 mL) and extracted with ethyl acetate (3×300 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated. The crude compound was purified by column chromatography using EtOAc:pet. ether (1:2) as eluent to yield the title compound (12.65 g, 58%) as a brown coloured liquid.
Reaction SMILES: [C:1]([NH:11][C@H:12]([C:14]([OH:16])=O)[CH3:13])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].C(N(CC)CC)C.C(Cl)(=O)OCC(C)C.Cl.C([O:35][C:36](=[O:48])[CH2:37][NH:38][CH:39]1[CH2:47][C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH2:40]1)C>O1CCCC1.C(Cl)(Cl)Cl>[C:1]([NH:11][C@H:12]([C:14]([N:38]([CH:39]1[CH2:47][C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH2:40]1)[CH2:37][C:36]([OH:48])=[O:35])=[O:16])[CH3:13])([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2]
Reactant: CCOC(=O)CNC1Cc2ccccc2C1
Reactant: C[C@H](NC(=O)OCc1ccccc1)C(=O)O
Agent: CC(C)COC(=O)Cl
Agent: Cl
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: C[C@H](NC(=O)OCc1ccccc1)C(=O)N(CC(=O)O)C1Cc2ccccc2C1
Reaction time: 8 h
Yield: 66.9 %

Procedure:
A solution of 22.3 g of N-carbobenzoxy-L-alanine and 14 ml of triethylamine in 200 ml of tetrahydrofuran is cooled to -10° C., and 13.1 ml of isobutyl chlorocarbonate is added dropwise in portions with stirring. After stirring for 30 minutes, a solution of 24.1 g of N-(indan-2-yl)glycine ethyl ester hydrochloride and 14 ml of triethylamine in 200 ml of chloroform is added dropwise at -10° C. to -5° C. After standing overnight at room temperature, the reaction mixture is washed in sequence with water, aqueous sodium hydrogen carbonate, 10% hydrochloric acid and water, and dried over anhydrous sodium sulfate. The solvent is distilled off under reduced pressure, the residue is dissolved in 100 ml of methanol, 75 ml of 2N sodium hydroxide is added, and the mixture is stirred at room temperature for 2 hours. Then, the mixture is made acidic with 10% hydrochloric acid to separate the resulting oil, which is extracted with 500 ml of ethyl acetate. The extract washed with water and dried, and the solvent is distilled off under reduced pressure to give 25 g of N-carbobenzoxy-L-alanyl-N-(indan-2-yl)glycine as an oil. This is dissolved in 50% ethanol and subjected to catalytic reduction in the presence of 4 g of 10% palladium-carbon. When the hydrogen absorption has ceased, the catalyst is filtered off, and the filtrate is concentrated under reduced pressure. Addition of 50 ml of methanol to the residue yields 11 g of L-alanyl-N-(indan-2-yl)glycine as colorless needles melting at 180°-182° C.
Reaction SMILES: [H-].[Na+].[CH2:3]([OH:8])[CH2:4][CH2:5][CH2:6][OH:7].[CH2:9](Br)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.O>CN(C=O)C>[CH2:9]([O:7][CH2:6][CH2:5][CH2:4][CH2:3][OH:8])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: BrCc1ccccc1
Reactant: OCCCCO
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: OCCCCOCc1ccccc1
Temperature: -20 °C
Reaction time: 0.5 h

Procedure:
42 g of sodium hydride (60%) is introduced at room temperature in portions into 900 ml of absolute DMF. 88.6 ml of 1,4-butanediol in 450 ml of absolute DMF is added in drops to the suspension that is cooled to −20° C. in such a way that the internal temperature does not exceed −15° C. After the addition has been completed, a solution of 121 ml of benzyl bromide in 870 ml of absolute DMF is quickly added in drops, and then the reaction mixture is stirred for 30 minutes at room temperature. The reaction is completed by careful addition of 315 ml of water. For working-up, the reaction mixture is stirred into 1.5 l of water and extracted 3 times with 1 l of ether in each case. The ethereal phases are combined, washed with water, dried on magnesium sulfate and concentrated by evaporation in a vacuum. Chromatography on silica gel with a hexane-ethyl acetate gradient yields 105 g of 4-benzyloxy-butan-1-ol as an oil.
Reaction SMILES: C(OC([NH:8][C@H:9]([CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)[CH:10]([OH:14])[C:11]([OH:13])=O)=O)(C)(C)C.Cl.[CH2:23]([O:30][NH2:31])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.CN1CCOCC1>ClCCl.ClCCl.CN(C=O)C>[NH2:8][C@H:9]([CH2:15][CH:16]1[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]1)[CH:10]([OH:14])[C:11]([NH:31][O:30][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:13]
Reactant: CC(C)(C)OC(=O)N[C@H](CC1CCCCC1)C(O)C(=O)O
Reactant: NOCc1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Product: N[C@H](CC1CCCCC1)C(O)C(=O)NOCc1ccccc1
Reaction time: 1 h

Procedure:
A solution of Example 1C (0.20 g, 0.66 mmol), O-benzyl hydroxylamine hydrochloride (0.22 g, 1.4 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.17 g, 0.89 mmol), 1-hydroxybenzotriazole (0.14 g, 1.0 mmol), and N-methylmorpholine (0.40 mL, 3.6 mmol) in 5:1 dichloromethane/DMF (6 mL) at room temperature was stirred for 16 hours, diluted with dichloromethane, washed sequentially with aqueous NaHCO3, brine, 10% KHSO4, and brine, dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 98:2/dichloromethane:methanol, and the purified concentrate was dissolved in saturated HCl/dioxane (8 mL), stirred for 1 hour, concentrated, treated with diethyl ether, then concentrated to provide the desired product.
Reaction SMILES: [NH2:1][C@H:2]([C:7]([O-:9])=[O:8])[CH2:3][C:4]([O-:6])=[O:5].[NH2:10][C@H:11]([C:16]([OH:18])=[O:17])[CH2:12][C:13](=[O:15])[NH2:14].[NH4+].[OH-]>>[NH2:1][C@H:2]([C:7]([OH:9])=[O:8])[CH2:3][C:4](=[O:5])[OH:6].[NH2:10][C@H:11]([C:16]([OH:18])=[O:17])[CH2:12][C:13](=[O:15])[NH2:14].[C:16]1(=[O:18])[NH:14][C:13](=[O:15])[CH2:12][CH2:11]1
Reactant: N[C@@H](CC(=O)[O-])C(=O)[O-]
Agent: NC(=O)C[C@H](N)C(=O)O
Agent: [NH4+]
Agent: [OH-]
Product: N[C@@H](CC(=O)O)C(=O)O
Product: O=C1CCC(=O)N1

Procedure:
This copolymer can then be converted, if desired, to a low molecular weight aspartate/asparagine copolymer, by treating with aqueous NH4OH and drying the solution, preferably at about 60° C. Finally, a low molecular weight Asp/Asn/succinimide terpolymer can be produced by acidifying an aqueous solution of the aspartate/asparagine copolymer, e.g. to about pH 4, drying the solution, preferably at about 60° C.-80° C., and heating the residue at about 170-180° C. under vacuum or an inert atmosphere.
Reaction SMILES: [Br:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][N+:3]=1[O-].[C:10]([NH2:14])([CH3:13])([CH3:12])[CH3:11].C1(C)C=CC(S(OS(C2C=CC(C)=CC=2)(=O)=O)(=O)=O)=CC=1>C(Cl)Cl.FC1C(F)=C(F)C=CC=1>[Br:1][C:2]1[N:3]=[C:4]([NH:14][C:10]([CH3:13])([CH3:12])[CH3:11])[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: [O-][n+]1cccc(F)c1Br
Reactant: CC(C)(C)N
Agent: Cc1ccc(S(=O)(=O)OS(=O)(=O)c2ccc(C)cc2)cc1
Agent: Fc1cccc(F)c1F
Solvent: ClCCl
Product: CC(C)(C)Nc1ccc(F)c(Br)n1
Temperature: 50 °C
Reaction time: 2 h
Yield: 4.5 %

Procedure:
To a solution of 2-bromo-3-fluoropyridine 1-oxide (511 mg, 2.7 mmol) in DCM (10 mL) and trifluorobenzene (4 mL) at 50° C. were added tert-butylamine (2.5 mL, 23.9 mmol) and p-toluenesulfonic anhydride (3.7 g, 11.4 mmol) portion-wise. The reaction mixture was stirred at 50° C. for 2 hours and then filtered. The filtrate was concentrated to give a residue that was purified by flash chromatography (Si—PPC, Et2O:pentane, gradient 0:100 to 5:95) to give (6-Bromo-5-fluoropyridin-2-yl)-tert-butylamine as a colourless oil (30 mg, 5%). 1H NMR (400 MHz, CHCl3-d): δ 7.13 (dd, J=8.8, 7.3 Hz, 1 H); 6.29 (dd, J=8.8, 2.5 Hz, 1 H); 4.49 (s, 1 H); 1.40 (s, 9 H).
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][C:7]([O:8][CH2:9][CH2:10][Br:11])=[CH:6][CH:5]=1)([O-])=O.[CH3:14][S:15](Cl)(=[O:17])=[O:16].O>CO.[H][H].[Pd]>[CH3:14][S:15]([NH:1][C:4]1[CH:13]=[CH:12][C:7]([O:8][CH2:9][CH2:10][Br:11])=[CH:6][CH:5]=1)(=[O:17])=[O:16]
Reactant: CS(=O)(=O)Cl
Reactant: [H][H]
Reactant: O=[N+]([O-])c1ccc(OCCBr)cc1
Agent: [Pd]
Solvent: O
Solvent: CO
Product: CS(=O)(=O)Nc1ccc(OCCBr)cc1
Reaction time: 8 h
Yield: 36.8 %

Procedure:
2-(4-nitrophenoxy)ethyl bromide (0.5 g, 2.03 mmol) was dissolved in methanol (30 ml) and, after adding 10% Pd/C (0.2 g), the solution was stirred for 1 h in hydrogen gas, followed by filtration. The filtrate was concentrated under vacuum and the residue was dissolved in pyridine (20 ml). To the resulting solution, methanesulfonyl chloride (0.25 ml, 3.2 mmol) was slowly added dropwise, followed by stirring overnight. Water was poured into the reaction mixture, followed by extraction with ethyl acetate and concentration under vacuum. The residue was subjected to column chromatography using a 1:1 solvent system of ethyl acetate and hexane as an eluent to yield the end compound 2-(4-methanesulfonamidophenoxy)ethyl bromide (0.22 g).
Reaction SMILES: [NH2:1][C:2]1[C:9]([F:10])=[CH:8][C:5]([C:6]#N)=[C:4]([F:11])[CH:3]=1.S(=O)(=O)(O)O.[OH2:17].[OH-].[Na+].[O:20]1CCO[CH2:22][CH2:21]1>>[NH2:1][C:2]1[C:9]([F:10])=[CH:8][C:5]([C:6]([O:20][CH2:21][CH3:22])=[O:17])=[C:4]([F:11])[CH:3]=1
Reactant: O
Reactant: N#Cc1cc(F)c(N)cc1F
Reactant: C1COCCO1
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Product: CCOC(=O)c1cc(F)c(N)cc1F
Temperature: 80 °C
Reaction time: 96 h
Yield: 42 %

Procedure:
To a solution of 4-amino-2,5-difluorobenzonitrile (6.21 g, 38.28 mmol) in dioxane (32.5 mL) was added sulphuric acid 73% (52.2 mL) and the resulting mixture was stirred at 80° C. for 4 days. The crude reaction was added into water (250 mL) and basified with sodium hydroxide 32% (220 mL) until basic pH. The mixture was washed with methylene chloride and the aqueous phase was neutralized and extracted with ethyl acetate. The resulting organic phase was washed with brine, dried and filtered. The solvent was removed under reduced pressure to give the title compound as a white solid (42%), which was used in the next step without further purification.
Reaction SMILES: [CH:1]([O:4][C:5](=[O:32])[NH:6][CH:7]1[CH2:12][CH2:11][CH:10]([NH:13][C:14](=[O:31])[C:15]2[CH:20]=[C:19]([OH:21])[CH:18]=[C:17]([O:22][C:23]3[CH:28]=[CH:27][C:26]([C:29]#[N:30])=[CH:25][CH:24]=3)[CH:16]=2)[CH2:9][CH2:8]1)([CH3:3])[CH3:2].[Br:33][C:34]1[CH:35]=[C:36](B(O)O)[CH:37]=[CH:38][CH:39]=1.N1C=CC=C[CH:44]=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[C:1]([O:4][C:5](=[O:32])[NH:6][CH:7]1[CH2:12][CH2:11][CH:10]([NH:13][C:14](=[O:31])[C:15]2[CH:16]=[C:17]([O:22][C:23]3[CH:28]=[CH:27][C:26]([C:29]#[N:30])=[CH:25][CH:24]=3)[CH:18]=[C:19]([O:21][C:38]3[CH:37]=[CH:36][CH:35]=[C:34]([Br:33])[CH:39]=3)[CH:20]=2)[CH2:9][CH2:8]1)([CH3:44])([CH3:3])[CH3:2]
Reactant: CC(C)OC(=O)NC1CCC(NC(=O)c2cc(O)cc(Oc3ccc(C#N)cc3)c2)CC1
Reactant: c1ccncc1
Reactant: OB(O)c1cccc(Br)c1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NC1CCC(NC(=O)c2cc(Oc3ccc(C#N)cc3)cc(Oc3cccc(Br)c3)c2)CC1
Temperature: 25 °C
Reaction time: 20 h
Yield: 22.5 %

Procedure:
{4-[3-(4-Cyano-phenoxy)-5-hydroxy-benzoylamino]-cyclohexyl}-carbamic acid isopropyl ester (1.0 g, 2.2 mmol) and copper acetate (0.4 g, 2.2 mmol), dissolved in 30 ml of dichloromethane, were charged in a 100 ml capacity seal-tube. 3-bromophenyl boronic acid (0.667 g, 3.32 mmol), 4 Å molecular sieves (3.0 g) and 0.438 g (5.53 mmol) of pyridine, in 20 ml of dichloromethane, was added to the reaction mixture in a sealed-tube and reaction mixture was stirred at RT for 20 h. After reaction completion 2.0 g of silica-gel was added and the mixture was filtered. Thus obtained filterate was concentrated under reduced pressure and subjected to column chromatography to afford 0.3 g of the required product. Percentage purity (LCMS): 86.0%, (M+1)=605.1+1.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH2:10][C:11]([O:13]C)=[O:12])[CH:7]=[CH:8][CH:9]=1)[CH3:2]>CO.[OH-].[Na+]>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH2:10][C:11]([OH:13])=[O:12])[CH:7]=[CH:8][CH:9]=1)[CH3:2]
Reactant: CCOc1cccc(CC(=O)OC)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCOc1cccc(CC(=O)O)c1
Yield: 103.4 %

Procedure:
A solution of methyl 3-ethoxyphenylacetate (92.6 g, 0.4 mole) in methanol (600 ml) and 6.25N NaOH (400 ml) was stirred overnight at room temperature and then filtered and concentrated in vacuo to remove the methanol. The solution was adjusted to pH 1 with concentrated HCl, the resulting precipitate filtered, washed with ice water, and dried under high vacuum to give 3-ethoxyphenyl acetic acid (74.5 g). M.p=89°-90° C. 1H NMR (DMSO-d6, 200 MHz) δ: 1.30 (6, J=7 Hz, 3H, CH3), 3.50 (s, 2H, ArCH2), 3.98 (q, J=7 Hz, 2H, ethyl CH2), 6.75-6.80 (m, 3H, Ar), 7.14-7.23 (m, 1H, Ar). (Lit. ref.: J. Med. Chem, 1980, 23(4) 437-444.
Reaction SMILES: [C:1]([N:3]1[C:11]2[CH:10]=[CH:9][C:8]([CH3:12])=[CH:7][C:6]=2[C:5]2[CH2:13][N:14]([CH3:17])[CH2:15][CH2:16][C:4]1=2)#[CH:2].Br[C:19]1[CH:23]=[CH:22][S:21][CH:20]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>O.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>[CH3:17][N:14]1[CH2:15][CH2:16][C:4]2[N:3]([C:1]#[C:2][C:19]3[CH:23]=[CH:22][S:21][CH:20]=3)[C:11]3[CH:10]=[CH:9][C:8]([CH3:12])=[CH:7][C:6]=3[C:5]=2[CH2:13]1
Reactant: Brc1ccsc1
Reactant: C#Cn1c2c(c3cc(C)ccc31)CN(C)CC2
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: O
Product: Cc1ccc2c(c1)c1c(n2C#Cc2ccsc2)CCN(C)C1
Yield: 6.5 %

Procedure:
A mixture of 5-ethynyl-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (165 mg, 0.736 mmol), 3-bromothiophene (100 mg, 0.613 mmol), TBAF.3H2O (580 mg, 1.84 mmol), and dichlorobis(triphenylphosphine)palladium (II) (13 mg, 0.018 mmol) were heated by microwave at 80° C. for 5 min. The reaction was monitored by TLC and LCMS. The reaction mixture was diluted with water (30 mL) and extracted with EtOAc (3×50 mL). The combined organic layers were washed with water (2×50 mL), dried over anhydrous sodium sulfate, and concentrated under vacuum. The crude product obtained was purified by HPLC to yield 12.2 mg of 2,8-dimethyl-5-thiophen-3-ylethynyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole. 1H NMR (CDCl3, freebase) δ (ppm): 7.50 (s, 1H), 7.40 (d, 1H), 7.38(d, 1H), 7.20 (m, 2H), 7.10 (d, 1H), 3.68(s, 2H), 2.98 (t, 2H), 2.90 (t, 2H), 2.58(s, 3H), 2.42 (s, 3H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.[OH-].[K+].Cl[C:12]1[CH:21]=[N:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([Cl:22])[CH:18]=2)[N:13]=1.O>CS(C)=O.O1CCOCC1>[Cl:22][C:17]1[CH:18]=[C:19]2[C:14](=[CH:15][CH:16]=1)[N:13]=[C:12]([O:8][C:4]1[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=1)[NH2:1])[CH:21]=[N:20]2
Reactant: Nc1cccc(O)c1
Reactant: Clc1ccc2nc(Cl)cnc2c1
Agent: [K+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: O
Solvent: C1COCCO1
Product: Nc1cccc(Oc2cnc3cc(Cl)ccc3n2)c1
Temperature: 25 °C
Yield: 54 %

Procedure:
6.6 g (0.06 mol) of m-aminophenol in 4.0 g (0.06 mol) of 85% potassium hydroxide and 80 ml of dimethylsulfoxide was heated under stirring. The water generated was distilled away under reduced pressure to make the potassium m-aminophenolate. To the solution which was allowed to cool to room temperature was added a solution of 11.9 g (0.06 mol) of 2,6-dichloroquinoxaline dissolved in 80 ml of dioxane. The mixture was reacted at 50°-60° C. for 5 hours. After the reaction was over, the reaction mixture was poured into ice and cold water. The formed solid was filtered off and washed with 5% aqueous solution of sodium hydroxide and then washed with water. The crude crystals thus obtained were recrystallized from ethanol, to produce 8.8 g (yield 54%) of white crystals, m.p. 119°-120° C.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH:8]([F:11])[C:9]#[CH:10])[N:3]=1.[CH3:12][Si:13]([CH2:16][N:17]=[N+:18]=[N-:19])([CH3:15])[CH3:14].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>CC(O)(C)C.O.C([O-])(O)=O.[Na+]>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH:8]([F:11])[C:9]2[N:19]=[N:18][N:17]([CH2:16][Si:13]([CH3:15])([CH3:14])[CH3:12])[CH:10]=2)[N:3]=1
Reactant: C#CC(F)c1cccc(Br)n1
Reactant: C[Si](C)(C)CN=[N+]=[N-]
Agent: O=C([O-])O
Agent: O=C1O[C@H]([C@@H](O)CO)C([O-])=C1O
Agent: [Na+]
Solvent: CC(C)(C)O
Solvent: O
Product: C[Si](C)(C)Cn1cc(C(F)c2cccc(Br)n2)nn1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
2-Bromo-6-(1-fluoroprop-2-yn-1-yl)pyridine (520 mg, 2.43 mmol) and trimethylsilylmethyl azide (377 mg, 2.92 mmol) were combined in t-BuOH (5.0 mL) and water (3.0 mL). CuSO4.5H2O (30 mg, 0.12 mmol) in water (1.0 mL) was added, followed by sodium ascorbate (96 mg, 0.49 mmol) in water (1.0 mL). The reaction was stirred at room temperature overnight, diluted with saturated NaHCO3, and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (MgSO4), filtered, and evaporated to a brown residue that was purified by flash chromatography (0-30% EtOAc/hexanes) to afford the title compound as a colorless solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4](=[O:10])[CH:5]=[CH:6][C:7](=[O:9])[CH:8]=1.[CH2:11]=[CH:12][CH:13]=[CH2:14]>>[CH3:1][O:2][C:3]1[C:4](=[O:10])[CH:5]2[CH:6]([C:7](=[O:9])[CH:8]=1)[CH2:14][CH:13]=[CH:12][CH2:11]2
Reactant: C=CC=C
Reactant: COC1=CC(=O)C=CC1=O
Product: COC1=CC(=O)C2CC=CCC2C1=O

Procedure:
Little is known, however, concerning the reaction of methoxy and 2,6-dimethoxy-p-benzoquinone. (The latter can be generated from lignin). It has been shown that methoxy-p-benzoquinone will react with 1,3-butadiene to give 2-methoxy-4a,5,8,8a -tetrahydronapthoquinone [G. I. Birnbaum, J. Org. Chem., 25, 1660-1, (1960)] and with 2,3-dimethyl-1,3-butadiene to give 5,8-dihydro-2-methoxy-6,7-dimethyl-1,4-napthoquinone [M. F. Ansell, J. Chem. Soc., 3020, (1963)]. A more recent publication has shown that 2,6-dimethoxy-p-benzoquinone can be combined with isoprene to give a mixture of 2-methoxy-6-methyl-1,4-napthoquinone and 2-methoxy-7-methyl-1,4-napthoquinone [I.-M. TegmoLarsson, Tetra. Letters, 22, 2043-6, (1981)].
Reaction SMILES: [OH-].[Na+].[CH2:3]([C:5]1[CH:6]=[CH:7][C:8]([CH:11]([OH:13])[CH3:12])=[N:9][CH:10]=1)[CH3:4].[C:14]1([CH3:24])[CH:19]=[CH:18][C:17]([S:20](Cl)(=[O:22])=[O:21])=[CH:16][CH:15]=1>O.O1CCCC1>[C:14]1([CH3:24])[CH:19]=[CH:18][C:17]([S:20]([OH:13])(=[O:22])=[O:21])=[CH:16][CH:15]=1.[CH2:3]([C:5]1[CH:6]=[CH:7][C:8]([CH2:11][CH3:12])=[N:9][CH:10]=1)[CH3:4]
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: CCc1ccc(C(C)O)nc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CCc1ccc(CC)nc1
Product: Cc1ccc(S(=O)(=O)O)cc1
Temperature: 0 °C
Reaction time: 2 h
Yield: 93.2 %

Procedure:
7.1 g of sodium hydroxide was dissolved in 33 ml of water, and 7.6 g of (5-ethyl-2-pyridyl)ethanol was dissolved in 33 ml of tetrahydrofuran. Both solutions were mixed and cooled. To the resultant solution was added dropwise gradually at 0° C. a solution of 11.7 g of p-toluenesulfonyl chloride in 51 ml of tetrahydrofuran, followed by stirring for 2 hours at the same temperature. To the reaction mixture was added ice water. The mixture was extracted twice with 100 ml each of methylene chloride. The extracted organic layers are combined. The resultant organic layer was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, whereby 14.4 g of (5-ethyl-2-pyridyl)ethane p-toluenesulfonate was obtained as a pale yellow oily product.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][N:11]=1.[Br:17]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:15]=[CH:14][C:13]([CH2:16][Br:17])=[CH:12][N:11]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1ccc(-c2nc3ccccc3s2)nc1
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: BrCc1ccc(-c2nc3ccccc3s2)nc1
Temperature: 25 °C
Yield: 70.7 %

Procedure:
In 800 ml of dry carbon tetrachloride was dissolved 20 g (0.088 mol) of 2-(benzothiazol-2-yl)-5-methylpyridine, followed by the addition of 16.4 g (0.092 mol) of N-bromosuccinimide and a catalytic amount of benzoyl peroxide. The mixture was heated at reflex for 10 hours, after which time it was allowed to cool down to room temperature. The precipitated succinimide was filtered off, the filtrate concentrated to 200 ml and the resulting crude crystals collected by filtration. Yield 24 g. Recrystallization from ligroine yielded 19 g of 2-(benzothiazol-2-yl)-5-bromomethylpyridine as colorless needles.