Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:5][CH2:6][CH2:7][CH2:8][CH3:9])CCC.C(Br)C=C.C([Mg]Br)(C)C.C(=O)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C(O[Ti](OC(C)C)(OC(C)C)OC(C)C)(C)C.Cl>[C:20]1([CH:6]([OH:5])[CH2:7][CH:8]=[CH2:9])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: O=Cc1ccccc1
Reactant: CCCCOCCCC
Agent: CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C
Agent: CC(C)[Mg]Br
Agent: Cl
Solvent: C=CCBr
Product: C=CCC(O)c1ccccc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 81 %

Procedure:
To 0.90 ml (3.0 mmol) of tetraisopropoxytitanium and 5 ml of n-butyl ether solution containing allyl bromide (3.0 mmol) was added dropwise at −78° C. 6.2 ml of 0.97M n-butyl ether solution containing isopropylmagnesium bromide (6.0 mmol). After stirring at −50° C. to −40° C. for 1 hour, the reaction liquid was given 0.21 ml (2.1 mmol) of benzaldehyde and heated to 0° C. over 30 minutes. With 10 ml of 3N hydrochloric acid added, the solution was heated to room temperature and separated into layers. The organic layer was washed with a saturated aqueous solution of sodium hydrogen carbonate. After drying with anhydrous magnesium sulfate, the solution was freed of solvent by vacuum distillation. The residues were purified by silica gel chromatography. Thus there was obtained 252 mg of 1-phenyl-3-buten-1-ol (81% yields based on benzaldehyde).
Reaction SMILES: Br[C:2]1[CH:6]=[CH:5][S:4][CH:3]=1.[Li]CCCC.[Br:12][CH2:13][CH2:14][CH2:15][CH2:16]Br>C1COCC1>[Br:12][CH2:13][CH2:14][CH2:15][CH2:16][C:2]1[CH:6]=[CH:5][S:4][CH:3]=1
Reactant: BrCCCCBr
Reactant: Brc1ccsc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: BrCCCCc1ccsc1
Temperature: -45 °C
Reaction time: 0.17 h
Yield: 50.9 %

Procedure:
3-bromothiophene (9 ml, 96 mmol) was dissolved in 120 ml dry hexanes. The solution was cooled down to −45° C., and 60 ml n-BuLi (60 ml 1.6M, 96 mmol) were added dropwise. The solution was stirred at −45° C. for 10 min, after which 6 ml dry THF were added and the lithium salt precipitated. After stirring at −45° C. for 1 h, the solution was warmed up to −10° C., and an excess of 1,4-dibromobutane (44 ml, 368 mmol) was added. After stirring at room temperature for 2 h, the solution was extracted with ether, washed with water, brine, dried over magnesium sulfate, and the solvent was removed. Excess 1,4-dibromobutane was removed under vacuum. Posterior filtration of the residue through a silica plug (hexanes), and solvent removal afforded the title compound (10.7 g, 51% yield) as a colorless oil. 1H-NMR (ppm, CDCl3): 1.75-1.81 (2H, m), 1.86-1.91 (2H, m), 2.67 (2H, t, J=7.32 Hz), 3.44 (2H, t, J=7.32 Hz), 6.92-6.94 (2H, m), 7.25-7.26 (1H, m); 13C-NMR (ppm, CDCl3): 29.2, 29.5, 32.4, 33.8, 120.4, 125.6, 128.3, 142.3; ESI-MS (m/z) found: 218.9843 [M+H], calculated: 218.9838.
Reaction SMILES: O.NN.C1(=O)[N:8]([CH2:9][CH2:10][N:11]2[C:15]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[C:14]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[N:13]=[CH:12]2)C(=O)C2=CC=CC=C12.Cl>CO>[NH2:8][CH2:9][CH2:10][N:11]1[C:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:14]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:13]=[CH:12]1
Reactant: O=C1c2ccccc2C(=O)N1CCn1cnc(-c2ccccc2)c1-c1ccccc1
Agent: Cl
Agent: NN
Solvent: O
Solvent: CO
Product: NCCn1cnc(-c2ccccc2)c1-c1ccccc1
Yield: 88.1 %

Procedure:
Step 3): 80% Hydrazine monohydrate (0.062 ml, 1.3 mmol) was added to a solution of 1-(2-phthalimidoethyl)-4,5-diphenylimidazole (0.32 g, 0.8 mmol) in methanol (20 ml) under refluxing. The reaction mixture was refluxed for 1 hour, then cooled. The mixture was made acidic slightly with 6N HCl and then filtered to remove phthalhydrazide. The filtrate was concentrated and then the residue was suspended in 2N NaOH. The suspended mixture was extracted with chloroform. The organic layer was washed with brine, dried (MgSO4) and concentrated. The precipitates were recrystallized (ethyl acetate/hexane) to give 1-(2-aminoethyl)-4,5-diphenylimidazole (88.1%): mp 96°-98° C.
Reaction SMILES: II.[OH:3][CH:4]1[CH2:8][CH2:7][CH:6]([CH:9]=[CH:10][CH:11]([OH:17])[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH:5]1[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]([O:26][CH3:27])=[O:25].[Cl-].[NH4+].I[CH2:31]I>C(OCC)C.[Cu].[Zn]>[OH:3][CH:4]1[CH2:8][CH2:7][CH:6]([CH:9]2[CH2:31][CH:10]2[CH:11]([OH:17])[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH:5]1[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]([O:26][CH3:27])=[O:25]
Reactant: CCCCCC(O)C=CC1CCC(O)C1CCCCCCC(=O)OC
Reactant: ICI
Agent: [Cu]
Agent: II
Agent: [Cl-]
Solvent: CCOCC
Product: CCCCCC(O)C1CC1C1CCC(O)C1CCCCCCC(=O)OC
Yield: 100 %

Procedure:
A suspension of zinc-copper couple (1.0 g.) (prepared by the method of R.S. Shank and H. Schechter, J. Org. Chem. (1959), 24, 1825) in diiodomethane (4.0 g.) and dry diethyl ether (10 ml.) was refluxed with a crystal of iodine for 0.5 hours. To the resulting suspension was added methyl 7-[2-hydroxy-5-(3-hydroxy-1-octenyl)cyclopentyl]heptanoate (1.0 g.) [prepared as described in Example 5] in dry diethyl ether (10 ml.) and the resulting mixture was refluxed for 24 hours. Addition of saturated ammonium chloride broke up the complex formed and the remaining zinc-copper couple was removed by filtration. The filtrate was separated and the diethyl ether layer dried over magnesium sulphate and evaporated to give methyl 7-[2-hydroxy-5-(3-hydroxy-1,2-methylene-1-octyl)cyclopentyl]heptanoate (1.04 g.). This was purified by preparative thin layer chromatography using the system employed in Example 10,νmax 3400 cm-1, 1730 cm-1 and 1170 cm-1.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([CH3:11])=[CH:5]2.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:19][C:20]([O:22][CH3:23])=[O:21]>CC(C)=O>[CH3:23][O:22][C:20](=[O:21])[CH2:19][N:7]1[C:8]2[C:4](=[CH:3][C:2]([F:1])=[CH:10][CH:9]=2)[CH:5]=[C:6]1[CH3:11]
Reactant: COC(=O)CBr
Reactant: Cc1cc2cc(F)ccc2[nH]1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC(C)=O
Product: COC(=O)Cn1c(C)cc2cc(F)ccc21

Procedure:
A mixture of 5-fluoro-2-methylindole (2.4 g), cesium carbonate (16.6 g) and methyl bromoacetate (5.4 ml) in acetone 240 ml was stirred and heated under reflux for 16 h. The solvent was removed, water and ethyl acetate were added and the organic phase separated. The aqueous phase was re-extraced with ethyl acetate and the combined organic solution dried and concentrated to a solid. Purification by flash chromaography using dichloromethane:ethylacetate gave the subtitle compound as a solid (2.9 g)
Reaction SMILES: [Na].[CH:2]1[C:11](C(O)=O)=[C:10]2[C:5]([C:6]([C:18]([OH:20])=[O:19])=[CH:7][CH:8]=[C:9]2[C:15](O)=O)=[C:4]([C:21]([OH:23])=O)[CH:3]=1>[Fe].[Co].[Mn]>[CH:11]1[C:10]([C:9]2[CH:8]=[CH:7][C:6]3[C:18]([O:20][C:21](=[O:23])[C:4]=3[CH:15]=2)=[O:19])=[CH:5][C:4]2[C:21]([O:20][C:18](=[O:19])[C:3]=2[CH:2]=1)=[O:23]
Reactant: O=C(O)c1ccc(C(=O)O)c2c(C(=O)O)ccc(C(=O)O)c12
Agent: [Co]
Agent: [Fe]
Agent: [Mn]
Product: O=C1OC(=O)c2cc(-c3ccc4c(c3)C(=O)OC4=O)ccc21

Procedure:
Monomers used in accordance with the examples which follow are preferably substantially analytically pure; for example, "electronic" grade 6FDA is preferable. This material contains more that 98.5% dianhydride, less that 1.5% of the corresponding monoanhydride-diacid and less than 0.1% of the corresponding tetra-acid. The 2,2-bis(3,4-dicarboxy phenyl) hexafluoropropane dianhydride specified herein (6FDA) is available from Hoechst-Celanese Corporation, Route 202-206 North, Somerville, N.J. 08876. Electronic grade dianhybride contains less than 10 ppm sodium, less than 5 ppm iron, less than 2 ppm cobalt and less that 2 ppm manganese, and has a melting point of 246.5 degrees Celsius. The BTDA utilized in the examples given hereinafter was a high purity polymer grade, 98.5% pure at a minimum with 1.5% monohydride and tetra acid at most with maximum ionic impurities of NA, K and FE of 0.6 ppm, 0.2 ppm and 1 ppm respectively. BPDA was obtained having an assay minimum of 99.5 per cent, maximum ionic impurities 1.4 ppm NA, 1.4 ppm K, 1.5 ppm FE. BTDA and BPDA specified above, i.e. high purity polymer grades, are available from Chriskev, of 5109 W. 111th Terrace, Leawood, Kansas. Likewise, the ODPA, greater than 99% pure was obtained from Occidental, 2801 Long Road, Grand Island New York.
Reaction SMILES: [Cl:1][CH:2]([CH3:6])[C:3](Cl)=[O:4].[N:7]1[C:12]2[NH:13][C:14]3[CH:22]=[CH:21][CH:20]=[CH:19][C:15]=3[C:16](=[O:18])[NH:17][C:11]=2[CH:10]=[CH:9][CH:8]=1>O1CCOCC1>[Cl:1][CH:2]([CH3:6])[C:3]([N:13]1[C:14]2[CH:22]=[CH:21][CH:20]=[CH:19][C:15]=2[C:16](=[O:18])[NH:17][C:11]2[CH:10]=[CH:9][CH:8]=[N:7][C:12]1=2)=[O:4]
Reactant: O=C1Nc2cccnc2Nc2ccccc21
Reactant: CC(Cl)C(=O)Cl
Solvent: C1COCCO1
Product: CC(Cl)C(=O)N1c2ccccc2C(=O)Nc2cccnc21

Procedure:
A solution of 2-chloropropionyl chloride and 5,11-dihydro-6H-pyrido[2,3-b][1,4]-benzodiazepine-6-one in dioxane were reacted to obtain 11-(2-chloropropionyl)-5,11-dihydro-6H-pyrido-[2,3-b][1,4]-benzodiazepine-6-one which melted at 215°-218° C. under crystallization from ethanol.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Br[CH2:10][CH2:11][CH2:12][C:13]#[N:14].Cl.[CH3:16][C:17]1[C:24]2[O:23][N:22]=[C:21]([CH:25]3[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)[C:20]=2[S:19][CH:18]=1>C(#N)C.O>[CH3:16][C:17]1[C:24]2[O:23][N:22]=[C:21]([CH:25]3[CH2:30][CH2:29][N:28]([CH2:10][CH2:11][CH2:12][C:13]#[N:14])[CH2:27][CH2:26]3)[C:20]=2[S:19][CH:18]=1
Reactant: N#CCCCBr
Reactant: Cc1csc2c(C3CCNCC3)noc12
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: CC#N
Solvent: O
Product: Cc1csc2c(C3CCN(CCCC#N)CC3)noc12
Temperature: 25 °C
Yield: 31 %

Procedure:
Add potassium carbonate (17.72 mmol, 2.45 g, 2.40 equivalents), potassium iodide (0.73 mmol, 123 mg, 0.10 equivalents), and 4-bromobutyronitrile (8.86 mmol, 0.88 mL, 1.20 equivalents) to a stirred solution of 6-methyl-3-piperidin-4-yl-thieno[2,3-d]isoxazole hydrochloride (7.38 mmol, 1.91 g, 1.00 equivalents) in acetonitrile (10.84 mL) and water (3.60 mL). Stir the resulting mixture at reflux overnight. Cool to room temperature, filter the reaction mixture and wash the solid material collected with dichloromethane and evaporate the filtrate. Take the residue up in dichloromethane (45 mL), wash with sodium hydroxide (aqueous, 18 mL, 2 M), water (18 mL), saturated sodium hydroxide (aqueous, 18 mL), dry over magnesium sulfate, filter and evaporate. Purify the residue via flash column chromatography using a gradient and eluting with a mixture of n-heptane : ethyl acetate (0.5:9.5) to ethyl acetate (100%) to yield the desired product as a brown oil (663 mg). LC/MS (ESI), m/e 290 (MH+), retention time 1.19 minutes. Condition II.
Reaction SMILES: [CH2:1]([S:3]([C:6]1[CH:11]=[CH:10][C:9]([I:12])=[CH:8][N:7]=1)(=[O:5])=[O:4])C.C[S-].[Na+]>>[CH3:1][S:3]([C:6]1[CH:11]=[CH:10][C:9]([I:12])=[CH:8][N:7]=1)(=[O:4])=[O:5]
Reactant: CCS(=O)(=O)c1ccc(I)cn1
Agent: C[S-]
Agent: [Na+]
Product: CS(=O)(=O)c1ccc(I)cn1

Procedure:
The titled compound is prepared substantially in accordance with the procedure of Intermediate 22 using sodium methanethiolate in place of sodium ethanethiolate.
Reaction SMILES: [F:1][CH:2]([F:12])[C:3]([OH:11])([CH2:7][CH2:8][CH2:9][CH3:10])[CH2:4][C:5]#[CH:6].N1C=CN=C1.[CH3:18][Si:19]([CH3:22])([CH3:21])Cl.C(=O)(O)[O-].[Na+]>CCCCCC.CN(C)C=O>[F:1][CH:2]([F:12])[C:3]([O:11][Si:19]([CH3:22])([CH3:21])[CH3:18])([CH2:7][CH2:8][CH2:9][CH3:10])[CH2:4][C:5]#[CH:6]
Reactant: C#CCC(O)(CCCC)C(F)F
Reactant: C[Si](C)(C)Cl
Agent: O=C([O-])O
Agent: [Na+]
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: CCCCCC
Product: C#CCC(CCCC)(O[Si](C)(C)C)C(F)F
Temperature: 0 °C

Procedure:
A solution of 11.5 g. of 4-difluoromethyl-4-hydroxy-1-octyne and 11.32 g. of imidazole in 45 ml. of dimethylformamide is cooled in an ice bath under nitrogen. A 10.3 ml. portion of trimethylchlorosilane is added using a syringe over a 15 minute period. The mixture is stirred in the ice bath for one hour and then overnight at room temperature. The solution is diluted with hexane and then poured into saturated aqueous sodium bicarbonate solution. The hexane solution is separated, washed with aqueous sodium bicarbonate solution and brine, dried over anhydrous sodium sulfate and the solvents are evaporated to dryness giving the desired product as a colorless liquid.
Reaction SMILES: [C:1]1([C:7]2([C:10]3[NH:15][C:14](=[S:16])[C:13]([NH:17][C:18]([C:20]4[CH:21]=[C:22]5[C:26](=[CH:27][CH:28]=4)[CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23]5)=O)=[CH:12][CH:11]=3)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C1(C)C=CC=CC=1.CCOC(C)=O>[CH2:25]1[C:26]2[C:22](=[CH:21][C:20]([C:18]3[S:16][C:14]4[C:13]([N:17]=3)=[CH:12][CH:11]=[C:10]([C:7]3([C:1]5[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=5)[CH2:8][CH2:9]3)[N:15]=4)=[CH:28][CH:27]=2)[CH2:23][NH:24]1
Reactant: CC(C)(C)OC(=O)N1Cc2ccc(C(=O)Nc3ccc(C4(c5ccccc5)CC4)[nH]c3=S)cc2C1
Agent: CC1(C)C2CCC1(CS(=O)(=O)O)C(=O)C2
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: c1ccc(C2(c3ccc4nc(-c5ccc6c(c5)CNC6)sc4n3)CC2)cc1
Temperature: 100 °C
Reaction time: 3 h

Procedure:
tert-Butyl 5-(6-(1-phenylcyclopropyl)-2-thioxo-1,2-dihydropyridin-3-ylcarbamoyl)i-soindoline-2-carboxylate (213 mg, 0.437 mmol) was dissolved in toluene (4.4 mL) before camphor sulfonic acid (91 mg, 0.393 mmol) was added and stirred at 100° C. for 3 h. The reaction mixture was diluted with 75 mL of EtOAc, added to a separatory funnel, partitioned with sodium bicarbonate (saturated, aqueous), washed with sodium bicarbonate (saturated, aqueous), separated, dried over sodium sulfate, and concentrated via rotovap to give 2-(isoindolin-5-yl)-5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridine after flash chromatography. MS (ESI) m/z: Calculated: 369.1; Observed: 370.4 (M++H).
Reaction SMILES: C([Li])CCC.[C:6](#[N:8])[CH3:7].[CH2:9]([O:11][C:12]1[C:21]([O:22][CH3:23])=[CH:20][C:15]([C:16]([O:18]C)=O)=[C:14]([N:24]=[CH:25]N(C)C)[CH:13]=1)[CH3:10].C(O)(=O)C>C1COCC1.O>[CH2:9]([O:11][C:12]1[CH:13]=[C:14]2[C:15]([C:16](=[O:18])[C:7]([C:6]#[N:8])=[CH:25][NH:24]2)=[CH:20][C:21]=1[O:22][CH3:23])[CH3:10]
Reactant: CCOc1cc(N=CN(C)C)c(C(=O)OC)cc1OC
Reactant: CC#N
Agent: [Li]CCCC
Solvent: CC(=O)O
Solvent: O
Solvent: C1CCOC1
Product: CCOc1cc2[nH]cc(C#N)c(=O)c2cc1OC
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 83.1 %

Procedure:
Added 54.0 ml (135 mmol) n-butyl lithium to 150 ml THF and chilled to -78° C. under N2. Added dropwise over 20 minutes 7.05 ml (135 mmol) acetonitrile in 200 ml THF. Stirred 15 minutes and added a solution of 17.99 g (64.2 mmol) methyl 4-ethoxy-5-methoxy-2-(dimethylaminomethyleneamino)benzoate in 150 ml THF dropwise over 20 minutes. Let stir for 0.5 hour at -78° C. Added 11.0 ml (193 mmol) acetic acid and warmed gradually to 25° C. After 2.5 hours, stripped solvent, slurried residue with water, collected solids and dried in vacuo, giving 13.025 g of yellow solid: mass spectrum (electrospray m/e): M+H=245.2.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[C:4]([N+:9]([O-])=O)[CH:3]=1.[CH:12]([Mg]Br)=[CH2:13]>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[C:4]2[C:3]=1[CH:12]=[CH:13][NH:9]2
Reactant: O=[N+]([O-])c1cc(Br)ccc1F
Reactant: C=C[Mg]Br
Solvent: C1CCOC1
Product: Fc1ccc(Br)c2cc[nH]c12
Reaction time: 1.5 h
Yield: 11.7 %

Procedure:
To a solution of 4-bromo-1-fluoro-2-nitrobenzene (1.1 g, 5.0 mmol) in THF (20 mL) at −40° C. under nitrogen atmosphere was added slowly vinylmagnesium bromide (1 M in THF, 15.5 mL, 15.5 mmol). The reaction mixture was stirred for 1.5 h then quenched with saturated NH4Cl aqueous solution (10 mL). The mixture was partitioned between EtOAc (300 mL) and water (50 mL). The organic layer was separated, washed with brine, dried (MgSO4), filtered and evaporated in vacuo. The residue was purified by SiO2 chromatography eluting with 2.5% EtOAc/petroleum ether to afford 0.125 g (12%) of 4-bromo-7-fluoro-1H-indole (110) as brown oil: MS (ESI) m/z=214 [M−1]+.
Reaction SMILES: [O:1]1[CH2:5][CH2:4][C:3]2[CH:6]=[CH:7][CH:8]=[C:9]([C:10]([OH:12])=O)[C:2]1=2.C(Cl)(=O)C([Cl:16])=O>ClCCl.CN(C)C=O>[O:1]1[CH2:5][CH2:4][C:3]2[CH:6]=[CH:7][CH:8]=[C:9]([C:10]([Cl:16])=[O:12])[C:2]1=2
Reactant: O=C(O)c1cccc2c1OCC2
Reactant: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C(Cl)c1cccc2c1OCC2
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 98.9 %

Procedure:
2,3-Dihydrobenzo[b]furan-7-oic acid (3 g) (see Preparation 32) was suspended in anhydrous dichloromethane (30 ml) and oxalyl chloride (3.5 g) added, followed by addition of dimethylformamide (3 drops). The mixture was stirred at room temperature for 2.5 hours, the solvent then removed under reduced pressure, the resulting residue dissolved in dichloromethane and the solvent removed under reduced pressure. The residue was again dissolved in dichloromethane and the solvent removed under reduced pressure to give 2,3-dihydrobenzo[b]furan-7-oyl chloride as a pink solid (3.3 g).
Reaction SMILES: [O:1]([CH2:8][CH2:9][CH2:10][O:11][C:12]1[CH:13]=[C:14]([C:22]([O:24]C)=O)[C:15](=[CH:20][CH:21]=1)[C:16]([O:18]C)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:26](#[N:28])[CH3:27].[H-].[Na+]>CCOCC>[C:26]([CH:27]1[C:22](=[O:24])[C:14]2[C:15](=[CH:20][CH:21]=[C:12]([O:11][CH2:10][CH2:9][CH2:8][O:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:13]=2)[C:16]1=[O:18])#[N:28]
Reactant: CC#N
Reactant: COC(=O)c1ccc(OCCCOc2ccccc2)cc1C(=O)OC
Agent: [H-]
Agent: [Na+]
Solvent: CCOCC
Product: N#CC1C(=O)c2ccc(OCCCOc3ccccc3)cc2C1=O
Reaction time: 6 h
Yield: 86 %

Procedure:
A mixture of dimethyl 4-(3-phenoxypropoxy)phthalate (6.5 g; 0.019 mole), acetonitrile (10 ml) and sodium hydride (0.69 g of 100%) was stirred at 100° for 6 hours and dry ether added to the cooled yellow product. The solid which separated was filtered off, dissolved in water and the solution strongly acidified with concentrated hydrochloric acid. Filtration of the precipitated solid gave the title compound which recrystallised from ethanol dilute hydrochloric acid with mp 148°-150° (dec) and in 86% yield. (Found; C, 69.00; H, 4.90; N, 4.41; C19H15NO4 0.5H2O requires; C, 69.08; H, 4.88; N, 4.24%).
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][C:10]([C:13]#[N:14])=[CH:9][C:8]=1[O:15][CH3:16])(=O)=O.[C:19]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])(=[O:22])[CH:20]=[CH2:21].C(N(CC)CC)C>CN(C=O)C.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>[C:13]([C:10]1[CH:11]=[CH:12][C:7](/[CH:21]=[CH:20]/[C:19]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[C:8]([O:15][CH3:16])[CH:9]=1)#[N:14]
Reactant: COc1cc(C#N)ccc1OS(=O)(=O)C(F)(F)F
Reactant: C=CC(=O)OC(C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COc1cc(C#N)ccc1/C=C/C(=O)OC(C)(C)C
Temperature: 100 °C
Reaction time: 24 h

Procedure:
4 g (5.7 mmol) of bis(triphenylphosphine)palladium(II) chloride are added to a degassed solution of 37.13 g (132 mmol) of 4-cyano-2-methoxyphenyl trifluoromethanesulfonate, 35 ml (245 mmol) of tert-butyl acrylate and 90 ml (645 mmol) of triethylamine in DMF (250 ml). The solution is stirred at 100° C. under a protective gas atmosphere for 24 h. Ice-water (1000 ml) is then added, and the suspension is extracted with ethyl acetate (3×100 ml). The organic phase is washed with saturated sodium chloride solution, dried over magnesium sulfate and concentrated. The residue is purified by column chromatography (silica gel, mobile phase: cyclohexane/ethyl acetate 10:1). 24.6 g (72% of theory) of the title compound are obtained as a white solid.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:9]([C:11]2[CH:16]=[CH:15][N:14]=[C:13]3[NH:17][CH:18]=[CH:19][C:12]=23)=[O:10])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.[Cl:20][C:21]1[CH:22]=[C:23]([S:28](Cl)(=[O:30])=[O:29])[CH:24]=[CH:25][C:26]=1[CH3:27].CO.[OH-].[Na+]>N1C=CC=CC=1.O>[Cl:20][C:21]1[CH:22]=[C:23]([S:28]([NH:1][C:2]2[C:3]([C:9]([C:11]3[C:12]4[CH:19]=[CH:18][NH:17][C:13]=4[N:14]=[CH:15][CH:16]=3)=[O:10])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=2)(=[O:30])=[O:29])[CH:24]=[CH:25][C:26]=1[CH3:27]
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1Cl
Reactant: Nc1cc(Cl)cnc1C(=O)c1ccnc2[nH]ccc12
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)Nc2cc(Cl)cnc2C(=O)c2ccnc3[nH]ccc23)cc1Cl

Procedure:
Prepared from 20 mg (0.075 mmol) of (3-amino-5-chloro-pyridin-2-yl)-(1H-pyrrolo[2,3-b]pyridin-4-yl)-methanone and 58 mg (0.25 mmol) of 3-chloro-4-methyl-benzenesulfonyl chloride in 0.15 mL pyridine using procedure x. After the sulfonylation was complete, 3 mL methanol, 0.5 mL water and 35 mg sodium hydroxide were used. Yield: 9 mg of a yellow solid. LC-MSD, m/z for C20H14Cl2N4O3S [M+H]+=460.9, 462.9
Reaction SMILES: [CH:1]1([C:4]2[CH2:8][C:7](=[O:9])[NH:6][N:5]=2)[CH2:3][CH2:2]1.[CH:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12][N+:11]=1[O-]>C(OC(=O)C)(=O)C>[CH:1]1([C:4]2=[N:5][NH:6][C:7](=[O:9])/[C:8]/2=[C:10]2\[NH:11][CH:12]=[CH:13][C:14]3[C:19]\2=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:3][CH2:2]1
Reactant: O=C1CC(C2CC2)=NN1
Reactant: [O-][n+]1ccc2ccccc2c1
Solvent: CC(=O)OC(C)=O
Product: O=C1NN=C(C2CC2)/C1=C1/NC=Cc2ccccc21

Procedure:
3-Cyclopropyl-1H-pyrazol-5(4H)-one (0.03 g, 0.27 mmol) and isoquinoline N-oxide (0.04 g, 0.27 mmol) were stirred in acetic anhydride (0.5 mL) for 30-40 minutes. The reaction mixture was concentrated and purified by LC-MS to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.78-0.86 (m, 4H) 1.77-1.86 (m, 1H) 7.91 (t, J=7.71 Hz, 1H) 8.10 (t, J=7.58 Hz, 1H) 8.26 (d, J=8.59 Hz, 3H) 8.58 (d, J=6.57 Hz, 1H); ESI-MS: m/z calc'd for C15H13N3O 251.28. found 252.2 (M+H)+.
Reaction SMILES: C(/[N:14]=[CH:15]/[C:16]1[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][CH:17]=1)(C1C=CC=CC=1)C1C=CC=CC=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Cl:36][C:37]1[C:42](Cl)=[N:41][CH:40]=[CH:39][N:38]=1>C1COCC1>[NH2:14][CH:15]([C:42]1[C:37]([Cl:36])=[N:38][CH:39]=[CH:40][N:41]=1)[C:16]1[CH:17]=[CH:18][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:24][CH:25]=1
Reactant: Clc1nccnc1Cl
Reactant: COC(=O)c1ccc(/C=N/C(c2ccccc2)c2ccccc2)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: C1CCOC1
Product: COC(=O)c1ccc(C(N)c2nccnc2Cl)cc1
Reaction time: 0.5 h
Yield: 81.2 %

Procedure:
To a solution of (E)-methyl 4-((benzhydrylimino)methyl)benzoate (67 g, 204 mmol) in THF (700 mL) was cooled to 0° C. and added dropwise NaHMDS (244 mL, 244 mmol). The mixture was stirred at this temperature for 30 minutes, and added a solution of 2,3-dichloropyrazine (33.2 g, 224 mmol) in THF (40 mL). The reaction mixture was stirred at 0° C. for 20 minutes and RT for 40 minutes. After the reaction was completed, the reaction mixture was extracted with EA and water. The organic layer was treated with 3M HCl (500 mL) for 10 minutes. The phases were separated and the organic layer was extracted with 3M HCl. The aqueous was washed with EA and then alkalified with Na2CO3 to pH=9. The aqueous solution was extracted with EA and the combined organics were dried and concentrated to give methyl 4-(amino(3-chloropyrazin-2-yl)methyl)benzoate (46 g, yield 81%).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][NH:8][C:9]([NH2:11])=[O:10].[CH2:12](OC(OCC)OCC)C>C(O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]1[CH:12]=[N:11][C:9]([OH:10])=[N:8]1
Reactant: CCOC(OCC)OCC
Reactant: NC(=O)NNc1ccccn1
Solvent: CCO
Product: Oc1ncn(-c2ccccn2)n1
Temperature: 15 °C

Procedure:
A mixture of 31.9 g (0.21 m) of 2-pyridinylhydrazinecarboxamide and 17.50 ml of triethylorthoformate was refluxed for 6 hours with the ethanol formed as a by-product being continuously removed by distillation thereby maintaning the reaction temperature at 130°-140° C. At the completion of the reaction, the reaction mixture was cooled to 15° C. and the solid 1-(2-pyridinyl)-1H-1,2,4-triazol-3-ol product was recovered by filtration. The product after washing with methylene chloride was recovered in a yield of 25.2 g (74 percent of theoretical). The product melted at 260°-262° C. and upon analysis was found to have carbon, hydrogen and nitrogen contents of 52.26, 3.90 and 34.79 percent, respectively, as compared with the theoretical contents of 51.89, 3.73 and 34.55 percent, respectively, calculated for the above named compound.