Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.[NH:10]1[CH:14]=[CH:13][N:12]=[CH:11]1.C(=O)([O-])[O-].[K+].[K+]>CN1CCCC1=O>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([N:10]2[CH:14]=[CH:13][N:12]=[CH:11]2)=[CH:3][CH:4]=1
Reactant: COc1ccc(Br)cc1
Reactant: c1c[nH]cn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Product: COc1ccc(-n2ccnc2)cc1
Yield: 49.9 %

Procedure:
A mixture of 37.4 g (0.20 mole) of 4-bromoanisole, 170 g (0.25 mole) of imidazole, 26 g (0.2 mole) of potassium carbonate, and 1.2 g of cuprous bromide in 150 ml of N-methylpyrrolidinone was heated at reflux under a blanket of nitrogen for 4 hr. The mixture was filtered and concentrated to remove the solvent. The residue was partitioned between dilute sodium hydroxide solution and methylene chloride. After filtration, the organic fraction was chromatographed. The desired fractions were concentrated and the crystalline residue was recrystallized from toluene/cyclohexane to give 17.4 g (50%) of the title compound as white plates, mp 63.0°-64.0° C.
Reaction SMILES: [C:1]([NH:4][C@@H:5]1[CH2:10][C@H:9]([NH:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:8][CH2:7][C@@H:6]1[N:16]1[CH2:20][CH2:19][C@H:18]([NH:21]C(=O)OCC2C=CC=CC=2)[C:17]1=[O:32])(=[O:3])[CH3:2]>CO.[OH-].[OH-].[Pd+2]>[NH2:21][C@H:18]1[CH2:19][CH2:20][N:16]([C@H:6]2[CH2:7][CH2:8][C@@H:9]([NH:11][C:12]([CH3:15])([CH3:13])[CH3:14])[CH2:10][C@H:5]2[NH:4][C:1](=[O:3])[CH3:2])[C:17]1=[O:32]
Reactant: CC(=O)N[C@@H]1C[C@H](NC(C)(C)C)CC[C@@H]1N1CC[C@H](NC(=O)OCc2ccccc2)C1=O
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: CC(=O)N[C@@H]1C[C@H](NC(C)(C)C)CC[C@@H]1N1CC[C@H](N)C1=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 83.8 %

Procedure:
To a solution of benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-(tert-butylamino)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate (22 mg, 0.05 mmol) in methanol (2 mL) was added Pd(OH)2 (20 mg of 50% wet catalyst). The flask was evacuated and back-filled with hydrogen from a hydrogen balloon. The mixture was stirred at room temperature for 1 h and the catalyst was removed by filtration. The filtrate was concentrated in vacuo to provide N-((1R,2S,5R)-2-((S)-3-amino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexyl)acetamide (13 mg, 85%). LC/MS found [M+H]+=311.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[CH2:20][CH2:19][C:18]3[C:13](=[CH:14][CH:15]=[C:16]([O:21][CH3:22])[CH:17]=3)[C:12]2=O)=[CH:7][CH:6]=1)(=[O:4])=[O:3].C1(C)C=CC=CC=1.P(Br)(Br)[Br:32]>C1COCC1>[Br:32][C:12]1[C:13]2[C:18](=[CH:17][C:16]([O:21][CH3:22])=[CH:15][CH:14]=2)[CH2:19][CH2:20][C:11]=1[C:8]1[CH:9]=[CH:10][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:6][CH:7]=1
Reactant: COc1ccc2c(c1)CCC(c1ccc(S(C)(=O)=O)cc1)C2=O
Reactant: BrP(Br)Br
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: COc1ccc2c(c1)CCC(c1ccc(S(C)(=O)=O)cc1)=C2Br
Temperature: 110 °C
Reaction time: 0.5 h

Procedure:
Combine 2-(4-methanesulfonylphenyl)-6-methoxytetralone (1.0 eq.), hyflo (20%/weight), and toluene (7.5 volumes). Add PBr3 (1.5˜1.75 eq.) in one portion while stirring at room temperature. Heat contents to reflux (˜110° C.) overnight. Upon reaction completion, as judged by HPLC analysis (usually 15 hours), cool solution to 45° C. and slowly add 20 volumes THF. Stir for 30 minutes at 45° and filter warm over a pad of hyflo. The pad is washed with 2×2 volumes THF at 45° C. Concentrate filtrate to approximately 7 volumes. Add 7.5 volumes water to the remaining mixture keeping the temperature below 40° C. (NOTE: initial addition of water is very exothermic with large evolution of HBr). Cool slurry to room temperature and stir for 2 to 3 hours. Filter over a polypropylene pad and wash with 2×2 volumes water. Dry filter cake overnight at 60° C. under vacuum to give 1-bromo-2-(4-methanesulfonylphenyl)-3,4-dihydro-6-methoxynaphthalene.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.F[C:10]1[CH:33]=[CH:32][C:13]([C:14]([C:16]2[CH:31]=[CH:30][C:19]([O:20][C:21]3[CH:22]=[C:23]([CH:27]=[CH:28][CH:29]=3)[C:24]([OH:26])=[O:25])=[CH:18][CH:17]=2)=[O:15])=[CH:12][CH:11]=1.C(=O)([O-])[O-].[K+].[K+].Cl>CS(C)=O.O>[NH2:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[O:8][C:32]1[CH:33]=[CH:10][CH:11]=[CH:12][C:13]=1[C:14]([C:16]1[CH:31]=[CH:30][C:19]([O:20][C:21]2[CH:22]=[C:23]([CH:27]=[CH:28][CH:29]=2)[C:24]([OH:26])=[O:25])=[CH:18][CH:17]=1)=[O:15]
Reactant: Nc1cccc(O)c1
Reactant: O=C(O)c1cccc(Oc2ccc(C(=O)c3ccc(F)cc3)cc2)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: Nc1cccc(Oc2ccccc2C(=O)c2ccc(Oc3cccc(C(=O)O)c3)cc2)c1
Reaction time: 8 h
Yield: 14 %

Procedure:
A mixture of m-aminophenol (0.64 g, 5.87 mmol), 3-[4-(4-fluorobenzoyl)phenoxy]benzoic acid (2.0 g, 5.95 mmol), and anhydrous potassium carbonate (4.0 g) was stirred in dry dimethylsulfoxide (20 ml) at 120° C. under nitrogen for 48 hours. The cooled reaction mixture was poured into water and carefully neutralized with conc. hydrochloric acid to precipitate 2.58 g of a white solid. The crude product was digested in hot toluene, and the toluene solution (after decanting from a large quantity of gum) was allowed to stand overnight at 0° C. The crystals thus obtained were recrystallized to give 0.35 g of product, m.p. 144°-150° C. dec. (14%).
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]([NH:9][C:10]([C:13]2[N:19]([CH3:20])[C:17](=[O:18])[C:16]([OH:21])=[C:15]([C:22]([NH:24][CH2:25][C:26]3[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=3)=[O:23])[N:14]=2)([CH3:12])[CH3:11])=[O:8])=[N:4][N:3]=1.[OH-].[K+:34]>C(O)C.O>[CH3:1][C:2]1[O:6][C:5]([C:7]([NH:9][C:10]([C:13]2[N:19]([CH3:20])[C:17](=[O:18])[C:16]([O-:21])=[C:15]([C:22]([NH:24][CH2:25][C:26]3[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=3)=[O:23])[N:14]=2)([CH3:12])[CH3:11])=[O:8])=[N:4][N:3]=1.[K+:34]
Reactant: Cc1nnc(C(=O)NC(C)(C)c2nc(C(=O)NCc3ccc(F)cc3)c(O)c(=O)n2C)o1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: Cc1nnc(C(=O)NC(C)(C)c2nc(C(=O)NCc3ccc(F)cc3)c([O-])c(=O)n2C)o1
Temperature: 27.5 °C
Reaction time: 16 h
Yield: 95.8 %

Procedure:
Raltegravir (50 gm) was suspended in ethanol (500 ml) and then added a solution of potassium hydroxide (8 gm) in water (10 ml) at 25 to 30° C. The reaction mass was stirred for 16 hours at 25 to 30° C. and filtered. The solid obtained was dried under vacuum at 60° C. for 9 hours to obtain 52 gm of raltegravir potassium crystalline form H1.
Reaction SMILES: ClC1C=C(C=CC=1)C(OO)=[O:6].[C:12]([N:19]1[CH2:24][CH:23]=[CH:22][CH2:21][CH2:20]1)([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].[O-]S([O-])(=S)=O.[Na+].[Na+].C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[CH3:16][C:15]([O:14][C:12]([N:19]1[CH2:20][CH2:21][CH:22]2[CH:23]([O:6]2)[CH2:24]1)=[O:13])([CH3:18])[CH3:17]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CC(C)(C)OC(=O)N1CC=CCC1
Agent: O=C([O-])[O-]
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC2OC2C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 100.4 %

Procedure:
A solution of 3-chloroperoxybenzoic acid (2.96 g, 12.0 mmol) in DCM (20 mL) was added to a solution of N-boc-1,2,3,6-tetrahydropyridine (2.0 g, 10.9 mmol) in DCM (10 mL) at 0° C. The mixture was stirred at room temperature overnight and then a 10% solution of Na2S2O3 was added and the mixture basified with a saturated solution of Na2CO3. The organic layer was separated, dried (Na2SO4), filtered and the solvent evaporated in vacuo to yield 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylic acid 1,1-dimethylethyl ester (2.18 g, 100% yield) that was used in the next step without further purification. C10H17NO3 GCMS (EI): Rt 8.96, MW (theor) 199; m/z [M]+ 199 (using method, GC-MS Method 1).
Reaction SMILES: B(Br)(Br)Br.[Cl:5][C:6]1[C:13]([Cl:14])=[C:12]([O:15]C)[CH:11]=[CH:10][C:7]=1[CH:8]=[O:9]>C(Cl)Cl>[OH:15][C:12]1[CH:11]=[CH:10][C:7]([CH:8]=[O:9])=[C:6]([Cl:5])[C:13]=1[Cl:14]
Reactant: COc1ccc(C=O)c(Cl)c1Cl
Agent: BrB(Br)Br
Solvent: ClCCl
Product: O=Cc1ccc(O)c(Cl)c1Cl
Temperature: 25 °C
Reaction time: 4 h
Yield: 95.3 %

Procedure:
A solution of 5.51 g of boron tribromide in methylene chloride is added dropwise to a solution of 2.05 g of 2,3-dichloro-4-methoxybenzaldehyde in methylene chloride. The mixture is stirred at room temperature for 4 hours, poured into ice-water and then extracted with ethyl acetate. The extract is washed with water, dried and evaporated to remove solvent. 10% hydrochloric acid and methanol are added to the residue and the mixture is stirred for 3 hours under ice-cooling and extracted with ethyl acetate again. The extract is washed with water, dried and evaporated to remove solvent. The residue is crystallized with isopropyl ether to give 1.82 g of 4-hydroxy-2,3-dichlorobenzaldehyde.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[CH3:9][C:10]1([CH3:18])[CH2:16][C:15](=O)[O:14][C:12](=[O:13])[CH2:11]1.C.O.C(O)C>C(O)C>[OH:8][C:5]1[CH:6]=[CH:7][C:2]([N:1]2[C:12](=[O:13])[CH2:11][C:10]([CH3:18])([CH3:9])[CH2:16][C:15]2=[O:14])=[CH:3][CH:4]=1
Reactant: Nc1ccc(O)cc1
Reactant: CC1(C)CC(=O)OC(=O)C1
Solvent: CCO
Solvent: O
Product: CC1(C)CC(=O)N(c2ccc(O)cc2)C(=O)C1
Temperature: 165 °C
Yield: 50.2 %

Procedure:
A mixture of 4-aminophenol (3.27 g, 30.0 mmol) and 3,3-dimethylglutaric anhydride (4.26 g, 30.0 mmol) was heated in a round bottom flask at 165° C. for 1 h, followed by heating at 180° C. for 7 h. After cooling to room temperature the solid material was dissolved in hot ethanol, activated charcoal was added and the solution was heated at reflux for 1 h. The solid material was removed by hot filtration. The solvent was evaporated and the residue was crystallised from water/ethanol yielding the title compound (3.51 g, 50% yield, pink solid).
Reaction SMILES: [Cl:1][C:2]1[N:3]=[N:4][C:5](Cl)=[CH:6][C:7]=1[C:8]([CH3:11])([CH3:10])[CH3:9].O.[NH2:14][NH2:15].Cl>C(O)C>[Cl:1][C:2]1[N:3]=[N:4][C:5]([NH:14][NH2:15])=[CH:6][C:7]=1[C:8]([CH3:11])([CH3:10])[CH3:9]
Reactant: CC(C)(C)c1cc(Cl)nnc1Cl
Reactant: NN
Agent: Cl
Solvent: O
Solvent: CCO
Product: CC(C)(C)c1cc(NN)nnc1Cl
Yield: 61.3 %

Procedure:
To a solution of 3,6-dichloro-4-(1,1-dimethylethyl)pyridazine (2.0 g, 9.76 mmol) in ethanol (30 ml) was added hydrazine hydrate (0.34 ml, 10.9 mmol) dropwise. The reaction mixture was heated at reflux for 18 h under an atmosphere of nitrogen. The solvent was removed under high vacuum to leave a residue to which was added 5N hydrochloric acid (50 ml). The solution obtained was washed with dichloromethane (20 ml) and the aqueous layer was poured on to a mixture of ice and aqueous ammonia. The resultant solid was collected by filtration and dried under vacuum to yield the title compound (1.2 g). Data for the title compound: 1H NMR (360 MHz, DMSO) δ1.39 (3H, t, J=7.3 Hz), 4.35 (2H), 7.07 (1H, s), 8.07 (1H, s); MS (ES+) m/e 201, 203 [MH]+.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:18](Br)[CH:19]=[CH2:20]>CC(C)=O>[CH2:20]([O:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:10][CH:11]=1)[CH:19]=[CH2:18]
Reactant: COC(=O)c1ccc(O)cc1
Reactant: C=CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: C=CCOc1ccc(C(=O)OC)cc1
Temperature: 25 °C
Yield: 84.6 %

Procedure:
A 2 L flask was equipped with a mechanical stirrer, a reflux condenser and a stopper, then charged with 50.05 g (0.329 mol) of methyl 4-hydroxybenzoate, 960 mL of acetone, 22.50 g (1.625 mol) of anhydrous potassium carbonate, 80.5 mL (112.6 g, 0.932 mol) of allyl bromide and the mixture was stirred and refluxed for 14 hours. The mixture was cooled to room temperature, filtered and concentrated to an oil. The residual oil was purified by distillation (97° C.@0.03 mm Hg) to afford 53.52 g (86%) of the title compound.
Reaction SMILES: [CH:1]1([C:6]#[CH:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.C([Li])CCC.C1(O[C:20]#[N:21])C=CC=CC=1.[OH-].[Na+]>C1COCC1.CCCCCC>[CH:1]1([C:6]#[C:7][C:20]#[N:21])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: C#CC1CCCC1
Reactant: N#COc1ccccc1
Agent: [Li]CCCC
Agent: [Na+]
Agent: [OH-]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: N#CC#CC1CCCC1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 95 %

Procedure:
To a solution of cyclopentylacetylene (0.50 g, 5.3 mmol) in THF (5 mL) at −78° C. was added 2.5 M n-butyllithium in hexane (2.23 mL). The mixture was stirred for 15 min followed by the dropwise addition of phenyl cyanate (0.70 g, 5.8 mmol) in THF (3 mL). The reaction was warmed to room temperature. Into the reaction mixture was poured 6 N NaOH, and the mixture was stirred for 5 minutes. The product was extracted with diethyl ether. The extracts were washed with 6 N NaOH and with brine, then dried over sodium sulfate, decanted and the solvent was removed in vacuo to afford product (600 mg, 95%). 1H NMR (300 MHz, CDCl3): δ □2.81-2.68 (m, 1H), 2.07-1.54 (m, 8H).
Reaction SMILES: [C:1](=[O:4])([O-])[O-:2].[K+].[K+].C(=O)=O.[CH:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12][C:11]=1[O-:20].[K+]>O>[OH:20][C:11]1[CH:12]=[CH:13][C:14]2[C:19](=[CH:18][CH:17]=[C:16]([C:1]([OH:2])=[O:4])[CH:15]=2)[CH:10]=1
Reactant: O=C([O-])[O-]
Reactant: [O-]c1ccc2ccccc2c1
Agent: O=C=O
Agent: [K+]
Solvent: O
Product: O=C(O)c1ccc2cc(O)ccc2c1
Temperature: 280 °C
Yield: 67 %

Procedure:
A stainless steel pressure autoclave is charged with 100 parts of kerosene and 38 parts of potassium carbonate and heated to 280° C. It is then pressurized with 10 bar of carbon dioxide. Over the course of 5 hours, 50 parts of potassium β-naphtholate are metered in as a suspension in kerosene via a metering pump, part of the kerosene being distilled off, condensed and transferred out of the reaction vessel at reduced pressure. After cooling, the reaction mixture is taken up in water and the kerosene upper phase is decanted off. After acidification with sulfuric acid to a pH of 7, unreacted β-naphthol can be precipitated and separated off. Further acidification to pH 4 precipitates first the 2-hydroxynaphthalene-6-carboxylic acid and at pH 1 finally the remaining acids. The 2-hydroxynaphthalene-6-carboxylic acid is obtained in a yield of 67% based on potassium β-naphtholate used. In addition, 23% of unreacted β-naphtholate and small amounts of 2-hydroxynaphthalene-3-carboxylic acid and 2-hydroxynaphthalene-3,6-dicarboxylic acid are obtained.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[N:4][C:5](Cl)=[CH:6][CH:7]=1.[F:9][C:10]([F:25])([C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[N:21]=[CH:20][CH:19]=[CH:18]2)[C:11]([NH:13][NH2:14])=O>CCCCO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]2[N:4]([C:11]([C:10]([F:25])([F:9])[C:15]3[CH:16]=[C:17]4[C:22](=[CH:23][CH:24]=3)[N:21]=[CH:20][CH:19]=[CH:18]4)=[N:13][N:14]=2)[N:3]=1
Reactant: Clc1ccc(Cl)nn1
Reactant: NNC(=O)C(F)(F)c1ccc2ncccc2c1
Solvent: CCCCO
Product: FC(F)(c1ccc2ncccc2c1)c1nnc2ccc(Cl)nn12
Temperature: 130 °C
Yield: 53.5 %

Procedure:
3,6-Dichloropyridazine (160 mg, 1.07 mmol) and difluoro-quinolin-6-yl-acetic acid hydrazide (254 mg, 1.07 mmol) were added in n-BuOH (20 mL). The reaction mixture was heated at 130° C. for 12 h. The solvent was removed under reduced pressure. The crude was partitioned in aqueous solution of K2CO3 and EtOAc. The organic layers were combined and concentrated to give a solid, which was purified by silica gel column to give the title compound as black solid (190 mg, 53%). 1H-NMR (400 MHz, DMSO-d6) δ ppm 7.62 (m, 2H), 7.90 (m, 1H), 8.22 (m, 1H), 8.35 (m, 1H), 8.65 (m, 2H), 9.02 (m, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[S:11][C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[CH:8]=[C:7]([C:16]#[C:17][CH2:18][OH:19])[C:6]=2[CH:20]=1.N1C=CC=CC=1.[CH3:27][S:28](Cl)(=[O:30])=[O:29].Cl>CCOCC>[S:28]([O:19][CH2:18][C:17]#[C:16][C:7]1[C:6]2[CH:20]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[S:11][C:10]2[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=2[CH:8]=1)(=[O:30])(=[O:29])[CH3:27]
Reactant: CS(=O)(=O)Cl
Reactant: OCC#CC1=Cc2ccccc2Sc2ccc(Cl)cc21
Agent: Cl
Solvent: CCOCC
Solvent: c1ccncc1
Product: CS(=O)(=O)OCC#CC1=Cc2ccccc2Sc2ccc(Cl)cc21

Procedure:
A solution of 6 g. of 3-(8-chloro-dibenzo[b,f]thiepin-10-yl)-2-propyn-1-ol in 50 ml. of pyridine is treated dropwise at -10° C. to 0° C. with 1.7 ml. of methanesulfonyl chloride in 10 ml. of pyridine and stirred at this temperature for 2 hours. After pouring onto ice, acidification with hydrochloric acid and extraction with ether, there is obtained 3-(8-chloro-dibenzo[b,f]thiepin-10-yl)-2-propyn-1-ol mesylate which melts at 100°-102° C. after recrystallizatin from ether.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH3:8].Cl[C:10]([CH3:18])([CH2:12][CH2:13][C:14](Cl)([CH3:16])[CH3:15])[CH3:11].[Cl-].[Al+3].[Cl-].[Cl-]>ClCCl.CCCCCC.Cl>[Br:1][C:2]1[C:3]([CH3:8])=[CH:4][C:5]2[C:14]([CH3:16])([CH3:15])[CH2:13][CH2:12][C:10]([CH3:18])([CH3:11])[C:6]=2[CH:7]=1
Reactant: CC(C)(Cl)CCC(C)(C)Cl
Reactant: Cc1ccccc1Br
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: CCCCCC
Solvent: ClCCl
Product: Cc1cc2c(cc1Br)C(C)(C)CCC2(C)C
Temperature: 25 °C
Reaction time: 16 h
Yield: 87.3 %

Procedure:
To a solution of 20 g (117 mmol) of 2-bromotoluene and 14.4 g (97.4 mmol) of 2,5-dichloro-2,5-dimethylhexane in 100 mL of dichloromethane was added 1.56 g (16.9 mmol) of aluminum chloride and the mixture heated at reflux. After 16 hours, the mixture was cooled to room temperature, diluted with 150 mL of hexane and 100 mL of 1 N HCl was added. The organic layer was separated and the aqueous layer was extracted with hexane. The combined organic layers were washed with saturated NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The product was purified by filtration through a pad of silica gel with elution with hexane and afforded 23.9 g (87%) of 2-bromo-3-methyl-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene as a solid. (m.p.: 81.1-85° C.).
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[C:8]([Cl:10])[CH:7]=[CH:6][C:3]=1[CH:4]=O.[C:11](#[N:15])[CH2:12][C:13]#[N:14].[OH-].[K+]>C(O)C>[Cl:1][C:2]1[CH:9]=[C:8]([Cl:10])[CH:7]=[CH:6][C:3]=1[CH:4]=[C:12]([C:11]#[N:15])[C:13]#[N:14]
Reactant: N#CCC#N
Reactant: O=Cc1ccc(Cl)cc1Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: N#CC(C#N)=Cc1ccc(Cl)cc1Cl
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 80.7 %

Procedure:
To a solution of 2,4-dichlorobenzaldehyde (1.75 g, 10 mmol) and malononitrile (660 mg, 10 mmol) in ethanol (10 ml) was added 200 μL of 10% aqueous KOH. The mixture was stirred at room temperature for 15 min, allowed to stand for 30 min, cooled with ice-bath and then filtered to give 2-(2,4-dichloro-benzylidene)-malononitrile (1a) as a white solid (1.8 g).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][NH2:11])=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH2:12]([S:14](Cl)(=[O:16])=[O:15])[CH3:13]>N1C=CC=CC=1>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:10][NH:11][S:14]([CH2:12][CH3:13])(=[O:16])=[O:15])=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: NCc1ccc([N+](=O)[O-])cc1
Reactant: CCS(=O)(=O)Cl
Solvent: c1ccncc1
Product: CCS(=O)(=O)NCc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 67.6 %

Procedure:
(4-Nitrophenyl)methanamine (715 mg, 4.7 mmol) was dissolved in pyridine (4 mL). The reaction mixture was added ethane sulfonyl chloride (0.58 mL, 6.11 mmol) and stirred for 1 h at room temperature. TLC showed complete consumption of starting material. The mixture was diluted with 1N HCl and extracted with ethyl acetate. The extract was dried over magnesium sulfate and concentrated under reduced pressure. The crude was purified by column chromatography to give N-(4-nitrobenzyl)ethanesulfonamide (776 mg, 68%).
Reaction SMILES: Cl.[NH2:2][OH:3].C([O-])(=O)C.[Na+].[CH:9]1([O:14][C:15]2[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=2[O:23][CH3:24])[CH:18]=O)[CH2:13][CH2:12][CH2:11][CH2:10]1>C(O)C>[CH:9]1([O:14][C:15]2[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=2[O:23][CH3:24])[CH:18]=[N:2][OH:3])[CH2:13][CH2:12][CH2:11][CH2:10]1
Reactant: NO
Reactant: COc1ccc(C=O)cc1OC1CCCC1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: COc1ccc(C=NO)cc1OC1CCCC1
Temperature: 25 °C
Reaction time: 0.83 h

Procedure:
Hydroxylamine hydrochloride (0.473 g, 6.8181 mmol) and sodium acetate (0.56 g, 6.8181 mmol) was added to a stirred solution of compound of Formula II (0.5 g, 2.2727 mmol) in ethanol (8 mL). The reaction mixture was stirred at room temperature for 50 minutes. Ethanol was evaporated under reduced pressure, which was diluted with water (20 mL) and the organic compound was extracted with ethyl acetate (2×15 mL). The ethyl acetate layer was dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to afford compound of Formula III. Analysis by 1H NMR spectroscopy gave the following peaks (CDCl3): 9.84 (s, 1H), 8.07 (s, 1H), 6.84-7.24 (m, 3H), 4.79-4.83 (m, 1H), 3.87 (s, 3H), 1.62-2.18 (m, 8H).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([CH3:9])[CH:8]=1)[NH2:5].[C:10](OC(=O)C)(=[O:12])[CH3:11]>>[CH3:1][C:2]1[CH:3]=[C:4]([NH:5][C:10](=[O:12])[CH3:11])[CH:6]=[C:7]([CH3:9])[CH:8]=1
Reactant: CC(=O)OC(C)=O
Reactant: Cc1cc(C)cc(N)c1
Product: CC(=O)Nc1cc(C)cc(C)c1
Temperature: 100 °C
Reaction time: 1 h
Yield: 93.7 %

Procedure:
A mixture of the 3,5-dimethylaniline (12.1 g, 100.0 mmol) and acetic anhydride (12.1 g, 118.6 mmol) was stirred at 100° C. for 1 h. The crude product was then recrystallized from methanol to provide N-(3,5-dimethylphenyl)acetamide (15.3 g, 93.9%) as a white flake; m.p. 140-142° C. (Lit. 139.6-140.2° C.5.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:16]1[CH:17]=[CH:18][N:19]=[C:20]2[C:25]=1[N:24]=[CH:23][C:22]([O:26][CH3:27])=[CH:21]2.O>CN(C=O)C>[CH3:27][O:26][C:22]1[CH:21]=[C:20]2[C:25]([C:16]([O:8][C:5]3[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][CH:4]=3)=[CH:17][CH:18]=[N:19]2)=[N:24][CH:23]=1
Reactant: Nc1ccc(O)cc1
Reactant: COc1cnc2c(Cl)ccnc2c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1cnc2c(Oc3ccc(N)cc3)ccnc2c1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
Five 20 mL microwave vials were each charged with 4-aminophenol (0.700 mg, 33 mmol) and 3 equivalents of cesium carbonate in 6.0 ml of DMF. The mixture was stirred at RT for 10 minutes. Following addition of 8-chloro-3-methoxy-1,5-naphthyridine (1 g, 26 mmol), the reaction vessels were capped and irradiated at 150° C. for 15 min in the microwave, at which time the reaction was determined complete by LCMS. The mixture was allowed to cool to ambient temperature and material from the five vessels was combined. A deep brown solid crashed out with addition of water. Filtered solids, washed with water and dried overnight in the vacuum oven to afford 4-(7-methoxy-1,5-naphthyridin-4-yloxy)benzenamine as a brown solid.
Reaction SMILES: [CH:1]1[C:6]([OH:7])=[CH:5][CH:4]=[C:3]([CH3:8])[CH:2]=1.Br[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH3:8][C:3]1[CH:4]=[CH:5][C:6]([O:7][CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:1][CH:2]=1
Reactant: CCOC(=O)CBr
Reactant: Cc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)COc1ccc(C)cc1
Yield: 96.6 %

Procedure:
In 70 ml of acetone were suspended 5.00 g of p-cresol, 7.72 g of ethyl bromoacetate and 6.39 g of potassium carbonate, and the resulting mixture was refluxed for 12 hours. After the solvent was distilled off under reduced pressure, water was added to the mixture, followed by extraction with methylene chloride. The organic phase was washed with in aqueous 2N sodium hydroxide solution and then with saturated sodium chloride solution, which was then dried over magnesium sulfate. On evaporation of the solvent under reduced pressure, 8.67 g of ethyl 4-methylphenoxyacetate was produced.