Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:3][C:4](=[O:32])[CH2:5][O:6][C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:17]3[O:18][C:19]4[CH:30]=[CH:29][CH:28]=[CH:27][C:20]=4[C:21]=3[CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[CH:13]=2)[C:8]=1[Br:31])C.[OH-].[K+]>C1COCC1.O>[Br:31][C:8]1[C:9]2[C:14](=[CH:13][C:12]([C:17]3[O:18][C:19]4[CH:30]=[CH:29][CH:28]=[CH:27][C:20]=4[C:21]=3[CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])=[CH:11][CH:10]=2)[CH:15]=[CH:16][C:7]=1[O:6][CH2:5][C:4]([OH:32])=[O:3]
Reactant: CCCCCc1c(-c2ccc3c(Br)c(OCC(=O)OCC)ccc3c2)oc2ccccc12
Agent: [K+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CCCCCc1c(-c2ccc3c(Br)c(OCC(=O)O)ccc3c2)oc2ccccc12
Yield: 76.1 %

Procedure:
Following the procedure described in Step 4 of Example 6, [1-bromo-6-(3-pentyl-benzofuran-2-yl)-naphthalen-2-yloxy]-acetic acid ethyl ester (1.25 g, 2.53 mmol), was hydrolyzed with potassium hydroxide (0.70 g, 12.5 mmol) in THF (30 mL) and water (10 mL). Crystallization from ethyl acetate/hexane furnished the title compound as an off-white solid (0.90 g), mp 159-161° C. Mass spectrum (+APCl, [M+H]+) m/z 467. 1HNMR (400 MHz, DMSO-d6): δ13.2 (br s, 1H), 8.32 (d, 1H, J=1.5 Hz), 8.22 (d, 1H, J=9.0 Hz), 8.10 (d, 1H, J=9.0 Hz), 8.03 (dd, 1H, J=9.0, 1.5 Hz), 7.69-7.67 (m, 1H), 7.61 (d, 1H, J=8.0 Hz), 7.45 (d, 1H, J=9.0 Hz), 7.35-7.28 (m, 2H), 5.00 (s, 2H), 3.00 (t, 2H, J=7.8 Hz), 1.75-1.66 (m, 2H), 1.40-1.27 (m, 4H), and 0.84-0.79 ppm (m, 3H). Elemental Analysis for C25H23BrO2.1.0H2O: Calculated: C, 61.86; H, 5.19; N, 0.00. Found: C, 61.87; H, 4.70; N, 0.04.
Reaction SMILES: [NH2:1][CH:2]([C:4]1[CH:13]=[C:12]2[C:7]([CH2:8][CH2:9][CH2:10][NH:11]2)=[CH:6][CH:5]=1)[CH3:3].S(OC)(O[CH3:18])(=O)=O.[O-2].[Mg+2]>C1(C)C=CC=CC=1>[NH2:1][CH:2]([C:4]1[CH:13]=[C:12]2[C:7]([CH2:8][CH2:9][CH2:10][N:11]2[CH3:18])=[CH:6][CH:5]=1)[CH3:3]
Reactant: COS(=O)(=O)OC
Reactant: CC(N)c1ccc2c(c1)NCCC2
Agent: [Mg+2]
Agent: [O-2]
Solvent: Cc1ccccc1
Product: CC(N)c1ccc2c(c1)N(C)CCC2
Temperature: 70 °C
Reaction time: 18 h

Procedure:
Example P-13:1.3 g of 7-(1-aminoethyl)-1,2,3,4-tetrahydro-quinoline, 0.73 gof dimethyl sulfate and 0.27 g of ground magnesium oxide in 50 ml of absolute toluene are placed in a sulfonation flask. The internal temperature is then increased to 100°-105° C. and the mixture is stirred at that temperature for 18 hours. After cooling, inorganic material is filtered off, 10 ml of cone. HCl are added to the toluene solution, and the batch is maintained at 70° C. for 2 hours. The batch is then neutralised with sodium hydroxide solution and the organic phase is removed. The aqueous phase is subsequently further extracted twice with ethyl acetate and the organic phases are dried over Na2SO4. After removal of the solvent under a water-jet vacuum, 1.2 g of crude product are obtained which can be purified by flash chromatography on silica gel (eluant: ethyl acetate/n-hexane 1: 1) to yield 1.05 g of 7-(1-aminoethyl)-1-methyl-1,2,3,4-tetrahydro-quinoline in the form of a red oil (1H-NMR).
Reaction SMILES: [N:1]([CH2:4][CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][O:15][CH2:16][CH2:17][O:18][CH2:19][CH2:20][NH2:21])=[N+:2]=[N-:3].[C:22]1(=[O:29])[O:28][C:26](=[O:27])[CH2:25][O:24][CH2:23]1>ClCCl.O>[N:1]([CH2:4][CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][O:15][CH2:16][CH2:17][O:18][CH2:19][CH2:20][NH:21][C:26](=[O:27])[CH2:25][O:24][CH2:23][C:22]([OH:29])=[O:28])=[N+:2]=[N-:3]
Reactant: [N-]=[N+]=NCCOCCOCCOCCOCCOCCN
Reactant: O=C1COCC(=O)O1
Solvent: O
Solvent: ClCCl
Product: [N-]=[N+]=NCCOCCOCCOCCOCCOCCNC(=O)COCC(=O)O
Reaction time: 8 h

Procedure:
To a solution of 17-azido-3,6,9,12,15-pentaoxaheptadecanamine (15 g, 50 mmol) in dichloromethane (100 mL) was added diglycolic anhydride (Acros, 6.4 g, 55 mmol). The reaction mixture was stirred overnight. The reaction was monitored by ESI-MS analysis, and more reagents were added to drive the reaction to completion. The solution was concentrated to give a yellow residue which was dissolved in water (250 mL). The product was isolated from the aqueous phase by continuous extraction with dichloromethane over night. Drying and evaporation of the solvent gave a yield of 18 g (85%). The product was characterized by ESI-MS analysis (MH+ calculated: 423.20; found 423.4). The product was used in the next step without further purification.
Reaction SMILES: [CH:1]1([CH3:13])[CH2:6][CH2:5][CH:4]([CH:7]([CH3:9])[CH3:8])[CH:3]([C:10](Cl)=[O:11])[CH2:2]1.[C:14]([OH:19])(=[O:18])[CH:15]([CH3:17])[OH:16]>O>[CH:1]1([CH3:13])[CH2:6][CH2:5][CH:4]([CH:7]([CH3:9])[CH3:8])[CH:3]([C:10]([O:16][CH:15]([CH3:17])[C:14]([OH:19])=[O:18])=[O:11])[CH2:2]1
Reactant: CC1CCC(C(C)C)C(C(=O)Cl)C1
Reactant: CC(O)C(=O)O
Solvent: O
Product: CC1CCC(C(C)C)C(C(=O)OC(C)C(=O)O)C1

Procedure:
p-Menth-3-oyl chloride (2.0 g.) was stirred with lactic acid (20 ml.) at room temperature for 20 hours. The reaction product was then poured into water (600 ml.) and extracted twice with ether. The extracts were dried (CaCl2) and the solvent removed under reduced pressure to leave 2-(p-menth-3-oyloxy)propionic acid as an oily liquid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][C:9]2=[O:15])=[CH:4][CH:3]=1.[Li+].CC([N-]C(C)C)C.Cl[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26]>C1COCC1.CCOC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:14][CH2:13][CH2:12][CH2:11][CH:10]([C:25]([O:27][CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[O:26])[C:9]2=[O:15])=[CH:4][CH:3]=1
Reactant: O=C1CCCCCN1c1ccc(F)cc1
Reactant: O=C(Cl)OCc1ccccc1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: O=C(OCc1ccccc1)C1CCCCN(c2ccc(F)cc2)C1=O
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 55.3 %

Procedure:
A solution of 1-(4-fluorophenyl)azepan-2-one (1.1 g, 5.3 mmol) was dissolved in THF (5 mL) and was added into LDA (11 mmol) at −78° C. and stirred for 5 minutes. Benzyl chloroformate (1.6 ml, 11 mmol) was added at −78° C. and the reaction warmed to ambient temperature. The solution was poured into ice and diluted with EtOAc (100 mL). The organic layer washed with brine, dried with Na2SO4, filtered and concentrated. The residue was purified by column chromatography (50% EtOAc in hexane) to afford the product (1 g, 55% yield) as brown oil.
Reaction SMILES: Cl.Cl.[OH:3][C:4]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)([CH2:7][NH2:8])[CH2:5][NH2:6].[OH-].[Na+].[CH3:17][C:18]([CH3:20])=O>O>[CH3:17][C:18]1([CH3:20])[NH:8][CH2:7][C:4]([OH:3])([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:5][NH:6]1
Reactant: CC(C)=O
Reactant: NCC(O)(CN)c1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC1(C)NCC(O)(c2ccccc2)CN1
Reaction time: 8 h
Yield: 68.5 %

Procedure:
4.4 g (0.01841 mol) of the dihydrochloride obtained in stage (c) above are dissolved in 50 ml of water. 2.2 g of sodium hydroxide pellets and 3 ml of acetone are added. The mixture is left to stand overnight at room temperature (15°-20° C.) and extracted with 3×100 ml of CHCl3, and the chloroform phase is washed with 30 ml of water, dried over MgSO4 and then filtered to remove MgSO4. The filtrate is evaporated to dryness; recrystallization from petroleum ether (fraction boiling at 45°-60° C.) gives 2.6 g (yield: 68.5%) of CRL 41 365. M.p.=108° C.
Reaction SMILES: [S:1]1[C:5]([C:6]([O-:8])=O)=[CH:4][CH:3]=[C:2]1[C:9]([O:11][CH3:12])=[O:10].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[S:36]1[CH:40]=[CH:39][CH:38]=[C:37]1[CH:41]([NH2:43])[CH3:42]>C(Cl)Cl>[CH3:12][O:11][C:9]([C:2]1[S:1][C:5]([C:6](=[O:8])[NH:43][CH:41]([C:37]2[S:36][CH:40]=[CH:39][CH:38]=2)[CH3:42])=[CH:4][CH:3]=1)=[O:10]
Reactant: CC(N)c1cccs1
Reactant: COC(=O)c1ccc(C(=O)[O-])s1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: ClCCl
Product: COC(=O)c1ccc(C(=O)NC(C)c2cccs2)s1
Reaction time: 1 h
Yield: 84 %

Procedure:
A solution of 500 mg (2.7 mmol) of methyl thiophen-2,5-dicarboxylate in CH2Cl2 (20 ml) is treated with 617 mg (4 mmol) 1-hydroxybenzotriazole hydrate and 772 mg (4 mmol) N′-(3-dimethylaminopropyl)-N-ethylcarbodiimid hydrochloride and stirring is continued at ambient temperature for 1 hour. 410 mg (3.2 mmol) of 1-thiophen-2-yl-ethylamine are added to the reaction mixture which is subsequently stirred at ambient temperature overnight. The product is isolated after acidic work-up and purification on silica gel as waxy solid in 84% yield (0.67 g).
Reaction SMILES: [CH3:1][N:2]([CH3:27])[CH2:3][CH2:4][NH:5][C:6]([C:8]1[C:21]2[C:12](=[N:13][C:14]3[C:19]([N:20]=2)=[C:18]2[CH:22]=[CH:23][CH:24]=[C:25]([OH:26])[C:17]2=[CH:16][CH:15]=3)[CH:11]=[CH:10][CH:9]=1)=[O:7].CC(C)([O-])C.[K+].Br[CH2:35][C:36]#[N:37]>CN(C)C=O.C(OCC)(=O)C>[CH3:1][N:2]([CH3:27])[CH2:3][CH2:4][NH:5][C:6]([C:8]1[C:21]2[C:12](=[N:13][C:14]3[C:19]([N:20]=2)=[C:18]2[CH:22]=[CH:23][CH:24]=[C:25]([O:26][CH2:35][C:36]#[N:37])[C:17]2=[CH:16][CH:15]=3)[CH:11]=[CH:10][CH:9]=1)=[O:7]
Reactant: CN(C)CCNC(=O)c1cccc2nc3ccc4c(O)cccc4c3nc12
Reactant: N#CCBr
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CN(C)CCNC(=O)c1cccc2nc3ccc4c(OCC#N)cccc4c3nc12
Temperature: 100 °C

Procedure:
To a suspension of 4-hydroxy-benzo[a]phenazine-11-carboxylic acid (2-dimethylamino-ethyl)-amide: hydrobromide salt (230 mg) in dry N,N-dimethylformamide (3 mL) was added potassium tert-butoxide (175 mg) and then bromoacetonitrile (47 μL). The reaction mixture was heated to 100° C. for 1 hour. The reaction mixture was then cooled, diluted with ethyl acetate, washed with sodium carbonate solution and brine, dried (MgSO4) and the solvent removed in vacuo to provide crude product. This was purified using flash chromatography (silica, 25% MeOH in ethyl acetate) to yield the title compound as a yellow solid (74 mg).
Reaction SMILES: [OH:1][C:2]1[C:10]([CH:11]([CH3:13])[CH3:12])=[CH:9][C:5](C(O)=O)=[CH:4][C:3]=1[CH:14]([CH3:16])[CH3:15].[OH-].[Na+].Cl>C(O)CO.O>[CH:11]([C:10]1[CH:9]=[CH:5][CH:4]=[C:3]([CH:14]([CH3:16])[CH3:15])[C:2]=1[OH:1])([CH3:13])[CH3:12]
Reactant: CC(C)c1cc(C(=O)O)cc(C(C)C)c1O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: OCCO
Product: CC(C)c1cccc(C(C)C)c1O
Temperature: 142.5 °C
Reaction time: 1 h
Yield: 93.5 %

Procedure:
To the solution of 4-hydroxy-3,5-diisopropyl benzoic acid 100 g (0.45 M) (example 1) in ethylene glycol (150 ml) was added sodium hydroxide pallets 41.5 g (1.03M) and heated to 140-145° C. under inert atmosphere. After 7 hrs of continued heating at 140-145° C., the reaction mass was cooled to room temperature and diluted with 5 times water. The pH of the mass was then adjusted to 1-2 using concentrated Hydrochloric acid, reaction mixture was stirred for one hour and extracted three times with 200 ml toluene, combined toluene layers were washed twice with 5% aq. sodium bicarbonate solution (50 ml) and finally with water (200 ml), solvent was removed under reduced pressure and a dark brown colored residue which remained was distilled under high vacuum condition (0.2 mm/Hg) to yield 75 g (93.5%) of 2,6-diisopropyl phenol collected as a colourless to pale yellow oily liquid, HPLC Purity 99.93%.
Reaction SMILES: [Br:1][C:2]1[CH:13]=[N:12][C:5]2[NH:6][C:7](=[O:11])[CH2:8][NH:9][CH2:10][C:4]=2[CH:3]=1.CCN(CC)CC.[C:21](Cl)([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22]>C(Cl)Cl>[CH2:24]([O:23][C:21]([N:9]1[CH2:10][C:4]2[CH:3]=[C:2]([Br:1])[CH:13]=[N:12][C:5]=2[NH:6][C:7](=[O:11])[CH2:8]1)=[O:22])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: O=C1CNCc2cc(Br)cnc2N1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C1CN(C(=O)OCc2ccccc2)Cc2cc(Br)cnc2N1
Reaction time: 8 h
Yield: 31 %

Procedure:
A suspension of 7-bromo-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one (1.08 g, 4.46 mmol) in CH2Cl2 (60 mL) was treated with Et3N (0.80 mL, 5.7 mmol) and then cooled in an ice bath. The chilled suspension was treated dropwise with CbzCl (4.5 mmol) to give a clear solution. The ice bath was removed and the solution was allowed to stir overnight. The mixture was diluted with CH2Cl2 (90 mL), washed with H2O (50 mL) and brine (50 mL), dried over Na2SO4, filtered and the solvent was removed in vacuo. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 99.5:0.5 to 99:1) gave the title compound (0.52 g, 31%) as a white solid: 1H NMR (300 MHz, CDCl3) δ 8.31-8.36 (m, 2H), 7.49-7.71 (m, 1H), 7.34-7.40 (m, 4H), 7.19-7.21 (m, 1H), 5.08-5.12 (m, 2H), 4.43-4.65 (m, 4H); MS (ESI) m/e 376 (M+H)+.
Reaction SMILES: [H-].[K+].[CH3:3][N:4]([CH3:18])[CH:5]1[CH2:17][C:16]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[NH:9][C:8]=2[CH2:7][CH2:6]1.[C:19]1([S:25](Cl)(=[O:27])=[O:26])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>O1CCCC1>[C:19]1([S:25]([N:9]2[C:8]3[CH2:7][CH2:6][CH:5]([N:4]([CH3:18])[CH3:3])[CH2:17][C:16]=3[C:15]3[C:10]2=[CH:11][CH:12]=[CH:13][CH:14]=3)(=[O:27])=[O:26])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: CN(C)C1CCc2[nH]c3ccccc3c2C1
Agent: [H-]
Agent: [K+]
Solvent: C1CCOC1
Product: CN(C)C1CCc2c(c3ccccc3n2S(=O)(=O)c2ccccc2)C1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Taken potassium hydride 153.80 mg, 1.15 mM (30% suspension in mineral oil) in tetrahydrofuran (15 ml) and stirred at 25° C. for 10 mt. The reaction mixture was cooled to 10-15° C. Dimethyl-(2,3,4,9-tetrahydro-1H-carbazol-3-yl)amine (190 mg, 0.88 mM), dissolved in 5 ml of THF, was added slowly under stirring maintaining mass temperature below 25° C. The reaction mass was further stirred for 1 hour at 25° C. Then added a solution of Benzene sulphonyl chloride (235 mg, 1.33 mM, dissolved in 5 ml of THF) drop wise over a period of 15 mts. The reaction mass was stirred, while monitoring the progress of the reaction by TLC, for 2 hours at 25° C. After the completion of reaction, the mixture was diluted with 75 mL of ice water and extracted with ethyl acetate; Organic layer was washed with brine solution. The ethyl acetate extract was dried over anhydrous sodium sulfate; filtered and solvent was removed under reduced pressure to obtain the exude product. The residual mass was purified by flash chromatography (silica gel, EtoAc/n-Hexane, 9/1) to get the title compound, which was characterized by IR, NMR and mass spectral analyses.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:11](=[O:12])[C@H:10]([S:13][CH2:14][C:15]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[O:16])[C@H:9]2[C:24]2[CH:38]=[CH:37][C:27]([O:28][CH2:29][C:30]([NH:32][CH2:33][C:34](O)=[O:35])=[O:31])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH2:68]([C:72]([C:78]([OH:80])=[O:79])([CH2:74][CH2:75][CH2:76][CH3:77])[NH2:73])[CH2:69][CH2:70][CH3:71]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:11](=[O:12])[C@H:10]([S:13][CH2:14][C:15]([C:17]3[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=3)=[O:16])[C@H:9]2[C:24]2[CH:25]=[CH:26][C:27]([O:28][CH2:29][C:30]([NH:32][CH2:33][C:34]([NH:73][C:72]([CH2:74][CH2:75][CH2:76][CH3:77])([C:78]([OH:80])=[O:79])[CH2:68][CH2:69][CH2:70][CH3:71])=[O:35])=[O:31])=[CH:37][CH:38]=2)=[CH:6][CH:7]=1
Reactant: O=C(O)CNC(=O)COc1ccc([C@@H]2[C@@H](SCC(=O)c3ccc(F)cc3)C(=O)N2c2ccc(F)cc2)cc1
Reactant: CCCCC(N)(CCCC)C(=O)O
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: ClCCl
Solvent: CN1CCOCC1
Product: CCCCC(CCCC)(NC(=O)CNC(=O)COc1ccc([C@@H]2[C@@H](SCC(=O)c3ccc(F)cc3)C(=O)N2c2ccc(F)cc2)cc1)C(=O)O
Reaction time: 1 h
Yield: 34.3 %

Procedure:
N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine (0.020 g, 0.037 mmol) and NMM (0.040 ml, 0.363 mmol) were dissolved in DCM (5 ml) at 30° C. TBTU (a total of 0.016 g, 0.050 mmol) were added in portions and the mixture was stirred for 1 h. 2-Butylnorleucine (0.007 g, 0.037 mmol) was added and the mixture was stirred at 30° C. for 18 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by preparative HPLC, using a gradient of 20-50% MeCN in 0.1M ammonium acetate buffer as eluent. After freeze-drying, 0.009 g (34% yield) of the title product was obtained as a white solid. M/z: 710.1. 1H NMR (DMSO, 400 MHz): δ 0.73-0.82 (m, 6H), 0.88-1.22 (m, 8H), 1.56-1.69 (m, 2H), 1.96-2.07 (m, 2H), 3.71 (d, 2H), 4.32 (d, 1H), 4.36 (ABq, 2H), 4.52 (s, 2H), 5.16 (d, 1H), 6.95-7.01 (m, 2H), 7.11-7.26 (m, 4H), 7.30-7.40 (m, 4H), 7.61 (s, 1H), 7.98-8.06 (m, 2H), 8.25-8.42 (m, 1H).
Reaction SMILES: [CH2:1]([NH2:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].CO[C:10](OC)([N:12]([CH3:14])[CH3:13])[CH3:11]>>[CH2:1]([N:7]=[C:10]([N:12]([CH3:14])[CH3:13])[CH3:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCCCN
Reactant: COC(C)(OC)N(C)C
Product: CCCCCCN=C(C)N(C)C
Reaction time: 0.5 h

Procedure:
N′-hexyl-N,N-dimethylacetamidine (1e) was synthesized by heating n-hexylamine (2.03 mL) with dimethylacetamide dimethyl acetal (2.5 mL) for 20 min at 60° C. under N2 in a 2-neck round bottom flask without solvent. A yellow solution formed and was allowed to cool. Methanol, a byproduct, was removed by evaporation under high vacuum. Diethyl ether (15 mL) and distilled water (3 drops) were added and CO2 was bubbled through the mixture for 1 h to convert the crude 1e into the bicarbonate salt 2e. The mixture was then put in a freezer for 30 min because the white solid so formed degrades back to the liquid readily upon exposure to air. This frozen material was used as the crude surfactant for emulsion stability tests. A sample of 1e was prepared by applying strong vacuum to a portion of the frozen material at room temperature.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([Cl:11])[CH:10]=1)[NH:7][C:6](=[O:12])[C:5]2([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]Cl)[CH2:13][CH3:14].[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([N:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)=[CH:24][CH:23]=1>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([Cl:11])[CH:10]=1)[NH:7][C:6](=[O:12])[C:5]2([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][N:31]1[CH2:30][CH2:29][N:28]([C:25]2[CH:24]=[CH:23][C:22]([Cl:21])=[CH:27][CH:26]=2)[CH2:33][CH2:32]1)[CH2:13][CH3:14]
Reactant: Clc1ccc(N2CCNCC2)cc1
Reactant: CCC1(CCCCCCl)C(=O)Nc2c(Cl)cc(Cl)cc21
Product: CCC1(CCCCCN2CCN(c3ccc(Cl)cc3)CC2)C(=O)Nc2c(Cl)cc(Cl)cc21

Procedure:
The title compound is prepared according to process H by applying processing method 1 from 5,7-dichloro-3-(5-chloropentyl)-3-ethyl-1,3-dihydro-2H-indol-2-one and 1-(4-chlorophenyl)-piperazine.
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[CH:5][O:4][C:3]=1[CH:7]=[C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:10][C:9]1=[O:17].C1C(=O)N([Br:25])C(=O)C1.O>CN(C=O)C>[Br:25][C:5]1[O:4][C:3]([CH:7]=[C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[NH:10][C:9]2=[O:17])=[C:2]([CH3:1])[CH:6]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1ccoc1C=C1C(=O)Nc2ccccc21
Solvent: O
Solvent: CN(C)C=O
Product: Cc1cc(Br)oc1C=C1C(=O)Nc2ccccc21
Temperature: 0 °C
Reaction time: 1 h
Yield: 71.6 %

Procedure:
To a solution of 3-((3-methylfuran-2-yl)methylene)indolin-2-one (330 mg, 1.47 mmol) in DMF (7.0 mL) was added NBS (265 mg, 1.49 mmol) in DMF (1.0 mL) at 0° C. The reaction was stirred at 0° C. for 1 h and added H2O (13 mL). The resulting precipitate was collected by filtration to yield desired 3-((5-bromo-3-methylfuran-2-yl)methylene)indolin-2-one (320 mg). LCMS (ES): m/z 304 [M+1]+.
Reaction SMILES: [CH3:1][C:2]1[C:6]([C:7]2[CH:16]=[C:15]3[C:10]([C:11]([OH:27])=[C:12]([C:19]([NH:21][CH2:22][C:23]([O:25]C)=[O:24])=[O:20])[C:13](=[O:18])[N:14]3[CH3:17])=[CH:9][CH:8]=2)=[C:5]([CH3:28])[O:4][N:3]=1.[OH-].[Na+].Cl>CO.C1COCC1>[CH3:1][C:2]1[C:6]([C:7]2[CH:16]=[C:15]3[C:10]([C:11]([OH:27])=[C:12]([C:19]([NH:21][CH2:22][C:23]([OH:25])=[O:24])=[O:20])[C:13](=[O:18])[N:14]3[CH3:17])=[CH:9][CH:8]=2)=[C:5]([CH3:28])[O:4][N:3]=1
Reactant: COC(=O)CNC(=O)c1c(O)c2ccc(-c3c(C)noc3C)cc2n(C)c1=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: Cc1noc(C)c1-c1ccc2c(O)c(C(=O)NCC(=O)O)c(=O)n(C)c2c1
Temperature: 24 °C
Reaction time: 4 h

Procedure:
Suspended Methyl 2-(7-(3,5-dimethylisoxazol-4-yl)-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamido)acetate in 3 ml MeOH, 1 ml THF, and 2 ml 1M aqueous NaOH and stirred at 24° C. for 4 hours. The mixture was acidified to pH=1 using 2M aqueous HCl and the solids collected by filtration, washed with H2O and dried in vacuo: 50 mg white solids.
Reaction SMILES: S(Cl)([Cl:3])=O.[NH2:5][C:6]1[C:15]2[N:16]=[C:17]([OH:24])[N:18]([CH2:19][CH2:20][CH2:21][CH2:22]O)[C:14]=2[C:13]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[N:7]=1>ClCCCl>[NH2:5][C:6]1[C:15]2[N:16]=[C:17]([OH:24])[N:18]([CH2:19][CH2:20][CH2:21][CH2:22][Cl:3])[C:14]=2[C:13]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[N:7]=1
Reactant: Nc1nc2ccccc2c2c1nc(O)n2CCCCO
Reactant: O=S(Cl)Cl
Solvent: ClCCCl
Product: Nc1nc2ccccc2c2c1nc(O)n2CCCCCl
Temperature: 50 °C
Reaction time: 8 h
Yield: 85.7 %

Procedure:
Thionyl chloride (1.1 mL, 15 mmol) was added to a solution of 4-amino-1-(4-hydroxybutyl)-1H-imidazo[4,5-c]quinolin-2-ol (3.5 g, 13 mmol) in 1,2-dichloroethane (60 mL), and the reaction was stirred at 50° C. overnight. A solid was present, which was collected by filtration and washed with diethyl ether (500 to 600 mL) to provide 3.24 g of 4-amino-1-(4-chlorobutyl)-1H-imidazo[4,5-c]quinolin-2-ol as a light gray solid.
Reaction SMILES: [ClH:1].Cl.[C:3]([C:6]1[CH:11]=[CH:10][C:9]([CH:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15][C:14]([N:22]([CH3:24])[CH3:23])=[N:13]2)=[CH:8][CH:7]=1)([OH:5])=[O:4].[CH3:25]O>>[ClH:1].[C:3]([C:6]1[CH:7]=[CH:8][C:9]([CH:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15][C:14]([N:22]([CH3:24])[CH3:23])=[N:13]2)=[CH:10][CH:11]=1)([O:5][CH3:25])=[O:4]
Reactant: CN(C)C1=NC(c2ccc(C(=O)O)cc2)c2ccccc2C1
Reactant: CO
Agent: Cl
Product: COC(=O)c1ccc(C2N=C(N(C)C)Cc3ccccc32)cc1

Procedure:
The basic aqueous solution from the above experiment was made acidic with 5N hydrochloric acid, and evaporated to dryness to leave a white solid, containing 1-(4-carboxyphenyl)-1,4-dihydro-3-dimethylaminoisoquinoline hydrochloride. The crude acid was suspended in methanol (100 ml) and ethereal hydrogen chloride (2 ml) at room temperature for 16 h. The suspension was filtered and the filtrate was evaporated under reduced pressure. The residue was dissolved in dilute hydrochloric acid, washed with ethyl acetate, then basified with 10% sodium hydroxide solution and extracted with ethyl acetate. The extracts were washed with brine, dried (MgSO4) and ethereal HCl was added. The solvent was removed under reduced pressure and the residual solid was recrystallised from dichloroethane/ethyl acetate to give 1-(4-carbomethoxyphenyl)-1,4-dihydro-3-dimethylamino-isoquinoline hydrochloride as a pale yellow powder, m.p. 187°-193° C.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[C:7]([OH:10])[CH:8]=[CH:9][C:4]=2[CH:3]=[CH:2]1.[I:11][C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=1)[CH2:15]Br.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(OCC)(=O)C>[I:11][C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=1)[CH2:15][O:10][C:7]1[CH:8]=[CH:9][C:4]2[CH:3]=[CH:2][O:1][C:5]=2[CH:6]=1
Reactant: Oc1ccc2ccoc2c1
Reactant: BrCc1cccc(I)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Ic1cccc(COc2ccc3ccoc3c2)c1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To a stirred solution of 1-benzofuran-6-ol (1.0 g, 7.5 mmol) and 3-iodobenzylbromide (2.7 g, 9.0 mmol) in DMF (10 mL) was added potassium carbonate (1.5 g, 11.0 mmol). The reaction mixture was stirred under nitrogen at room temperature for 3 days. The reaction was diluted with ethyl acetate, washed with water (2×) and brine, dried over magnesium sulfate, filtered and concentrated. The crude product was purified on a silica gel column, eluting with ethyl acetate (10-50%) in hexane. The final product was collected as a slightly yellow viscous oil.