Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1](Cl)(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[F:21][C:22]([F:26])([F:25])[CH2:23][OH:24].Cl>>[C:1]([O:24][CH2:23][C:22]([F:26])([F:25])[F:21])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: OCC(F)(F)F
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)Cl
Agent: Cl
Product: CCCCCCCC/C=C\CCCCCCCC(=O)OCC(F)(F)F
Yield: 96.1 %

Procedure:
Oleoyl chloride (75 g, 250 mmol) is heated at reflux with 2,2,2-trifluoroethanol (60 g, 600 mmol) for 16 hrs. After the evolution of HCl ceased, excess trifluoroethanol is removed in vacuo. Vacuum distillation of the residue afforded 87.6 g of 2,2,2-trifluoroethyl oleate as colorless liquid, by 150°/0.3.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][C:9]2=[O:12])=[CH:4][CH:3]=1.N1C=CC=CC=1.[CH:19]1([CH2:24][C:25](Cl)=[O:26])[CH2:23][CH2:22][CH2:21][CH2:20]1>C(Cl)Cl>[CH:19]1([CH2:24][C:25]([NH:1][C:2]2[CH:11]=[C:10]3[C:5]([CH2:6][CH2:7][CH2:8][C:9]3=[O:12])=[CH:4][CH:3]=2)=[O:26])[CH2:23][CH2:22][CH2:21][CH2:20]1
Reactant: Nc1ccc2c(c1)C(=O)CCC2
Reactant: O=C(Cl)CC1CCCC1
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=C(CC1CCCC1)Nc1ccc2c(c1)C(=O)CCC2
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 74.7 %

Procedure:
To a mixture of 7-amino-1-tetralone (13.2 g) (prepared as described above and used without further purification) and pyridine (8.4 ml) in methylene chloride (130 ml) at 0° C. was added a solution of cyclopentylacetyl chloride (13.2 g) in methylene chloride (20 ml). The reaction was stirred for 30 min and at room temperature for 1.5 h. The mixture was evaporated and the residue was diluted with ethyl acetate, washed (saturated sodium bicarbonate, 1N HCl, brine), dried (MgSO4) and evaporated. The residue was flash chromatographed, eluting with ethyl acetate:methylene chloride (5:95, 7.5:92.5, and 1:9, successively), to give 7-cyclopentylacetamido-1-tetralone (16.6 g, 74%) as a colorless solid; mp 117.0°-118.0° C.
Reaction SMILES: [CH3:1][C:2]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[NH2:13])([CH3:4])[CH3:3].C(O)(=O)C.[C:19]1(=O)[CH2:23][CH2:22][CH2:21][CH2:20]1.C([BH3-])#N.[Na+]>CO>[C:2]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[NH:13][CH:19]1[CH2:23][CH2:22][CH2:21][CH2:20]1)([CH3:1])([CH3:3])[CH3:4]
Reactant: O=C1CCCC1
Reactant: CC(C)(C)OC(=O)NC1CCCC1N
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: CC(C)(C)OC(=O)NC1CCCC1NC1CCCC1
Temperature: 50 °C
Yield: 58.2 %

Procedure:
To a solution of [(1RS,2SR)-2-aminocyclopentyl-carbamic acid 1,1-dimethylethyl ester (CAS 365996-19-6) (500 mg, 2.497 mmol) in 10 ml methanol was added acetic acid (0.714 ml, 12.49 mmol) and cyclopentanone (0.665 ml, 7.491 mmol). The mixture was heated in a 50° C. oil bath for 1.5 hour. The solution was cooled to room temperature and sodium cyanoborohydride (370 mg, 5.0 mmol) was added portionwise. The mixture was heated in a 50° C. oil bath for 2.5 hours. The solution was cooled in an ice bath and quenched by dropwise addition of 6 ml 2N NaOH. The methanol was removed in vacuo. The aqueous layer was diluted with water and extracted 3 times with ethyl acetate. The combined extracts were dried over Na2SO4, filtered and concentrated in vacuo. The crude oil was purified on silica gel (eluent: heptane/ethyl acetate 0 to 100%) to provide 0.39 g (58%) of the title compound as a light brown solid. MS (m/e): 269.3 (M+H).
Reaction SMILES: [OH-].[K+].C([O:6][CH2:7][C:8]1[CH:9]=[C:10]([CH2:14][N:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[O:27][CH:28]([CH3:30])[CH3:29])[CH2:17][CH2:16]2)[CH:11]=[CH:12][CH:13]=1)(=O)C>CO.C(O)(C)C>[OH:6][CH2:7][C:8]1[CH:9]=[C:10]([CH2:14][N:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[O:27][CH:28]([CH3:30])[CH3:29])[CH2:17][CH2:16]2)[CH:11]=[CH:12][CH:13]=1
Reactant: CC(=O)OCc1cccc(CN2CCN(c3ccccc3OC(C)C)CC2)c1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: CC(C)O
Product: CC(C)Oc1ccccc1N1CCN(Cc2cccc(CO)c2)CC1
Reaction time: 8 h
Yield: 84.6 %

Procedure:
To a solution of 85% KOH (0.5 g, 7.57 mmol) in 50 mL of methanol was added compound 3 (2.50 g, 5.97 mmol). After overnight stirring, thin layer chromatography indicated very little reaction progress so the reaction mixture was refluxed under argon for several minutes. Chromatographic analysis still indicated little reaction progress so the reaction mixture was cooled. Additional KOH (0.53 g) was added and reflux was continued another 15 minutes. After this period of time, the starting material was completely consumed. The reaction mixture was concentrated, and the residue was partitioned between methylene chloride and water. The layers were separated, and the aqueous layer was further extracted with methylene chloride. The organic extracts were combined, washed with brine, and dried (MgSO4). The organic extract was concentrated to provide an oil which was dissolved in isopropanol and filtered through MgSO4. To the filtrate was added maleic acid (0.725 g), and the resulting mixture was concentrated in vacuo to provide an oil which was partitioned between 3N NaOH and methylene chloride. The layers were separated and the aqueous layer was extracted with dichloromethane. The organic extracts were combined, washed with brine, and dried (MgSO4). The organic extract was concentrated, and the resulting oil was purified on TLC mesh silica (97:3 methylene chloride:methanol). The purified material was dissolved in ethyl ether and added to ethereal HCl. The resulting precipitate was collected by suction filtration and washed with ether. The sample was dried to provide 1.72 g (70%) of benzyl alcohol dihydrochloride 4, mp 201° C. (dec). The 1H NMR supported the desired structure.
Reaction SMILES: Cl.[Cl:2][CH2:3][CH2:4][N:5]([CH2:13][CH2:14][Cl:15])[C:6]1[CH:11]=[CH:10][C:9]([NH2:12])=[CH:8][CH:7]=1.C(N(CC)CC)C.Cl[C:24](Cl)([O:26]C(=O)OC(Cl)(Cl)Cl)Cl>C(Cl)(Cl)Cl>[Cl:2][CH2:3][CH2:4][N:5]([C:6]1[CH:11]=[CH:10][C:9]([N:12]=[C:24]=[O:26])=[CH:8][CH:7]=1)[CH2:13][CH2:14][Cl:15]
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: Nc1ccc(N(CCCl)CCCl)cc1
Agent: Cl
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: O=C=Nc1ccc(N(CCCl)CCCl)cc1
Temperature: -10 °C
Reaction time: 0.5 h

Procedure:
To a suspension of N,N-bis(2-chloroethyl)benzene-1,4-diamine hydrochloride 18 (1.22 g, 4 mmol) in dry chloroform (50 mL) was added triethylamine (0.72 mL) at room temperature. The clear solution obtained was then cooled to −10° C. and a solution of triphosgene (0.712 g, 2.4 mmole) in dry chloroform (10 mL) was added dropwise into a reaction mixture at 0° C. After being stirred for 30 min, the reaction mixture was evaporated to dryness under reduced pressure. The solid residue was triturated with dry THF (100 ml), filtered, and washed with small amount of THF. The combined filtrate and washings was evaporated to dryness to give the crude isocyanate 19, which was then dissolved in dry DMF (5 mL) and added dropwise to a solution of N1-(6-methoxy-2-methylquinolin-4-yl)benzene-1,3-diamine (0.56 g, 2 mmol) in dry DMF (10 mL) containing Et3N (1 mL). After being stirred for 5 h at room temperature, the solid separated was filtered and washed with dry DMF. The filtrate was evaporated to dryness in vacuo. The residue was purified by column chromatography using CHCl3/MeOH (100:3 v/v) as an eluent. The fractions containing the main product were combined and evaporated to dryness and the residue was recrystallized from CHCl3 to give BO-1547 (0.87 g, 81%); mp 225-227° C.; 1H NMR (DMSO-d6) δ 2.58 (3H, s, Me), 3.68-3.70 (8H, m, CH2), 3.97 (3H, s, OMe), 6.73-6.69 (3H, m, Ar—H), 7.03 (1H, d, J=7.6 Hz, Ar—H), 7.28 (2H, d, J=9.0 Hz, Ar—H), 7.35 (1H, d, J=7.7 Hz, Ar—H), 7.44 (1H, t, J=8.0 Hz, Ar—H), 7.64-7.62 (1H, m, Ar—H), 7.71 (1H, s, Ar—H), 7.93 (1H, d, J=9.1 Hz, Ar—H), 8.09 (1H, s, Ar—H), 8.84 (1H, s, NH, Exchangeable), 9.31 (1H, s, NH, Exchangeable), 10.49 (1H, s, NH, Exchangeable); ESI-HRMS calcd for C28H29Cl2N5O2 m/z 538.4682 (M+H). found 538.2451 (M+H).
Reaction SMILES: [CH3:1][N:2]([CH2:4][C:5]1[S:9][C:8]([CH:10]=O)=[CH:7][CH:6]=1)[CH3:3].N1CCCCC1.C(O)(=O)[CH2:19][C:20]([OH:22])=[O:21]>N1C=CC=CC=1>[CH3:3][N:2]([CH2:4][C:5]1[S:9][C:8]([CH:10]=[CH:19][C:20]([OH:22])=[O:21])=[CH:7][CH:6]=1)[CH3:1]
Reactant: CN(C)Cc1ccc(C=O)s1
Reactant: O=C(O)CC(=O)O
Solvent: C1CCNCC1
Solvent: c1ccncc1
Product: CN(C)Cc1ccc(C=CC(=O)O)s1
Yield: 54.8 %

Procedure:
5-(Dimethylaminomethyl)thiophene-2-carboxaldehyde (40.09 g) and piperidine (3 ml) were added to a solution of malonic acid (24.65 g) in pyridine (150 ml). The mixture was stirred under reflux for 7 hours. During the reaction a solid precipitated and slowly re-dissolved. The solution was allowed to cool and was then poured on to 2 M hydrochloric acid (150 ml). The volume of the solution was reduced to about 120 ml by evaporation at reduced pressure and extracted with diethyl ether. The ether extracts were washed with water. The aqueous phase was cooled and the solid, which precipitated out, was filtered off and washed with water-isopropanol. More solid was obtained by evaporating the filtrate to about 100 ml and adding isopropanol and cooling the mixture in ice for about 15 minutes. This solid was filtered off, and washed with isopropanol. The solids were combined and recrystallised from isopropanol-water to give 3-(5-dimethylaminomethyl-2-thienyl)acrylic acid (27.45 g) m.p. 223.5°-225° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:14]([N:15]=1)=[C:13]1[C:8]([CH:9]=[CH:10][C:11](=O)[N:12]1C)=[CH:7][CH:6]=2.P(Cl)(Cl)([Cl:20])=O.P(Cl)(Cl)(Cl)(Cl)Cl>>[Cl:20][C:11]1[CH:10]=[CH:9][C:8]2[C:13](=[C:14]3[C:5](=[CH:6][CH:7]=2)[CH:4]=[CH:3][C:2]([Cl:1])=[N:15]3)[N:12]=1
Reactant: Cn1c(=O)ccc2ccc3ccc(Cl)nc3c21
Reactant: O=P(Cl)(Cl)Cl
Agent: ClP(Cl)(Cl)(Cl)Cl
Product: Clc1ccc2ccc3ccc(Cl)nc3c2n1
Yield: 94 %

Procedure:
Under a stream of argon, to compound (5) (4.26 g; 17.4 mmol), phosphorus oxychloride (39 mL) and phosphorus pentachloride (4.48 g; 21.8 mmol) were added in an ice bath. The resulting reaction mixture was stirred and refluxed for 7 hours, and then evaporated under reduced pressure to remove phosphorus oxychloride. To the resulting residue, ice water and concentrated aqueous ammonia were added and the resulting reaction mixture was made alkaline. The solids which precipitated out were separated by filtration and washed with water, and then dried under reduced pressure to give 4.06 g (yield: 94%) of the title compound (6).
Reaction SMILES: C[O:2][C:3]1(OC)[CH2:9][CH2:8][CH2:7][CH2:6][CH:5]([C:10](=O)[C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:4]1=O.[CH3:20][NH:21][NH2:22]>CCO.CC(O)=O>[CH3:20][N:21]1[C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:5]2[CH2:6][CH2:7][CH2:8][CH2:9][C:3](=[O:2])[C:4]2=[N:22]1
Reactant: CNN
Reactant: CCOC(=O)C(=O)C1CCCCC(OC)(OC)C1=O
Solvent: CCO
Solvent: CC(=O)O
Product: CCOC(=O)c1c2c(nn1C)C(=O)CCCC2
Temperature: 25 °C
Reaction time: 8 h
Yield: 379.8 %

Procedure:
To a solution of ethyl (3,3-dimethoxy-2-oxocycloheptyl)(oxo)acetate 0.090 g (0.33 mmol) in 2 mL of EtOH and 4 mL of AcOH, 0.020 mL (0.039 mmol) of N-methylhydrazine was added. The mixture was stirred overnight at room temperature. The solvent was removed under reduced pressure and the crude solid was purified by flash chromatography on silica gel (eluant: AcOEt/hexane 8/2) to afford 0.035 g (38% yield) of the title compound as colorless oil.
Reaction SMILES: [Br:1][C:2]1[CH:12]=[CH:11][C:5]([O:6][CH2:7][CH2:8][CH2:9][OH:10])=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:16][CH2:17][CH3:18].O>CN(C=O)C>[Br:1][C:2]1[CH:12]=[CH:11][C:5]([O:6][CH2:7][CH2:8][CH2:9][O:10][CH2:16][CH2:17][CH3:18])=[CH:4][CH:3]=1
Reactant: OCCCOc1ccc(Br)cc1
Reactant: CCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCOCCCOc1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
In DMF (100 ml) was dissolved 3-(4-bromophenoxy)-1-propanol (10.0 g). To the mixture was added under ice-cooling 65% sodium hydride (2.4 g),and the mixture was stirred at room temperature for 2 hours. To the mixture was added dropwise bromopropane (5.5 ml), and the mixture was stirred for 3 hours. To the mixture was added 65% sodium hydride (0.8 g), and the mixture was stirred at 70 for 1 hour and cooled to room temperature. The reaction mixture was added to water, and the mixture was extracted with ethyl acetate, washed with saturated brine and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was purified with silica gel column chromatography (hexane/ethyl acetate=5/1) to give 1-bromo-4-(3-propoxypropoxy)benzene (6.7 g).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[OH:10])[CH:5]=O.[NH:11]1[CH2:17][C:15](=[O:16])[NH:14][C:12]1=[O:13].C(CN)O>O>[OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[OH:10])[CH:5]=[C:17]1[NH:11][C:12](=[O:13])[NH:14][C:15]1=[O:16]
Reactant: O=C1CNC(=O)N1
Reactant: O=Cc1ccc(O)c(O)c1
Solvent: NCCO
Solvent: O
Product: O=C1NC(=O)C(=Cc2ccc(O)c(O)c2)N1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 3,4-dihydroxybenzaldehyde (2.072 g.) and hydantoin (1.50 g.) in water (15 ml) was heated to 70° to give a clear solution. To this was added monoethanolamine (1.38 g.) and the magnetically stirred mixture was heated (90°-92°, bath temperature) for 4 hours. Within 10 minutes crystallization occurred. The product was allowed to cool to room temperature and was stored overnight. After immersing in an ice-bath, the mixture was acidified with ECl, refrigerated 5 hours, filtered, washed with cold (-10°) 1:1 methanol-water and dried. The title compound was obtained as a pale brown solid: 2.776 g, m.p. 300°-310°. (Trituration with hot absolute ethanol gave a pale brown solid in ca 65% recovery, m.p. 320° decomp.)
Reaction SMILES: [O:1]([C:8]1[CH:9]=[C:10]([CH:12]=[CH:13][CH:14]=1)[NH2:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][CH:23]=1)[CH:19]=O.C(O)(=O)C.[OH-].[Na+]>ClCCCl>[O:1]([C:8]1[CH:9]=[C:10]([NH:11][CH2:19][C:18]2[CH:21]=[CH:22][CH:23]=[C:16]([OH:15])[CH:17]=2)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Nc1cccc(Oc2ccccc2)c1
Reactant: O=Cc1cccc(O)c1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCCl
Solvent: CC(=O)O
Product: Oc1cccc(CNc2cccc(Oc3ccccc3)c2)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 69.7 %

Procedure:
The 3-(phenoxy)aniline (555 mg, 3 mmol) and 3-hydroxybenzaldehyde (366 mg, 3 mmol) were dissolved in 7 mL of 1,2-dichloroethane. Acetic acid (0.189 mL 3.15 mmol) and solid NaBr(OAc)3 (1.01 g, 5 mmol) were added. The mixture was stirred at room temperature for 3 h, then acidified with 1NHCl solution. After neutralizing to pH 7.5 with 2.5 N sodium hydroxide, the mixture was extracted with methylene chloride. The organic layer was washed with brine and water, then dried over anhydrous MgSO4, and evaporated to give 609 mg (69%) of the desired N-(3-phenoxyphenyl)[[3-hydroxyphenyl]methyl]amine product as a brown oil, which was greater than 90% pure by reverse phase HPLC analysis. MS m/z=291.
Reaction SMILES: [Na].[C:2]([O:11][CH3:12])(=[O:10])[C:3]1[C:4](=[CH:6][CH:7]=[CH:8][CH:9]=1)S.S([O-])(=O)(=O)C.Cl>CO.O>[CH3:12][O:11][C:2](=[O:10])[C:3]1[CH:4]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: COC(=O)c1ccccc1S
Agent: CS(=O)(=O)[O-]
Agent: Cl
Agent: [Na]
Solvent: CO
Solvent: O
Product: COC(=O)c1ccccc1
Reaction time: 0.08 h

Procedure:
To a cooled (0° C.) solution of 27 mg (1.17 m atoms) of sodium in 4 ml of absolute methanol there were added 78 mg (0.47 mmol) of methyl thiosalicylate. After stirring 5 minutes, a solution of 128 mg (0.39 mmol) of the foregoing mesylate in 3 ml of methanol was added. The reaction mixture was stirred at room temperature for 1 hour, diluted with 5 ml of water, acidified with 10% hydrochloric acid, and extracted with methylene chloride (3×6 ml). The combined extracts were washed with brine (5 ml), dried and evaporated in vacuo. The residue was purified by thin layer chromatography, using hexane-ethyl acetate (95:5) as gradient, to afford the title compound, as an oil.
Reaction SMILES: N([N:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6][CH2:5][CH2:4]1)=O.[NH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][C:14]1=O>C(O)(=O)C.[Zn]>[CH:10]1[C:11]2[C:15]3[CH2:14][NH:13][CH2:18][CH2:17][C:16]=3[N:3]3[C:12]=2[C:7]([CH2:6][CH2:5][CH2:4]3)=[CH:8][CH:9]=1
Reactant: O=NN1CCCc2ccccc21
Reactant: O=C1CCCCN1
Agent: [Zn]
Solvent: CC(=O)O
Product: c1cc2c3c(c1)c1c(n3CCC2)CCNC1
Temperature: 0 °C
Yield: 81.8 %

Procedure:
1-Nitroso-1,2,3,4-tetrahydroquinoline (5.8 g, 0.0357 mol) was dissolved in acetic acid (50 mL). NH-piperidone (7.97 g, 0.0464 mol) was added and cooled to 0° C. Zinc dust was added (11.67 g, 0.1785 mol) in small portions. After addition, the reaction mixture was heated at 85° C. for 1 h. The reaction was monitored by TLC & LCMS. After completion of reaction, the mixture was filtered and the filtrate neutralized by aq. NaHCO3. The mixture was extracted with EtOAc (3×200 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to obtain 6.2 g product that was purified by column chromatography using 100-200 mesh silica and 5-7% MeOH in DCM+2 drops NH4OH to give pure product.
Reaction SMILES: C(O)(=O)C.[CH3:5][C:6]([CH2:8][C:9]([CH3:11])=O)=O.[N+:12]([N:15]=[C:16]([NH:18][NH2:19])[NH2:17])([O-:14])=[O:13]>O>[CH3:5][C:6]1[CH:8]=[C:9]([CH3:11])[N:18]([C:16](=[N:15][N+:12]([O-:14])=[O:13])[NH2:17])[N:19]=1
Reactant: NNC(N)=N[N+](=O)[O-]
Reactant: CC(=O)CC(C)=O
Solvent: O
Solvent: CC(=O)O
Product: Cc1cc(C)n(C(N)=N[N+](=O)[O-])n1
Yield: 89 %

Procedure:
2.7 ml of acetic acid and 2,4-pentadione (0.785 mg, 7.83 mmol) are added to a mixture heated under reflux containing the N′-nitrohydrazinecarboximidamide compound isolated previously (0.5 g, 4.20 mmol) in 15 ml of water. The reaction medium is returned to ambient temperature then filtered. The solid obtained is washed with dichloromethane. A white solid in the form of white powder is obtained with a yield of 89%.
Reaction SMILES: [I:1]I.[Cl:3][C:4]1[CH:5]=[C:6]([Cl:14])[C:7]2[O:11][C:10]([CH3:12])=[CH:9][C:8]=2[CH:13]=1.[N+]([O-])([O-])=O.[Na+]>C(O)(=O)C>[Cl:3][C:4]1[CH:5]=[C:6]([Cl:14])[C:7]2[O:11][C:10]([CH3:12])=[C:9]([I:1])[C:8]=2[CH:13]=1
Reactant: II
Reactant: Cc1cc2cc(Cl)cc(Cl)c2o1
Agent: O=[N+]([O-])[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: Cc1oc2c(Cl)cc(Cl)cc2c1I
Temperature: 85 °C
Reaction time: 6 h

Procedure:
A suspension of 1.7 mmol of pulverized iodine in 10 ml of glacial acetic acid is admixed with 3 mmol of 5,7-dichloro-2-methylbenzofuran [42969-57] and with 0.3 mmol of sodium nitrate. The mixture is stirred at 85° C. for 6 hours. If necessary further sodium nitrate is added after 1 hour. The reaction mixture is cooled to room temperature and quenched with 10% sodium hydrogen sulphite solution, and tert-butyl methyl ether is added. The phases are separated and the aqueous phase is extracted with tert-butyl methyl ether (3×). The combined organic phases are washed with brine, dried with sodium sulphate and evaporated. From the residue the title compound is identified by means of flash chromatography (SiO2 60F) on the basis of the Rf value.
Reaction SMILES: COC(C1N=C2N([CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]3)C3C=CC=CC=3N2C(=O)C=1OC(=O)C)=O.C(OC(N1CCN(CC[N:53]2[C:57]3=[N:58][C:59]([C:64](=[O:75])[NH:65][CH2:66][C:67]4[CH:72]=[CH:71][C:70]([Cl:73])=[C:69]([Cl:74])[CH:68]=4)=[C:60]([OH:63])[C:61](=[O:62])[N:56]3[C:55]3[CH:76]=[CH:77][CH:78]=[CH:79][C:54]2=3)CC1)=O)(C)(C)C>>[C:30]([O:29][C:27]([N:24]1[CH2:25][CH2:26][N:21]([CH2:20][CH2:19][N:58]2[C:59]([C:64](=[O:75])[NH:65][CH2:66][C:67]3[CH:72]=[CH:71][C:70]([Cl:73])=[C:69]([Cl:74])[CH:68]=3)=[C:60]([OH:63])[C:61](=[O:62])[N:56]3[C:55]4[CH:76]=[CH:77][CH:78]=[CH:79][C:54]=4[N:53]=[C:57]23)[CH2:22][CH2:23]1)=[O:28])([CH3:33])([CH3:32])[CH3:31]
Reactant: CC(C)(C)OC(=O)N1CCN(CCn2c3ccccc3n3c(=O)c(O)c(C(=O)NCc4ccc(Cl)c(Cl)c4)nc23)CC1
Reactant: COC(=O)c1nc2n(CCN3CCN(C(=O)OC(C)(C)C)CC3)c3ccccc3n2c(=O)c1OC(C)=O
Product: CC(C)(C)OC(=O)N1CCN(CCn2c(C(=O)NCc3ccc(Cl)c(Cl)c3)c(O)c(=O)n3c4ccccc4nc23)CC1

Procedure:
The product from Example 15.2 was converted to 4-{2-[2-(3,4-Dichloro-benzylcarbamoyl)-3-hydroxy-4-oxo-4H-benzo[4,5]imidazo[1,2-a]pyrimidin-10-yl]-ethyl}-piperazine-1-carboxylic acid tert-butyl ester following a procedure adapted from Example 6.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[N:8]=[C:7]([S:9][CH3:10])[N:6]=[C:5]([S:11][CH3:12])[CH:4]=1.[C:13](OC(=O)C)(=[O:15])[CH3:14]>>[C:13]([NH:1][CH2:2][C:3]1[N:8]=[C:7]([S:9][CH3:10])[N:6]=[C:5]([S:11][CH3:12])[CH:4]=1)(=[O:15])[CH3:14]
Reactant: CC(=O)OC(C)=O
Reactant: CSc1cc(CN)nc(SC)n1
Product: CSc1cc(CNC(C)=O)nc(SC)n1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A mixture of 11 g (16.5 mmole) of 6-aminomethyl-2,4-bis(methylthio)pyrimidine and 75 ml of acetic anhydride was stirred at room temperature for 16 hours, then evaporated. The residue was isolated by filtration and washed with a small amount of methanol to provide white solid 6-acetylaminomethyl-2,4-bis(methylthio)pyrimidine. The structural assignment was supported by infrared spectral analysis.
Reaction SMILES: [N+:1]([C:4]1[CH:17]=[CH:16][C:15]2[C:14](=[O:18])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:19])[C:6]=2[CH:5]=1)([O-])=O>[C].[Pd].O>[NH2:1][C:4]1[CH:17]=[CH:16][C:15]2[C:14](=[O:18])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:19])[C:6]=2[CH:5]=1
Reactant: O=C1c2ccccc2C(=O)c2cc([N+](=O)[O-])ccc21
Agent: [Pd]
Solvent: O
Product: Nc1ccc2c(c1)C(=O)c1ccccc1C2=O
Temperature: 100 °C
Yield: 98.6 %

Procedure:
2.5 g (0.01 mole) of 2-nitroanthraquinone (purity above 99%) containing about 10% of particles having a particle diameter of more than 100 microns was placed in a 200 ml. electromagnetically stirred autoclave together with 25 g of small glass balls each with a diameter of 1 mm, 75 g of water and 0.025 g of 5% palladium-carbon. The inside of the autoclave was purged with hydrogen, and then, the 2-nitroanthraquinone was hydrogenated with stirring at a temperature of 100° C. and a pressure of 2 to 6 Kg/cm2.G. The reaction proceeded smoothly, and stopped in 4 hours with the absorption of a theoretical amount of hydrogen. The reaction mixture was filtered, and the 22 g of conc. sulfuric acid was added to the filtrate mass to dissolve the reaction product. Then, the catalyst and the small glass balls were separated by filtration. The filtrate was diluted with water. The precipitated crystals were collected by filtration to afford 2.2 g of 2-aminoanthraquinone. The purity of the product was 99%, and its yield was almost quantitative.
Reaction SMILES: [H-].[Na+].[NH:3]1[CH:7]=[CH:6][N:5]=[CH:4]1.[CH3:8][O:9][C:10]1[CH:17]=[CH:16][C:13]([CH2:14]Cl)=[CH:12][CH:11]=1>CN(C)C=O>[NH:3]1[CH:7]=[CH:6][N:5]=[C:4]1[CH2:14][C:13]1[CH:16]=[CH:17][C:10]([O:9][CH3:8])=[CH:11][CH:12]=1
Reactant: c1c[nH]cn1
Reactant: COc1ccc(CCl)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc(Cc2ncc[nH]2)cc1
Reaction time: 0.33 h
Yield: 71.9 %

Procedure:
To a suspension of 5.21 g of 50% sodium hydride in 100 ml of dry dimethylformamide was added slowly 7.39 g of imidazole at room temperature, and the mixture was stirred for 20 minutes. A solution of 20 g of p-methoxybenzyl chloride in 30 ml of dry dimethylformamide was added to the mixture at room temperature over a period of 1 hour, and then the reaction mixture was stirred for 18 hours at 50° C. After removal of the solvent under reduced pressure, 100 ml of dichloromethane was added to the residual oil and the mixture was washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residual solid was recrystallized from diethyl ether-ligroin to give 14.7 g of p-(1-imidazolylmethyl)anisole as colorless platelets. Then a solution of 14.7 g of p-(1-imidazolylmethyl)anisole in 50 ml of 47% hydrobromic acid was refluxed for 3 hours. After concentration under reduced pressure, the residual solid was recrystallized from ethanol-diethyl ether to give 18.4 g of p-(1-imidazolylmethyl)phenol hydrobromide as colorless platelets. M.P.: 189°-190° C.