Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:12]=[CH:11][C:5]2[NH:6][C:7](=[S:10])[CH2:8][O:9][C:4]=2[C:3]=1[C:13]([O:15][CH3:16])=[O:14].CI.[C:19](=O)([O-])[O-].[K+].[K+]>CC(C)=O>[NH2:1][C:2]1[CH:12]=[CH:11][C:5]2[N:6]=[C:7]([S:10][CH3:19])[CH2:8][O:9][C:4]=2[C:3]=1[C:13]([O:15][CH3:16])=[O:14]
Reactant: COC(=O)c1c(N)ccc2c1OCC(=S)N2
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CC(C)=O
Product: COC(=O)c1c(N)ccc2c1OCC(SC)=N2
Temperature: 25 °C
Reaction time: 2 h
Yield: 77 %

Procedure:
A mixture of methyl 7-amino-3-thioxo-3,4-dihydro-2H-benzo[1,4]oxazine-8-carboxylate (Intermediate 29, 0.795 g), methyl iodide (0.710 g) and potassium carbonate (1.38 g) in acetone (20 mL) was stirred at room temperature for 2 hours. The resultant mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 5-25% to give methyl 7-amino-3-methylsulfanyl-2H-benzo[1,4]oxazine-8-carboxylate (0.648 g) as a sandy coloured solid.
Reaction SMILES: C([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:23]3[CH:22]=[C:21]4[N:24]([CH2:30][CH3:31])[C:25](=[O:29])[N:26]([CH2:27][CH3:28])[C:20]4=[CH:19][C:18]=3[C:17](Cl)=[N:16][N:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.[N+:40]([C:43]1[CH:48]=[CH:47][C:46]([N:49]=C=O)=[CH:45][CH:44]=1)([O-:42])=[O:41].[Cl-].[Na+]>ClCCl.O>[CH2:27]([N:26]1[C:20]2=[CH:19][C:18]3[CH:17]=[N:16][N:15]=[C:14]([N:11]4[CH2:12][CH2:13][N:8]([C:6]([NH:49][C:46]5[CH:47]=[CH:48][C:43]([N+:40]([O-:42])=[O:41])=[CH:44][CH:45]=5)=[O:5])[CH2:9][CH2:10]4)[C:23]=3[CH:22]=[C:21]2[N:24]([CH2:30][CH3:31])[C:25]1=[O:29])[CH3:28]
Reactant: CCn1c(=O)n(CC)c2cc3c(N4CCN(C(=O)OC(C)(C)C)CC4)nnc(Cl)c3cc21
Reactant: O=C=Nc1ccc([N+](=O)[O-])cc1
Agent: [Cl-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Solvent: O
Product: CCn1c(=O)n(CC)c2cc3c(N4CCN(C(=O)Nc5ccc([N+](=O)[O-])cc5)CC4)nncc3cc21
Reaction time: 5 h
Yield: 53 %

Procedure:
To a solution of 758.4 mg (1.65 mmol) of 4-(8-chloro-1,3-diethyl-1,3-dihydro-2-oxo-2H-imidazo[4,5-g]phthalazin-5-yl)-1-piperazinecarboxylic acid tert-butyl ester obtained in Reference Example 21 (5) in 20 ml of dichloromethane was added 50 ml of trifluoroacetic acid under ice-cooling, followed by stirring at the same temperature for 5 hours. After the solvent was evaporated, the residue was subjected to azeotropic distillation with toluene twice. The obtained residue was dissolved in 20 ml of acetic acid, and a suspension of 300 mg of 10% palladium-carbon in 5 ml of water was added thereto, followed by overnight stirring at room temperature in an atmosphere of hydrogen. After the catalyst was separated by filtration using Celite, the solvent was evaporated, and the residue was subjected to azeotropic distillation with triethylamine. The obtained residue was dissolved in 10 ml of dimethylformamide, and 297.3 mg (1.81 mmol) of 4-nitrophenyl isocyanate was added thereto, followed by stirring at room temperature for 2 hours. The reaction mixture was poured into water, and sodium chloride was added thereto. The precipitated crystals were collected by filtration, washed with water, and dried, followed by purification by silica gel chromatography to give the desired compound as colorless crystals.
Reaction SMILES: [CH:1]([C:4]([CH:15]([CH3:17])[CH3:16])=[C:5]([C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([OH:14])[CH:9]=1)[O:6][CH3:7])([CH3:3])[CH3:2].[C:18](Cl)(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C(Cl)Cl.C(N(CC)CC)C>[C:18]([O:14][C:10]1[CH:9]=[C:8]([C:5]([O:6][CH3:7])=[C:4]([CH:1]([CH3:3])[CH3:2])[CH:15]([CH3:17])[CH3:16])[CH:13]=[CH:12][CH:11]=1)(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: COC(=C(C(C)C)C(C)C)c1cccc(O)c1
Reactant: O=C(Cl)c1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=C(C(C)C)C(C)C)c1cccc(OC(=O)c2ccccc2)c1
Reaction time: 1 h

Procedure:
Alkene 1b (4.5 g, 1.9 mmol) was dissolved in 50 mL of dry CH2Cl2 with 5.3 mL of anhydrous triethylamine. The flask was purged with argon and cooled in an ice bath. Benzoyl chloride (4.05 g, 2.9 mmol) was added dropwise. The cooling bath was removed and stirring continued for 1 hour at room temperature. The mixture was filtered and the solution was washed with water, dried over MgSO4 and evaporated. The residue was suspended in hexane, the solid filtered away and the solution evaporated. The residue was purified by column chromatography on silica gel, eluting with 1% ethyl acetate in hexane yielding 3.7 g of dioxetane 1d: 1H NMR (CDCl3) δ 8.25-7.05 (m, 9H), 3.25 (s, 1H), 2.54 (sept, 1H, J=6.9 Hz), 2.40 (sept, 1H, J=6.9 Hz), 2.29 (s, 3H), 1.26 (d, 6H, J=6.9 Hz), 0.95 (d, 6H, J=6.9 Hz).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][C@@H:13]2[O:18][C:17]3[C:19]([CH:26]=O)=[C:20]([N+:23]([O-:25])=[O:24])[CH:21]=[CH:22][C:16]=3[O:15][CH2:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[N+:28]([CH2:31][CH2:32][CH3:33])([O-:30])=[O:29].C([O-])(=O)C.[NH4+]>C(O)(=O)C>[N+:23]([C:20]1[CH:21]=[CH:22][C:16]2[O:15][CH2:14][CH:13]([CH2:12][O:11][S:8]([C:5]3[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=3)(=[O:9])=[O:10])[O:18][C:17]=2[C:19]=1[CH:26]=[C:31]([N+:28]([O-:30])=[O:29])[CH2:32][CH3:33])([O-:25])=[O:24]
Reactant: Cc1ccc(S(=O)(=O)OC[C@H]2COc3ccc([N+](=O)[O-])c(C=O)c3O2)cc1
Reactant: CCC[N+](=O)[O-]
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CC(=O)O
Product: CCC(=Cc1c([N+](=O)[O-])ccc2c1OC(COS(=O)(=O)c1ccc(C)cc1)CO2)[N+](=O)[O-]
Temperature: 80 °C

Procedure:
To a solution of 1.0 g (2.45 mmole) of (2R)-(8-formyl-7-nitro-2,3-dihydro-1,4-benzodioxin-2-yl)methyl 4-methylbenzenesulfonate in 15 mL of acetic acid was added 0.87 mL (9.8 mmole) of nitropropane and 0.38 g (4.9 mmole) of ammonium acetate and the mixture was heated at 80° C. under nitrogen for 6 hours. After the mixture cooled, the solvent was removed in vacuum and replaced with 200 mL of ethyl acetate. The solution was washed with 200 mL of water and the aqueous wash was back-extracted with an additional 200 mL of ethyl acetate. The combined organics were washed with 200 mL each of saturated aqueous sodium bicarbonate and saturated brine, dried over magnesium sulfate, filtered and concentrated in vacuum to an oily yellow solid. Column chromatography on silica gel with 1:1 hexane/ethyl acetate as eluant gave 0.70 g of the (R)-enantiomer of the title compound as a yellow solid. 1H-NMR (CDCl3): doublet 7.8 δ (2H); doublet 7.75 δ (1H); doublet 7.4 δ (2H); doublet 7.03 δ (1H); singlet 5.3 δ (1H); multiplet 4.45 δ (1H); multiplet 4.4 δ (1H); multiplet 4.21 δ (3H); singlet 2.45 δ (3H); quartet 2.4 δ (2H); triplet 1.0 δ (3H).
Reaction SMILES: [H][H].[C:3]1([S:9]([NH:12][C:13]2[CH:14]=[C:15]([CH:17]=[CH:18][CH:19]=2)[NH2:16])(=[O:11])=[O:10])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:20]([C:23]1[C:24](=[O:34])[O:25][C:26]([OH:33])=[C:27]([C:30](=O)[CH3:31])[C:28]=1[OH:29])(=[O:22])[CH3:21]>[Pd].C(O)C>[C:20]([C:23]1[C:24](=[O:34])[O:25][C:26](=[O:33])[C:27](=[C:30]([NH:16][C:15]2[CH:17]=[CH:18][CH:19]=[C:13]([NH:12][S:9]([C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=3)(=[O:10])=[O:11])[CH:14]=2)[CH3:31])[C:28]=1[OH:29])(=[O:22])[CH3:21]
Reactant: [H][H]
Reactant: Nc1cccc(NS(=O)(=O)c2ccccc2)c1
Reactant: CC(=O)c1c(O)oc(=O)c(C(C)=O)c1O
Agent: [Pd]
Solvent: CCO
Product: CC(=O)C1=C(O)C(=C(C)Nc2cccc(NS(=O)(=O)c3ccccc3)c2)C(=O)OC1=O

Procedure:
To a solution of 2.76 g. (0.02 mol) of m-nitroaniline in 5 ml. of pyridine cooled to 0° C. is added 3.52 g. (0.02 mol) of benzenesulfonyl chloride dropwise and the mixture is stirred for one hour at room temperature. The reaction mixture is decomposed with dilute hydrochloric acid and ice, and the solid filtered off to give m-(phenylsulfonamido)-nitrobenzene, m.p. 132°-134° C. The latter, 1.4 g. (0.005 mol), is dissolved in 100 ml. of ethanol, 300 mg. of 10% palladium-on-carbon is added and the mixture is hydrogenated in a Parr shaker. After hydrogen uptake has ceased, the catalyst is filtered off and the filtrate is used directly in the subsequent reaction. Thus the ethanolic solution (100 ml.) containing 1.2 g. (0.005 mol) of 3-phenylsulfonamidoaniline and 1.06 g. (0.005 mol) of 3,5-diacetyl-4,6-dihydroxy-2H-pyran-2-one is refluxed for one hour. The reaction mixture is concentrated and filtered to give 5-acetyl-4-hydroxy-3 -[1-(3-phenylsulfonamidophenylamino)ethylidene]-2H-pyran-2,6(3H)-dione, m.p. 209° C.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].S(Cl)(Cl)=O.[NH2:17][CH2:18][CH2:19][CH2:20][Si:21]([O:28][CH2:29][CH3:30])([O:25][CH2:26][CH3:27])[O:22][CH2:23][CH3:24].C(N(CC)CC)C>C(OCC)C>[CH2:26]([O:25][Si:21]([O:28][CH2:29][CH3:30])([O:22][CH2:23][CH3:24])[CH2:20][CH2:19][CH2:18][NH:17][C:8](=[O:10])[C:7]1[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:12][CH:11]=1)[CH3:27]
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1
Reactant: CCO[Si](CCCN)(OCC)OCC
Solvent: CCOCC
Solvent: O=S(Cl)Cl
Solvent: CCN(CC)CC
Product: CCO[Si](CCCNC(=O)c1ccc([N+](=O)[O-])cc1)(OCC)OCC
Reaction time: 2 h

Procedure:
p-nitrobenzoic acid (10 g; 60 mmol) was added to 15 g thionylchloride. This mixture was heated during 2 h under reflux. Subsequently the thionylchloride was removed at reduced pressure. To the remainder γ-aminopropyltriethoxysilane (13,3 g; 60 mmol) was added, dissolved in 50 ml diethylether with 10 g triethylamine. After 2 h agitation at room temperature, the mixture was filtered. The filtrate was evaporated at reduced pressure. The remainder was washed in water, filtered, and dried at reduced pressure over KOH. Yield: 9,5 g (43%). Melting point 99° . . . 105° C.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:22])[C:5](=O)[CH2:6][C:7]1[CH:17]=[CH:16][C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:9][C:8]=1[N+:18]([O-])=O)[CH3:2].O.CCOC(C)=O>C(O)(=O)C.[Zn]>[NH:18]1[C:8]2[C:7](=[CH:17][CH:16]=[C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:9]=2)[CH:6]=[C:5]1[C:4]([O:3][CH2:1][CH3:2])=[O:22]
Reactant: CCOC(=O)C(=O)Cc1ccc(C(=O)OCC)cc1[N+](=O)[O-]
Agent: [Zn]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CC(=O)O
Product: CCOC(=O)c1ccc2cc(C(=O)OCC)[nH]c2c1
Temperature: 75 °C
Yield: 58.9 %

Procedure:
Ethyl 4-(3-ethoxy-2,3-dioxopropyl)-3-nitrobenzoate (91 g, 0.29 mol) is suspended in 800 mL of acetic acid and it is heated with stirring to 75° C. Once the solid is dissolved, water (600 mL) is added. Zinc dust (189 g, 2.9 mol) is added carefully in small portions and the reaction temperature is kept below 85° C. The mixture is then stirred vigorously for 1 hour after the addition. EtOAc (1500 mL) is added and the mixture was filtered through Celite. The solid is washed with more EtOAc (1500 mL) and the filtrates are combined, washed twice with water (1500 mL), four times with saturated NaHCO3 (1000 mL), and once with brine (1000 mL). The filtrate is dried (Na2SO4), filtered, and concentrated to afford the crude compound which was recrystallized from toluene to afford the title compound (44.6 g, 58%) as a yellow powder.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:7])[CH2:5][OH:6])[CH3:2].[H-].[Na+].Br.[Br:11][C:12]1[CH:13]=[C:14]([CH2:19]Br)[C:15]([NH2:18])=[N:16][CH:17]=1.O>CN(C=O)C.CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:7])[CH2:5][O:6][CH2:19][C:14]1[C:15]([NH2:18])=[N:16][CH:17]=[C:12]([Br:11])[CH:13]=1)[CH3:2]
Reactant: CCOC(=O)CO
Reactant: Nc1ncc(Br)cc1CBr
Agent: Br
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOC(C)=O
Product: CCOC(=O)COCc1cc(Br)cnc1N
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
Hydroxy acetic acid ethyl ester (294 mg, 2.8 mmol) is dissolved in 5.0 mL of DMF and 60% sodium hydride (113 mg, 2.8 mmol) is added at 0° C. The mixture is stirred for 15 min and 5-bromo-3-bromomethyl-pyridin-2-ylamine hydrobromide (392 mg, 1.1 mmol) is added. The mixture is warmed up to room temperature for 2.5 hr. Then water (15 mL) is added along with EtOAc (30 mL). The mixture is stirred for 10 min and the aqueous layer is separated and extracted with EtOAc (2×20 mL). The organic layers are combined and concentrated to give (2-amino-5-bromo-pyridin-3-ylmethoxy)-acetic acid ethyl ester.
Reaction SMILES: CS[C:3](SC)(SC)[CH:4]1[C:14]2=[C:15]3[C:10](=[CH:11][CH:12]=[CH:13]2)[CH:9]=[CH:8][CH:7]=[C:6]3[CH2:5]1.[CH3:20][OH:21].[OH2:22]>[Hg](Cl)Cl.[Hg]=O>[CH:4]1([C:3]([O:21][CH3:20])=[O:22])[C:14]2=[C:15]3[C:10](=[CH:11][CH:12]=[CH:13]2)[CH:9]=[CH:8][CH:7]=[C:6]3[CH2:5]1
Reactant: CSC(SC)(SC)C1Cc2cccc3cccc1c23
Reactant: CO
Reactant: O
Agent: Cl[Hg]Cl
Agent: O=[Hg]
Product: COC(=O)C1Cc2cccc3cccc1c23

Procedure:
1-Tris(methylthio)methyl acenaphthene (18.4 g), Mercury (II) Chloride (68 g) and Mercury (II) Oxide (22 g) were slurried in MeOH/H2O, 12/1 (1500 ml), stirred at room temperature for 18 hours, then refluxed for two hours, and then allowed to cool.
Reaction SMILES: [CH2:1]([C:3]([CH2:12][CH3:13])([C:8]([O:10][CH3:11])=[O:9])[C:4]([O:6][CH3:7])=[O:5])[CH3:2].[CH2:14]([N:17]1[C:22]([CH3:24])([CH3:23])[CH2:21]C(O)[CH2:19][C:18]1([CH3:27])[CH3:26])[CH:15]=[CH2:16]>C1(C)C(C)=CC=CC=1>[CH2:14]([N:17]1[C:22]([CH3:24])([CH3:23])[CH2:21][CH:7]([O:6][C:4](=[O:5])[C:3]([CH2:1][CH3:2])([CH2:12][CH3:13])[C:8]([O:10][CH:11]2[CH2:27][C:18]([CH3:19])([CH3:26])[N:17]([CH2:14][CH:15]=[CH2:16])[C:22]([CH3:21])([CH3:23])[CH2:24]2)=[O:9])[CH2:19][C:18]1([CH3:27])[CH3:26])[CH:15]=[CH2:16]
Reactant: C=CCN1C(C)(C)CC(O)CC1(C)C
Reactant: CCC(CC)(C(=O)OC)C(=O)OC
Solvent: Cc1ccccc1C
Product: C=CCN1C(C)(C)CC(OC(=O)C(CC)(CC)C(=O)OC2CC(C)(C)N(CC=C)C(C)(C)C2)CC1(C)C
Reaction time: 6 h

Procedure:
After the addition of 1 g of tetrabutyl-orthotitanate, 47 g of dimethyl diethylmalonate and 98.6 g of 1-allyl-2,2,6,6-tetramethyl-4-hydroxypiperidine in 100 ml of xylene are heated under a gentle stream of nitrogen to about 140°. The methanol forming during the reaction is continuously distilled off, and after about 6 hours the reaction is virtually completed. The reaction mixture is diluted with 200 ml of toluene, extracted three times with 100 ml of water each time, dried over sodium sulphate and concentrated by evaporation. Crystallisation of the residue from hexane yields bis-(1-allyl-2,2,6,6-tetramethyl-4-piperidinyl)diethylmalonate (compound 18), m.p. 135°-136°.
Reaction SMILES: C([O:8][C:9]1[C:10](=[O:24])[CH:11]=[C:12]([CH2:16][NH:17][C@@H:18]([CH3:23])[C:19]([NH:21][CH3:22])=[O:20])[N:13]([CH3:15])[CH:14]=1)C1C=CC=CC=1.[H][H]>CO.[Pd]>[OH:8][C:9]1[C:10](=[O:24])[CH:11]=[C:12]([CH2:16][NH:17][C@@H:18]([CH3:23])[C:19]([NH:21][CH3:22])=[O:20])[N:13]([CH3:15])[CH:14]=1
Reactant: [H][H]
Reactant: CNC(=O)[C@H](C)NCc1cc(=O)c(OCc2ccccc2)cn1C
Agent: [Pd]
Solvent: CO
Product: CNC(=O)[C@H](C)NCc1cc(=O)c(O)cn1C
Yield: 96 %

Procedure:
A mixture of (S)-2-((5-(benzyloxy)-1-methyl-4-oxo-1,4-dihydropyridin-2-yl)methylamino)-N-methylpropanamide (7.04 g, 21.4 mmol) and 10% Pd/C (0.90 g) in MeOH (70 mL) was subjected to hydrogenation in a Parr apparatus at 50 psi of hydrogen pressure for 2 h. The reaction mixture was filtered over celite and the filtrate was concentrated in vacuo. The resulting solid was dried in a vacuum oven at 44° C. for overnight. Thus, (S)-2-((5-hydroxy-1-methyl-4-oxo-1,4-dihydropyridin-2-yl)methylamino)-N-methylpropanamide was obtained as an orange solid (4.90 g) in 96% yield. 1H NMR (CD3COOD) δ (ppm): 7.77 (s, 1H), 7.03 (s, 1H), 4.30-4.34 (m, 3H, OCH2+CHCH3), 3.98 (s, 3H), 2.80 (s, 3H), 1.56 (d, J=6.3 Hz, 3H, CHCH3); MS m/z 262 [M+Na]+, 240 (100%) [M+1]+, 138, 110.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]3[CH:26]=[CH:25][C:24]([CH:27]=O)=[CH:23][CH:22]=3)=[CH:16][CH:15]=2)[C:11]([OH:13])=[O:12])[CH:5]=[C:6]([CH3:8])[CH:7]=1.[S:29]1[CH2:33][C:32](=[O:34])[NH:31][C:30]1=[O:35].C(O)(=O)C1C=CC=CC=1.N1CCCCC1>>[CH3:8][C:6]1[CH:5]=[C:4]([CH:9]=[C:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]3[CH:22]=[CH:23][C:24]([CH:27]=[C:33]4[S:29][C:30](=[O:35])[NH:31][C:32]4=[O:34])=[CH:25][CH:26]=3)=[CH:16][CH:15]=2)[C:11]([OH:13])=[O:12])[CH:3]=[C:2]([CH3:1])[CH:7]=1
Reactant: Cc1cc(C)cc(C=C(C(=O)O)c2ccc(Oc3ccc(C=O)cc3)cc2)c1
Reactant: O=C1CSC(=O)N1
Agent: O=C(O)c1ccccc1
Solvent: C1CCNCC1
Product: Cc1cc(C)cc(C=C(C(=O)O)c2ccc(Oc3ccc(C=C4SC(=O)NC4=O)cc3)cc2)c1
Yield: 92.4 %

Procedure:
In a 100 mL round-bottomed flask equipped with a Dean-Stark apparatus, a mixture of 45 (1.55 g, 4.2 mmol), 2,4-thiazolidinedione (0.5 g, 4.2 mmol), benzoic acid (0.62 g, 5.0 mmol) and piperidine (0.62 mL, 6.3 mmol) was azeotroped in toluene (60 mL) for 45 min under vigorous reflux. The reaction mixture was cooled then poured over 10% citric acid (40 mL) and stirred until a bright yellow solid formed. The solid was filtered and washed with water and the wet solid was azeotroped and recrystallized from toluene to yield 1.83 g (93%) of 46. 1H NMR (400 MHz, DMSO-d6): δ 12.72 (br s, 1H), 12.57 (br s, 1H), 7.77 (s, 1H), 7.70 (s, 1H), 7.63 (d, J=8.8 Hz, 2H), 7.22 (d, J=8.4 Hz, 2H), 7.14 (d, J=8.4 Hz, 2H), 7.12 (d, J=8.8 Hz, 2H), 6.92 (s, 1H), 6.69 (s, 2H), 2.16 (s, 6H).
Reaction SMILES: [Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1.[Cl:12][C:13]1[CH:26]=[CH:25][C:16]([O:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][OH:24])=[CH:15][CH:14]=1>C(Cl)Cl.C(OCC)C>[Cl:12][C:13]1[CH:26]=[CH:25][C:16]([O:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH:23]=[O:24])=[CH:15][CH:14]=1
Reactant: OCCCCCCOc1ccc(Cl)cc1
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Solvent: CCOCC
Product: O=CCCCCCOc1ccc(Cl)cc1
Reaction time: 1.5 h

Procedure:
To a suspension of 32 g (0.15 mol) of pyridinium chlorochromate in 450 ml of methylene chloride is added 23 g (0.1 mol) of 6-(4-chlorophenoxy)-1-hexanol. The mixture is maintained under a nitrogen atmosphere for 2 hours, is diluted with 1000 ml of ethyl ether and is stirred for 1.5 hours.
Reaction SMILES: [Cl:1][C:2]1[CH:19]=[CH:18][C:5]([C:6]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][S:15]([CH3:17])=[O:16])=[CH:10][CH:9]=2)=O)=[CH:4][CH:3]=1.[C:20]([O:24][CH2:25][CH3:26])(=[O:23])[NH:21][NH2:22]>C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.C(O)C>[CH2:25]([O:24][C:20]([NH:21][N:22]=[C:6]([C:8]1[CH:13]=[CH:12][C:11]([CH2:14][S:15]([CH3:17])=[O:16])=[CH:10][CH:9]=1)[C:5]1[CH:18]=[CH:19][C:2]([Cl:1])=[CH:3][CH:4]=1)=[O:23])[CH3:26]
Reactant: CS(=O)Cc1ccc(C(=O)c2ccc(Cl)cc2)cc1
Reactant: CCOC(=O)NN
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: CCO
Product: CCOC(=O)NN=C(c1ccc(Cl)cc1)c1ccc(CS(C)=O)cc1
Temperature: 25 °C
Yield: 85.3 %

Procedure:
An ethanol solution (100 ml) of 4-chloro-4'-methylsulfinylmethyl benzophenone (5.8 g), ethyl carbazate (6.3 g) and pyridinium p-toluenesulfonate (0.1 g) was heated for 6 hours with refluxing. After cooling to a room temperature, the reaction mixture was poured into ice-water, and the precipitated crystals were collected by filtration, and washed successively with an aqueous sodium bicarbonate solution and water. After air-drying, 4-chloro-4'-methylsulfinylmethylbenzophenone ethoxycarbonylhydrazone (6.4 g) was obtained as an isomer mixture.
Reaction SMILES: [CH:1]([OH:3])=O.C(OC(=O)C)(=O)C.Cl.[CH3:12][C:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]2[CH2:22][CH2:23][CH2:24][CH:25]([NH2:26])[C:14]=12.O>O1CCCC1>[CH3:12][C:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]2[CH2:22][CH2:23][CH2:24][CH:25]([NH:26][CH:1]=[O:3])[C:14]=12
Reactant: Cc1c2n(c3ccccc13)CCCC2N
Reactant: O=CO
Agent: Cl
Solvent: O
Solvent: C1CCOC1
Solvent: CC(=O)OC(C)=O
Product: Cc1c2n(c3ccccc13)CCCC2NC=O
Temperature: 60 °C
Reaction time: 2 h
Yield: 99 %

Procedure:
A mixture of formic acid (6 mL) and acetic anhydride (12 mL) was heated at 60° C. for 4 hours. A solution of 6,7,8,9-tetrahydro-10-methylpyrido[1,2-a]indol-9-amine hydrochloride (7.5 g, 37.5 mmol), in dry tetrahydrofuran (60 mL) was added upon cooling to the resultant mixed anhydride. The reaction mixture was stirred at 25° C. for 2 hours, poured into water (150 mL) and extracted with ether (3×100 mL). The combined extracts were washed successively with 5% hydrochloric acid, 5% sodium bicarbonate, and water. The ethereal solution was dried over MgSO4, filtered, and evaporated. The solid residue was crystallized from benzene/hexane to give 8.5 g (99%) of the title formamide as a yellow solid, m.p. 133°-5° C. Analytical sample melted at 136° C.
Reaction SMILES: Cl[CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[CH2:6][CH2:5]1.[CH:18]1[C:23]([C:24]2[C:29](=[O:30])[C:28]3[CH:31]=[CH:32][C:33]([OH:35])=[CH:34][C:27]=3[O:26][CH:25]=2)=[CH:22][CH:21]=[C:20]([OH:36])[CH:19]=1.[OH-].[K+].CO>CC(C)=O>[OH:36][C:20]1[CH:21]=[CH:22][C:23]([C:24]2[C:29](=[O:30])[C:28]3[C:27](=[CH:34][C:33]([O:35][CH2:2][CH2:3][N:4]4[CH2:9][CH2:8][N:7]([C:10]5[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=5)[CH2:6][CH2:5]4)=[CH:32][CH:31]=3)[O:26][CH:25]=2)=[CH:18][CH:19]=1
Reactant: O=c1c(-c2ccc(O)cc2)coc2cc(O)ccc12
Reactant: COc1ccc(N2CCN(CCCl)CC2)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: CC(C)=O
Product: COc1ccc(N2CCN(CCOc3ccc4c(=O)c(-c5ccc(O)cc5)coc4c3)CC2)cc1

Procedure:
To a solution of 1-[4-(2-chloroethyl)piperazinyl]-4-methoxybenzene (0.929 mmol) and 4,7-dihydroxyisoflavone (0,929 mmol) in acetone (10 ml)was added 11% potassium hydroxide (0.5 ml), and the mixture stirred at reflux temperature for 48 hours. Sufficient methanol was added to precipitate unreacted starting material, which was filtered off, and solvent was removed from the filtrate under reduced pressure. The residue was purified by biotage column chromatography, eluting with 5% methanol/methylene chloride, to provide pure 3-(4-hydroxyphenyl)-7-{2-[4-(4-methoxyphenyl)piperazinyl]ethoxy}chromen-4-one.
Reaction SMILES: OCCO[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1O.C(N(CC)CC)C.[C:19](Cl)(=[O:22])[CH:20]=[CH2:21].[O:24]1CCCC1>C1C2NC3C(=CC=CC=3)SC=2C=CC=1>[C:19]([O:22][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)(=[O:24])[CH:20]=[CH2:21]
Reactant: C=CC(=O)Cl
Reactant: C1CCOC1
Reactant: OCCOc1ccccc1O
Agent: c1ccc2c(c1)Nc1ccccc1S2
Solvent: CCN(CC)CC
Product: C=CC(=O)Oc1ccccc1
Yield: 62 %

Procedure:
A 500-ml, two necked flask was equipped with magnetic stirring bar, nitrogen atmosphere and an addition funnel. The flask was charged with 25 g of 2-(2-hydroxyethoxy)phenol (0.16 mol.), 33 g of triethylamine (0.32 mol.), 250 ml of tetrahydrofuran and 1 g of phenothiazine. Next, 30 g of acryloyl chloride (0.18 mol.) was slowly added to the reaction over 1 hour via the addition funnel. The triethylamine hydrochloride salt was removed by filtration and the mother liquor was evaporated with a rotoevaporator. The remaining liquid was dissolved in chloroform and washed with NaCl(aq.), NH4OH(10%), NaCl(aq.) and dried over MgSO4. The chloroform was removed with a rotoevaporator to yield 26 g (62%) of a reddish brown liquid. The product was confirmed by IR and 13C NMR.