Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]([NH:5][C:6]1[N:7]=[C:8]2[CH:13]=[CH:12][C:11]([S:14][C:15]3[CH:20]=[CH:19][C:18]([O:21]C(=O)C)=[CH:17][CH:16]=3)=[CH:10][N:9]2[CH:25]=1)=[O:4].[OH-].[K+]>CO.O>[CH3:1][O:2][C:3]([NH:5][C:6]1[N:7]=[C:8]2[CH:13]=[CH:12][C:11]([S:14][C:15]3[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=3)=[CH:10][N:9]2[CH:25]=1)=[O:4]
Reactant: COC(=O)Nc1cn2cc(Sc3ccc(OC(C)=O)cc3)ccc2n1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: COC(=O)Nc1cn2cc(Sc3ccc(O)cc3)ccc2n1

Procedure:
1.0 Gm. of the acetate derivative obtained in Example 15 is heated with a 10 ml. 50% methanol-water solution of 0.5 g. of potassium hydroxide for one hour. After evaporation of the methanol in vacuo the reaction mixture is acidified with glacial acetic acid. The resultant solids are removed by filtration, washed with water and dried to yield 2-(methoxycarbonylamino) 6-(p-hydroxyphenylthio) imidazo [1,2-a] pyridine.
Reaction SMILES: [C:1]1([CH3:10])[C:2]([C:7](Cl)=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1.[CH3:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[O:18][CH3:19]>O>[CH3:19][O:18][C:13]1[CH:14]=[CH:15][C:16]([C:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=2[CH3:10])=[O:8])=[CH:17][C:12]=1[CH3:11]
Reactant: Cc1ccccc1C(=O)Cl
Reactant: COc1ccccc1C
Solvent: O
Product: COc1ccc(C(=O)c2ccccc2C)cc1C
Reaction time: 60 h
Yield: 31.2 %

Procedure:
o-Toluoyl chloride (15.4 g, 0.10 mole) and o-methylanisole (12.2 g, 0.10 mole) are combined in 50 ml of polyphosphoric acid (PPA) and warmed with stirring on a steam bath for 2-3 days. The cooled reaction mixture is then poured into water and extracted into benzene, dried (anhydrous MgSO4) and the solvent removed in vacuo to give 7.5 g of product (31%), m.p. 72°-73°C.
Reaction SMILES: [NH2:1][CH2:2][C@H:3]1[C@@H:7]([OH:8])[CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1.CCN(CC)CC.[CH2:23]([O:30][C:31](ON1C(=O)CCC1=O)=[O:32])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>CN(C=O)C>[OH:8][C@H:7]1[C@@H:3]([CH2:2][NH:1][C:31]([O:30][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:32])[CH2:4][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:6]1
Reactant: O=C(OCc1ccccc1)ON1C(=O)CCC1=O
Reactant: CC(C)(C)OC(=O)N1C[C@@H](CN)[C@@H](O)C1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1C[C@H](CNC(=O)OCc2ccccc2)[C@H](O)C1
Reaction time: 18 h
Yield: 94.9 %

Procedure:
To a solution of (±)-1,1-dimethylethyl cis-3-(aminomethyl)-4-hydroxy-1-pyrrolidinecarboxylate (10.0 g, 46.0 mmole) in DMF (50 mL) at RT was added Et3N (8.4 mL, 60.0 mmole) and N-(benzyloxycarbonyloxy)succinimide (14.95 g, 60.0 mmole). After 18 h, the DMF was removed under vacuum and the residue purified on silica (25-50% DCM/EtOAc) to give the title compound (15.3 g, 95%) as a white foam: LC-MS (ES) m/e 351 (M+H)+; and a small amount of an N-methylated byproduct [1,1-dimethylethyl (3S,4S)-3-hydroxy-4-[(methyl{[(phenylmethyl)oxy]carbonyl}amino)methyl]-1-pyrrolidinecarboxylate] (0.33 g, 2%): LC-MS (ES) m/e 365 (M+H)+.
Reaction SMILES: [C:1]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][C:20](Cl)=[CH:19][C:18]=2[N+:24]([O-])=O)[CH:13]([C:27](O)=[O:28])[CH2:12]1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[ClH:30]>C(O)(=O)C.[Fe]>[Cl:30][C:21]1[CH:22]=[C:17]2[C:18]([NH:24][C:27](=[O:28])[CH:13]3[CH2:12][N:11]([C:1]([O:3][CH2:4][C:5]4[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=4)=[O:2])[CH2:16][CH2:15][N:14]32)=[CH:19][CH:20]=1
Reactant: Cl
Reactant: O=C(O)C1CN(C(=O)OCc2ccccc2)CCN1c1ccc(Cl)cc1[N+](=O)[O-]
Agent: [Fe]
Solvent: CC(=O)O
Product: O=C1Nc2ccc(Cl)cc2N2CCN(C(=O)OCc3ccccc3)CC12
Temperature: 60 °C
Yield: 37 %

Procedure:
To a solution of the above residue 4-carbobenzyloxy-l-(4-chloro-2-nitrophenyl)piperazine-2-carboxylic acid in 200 ml glacial acetic acid warmed to 60° C. was added iron powder (14 g) in portions. The reaction was heated at 60° C. for 3 h. The reaction was cooled to rt and 1N HCl was added. The resulting precipitate was filtered and dried. The crude material was dissolved in methylene chloride and passed through a plug of celite. The filtrate was concentrated to a dark red residue. This was purified by the Biotage 40i (4.0×15.0 cm column, load methylene chloride, elute 30-50% ethyl acetate/hexanes) to give 9-chloro-3-carbobenzyloxy-2,3,4,4a-tetrahydro-1H-pyrazino[1,2-a]-quinoxalin-5(6H)-one as an off-white solid (4.8 g, 37% yield over 3 steps). 1H NMR (CDCl3, 300 MHz) δ7.32-7.37 (m, 5H), 6.82-6.85 (m, 1H), 6.68-6.75 (m, 2H), 5.18 (m, 2H), 4.73 (m, 1H), 4.31 (m, 1H), 3.49-3.54 (m, 2H), 3.07 (m, 2H), 2.74-2.81 (m, 1H) ppm. MS (ESI) m/z=372 [M+H]+.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[S:9][C:10]([Cl:13])=[CH:11][CH:12]=2)[CH:5]=[C:4]([C:14]([F:17])([F:16])[F:15])[N:3]=1.[I:18][C:19]1[N:20]=[CH:21][NH:22][CH:23]=1>>[Cl:13][C:10]1[S:9][C:8]([C:6]2[CH:5]=[C:4]([C:14]([F:17])([F:16])[F:15])[N:3]=[C:2]([N:22]3[CH:23]=[C:19]([I:18])[N:20]=[CH:21]3)[N:7]=2)=[CH:12][CH:11]=1
Reactant: Ic1c[nH]cn1
Reactant: FC(F)(F)c1cc(-c2ccc(Cl)s2)nc(Cl)n1
Product: FC(F)(F)c1cc(-c2ccc(Cl)s2)nc(-n2cnc(I)c2)n1

Procedure:
The title compound was prepared from 2-chloro-4-(5-chloro-thiophen-2-yl)-6-trifluoromethyl-pyrimidine (example A.1) (1.2 g, 4.0 mmol) and commercially available 4-iodo-imidazole (0.85 g, 4.4 mmol) according to the general procedure IIa. Obtained as an off-white solid (1.78 g, 97%). MS (ISP) 457.0 [(M+H)+]; mp 251° C.
Reaction SMILES: [CH2:1]([NH2:3])[CH3:2].[CH3:4][C:5]1([CH2:10]Br)[O:9][CH2:8][CH2:7][O:6]1.[OH-].[Na+]>CCOCC>[CH2:1]([NH:3][CH2:4][C:5]1([CH3:10])[O:9][CH2:8][CH2:7][O:6]1)[CH3:2]
Reactant: CC1(CBr)OCCO1
Reactant: CCN
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Product: CCNCC1(C)OCCO1
Temperature: 120 °C
Reaction time: 5 h
Yield: 40.1 %

Procedure:
Ethylamine (115 grams; 1.77 mole) and 2-methyl-2-bromomethyl-1,3-dioxolane (32 grams; 0.177 mole) were placed in a stainless steel bomb and placed on a steam bath for 5 hours. The temperature of the mixture was raised to 120° C. for 15 hours. The mixture was cooled and ether (200 ml) added to it. Sodium hydroxide (25 grams) was added and the ether layer separated and dried over magnesium sulfate. The ether was evaporated leaving the desired product (10.3 grams) as identified by nuclear magnetic resonance.
Reaction SMILES: [C:1]([O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][OH:15])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:16](Cl)(=[O:38])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]/[CH:28]=[CH:29]\[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37]>>[C:16]([O:15][CH2:14][CH2:13][O:12][CH2:11][CH2:10][O:9][C:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)(=[O:38])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]/[CH:28]=[CH:29]\[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37]
Reactant: O=C(OCCOCCO)c1ccccc1
Reactant: CCCCCCCC/C=C\CCCCCCCCCCCC(=O)Cl
Product: CCCCCCCC/C=C\CCCCCCCCCCCC(=O)OCCOCCOC(=O)c1ccccc1

Procedure:
2-Benzoyloxyethoxyethyl erucate was prepared by the procedure of Example 1 from 21 gms (0.1 mole) of diethylene glycol monobenzoate and 35.5 gms (0.1 mole) of erucoyl chloride. The structure of the final product was characterized on the basis of NMR and IR spectral analyses as described in Example 1.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[CH:16]=[C:15]([O:18][CH3:19])[CH:14]=[CH:13][C:12]=3[C:11](=[O:20])[N:10]3[CH2:21][CH2:22][CH2:23][C:24](=O)[C:9]=23)[CH:5]=[CH:6][CH:7]=1.Cl.[NH2:27][OH:28]>N1C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[CH:16]=[C:15]([O:18][CH3:19])[CH:14]=[CH:13][C:12]=3[C:11](=[O:20])[N:10]3[CH2:21][CH2:22][CH2:23]/[C:24](=[N:27]\[OH:28])/[C:9]=23)[CH:5]=[CH:6][CH:7]=1
Reactant: NO
Reactant: COc1ccc2c(=O)n3c(c(-c4cccc(F)c4)c2c1)C(=O)CCC3
Agent: Cl
Solvent: c1ccncc1
Product: COc1ccc2c(=O)n3c(c(-c4cccc(F)c4)c2c1)/C(=N/O)CCC3
Temperature: 25 °C

Procedure:
To a solution of 11-(3-fluorophenyl)-9-methoxy-3,4-dihydro-2H-pyrido[1,2-b]isoquinoline-1,6-dione (125 mg) in 4 mL pyridine was added hydroxylamine hydrochloride (51 mg). The reaction was heated to reflux for 5 h, then cooled to room temp and partitioned between ether and water. The aqueous solution was extracted with ether (2×). The combined organic solutions were washed with 1 N HCl (1×), and 10% bicarb (1×), then dried (MgSO4) and concentrated. Flash chromatography (10-70% EtOAc/hexanes) gave the titled compound.
Reaction SMILES: [C:1]([O:5][C:6](=[O:28])[NH:7][C@@H:8]1[CH2:12][CH2:11][N:10]([C:13](=[O:26])[CH2:14][NH:15]C(OCC2C=CC=CC=2)=O)[C@H:9]1[CH3:27])([CH3:4])([CH3:3])[CH3:2].[H][H]>C(O)C.[Pd]>[NH2:15][CH2:14][C:13]([N:10]1[CH2:11][CH2:12][C@@H:8]([NH:7][C:6](=[O:28])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])[C@@H:9]1[CH3:27])=[O:26]
Reactant: C[C@H]1[C@H](NC(=O)OC(C)(C)C)CCN1C(=O)CNC(=O)OCc1ccccc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: C[C@H]1[C@H](NC(=O)OC(C)(C)C)CCN1C(=O)CN
Yield: 99.2 %

Procedure:
To [(2S,3R)-1-(2-benzyloxycarbonylamino-acetyl)-2-methyl-pyrrolidin-3-yl]-carbamic acid tert-butyl ester (example #14) (0.75 g, 1.916 mmol) in ethanol (101 mL) was added 10% palladium on carbon (0.020 g, 0.19 mmol). The flask was fitted with a hydrogen balloon and hydrogenated for about 16 h. The reaction mixture was filtered, washing with EtOH. The filtrate was concentrated under reduced pressure to afford tert-butyl (2S,3R)-1-(2-aminoacetyl)-2-methylpyrrolidin-3-ylcarbamate (0.50 g, 1.9 mmol). RP-HPLC (Table 1, Method d) Rt 3.05; m/z: (M+H)+ 258.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9](C(OCC)=O)[C:10]([O:12]CC)=[O:11])=[C:5]([N+:20]([O-:22])=[O:21])[CH:4]=1.[OH-].[Na+]>CCO>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=[O:11])=[C:5]([N+:20]([O-:22])=[O:21])[CH:4]=1
Reactant: CCOC(=O)C(C(=O)OCC)c1ccc(OC)cc1[N+](=O)[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: COc1ccc(CC(=O)O)c([N+](=O)[O-])c1
Temperature: 90 °C
Yield: 114 %

Procedure:
A solution of diethyl (4-methoxy-2-nitrophenyl)malonate (1.1 g; 3.53 mmol; 1 eq) in a mixture of EtOH (25 mL) and sodium hydroxide (25 mL; 1 M; 25 mmol; 7.07 eq) is heated for 1 h at 90° C. The solvents are removed under reduced pressure and the orange-yellow powder is suspended in THF (20 mL). After cooling down to 0° C., 5M HCl (20 mL) is added. The reaction mixture is refluxed at 85° C. for 1 h. After cooling down to room temperature, the 2 phases are separated and the organic phase is dried over MgSO4. The aqueous phase is treated twice with EtOAc (50 mL) and the combined organic phases are dried over MgSO4 then concentrated to dryness to afford 850 mg (100%) of the title compound as a brown solid. 1H NMR (DMSO-d6) δ 8.20-8.10 (m, 1H), 7.45 (d, J=3.0 Hz, 1H), 7.05 (d, J=8.0 Hz, 1H), 6.95 (dd, J=8.0, 3.0 Hz, 1H), 3.78 (s, 2H), 3.67 (s, 3H). HPLC (max plot) 89%; Rt 2.54 min. LC/MS: (ES+): 229.0 (M+NH4+).
Reaction SMILES: [OH:1][C:2]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:3]=1[NH2:4].O(CC)[C:12]([S-])=[S:13].[K+].Cl>N1C=CC=CC=1>[CH3:10][O:9][C:7]1[CH:6]=[CH:5][C:3]2[NH:4][C:12](=[S:13])[O:1][C:2]=2[CH:8]=1
Reactant: COc1ccc(N)c(O)c1
Reactant: CCOC(=S)[S-]
Agent: Cl
Agent: [K+]
Solvent: c1ccncc1
Product: COc1ccc2[nH]c(=S)oc2c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
2-Hydroxy-4-methoxyaniline (1.00 g, 7.19 mmol) and potassium O-ethyl xanthate (1.27 g, 7.91 mmol) were heated to reflux in pyridine (20 mL). After 2 h, the reaction mixture was allowed to cool to rt and was poured into a solution of conc. HCl (10 mL) in ice water (80 mL). The resulting white solid was collected by filtration, washed with water (3×), and dried in a vacuum oven. This gave 0.733 g (56%) of the desired product. LC-MS: RT=6.67 min., [M+H]+=182.1.
Reaction SMILES: S(OOS([O-])(=O)=O)([O-])(=O)=[O:2].[K+].[K+].[CH3:13][S:14][C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1.[Cl-].[Na+]>O.CO>[CH3:13][S:14]([C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1)=[O:2]
Reactant: O=S(=O)([O-])OOS(=O)(=O)[O-]
Reactant: CSc1c[nH]c2ccccc12
Agent: [Cl-]
Agent: [K+]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CS(=O)c1c[nH]c2ccccc12

Procedure:
Potassium persulfate (KHSO5, 55 g, 179 mmol) in water (300 ml) was slowly added to a solution of 3-methylthioindole (29.3 g, 179 mmol) in methanol (300 ml) cooled in a ice bath. One half hour after the addition was completed, water was added, the solution was saturated with sodium chloride and the product was extracted into chloroform. The extract was dried, evaporated in vacuo and the residue was crystallized from chloroform-ethyl acetate to give the title product.
Reaction SMILES: [CH3:1][C:2]1[C:3](=[S:8])[NH:4][CH:5]=[CH:6][CH:7]=1.Br[C:10]1[CH:11]=[C:12]([O:18][C:19]2[C:20]([CH3:25])=[N:21][CH:22]=[CH:23][CH:24]=2)[C:13]([C:16]#[N:17])=[N:14][CH:15]=1.[H-].[Na+].O>CN(C=O)C>[CH3:1][C:2]1[C:3]([S:8][C:10]2[CH:11]=[C:12]([O:18][C:19]3[C:20]([CH3:25])=[N:21][CH:22]=[CH:23][CH:24]=3)[C:13]([C:16]#[N:17])=[N:14][CH:15]=2)=[N:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1ncccc1Oc1cc(Br)cnc1C#N
Reactant: Cc1ccc[nH]c1=S
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1cccnc1Sc1cnc(C#N)c(Oc2cccnc2C)c1
Temperature: 0 °C
Reaction time: 8 h
Yield: 60.8 %

Procedure:
3-Methylpyridine-2(1H)-thione (0.906 g, 7.24 mmol) and 5-bromo-3-(2-methylpyridin-3-yloxy)picolinonitrile (2.00 g, 6.89 mmol) were dissolved in DMF (12 mL) and the mixture was cooled to 0° C. Sodium hydride (95%; 0.183 g, 7.24 mmol) was slowly added and the reaction was warmed to ambient temperature and stirred overnight. The reaction mixture was poured into water (100 mL), stirred for 30 minutes, then filtered to afford a solid which was purified over silica gel (2:3 hexanes:ethyl acetate). Concentration of the second UV active fraction to elute afforded 5-(3-methylpyridin-2-ylthio)-3-(2-methylpyridin-3-yloxy)picolinonitrile (1.40 g, 4.19 mmol, 60.7% yield) as a pale yellow/off white powder/crystals.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:13]=2[NH:12][C:11](=[S:20])[CH2:10][N:9]=1.[OH-].[Na+].CO.Cl.Cl[CH2:27][CH2:28][N:29]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1>O>[N:29]1([CH2:28][CH2:27][S:20][C:11]2[CH2:10][N:9]=[C:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])[C:14]3[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:13]=3[N:12]=2)[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1
Reactant: ClCCN1CCCCCC1
Reactant: S=C1CN=C(c2ccccc2Cl)c2cc(Cl)ccc2N1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: Clc1ccc2c(c1)C(c1ccccc1Cl)=NCC(SCCN1CCCCCC1)=N2
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of 7.5 g of 1,3-dihydro-5-(2-chlorophenyl)-7-chloro-2H-1,4-benzodiazepine-2-thione in a solvent mixture comprising 30 ml of a 10% aqueous sodium hydroxide solution and 30 ml of methanol is added dropwise under ice cooling with stirring an aqueous solution of 7.0 g of 1-chloro-2-(perhydroazepin-1-yl)ethane hydrochloride over a period of about 10 minutes, and the resulting mixture is stirred at room temperature for 4 hours. The reaction mixture is diluted with water and extracted with ethyl acetate. The extract is rinsed with a 5% aqueous sodium hydroxide solution, washed with water and dried. Thereafter the solvent is distilled off to obtain an oily residue of 2-(2-perhydroazepin-1-ylethylthio)-5-(2-chlorophenyl)-7-chloro-3H-1,4-benzodiazepine. The oily product thus obtained is treated, according to usual procedure, with 2.74 g of fumaric acid and recrystallized from isopropyl alcohol to obtain 9.9 g of 2-(2-perhydroazepin-1-ylethylthio)-5-(2-chlorophenyl)-7 -chloro-3H-1,4-benzodiazepine fumarate, m.p. 170°-171° C.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][CH:5]=1)=[O:3].[CH3:12][O:13][C:14]1[C:23]([O:24][CH3:25])=[CH:22][CH:21]=[CH:20][C:15]=1[C:16](OC)=[O:17].[H-].[Na+]>CN(C=O)C>[CH3:12][O:13][C:14]1[C:23]([O:24][CH3:25])=[CH:22][CH:21]=[CH:20][C:15]=1[C:16](=[O:17])[CH2:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][CH:5]=1)=[O:3]
Reactant: COC(=O)c1cccc(OC)c1OC
Reactant: COc1ccc(C(C)=O)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc(C(=O)CC(=O)c2cccc(OC)c2OC)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 74.2 %

Procedure:
To a solution of 4-methoxyacetophenone (2.0 g, 13.3 mmol) and methyl 2,3-dimethoxybenzoate (3.135 g, 15.98 mmol) in DMF (100 mL), was added a NaH (1.065 g, 26.63 mmol) and the reaction mixture was stirred for 24 h at rt under N2. The reaction mixture was poured into ice water and products were extracted with EtOAc. The organic layer was separated, washed with water, dried and concentrated to afford 1-(2,3-dimethoxy-phenyl)-3-(4-methoxy-phenyl)-propane-1,3-dione (3.1 g, 74%).
Reaction SMILES: [CH3:1][C:2](=[CH2:10])[CH2:3][C:4](=[N:8][OH:9])[C:5](=[O:7])[CH3:6].[C:11](=O)([O-])[O-].[K+].[K+].S(OC)(OC)(=O)=O>CC(C)=O>[CH3:11][O:9][N:8]=[C:4]([CH2:3][C:2]([CH3:1])=[CH2:10])[C:5](=[O:7])[CH3:6]
Reactant: O=C([O-])[O-]
Reactant: C=C(C)CC(=NO)C(C)=O
Agent: [K+]
Solvent: CC(C)=O
Solvent: COS(=O)(=O)OC
Product: C=C(C)CC(=NOC)C(C)=O
Temperature: 23 °C
Reaction time: 4 h

Procedure:
141 g of 5-methylhex-5-ene-2,3-dione 3-oxime from Example 1 were dissolved in 750 ml of acetone and admixed with 165.6 g of potassium carbonate. 145 g of dimethyl sulfate in 100 ml of acetone were then added dropwise, and the mixture was stirred at 23° C. for 4 hours. The solvent was subsequently removed under reduced pressure, the residue was taken up with methyl tert-butyl ether/water and the aqueous phase was extracted repeatedly with methyl tert-butyl ether. The combined organic phases were washed with 15% strength ammonia solution and water and dried over sodium sulfate, and the solvent was removed under reduced pressure. This gave 141 g of the title compound as a yellow oil.
Reaction SMILES: Cl.[NH2:2][CH2:3][CH2:4][C:5]1[CH:15]=[CH:14][C:8]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:7][CH:6]=1.C(N(CC)CC)C.[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([S:30](Cl)(=[O:32])=[O:31])=[CH:26][CH:25]=1>C(Cl)Cl>[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([S:30]([NH:2][CH2:3][CH2:4][C:5]2[CH:15]=[CH:14][C:8]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:7][CH:6]=2)(=[O:32])=[O:31])=[CH:26][CH:25]=1
Reactant: CCOC(=O)c1ccc(CCN)cc1
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=O)c1ccc(CCNS(=O)(=O)c2ccc(Cl)cc2)cc1
Temperature: 0 °C

Procedure:
A suspension of 11.5 g. (50 mMol) ethyl 4-(2-aminoethyl)-benzoate hydrochloride (J.A.C.S., 65, 2281, 2284/1943) and 12.65 g. (125 mMol) triethylamine in 150 ml. methylene chloride is stirred for 30 minutes at ambient temperature, cooled to 0° C. and a solution of 11.55 g. (50 mMol) 4-chlorobenzenesulphonic acid chloride in 50 ml. methylene chloride slowly added dropwise thereto. After ending of the reaction, the reaction mixture is extracted twice with dilute hydrochloric acid, washed with water and the organic phase then dried over anhydrous sodium sulphate. After evaporation of the solvent, there are obtained 11.4 g. (62% of theory) of colourless crystals; m.p. 88° C., after recrystallisation from ethanol.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([O:12][CH3:13])[CH:3]=1.[N:14]([O-])=O.[Na+].Cl>O>[NH:1]([C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([O:12][CH3:13])[CH:3]=1)[NH2:14]
Reactant: COC(=O)c1ccc(N)cc1OC
Reactant: O=N[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Product: COC(=O)c1ccc(NN)cc1OC
Yield: 108113 %

Procedure:
The title compound was prepared according to the procedure described in step-2 of Intermediate-7 by using methyl 4-amino-2-methoxybenzoate (10.0 g, 0.055 mol), stannous chloride (31.00 g, 0.138 mmol), sodium nitrite (4.57 g, 0.066 mmol), 6 N HCl (200 mL) and water (100 mL) to afford 14.0 g of desired product. 1H NMR (300 MHz, DMSO d6): δ 3.73 (s, 3H), 3.80 (s, 3H), 6.51 (d, J=8.4 Hz, 1H), 6.69 (s, 1H), 7.68 (d, J=8.4 Hz, 1H), 8.75 (br s, 1H), 10.28 (br hump, 2H); MS (m/z): 197.01 (M+H)+.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][NH:4][C:5]([N:7]([CH2:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH:8]1[O:16][C@H:15]([CH2:17][OH:18])[C@H:13]([OH:14])[C@H:11]([OH:12])[C@H:9]1[OH:10])=[O:6].C(=O)([O-])[O-].[Na+].[Na+].[N+:30]([O-])([N+]([O-])=O)=[O:31]>O1CCCC1.C(Cl)Cl>[Cl:1][CH2:2][CH2:3][N:4]([N:30]=[O:31])[C:5]([N:7]([CH2:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH:8]1[O:16][C@H:15]([CH2:17][OH:18])[C@H:13]([OH:14])[C@H:11]([OH:12])[C@H:9]1[OH:10])=[O:6]
Reactant: CC(C)(C)CN(C(=O)NCCCl)C1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O
Reactant: O=[N+]([O-])[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: ClCCl
Product: CC(C)(C)CN(C(=O)N(CCCl)N=O)C1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O
Yield: 74.5 %

Procedure:
3.6 g of 1-(2-chloroethyl)-3-neopentyl-3-D-galactopyranosylurea are dissolved in a mixture of 60 ml of tetrahydrofuran and 60 ml of methylene chloride, and 15 g of sodium carbonate anhydrate are added thereto. 5 g of nitrogen tetroxide gas are introduced into the mixture for 10 minutes under ice-cooling. The mixture is treated in the same manner as described in Example 2. 2.9 g of 1-(2-chloroethyl)-1-nitroso-3-neopentyl-3-D-galactopyranosylurea are thereby obtained as yellow caramel.
Reaction SMILES: ClC1C=C(C=CC=1)C(OO)=[O:6].[C:12]1([C:18]2([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:23]=[CH:22][S:21](=[O:24])[CH2:20][CH2:19]2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>ClCCl>[C:12]1([C:18]2([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:19]=[CH:20][S:21](=[O:6])(=[O:24])[CH2:22][CH2:23]2)[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: O=S1C=CC(c2ccccc2)(c2ccccc2)CC1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: O=S1(=O)C=CC(c2ccccc2)(c2ccccc2)CC1
Temperature: 20 °C
Reaction time: 20 h
Yield: 83.5 %

Procedure:
A solution of 1.12 g of 3-chloroperoxybenzoic acid (at 85%) in 25 cm3 of dry dichloromethane is added to a solution of 1.47 g of 3,4-dihydro-4,4-diphenyl-2H-thiapyran 1-oxide in 15 cm3 of dry dichloromethane. After stirring for 20 hours at 20° C. the reaction mixture is washed with 50 cm3 of a 10% aqueous solution of sodium thiosulphate and then with 50 cm3 of a saturated aqueous solution of sodium hydrogen carbonate. The organic phase is dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The crystalline residue is washed with ethyl ether, drained and dried under reduced pressure (2.7 kPa). 1.3 g of 3,4-dihydro-4,4-diphenyl2H-thiapyran 1,1-dioxide are obtained in the form of white crystals; melting point 166° C.
Reaction SMILES: [CH:1]1[C:14]2[C:13](=[O:15])[C:12]3[C:7](=[CH:8][CH:9]=[C:10]([S:16](Cl)(=[O:18])=[O:17])[CH:11]=3)[C:6](=[O:20])[C:5]=2[CH:4]=[CH:3][C:2]=1[S:21](Cl)(=[O:23])=[O:22].C([N:28]([CH:31]([CH3:33])C)[CH2:29][CH3:30])(C)C>C(Cl)Cl>[N:28]1([S:21]([C:2]2[CH:3]=[CH:4][C:5]3[C:6](=[O:20])[C:7]4[C:12](=[CH:11][C:10]([S:16]([N:28]5[CH2:29][CH2:30][CH2:5][CH2:4][CH2:3][CH2:33][CH2:31]5)(=[O:18])=[O:17])=[CH:9][CH:8]=4)[C:13](=[O:15])[C:14]=3[CH:1]=2)(=[O:23])=[O:22])[CH2:31][CH2:33][CH2:14][CH2:1][CH2:2][CH2:30][CH2:29]1
Reactant: O=C1c2ccc(S(=O)(=O)Cl)cc2C(=O)c2cc(S(=O)(=O)Cl)ccc21
Reactant: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=C1c2ccc(S(=O)(=O)N3CCCCCCC3)cc2C(=O)c2cc(S(=O)(=O)N3CCCCCCC3)ccc21
Temperature: -50 °C
Reaction time: 4 h
Yield: 91 %

Procedure:
Anthraquinone-2,7-disulfonylchloride (1215 mg, 3 mmole) was dissolved in 100 mL DCM. The solution was cooled to −50° C. To this solution was added 1 mL (8 mmole) of heptamethyleneimine, followed by 1 mL of diisopropylethylamine. The reaction mixture was stirred at room temperature for 4 hrs. Solvent was evaporated and the residue was treated with 1N HCl, filtered off, washed with water and dried. Crude material was crystallized from chloroform-hexane to give 1.014 g (91%) of yellow compound 1-27. H1-NMR (CDCl3): 8.70 (2H, d, C1 and C8), 8.47 (2H, d, C4 and C5), 8.22 (2H, dd, C3 and C6), 3.22 (8H, m), 1.70 (20H, m).