Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([C:3]1[C:11]2[C:6](=[N:7][C:8]([C:19]3[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=3)=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=3)[N:10]=2)[N:5]([CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:4]=1)=[O:2].N#N.[BH4-].[Na+].Cl>CCO.O>[OH:2][CH2:1][C:3]1[C:11]2[C:6](=[N:7][C:8]([C:19]3[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=3)=[C:9]([C:12]3[CH:13]=[CH:14][C:15]([CH3:18])=[CH:16][CH:17]=3)[N:10]=2)[N:5]([CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:4]=1
Reactant: CCOC(=O)CCCCCCn1cc(C=O)c2nc(-c3ccc(C)cc3)c(-c3ccc(C)cc3)nc21
Agent: Cl
Agent: N#N
Agent: [BH4-]
Solvent: CCO
Solvent: O
Product: CCOC(=O)CCCCCCn1cc(CO)c2nc(-c3ccc(C)cc3)c(-c3ccc(C)cc3)nc21
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Ethyl 7-(7-Formyl-2,3-di-p-tolyl-5H-pyrrolo[2,3-b]pyrazin-5-yl)heptanoate (Intermediate C)(47 mg, 0.097 mmol) in EtOH (2 ml) was degassed with N2 treated with sodium borohydride (5.52 mg, 0.146 mmol) was added. After stirring at RT for 3 hours, the mixture was diluted with water (30 ml) and the pH was adjusted to pH 1 using 2M HCl. The aqueous portion was extracted with DCM (×3) and the combined extracts were concentrated under reduced pressure. Purification of the crude product by chromatography on silica eluting with 0-40% EtOAc in iso-hexane afforded the titled compound as an orange oil;
Reaction SMILES: C([N:8]1[C:13](=[O:14])[C:12]([C:15]2[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=2)=[C:11]([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)[CH:10]=[N:9]1)C1C=CC=CC=1.[Cl-].[Al+3].[Cl-].[Cl-].O>C1(C)C=CC=CC=1>[F:27][C:24]1[CH:23]=[CH:22][C:21]([C:11]2[CH:10]=[N:9][NH:8][C:13](=[O:14])[C:12]=2[C:15]2[CH:16]=[CH:17][N:18]=[CH:19][CH:20]=2)=[CH:26][CH:25]=1
Reactant: O=c1c(-c2ccncc2)c(-c2ccc(F)cc2)cnn1Cc1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Solvent: Cc1ccccc1
Product: O=c1[nH]ncc(-c2ccc(F)cc2)c1-c1ccncc1
Temperature: 90 °C
Reaction time: 0.5 h
Yield: 72 %

Procedure:
To a solution of 2-benzyl-5-(4-fluorophenyl)-4-(pyridin-4-yl)pyridazin-3(2H)-one (1.04 g, 2.91 mmol) in toluene (15 mL) was added aluminum chloride (970 mg, 7.28 mmol). The reaction was stirred at 90° C. for 30 min. After cooling to RT, the reaction mixture was poured into water (50 mL). The resulting mixture was extracted with EtOAc (3×50 mL). The combined organic layers were washed with saturated aqueous NaHCO3, saturated aqueous NaCl. The organic layer was dried (Na2SO4), filtered and concentrated. The resulting residue was triturated with EtOAc-hexane to give the title compound, 5-(4-fluorophenyl)-4-(pyridin-4-yl)pyridazin-3(2H)-one as an off-white solid (560 mg, 70%). LC/MS (method A): RT=1.25 min, (M+H)+=268.
Reaction SMILES: [Na].[O:2]=[C:3]1[NH:7][C:6](=[O:8])[CH:5](P(OCC)(=O)OCC)[NH:4]1.[CH:17]1([NH:23][C:24]([NH:26][CH2:27][CH2:28][CH2:29][O:30][C:31]2[CH:36]=[CH:35][C:34]([N+:37]([O-:39])=[O:38])=[C:33]([CH:40]=O)[CH:32]=2)=[O:25])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.Cl>CCO>[CH:17]1([NH:23][C:24]([NH:26][CH2:27][CH2:28][CH2:29][O:30][C:31]2[CH:36]=[CH:35][C:34]([N+:37]([O-:39])=[O:38])=[C:33]([CH:40]=[C:5]3[NH:4][C:3](=[O:2])[NH:7][C:6]3=[O:8])[CH:32]=2)=[O:25])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1
Reactant: O=Cc1cc(OCCCNC(=O)NC2CCCCC2)ccc1[N+](=O)[O-]
Reactant: CCOP(=O)(OCC)C1NC(=O)NC1=O
Agent: Cl
Agent: [Na]
Solvent: CCO
Product: O=C1NC(=O)C(=Cc2cc(OCCCNC(=O)NC3CCCCC3)ccc2[N+](=O)[O-])N1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 100.4 %

Procedure:
Sodium (0.50 g, 20 mg atom) was dissolved in absolute EtOH (100 mL), diethyl 2,4-dioxoimidazolidine-5-phosphonate (4.70 g, 20 mmol) added and the mixture stirred at room temperature for about 15 minutes. N-Cyclohexyl-N'-[3-(3-formyl-4-nitrophenoxy)propyl]urea (5.33 g, 15 mmol) in EtOH (75 mL) was added and the mixture stirred for about 1 hour. The solution was acidifed with 2N HCl solution, concentrated to ca. 75 mL and diluted with water. After stirring overnight, a pale yellow solid was filtered off and dried in air to give N-cyclohexyl-N'-[3-[4-nitro-3-[(2,4-dioxoimidazolidin-5-ylidene)-methyl]phenoxy] propyl]urea (6.50 g, 99 %). A 1.00 g sample was recrystallized from aqueous acetonitrile to give 0.79 g as a 5:1 (Z) to (E) mixture, mp 132°-138° C. IR (KBr) 1760, 1725, 1650, 1570, 1500, 1375, 1340, 1290, 1250 cm-1 ; 1 H NMR (DMSO-d6) δ 1.00 to 2.00 (10H, m, CH2 of cyclohexyl ring), 3.30 (2H, quintet, J=6 Hz, CO.NH.CH2), 3.35 (1H, m, N-CH), 4.11 (0.32H, t, J=6Hz, OCH2 of (Z) isomer), 4.20 (1.67H, t, J=6 Hz, OCH2 of (E) isomer), 6.62 (0.16H, s, olefinic H of (Z) isomer), 6.74 (0.84H, s, olefinic H of (E) isomer), 7.05 to 7.20 (2H, m, aryl H), 8.15 (1H, 2×d, aryl H ortho to NO2); MS m/Z 432 (MH+).
Reaction SMILES: [Br:1][C:2]1[C:3]([OH:14])=[CH:4][C:5]2[C:6]([CH3:13])([CH3:12])[CH2:7][CH2:8][CH2:9][C:10]=2[CH:11]=1.I[CH2:16][CH3:17].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[Br:1][C:2]1[CH:11]=[C:10]2[C:5](=[CH:4][C:3]=1[O:14][CH2:16][CH3:17])[C:6]([CH3:12])([CH3:13])[CH2:7][CH2:8][CH2:9]2
Reactant: CCI
Reactant: CC1(C)CCCc2cc(Br)c(O)cc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOc1cc2c(cc1Br)CCCC2(C)C

Procedure:
A mixture of 3-bromo-8,8-dimethyl-5,6,7,8-tetrahydronaphthalen-2-ol (Compound A-2, 5.77 g, 22.62 mmol); iodoethane (7.2 mL, 90.5 mmol), and potassium carbonate (4.68 g, 34 mmol) in acetone (50 mL) was stirred at 70° C. overnight. The solvent was removed in vacuo. The residue was purified by column chromatography (silica gel, 2.5% ethyl acetate in hexane) to afford the title compound as a pale yellow oil.
Reaction SMILES: [OH-].[Na+].[CH3:3][C:4]1[O:8][C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:6][C:5]=1[CH2:15][O:16][C:17]1[CH:45]=[CH:44][C:20]([CH2:21][O:22]/[N:23]=[C:24](/[C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)=[CH2:37])[CH:31]=2)\[C:25]([O:27]CC)=[O:26])=[CH:19][CH:18]=1.CO.Cl>O1CCCC1>[CH3:3][C:4]1[O:8][C:7]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[N:6][C:5]=1[CH2:15][O:16][C:17]1[CH:45]=[CH:44][C:20]([CH2:21][O:22]/[N:23]=[C:24](/[C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=3)=[CH2:37])[CH:31]=2)\[C:25]([OH:27])=[O:26])=[CH:19][CH:18]=1
Reactant: C=C(c1ccccc1)c1cccc(/C(=N/OCc2ccc(OCc3nc(-c4ccccc4)oc3C)cc2)C(=O)OCC)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: C=C(c1ccccc1)c1cccc(/C(=N/OCc2ccc(OCc3nc(-c4ccccc4)oc3C)cc2)C(=O)O)c1
Temperature: 40 °C
Reaction time: 2 h
Yield: 94.5 %

Procedure:
A 1N aqueous saturated solution of sodium hydroxide (5 ml) was added to a solution of ethyl Z-2-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyloxyimino]-2-[3-(1-phenylvinyl)phenyl]acetate (780 mg) in tetrahydrofuran (10 ml)-methanol (5 ml) and stirred at 40° C. for 2 hours. 1N hydrochloric acid (5.5 ml) was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The residue was recrystallized from ethyl acetate-hexane to obtain Z-2-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyloxyimino]-2-[3-(1-phenylvinyl)phenyl]acetic acid (701 mg, yield 95%) as colorless crystals. m.p. 171-172° C.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:17])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][NH2:16])=[CH:11][CH:10]=1)([CH3:7])[CH3:6])[CH3:2].[CH3:18][C:19]1[N:27]=[C:26]([C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=2)[CH:25]=[CH:24][C:20]=1[C:21](O)=[O:22].COC(=O)C1C=CC(C2C=CC(C(F)(F)F)=CC=2)=NC=1C>>[CH2:1]([O:3][C:4](=[O:17])[C:5]([CH3:7])([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:15][NH:16][C:21]([C:20]2[C:19]([CH3:18])=[N:27][C:26]([C:28]3[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:35])[F:36])=[CH:30][CH:29]=3)=[CH:25][CH:24]=2)=[O:22])=[CH:13][CH:14]=1)[CH3:6])[CH3:2]
Reactant: Cc1nc(-c2ccc(C(F)(F)F)cc2)ccc1C(=O)O
Reactant: CCOC(=O)C(C)(C)Oc1ccc(CN)cc1
Agent: COC(=O)c1ccc(-c2ccc(C(F)(F)F)cc2)nc1C
Product: CCOC(=O)C(C)(C)Oc1ccc(CNC(=O)c2ccc(-c3ccc(C(F)(F)F)cc3)nc2C)cc1

Procedure:
In analogy to the procedures described in example 26B] and 26C], 2-(4-aminomethyl-phenoxy)-2-methyl-propionic acid ethyl ester [PCT Int. Appl. (2002), WO 2002/096895A1] was reacted with 2-methyl-6-(4-trifluoromethyl-phenyl)-nicotinic acid (prepared from 2-methyl-6-(4-trifluoromethyl-phenyl)-nicotinic acid methyl ester (example 1L]) in analogy to the procedure described in example 53B]) to give 2-methyl-2-[4-({[2-methyl-6-(4-trifluoromethyl-phenyl)-pyridine-3-carbonyl]-amino}-methyl)-phenoxy]-propionic acid ethyl ester, which was subsequently saponified to yield the title compound as colorless oil.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[O:12][N:11]=[C:10]([CH2:13][CH2:14][S:15]([CH2:18][CH2:19][OH:20])(=[O:17])=[O:16])[N:9]=1.[S:21](=O)(=[O:24])([OH:23])[OH:22].OS(O)(=O)=O.O=S(=O)=O.C(=O)(O)[O-].[Na+].[Cl-].[K+]>>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:21]([OH:24])(=[O:23])=[O:22])=[CH:4][C:3]=1[C:8]1[O:12][N:11]=[C:10]([CH2:13][CH2:14][S:15]([CH2:18][CH2:19][OH:20])(=[O:17])=[O:16])[N:9]=1
Reactant: Nc1ccccc1-c1nc(CCS(=O)(=O)CCO)no1
Reactant: O=S(=O)(O)O
Agent: O=C([O-])O
Agent: O=S(=O)=O
Agent: [Cl-]
Product: Nc1ccc(S(=O)(=O)O)cc1-c1nc(CCS(=O)(=O)CCO)no1
Temperature: 40 °C
Reaction time: 1 h

Procedure:
59.4 g (0.2 mol) of 5-(2′-aminophenyl)-3-[2-(2-hydroxyethylsulfonyl)ethyl]-1,2,4-oxadiazole were added at 10-15° C. to 100% strength sulfuric acid and stirred in at 40° C. for 1 h. 240 ml of 24% strength by weight oleum were then added at 40° C. a little at a time over 20 h. After heating at 60° C. for 8 h, the reaction solution was poured onto ice, the pH was adjusted to pH 4-5 with sodium bicarbonate, and the product was salted out with 500 g of potassium chloride to afford 95.3 g of 5-(2′-amino-5′-sulfophenyl)-3-[2-(2-hydroxyethylsulfonyl)ethyl]-1,2,4-oxadiazole.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([S:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:22])[C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH3:14])[N:13]=2)=[N:6][CH:7]=1.[SH:23][CH2:24][CH2:25][C:26]([O:28][CH3:29])=[O:27]>>[Cl:22][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[S:15][C:4]1[CH:3]=[C:2]([S:23][CH2:24][CH2:25][C:26]([O:28][CH3:29])=[O:27])[CH:7]=[N:6][C:5]=1[NH:8][C:9]1[S:10][CH:11]=[C:12]([CH3:14])[N:13]=1
Reactant: Cc1csc(Nc2ncc(Br)cc2Sc2ccccc2Cl)n1
Reactant: COC(=O)CCS
Product: COC(=O)CCSc1cnc(Nc2nc(C)cs2)c(Sc2ccccc2Cl)c1

Procedure:
Prepared according to the method of Example 13 from N-(5-bromo-3-(2-chlorophenylthio)pyridin-2-yl)-4-methylthiazol-2-amine (prepared according to Example 47) and methyl 3-mercaptopropanoate. 1H NMR (CDCl3) δ 9.01 (bs, 1H), 8.52 (d, 1H), 7.95 (d, 1H), 7.40 (dd, 1H), 7.16-7.06 (m, 2H), 6.66 (dd, 1H), 6.46 (s, 1H), 3.68 (s, 3H), 3.07 (t, 2H), 2.61 (t, 2H), 2.32 (s, 3H); Mass spectrum (esi) m/z=452.1 (M+H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([OH:8])[CH:7]=1.[C:12]1(P(C2C=CC=CC=2)C2C=CC=CC=2)[CH:17]=CC=C[CH:13]=1.CC(O)C.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([O:8][CH:12]([CH3:17])[CH3:13])[CH:7]=1
Reactant: O=[N+]([O-])c1ccc(F)cc1O
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Solvent: C1CCOC1
Solvent: CC(C)O
Product: CC(C)Oc1cc(F)ccc1[N+](=O)[O-]
Temperature: 0 °C
Yield: 77.6 %

Procedure:
5-Fluoro-2-nitrophenol (48 g) was dissolved in dry tetrahydrofuran (THF) (300 mL). Triphenylphosphine (88 g) and 2-propanol (47 mL) were added, and the resulting mixture was cooled to 0° C. Diisopropylazodicarboxylate (66 mL) was added dropwise. The resulting mixture was allowed to warm to room temperature and stirred over night. The solvent was evaporated in vacuo and the resulting mixture was filtered through silica (heptane/ethyl acetate 1:1). The solvent was evaporated in vacuo and the resulting mixture was recrystallised from heptane/ethyl acetate (1:1). The organic phase was separated from the crystalline solid by filtration, the solvent was evaporated in vacuo, and the remaining product was purified by flash chromatography (silica gel, heptane/ethyl acetate 9:1), yielding the title compound as colourless oil (47.2 g, 78%).
Reaction SMILES: Cl[CH2:2][C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[S:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)=[CH:5][CH:4]=1.[C:19]([O:23][C:24]([N:26]1[CH2:31][C@@H:30]2[CH2:32][C@H:27]1[CH2:28][NH:29]2)=[O:25])([CH3:22])([CH3:21])[CH3:20].C(N(CC)CC)C>CC#N>[C:19]([O:23][C:24]([N:26]1[CH2:31][C@@H:30]2[CH2:32][C@H:27]1[CH2:28][N:29]2[CH2:2][C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[S:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)=[CH:5][CH:4]=1)=[O:25])([CH3:22])([CH3:20])[CH3:21]
Reactant: CC(C)(C)OC(=O)N1C[C@@H]2C[C@H]1CN2
Reactant: ClCc1ccc(Oc2nc3ccccc3s2)cc1
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CC(C)(C)OC(=O)N1C[C@@H]2C[C@H]1CN2Cc1ccc(Oc2nc3ccccc3s2)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 71.1 %

Procedure:
To a stirred solution of 2-(4-chloromethyl-phenoxy)-benzothiazole (15.3 g, 55.3 mmol) and (S,S)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (13.2 g, 66.4 mmol) in CH3CN (200 mL) was added triethylamine (Et3N) (11.5 mL, 82.9 mmol). The resulting solution was stirred at rt for 24 h and then concentrated. The crude residue was then partitioned between CH2Cl2 (800 mL) and saturated (satd.) aqueous (aq.) NaHCO3 (200 mL). The organic layer was separated, dried (Na2SO4), filtered and concentrated. Purification by silica gel flash chromatography (10% to 40% ethyl acetate (EtOAc) in hexanes) afforded the title compound as a white foam (17.2 g, 71%). MS (ESI): mass calcd. for C24H27N3O3S, 437.18; m/z found, 438.2 [M+H]+. 1H NMR (500 MHz, CDCl3, mixture of rotamers): 7.73 (d, J=7.1 Hz, 1H), 7.66 (d, J=7.1 Hz, 1H), 7.42 (d, J=8.1 Hz, 2H), 7.38 (m, 1H), 7.32-7.24 (br m, 3H), 4.40 (br m, 0.5H), 4.26 (br m, 0.5H), 3.76 (br d, J=9.7 Hz, 2H), 3.63 (br d, J=10.5 Hz, 0.5H), 3.50 (br m, 1H), 3.46 (m, 0.5H), 3.18 (br m, 1H), 2.93 (br d, J=8.8 Hz, 0.5H), 2.88 (br d, J=9.4 Hz, 0.5H), 2.73 (br d, J=9.2 Hz, 0.5H), 2.55 (br d, J=9.2 Hz, 0.5H), 1.87 (br t, J=8.8 Hz, 1H), 1.74 (br d, J=9.3 Hz, 0.5H), 1.68 (br d, J=9.3 Hz, 0.5H), 1.47 (s, 9H).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:10])[C:5](=O)[CH:6]([CH3:8])[CH3:7])[CH3:2].[C:11](=[O:15])([O:13][CH3:14])[NH2:12].CC1C=CC(S(O)(=O)=O)=CC=1.N1C=CC=CC=1>C1C=CC=CC=1>[CH3:14][O:13][C:11]([NH:12][C:5](=[C:6]([CH3:8])[CH3:7])[C:4]([O:3][CH2:1][CH3:2])=[O:10])=[O:15]
Reactant: CCOC(=O)C(=O)C(C)C
Reactant: COC(N)=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccccc1
Solvent: c1ccncc1
Product: CCOC(=O)C(NC(=O)OC)=C(C)C

Procedure:
A benzene solution (90 mL) of ethyl-3-methyl-2-oxobutanoate (4.03 g, 28.0 mmol), methyl carbamate (2.098 g, 28.0 mmol) and pyridine 4-methylbenzenesulfonate (0.70 g, 2.80 mmol) was heated to reflux in a round bottom flask equipped with a Dean-Stark trap and reflux condenser. After 44 hours of heating the mixture was cooled and then partitioned between ethyl acetate (50 mL) and brine (50 mL). The organic phase was washed with brine (2×50 mL) then dried (MgSO4) and concentrated in vacuo. The crude product was purified by chromatography on silica gel (ethyl acetate-hexanes) to provide the title compound as an off white crystalline solid (1.487 g, 26%).
Reaction SMILES: CO[CH:3]=[CH:4][C:5]1[CH:6]=[N:7][CH:8]=[CH:9][CH:10]=1.[N+:11]([C:14]1[CH:19]=[CH:18][C:17]([NH:20][NH2:21])=[CH:16][CH:15]=1)([O-:13])=[O:12]>C(O)C.Cl>[N+:11]([C:14]1[CH:15]=[CH:16][C:17]([NH:20][N:21]=[CH:3][CH2:4][C:5]2[CH:6]=[N:7][CH:8]=[CH:9][CH:10]=2)=[CH:18][CH:19]=1)([O-:13])=[O:12]
Reactant: COC=Cc1cccnc1
Reactant: NNc1ccc([N+](=O)[O-])cc1
Agent: Cl
Solvent: CCO
Product: O=[N+]([O-])c1ccc(NN=CCc2cccnc2)cc1
Yield: 81.8 %

Procedure:
A solution of 3-(2-EZ-methoxyethenyl)pyridine (3.43 g) in ethanol (15 ml) and 2N hydrochloric acid (25 ml) was heated under reflux for 1 hour and then cooled. 4-nitrophenylhydrazine (3.89 g) was added portionwise with stirring to give a solution which deposited a yellow solid. The mixture was cooled in ice and the solid was filtered off, washed with isopropanol,ether and then dried to give the title compound (5.32 g), m.p. 212°-214° C. Found: C,53.54; H,4.51; N,19.00. C13 H12N4O2 requires: C,53.34; H,4.48; N,19.14%.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]2[C:9](=[O:10])[NH:8][C:6](=[O:7])[C:5]2=[CH:11][CH:12]=1.[C:13](=O)([O-])[O-].[K+].[K+].CI.O>CN(C=O)C.C(OCC)(=O)C>[I:1][C:2]1[CH:3]=[C:4]2[C:9](=[O:10])[N:8]([CH3:13])[C:6](=[O:7])[C:5]2=[CH:11][CH:12]=1
Reactant: O=C([O-])[O-]
Reactant: O=C1NC(=O)c2cc(I)ccc21
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CI
Product: CN1C(=O)c2ccc(I)cc2C1=O
Temperature: 25 °C
Reaction time: 4.5 h
Yield: 47.9 %

Procedure:
4-Iodophthalimide (358 mg, 1.31 mmol) obtained in Step 1 was dissolved in DMF (6.7 mL), and the mixture was stirred at room temperature for 4.5 hours after adding potassium carbonate (272 mg, 1.97 mmol) and methyl iodide (0.10 mL, 1.57 mmol). The mixture was further stirred for 45 minutes after adding potassium carbonate (544 mg, 3.94 mmol) and methyl iodide (1.0 mL, 15.7 mmol). Thereafter, water and ethyl acetate were added to the mixture to separate the organic layer. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was then purified by silica gel column chromatography to give 4-iodo-N-methylphthalimide (180 mg, 48%).
Reaction SMILES: [C:1]1([CH2:7][C:8](Cl)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:11]1(=[O:30])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13](=[O:20])[N:12]1[CH:21]1[CH2:29][C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:22]1.[Cl-].[Al+3].[Cl-].[Cl-]>ClC(Cl)C>[C:11]1(=[O:30])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13](=[O:20])[N:12]1[CH:21]1[CH2:22][C:23]2[C:28](=[CH:27][CH:26]=[C:25]([C:8](=[O:9])[CH2:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH:24]=2)[CH2:29]1
Reactant: O=C1c2ccccc2C(=O)N1C1Cc2ccccc2C1
Reactant: O=C(Cl)Cc1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: CC(Cl)Cl
Product: O=C(Cc1ccccc1)c1ccc2c(c1)CC(N1C(=O)c3ccccc3C1=O)C2
Temperature: 0 °C
Reaction time: 2 h
Yield: 72.5 %

Procedure:
0.70 g of phenylacetic acid chloride dissolved in 5 ml of dichloroethane was added under ice cooling to 1.00 g of 2-(1,3-isoindolinedion-2-yl)indane and 1.27 g of anhydrous aluminum chloride suspended in 15 ml of dichloroethane, and the mixture was stirred at the same temperature for 2 hours and then at room temperature for l hour. The reaction mixture was poured into ice water and extracted with chloroform. After the organic layer was washed with water and dried, the solvent was removed. The resulting crystals were recrystallized from ethyl acetate to obtain 1.05 g of 2-(1,3-isoindolinedion-2-yl)-5-(2-phenylacetyl)indane.
Reaction SMILES: [NH:1]([CH2:3][C:4]([OH:6])=[O:5])[CH3:2].C(N(CC)CC)C.[C:14](Cl)(=[O:16])[CH3:15].Cl>CN(C)C1C=CN=CC=1.O.O1CCOCC1.O1CCOCC1>[C:14]([N:1]([CH2:3][C:4]([OH:6])=[O:5])[CH3:2])(=[O:16])[CH3:15]
Reactant: CNCC(=O)O
Reactant: CC(=O)Cl
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: C1COCCO1
Solvent: O
Solvent: CCN(CC)CC
Product: CC(=O)N(C)CC(=O)O
Temperature: 0 °C
Reaction time: 1 h

Procedure:
4-Dimethylaminopyridine (3.66 g) was added to a solution of sarcosine (26.7 g) and triethylamine (50 ml) in (1:1) dioxane water (150 ml) cooled at 0° C. A solution of acetyl chloride (22.37 ml) in dioxane (20 ml) was added dropwise over a period of 30 min. The reaction solution was then stirred at room temperature for 1 hour and subsequently was acidified to pH 3 with cold 50% aqueous HCl. The mixture was extracted three times with ethyl acetate. The extracts were washed with a saturated NaCl solution, dried over Na2SO4 and concentrated. The residue was crystallized from ethyl acetate to give N-acetyl-sarcosine, m.p. 135°-137° C. Fab Mass spec. m/e 132 (M+H); Anal. for C5H9NO3, Calcd: C, 45.79; H, 6.91; N, 10.68; Found: C, 45.78; H, 7.03; N, 10.64.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[NH:8][C:9]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)=[CH:10][C:11](=O)[CH:12]=1.P(Cl)(Cl)(Cl)(Cl)[Cl:21]>P(Cl)(Cl)(Cl)=O>[Cl:21][C:11]1[CH:12]=[C:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[N:8]=[C:9]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[CH:10]=1
Reactant: ClP(Cl)(Cl)(Cl)Cl
Reactant: O=c1cc(-c2ccccn2)[nH]c(-c2ccccn2)c1
Solvent: O=P(Cl)(Cl)Cl
Product: Clc1cc(-c2ccccn2)nc(-c2ccccn2)c1

Procedure:
A mixture of 3.99 g (16 mmol) of 1′H-[2,2′;6′,2″]terpyridin-4′-one (L1) and 8.0 g (38 mmol) of phosphorus pentachloride is boiled at reflux in 200 ml of phosphorus oxychloride for sixteen hours. The mixture is allowed to cool and concentrated to dryness. 200 ml of ice-water are then added cautiously to the residue, and the solution is then adjusted to pH 9 with aqueous potassium hydroxide solution. Extraction is carried out three times using chloroform and the organic extracts are dried over sodium sulfate, filtered and concentrated. After recrystallisation from ethanol, 4′-chloro-[2,2′;6′,2″]terpyridine is obtained in the form of white needles.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][C:4]1([CH2:18][CH2:19][Cl:20])[C:17]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[S:11][C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2.[Cl-].[Cl-].IC1C=CC=CC=1.Cl.[OH2:31]>N1C=CC=CC=1>[Cl:20][CH2:19][CH2:18][C:4]1([CH2:3][CH2:2][Cl:1])[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:10]=2[S:11](=[O:31])[C:12]2[C:17]1=[CH:16][CH:15]=[CH:14][CH:13]=2
Reactant: O
Reactant: ClCCC1(CCCl)c2ccccc2Sc2ccccc21
Agent: Cl
Agent: [Cl-]
Solvent: Ic1ccccc1
Solvent: c1ccncc1
Product: O=S1c2ccccc2C(CCCl)(CCCl)c2ccccc21
Reaction time: 0.25 h

Procedure:
A solution of 9,9-bis(2'-chloroethyl)thioxanthene in pyridine (25 ml.) and water (5 ml.) is cooled in an ice/salt bath to -5° to 0° C. and a solution of iodobenzene dichloride (2.7 g.) in dry pyridine (10 ml.) is added slowly during 15 minutes with stirring. Stirring at 0° C. is continued for a further 15 minutes, the reaction mixture is poured into water, acidified with concentrated hydrochloric acid and extracted with chloroform. The product is crystallised from cyclohexane to give 9,9-bis(2'-chloroethyl)-thioxanthene 10-oxide, m.p. 126°-127° C.
Reaction SMILES: ClCC(SC1C(Cl)=CC=CC=1Cl)C[O:5][C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][CH:7]=1.Br[CH2:23][CH2:24][C:25]([OH:27])=[O:26]>>[Cl:12][C:9]1[CH:10]=[CH:11][C:6]([O:5][CH2:23][CH2:24][C:25]([OH:27])=[O:26])=[CH:7][CH:8]=1
Reactant: ClCC(COc1ccc(Cl)cc1)Sc1c(Cl)cccc1Cl
Reactant: O=C(O)CCBr
Product: O=C(O)CCOc1ccc(Cl)cc1

Procedure:
38.2 g of 1-chloro-2-(2,6-dichlorophenylthio)-3-p-chlorophenoxypropane [obtainable by reaction of 3-bromo-propionic acid with Na p-chlorophenolate to give 3-p-chlorophenoxypropionic acid, bromination to give 2-bromo-3-p-chlorophenoxypropionic acid, reaction with Na 2,6-dichlorothiophenolate to give 2-(2,6-dichlorophenylthio)-3-p-chlorophenoxypropionic acid, LiAlH4 reduction to give the alcohol and reaction with SOCL2 ]is heated at 120° with 40 g of imidazole for 5 hours, then cooled, worked up as usual and Ia of m.p. 175°-177° is obtained.