Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]1[C@H:9]([OH:10])[C@H:8]2[N:3]([CH2:4][C@H:5]([OH:13])[C@@H:6]([OH:12])[C@@H:7]2[OH:11])[CH2:2]1.[CH3:14][C:15]1[CH:23]=[CH:22][C:18]([C:19](Cl)=[O:20])=[CH:17][CH:16]=1.C>N1C=CC=CC=1.O.CO>[CH3:14][C:15]1[CH:23]=[CH:22][C:18]([C:19]([O:13][CH:5]2[CH:6]([OH:12])[CH:7]([OH:11])[CH:8]3[N:3]([CH2:2][CH2:1][CH:9]3[OH:10])[CH2:4]2)=[O:20])=[CH:17][CH:16]=1
Reactant: Cc1ccc(C(=O)Cl)cc1
Reactant: O[C@H]1[C@H](O)[C@@H](O)CN2CC[C@H](O)[C@H]12
Solvent: c1ccncc1
Solvent: O
Solvent: CO
Product: Cc1ccc(C(=O)OC2CN3CCC(O)C3C(O)C2O)cc1
Temperature: 25 °C
Yield: 12 %

Procedure:
To a suspension of 3 g of castanospermine in 30 ml of pyridine at 0° C. was added dropwise a solution of 3 g of 4-methylbenzoyl chloride. After the addition, the mixture was allowed to warm to room temperature and then heated at 55° C. for 24 hours. The reaction mixture was diluted with 10 ml of water and evaporated to dryness in vacuo. The resulting residue was stirred in 150 ml of a 1:2 mixture of water:methylene chloride. The insoluble material was separated by filtration to provide an amorphous off-white solid which was dissolved in 60 ml of hot methanol, treated with 0.5 g of activated charcoal and filtered. The colorless liltrate was cooled to give colorless crystals of [1S-(1α, 6β, 7α, 8β, 8αβ)]-octahydro-1,6,7,8-indolizine-tetrol 6-(4-methylbenzoate) melting at about 255°-258° C. with decomposition (580 mg, 12% yield).
Reaction SMILES: [P:1](=[O:5])([OH:4])([OH:3])[OH:2].[CH3:6][O:7][C:8]1[N:13]=[C:12](/[CH:14]=[CH:15]/[C:16]2[N:34]=[C:19]3[C@H:20]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[C:30]([F:33])([F:32])[F:31])[CH2:21][CH2:22][CH2:23][N:18]3[N:17]=2)[CH:11]=[CH:10][C:9]=1[N:35]1[CH:39]=[C:38]([CH3:40])[N:37]=[CH:36]1>C(O)C.CCCCCCC>[OH:5][P:1]([O:4][P:1]([OH:4])([OH:3])=[O:2])(=[O:3])[OH:2].[CH3:6][O:7][C:8]1[N:13]=[C:12](/[CH:14]=[CH:15]/[C:16]2[N:34]=[C:19]3[C@H:20]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[C:30]([F:33])([F:32])[F:31])[CH2:21][CH2:22][CH2:23][N:18]3[N:17]=2)[CH:11]=[CH:10][C:9]=1[N:35]1[CH:39]=[C:38]([CH3:40])[N:37]=[CH:36]1
Reactant: O=P(O)(O)O
Agent: COc1nc(/C=C/c2nc3n(n2)CCC[C@H]3c2ccccc2C(F)(F)F)ccc1-n1cnc(C)c1
Solvent: CCCCCCC
Solvent: CCO
Product: O=P(O)(O)OP(=O)(O)O
Temperature: 25 °C

Procedure:
A solution of phosphoric acid (13.2 mg) in ethanol (0.05 mL) was added to a mixed solution of (8S)-2-{(E)-2-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]vinyl}-8-(2-trifluoromethylphenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridine (50 mg) in heptane (0.6 mL)-ethanol (0.15 mL) at room temperature. The reaction solution was stirred at room temperature, and the precipitated solid was collected by filtration through a glass filter. The solid was washed with heptane-ethanol (3:1) and then dried under reduced pressure at room temperature to obtain 37.6 mg of the title compound as white solid crystals.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][C:5](=[O:11])[NH:6]2.[Br:12]N1C(=O)CCC1=O.C(OCC)(=O)C.CCCCCC>C(#N)C>[Br:12][C:10]1[C:2]([CH3:1])=[C:3]2[C:7](=[CH:8][CH:9]=1)[NH:6][C:5](=[O:11])[CH2:4]2
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1cccc2c1CC(=O)N2
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: CC#N
Product: Cc1c(Br)ccc2c1CC(=O)N2
Temperature: 25 °C
Reaction time: 4 h
Yield: 21.7 %

Procedure:
4-Methyl-2-oxindole (5 g) in 40 mL of acetonitrile was treated with 7.26 g of N-bromosuccinimide and stirred at room temperature for 4 hours. Thin layer chromatography (ethyl acetate:hexane 1:2, silica gel) showed a mixture of 5-bromo (Rf 0.3) and 5,7-dibromo (Rf 0.5) products. Another 7.26 g of N-bromosuccinimide was added and the mixture stirred for 4 additional hours. The solid was collected by vacuum filtration, washed with 20 mL of acetonitrile and dried to give a 1:1 mixture of mono and dibromo compounds. The filtrate was concentrated and chromatographed on silica gel (ethyl acetate:hexane (1:2)) to give 1.67 g of 5-bromo-4-methyl-2-oxindole as a beige solid. The remaining 1:1 mixture of solids was recrystallized twice from glacial acetic acid to give 3.2 g of 5,7-dibromo-4-methyl-2-oxindole as a light orange solid. The filtrates from this material were chromatographed as above to give 0.6 g of 5-bromo-4-methyl-2-oxindole and 0.5 g of 5,7-dibromo-4-methyl-2-oxindole.
Reaction SMILES: [Co:1].[N+:2]([O-:5])([OH:4])=[O:3].[C:6](=[O:9])([O-:8])[O-:7].[NH4+].[NH4+]>>[N+:2]([O-:5])([O-:4])=[O:3].[Co+2:1].[N+:2]([O-:5])([O-:4])=[O:3].[C:6](=[O:7])([O-:9])[O-:8].[Co+2:1]
Reactant: [Co]
Reactant: O=[N+]([O-])O
Agent: O=C([O-])[O-]
Agent: [NH4+]
Product: O=[N+]([O-])[O-]
Product: [Co+2]

Procedure:
A cobalt nitrate solution is prepared by reacting 125 parts of electrolytic grade cobalt with 1,125 parts of 40 percent nitric acid. About 33 percent of this solution is reserved for later use in this example. The remaining solution is mixed with 1,125 parts of 40 percent ammonium carbonate solution to form a precipitate of basic cobalt carbonate. The precipitate is separated from the solution by filtration, washed with water, dried, and placed in a furnace at 500° C. for 4 hours to form a first porous mass of cobalt oxide; this first porous mass of cobalt oxide is very soft and not suitable for use as a particulate catalyst. The first porous mass is cooled to ambient temperature and saturated with the portion of cobalt nitrate previously reserved. The resulting saturated mass is heated in the furnace at 500° C. for 4 hours to form a second porous of cobalt oxide, Co3O4, containing 48.9 percent trivalent cobalt. Surprisingly, this second porous mass is hard enough for use as a catalyst; it is cooled to ambient temperature, ground, and screened to provide a particulate cobalt oxide catalyst. The catalyst particles have a mean crushing strength of about 3,900 grams per particle. As in Example 1, the catalyst is tested in the small ammonia oxidation plant. The yield of nitric oxide is 99.3 percent of theory in a series of tests using an ammonia-air feed mixture containing 9.3 to 9.9 percent ammonia, by volume, and a linear gas velocity of about 60 to 230 cm. per second. For this catalyst, the critical velocity is surprisingly high, about 370 cm. per second at 7.5 volume percent ammonia in the feed gas.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[C:8]([C:13]([O:15][CH3:16])=[O:14])[C:7]([CH3:17])=[C:6]2[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1.[Br:26]N1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N>C1C=CC=CC=1>[Br:26][CH2:17][C:7]1[C:8]([C:13]([O:15][CH3:16])=[O:14])=[N:9][C:10]2[C:5]([C:6]=1[C:18]1[CH:19]=[CH:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=1)=[CH:4][C:3]([O:2][CH3:1])=[CH:12][CH:11]=2
Reactant: O=C1CCC(=O)N1Br
Reactant: COC(=O)c1nc2ccc(OC)cc2c(-c2ccc(OC)cc2)c1C
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: c1ccccc1
Product: COC(=O)c1nc2ccc(OC)cc2c(-c2ccc(OC)cc2)c1CBr
Temperature: 25 °C
Yield: 97.3 %

Procedure:
Methyl 6-methoxy-4-(4-methoxyphenyl)-3-methylquinoline-2-carboxylate (8.27 g) was dissolved in benzene (100 ml); N-bromosuccinimide (5.24 g) and 2,2′-azobis(isobutyronitrile) (0.40 g) were added; followed by refluxing for 2 hours. After cooling to room temperature, the resulting precipitate was filtered off. The filtrate was diluted with ethyl acetate (100 ml), after which it was washed with 1 N sodium hydroxide and brine successively, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure; the residue obtained was purified by column chromatography (silica gel: 50 g, eluent: ethyl acetate-hexane=1:2). The crude crystal obtained was recrystallized from ethyl acetate-hexane to yield the title compound (9.93 g) as a colorless needle crystal.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([NH:9][C:10]1[CH:11]=[C:12]([O:21][CH3:22])[CH:13]=[C:14]2[C:19]=1[N:18]=[CH:17][CH:16]=[C:15]2[CH3:20])=[O:8].[N:23]1([CH2:29][CH2:30][CH2:31][OH:32])[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1>C(OCC)(=O)C.C(N(CC)CC)C>[OH:32][CH2:31][CH2:30][CH2:29][N:23]1[CH2:28][CH2:27][N:26]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([NH:9][C:10]2[CH:11]=[C:12]([O:21][CH3:22])[CH:13]=[C:14]3[C:19]=2[N:18]=[CH:17][CH:16]=[C:15]3[CH3:20])=[O:8])[CH2:25][CH2:24]1
Reactant: COc1cc(NC(=O)CCCCCBr)c2nccc(C)c2c1
Reactant: OCCCN1CCNCC1
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: COc1cc(NC(=O)CCCCCN2CCN(CCCO)CC2)c2nccc(C)c2c1
Yield: 95.3 %

Procedure:
A mixture of 4.3 g (0.012 mole) of 6-bromo-N-(6-methoxy-4-methyl-8-quinolinyl)hexanamide and 3.5 g (0.024 mole) of 1-piperazinepropanol was heated at 120° for 2 hr and allowed to cool. The mixture was diluted with ethyl acetate and excess triethylamine, washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to dryness to afford 4.9 g (96%) of the desired compound as a gum. The IR and NMR (CDCl3) were consistent with the assigned structure.
Reaction SMILES: O.[N+:2]([C:5]1[CH:6]=[C:7]([C:19]2[CH:24]=[CH:23][C:22]([NH:25][C:26]([C:28]3[O:29][CH:30]=[CH:31][CH:32]=3)=[O:27])=[C:21]([N+:33]([O-])=O)[CH:20]=2)[CH:8]=[CH:9][C:10]=1[NH:11][C:12]([C:14]1[O:15][CH:16]=[CH:17][CH:18]=1)=[O:13])([O-])=O.[Cl-].[NH4+].[In]>C(O)C.CN1CCCC1=O>[NH2:33][C:21]1[CH:20]=[C:19]([C:7]2[CH:8]=[CH:9][C:10]([NH:11][C:12]([C:14]3[O:15][CH:16]=[CH:17][CH:18]=3)=[O:13])=[C:5]([NH2:2])[CH:6]=2)[CH:24]=[CH:23][C:22]=1[NH:25][C:26]([C:28]1[O:29][CH:30]=[CH:31][CH:32]=1)=[O:27]
Reactant: O=C(Nc1ccc(-c2ccc(NC(=O)c3ccco3)c([N+](=O)[O-])c2)cc1[N+](=O)[O-])c1ccco1
Agent: [Cl-]
Agent: [In]
Agent: [NH4+]
Solvent: CCO
Solvent: CN1CCCC1=O
Solvent: O
Product: Nc1cc(-c2ccc(NC(=O)c3ccco3)c(N)c2)ccc1NC(=O)c1ccco1
Temperature: 80 °C
Reaction time: 1 h
Yield: 23.3 %

Procedure:
Into a separable flask equipped with a stirrer and a reflux condenser cooled with water, 7.4 g of 3,3′-dinitro-4,4′-di-2-furoylaminobiphenyl, 100 ml of N-methyl-2-pyrrolidone and 75 ml of ethyl alcohol were placed. After adding 40 ml of a saturated aqueous solution of ammonium chloride, 25.6 g of powder of indium metal was added to the prepared solution. The obtained mixture was stirred at 80° C. for 1 hour. After the reaction solution was cooled to the room temperature, the solid substance was removed by filtration. The filtrate was concentrated to about one half at a reduced pressure. To the concentrated filtrate, 300 ml of water was added and the formed solid substance was separated by filtration to obtain 2.9 g of a crude product. The crude product was purified in accordance with the silica gel column chromatography to obtain 1.5 g of 3,3′-diamino-4,4′-di-2-furoylaminobiphenyl. The yield of the isolated product was 23%. This product was recrystallized from N-methyl-2-pyrrolidone/ethyl acetate (the volume ratio: 25/75) and needle crystals having a decomposition temperature of 256 to 259° C. were obtained.
Reaction SMILES: [C:1]([O:5][C:6](=[O:20])[C@H:7]([CH2:16][CH2:17][CH2:18][NH2:19])[NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])([CH3:4])([CH3:3])[CH3:2].[N:21]#[C:22]Br.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.[Pd].CCOCC>[C:1]([O:5][C:6](=[O:20])[C@H:7]([CH2:16][CH2:17][CH2:18][NH:19][C:22]#[N:21])[NH:8][C:9]([O:11][C:12]([CH3:13])([CH3:14])[CH3:15])=[O:10])([CH3:4])([CH3:2])[CH3:3]
Reactant: N#CBr
Reactant: CC(C)(C)OC(=O)N[C@@H](CCCN)C(=O)OC(C)(C)C
Agent: [Pd]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOCC
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N[C@@H](CCCNC#N)C(=O)OC(C)(C)C
Temperature: 22 °C
Reaction time: 0.75 h
Yield: 67 %

Procedure:
To a solution of 6.1 g (14.44 mmol) N5-((Benzyloxy)carbonyl-N2-(tert-butoxycarbonyl-L-ornithine tert-butyl ester in 100 mL ethyl acetate was added 1.0 g 10% palladium on carbon. The suspension was shaken at 22° C. under 50 psi H2 for 45 minutes in a 500 mL Parr bottle. The catalyst was removed by filtration through celite. The resulting solution was concentrated to yield a crude oil. The oil was disolved into 50 mL of diethyl ether and added dropwise to a 0° C. stirred solution of 1.52 g (14.3 mmol) of cyanogen bromide in 30 mL ether. The solution was stirred for 2 h, poured into aqueous sodium bicarbonate, and extraced with ether. The ether solution was dried (magnesium sulfate), concentrated, and purified by silica gel chromatography (100 g, 230-400 mesh silica gel). Elution with a gradient of ethyl acetate in hexanes (30%-60%) gave 3.0 g (67% yield) N2-(tert-butoxycarbonyl)-N5-cyano-L-ornithine tert-butyl ester as an oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:23]=[CH:22][C:6]([O:7][C:8]2[CH:13]=[C:12]([CH3:14])[C:11]([C:15]3[N:16]=[C:17]([NH2:20])[S:18][CH:19]=3)=[C:10]([CH3:21])[CH:9]=2)=[CH:5][CH:4]=1.[C:24]([O-])(=[O:26])[CH3:25].[Na+].O>C(OC(=O)C)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([O:7][C:8]2[CH:9]=[C:10]([CH3:21])[C:11]([C:15]3[N:16]=[C:17]([NH:20][C:24](=[O:26])[CH3:25])[S:18][CH:19]=3)=[C:12]([CH3:14])[CH:13]=2)=[CH:22][CH:23]=1
Reactant: CC(=O)[O-]
Reactant: COc1ccc(Oc2cc(C)c(-c3csc(N)n3)c(C)c2)cc1
Agent: [Na+]
Solvent: CC(=O)OC(C)=O
Solvent: O
Product: COc1ccc(Oc2cc(C)c(-c3csc(NC(C)=O)n3)c(C)c2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 84.1 %

Procedure:
To a solution of 4-(4-(4-methoxyphenoxy)-2,6-dimethylphenyl)thiazol-2-amine (2-1, 500 mg, 1.5 mmol) in acetic anhydride (2.0 mL) was added sodium acetate (125.7 mg, 1.5 mmol). The reaction was stirred at room temperature for 1.0 h. The solution was added with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous MgSO4(s), and concentrated under reduced pressure to give N-{4-(4-(4-methoxyphenoxy)-2,6-dimethylphenyl)thiazol-2-yl}acetamide (2-2, 465 mg) as yellow oil in 82% yield: 1H NMR (500 MHz, DMSO-d6) δ 12.09 (s, 1H), 6.96-7.03 (m, 5 H), 6.64 (s, 2 H), 3.75 (s, 3 H), 2.15 (s, 3 H), 2.01 (s, 6 H). ESI-MS: m/z 368.9 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@H:9]([NH:20][C@H:21]([C:26]([O:28][CH3:29])=[O:27])[CH2:22][CH:23]([CH3:25])[CH3:24])[C:10]([NH:12][C:13]1C=CC=CC=1O)=[O:11].[C:30](N1C=CN=C1)(N1C=CN=C1)=S.[NH2+]1C2C=CC=CC=2N=N1.CNC>ClCCl.O1CCCC1.O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]([NH:20][C@H:21]([C:26]([O:28][CH3:29])=[O:27])[CH2:22][CH:23]([CH3:25])[CH3:24])[C:10]([N:12]([CH3:13])[CH3:30])=[O:11]
Reactant: COC(=O)[C@H](CC(C)C)N[C@@H](C(=O)Nc1ccccc1O)c1ccc(F)cc1F
Reactant: S=C(n1ccnc1)n1ccnc1
Agent: CNC
Agent: c1ccc2c(c1)N=N[NH2+]2
Solvent: O
Solvent: ClCCl
Solvent: C1CCOC1
Product: COC(=O)[C@H](CC(C)C)NC(C(=O)N(C)C)c1ccc(F)cc1F
Reaction time: 18 h
Yield: 58.5 %

Procedure:
A solution of methyl N-{(1R)-1-(2,4-difluorophenyl)-2-[(2-hydroxyphenyl)amino]-2-oxoethyl}-L-leucinate (203 mg) and 1,1′-thiocarbonyldiimidazole (100 mg) in dichloromethane (5 ml) was left to stand for 18 hours. Water (10□1) was added to the reaction mixture and this was then stirred rapidly for 30 minutes. After this, 1H-Benzotriazolium, 1-[bis(dimethylamino)methylene]-, tetrafluoroborate(1-), 3-oxide (TBTU, 321 mg) and a solution of dimethylamine in tetrahydrofuran (0.5 ml of 2M solution) were added. The reaction mixture was stirred for a further 18 hours and was then passed down an SPE (5 g, silica) eluting with a gradient (8:1 to 1:2 cyclohexane:ethyl acetate). The required fractions were combined and evaporated to furnish methyl N-[1-(2,4-difluorophenyl)-2-(dimethylamino)-2-oxoethyl]-L-leucinate (100 mg).
Reaction SMILES: CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[C:23]([SiH2:27][O:28][C:29]([CH3:40])([CH3:39])[C:30]1[CH:31]=[C:32]([CH:35]=[CH:36][C:37]=1[Cl:38])[CH2:33][NH2:34])([CH3:26])([CH3:25])[CH3:24].CCN(C(C)C)C(C)C.[F:50][C:51]([F:57])([F:56])[CH2:52][C:53](O)=[O:54]>C(Cl)Cl>[C:23]([SiH2:27][O:28][C:29]([CH3:40])([CH3:39])[C:30]1[CH:31]=[C:32]([CH:35]=[CH:36][C:37]=1[Cl:38])[CH2:33][NH:34][C:53](=[O:54])[CH2:52][C:51]([F:57])([F:56])[F:50])([CH3:26])([CH3:24])[CH3:25]
Reactant: O=C(O)CC(F)(F)F
Reactant: CC(C)(C)[SiH2]OC(C)(C)c1cc(CN)ccc1Cl
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)[SiH2]OC(C)(C)c1cc(CNC(=O)CC(F)(F)F)ccc1Cl
Temperature: 25 °C
Reaction time: 1 h
Yield: 64.9 %

Procedure:
TBTU (3.37 g, 10.5 mmol) was added to a sol. of 3-(tert-butyl-dimethyl-silanyloxymethyl)-4-chloro-benzylamine (2.00 g, 7.00 mmol), DIPEA (4.80 mL, 28.0 mmol) and 3,3,3-trifluoropropionic acid (0.927 mL, 10.5 mmol) in CH2Cl2 (70 mL). The mixture was stirred at rt for 1 h. CH2Cl2 (30 mL) was added, and the mixture was washed with aq. sat. NH4Cl (2×), aq. 1M NaOH (1×) and brine (1×). The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (EtOAc/heptane 40:60) yielded the title compound (1.80 g, 65%). LC-MS: tR=1.10 min; ES+: 396.15.
Reaction SMILES: C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[N:8]2[CH2:13][CH2:12][N:11]([C:14]([CH2:16][C:17]3[CH2:22][CH2:21][CH2:20][CH2:19][C:18]=3[N:23]3[C:28](=[O:29])[CH:27]=[CH:26][C:25]([C:30]4[C:31]([C:39]5[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=5)=[N:32][N:33]5[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=45)=[N:24]3)=[O:15])[CH2:10][CH2:9]2)C=CC=CC=1.C(O)=O.Cl.C(OCC)(=O)C>O>[N:11]1([C:14]([CH2:16][C:17]2[CH2:22][CH2:21][CH2:20][CH2:19][C:18]=2[N:23]2[C:28](=[O:29])[CH:27]=[CH:26][C:25]([C:30]3[C:31]([C:39]4[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=4)=[N:32][N:33]4[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=34)=[N:24]2)=[O:15])[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1
Reactant: O=C(CC1=C(n2nc(-c3c(-c4ccccc4)nn4ccccc34)ccc2=O)CCCC1)N1CCN(C(c2ccccc2)(c2ccccc2)c2ccccc2)CC1
Agent: Cl
Solvent: O
Solvent: O=CO
Solvent: CCOC(C)=O
Product: O=C(CC1=C(n2nc(-c3c(-c4ccccc4)nn4ccccc34)ccc2=O)CCCC1)N1CCNCC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 78 %

Procedure:
The mixture of 3-[2-{2-(4-triphenylmethylpiperazin-1-ylcarbonyl)methyl-1-cyclohexenyl}-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine (4.2 g), formic acid (10 ml) and concentrated hydrochloric acid (1.43 ml) was stirred for 2 hours at room temperature. The reaction mixture was poured into a mixture of ethyl acetate (200 ml) and water (100 ml). Aqueous layer was separated, and the pH was adjusted to pH 12.0 with 4N-aqueous sodium hydroxide solution, which was extracted with dichloromethane (300 ml and 150 ml). Organic phase was combined and dried over magnesium sulfate. Evaporation of the solvent gave a residue, which was chromatographed on silica gel eluting in turn with 5% and 10% methanol in dichloromethane. Fractions containing desired product were collected, and solvent was removed under reduced pressure to give solid, which was recrystallized from ethyl acetate to give 3-[2-{2-(piperazin-1-ylcarbonyl)methyl-1-cyclohexenyl}-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine (2.2 g).
Reaction SMILES: [C:1]([CH2:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])[CH2:13][CH:12]2[O:27][CH2:28][C:29]2[CH:30]=[CH:31][C:32]3[O:37][CH2:36][CH2:35][N:34]([CH2:38][CH2:39][CH2:40][O:41][CH3:42])[C:33]=3[CH:43]=2)=[CH:7][CH:6]=1)(O)=[O:2].[NH:44]1[C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH2:47][CH2:46][CH2:45]1.C(N(CC)CC)C>ClCCl.COC(C)(C)C>[N:44]1([C:1](=[O:2])[CH2:4][C:5]2[CH:6]=[CH:7][C:8]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)=[O:18])[CH2:13][CH:12]3[O:27][CH2:28][C:29]3[CH:30]=[CH:31][C:32]4[O:37][CH2:36][CH2:35][N:34]([CH2:38][CH2:39][CH2:40][O:41][CH3:42])[C:33]=4[CH:43]=3)=[CH:9][CH:10]=2)[C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH2:47][CH2:46][CH2:45]1
Reactant: c1ccc2c(c1)CCCN2
Reactant: COCCCN1CCOc2ccc(COC3CN(C(=O)OCc4ccccc4)CCC3c3ccc(CC(=O)O)cc3)cc21
Solvent: CCN(CC)CC
Solvent: COC(C)(C)C
Solvent: ClCCl
Product: COCCCN1CCOc2ccc(COC3CN(C(=O)OCc4ccccc4)CCC3c3ccc(CC(=O)N4CCCc5ccccc54)cc3)cc21
Temperature: 0 °C
Reaction time: 1.5 h

Procedure:
The solution of 0.151 g of benzyl 4-(4-carboxymethylphenyl)-3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate in 3 ml of dichloromethane is admixed with 0.0376 g of 1,2,3,4-tetrahydroquinoline and 0.101 ml of triethylamine, cooled to 0° C. and subsequently admixed with 0.231 g of N-propylphosphonous anhydride (cyclic trimer). The reaction mixture is stirred at 0° C. for another 1.5 hours, then diluted with 70 ml of tert-butyl methyl ether. The organic phase is washed with 15 ml of water and then 15 ml of brine, dried over sodium sulphate, filtered and concentrated by evaporation. The title compound is obtained as a yellowish oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.75 (EtOAc). Rt=5.62.
Reaction SMILES: [Cl-].[NH2:2][C:3]1[CH:8]=[C:7]([NH:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[C:6]([C:16]#[N:17])=[C:5]([Cl:18])[N+:4]=1[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24].[C:25]1([SH:31])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(N(CC)CC)C.O>C(O)C>[Cl-:18].[NH2:2][C:3]1[CH:8]=[C:7]([NH:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[C:6]([C:16]#[N:17])=[C:5]([S:31][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[N+:4]=1[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]
Reactant: CCCCCCNc1cc(N)[n+](CCCCCC)c(Cl)c1C#N
Reactant: Sc1ccccc1
Agent: [Cl-]
Solvent: CCO
Solvent: CCN(CC)CC
Solvent: O
Product: CCCCCCNc1cc(N)[n+](CCCCCC)c(Sc2ccccc2)c1C#N
Reaction time: 16 h
Yield: 51.9 %

Procedure:
3.7 gms (.01 ml) of 2-amino-6-chloro-5-cyano-1-n-hexyl-4-n-hexylamino pyridinium chloride (compound 11 - Table 1) was dissolved in ethanol and 1.1 gm (.01 mole) thiophenol and 1.0 gm (0.01 mole) of triethylamine added. The solution was left 16 hours at room temperature poured into iced water and 2.3 gms (50% yield) of 2-amino-5-cyano-1-n-hexyl-4-n-hexylamino-6-phenylmercapto pyridinium chloride (compound 78 - Table 5) filtered off (MPt 227° -228°C).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][C:4]2([O:11][C:10]3[C:12]4[C:17]([C:18](=[O:21])[C:19](=[O:20])[C:9]=3[S:8][CH2:7]2)=[CH:16][CH:15]=[CH:14][CH:13]=4)[CH2:3][CH2:2]1.[S:22]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[CH:24]=[C:23]1[C:31](Cl)=[O:32]>>[S:22]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[CH:24]=[C:23]1[C:31]([N:1]1[CH2:2][CH2:3][C:4]2([O:11][C:10]3[C:12]4[C:17]([C:18](=[O:21])[C:19](=[O:20])[C:9]=3[S:8][CH2:7]2)=[CH:16][CH:15]=[CH:14][CH:13]=4)[CH2:5][CH2:6]1)=[O:32]
Reactant: O=C1C(=O)c2ccccc2C2=C1SCC1(CCNCC1)O2
Reactant: O=C(Cl)c1cc2ccccc2s1
Product: O=C1C(=O)c2ccccc2C2=C1SCC1(CCN(C(=O)c3cc4ccccc4s3)CC1)O2

Procedure:
Compound 51 was synthesized using spiro[naphtho[1,2-b][1,4]oxathiine-2,4′-piperidine]-5,6-dione, 1-benzothiophene-2-carbonyl chloride and conditions outlined in procedure N. M.p.=110-112° C.; 300 MHz 1H NMR (DMSO-d6) δ 8.20 (m, 1H), 7.93 (m, 3H), 7.77 (m, 2H), 7.58 (t, 1H), 7.45 (m, 2H), 4.22 (brm, 2H), 3.41 (brm, 2H), 3.15 (s, 2H), 2.17 (m, 2H), 1.88 (m, 2H); LCMS: 462 [M+H].
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[C:10]1(=O)[CH2:15][CH2:14][CH2:13][C:12](=[O:16])[CH2:11]1>>[N:1]1([C:10]2[CH2:15][CH2:14][CH2:13][C:12](=[O:16])[CH:11]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1
Reactant: c1ccc2c(c1)CCN2
Reactant: O=C1CCCC(=O)C1
Product: O=C1C=C(N2CCc3ccccc32)CCC1
Yield: 75.7 %

Procedure:
A mixture of indoline (5.39 g) and cyclohexane-1,3-dione (5.07 g) was heated at ca. 150° for 7 h. After cooling, the mixture was purified by FCC eluting with ethyl acetate: methanol (10:1) to give a solid (7.30 g) which was recrystallised from ethyl acetate: ether (ca. 4:1) to give the title compound (5.08 g), m.p. 85°-86°.