Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([CH:8]=[CH:7][CH:6]=[C:4]([OH:5])[CH:3]=1)O.C[N+](CCCC)(CCCC)[CH2:11][CH2:12][CH2:13]C.[OH-].[Na+].[C:25]1([OH:31])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(Cl)(Cl)=O>O.C(N(CC)CC)C.C(Cl)Cl>[CH3:11][C:12]([C:28]1[CH:27]=[CH:26][C:25]([OH:31])=[CH:30][CH:29]=1)([C:8]1[CH:1]=[CH:3][C:4]([OH:5])=[CH:6][CH:7]=1)[CH3:13]
Reactant: CCCC[N+](C)(CCCC)CCCC
Reactant: Oc1ccccc1
Reactant: Oc1cccc(O)c1
Agent: O=C(Cl)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O
Solvent: CCN(CC)CC
Product: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1

Procedure:
Into a 500 ml Morton flask equipped with a mechanical stirrer, a reflux condenser, a nitrogen bypass, a pH probe and a phosgene dip tube was placed 6.88 g of resorcinol, 100 ml of methylene chloride, 20 ml of water and 0.5 ml of 75 wt % aqueous methyltributylammonium (MTBA). The pH was adjusted to and maintained at 7 with 25 wt % of NaOH as 29 g of a 35 wt % solution of diacid chlorides (DACS) in methylene chloride (delivers 50 mmol of 50/50 isophthaloyl chloride (IPC)/terephthaloyl chloride (TPC)) was added over 4 minutes. The pH was raised to 10 and 100 μl of triethylamine (TEA), 50 mg of water and 0.21 g of phenol were added. The pH was maintained at 10 and 4.0 g of phosgene was added at 0.5 g/min. The final pH was 10.1. The polymer solution was separated from the brine by centrifugation and washed 1 time with 1N HCl and 3 times with deionized water. The polymer was isolated by hot water crumbing in a blender and collected by filtration and washed with water and dried in a vacuum oven at 110° C. overnight.
Reaction SMILES: [CH2:1]([O:11][C:12]1[C:13]([C:22]([NH:24][O-:25])=[O:23])=[CH:14][C:15]2[C:20]([CH:21]=1)=CC=CC=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[Na+].C[O-].[Na+].C(#[N:32])C.C(OCC)(=O)C.O1[CH2:43][CH2:42][CH2:41][CH2:40]1>>[CH2:1]([O:11][C:12]1[CH:21]=[CH:20][CH:15]=[CH:14][C:13]=1[C:22]([NH:24][OH:25])=[O:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:40][CH2:41][CH2:42][CH3:43].[CH2:1]([O:11][C:12]1[CH:21]=[CH:20][CH:15]=[CH:14][C:13]=1[NH2:32])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:40][CH2:41][CH2:42][CH3:43]
Reactant: CC#N
Reactant: C1CCOC1
Reactant: CCCCCCCCCCOc1cc2ccccc2cc1C(=O)N[O-]
Agent: C[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Product: CCCCCCCCCCCCCCOc1ccccc1C(=O)NO
Product: CCCCCCCCCCCCCCOc1ccccc1N
Temperature: 60 °C
Reaction time: 1.5 h

Procedure:
2-Myristyloxybenzohydroxamic acid was synthesized according to the method provided in part (i) of Example 1. Thereafter, one gram of said compound was dissolved in 5 ml of tetrahydrofuran, and thereto were added 0.83 ml of sodium methylate (28 wt % methanol solution) and 20 ml of acetonitrile. The mixture was heated to 60° C. and kept there for 1.5 hours with stirring (the formation rate of the desired compound in this reaction system was found to be 100% by an analysis using high-speed liquid chromatography). The resulting solution was admixed with 50 ml of ethyl acetate, and washed once with 50 ml of saturated brine and then twice with water. The organic layer was separated from the aqueous layer, dried with Glauber's salt, and then concentrated. The residue was admixed with 5 ml of methanol, and cooled in an ice bath to precipitate white crystals. These white crystals were filtered off, washed with 0.5 ml of ice-cold methanol, and then dried. Thus, 400 mg of 2-myristyloxyaniline (Compound 3) was obtained in a 67% yield. The melting point thereof was 45.5°-46.5° C.
Reaction SMILES: [CH3:1][O:2][C:3]([NH:5][C@H:6]([CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)[C:7]([N:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[C:14]([OH:16])=O)=[O:8])=[O:4].[NH2:23][CH2:24][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][CH:34]=1)[C:31]([NH2:35])=[N:30][CH:29]=[CH:28]2.CN1CCOCC1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C)C=O>[CH3:1][O:2][C:3](=[O:4])[NH:5][C@H:6]([CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)[C:7]([N:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[C:14](=[O:16])[NH:23][CH2:24][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][CH:34]=1)[C:31]([NH2:35])=[N:30][CH:29]=[CH:28]2)=[O:8]
Reactant: NCc1ccc2c(N)nccc2c1
Reactant: COC(=O)N[C@@H](C(=O)N1CCC[C@H]1C(=O)O)C1CCCCC1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Product: COC(=O)N[C@@H](C(=O)N1CCC[C@H]1C(=O)NCc1ccc2c(N)nccc2c1)C1CCCCC1
Temperature: 25 °C
Reaction time: 3 h
Yield: 57.1 %

Procedure:
A mixture of 1-[(R)-methoxycarbonylamino-cyclohexyl-acetyl]-pyrrolidine-2-(S)-carboxylic acid (0.410 g), 6-aminomethyl-isoquinolin-1-ylamine (0.227 g), N-methyl morpholine (0.58 mL) and 0.423 g of 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) in 10 mL of dry N,N-dimethyl formamide was stirred for 3 h at ambient temperature. The mixture was concentrated and the remaining residue was purified by HPLC (RP-18, H2O/CH3OH 95/5→0/100) to give 0.350 g (58%) of the title compound as a white solid. (+)-APCI-MS: 468 (MH+).
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[S:3]([O:6]S(C(F)(F)F)(=O)=O)(=[O:5])=[O:4].[CH3:16][N:17]1[C:22]2=[C:23]3[C:28](=O)[CH2:27][CH2:26][NH:25][N:24]3[C:30]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[C:21]2[C:20](=[O:37])[N:19]([CH3:38])[C:18]1=[O:39].N1C(C)=CC=CC=1C>C(Cl)Cl>[CH3:16][N:17]1[C:18](=[O:39])[N:19]([CH3:38])[C:20](=[O:37])[C:21]2[C:22]1=[C:23]1[N:24]([C:30]=2[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[NH:25][CH2:26][CH:27]=[C:28]1[O:6][S:3]([C:2]([F:15])([F:14])[F:1])(=[O:5])=[O:4]
Reactant: Cn1c(=O)c2c(-c3ccccc3)n3c(c2n(C)c1=O)C(=O)CCN3
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: Cc1cccc(C)n1
Solvent: ClCCl
Product: Cn1c(=O)c2c(-c3ccccc3)n3c(c2n(C)c1=O)C(OS(=O)(=O)C(F)(F)F)=CCN3
Reaction time: 1.75 h

Procedure:
Trifluoromethanesulfonic anhydride (0.254 ml, 1.506 mmol) was added slowly to a solution of 1,3-dimethyl-5-phenyl-8,9-dihydropyrimido[4′,5′:3,4]pyrrolo[1,2-b]pyridazine-2,4,10(1H,3H,7H)-trione (step 4) (222 mg, 0.684 mmol) and 2,6-lutidine (commercial) (0.159 ml, 1.369 mmol) in DCM (10 ml) at 0° C. and the mixture stirred for 1.75 hours. The reaction mixture was quenched with sat. NaHCO3(aq) and extracted with DCM. The organic phase was passed through a hydrophobic frit and evaporated under reduced pressure. Purification of the residue by chromatography on silica, eluting with 20% EtOAc/hexane then 40% EtOAc/hexane afforded the title compound as a yellow solid.
Reaction SMILES: [CH3:1][NH:2][C:3]([CH2:5][CH:6]=[C:7]([CH2:11][CH:12]([CH3:14])[CH3:13])[C:8]([OH:10])=[O:9])=[O:4].[CH3:15][C:16](=[CH2:18])[CH3:17]>C(Cl)(Cl)Cl.S(=O)(=O)(O)O>[CH3:1][NH:2][C:3]([CH2:5][CH:6]=[C:7]([CH2:11][CH:12]([CH3:14])[CH3:13])[C:8]([O:10][C:16]([CH3:18])([CH3:17])[CH3:15])=[O:9])=[O:4]
Reactant: CNC(=O)CC=C(CC(C)C)C(=O)O
Reactant: C=C(C)C
Agent: O=S(=O)(O)O
Solvent: ClC(Cl)Cl
Product: CNC(=O)CC=C(CC(C)C)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 192 h
Yield: 81 %

Procedure:
A suspension of 4-methylaminocarbonyl-2-(2-methylpropyl)but-2-enoic acid (2.4 g) in chloroform (35 ml) was treated with an excess of isobutylene (30 ml) and concentrated sulphuric acid (3 drops) was added as catalyst. The mixture was stirred at room temperature in a sealed vessel for 8 days. The product was purified by silica gel chromatography [chloroformpentane (1:1) as eluant] to give the title compound (2.5 g, 81%), m.p. 35°-36° C. (pentane).
Reaction SMILES: [O:1]=C=NC1CC(C)(C)CC(C)(CN=C=O)C1.C[O:18][C:19]1[CH:24]=[CH:23][C:22]([OH:25])=C[CH:20]=1.[N-:26]=[C:27]=[O:28]>C([O-])(=O)CCCCCCCCCCC.C([O-])(=O)CCCCCCCCCCC.C([Sn+2]CCCC)CCC.O>[C:22]([OH:25])(=[O:1])[CH:23]=[CH2:24].[NH2:26][C:27]([O:18][CH2:19][CH3:20])=[O:28]
Reactant: COc1ccc(O)cc1
Reactant: CC1(C)CC(N=C=O)CC(C)(CN=C=O)C1
Reactant: [N-]=C=O
Agent: CCCCCCCCCCCC(=O)[O-]
Agent: CCCC[Sn+2]CCCC
Solvent: O
Product: C=CC(=O)O
Product: CCOC(N)=O

Procedure:
An amount of isophorone diisocyanate was added to a reaction vessel at room temperature. Heating jacket temperature was adjusted to 45° C. suspended in a room temperature water bath and stirred. When the reaction batch temperature was 45° C., dibutyltin dilaurate (DBTDL), as catalyst, and 4-methoxy phenol (MEHQ), as free-radical polymerization inhibitor, were also added. Pentaerytritol triacrylate was added incrementally to control exothermic activity. When the exothermic activity ceased, the result of Stage I was added and batch temperature was adjusted to 60° C. The batch was kept at 60° C. until no free isocyanate was detected by FTIR. Reaction scheme is given below. Viscosity of the product was 13,000 cP at 25° C. and it readily mixes with water. When the product was diluted with equal amount (by weight) of water viscosity was 50 cP at 25° C.
Reaction SMILES: [H-].[Na+].[C:3]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:4][C:5]([O-:7])=[O:6].[Br:12][C:13]1[CH:14]=[C:15]([N+:20]([O-:22])=[O:21])[C:16](Cl)=[N:17][CH:18]=1.[CH3:23][C:24](O)=O>CN(C=O)C>[CH2:10]([O:9][C:3](=[O:8])[CH:4]([C:16]1[C:15]([N+:20]([O-:22])=[O:21])=[CH:14][C:13]([Br:12])=[CH:18][N:17]=1)[C:5]([O:7][CH2:23][CH3:24])=[O:6])[CH3:11]
Reactant: O=[N+]([O-])c1cc(Br)cnc1Cl
Reactant: CCOC(=O)CC(=O)[O-]
Reactant: CC(=O)O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)C(C(=O)OCC)c1ncc(Br)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 99 %

Procedure:
To a suspension of NaH (60% in mineral oil, 27.9 g, 0.69 mol) in DMF (300 mL) at 5-10° C. was slowly added ethyl malonate (125 mL, 0.69 mol) over 30 min. The mixture was allowed to stir for 20 min at rt, during which time the suspension became a solution. A solution of 5-bromo-2-chloro-3-nitropyridine (75 g, 0.32 mol) in DMF (75 mL) was added slowly at 5-10° C. The resulting dark red mixture was allowed to stir at 40° C. for 2 h. The reaction mixture was then poured into 1M AcOH (0.75 L) and extracted with DCM (3×250 mL). The organic solutions were combined, washed with water and brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography to give diethyl(5-bromo-3-nitropyridin-2-yl)malonate (260 g, 99%) as a yellow oil.
Reaction SMILES: [CH3:1][N:2]([CH:4]=[N:5][S:6]([CH2:9][CH2:10][C:11]([CH3:15])([CH3:14])[CH2:12]I)(=[O:8])=[O:7])[CH3:3].[C-:16]#[N:17].[K+].CS(C)=O>O.C1OCCOCCOCCOCCOCCOC1>[C:16]([CH2:12][C:11]([CH3:15])([CH3:14])[CH2:10][CH2:9][S:6]([N:5]=[CH:4][N:2]([CH3:3])[CH3:1])(=[O:8])=[O:7])#[N:17]
Reactant: [C-]#N
Reactant: CN(C)C=NS(=O)(=O)CCC(C)(C)CI
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: CN(C)C=NS(=O)(=O)CCC(C)(C)CC#N
Temperature: 100 °C
Reaction time: 14 h
Yield: 84.7 %

Procedure:
A mixture of 1.85 g of 4-(N,N-dimethylaminomethylene)aminosulfonyl-1-iodo-2,2-dimethylbutane, 0.49 g of potassium cyanide, 0.06 g of 18-crown-6 and 30 ml of dimethyl sulfoxide was stirred at 100° C. for 14 hours. After cooling, the reaction mixture was diluted with 100 ml of water and extracted with ethyl acetate. The extract was washed with water and dried (MgSO4) and the solvent was distilled off. The residue was subjected to silica gel (70 g) column chromatography and elution was carried out with ethyl acetate-hexane (9:1). The fractions containing the objective compound were pooled and concentrated and the residue was recrystallized from ethyl ether to provide 1.11 g of the title compound. m.p. 53°-54° C.
Reaction SMILES: [O:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][C:2]1=[O:11].[CH3:12][NH:13][CH3:14]>C1COCC1>[OH:1][C:10]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:4][CH2:3][C:2]([N:13]([CH3:14])[CH3:12])=[O:11]
Reactant: O=C1CCc2ccccc2O1
Reactant: CNC
Solvent: C1CCOC1
Product: CN(C)C(=O)CCc1ccccc1O
Temperature: 25 °C
Reaction time: 5 h

Procedure:
A solution of chroman-2-one (444 mg) in THF (1 mL) was treated with dimethylamine (7.5 mL) and stirred at room temperature for 5 hours. The solution was concentrated. The concentrate was filtered through a small pad of silica gel.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8]OS(C)(=O)=O)=[N:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[O:20]1[C:24]2([CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)[CH2:23][NH:22][C:21]1=[O:30]>C(#N)C.ClCCl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][N:22]2[CH2:23][C:24]3([CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]3)[O:20][C:21]2=[O:30])=[N:6][CH:7]=1
Reactant: CS(=O)(=O)OCc1ccc(Br)cn1
Reactant: O=C1NCC2(CCCCC2)O1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: ClCCl
Solvent: CC#N
Product: O=C1OC2(CCCCC2)CN1Cc1ccc(Br)cn1
Temperature: 70 °C
Yield: 57.8 %

Procedure:
Methanesulfonic acid 5-bromo-pyridin-2-ylmethyl ester (85 mg, 0.319 mmol), cesium carbonate (312 mg, 0.957 mmol) and 1-oxa-3-aza-spiro[4.5]decan-2-one (49.5 mg, 0.319 mmol) were mixed in acetonitrile (2 mL). The reaction mixture was heated at 70° C. for 5 hours and then diluted with dichloromethane (8 mL). The mixture was washed with water (3 mL) and brine (3 mL). The combined organic phase was dried over sodium sulfate and concentrated. The residue was purified on silica gel eluting with 10 to 20% ethyl acetate in hexanes to give the product as an off-white solid (60 mg, 58%). 1H NMR (300 MHz, CDCl3): δ 8.6 (d, 1H), 7.81 (dd, 1H), 7.23 (d, 1H), 4.49 (s, 2H), 3.27 (s, 2H), 1.79 (m, 4H), 1.47 (m, 6H).
Reaction SMILES: [CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[C:18]([C:23]([O:25]C(C)(C)C)=[O:24])=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:13][CH:12]=2)[C:8]2[C:30]([O:35][CH2:36][CH2:37][N:38]3[C:42]4[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=4[N:40]=[CH:39]3)=[CH:31][CH:32]=[C:33]([CH3:34])[C:7]=2[N:6]=1)[CH2:2][CH2:3][CH3:4].FC(F)(F)C(O)=O>C(Cl)Cl>[CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]3[C:18]([C:23]([OH:25])=[O:24])=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:15][CH:16]=2)[C:8]2[C:30]([O:35][CH2:36][CH2:37][N:38]3[C:42]4[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=4[N:40]=[CH:39]3)=[CH:31][CH:32]=[C:33]([CH3:34])[C:7]=2[N:6]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc2c(C)ccc(OCCn3cnc4ccccc43)c2n1Cc1ccc(-c2ccccc2C(=O)OC(C)(C)C)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCCCc1nc2c(C)ccc(OCCn3cnc4ccccc43)c2n1Cc1ccc(-c2ccccc2C(=O)O)cc1

Procedure:
Prepared analogously to Example 1 from tert.-butyl 4'-[[2-n-butyl-7-[2-(benzimidazol-1-yl)-ethoxy]-4-methyl-benzimidazol-1-yl]-methyl]-biphenyl-2-carboxylate and trifluoroacetic acid in methylene chloride.
Reaction SMILES: [CH3:1][CH:2]([CH3:12])[CH:3]([NH:5][C:6](=[O:11])[CH2:7][C:8](=[O:10])[CH3:9])[CH3:4].CO[CH:15](OC)[N:16]([CH3:18])[CH3:17]>CN(C)C=O>[CH3:15][N:16]([CH:18]=[C:7]([C:8](=[O:10])[CH3:9])[C:6]([NH:5][CH:3]([CH:2]([CH3:12])[CH3:1])[CH3:4])=[O:11])[CH3:17]
Reactant: COC(OC)N(C)C
Reactant: CC(=O)CC(=O)NC(C)C(C)C
Solvent: CN(C)C=O
Product: CC(=O)C(=CN(C)C)C(=O)NC(C)C(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 95.3 %

Procedure:
To a solution of N-(3-methylbutan-2-yl)-3-oxobutanamide obtained in Step A (500 mg) in N,N-dimethylformamide (6.0 mL) was added dropwise 1,1-dimethoxy-N,N-dimethylmethanamine (696 mg) over 5 min at room temperature, and the reaction mixture was stirred overnight at room temperature. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (methanol/ethyl acetate) to give the title compound (630 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8](F)(F)F)[CH:5]=[CH:6][CH:7]=1.[Al+3].[Cl-:13].[Cl-:14].[Cl-].[F:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]([C:20]2[CH:21]=[CH:22][C:17]([F:16])=[CH:18][CH:19]=2)([Cl:14])[Cl:13])[CH:5]=[CH:6][CH:7]=1
Reactant: Fc1ccccc1
Reactant: [Cl-]
Reactant: FC(F)(F)c1cccc(Cl)c1
Agent: [Al+3]
Product: Fc1ccc(C(Cl)(Cl)c2cccc(Cl)c2)cc1

Procedure:
From 3-chlorobenzotrifluoride (180 mg, 1 mmol), AlCl3 (400 mg, 3 mmol) and fluorobenzene (96 mg, 1 mmol), light yellow oil (384 mg, 132% crude).
Reaction SMILES: C(OP([CH2:9][C:10]1[CH:15]=[C:14]([O:16][CH3:17])[C:13]([CH:18]([CH3:20])[CH3:19])=[C:12]([O:21][CH3:22])[CH:11]=1)(=O)OCC)C.[CH:23](=O)[C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=1>>[CH3:17][O:16][C:14]1[CH:15]=[C:10]([CH:9]=[CH:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)[CH:11]=[C:12]([O:21][CH3:22])[C:13]=1[CH:18]([CH3:19])[CH3:20]
Reactant: COc1ccc(C=O)cc1
Reactant: CCOP(=O)(Cc1cc(OC)c(C(C)C)c(OC)c1)OCC
Product: COc1ccc(C=Cc2cc(OC)c(C(C)C)c(OC)c2)cc1
Yield: 63 %

Procedure:
This material was prepared from diethyl(3,5-dimethoxy-4-i-propylbenzyl)phosphonate and 4-anisaldehyde in 63% yield as the same procedure as described in example 5(b). 1H NMR (CDCl3, ppm): δ 1.31 (d, J=7.1 Hz, 6H), 3.51-3.74 (m, 1H), 3.86 (s, 3H), 3.91 (s, 6H), 6.71 (s, 2H), 6.84-7.09 (m, 4H), 7.39-7.60 (m, 2H).
Reaction SMILES: [CH2:1]([C:4]12[CH2:10][CH:7]([CH:8]=[CH:9]1)[CH:6]1[C:11]([O:13][C:14](=[O:15])[CH:5]21)=[O:12])[CH:2]=[CH2:3].[CH2:16]([NH2:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[CH2:16]([N:23]=[C:14]([CH:5]1[CH:6]([C:11]([OH:13])=[O:12])[CH:7]2[CH2:10][C:4]1([CH2:1][CH:2]=[CH2:3])[CH:9]=[CH:8]2)[OH:15])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: NCc1ccccc1
Reactant: C=CCC12C=CC(C1)C1C(=O)OC(=O)C12
Product: C=CCC12C=CC(C1)C(C(=O)O)C2C(O)=NCc1ccccc1

Procedure:
102 g of allyl-bicyclo[2.2.1]-hept-5-ene-2,3-dicarboxylic acid anhydride and 85.6 g of benzylamine are boiled under reflux for 2 hours. Water and excess benzylamine are then distilled off (39 ml at 105° C. under 4,132 Pa).
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13](=[O:22])[N:14]([CH2:18][C:19]([OH:21])=O)[CH:15]=[CH:16][CH:17]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[CH2:64]([NH2:69])[CH2:65][CH:66]([CH3:68])[CH3:67]>CN(C=O)C>[CH2:64]([NH:69][C:19](=[O:21])[CH2:18][N:14]1[CH:15]=[CH:16][CH:17]=[C:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:13]1=[O:22])[CH2:65][CH:66]([CH3:68])[CH3:67]
Reactant: CC(C)CCN
Reactant: O=C(O)Cn1cccc(NC(=O)OCc2ccccc2)c1=O
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(C)CCNC(=O)Cn1cccc(NC(=O)OCc2ccccc2)c1=O
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
A mixture of 900 mg of 2-(3-(benzyloxycarbonylamino)-2-oxopyridin-1(2H)-yl)acetic acid (˜2.32 mmol), 744 mg of TBTU (2.32 mmol), 313 mg of HOBt (2.32 mmol) is dissolved in 25 mL of DMF. By addition of 985 μL of DIPEA (5.79 mmol, 2.5 eq) a pH value is adjusted to ˜9. 539 μL of isopentylamine (4.63 mmol) is added and the mixture is stirred at RT for 2.5 h. The solvent is removed in vacuo and the obtained residue is taken up in 100 mL of DCM and subsequently washed with 10% citric acid (3×75 ml), saturated NaHCO3 solution (3×75 ml) and brine (75 mL). The organic phase is dried over Na2SO4, filtered and concentrated in vacuo in dryness. Brown solid is obtained and it is suitable for further processing without purification.
Reaction SMILES: C(OCC1C[CH2:34][N:9]2[C:10]3[C:15]([C:16]([C:17]4[C:18](=[O:33])[O:19][C:20](=O)[C:21]=4[C:22]4[C:30]5[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=5)[N:24]([CH3:31])[CH:23]=4)=[C:8]2C1)=[CH:14][CH:13]=[CH:12][CH:11]=3)(=O)C.[NH3:36]>CN(C)C=O>[OH:19][CH2:18][CH:17]1[CH2:21][CH2:34][N:9]2[C:10]3[C:15]([C:16]([C:17]4[C:18](=[O:33])[NH:36][C:20](=[O:19])[C:21]=4[C:22]4[C:30]5[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=5)[N:24]([CH3:31])[CH:23]=4)=[C:8]2[CH2:16]1)=[CH:14][CH:13]=[CH:12][CH:11]=3
Reactant: N
Reactant: CC(=O)OCC1CCn2c(c(C3=C(c4cn(C)c5ccccc45)C(=O)OC3=O)c3ccccc32)C1
Solvent: CN(C)C=O
Product: Cn1cc(C2=C(c3c4n(c5ccccc35)CCC(CO)C4)C(=O)NC2=O)c2ccccc21

Procedure:
A solution of 2.90 g of 3-[8-(acetoxymethyl)-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]-4-(1-methyl-3-indolyl)furan-2,5-dione in 30 ml of dimethylformamide and 23 ml of 33% aqueous ammonia was heated to 140° C. for 7 hours. The mixture was extracted with ethyl acetate and the combined organic extracts were washed with water, dried over anhydrous sodium sulfate and evaporated to dryness. Crystallization of the residue from ethyl acetate gave 1.87 g of 3-[6,7,8,9-tetrahydro-8-(hydroxymethyl)pyrido-[1,2-a]indol-10-yl]-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione in the form of a red solid of melting point 262°-263° C.
Reaction SMILES: [O-]CC.[Na+].[CH3:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]#[CH:14])=[CH:9][CH:8]=1.C1(C)C=CC=CC=1.Br[C:23]1[S:24][C:25]([C:28]#[N:29])=[CH:26][CH:27]=1>O>[CH3:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]#[C:14][C:23]2[S:24][C:25]([C:28]#[N:29])=[CH:26][CH:27]=2)=[CH:9][CH:8]=1
Reactant: N#Cc1ccc(Br)s1
Reactant: C#Cc1ccc(OC)cc1
Agent: CC[O-]
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1
Product: COc1ccc(C#Cc2ccc(C#N)s2)cc1
Reaction time: 2 h
Yield: 33.7 %

Procedure:
A mixture of sodium ethoxide (0.7 g), 1-(4-methoxyphenyl)acetylene (0.5 g), and toluene (40 cm3) is stirred for 2 h, 2-bromo-5-cyanothiophene (0.7 g), is added and the resultant mixture heated under reflux for 3 h. The reaction mixture is poured into water (500 cm3) and the organic layer separated off. The aqueous layer is then extracted with toluene (2×50 cm3). The combined organic layers are washed with water (2×200 cm3), dried (MgSO4), filtered and then evaporated down. The residue is purified by column chromatography on silica gel using a 95:5 hexane/ethyl acetate mixture as eluent and recrystallisation from ethanol to yield 0.3 g of 1-(4-methoxyphenyl)-2-(2-cyanothiophen-5-yl)acetylene.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][CH3:11])[CH:3]=1.[Br:12][CH2:13][CH2:14][CH2:15][CH2:16]Br>>[Br:12][CH2:13][CH2:14][CH2:15][CH2:16][O:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][CH3:11])[CH:3]=1
Reactant: BrCCCCBr
Reactant: COc1cc(O)ccc1C#N
Product: COc1cc(OCCCCBr)ccc1C#N

Procedure:
The procedure is as for Example 53, Step A, using as substrate 4-hydroxy-2-methoxy-benzonitrile and 1,4-dibromobutane.
Reaction SMILES: [F:1][P-:2]([F:7])([F:6])([F:5])([F:4])[F:3].[CH:8]1[C:17]2[CH:16]=[C:15]3[CH:18]=[CH:19][CH:20]=[CH:21][C:14]3=[CH:13][N+:12]=2[CH:11]=[CH:10][CH:9]=1.F[P-](F)(F)(F)(F)F.C1C2CC3C=CC=CC=3C[N+]=2C=CC=1>[N+](C)([O-])=O.C(O)(C)C.C(Cl)Cl>[F:1][P-:2]([F:7])([F:6])([F:5])([F:4])[F:3].[CH2:8]1[C:17]2[CH:16]=[C:15]3[CH:18]=[CH:19][CH:20]=[CH:21][C:14]3=[CH:13][N+:12]=2[CH:11]=[CH:10][CH2:9]1
Reactant: c1ccc2c[n+]3ccccc3cc2c1
Agent: F[P-](F)(F)(F)(F)F
Agent: c1ccc2c(c1)Cc1cccc[n+]1C2
Solvent: CC(C)O
Solvent: C[N+](=O)[O-]
Solvent: ClCCl
Product: C1=C[n+]2cc3ccccc3cc2CC1

Procedure:
A mixture of 6 g (0.0196 mol) of benzo[b]quinolizinium hexafluorophosphate and 5.12 g (0.023 mol) of 4-(3-furyl)-6,7-dihydrothianaphthene in 100 mL of nitromethane was heated to reflux for 14 h, cooled, and concentrated in vacuo. The residue was dissolved in ethyl acetate (200 mL), filtered, and the filtrate was concentrated in vacuo, the residue was dissolved in ether, and the ether solution was cooled to yield 11 g of 6,11[5',']-4'-(3-furyl)-4',5',6',7'-tetrahydrothianaphthyl]6,11-dihydrobenzo[b]quinolizinium hexafluorophosphate as a gray solid, (1:1.03 mixture of isomers). The gray solid, product was dissolved in 500 mL of isopropanol/methylene chloride (3:2) on a steam-bath while distilling 150 mL of methylene chloride and cooled to afford 6,11[[5',4']-4'-(3-furyl)-4',5',6',7'-tetrahydrothianaphthyl]6,11]-dihydrobenzo[b]quinolizinium hexafluorophosphate, (Formula I: R1 =R2 =R3 =R7 =H; ##STR56## R5 =3-furyl; X- =PF6- ; and Formula I: R1 =R2 =R4 =R7 =H; ##STR57## R6 =3-furyl; X-=PF6-), as a tan solid (1:1 mixture of isomers).