Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][N:15]=[CH:14]3)=[N:8][CH:9]=1)([O-:3])=[O:2].[H-].[Na+].[CH3:22]I>CN(C=O)C.O>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([CH3:22])[N:15]=[CH:14]3)=[N:8][CH:9]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccc(Oc2ccc3[nH]ncc3c2)nc1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cn1ncc2cc(Oc3ccc([N+](=O)[O-])cn3)ccc21
Reaction time: 3.5 h

Procedure:
To a solution of 5-(5-Nitro-pyridin-2-yloxy)-1H-indazole (1.0 g, 3.9 mmol) in 15 mL of DMF is added sodium hydride (3.9 mmol) and methyl iodide (20 mmol). The resulting mixture is stirred at room temperature to 50° C. for 1-6 hours. The mixture is diluted with water, extracted 3× with ethyl acetate, and the combined organic layers are dried over sodium sulfate, filtered and concentrated in vacuo. Purification by column chromatography eluting with ethyl acetate-hexanes, affords 5-(5-Nitro-pyridin-2-yloxy)-1-methyl-1H-indazole.
Reaction SMILES: Br[CH2:2][C:3]1[CH:4]=[C:5]([C:17]([NH:19][CH2:20][C:21]2[C:22](=[O:29])[NH:23][C:24]([CH3:28])=[CH:25][C:26]=2[CH3:27])=[O:18])[C:6]2[CH:7]=[N:8][N:9]([CH:12]3[CH2:16][CH2:15][CH2:14][CH2:13]3)[C:10]=2[CH:11]=1>CO.[Pd]>[CH:12]1([N:9]2[C:10]3[CH:11]=[C:3]([CH3:2])[CH:4]=[C:5]([C:17]([NH:19][CH2:20][C:21]4[C:22](=[O:29])[NH:23][C:24]([CH3:28])=[CH:25][C:26]=4[CH3:27])=[O:18])[C:6]=3[CH:7]=[N:8]2)[CH2:13][CH2:14][CH2:15][CH2:16]1
Reactant: Cc1cc(C)c(CNC(=O)c2cc(CBr)cc3c2cnn3C2CCCC2)c(=O)[nH]1
Agent: [Pd]
Solvent: CO
Product: Cc1cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c2cnn(C3CCCC3)c2c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
6-(bromomethyl)-1-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydro pyridine-3-yl)methyl)-1H-indazole-4-carboxamide (0.05 g, 0.13 mmol) was dissolved in methanol (2 mL) and Pd—C(10%, 0.01 g) was added to it. The resulting reaction mixture was stirred at room temperature for 1 h. On completion, the reaction mixture was filtered and concentrated to obtain solid compound which was washed with ether and pentane affording pure target compound (0.045 g, 91.89%). LCMS: 379.30 (M+1)+; HPLC: 98.15% (@ 254 nm) (Rt; 6.603); 1H NMR (CD3OD, 400 MHz) δ 8.28 (s, 1H), 7.63 (s, 1H), 7.48 (s, 1H), 6.70 (s, 1H), 5.12 (m, 1H), 4.61 (s, 2H), 2.56 (s, 3H), 2.55 (s, 3H), 2.42 (s, 3H), 2.19-2.14 (m, 2H), 2.12-2.04 (m, 2H), 2.00-1.92 (m, 2H), 1.82-1.75 (m, 2H).
Reaction SMILES: [CH3:1][C:2]1([C:7]23[CH2:14][CH:13]4[CH2:15][C:9]([CH2:16][OH:17])([CH2:10][CH:11]2[CH2:12]4)[CH2:8]3)[O:6][CH2:5][CH2:4][O:3]1.C(N(CC)CC)C.[CH3:25][S:26](Cl)(=[O:28])=[O:27]>C1COCC1.CN(C1C=CN=CC=1)C.O>[CH3:25][S:26]([O:17][CH2:16][C:9]12[CH2:15][CH:13]3[CH2:12][CH:11]([CH2:10]1)[C:7]([C:2]1([CH3:1])[O:3][CH2:4][CH2:5][O:6]1)([CH2:14]3)[CH2:8]2)(=[O:28])=[O:27]
Reactant: CC1(C23CC4CC2CC(CO)(C4)C3)OCCO1
Reactant: CS(=O)(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: C1CCOC1
Solvent: O
Solvent: CCN(CC)CC
Product: CC1(C23CC4CC2CC(COS(C)(=O)=O)(C4)C3)OCCO1
Reaction time: 0.5 h
Yield: 89.6 %

Procedure:
To a solution of [3-(2-Methyl-1,3-dioxolan-2-yl)tricyclo[3.3.1.03,7]non-1-yl]methanol (2.0 g, 8.47 mmol) obtained in step IV, in THF (35 mL) at ice bath temperature, was sequentially added triethylamine (3.5 mL, 25.4 mmol), DMAP (52 mg, 0.42 mmol), and methanesulfonyl chloride (0.97 mL, 12.7 mmol). After stirring the reaction mixture at the same temperature for 0.5 h, it was diluted with water and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by column chromatography to obtain title compound [3-(2-Methyl-1,3-dioxolan-2-yl) tricyclo[3.3.1.03,7]non-1-yl]methyl methane sulfonate (2.4 g) in 90% yield as viscous liquid. m/z (M+1) 317. IR cm−1 2954, 1461, 1356, 1216, 1174, 1048, 756. 1H NMR (CDCl3) 300 MHz δ 4.15-3.90 (m, 4H), 3.00 (s 3H), 2.44-2.36 (m 2H), 1.89-1.79 (m, 2H), 1.78-1.42 (m, 8H), 1.29 (s, 3H). 13C NMR (CDCl3) 75 MHz δ 112.1, 76.3, 64.95, 64.9, 57.3, 46.6, 45.3, 44.9, 44.5, 42.9, 39.8, 36.9, 36.7, 36.3, 20.
Reaction SMILES: [CH2:1]([NH:3][C:4]([NH:6][C:7]1[S:11][C:10]2[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=2[C:8]=1[C:16]([N:18]1[CH2:23][CH2:22][C:21](=O)[CH2:20][CH2:19]1)=[O:17])=[O:5])[CH3:2].[NH4+:25].[Cl-].[C-:27]#[N:28].[K+]>CO>[NH2:25][C:21]1([C:27]#[N:28])[CH2:20][CH2:19][N:18]([C:16]([C:8]2[C:9]3[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=3[S:11][C:7]=2[NH:6][C:4]([NH:3][CH2:1][CH3:2])=[O:5])=[O:17])[CH2:23][CH2:22]1
Reactant: [C-]#N
Reactant: [NH4+]
Reactant: CCNC(=O)Nc1sc2ccccc2c1C(=O)N1CCC(=O)CC1
Agent: [Cl-]
Agent: [K+]
Solvent: CO
Product: CCNC(=O)Nc1sc2ccccc2c1C(=O)N1CCC(N)(C#N)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 79 %

Procedure:
A solution of 6B (1.0 equivalent) in MeOH (0.06M), was slowly added NH4Cl (1.2 equivalents) and 30% aq. NH3OH (0.06M) and stirred at room temperature for 30 minutes. The mixture was cooled at 0° C., and KCN was added in portions. After 12 hrs, 80% of MeOH was removed under reduced pressure, and then replaced MeOH with diethyl ether at 0° C. Filtered crystallized solid and washed crystals with cold diethyl ether twice to afford the 1-(3-(4-amino-4-cyanopiperidine-1-carbonyl)benzo[b]thiophen-2-yl)-3-ethylurea (6, 79%). Two rotamers observed (ratio 1:1).
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:7]=1[C:8]([OH:10])=O)[CH2:2][CH2:3][CH3:4].[CH3:19][NH:20][O:21][CH3:22].CN1CCOCC1.C[N+]1(C2N=C(OC)N=C(OC)N=2)CCOCC1.[Cl-]>CCOC(C)=O>[CH2:1]([O:5][C:6]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:7]=1[C:8]([N:20]([O:21][CH3:22])[CH3:19])=[O:10])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOc1cc(C(F)(F)F)ccc1C(=O)O
Reactant: CNOC
Agent: COc1nc(OC)nc([N+]2(C)CCOCC2)n1
Agent: [Cl-]
Solvent: CN1CCOCC1
Solvent: CCOC(C)=O
Product: CCCCOc1cc(C(F)(F)F)ccc1C(=O)N(C)OC
Yield: 103.1 %

Procedure:
2-Butoxy-4-trifluoromethyl-benzoic acid (687 mg) was reacted with N,O-dimethylhydroxy amine (331 mg), NMM (0.65 ml) and DMTMM (911 mg) as described above to yield the title compound (825 mg) after column chromatography (Hex/EtOAc=7.5/1).
Reaction SMILES: Cl[CH:2]1[N:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]1[CH:17]=[O:18].[NH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1>>[C:11]1([N:10]2[C:5]3=[N:6][CH:7]=[CH:8][CH:9]=[C:4]3[CH:3]([CH:17]=[O:18])[CH:2]2[N:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: O=CC1c2cccnc2N(c2ccccc2)C1Cl
Reactant: C1CNCCN1
Product: O=CC1c2cccnc2N(c2ccccc2)C1N1CCNCC1
Yield: 63 %

Procedure:
2-Chloro-1-phenyl-1,3-dihydropyrrolo[2,3-b]pyridine-3-carboxaldehyde is reacted with piperazine as described in Example 2 to give 1-phenyl-2-(piperazin-1-yl)-1,3-dihydropyrrolo[2,3-b]pyridine-3-carboxaldehyde (63% yield).
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][N:7]=1.C(N(CC)CC)C.C1(C)C=CC=CC=1.[CH3:30][S:31](Cl)(=[O:33])=[O:32]>O>[CH3:30][S:31]([O:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:13])[F:14])=[CH:8][N:7]=1)(=[O:33])=[O:32]
Reactant: CS(=O)(=O)Cl
Reactant: OCCCOc1ccc(C(F)(F)F)cn1
Solvent: O
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCCCOc1ccc(C(F)(F)F)cn1
Reaction time: 1.5 h
Yield: 117.4 %

Procedure:
A mixture of 4.0 g of 2-(3-hydroxypropyloxy)-5-trifluoromethylpyridine, 3.4 ml of triethylamine and 25 ml of toluene was vigorously stirred under a nitrogen stream, while cooling in chilled water bath to 5° C. Then, 1.63 g of methanesulfonyl chloride was added dropwise to this mixture at such a rate that the reaction temperature did not exceed 10° C., and the chilled water bath was removed. After further stirring continued at room temperature for 1.5 hours, 250 ml of water was added thereto, and the mixture was vigorously stirred for further 30 minutes, followed by phase separation. The toluene layer was washed once with water, dried with magnesium sulfate, and concentrated, which afforded 5 g of 2-(3-methanesulfonyloxypropyloxy)-5-trifluoromethylpyridine as an oily product (92% yield).
Reaction SMILES: Cl[C:2]1[C:6]([C:7]2[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][C:8]=2[Cl:14])=[N:5][S:4][N:3]=1.[NH3:15]>CO.[Cu]>[NH2:15][C:2]1[C:6]([C:7]2[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][C:8]=2[Cl:14])=[N:5][S:4][N:3]=1
Reactant: Clc1cccc(Cl)c1-c1nsnc1Cl
Reactant: N
Agent: [Cu]
Solvent: CO
Product: Nc1nsnc1-c1c(Cl)cccc1Cl
Temperature: 120 °C
Reaction time: 24 h

Procedure:
A solution in methanol containing 5.31 g of 3-chloro-4-(2,6-dichlorophenyl)-1,2,5-thiadiazole, 1.91 g of copper powder and 1.97 g of cuprous chloride saturated with ammonia gas was placed in a stainless steel vessel. After sealing the vessel, the solution was stirred at 120° C. for 24 hours. After allowing the mixture to cool, insoluble materials were removed by filtration. The filtrate was concentrated and the residue was purified by silica gel column chromatography to obtain 2.19 g of 3-amino-4-(2,6-dichlorophenyl)-1,2,5-thiadiazole.
Reaction SMILES: Br[C:2]1[S:3][CH:4]=[C:5]([C:7]([NH:9][C:10]2[CH:11]=[N:12][N:13]([CH3:31])[C:14]=2[C@H:15]2[O:21][CH2:20][C@@H:19]([F:22])[C@H:18]([NH:23]C(=O)OC(C)(C)C)[CH2:17][CH2:16]2)=[O:8])[N:6]=1.[CH3:32][N:33]1[C:37]([CH3:38])=[C:36](B2OC(C)(C)C(C)(C)O2)[CH:35]=[N:34]1>>[NH2:23][C@H:18]1[C@H:19]([F:22])[CH2:20][O:21][C@H:15]([C:14]2[N:13]([CH3:31])[N:12]=[CH:11][C:10]=2[NH:9][C:7]([C:5]2[N:6]=[C:2]([C:36]3[CH:35]=[N:34][N:33]([CH3:32])[C:37]=3[CH3:38])[S:3][CH:4]=2)=[O:8])[CH2:16][CH2:17]1
Reactant: Cc1c(B2OC(C)(C)C(C)(C)O2)cnn1C
Reactant: Cn1ncc(NC(=O)c2csc(Br)n2)c1[C@@H]1CC[C@@H](NC(=O)OC(C)(C)C)[C@H](F)CO1
Product: Cc1c(-c2nc(C(=O)Nc3cnn(C)c3[C@@H]3CC[C@@H](N)[C@H](F)CO3)cs2)cnn1C

Procedure:
Following the procedure for Example 101 starting from tert-butyl ((3S,4R,7S)-7-(4-(2-bromothiazole-4-carboxamido)-1-methyl-1H-pyrazol-5-yl)-3-fluorooxepan-4-yl)carbamate (Intermediate 99), and replacing 3,6-dihydro-2H-pyran-4-boronic acid pinacol ester with 1,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole gave 242. 1H NMR (400 MHz, DMSO-d6) δ 9.61 (s, 1H), 8.24 (s, 1H), 7.95 (s, 1H), 7.83 (s, 1H), 4.84 (dd, J=10.6, 3.8 Hz, 1H), 4.55-4.32 (m, 1H), 4.28-4.14 (m, 1H), 4.13-3.94 (m, 1H), 3.81 (s, 3H), 3.78 (s, 3H), 3.29-3.16 (m, 1H), 2.61 (s, 3H), 2.12-2.02 (m, 1H), 1.91-1.78 (m, 1H), 1.75-1.64 (m, 4H). LCMS (ES+) m/z 434 (M+1).
Reaction SMILES: [CH2:1]([O:8][C@@H:9]([C@@H:16]([CH:33]=[CH2:34])[CH:17]=[CH:18][C@@H:19](OCC1C=CC=CC=1)[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:10][CH:11](OC)OC)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:35](=[O:38])(O)[O-].[Na+].[C:40]([OH:43])(=O)[CH3:41]>O1CCCC1>[CH2:1]([O:8][C@@H:9]([C@@H:16]([CH:33]=[CH2:34])[CH:17]=[CH:18][C@@H:19]([O:43][CH2:40][C:41]1[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=1)[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:10][CH2:11][CH:35]=[O:38])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C([O-])O
Reactant: CC(=O)O
Reactant: C=C[C@@H](C=C[C@H](CCCCC)OCc1ccccc1)[C@@H](CC(OC)OC)OCc1ccccc1
Agent: [Na+]
Solvent: C1CCOC1
Product: C=C[C@@H](C=C[C@H](CCCCC)OCc1ccccc1)[C@@H](CCC=O)OCc1ccccc1

Procedure:
While stirring, 776 mg (1.67 mM) of (3R,4S,7S) 3,7-dibenzyloxy-4-vinyl-1,1-dimethoxydodeca-5-ene [8] described above was heated in a mixture of 13 ml of 80% acetic acid and 2 ml of tetrahydrofuran at 40° C. for 5 hours. Completion of the reaction was confirmed by thin layer chromatography. Then, the reaction solution was poured into saturated sodium bicarbonate aqueous solution. The mixture was extracted 3 times with a solvent mixture of diethyl ether:hexane=7:3. The extracts were combined and washed sequentially with saturated sodium bicarbonate aqueous solution and saturated sodium chloride aqueous solution. After drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to give 701 mg (1.67 mM) of (3R,4S,7S) 3,7-dibenzyloxy-4-vinyldodeca-5-enecarboaldehyde [9]. Yield, 100%.
Reaction SMILES: [S:1]1[CH2:5][CH2:4][N:3]=[C:2]1[C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][C:9]=2[NH2:15].C=O.N1C2C=CC=C[C:21]=2N=N1.O>C(O)C.O1CCCC1>[S:1]1[CH2:5][CH2:4][N:3]=[C:2]1[C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][C:9]=2[NH:15][CH3:21]
Reactant: Nc1cccc2cc(C3=NCCS3)[nH]c12
Reactant: c1ccc2[nH]nnc2c1
Agent: C=O
Solvent: CCO
Solvent: O
Solvent: C1CCOC1
Product: CNc1cccc2cc(C3=NCCS3)[nH]c12
Yield: 31.3 %

Procedure:
2-(4,5-Dihydro-1,3-thiazol-2-yl)-1H-indole-7-amine (1.08 g), aqueous formaldehyde solution (37%, 372 μL) and benzotriazole (595 mg) were dissolved in ethanol (15 mL) and tetrahydrofuran (15 mL), and the mixture was stirred at room temperature for 2 days. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The obtained residue was subjected to silica gel column chromatography (ethyl acetate:hexane=1:1) to give a yellow oil (360 mg, yield 31%). M+1=232.
Reaction SMILES: [Cl:1][C:2]1[C:19]([N+:20]([O-:22])=[O:21])=[CH:18][CH:17]=[C:16]([Cl:23])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([CH:12]=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1.[Br:24]N1C(=O)CCC1=O>C(O)C.O1CCOCC1>[Br:24][C:12]1[N:8]2[CH:9]=[CH:10][CH:11]=[C:6]([O:5][CH2:4][C:3]3[C:16]([Cl:23])=[CH:17][CH:18]=[C:19]([N+:20]([O-:22])=[O:21])[C:2]=3[Cl:1])[C:7]2=[N:14][C:13]=1[CH3:15]
Reactant: Cc1cn2cccc(OCc3c(Cl)ccc([N+](=O)[O-])c3Cl)c2n1
Reactant: O=C1CCC(=O)N1Br
Solvent: CCO
Solvent: C1COCCO1
Product: Cc1nc2c(OCc3c(Cl)ccc([N+](=O)[O-])c3Cl)cccn2c1Br
Reaction time: 1 h
Yield: 81.7 %

Procedure:
To a solution of 8-(2,6-dichloro-3-nitrobenzyloxy)-2-methylimidazo[1,2-a]pyridine (85 mg) in a mixture of ethanol (1 ml) and 1,4-dioxane (1 ml) was added in one portion N-bromosuccinimide (43 mg) at ambient temperature. After stirring for one hour at the same temperature, the mixture was filtered to give 3-bromo-8-(2,6-dichloro-3-nitrobenzyloxy)-2-methylimidazo[1,2-a]pyridine (85 mg) as a yellow solid.
Reaction SMILES: C([N:4]1[CH2:13][CH2:12][C:11]2[C:6](=[C:7]([S:15](=[O:18])(=[O:17])[NH2:16])[C:8]([Cl:14])=[CH:9][CH:10]=2)[CH2:5]1)(=O)C>Cl>[ClH:14].[Cl:14][C:8]1[C:7]([S:15](=[O:18])(=[O:17])[NH2:16])=[C:6]2[C:11]([CH2:12][CH2:13][NH:4][CH2:5]2)=[CH:10][CH:9]=1
Reactant: CC(=O)N1CCc2ccc(Cl)c(S(N)(=O)=O)c2C1
Agent: Cl
Product: NS(=O)(=O)c1c(Cl)ccc2c1CNCC2

Procedure:
2-Acetyl-7-chloro-8-sulfamyl-1,2,3,4-tetrahydroisoquinoline is hydrolyzed in refluxing 10% hydrochloric acid (60 ml.) for 2.5 hours. The reaction mixture is evaporated and the residue treated with methanol and ether. The solid is filtered off to give 7-chloro-8-sulfamoyl-1,2,3,4-tetrahydroisoquinoline hydrochloride. The hydrochloride is treated with ammonium hydroxide as in Example 9 to give 7-chloro-8-sulfamoyl-1,2,3,4-tetrahydroisoquinoline.
Reaction SMILES: Cl.[C:2]1([N:8]([CH2:32][CH2:33][C:34]([O:36]CC)=[O:35])[C:9]([C:11]2[CH:31]=[CH:30][C:14]3[N:15]([CH3:29])[C:16]([CH2:18][NH:19][C:20]4[CH:25]=[CH:24][C:23]([C:26](=[NH:28])[NH2:27])=[CH:22][CH:21]=4)=[N:17][C:13]=3[CH:12]=2)=[O:10])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)C.[OH-].[Na+].C(O)(=O)C>O>[C:2]1([N:8]([CH2:32][CH2:33][C:34]([OH:36])=[O:35])[C:9]([C:11]2[CH:31]=[CH:30][C:14]3[N:15]([CH3:29])[C:16]([CH2:18][NH:19][C:20]4[CH:25]=[CH:24][C:23]([C:26](=[NH:27])[NH2:28])=[CH:22][CH:21]=4)=[N:17][C:13]=3[CH:12]=2)=[O:10])[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)CCN(C(=O)c1ccc2c(c1)nc(CNc1ccc(C(=N)N)cc1)n2C)c1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(=O)O
Solvent: CCO
Product: Cn1c(CNc2ccc(C(=N)N)cc2)nc2cc(C(=O)N(CCC(=O)O)c3ccccc3)ccc21
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of 300 mg (0.56 mMol) of 1-methyl-2-[N-(4-amidinophenyl)-aminomethyl]-benzimidazol-5-yl-carboxylic acid-N-phenyl-N-(2-ethoxycarbonylethyl)-amide-hydrochloride, 15 ml of ethanol, 4 ml of water and 120 mg (3.0 mMol) of sodium hydroxide was stirred for two hours at room temperature. Then the mixture was diluted with about 20 ml of water and made weakly alkaline with glacial acetic acid. The product which crystallised out was suction filtered, washed with water and dried at 60° C. in vacuo. Yield: 250 mg (95% of theory), C26H26N6O3 (470.5) ##EQU9##
Reaction SMILES: [CH2:1]([O:5][CH2:6][CH:7]=[CH2:8])[CH:2]1[O:4][CH2:3]1.[H-].[O-2:10].[Al+3].[O-2].[O-2].[Al+3]>C1(C)C=CC=CC=1.O=[Pt]=O>[CH2:1]([O:5][CH2:6][CH:7]1[O:10][CH2:8]1)[CH:2]1[O:4][CH2:3]1
Reactant: [O-2]
Reactant: C=CCOCC1CO1
Agent: O=[Pt]=O
Agent: [Al+3]
Agent: [H-]
Solvent: Cc1ccccc1
Product: C(OCC1CO1)C1CO1
Temperature: 90 °C

Procedure:
Allyl glycidyl ether (13.2 mL, 0.111 mol) was added to HMS-501 (10.0 g, 0.0741 mol) in toluene. A catalytic amount of PtO2 was added, and the mixture was heated at 90° C., overnight. An NMR spectrum taken the following day showed there to be substantially no remaining hydride (peak at approx. 4.7 ppm). The reaction mixture was then cooled and passed through a bed of aluminum oxide layered on top of a fitted glass filter. The frit was washed with additional toluene. The eluent was collected in a round-bottom flask. The solvent and residual allyl gylcidyl ether were then removed in vacuo at 50° C., to yield the epoxy-PDMS as a thick clear liquid (16.09 g, 87.2
Reaction SMILES: C(O)(C(F)(F)F)=O.[S:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[NH:17][C:18]([C:20]1[CH:21]=[CH:22][CH:23]=[C:24]2[C:29]=1[CH2:28][N:27]([C:30]1[S:31][C:32]([CH2:38][CH2:39][CH2:40][O:41][C:42]3[CH:47]=[CH:46][C:45](C4C(C#N)=CSC=4)=[CH:44][CH:43]=3)=[C:33]([C:35]([OH:37])=[O:36])[N:34]=1)[CH2:26][CH2:25]2)=[O:19].[N:55]1([CH2:60][CH2:61][O:62]C2C=CC(O)=CC=2)[CH2:59][CH2:58][CH2:57][CH2:56]1>>[S:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[NH:17][C:18]([C:20]1[CH:21]=[CH:22][CH:23]=[C:24]2[C:29]=1[CH2:28][N:27]([C:30]1[S:31][C:32]([CH2:38][CH2:39][CH2:40][O:41][C:42]3[CH:47]=[CH:46][C:45]([O:62][CH2:61][CH2:60][N:55]4[CH2:59][CH2:58][CH2:57][CH2:56]4)=[CH:44][CH:43]=3)=[C:33]([C:35]([OH:37])=[O:36])[N:34]=1)[CH2:26][CH2:25]2)=[O:19]
Reactant: N#Cc1cscc1-c1ccc(OCCCc2sc(N3CCc4cccc(C(=O)Nc5nc6ccccc6s5)c4C3)nc2C(=O)O)cc1
Reactant: Oc1ccc(OCCN2CCCC2)cc1
Solvent: O=C(O)C(F)(F)F
Product: O=C(Nc1nc2ccccc2s1)c1cccc2c1CN(c1nc(C(=O)O)c(CCCOc3ccc(OCCN4CCCC4)cc3)s1)CC2

Procedure:
The title compound 114 was prepared as a TFA salt in a similar manner to the synthesis of compound 51 by substituting compound 51A with compound 106B: 1H NMR (DMSO-d6): δ 12.90 (s, 1H), 9.75 (s, 1H), 8.04 (d, J=7.93 Hz, 1H), 7.80 (d, J=7.93 Hz, 1H), 7.68 (d, J=7.32 Hz, 2H), 7.35-7.50 (m, 4H), 6.86-6.93 (m, 4H), 4.83 (s, 2H), 4.19-4.21 (m, 2H), 3.92 (d, J=6.26 Hz, 2H), 3.72 (d, J=5.95 Hz, 1H), 3.55 (br, 4H), 3.10-3.18 (m, 4H), 3.03 (t, J=5.8 Hz, 2H), 1.85-2.02 (m, 6H). ESI (+)/MS: 684 (M+H)+.
Reaction SMILES: [CH:1]1[C:13]2[N:12]([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][OH:20])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.CC1C=CC(S(O)(=O)=O)=CC=1.[C:32](O)(=[O:35])[CH:33]=[CH2:34].COC1C=CC(O)=CC=1>C1(C)C=CC=CC=1>[CH:10]1[C:11]2[N:12]([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][O:20][C:32](=[O:35])[CH:33]=[CH2:34])[C:13]3[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=3)[C:6]=2[CH:7]=[CH:8][CH:9]=1
Reactant: OCCCCCCn1c2ccccc2c2ccccc21
Reactant: C=CC(=O)O
Agent: COc1ccc(O)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: C=CC(=O)OCCCCCCn1c2ccccc2c2ccccc21
Temperature: 25 °C

Procedure:
To a 500 ml three-neck round bottom flask was added 33 g. of 6-carbazol-9-yl-hexan-1-ol, 170 g. toluene, 2.2 g. PTSA, 10.7 g. acrylic acid and 0.07 g. hydroquinone monomethyl ether (MEHQ). The mixture was heated to reflux and the water was removed by azeotropic distillation using a Dean-Stark trap. After five hours of reflux, 1 gram additional acrylic acid was added and the mixture heated for one additional hour. The reaction mixture was cooled to room temperature, washed with 100 g 5% HCl in water, then 100 g. 10% sodium carbonate in water, then 100 g. of saturated brine. The solvent was removed on a rotary evaporator.
Reaction SMILES: O[C:2]1[C:15]2[C:6](=[C:7]3[C:12](=[CH:13][CH:14]=2)[C:11]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:10][CH:9]=[N:8]3)[N:5]=[CH:4][C:3]=1C(O)=O.C1(C2C3C(N=CC=2)=C2C(C(O)=CC=N2)=CC=3)C=CC=CC=1.P(Br)(Br)([Br:48])=O.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[Br:48][C:2]1[C:15]2[C:6](=[C:7]3[C:12](=[CH:13][CH:14]=2)[C:11]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:10][CH:9]=[N:8]3)[N:5]=[CH:4][CH:3]=1
Reactant: O=C(O)c1cnc2c(ccc3c(-c4ccccc4)ccnc32)c1O
Reactant: O=P(Br)(Br)Br
Agent: O=C([O-])O
Agent: Oc1ccnc2c1ccc1c(-c3ccccc3)ccnc12
Agent: [Na+]
Solvent: Cc1ccccc1
Product: Brc1ccnc2c1ccc1c(-c3ccccc3)ccnc12
Temperature: 260 °C

Procedure:
4-Hydroxy-7-phenyl-1,10-phenanthroline-3-carboxylic acid is de-carboxylated in three gram amounts by heating at 250-270° C. in a Woods metal bath until effervescence ceases. A cake, principally comprising 7-phenyl-1,10-phenanthrolin-4-ol, cracks away from the sides of the beaker and is ground up in a mortar. This material is treated with excess phosphoryl bromide (15 mL) and the mixture is heated to 140° C. for 8 hrs. The reaction mixture is cooled to room temperature, and the remaining phosphoryl bromide is distilled off under reduced pressure to yield a semi-crystalline mass. This solid is stirred into a mixture of toluene and dilute sodium bicarbonate sufficient to make the mixture slightly basic. The mixture is stirred for several hours, after which time the toluene layer is separated and the aqueous layer is extracted with additional toluene. The toluene fractions are combined, treated with decolorizing charcoal, filtered, and evaporated to yield the desired product, which is collected by filtration and re-crystallized from toluene.
Reaction SMILES: [CH3:1][NH:2][C:3](=[O:5])[CH3:4].[C:6](N)(=[O:8])[CH3:7].[CH2:10](O)[CH3:11]>>[CH3:1][N:2]([CH:6]([O:8][CH2:10][CH3:11])[CH3:7])[C:3](=[O:5])[CH3:4]
Reactant: CC(N)=O
Reactant: CNC(C)=O
Reactant: CCO
Product: CCOC(C)N(C)C(C)=O
Temperature: 275 °C

Procedure:
The general cracking process in the present invention was carried out to attempt to crack a tertiary amide. N-(methyl)-N-(1-ethoxyethyl)acetamide (NEEA) was prepared, analyzed by NMR, and its purity estimated to be 42%. The other primary component was N-methyl acetamide. An ethanolic solution containing MEEA was prepared by mixing 25.01 g of the MEEA acetamide and 45.0 g ethanol. The solution was deoxygenated by purging the headspace of a glass bottle with N2, shaking the capped bottle well and repeating this procedure. 2.05 cc of Harshaw MgO catalyst was loaded into a 9/16" O.D. 316 ss tube with 10.0 g of 10-16 mesh quartz chips pre-bed vaporizer and 7.4 g as post-bed support material. The tube was assembled into a down-flow reactor and heated to 275° C. under 900 sccm He. The MEEA solution was pumped to the heated reactor at a flow rate of 19.3 ml/hr and total pressure of 850 torr. The reactor effluent was cooled and samples were collected over a four hour period. 1.00 g of the effluent was added to 9.00 g methanol and 0.15 g N-methyl pyrrolidone for quantitative analysis by gas chromatography. The results indicated that there was no MEEA conversion, clearly demonstrating that the process of the present invention is not effective for tertiary amides.