Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH:13]1[C:22]2[C:17](=[CH:18][C:19]([O:23][CH2:24][O:25][CH3:26])=[CH:20][CH:21]=2)[O:16][CH2:15][C:14]1([C:28]1[CH:33]=[CH:32][C:31]([O:34][CH2:35][O:36][CH3:37])=[CH:30][CH:29]=1)[CH3:27])=[N+]=[N-]>CO.[Pd]>[NH2:1][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH:13]1[C:22]2[C:17](=[CH:18][C:19]([O:23][CH2:24][O:25][CH3:26])=[CH:20][CH:21]=2)[O:16][CH2:15][C:14]1([C:28]1[CH:29]=[CH:30][C:31]([O:34][CH2:35][O:36][CH3:37])=[CH:32][CH:33]=1)[CH3:27]
Reactant: COCOc1ccc(C2(C)COc3cc(OCOC)ccc3C2CCCCCCCCCN=[N+]=[N-])cc1
Agent: [Pd]
Solvent: CO
Product: COCOc1ccc(C2(C)COc3cc(OCOC)ccc3C2CCCCCCCCCN)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 100.6 %

Procedure:
To a solution of 4-(9-azidononyl)-7-methoxymethoxy-3-(4-methoxymethoxyphenyl)-3-methylchroman (411 mg, 0.80 mmol) in methanol (100 ml) was added 10% Pd—C (100 mg), which was then stirred overnight at room temperature under hydrogen (atmospheric pressure). The resulting mixture was filtered through cellite and concentrated under reduced pressure to give the title compound (391 mg, stoichiometric yield) as a white solid.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]=[CH:8][C:9]2[NH:10][C:11]3[C:16]([C:17]=2[C:18]=1[CH3:19])=[CH:15][C:14](I)=[CH:13][CH:12]=3)=[O:5])[CH3:2].C(N(CC)CC)C.[C:28]1(=[O:34])[CH2:33][CH2:32][CH2:31][CH:30]=[CH:29]1>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[CH:8][C:9]2[NH:10][C:11]3[C:16]([C:17]=2[C:18]=1[CH3:19])=[CH:15][C:14]([C:30]1[CH2:31][CH2:32][CH2:33][C:28](=[O:34])[CH:29]=1)=[CH:13][CH:12]=3)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1ncc2[nH]c3ccc(I)cc3c2c1C
Reactant: O=C1C=CCCC1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CCOC(=O)c1ncc2[nH]c3ccc(C4=CC(=O)CCC4)cc3c2c1C
Yield: 7.2 %

Procedure:
In a pressure vessel, 1.08 g (3 mmol) of 6-iodo-4-methyl-β-carboline-3-carboxylic acid ethyl ester is heated to 140° C. for 3 hours with 72 mg (0.06 mmol) of palladium(II) acetate, 0.48 ml (3.6 mmol) of triethylamine, and 432 mg (4.5 mmol) of 2-cyclohexen-1-one in 10 ml of absolute dimethylformamide. After concentration, the mixture is chromatographed over silica gel with methylene chloride:ethanol=10:2. After recrystallization of the combined polar fractions from methylene chloride/cyclohexane, 75 mg (6.7% of theory) of 6-(1-oxo-2-cyclohexen-3-yl)-4-methyl-β-carboline-3-carboxylic acid ethyl ester is obtained, mp 245°-248° C. After recrystallization from ethyl acetate, the combined nonpolar fractions, which are chromatographed twice over silica gel with toluene:glacial acetic acid:water=10:10:1, yield 60 mg (5.8% of theory) of 6-(1-oxocyclohex-3-yl)-4-methyl-β-carboline-3-carboxylic acid ethyl ester, mp 182°-189° C.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][N:3]=1.C(O[Na])(C)(C)C.[C:15]([O:19][C:20]([N:22]([C:30]1[S:31][CH2:32][C@@H:33]2[CH2:38][CH2:37][CH2:36][C@:34]2([C:39]2[CH:44]=[C:43]([NH2:45])[CH:42]=[CH:41][C:40]=2[F:46])[N:35]=1)[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[O:21])([CH3:18])([CH3:17])[CH3:16].O>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:15]([O:19][C:20]([N:22]([C:30]1[S:31][CH2:32][C@@H:33]2[CH2:38][CH2:37][CH2:36][C@:34]2([C:39]2[CH:44]=[C:43]([NH:45][C:2]3[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][N:3]=3)[CH:42]=[CH:41][C:40]=2[F:46])[N:35]=1)[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[O:21])([CH3:16])([CH3:17])[CH3:18]
Reactant: Clc1ccc(Br)nc1
Reactant: CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)C1=N[C@@]2(c3cc(N)ccc3F)CCC[C@H]2CS1
Agent: [Pd]
Agent: CC(C)(C)O[Na]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: Cc1ccccc1
Solvent: O
Product: CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)C1=N[C@@]2(c3cc(Nc4ccc(Cl)cn4)ccc3F)CCC[C@H]2CS1
Temperature: 100 °C
Reaction time: 5 h
Yield: 200.1 %

Procedure:
2-Bromo-5-chloropyridine (10 mg), (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (4.86 mg), tris(dibenzylideneacetone)dipalladium (0) (2.38 mg) and tert-butoxysodium (6.5 mg) were added to a solution of (±)-di-tert-butyl[(4aR*,7aS*)-7a-(5-amino-2-fluorophenyl)-4,4a,5,6,7,7a-hexahydrocyclopenta[d][1,3]thiazin-2-yl]imidodicarbonate (29.1 mg) in toluene (10 mL). The mixture was heated with stirring under a nitrogen atmosphere at 100° C. for five hours. The reaction solution was returned to room temperature and poured into water, followed by extraction with ethyl acetate. The extract was washed with brine and dried over anhydrous magnesium sulfate. The title compound (60 mg) was obtained by removal of the drying agent and concentration under reduced pressure.
Reaction SMILES: [CH:1]1[C:14]2[C:13](=O)[C:12](=[O:16])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[NH:17]([C:19]1[C:24]([CH3:25])=[N:23][CH:22]=[C:21]([CH3:26])[N:20]=1)[NH2:18]>C(O)(=O)C>[CH3:25][C:24]1[C:19]([N:17]=[N:18][C:13]2[C:14]3[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=3[C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[C:12]=2[OH:16])=[N:20][C:21]([CH3:26])=[CH:22][N:23]=1
Reactant: O=C1C(=O)c2ccccc2-c2ccccc21
Reactant: Cc1cnc(C)c(NN)n1
Solvent: CC(=O)O
Product: Cc1cnc(C)c(N=Nc2c(O)c3ccccc3c3ccccc23)n1
Temperature: 90 °C

Procedure:
Next, a reaction flask was loaded with acetic acid (80 ml) and 9,10-phenanthrenequinone (4.0 g), and heated up to 90° C. with stirring to dissolve 9,10-phenanthrenequinone. To the resultant, the crystals of 2-hydrazino-3,6-dimethylpyrazine (2.7 g) was added in 20 minutes. After stirring at 90 to 100° C. for two hours, the reaction mixture was cooled and filtrated. An aqueous solution of sodium hydroxide was added to the filtrate with stirring so that crystals precipitated. The crystals were filtrated and washed with methanol, followed by being recrystallized with dioxane-water. The crystals were then filtrated and dried to give intended crystals (3.3 g).
Reaction SMILES: [NH2:1][C@H:2]([C:6]([OH:8])=[O:7])[CH2:3][CH2:4]O.C(=O)([O-])O.[Na+].O.Cl[C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17]>C(OCC)(=O)C.CCOCC>[O:8]=[C:6]1[C@@H:2]([NH:1][C:16](=[O:17])[O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:3][CH2:4][O:7]1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: N[C@@H](CCO)C(=O)O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOCC
Solvent: O
Solvent: CCOC(C)=O
Product: O=C(N[C@H]1CCOC1=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To L-homoserine (2 g) were added sodium hydrogen carbonate (3.7 g) and water (30 ml), and the mixture was stirred at room temperature for 1 hr. To the reaction mixture were further added benzyl chloroformate (3.9 ml) and ether (10 ml), and the mixture was stirred at room temperature for 18 hrs. The reaction mixture was diluted with ethyl acetate and washed with 1N hydrochloric acid. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated. The obtained crude product was purified by silica gel chromatography (ethyl acetate-hexane) to give the title compound (2.5 g).
Reaction SMILES: FC(F)(F)C(OC(=O)C(F)(F)F)=O.[C:14]([N:21]1[CH2:28][CH2:27][CH2:26][C@H:22]1[C:23]([NH-:25])=O)([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].C(N(CC)CC)C.O>O1CCCC1>[C:14]([N:21]1[CH2:28][CH2:27][CH2:26][C@H:22]1[C:23]#[N:25])([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15]
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1C([NH-])=O
Solvent: O
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCC[C@H]1C#N
Reaction time: 2 h

Procedure:
2.89 ml (20.8 mmol) trifluoroacetic acid anhydride was added to a solution of 4.05 g (18.9 mmol) BOC-L-prolyl-amide and 5.80 ml (41.6 mmol) triethyl amine in tetrahydrofuran at 0° C. The reaction was kept at rt for 2 h. 20 ml water was added, and the reaction was evaporated. The residue was dissolved in dichloromethane, and the organic phase was washed with 0.1 M HCl aq and 0.1 M NaOH aq. The organic phase was dried with anhydrous Na2SO4 and evaporated. Yield of crude product 3.64 g. The product was purified with a silica column using 25% ethyl acetate in petroleum ether as eluent. Yield 3.37 g (17.2 mmol, 91%).
Reaction SMILES: [CH3:1][C:2]1([CH3:20])[CH:7]=[C:6]([CH3:8])[C:5]([CH3:10])([CH3:9])[C:4](=[CH2:11])/[C:3]/1=[C:12](/[O:15][Si:16]([CH3:19])([CH3:18])[CH3:17])\[CH:13]=[CH2:14].[CH3:21]C1C(C)(C)C(C)=C(C)C(C)(C)C=1C(OC)=O>>[CH3:1][C:2]1([CH3:20])[C:7]([CH3:21])=[C:6]([CH3:8])[C:5]([CH3:9])([CH3:10])[C:4](=[CH2:11])/[C:3]/1=[C:12](/[O:15][Si:16]([CH3:18])([CH3:19])[CH3:17])\[CH:13]=[CH2:14]
Reactant: C=C/C(O[Si](C)(C)C)=C1\C(=C)C(C)(C)C(C)=CC1(C)C
Reactant: COC(=O)C1=C(C)C(C)(C)C(C)=C(C)C1(C)C
Product: C=C/C(O[Si](C)(C)C)=C1\C(=C)C(C)(C)C(C)=C(C)C1(C)C
Yield: 75 %

Procedure:
As described above for (5a) provided it used (4b) as starting material. Yield: 75%.
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:11]=[C:10]([CH2:12][O:13][CH2:14][CH2:15][C:16]([F:19])([F:18])[F:17])[N:9]=[C:8]([NH:20][C:21]2[CH:26]=[CH:25][C:24]([N:27]3[CH:31]=[C:30]([CH3:32])[N:29]=[CH:28]3)=[C:23]([O:33][CH3:34])[CH:22]=2)[N:7]=1)=[CH2:5])C.O.Cl>O1CCOCC1>[CH3:34][O:33][C:23]1[CH:22]=[C:21]([NH:20][C:8]2[N:7]=[C:6]([C:4](=[O:3])[CH3:5])[CH:11]=[C:10]([CH2:12][O:13][CH2:14][CH2:15][C:16]([F:17])([F:18])[F:19])[N:9]=2)[CH:26]=[CH:25][C:24]=1[N:27]1[CH:31]=[C:30]([CH3:32])[N:29]=[CH:28]1
Reactant: C=C(OCC)c1cc(COCCC(F)(F)F)nc(Nc2ccc(-n3cnc(C)c3)c(OC)c2)n1
Agent: Cl
Solvent: C1COCCO1
Solvent: O
Product: COc1cc(Nc2nc(COCCC(F)(F)F)cc(C(C)=O)n2)ccc1-n1cnc(C)c1
Temperature: 50 °C
Reaction time: 0.33 h

Procedure:
To a solution of 4-(1-ethoxyvinyl)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-((3,3,3-trifluoropropoxy)methyl)pyrimidin-2-amine (93 mg, 0.19 mmol) in dioxane (13.5 mL) was added water (0.9 mL) and HCl (0.048 mL, 0.58 mmol). The mixture was stirred at 50° C. for 20 minutes. The solvents were evaporated. Sodium bicarbonate (aq, 50% saturated) was added and the mixture was extracted with DCM. The organic phase was separated on phase separator and evaporated to give the title compound as a gum, 85 mg (97%).
Reaction SMILES: [CH:1]([NH:4][C:5]1[O:6][C:7]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[NH:15][CH:14]=[C:13]3[C:19]2[CH:24]=[C:23]([O:25]CC3C=CC(OC)=CC=3)[N:22]=[C:21]([NH:35][CH:36]([CH3:38])[CH3:37])[N:20]=2)=[N:8][N:9]=1)([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:36]([NH:35][C:21]1[NH:22][C:23](=[O:25])[CH:24]=[C:19]([C:13]2[C:12]3[C:16](=[CH:17][CH:18]=[C:10]([C:7]4[O:6][C:5]([NH:4][CH:1]([CH3:3])[CH3:2])=[N:9][N:8]=4)[CH:11]=3)[NH:15][CH:14]=2)[N:20]=1)([CH3:38])[CH3:37]
Reactant: COc1ccc(COc2cc(-c3c[nH]c4ccc(-c5nnc(NC(C)C)o5)cc34)nc(NC(C)C)n2)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC(C)Nc1nc(-c2c[nH]c3ccc(-c4nnc(NC(C)C)o4)cc23)cc(=O)[nH]1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 34 %

Procedure:
To a 15-mL round-bottomed flask was added N-isopropyl-5-(3-(2-(isopropylamino)-6-((4-methoxybenzyl)oxy)pyrimidin-4-yl)-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine (77 mg, 0.150 mmol) and TFA (0.3 mL, 4.04 mmol) in DCM (1 mL). The reaction was stirred at RT for 15 min and then the solvent was removed. The residue was purified with preparative HPLC (10-50% MeCN in water with 0.1% TFA in each solvent) and the fractions containing the product were combined and concentrated in vacuo to remove MeCN. The resulting mixture was extracted with CHCl3/iPrOH (4:1) and the combined organic layers were dried (MgSO4), filtered and concentrated to give 2-(isopropylamino)-6-(5-(5-(isopropylamino)-1,3,4-oxadiazol-2-yl)-1H-indol-3-yl)pyrimidin-4(3H)-one (20.0 mg, 0.051 mmol, 33.9% yield) as a light yellow solid. MS (ESI, pos. ion) m/z: 394.1 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 11.90 (1H, br. s.), 10.14-10.38 (1H, m), 8.75 (1H, s), 8.15 (1H, s), 7.63-7.70 (1H, m), 7.48-7.62 (2H, m), 6.23-6.40 (1H, m), 6.03 (1H, s), 4.24 (1H, dq, J=13.3, 6.5 Hz), 3.75 (1H, dq, J=13.6, 6.6 Hz), 1.29 (6H, d, J=6.5 Hz), 1.24 (6H, d, J=6.7 Hz).
Reaction SMILES: [Cl:1][C:2]1[S:3][CH:4]=[CH:5][N:6]=1.[Li]CCCC.CON(C)[C:15](=[O:17])[CH3:16]>C1COCC1>[Cl:1][C:2]1[S:3][C:4]([C:15](=[O:17])[CH3:16])=[CH:5][N:6]=1
Reactant: CON(C)C(C)=O
Reactant: Clc1nccs1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC(=O)c1cnc(Cl)s1
Temperature: 25 °C
Reaction time: 1 h
Yield: 86.9 %

Procedure:
A solution of 2-chlorothiazole (5.0 g, 42 mmol) in THF (10 mL) was added dropwise to a −78° C. solution of n-BuLi (2.5 M in hexanes; 18.4 mL, 46 mmol) in THF (140 mL). The solution was stirred for 1 hour, and then N-methoxy-N-methylacetamide (4.7 g, 46 mmol) was added. The mixture was stirred for another hour, and then it was warmed to approximately 25° C. The reaction was quenched by the addition of a saturated aqueous ammonium chloride solution and extracted with ether (3×75 mL). The organics were combined, washed with brine, filtered and then concentrated. The residue was purified by flash chromatography (20 percent ether/pentane on silica gel), yielding 5.9 grams of yellow semi-solid.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:28])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][C:16]=2[CH2:24][NH:25][CH2:26][CH3:27])[CH:7]=1)[CH3:2].[C:29](Cl)(=[O:31])[CH3:30]>>[CH2:1]([O:3][C:4](=[O:28])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][C:16]=2[CH2:24][N:25]([C:29](=[O:31])[CH3:30])[CH2:26][CH3:27])[CH:7]=1)[CH3:2]
Reactant: CCNCc1cc([N+](=O)[O-])ccc1Oc1cc(CC(=O)OCC)ccc1OC
Reactant: CC(=O)Cl
Product: CCOC(=O)Cc1ccc(OC)c(Oc2ccc([N+](=O)[O-])cc2CN(CC)C(C)=O)c1

Procedure:
Prepared according to the procedure described in Example 42, Step 3, using the following starting materials: [3-(2-ethylaminomethyl-4-nitro-phenoxy)-4-methoxy-phenyl]-acetic acid ethyl ester and acetyl chloride.
Reaction SMILES: CN1C(C(OC(C)(C)C)=O)CNC1=O.ClC1C=NC=CN=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.FC(F)(F)C(O)=O.[CH3:77][N:78]1[CH:82]([C:83]([O:85]C(C)(C)C)=[O:84])[CH2:81][N:80]([C:90]2[CH:95]=[N:94][CH:93]=[CH:92][N:91]=2)[C:79]1=[O:96]>O1CCOCC1.ClCCl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:77][N:78]1[CH:82]([C:83]([OH:85])=[O:84])[CH2:81][N:80]([C:90]2[CH:95]=[N:94][CH:93]=[CH:92][N:91]=2)[C:79]1=[O:96]
Reactant: CN1C(=O)N(c2cnccn2)CC1C(=O)OC(C)(C)C
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: CN1C(=O)NCC1C(=O)OC(C)(C)C
Solvent: ClCCl
Solvent: C1COCCO1
Solvent: O=C(O)C(F)(F)F
Product: CN1C(=O)N(c2cnccn2)CC1C(=O)O
Temperature: 25 °C
Yield: 98.7 %

Procedure:
To a solution of 1,1-dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate (400 mg, 1.998 mmol) (prepared as described in step (iii) of Example 13, starting from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid) and 2-chloropyrazine (0.179 ml, 1.998 mmol) in 1,4-dioxane (20 ml) was added cesium carbonate (2604 mg, 7.99 mmol), tris(dibenzylideneacetone)dipalladium(0) (91 mg, 0.100 mmol) and Xantphos™ (87 mg, 0.150 mmol) and the reaction mixture was stirred at reflux overnight. The reaction mixture was allowed to cool to room temperature and the solvent was removed under vacuum and the residue was partitioned between dichloromethane and water. The organic layer was washed with saturated sodium hydrogen carbonate solution, water and brine and separated by hydrophobic frit. The solution was reduced under vacuum and the residue purified by silica gel chromatography eluting with 10-75% ethyl acetate in isohexane to give the crude 1,1-dimethylethyl 3-methyl-2-oxo-1-(2-pyrazinyl)-4-imidazolidinecarboxylate (322 mg, 38.2% yield) which was used in the next step. LC/MS [M+H]+=279. (ii) Trifluoroacetic acid (1 ml) was added to a solution of 1,1-dimethylethyl 3-methyl-2-oxo-1-(2-pyrazinyl)-4-imidazolidinecarboxylate (290 mg, 0.709 mmol) in dichloromethane and the solution was stirred at room temperature overnight. The reaction mixture was reduced to dryness azeotroping with toluene and dried under heated vacuum. The residue was taken up in dichloromethane and extracted with saturated sodium hydrogen carbonate solution (×3) and aqueous layer reduced under vacuum. The residue was taken up in water and the solution acidified to pH 4 by the slow addition of 2N hydrochloric acid. The solution was washed with dichloromethane (×2) and the solvent was reduced under vacuum. The residue was triturated with the minimal amount of methanol, the solid was filtered off and the filtrate reduced under vacuum to leave a white solid which was dried under heated vacuum to give 3-methyl-2-oxo-1-(2-pyrazinyl)-4-imidazolidinecarboxylic acid (242 mg, ˜0.7 mmol) which was used in the next step. LC/MS [M+H]+=223.
Reaction SMILES: [SH:1][C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[CH2:11](N(CC)CC)[CH3:12].ICC>>[CH2:11]([S:1][C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1)[CH3:12]
Reactant: Sc1nc2ccccc2s1
Reactant: CCN(CC)CC
Solvent: CCI
Product: CCSc1nc2ccccc2s1
Yield: 55.7 %

Procedure:
2-Mercaptobenzothiazole (16.72 g, 0.1 mol) in 52 ml 95% alcohol was reacted with 10.1 g (0.1 mol) triethylamine to give a brown solution. Iodoethane (15.6 g, 0.1 mol) was added and the mixture refluxed 45 minutes. The mixture was cooled and the solvent removed by rotary evaporation. Water (100 ml) was added to the residue and an oil separated. The aqueous phase was extracted 2×50 ml methylene chloride, the combined organic phases washed with 50 ml water, and then dried over Na2SO4. Filtration and rotary evaporation yielded a brown liquid which was distilled at 140°-141.5° C. (0.15 mm) to give 10.87 g (56%) pale yellow liquid.
Reaction SMILES: C1([Si](OC)(OC)OC)C=CC=CC=1.C(O[Si](OCC)(OCC)OCC)C.C[Si](OCC)(OCC)OCC.[C:38]([O-:45])(=[O:44])/[CH:39]=[CH:40]\[C:41]([O-:43])=[O:42].CO[Si](CCC[NH+:56](C)C)(OC)OC.CO[Si](CCC[NH+:69](C)C)(OC)OC.Cl.C(OCC(O)C)C>O.CC(C)=O.CO.C(O)C>[C:38]([O-:45])(=[O:44])/[CH:39]=[CH:40]\[C:41]([O-:43])=[O:42].[NH4+:56].[NH4+:69]
Reactant: CO[Si](CCC[NH+](C)C)(OC)OC
Agent: CCOCC(C)O
Agent: CCO[Si](C)(OCC)OCC
Agent: CCO[Si](OCC)(OCC)OCC
Solvent: CC(C)=O
Solvent: CCO
Solvent: CO
Product: [NH4+]
Temperature: 25 °C

Procedure:
4.93 g of phenyltrimethoxysilane, 72.47 g of tetraethoxysilane, 22.06 g of methyltriethoxysilane, 0.54 g of the 30% methanol solution of trimethoxysilylpropyldimethylammonium maleate, and 150 g of acetone were charged into a 500 mL flask to be dissolved and the resultant mixed solution was warmed while stirring the mixed solution with a magnetic stirrer to reflux. Next, 33.14 g of 0.01 M hydrochloric acid was added to the mixed solution. The mixed solution was subjected to the reaction for 240 minutes and then the resultant reaction solution was cooled down to room temperature. Then, 200 g of propylene glycol monoethyl ether was added to the reaction solution, and ethanol and methanol as reaction by-products, acetone, water, and hydrochloric acid were distilled off under reduced pressure to obtain a hydrolysis-condensation product. The polymer thus obtained corresponded to Formula (VII-26):
Reaction SMILES: [OH-].[Li+].[CH3:3][C:4]1[C:13]2[C:8](=[CH:9][C:10]([CH3:14])=[CH:11][CH:12]=2)[C:7]([N:15]2[CH:19]=[N:18][N:17]=[C:16]2[S:20][CH2:21][C:22]([O:24]CC)=[O:23])=[CH:6][CH:5]=1>C1COCC1.C(O)C.O>[CH3:3][C:4]1[C:13]2[C:8](=[CH:9][C:10]([CH3:14])=[CH:11][CH:12]=2)[C:7]([N:15]2[CH:19]=[N:18][N:17]=[C:16]2[S:20][CH2:21][C:22]([OH:24])=[O:23])=[CH:6][CH:5]=1
Reactant: CCOC(=O)CSc1nncn1-c1ccc(C)c2ccc(C)cc12
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CCO
Product: Cc1ccc2c(C)ccc(-n3cnnc3SCC(=O)O)c2c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 93.6 %

Procedure:
Lithium hydroxide solution (1M aqueous, 0.88 mL, 0.488 mmol) was added to a solution of 4 ethyl 2-(4-(4,7-dimethylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetate (0.15 g, 0.44 mmol) in THF/ethanol/water (1:1:1, 7 mL) and the mixture stirred for 2 h at room temperature. The crude reaction mixture was then concentrated, acidified with HCl (1M, 3 mL) and extracted with ethyl acetate (3×5 mL). The combined organics extracts were concentrated to afford 2-(4-(4,7-dimethylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid as an off-white solid (0.129 g, 94%).
Reaction SMILES: [N:1]([CH2:4][C:5]1[O:6][CH:7]=[C:8]([OH:12])[C:9](=[O:11])[CH:10]=1)=[N+:2]=[N-:3].[OH-].[Na+].[CH2:15](Br)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CO>[N:1]([CH2:4][C:5]1[O:6][CH:7]=[C:8]([O:12][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:9](=[O:11])[CH:10]=1)=[N+:2]=[N-:3]
Reactant: [N-]=[N+]=NCc1cc(=O)c(O)co1
Reactant: BrCc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: [N-]=[N+]=NCc1cc(=O)c(OCc2ccccc2)co1
Temperature: 25 °C
Reaction time: 1 h
Yield: 55.7 %

Procedure:
To a stirred solution of 2-azidomethyl-5-hydroxy-pyran-4-one (3) (70.0 g, 419.1 mmol) in methanol (500 mL) was added NaOH (20 g, 502.9 mmol, 2M) and benzyl bromide (60.14 mL, 502.9 mmol) and the reaction mixture was stirred at room temperature for 1 h. After completion of the reaction, solvent was evaporated to remove volatile compounds under reduce pressure, then it was diluted with water and extracted with ethyl acetate. Then the combined organic layer was washed with water and brine, dried over Na2SO4, concentrated under reduced pressure and purified using normal column chromatography (using 20% ethyl acetate in hexane) to get 2-azidomethyl-5-benzyloxy-pyran-4-one (4) (60.0 g, 55.0%) as a light brown solid.