Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C@@H:2]([CH3:21])[C:3]([NH:5][CH:6]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:10]=[CH:9][N:8]([CH3:19])[C:7]1=[O:20])=[O:4].[OH:22][C@@H:23]([CH:27]([CH3:29])[CH3:28])[C:24](O)=[O:25].O.OC1C2N=NNC=2C=CC=1.C(N(C(C)C)CC)(C)C.Cl.CN(C)CCCN=C=NCC>ClCCl>[OH:22][C@@H:23]([CH:27]([CH3:29])[CH3:28])[C:24]([NH:1][C@H:2]([C:3](=[O:4])[NH:5][C@H:6]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:10]=[CH:9][N:8]([CH3:19])[C:7]1=[O:20])[CH3:21])=[O:25]
Reactant: C[C@H](N)C(=O)NC1C=C(c2ccccc2)C=CN(C)C1=O
Reactant: CC(C)[C@H](O)C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: Oc1cccc2[nH]nnc12
Solvent: O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)[C@H](O)C(=O)N[C@@H](C)C(=O)N[C@H]1C=C(c2ccccc2)C=CN(C)C1=O
Temperature: 1 °C
Reaction time: 4.5 h
Yield: 92.1 %

Procedure:
The (S)-2-amino-N-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-azepin-3-yl)-propionamide (406 g, 1.423 mol) is combined with dichloromethane (3 L) and the solution cooled to 0-2° C. To this solution is added (S)-2-hydroxy-3-methyl-butyric acid (168.1 g, 1.423 mol), hydroxybenzotriazole hydrate (239.7 g, 1.565 mol) and diisopropylethylamine (310 mL, 1.779 mol) which provides a slight exotherm. The contents are cooled back to about 4° C. and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (286.5 g, 1.494 mol) is added. The reaction contents are allowed to gradually warm to room temperature. High-performance liquid chromatography analysis at 4.5 hours (temperature at 14° C.) indicates about 5% unreacted starting amine present. After stirring an additional 1-1.5 hour, the reaction contents are quenched into water (1000 mL) and the layers are separated. The dichloromethane layer is further extracted with water (1000 mL), 0.1 N HCl (1000 mL), saturated sodium bicarbonate (1000 mL) and finally saturated aqueous sodium chloride. The dichloromethane layer is then dried over magnesium sulfate, filtered and concentrated via rotary evaporation to provide the crude diastereomeric mixture (505 g) of the coupled product as tan foam. The isomers are separated by chiral chromatography employing a Chiralpak® AD column eluting with 100% methanol. Upon removal of the elution solvent from the isomer fractions, approximately 210 g of the first eluting isomer is recovered as a tan foam and for the desired isomer 2, approximately 220 g (44%) is recovered, also as a tan powder. The second eluting isomer is the desired (S,S,S)-diastereomer. Approximately 140 g of the title compound is taken up in acetone (1000 mL) and water (95 mL). The solution is heated on the rotary evaporator until no suspended particles are observed. The solution is transferred to a flask, equipped with overhead stirring, and water (2750 mL) is gradually added over 15 minutes. The resulting slurry is allowed to cool to room temperature, then filtered and the cake is rinsed with 20% acetone/water solution (650 mL). After vacuum drying at 40° C. overnight, approximately 102 g of the title example is recovered.
Reaction SMILES: O=[C:2]1[CH2:7][CH2:6][CH:5]([N:8]2[C:13](=[O:14])[C:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[C:28]4[NH:32][C:31](=[O:33])[O:30][N:29]=4)=[CH:18][CH:17]=3)=[C:11]([CH2:34][CH2:35][CH3:36])[N:10]3[N:37]=[CH:38][N:39]=[C:9]23)[CH2:4][CH2:3]1.[NH2:40][O:41][CH:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1.N1C=CC=CC=1.Cl>O.C(OCC)(=O)C>[O:33]=[C:31]1[O:30][N:29]=[C:28]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2[C:19]2[CH:18]=[CH:17][C:16]([CH2:15][C:12]3[C:13](=[O:14])[N:8]([CH:5]4[CH2:4][CH2:3][C:2](=[N:40][O:41][CH:42]5[CH2:47][CH2:46][O:45][CH2:44][CH2:43]5)[CH2:7][CH2:6]4)[C:9]4[N:10]([N:37]=[CH:38][N:39]=4)[C:11]=3[CH2:34][CH2:35][CH3:36])=[CH:21][CH:20]=2)[NH:32]1
Reactant: CCCc1c(Cc2ccc(-c3ccccc3-c3noc(=O)[nH]3)cc2)c(=O)n(C2CCC(=O)CC2)c2ncnn12
Reactant: NOC1CCOCC1
Agent: Cl
Solvent: O
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: CCCc1c(Cc2ccc(-c3ccccc3-c3noc(=O)[nH]3)cc2)c(=O)n(C2CCC(=NOC3CCOCC3)CC2)c2ncnn12
Temperature: 100 °C
Reaction time: 16 h
Yield: 75.7 %

Procedure:
A mixture of 4-(4-oxocyclohexyl)-6-{[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-one (0.2 g), 4-(aminooxy)tetrahydro-2H-pyran (0.45 g) and pyridine (5 mL) was stirred at 100° C. for 16 hr. Ethyl acetate and water were added to the reaction mixture, and the mixture was adjusted to pH 4 with 1 N hydrochloric acid. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound as colorless crystals (0.18 g, 76%).
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:19])[NH:10][C:11]1[C:12](=[O:18])[NH:13][CH:14]=[C:15]([I:17])[CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:20]I>C(=O)([O-])[O-].[Ag+2].C(Cl)(Cl)Cl>[CH2:1]([O:8][C:9](=[O:19])[NH:10][C:11]1[C:12]([O:18][CH3:20])=[N:13][CH:14]=[C:15]([I:17])[CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Nc1cc(I)c[nH]c1=O)OCc1ccccc1
Reactant: CI
Agent: [Ag+2]
Agent: O=C([O-])[O-]
Solvent: ClC(Cl)Cl
Product: COc1ncc(I)cc1NC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 102.8 %

Procedure:
(5-Iodo-2-oxo-1,2-dihydro-pyridin-3-yl)-carbamic acid benzyl ester 3 (551 g, 1.49 mol, 1.0 Eq.) was charged to a flask followed by CHCl3 (7.4 L). In the dark, silver carbonate (528.9 g, 1.92 mol, 1.3 Eq.) and methyl iodide (940 mL, 15.1 mol, 10.1 Eq.) were charged to the flask and the reaction allowed to stir at ambient temperature overnight. LC analysis showed approximately 68% conversion to product, so a further mount of silver carbonate (35 g, 127 mmol, 0.09 Eq.) was added and the reaction allowed to stir at ambient temperature for 66 hours. The reaction mixture was filtered through celite (300 g) and the filter pad washed with CHCl3 (5×500 mL). The combined organic extracts were concentrated in vacuo to give an orange oil (588.5 g) which was split into two batches and purified by column chromatography using silica gel (2×2 Kg) eluting with 1;1 EtOAc/hexane to give the desired product as an orange oil which solidified to a pale pink solid on standing (495.7 g, 1.29 mol, 87%)
Reaction SMILES: IC[C:3]1[CH2:10][S:9][C@H:8]2[N:5]([C:6](=[O:23])[C@H:7]2[NH:11][C:12](=[S:22])[CH2:13][C:14]2[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=2[Cl:21])[C:4]=1[C:24]([O-:26])=[O:25].[SH:27][C:28]1[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=1.N1C(C)=CC=C[C:35]=1C.CCOCC>C1COCC1.C(OCC)(=O)C>[N:31]1[CH:32]=[CH:33][C:28]([S:27][CH2:35][O:26][C:24]([C:4]2[N:5]3[CH:8]([S:9][CH2:10][CH:3]=2)[CH:7]([NH:11][C:12](=[S:22])[CH2:13][C:14]2[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=2[Cl:21])[C:6]3=[O:23])=[O:25])=[CH:29][CH:30]=1
Reactant: Cc1cccc(C)n1
Reactant: O=C([O-])C1=C(CI)CS[C@@H]2[C@H](NC(=S)Cc3cc(Cl)ccc3Cl)C(=O)N12
Reactant: Sc1ccncc1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: CCOCC
Product: O=C(OCSc1ccncc1)C1=CCSC2C(NC(=S)Cc3cc(Cl)ccc3Cl)C(=O)N12
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
(6R)-trans-3-Iodomethyl-7-[(2,5-dichlorophenyl)thioacetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate, diphenylmethyl ester (3.00 g, 4.14 mmol) was dissolved in THF (50 mL) at 0° C. and treated with 4-mercaptopyridine (0.504 g, 4.54 mmol). A solution of 2,6-lutidine (0.576 g, 5.38 mmol) in THF (1 mL) was added next, and the reaction mixture was stirred at 0° C. for 0.5 h and then at 20° C. for 1 h. The mixture was diluted with ethyl acetate (500 mL) and the organic solution was washed with water (2×500 mL) and brine (100 mL). The solution was then dried (MgSO4) and evaporated under reduced pressure to give an oil which was treated with Et2O (50 mL) to give a solid. The solid was collected by filtration and purified by column chromatography on silica gel (CH2Cl2 to 30% EtOAc/CH2Cl2) to give 1.50 g of (6R)-trans-3-[(4-pyridylthiomethyl]-7-[(2,5-dichlorophenyl)-thioacetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate, diphenylmethyl ester as a tan solid (49% yield), m.p. 122° C. 1H NMR (300 MHz, CDCl3) δ3.37 (d, J=18 Hz, 1H), 3.52 (d, J=18 Hz, 1H), 3.68 (d, J=17 Hz, 1H), 3.76 (d, J=17 Hz, 1H), 3.96 (d, J=13 Hz, 1H), 4.16 (d, J=13 Hz, 1H), 4.93 (d, J=5 Hz, 1H), 5.76 (dd, J=5, 9 Hz, 1H), 6.95-7.42 (m, 16H), 7.49 (d, J=9 Hz, 1H), 8.29 (d, J=6 Hz, 2H). Anal. Calcd. for C34H27N3O4S3Cl2 : C, 57.62; H, 3.84; N, 5.93. Found: C, 57.27;H, 3.68; N, 5.79.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].C([O-])(=O)C.[Na+].Cl.Cl.[Cl:18][CH:19]([CH3:33])[CH2:20][N:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:23][CH2:22]1.Cl>C(O)C.C(Cl)(Cl)Cl.O>[ClH:18].[CH3:33][CH:19]([NH:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5])[CH2:20][N:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:23][CH2:22]1
Reactant: NC(=O)c1ccccc1N
Reactant: CC(Cl)CN1CCN(c2ccccc2)CC1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: ClC(Cl)Cl
Solvent: O
Product: CC(CN1CCN(c2ccccc2)CC1)Nc1ccccc1C(N)=O
Reaction time: 8 h

Procedure:
A mixture of 75 g. 2-aminobenzamide, 138 g. sodium acetate, 174 g. 1-(2-chloropropyl)-4-phenylpiperazine dihydrochloride, and 455 ml. water was refluxed 4 hours and left overnight at room temperature. Chloroform (200 ml.) was added, the mixture stirred, then filtered. The solid was washed with chloroform which dissolved most of it. The chloroform was separated, the aqueous layer washed with chloroform. The combined chloroform extracts were washed with water, dried, and concentrated to dryness. The residue was recrystallized from 1800 ml. ethanol to give 26.3 g., m.197-8. A 3rd recrystallization from 1600 ml. ethanol gave 22.4 g. m.196-8.5. A 10 g. portion of this was suspended in 100 ml. 95% ethanol, heated to near reflux and 15 ml. 10% hydrochloric acid added. The mixture was cooled with stirring and the solid filtered, washed with ethanol, and dried over P2O5 under vacuum to give 10.8 g., m.274-81(dec.)
Reaction SMILES: C[O:2][C:3](=[O:36])[CH2:4][CH2:5][NH:6][C:7]([NH:9][C:10]1[CH:15]=[C:14]([Cl:16])[CH:13]=[CH:12][C:11]=1[O:17][CH2:18][C:19]([N:21]1[CH2:26][CH2:25][N:24]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[CH2:23][C@H:22]1[CH3:35])=[O:20])=[O:8].O.[OH-].[Li+]>O1CCCC1.CO.O>[Cl:16][C:14]1[CH:13]=[CH:12][C:11]([O:17][CH2:18][C:19]([N:21]2[CH2:26][CH2:25][N:24]([CH2:27][C:28]3[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=3)[CH2:23][C@H:22]2[CH3:35])=[O:20])=[C:10]([NH:9][C:7](=[O:8])[NH:6][CH2:5][CH2:4][C:3]([OH:36])=[O:2])[CH:15]=1
Reactant: COC(=O)CCNC(=O)Nc1cc(Cl)ccc1OCC(=O)N1CCN(Cc2ccc(F)cc2)C[C@H]1C
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1NC(=O)NCCC(=O)O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 3-[3-(5-chloro-2-{2-[4-(4-fluoro-benzyl)-(2R)-2-methyl-piperazin-1-yl]-2-oxo-ethoxy}-phenyl)-ureido]-propionic acid methyl ester (0.057 g, 0.11 mmol) in tetrahydrofuran (3 mL), methanol (3 mL) and water (1 mL) was added lithium hydroxide monohydrate (0.023 g, 0.55 mmol). The reaction was stirred at ambient temperature overnight, concentrated in vacuo, taken up in methanol, passed through an ion exchange column and then treated with hydrogen chloride gas to give the title compound as its hydrochloride salt (0.035 g, LRMS: 507.2).
Reaction SMILES: [C:1]1([NH:7][C:8]#[N:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[O:10]1[CH:12]([CH2:13][CH3:14])[CH2:11]1.C(=O)([O-])[O-].[K+].[K+]>C(C(C)=O)C>[NH:9]=[C:8]1[N:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:11][CH:12]([CH2:13][CH3:14])[O:10]1
Reactant: CCC1CO1
Reactant: N#CNc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Product: CCC1CN(c2ccccc2)C(=N)O1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
In a flask were combined 3.0 grams (g) (25.4 mmol) phenyl cyanamide, 1.83 g (25.4 mmol) 1,2-epoxy butane, 3.51 g (25.4 mmol) potassium carbonate and 50 milliliters (ml) methyl ethyl ketone. The mixture was stirred overnight under a nitrogen blanket at room temperature. It was then filtered and the methyl ethyl ketone removed in vacuo. The solids recovered from the filter were extracted with acetone and combined with the residue from the main portion. The combined solids were dissolved in water and extraced with 15% isopropanol in chloroform. The solvents were removed in vacuo producing 2.30 g (48% of theoretical yield) of the desired product. Spectroscopic analysis confirmed the structure of the desired product. No type II product was detected.
Reaction SMILES: [I:1]Cl.[CH3:3][C:4]1[CH:10]=[C:9]([N:11]2[CH:15]=[N:14][N:13]=[N:12]2)[CH:8]=[CH:7][C:5]=1[NH2:6].C(=O)([O-])[O-].[Na+].[Na+]>C(O)(=O)C>[NH2:6][C:5]1[C:4]([CH3:3])=[CH:10][C:9]([N:11]2[CH:15]=[N:14][N:13]=[N:12]2)=[CH:8][C:7]=1[I:1]
Reactant: Cc1cc(-n2cnnn2)ccc1N
Reactant: ClI
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: Cc1cc(-n2cnnn2)cc(I)c1N

Procedure:
A solution of iodine monochloride (4.46 g) in acetic acid (30 cm3) was added dropwise to a stirred solution of 2-methyl-4-(tetrazol-1-yl)aniline (4 g) in acetic acid (30 cm3). After 2 hours the mixture was brought to pH 6 by addition of aqueous sodium carbonate solution and extracted with dichloromethane (250 cm3). The organic phase was dried (MgSO4), filtered and evaporated to yield a dark brown solid. This solid was chromatographed on silica (Merck "MK 60.9385" Trade Mark]) eluting with dichloromethane to afford 1-(4-amino-3-iodo-5-methylphenyl)tetrazole, m.p. 172°-175°, (6.2 g).
Reaction SMILES: [CH2:1]([N:8]1[CH:12]=[C:11]([C:13]2([CH2:22][OH:23])[CH2:21][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:14]2)[N:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:24]I.[H-].[Na+]>O1CCCC1>[CH2:1]([N:8]1[CH:12]=[C:11]([C:13]2([CH2:22][O:23][CH3:24])[CH2:21][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:14]2)[N:10]=[CH:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CI
Reactant: OCC1(c2cn(Cc3ccccc3)cn2)Cc2ccccc2C1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COCC1(c2cn(Cc3ccccc3)cn2)Cc2ccccc2C1

Procedure:
The reaction was performed according to example 9c using 1,66 g of [2-(1-benzyl-1H-imidazol-4-yl)-2,3-dihydro-1H-inden-2-yl]methanol (base) and 1,42 g of methyl iodide as starting materials, sodium hydride (0,84 g of a 50% dispersion of NaH in mineral oil) as reagent and dry tetrahydrofuran as solvent.
Reaction SMILES: [Cl:1][C:2]1[C:11]([NH:12][NH2:13])=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[CH:14](OCC)(OCC)OCC>>[Cl:1][C:2]1[C:11]2[N:10]([CH:14]=[N:13][N:12]=2)[C:9]2[C:4]([N:3]=1)=[CH:5][CH:6]=[CH:7][CH:8]=2
Reactant: NNc1nc2ccccc2nc1Cl
Reactant: CCOC(OCC)OCC
Product: Clc1nc2ccccc2n2cnnc12
Temperature: 25 °C
Yield: 94 %

Procedure:
2-Chloro-3-hydrazinoquinoxaline (9.0 g., 0.046 mole) the product of Example 1, was stirred with triethyl orthoformate (90 ml.) at 100° C. for one hour. The mixture was cooled to room temperature and the solid precipitate was collected by filtration and washed with cyclohexane and dried to afford 8.8 g. (94% yield) of 4-chloro-[1,2,4]triazolo[4,3-a]quinoxaline, m.p. 287°-290° C. (decomp.). Mass spectrum: m/e, 204 (P).
Reaction SMILES: [CH3:1][N:2]([CH3:16])[S:3]([C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][C:13]=1[O:14][CH3:15])[CH2:9]O)(=[O:5])=[O:4].S(Cl)([Cl:19])=O>C(Cl)Cl>[CH3:1][N:2]([CH3:16])[S:3]([C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][C:13]=1[O:14][CH3:15])[CH2:9][Cl:19])(=[O:5])=[O:4]
Reactant: O=S(Cl)Cl
Reactant: COc1ccc(CO)cc1S(=O)(=O)N(C)C
Solvent: ClCCl
Product: COc1ccc(CCl)cc1S(=O)(=O)N(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 88.3 %

Procedure:
To a solution of OBS02053 (2.33 g, 8.89 mmol) in anhydrous DCM (50 mL) was added thionyl chloride (0.97 mL, 13.34 mmol). The mixture was stirred at room temperature for 2 h and the volatiles removed in vacuo. The residue was re-dissolved and co-evaporated three times with DCM (3×20 mL) to give OBS02058 as a light-sensitive brown oil (2.07 g, 83%); 1H-NMR (270 MHz, CDCl3)=2.98 (6H, s), 3.899 (3H, s), 4.54 (2H, s), 6.94 (1H, d, J=8.4), 7.25 (1H, dd, J=2.2, 8.4), 7.40 (1H, d, J=2.2).
Reaction SMILES: [B:1]([OH:4])([OH:3])[OH:2].[Zn:5]>O>[B:1]([O-:4])([O-:3])[O-:2].[Zn+2:5].[B:1]([O-:4])([O-:3])[O-:2].[Zn+2:5].[Zn+2:5]
Reactant: [Zn]
Reactant: OB(O)O
Solvent: O
Product: [O-]B([O-])[O-]
Product: [Zn+2]

Procedure:
An aqueous solution was prepared by dissolving 72.5 g of boric acid (B2O3 content of 56.3%) in 1000 ml of pure water. To the aqueous solution were added 95.7 g of a zinc flower (ZnO content of 99.4%) and 217.5 g of boric acid (B2O3 content of 56.3%), and were stirred and mixed together such that the molar ratio of B2O3/ZnO was 2.0. Next, the solution was stirred and reacted at 45° C. for 120 minutes. The solution was further stirred and reacted at 90° C. for 4 hours. The obtained product was filtered, washed with water and was, then, dried at 105° C. to obtain a zinc borate (sample A-3). Table 3 shows the chemical composition and properties of the thus obtained zinc borate (sample A-3), FIG. 6 shows an X-ray diffraction image thereof, and FIG. 7 shows an electron microphotograph thereof.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([CH2:13][C:14](O)=[O:15])=[CH:10][C:9]=2[C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=2)=[CH:4][CH:3]=1.C(N1C=CN=C1)([N:29]1C=CN=C1)=O.O.N>O1CCCC1.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([CH2:13][C:14]([NH2:29])=[O:15])=[CH:10][C:9]=2[C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=2)=[CH:4][CH:3]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: CS(=O)(=O)c1ccc(-c2cc(CC(=O)O)sc2-c2ccc(F)cc2)cc1
Agent: N
Solvent: O
Solvent: C1CCOC1
Product: CS(=O)(=O)c1ccc(-c2cc(CC(N)=O)sc2-c2ccc(F)cc2)cc1
Temperature: 0 °C
Yield: 78.2 %

Procedure:
A mixture of 5-(4-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]thiophene-2-acetic acid (4.1 g) and 1,1'-carbonyldiimidazole (1.8 g) in tetrahydrofuran (50 ml) was stirred and refluxed for 1 hour. The mixture was added dropwise to an ice-cooled mixture of ammonia water (28%; 5 ml) and tetrahydrofuran (10 ml). The resulting mixture was stirred overnight, diluted with water, and extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium bicarbonate, water, and dilute hydrochloric acid, successively. The organic layer was dried and concentrated, and the residue was recrystallized from a mixture of chloroform, ethyl acetate and ethanol to give crystals of 5-(4-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]thiophene-2-acetamide (3.2 g).
Reaction SMILES: [O:1]([CH2:8][C:9]([O:11]CC)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].C(O)(=O)C>C1COCC1.O>[O:1]([CH2:8][C:9]([OH:11])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)COc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: O=C(O)COc1ccccc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 94.4 %

Procedure:
Compound 34 (2 g, 0.011 mol) was dissolved in 100 mL of THF, and 1 M NaOH (110 mL, 0.11 mol) was added. The reaction mixture was stirred at RT for 24 h. The solution was then acidified by the addition of 40 mL of acetic acid. The reaction mixture was diluted with 150 mL of H2O and the product was extracted with ethyl acetate. The organic extracts were dried over magnesium sulfate and concentrated. The crude product was washed several times with hexane:ethylacetate (9:1) to give a pale white solid (1.58 g, 94%). 1H NMR (300 MHz, CD2Cl2) δ 4.69 (s, 2H), 6.92 (d, J=8.2 Hz, 2H), 7.03 (t, J=7.0 Hz, 1H), 7.32 (t, J=7.6 Hz, 2H).
Reaction SMILES: CS(O[CH:6]([C:8]1[CH:21]=[C:20]2[C:11]([O:12][CH2:13][CH2:14][N:15]3[C:19]2=[N:18][C:17]([C:22]2[N:23]([CH:28]([CH3:30])[CH3:29])[CH:24]=[C:25]([CH3:27])[N:26]=2)=[CH:16]3)=[CH:10][CH:9]=1)[CH3:7])(=O)=O.[NH:31]1[CH2:36][CH2:35][CH:34]([C:37]([OH:40])([CH3:39])[CH3:38])[CH2:33][CH2:32]1>O1CCOCC1>[CH:28]([N:23]1[CH:24]=[C:25]([CH3:27])[N:26]=[C:22]1[C:17]1[N:18]=[C:19]2[C:20]3[CH:21]=[C:8]([CH:6]([N:31]4[CH2:36][CH2:35][CH:34]([C:37]([OH:40])([CH3:39])[CH3:38])[CH2:33][CH2:32]4)[CH3:7])[CH:9]=[CH:10][C:11]=3[O:12][CH2:13][CH2:14][N:15]2[CH:16]=1)([CH3:29])[CH3:30]
Reactant: CC(C)(O)C1CCNCC1
Reactant: Cc1cn(C(C)C)c(-c2cn3c(n2)-c2cc(C(C)OS(C)(=O)=O)ccc2OCC3)n1
Solvent: C1COCCO1
Product: Cc1cn(C(C)C)c(-c2cn3c(n2)-c2cc(C(C)N4CCC(C(C)(C)O)CC4)ccc2OCC3)n1
Temperature: 90 °C
Yield: 18.7 %

Procedure:
To a solution of 1-{4-[4-methyl-1-(propan-2-yl)-1H-imidazol-2-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaen-13-yl}ethyl methanesulfonate (12 mg, 0.028 mmol) in dioxane (2 mL) was added 2-(piperidin-4-yl)propan-2-ol (40 mg, 0.280 mmol). The resulting mixture was heated at 90° C. overnight. The solvent was removed under reduce pressure and the residue was purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min) to afford 202 (2.5 mg, 18% yield) as a white solid. LCMS (ESI): RT=5.23 min, m/z: 478.4 [M+H+]. 1H NMR (500 MHz, DMSO-d6) δ 8.36 (s, 1H), 7.55 (s, 1H), 7.30-7.28 (d, J=9.0 Hz, 1H), 7.05-7.04 (d, J=8.0 Hz, 1H), 7.02 (s, 1H), 5.48 (m, 1H), 4.52 (s, 4H), 3.57 (m, 1H), 3.21-3.18 (m, 1H), 2.99 (m, 1H), 2.23 (s, 3H), 2.10-1.60 (m, 4H), 1.52-1.47 (m, 10H), 1.35-1.22 (m, 3H), 1.13 (s, 6H)
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1.[I:11]I.[N:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>O>[I-:11].[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH2:9][N+:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:4][CH:3]=1
Reactant: c1ccncc1
Reactant: II
Reactant: CC(=O)c1ccc(Br)cc1
Solvent: O
Product: O=C(C[n+]1ccccc1)c1ccc(Br)cc1
Product: [I-]
Temperature: 100 °C
Reaction time: 3 h
Yield: 76 %

Procedure:
To 10.0 g of 4′-bromoacetophenone were added 12.8 g of iodine and 80 mL of pyridine and heated, and the mixture was stirred at 100° C. for 3 hours. After cooling to room temperature, 100 mL of water was added, and purification was performed by recrystallization. Drying was performed under reduced pressure at 70° C. for 12 hours to give 15.5 g (yield: 76%) of 4-bromophenacylpyridinium iodide as a brown powder.
Reaction SMILES: [CH:1]1[C:6]([NH2:7])=[CH:5][CH:4]=[C:3]([NH2:8])[CH:2]=1.CN(C)P(N(C)C)(N(C)C)=[O:12].N[C:21]1[CH:29]=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=1.[C:30](Cl)(=[O:40])C1C=CC(C(Cl)=O)=CC=1>O>[CH:23]1[C:24]([C:25]([OH:27])=[O:26])=[CH:28][CH:29]=[C:21]([C:30]([OH:40])=[O:12])[CH:22]=1.[CH:5]1[C:6]([NH2:7])=[CH:1][CH:2]=[C:3]([NH2:8])[CH:4]=1
Reactant: O=C(Cl)c1ccc(C(=O)Cl)cc1
Reactant: Nc1ccc(C(=O)O)cc1
Reactant: CN(C)P(=O)(N(C)C)N(C)C
Agent: Nc1ccc(N)cc1
Solvent: O
Product: O=C(O)c1ccc(C(=O)O)cc1
Reaction time: 8 h

Procedure:
To a solution of p-phenylenediamine (31.08 g., 0.287 mole) in a mixture of 360 ml. of hexamethylphosphoramide and 180 ml. of N-methylpyrrolidone-2 is added 3.36 g. of p-aminobenzoic acid, using water bath cooling. To this cooled solution is added terephthaloyl chloride (60.90 g., 0.300 mole.) The reaction mixture is stirred overnight, then combined with water in a blender to precipitate polymer. The product is washed with water and dried in a vacuum oven at 65° C. The product is then combined with acetone in a blender, the mixture filtered, and the product collected and dried at 65° C. in a vaccum oven. There is obtained a quantitative yield of poly(p-phenylene terephthalamide) (ηinh=1.32).