Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:9]2[C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[O:6][C:5]=2[C:4](B(O)O)=[CH:3][CH:2]=1.[Br:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20](I)[CH:19]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:17][C:18]1[CH:19]=[C:20]([C:4]2[C:5]3[O:6][C:7]4[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=4[C:9]=3[CH:1]=[CH:2][CH:3]=2)[CH:21]=[CH:22][CH:23]=1
Reactant: OB(O)c1cccc2c1oc1ccccc12
Reactant: Brc1cccc(I)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: Brc1cccc(-c2cccc3c2oc2ccccc23)c1
Temperature: 80 °C

Procedure:
A mixture of 4-dibenzofuranboronic acid (51 mmol), 1-Bromo-3-iodo-benzene (51 mmol), and Pd(PPh3)4, (4 mmol) in 250 mL of toluene and 150 mL of ethanol was heated to obtain a clear solution, then Na2CO3 (155 mmol) in 250 mL water was added. The reaction mixture refluxed for 4 h at 80° C. The mixture was cooled to room temperature and diluted with 300 mL ethyl acetate. The organic layer was washed with 2×300 mL portions of water, 2×300 mL portions of sat. aq. NaCl, and dried (MgSO4). After the solution was concentrated, the residue was purified by column chromatography (eluted with 2% EtOAc-Heptane) to afford 4-(3-Bromo-phenyl)-dibenzofuran.
Reaction SMILES: [CH3:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH:4]([CH3:8])[CH:3]1[OH:9].[OH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18](O)=[O:19])=[CH:13][CH:12]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1C=CC=CC=1>O>[OH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([O:9][CH:3]2[CH:4]([CH3:8])[CH2:5][CH2:6][CH2:7][CH:2]2[CH3:1])=[O:19])=[CH:13][CH:12]=1
Reactant: CC1CCCC(C)C1O
Reactant: O=C(O)Cc1ccc(O)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccccc1
Solvent: O
Product: CC1CCCC(C)C1OC(=O)Cc1ccc(O)cc1
Yield: 51 %

Procedure:
A mixture of 2,6-dimethylcyclohexyl alcohol (11.4 g), 4-hydroxyphenylacetic acid (9.12 g), p-toluenesulfonic acid (1 g) and benzene (300 mL) was refluxed with continuous water separation for 20 hours. The mixture was filtered and the filtrate was washed with a 10% Na2CO3 solution, then with water. Drying over MgSO4 and evaporation in vacuo afforded 8.02 g of 2,6-dimethylcyclohexyl 4-hydroxyphenylacetate. That product has the structural formula: ##STR25##
Reaction SMILES: [CH:1]([C:4]1[CH:11]=[C:10]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[CH:9]=[C:8]([O:18][CH3:19])[C:5]=1[C:6]#[N:7])([CH3:3])[CH3:2].N.S(=O)(=O)(O)[OH:22]>>[CH:1]([C:4]1[CH:11]=[C:10]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[CH:9]=[C:8]([O:18][CH3:19])[C:5]=1[C:6]([NH2:7])=[O:22])([CH3:3])[CH3:2]
Reactant: O=S(=O)(O)O
Reactant: COc1cc(N2CCOCC2)cc(C(C)C)c1C#N
Agent: N
Product: COc1cc(N2CCOCC2)cc(C(C)C)c1C(N)=O
Yield: 86 %

Procedure:
A solution of 2-isopropyl-6-methoxy-4-morpholin-4-yl-benzonitrile (0.37 g, 1.42 mmol) in sulfuric acid (20 ml) is heated at 100° C. for 3 h. After completion of the reaction (monitored by TLC), the mixture is poured onto ice water. The aqueous layer is basified with aqueous ammonia to pH 10 and extracted with ethyl acetate (3×20 ml). The combined organic layers are washed with water (10 ml), dried over sodium sulfate and concentrated in vacuo yielding 2-isopropyl-6-methoxy-4-morpholin-4-yl-benzamide (0.34 g, 1.22 mmol, 86%).
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:5]2[S:10][C:9](S(C)(=O)=O)=[N:8][C:6]=2[N:7]=1.[CH3:21][N:22]1[CH2:27][CH2:26][CH:25]([NH:28][CH3:29])[CH2:24][CH2:23]1>C(N(CC)CC)C>[Cl:1][C:2]1[N:3]=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:5]2[S:10][C:9]([N:28]([CH3:29])[CH:25]3[CH2:26][CH2:27][N:22]([CH3:21])[CH2:23][CH2:24]3)=[N:8][C:6]=2[N:7]=1
Reactant: CNC1CCN(C)CC1
Reactant: CS(=O)(=O)c1nc2nc(Cl)nc(N3CCOCC3)c2s1
Solvent: CCN(CC)CC
Product: CN1CCC(N(C)c2nc3nc(Cl)nc(N4CCOCC4)c3s2)CC1

Procedure:
Alternatively, 5-chloro-2-(methylsulfonyl)-7-morpholinothiazolo[4,5-d]pyrimidine was reacted with 1-methyl-4-(methylamino)piperidine, without triethylamine, via General Procedure C, to give crude 5-chloro-N-methyl-N-(1-methylpiperidin-4-yl)-7-morpholinothiazolo[4,5-d]pyrimidin-2-amine, which was then reacted with 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine via General Procedure C again to give 144 after purification by silica gel chromatography. MS (Q1) 441 (M+)
Reaction SMILES: [CH2:1]([OH:13])[C:2]([C@@H:4]([OH:12])[C@H:5]([OH:11])[C:6]([C:8](O)=[O:9])=[O:7])=[O:3].[CH2:14]([OH:26])[C@H:15]([OH:25])[C@@H:16]([OH:24])[C@H:17]([OH:23])[C:18]([C:20]([OH:22])=[O:21])=[O:19]>>[O:9]=[CH:8][C@@H:6]([C@H:5]([C@@H:4]([C@@H:2]([CH2:1][OH:13])[OH:3])[OH:12])[OH:11])[OH:7].[CH2:14]([OH:26])[C:15]([C@@H:16]([OH:24])[C@H:17]([OH:23])[C:18]([C:20]([OH:22])=[O:21])=[O:19])=[O:25]
Reactant: O=C(O)C(=O)[C@@H](O)[C@H](O)[C@@H](O)CO
Agent: O=C(O)C(=O)[C@@H](O)[C@H](O)C(=O)CO
Product: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO

Procedure:
The present inventors have now found the fact that the 2,5-diketo-D-gluconic acid producing strain and the 2-keto-L-gulonic acid producing strain can coexist in the same fermentation broth and that the 2,5-diketo-D-gluconic acid produced from D-glucose by the 2,5-diketo-D-gluconic acid producing strain accumulated in a crude state, can be utilized by the 2-keto-L-gulonic acid producing strain without any disadvantages, and that the aforesaid undesired optical isomer which is by-produced along with the end product by the 2-keto-L-gulonic acid producing strain is, actually, not accumulated in the broth; the by-produced 2-keto-D-gluconic acid is converted again into 2,5-diketo-D-gluconic acid by the 2,5-diketo-D-gluconic acid producing strain for the repeated utilization by the 2-keto-L-gulonic acid producing strain.
Reaction SMILES: [C:1]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[N:8]=[C:9]([N:12](COC)[S:13]([C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=3)(=[O:15])=[O:14])[S:10][CH:11]=2)[CH:2]=1.Cl.O>O1CCCC1>[C:1]1([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[N:8]=[C:9]([NH:12][S:13]([C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=3)(=[O:15])=[O:14])[S:10][CH:11]=2)[CH:2]=1
Reactant: COCN(c1nc(-c2cccc(-c3ccccc3)c2)cs1)S(=O)(=O)c1ccc(C)cc1
Agent: Cl
Solvent: O
Solvent: C1CCOC1
Product: Cc1ccc(S(=O)(=O)Nc2nc(-c3cccc(-c4ccccc4)c3)cs2)cc1
Yield: 45.9 %

Procedure:
A solution of 0.29 g of N-(4-biphenyl-3-yl-thiazol-2-yl)-N-methoxymethyl-4-methyl-benzenesulfonamide in 6 ml of tetrahydrofuran was stirred at room temperature for 6 hours after the addition of 1.5 ml of 6N hydrochloric acid. The reaction mixture was added to 40 ml of water and extracted with ethyl acetate. The organic phases were combined, dried with magnesium sulphate and concentrated. Recrystallization from 10 ml of 50% ethanol yielded 120 mg of N-(4-biphenyl-3-yl-thiazol-2-yl)-4-methyl-benzenesulfonamide as colorless crystals.
Reaction SMILES: [F:1][C:2]1[C:7]2[NH:8][C:9](=[O:13])[O:10][C:11](=[O:12])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[C:14]([O-])([O-])=O.[Na+].[Na+].CI>CN(C=O)C.C(OCC)(=O)C>[F:1][C:2]1[C:7]2[N:8]([CH3:14])[C:9](=[O:13])[O:10][C:11](=[O:12])[C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: O=c1[nH]c2c(F)cccc2c(=O)o1
Reactant: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CI
Product: Cn1c(=O)oc(=O)c2cccc(F)c21
Temperature: 25 °C
Reaction time: 18 h
Yield: 88.5 %

Procedure:
To a solution of 8-fluoro-1H-benzo[d][1,3]oxazine-2,4-dione (200 mg, 1.10 mmol) in DMF (2 ml) was added Na2CO3 (129 mg, 1.22 mmol), followed by methyl iodide (104 μl, 1.66 mmol) and the reaction mixture was stirred at RT for 18 h. The reaction mixture was diluted with ethyl acetate and the mixture was washed with water and brine. The organic phase was dried (MgSO4), filtered and concentrated in vacuo to give 8-fluoro-1-methyl-1H-benzo[d][1,3]oxazine-2,4-dione (190 mg, 88%) which was not purified due to its poor solubility but directly used in the following step without further purification. To a suspension of the residue (190 mg, 0.97 mmol) in ethanol (4 ml) was added DMAP (12 mg, 0.09 mmol) and the reaction mixture was heated to reflux for 3 h. The reaction mixture was cooled to RT and then concentrated in vacuo to give a residue which was partitioned between ethyl acetate and 0.1M HCl solution. The organic phase was washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography to give the desired product (132 mg, 69%) as a light yellow oil. 1H NMR (CDCl3, 300 MHz): 7.69 (aptd, J=8.0 Hz, 1H), 7.50 (brds, 1H), 7.08 (ddd, J=14.0, 8.0, 1.5 Hz, 1H), 6.51 (aptdt, J=8.0, 4.5 Hz, 1H), 4.31 (q, J=7.0 Hz, 2H), 3.12 (m, 3H), 1.37 (t, J=7.0 Hz, 3H).
Reaction SMILES: [CH:1]1([C:4]2[N:9]3[N:10]=[CH:11][C:12]([C:13]([OH:15])=O)=[C:8]3[N:7]=[C:6]([C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=3)[CH:5]=2)[CH2:3][CH2:2]1.O[NH:27][C:28](=[NH:39])[C:29]1[CH:34]=[CH:33][C:32]([S:35](=[O:38])(=[O:37])[NH2:36])=[CH:31][CH:30]=1>>[CH:1]1([C:4]2[N:9]3[N:10]=[CH:11][C:12]([C:13]4[O:15][N:39]=[C:28]([C:29]5[CH:30]=[CH:31][C:32]([S:35]([NH2:36])(=[O:37])=[O:38])=[CH:33][CH:34]=5)[N:27]=4)=[C:8]3[N:7]=[C:6]([C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=3)[CH:5]=2)[CH2:2][CH2:3]1
Reactant: O=C(O)c1cnn2c(C3CC3)cc(-c3ccc(C(F)(F)F)cc3)nc12
Reactant: N=C(NO)c1ccc(S(N)(=O)=O)cc1
Product: NS(=O)(=O)c1ccc(-c2noc(-c3cnn4c(C5CC5)cc(-c5ccc(C(F)(F)F)cc5)nc34)n2)cc1

Procedure:
The title compound was prepared from 7-cyclopropyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C.29) (174 mg, 0.5 mmol) and N-hydroxy-4-sulfamoyl-benzamidine [CAS-No. 4476-10-2] (161 mg, 0.75 mmol) according to general procedure II. Obtained after purification by column chromatography (dichloromethane/MeOH/NH4OH) and crystallization (dichloromethane/MeOH/hexane) as a light yellow solid (191 mg, 73%). MS (EI) 526.1 [(M)+]; mp 313° C.
Reaction SMILES: [I:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:4]([C:5]([OH:7])=O)[C:3]=1[C:11]([OH:13])=[O:12]>C(O)(=O)C>[I:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:4]2[C:5]([O:13][C:11](=[O:12])[C:3]=12)=[O:7]
Reactant: O=C(O)c1cccc(I)c1C(=O)O
Solvent: CC(=O)O
Product: O=C1OC(=O)c2c(I)cccc21
Temperature: 145 °C
Reaction time: 1 h
Yield: 95.9 %

Procedure:
3-Iodophthalic acid (4.00 g, 13.7 mmol) was dissolved in anhydrous acetic acid, and the solution was stirred at 145° C. for 1 hour. The solvent of the reaction mixture was evaporated under reduced pressure and the residue was purified by slurry using diisopropylether to obtain 3-iodophthalic acid anhydride (3.6 g, yield 96%).
Reaction SMILES: CN(C)[CH:3]=[CH:4][C:5]([C:7]1[N:14]2[C:10]([S:11][CH:12]=[CH:13]2)=[N:9][C:8]=1[C:15]1[CH:20]=[CH:19][C:18]([F:21])=[C:17]([O:22][CH3:23])[CH:16]=1)=O.Cl.[NH2:26]/[C:27](/[NH:30][C@@H:31]1[CH2:36][CH2:35][CH2:34][N:33]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:32]1)=[N:28]/[H].[O-]CC.[Na+]>C(O)C>[F:21][C:18]1[CH:19]=[CH:20][C:15]([C:8]2[N:9]=[C:10]3[N:14]([C:7]=2[C:5]2[CH:4]=[CH:3][N:28]=[C:27]([NH:30][C@@H:31]4[CH2:36][CH2:35][CH2:34][N:33]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:32]4)[N:26]=2)[CH:13]=[CH:12][S:11]3)=[CH:16][C:17]=1[O:22][CH3:23]
Reactant: [H]/N=C(/N)N[C@@H]1CCCN(C(=O)OC(C)(C)C)C1
Reactant: COc1cc(-c2nc3sccn3c2C(=O)C=CN(C)C)ccc1F
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: COc1cc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(C(=O)OC(C)(C)C)C3)n2)ccc1F
Yield: 86 %

Procedure:
A mixture of 3-(dimethylamino)-1-[6-(4-fluoro-3-methoxyphenyl)imidazo[2,1-b][1,3]thiazol-5-yl]prop-2-en-1-one (0.6 g, 1.74 mmol) and tert-butyl (3R)-3-{[(Z)-amino (imino)methyl]amino}piperidine-1-carboxylate hydrochloride (0.726 g, 2.61 mmol) was diluted with 13 ml of absolute ethanol and treated with 1.35 eq. of a 21% w/w solution of sodium ethoxide in ethanol (875 μl) to form a reaction mixture. The reaction mixture was heated to reflux for 24 hours. HPLC revealed remaining starting enaminone. More tert-butyl (3R)-3-{[(Z)-amino(imino)methyl]amino}piperidine-1-carboxylate hydrochloride (0.243 g, 0.87 mmol) was added followed by a 21% w/w solution of sodium ethoxide in ethanol (270 μl). The mixture was kept at reflux for an additional 15 hours. Volatiles were removed in vacuo and the residue was taken up in 50 ml of ethyl acetate and 50 ml of water. The phases were separated and the aqueous phase was extracted with 50 ml of ethyl acetate. The combined organic extracts were washed with 100 ml of water, and then with a saturated sodium chloride solution (100 ml). The organic phase was dried with sodium sulfate, filtered and concentrated in vacuo, to give a brown oil. The product was purified by flash chromatography on silica gel (gradient 50% to 75% ethyl acetate in hexanes) to yield 0.785 g of a pale yellow solid (86%). 400 MHz 1H NMR (DMSO-d6 at 60° C.) δ: 8.72 (br. s, 1H), 8.13 (d, J=5.5 Hz, 1H), 7.41 (d, J=4.7 Hz, 1H), 7.35 (dd, J=8.6, 2.0 Hz, 1H), 7.26 (dd, J=11.7, 8.6 Hz, 1H), 7.18-7.08 (m, 2H), 6.41 (d, J=5.5 Hz, 1H), 4.00-3.90 (m, 1H), 3.84 (s, 3H), 3.85-3.75 (m, 1H), 3.72-3.63 (m, 1H), 3.00-2.88 (m, 2H), 2.04-1.94 (m, 1H), 1.82-1.73 (m, 1H), 1.62-1.50 (m, 1H), 1.50-1.38 (m, 1H), 1.34 (s, 9H). LCMS: 525 [M+H].
Reaction SMILES: [BrH:1].[CH2:2]([C:6]1[CH:11]=[CH:10][C:9]([CH2:12]O)=[CH:8][CH:7]=1)[CH:3]([CH3:5])[CH3:4]>CCOCC>[CH2:2]([C:6]1[CH:11]=[CH:10][C:9]([CH2:12][Br:1])=[CH:8][CH:7]=1)[CH:3]([CH3:5])[CH3:4]
Reactant: Br
Reactant: CC(C)Cc1ccc(CO)cc1
Solvent: CCOCC
Product: CC(C)Cc1ccc(CBr)cc1
Reaction time: 1 h

Procedure:
HBr gas was bubbled through a solution of (4-isobutyl-phenyl)-methanol (5 g, 28 mmol) in Et2O (50 mL) for 10–15 minutes. The reaction was stirred for 1 h and was poured onto ice (100 g). Et2O was added and the organic solution was washed with brine (2×). The organic solution was dried (MgSO4), filtered, and concentrated to provide the title compound (6 g). 1H NMR (400 MHz, CDCl3) δ 7.28 (d, 2H), 7.10 (d, 2H), 4.49 (s, 2H), 2.45 (d, 2H), 1.84 (m, 1H), 0.89 (d, 6H).
Reaction SMILES: [CH2:1]([O:5][C:6]1[C:15]([O:16][CH3:17])=[CH:14][C:9]([C:10]([O:12]C)=[O:11])=[CH:8][C:7]=1[O:18][CH3:19])[CH2:2][CH2:3][CH3:4]>[OH-].[K+].CO>[CH2:1]([O:5][C:6]1[C:15]([O:16][CH3:17])=[CH:14][C:9]([C:10]([OH:12])=[O:11])=[CH:8][C:7]=1[O:18][CH3:19])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOc1c(OC)cc(C(=O)OC)cc1OC
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: CCCCOc1c(OC)cc(C(=O)O)cc1OC
Temperature: 25 °C
Yield: 78 %

Procedure:
After agitating a solution of methyl 4-n-butoxy-3,5-dimethoxybenzoate represented by Formula 92 (5.83 g, 21.74 mmol) dissolved in a potassium hydroxide solution (KOH, 44%, 10 mL) and methanol (120 mL) at 65° C. for 2 hours, the prepared solution was cooled to room temperature and the solvent was removed under reduced pressure. The concentrate mixture was dissolved again in water and washed with ethylether (×3). Then, a 5N-hydrochloric acid solution was added to the above prepared solution to reach pH 1, and a precipitate generated during this process was obtained through filtration. The obtained precipitate was washed using water several times and dried, followed by recrystallization using methanol (20 mL), resulting in benzoic acid represented by Formula 90 as a desired product (4.28 g, 78%). Analysis data of the product is provided as follows:
Reaction SMILES: CC1C(=CC(=CC=1)N=C=O)[N:4]=C=O.[CH3:14][S:15][C:16]1[CH:21]=[C:20]([CH3:22])[C:19]([NH2:23])=[C:18]([S:24][CH3:25])[C:17]=1N>>[CH3:22][C:20]1[C:21]([NH2:4])=[C:16]([S:15][CH3:14])[CH:17]=[C:18]([S:24][CH3:25])[C:19]=1[NH2:23]
Reactant: Cc1ccc(N=C=O)cc1N=C=O
Reactant: CSc1cc(C)c(N)c(SC)c1N
Agent: *O[Si](*)(C)C
Product: CSc1cc(SC)c(N)c(C)c1N

Procedure:
To a glass kettle there were added 80.76 g of a polytetramethylene glycol/polypropylene glycol based resin end-capped with an excess of toluene diisocyanate, obtained from Dow Chemical Company, 18.0 g of bis[oxydiethylenebis(polycaprolactone)yl]-5-methyltriphenylphosphoniumsulfo-1,3-benzenedicarboxylate, three drops of a polydimethylsiloxane anti-foam agent obtained from Union Carbide Company as SAG 47™, and 21.5 g of di(methylthio)-2,4-toluenediamine, an aromatic diamine sold by and obtained from Ethyl Corporation under the tradename Ethacure 300. The reaction mixture was stirred at room temperature, under nitrogen, for four minutes, degassed under reduced pressure (0.01 mm Hg) and poured into a stainless steel mold. The polymer was cured at 100° C. for sixteen hours and demolded. The slab was then cooled to room temperature and the resistiviities of the slab molded to a thickness of 0.25 in (0.635 cm) were measured as described above at the two designated relative humidities and the relative humidity sensitivity was determined after an equilibration time of fourteen days in a relative humidity chamber. The results are shown in Table I, Example 5 below.
Reaction SMILES: [Cl:1][C:2]1[C:7]([C:8]2[CH:9]=[C:10]([C:14]([C:16]3[O:17][CH:18]=[CH:19][N:20]=3)=[O:15])[CH:11]=[CH:12][CH:13]=2)=[CH:6][N:5]=[C:4]2[N:21]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[CH:22]=[C:23]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[F:30])[C:3]=12.[BH4-].[Na+]>CO>[Cl:1][C:2]1[C:7]([C:8]2[CH:9]=[C:10]([CH:14]([C:16]3[O:17][CH:18]=[CH:19][N:20]=3)[OH:15])[CH:11]=[CH:12][CH:13]=2)=[CH:6][N:5]=[C:4]2[N:21]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[CH:22]=[C:23]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[F:30])[C:3]=12
Reactant: C[Si](C)(C)CCOCn1cc(-c2ccccc2F)c2c(Cl)c(-c3cccc(C(=O)c4ncco4)c3)cnc21
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: C[Si](C)(C)CCOCn1cc(-c2ccccc2F)c2c(Cl)c(-c3cccc(C(O)c4ncco4)c3)cnc21
Reaction time: 1 h
Yield: 72.7 %

Procedure:
A solution of {3-[4-chloro-3-(2-fluoro-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-oxazol-2-yl-methanone (22 mg, 0.040 mmol) in MeOH (0.25 mL) was added to a cold suspension (0° C.) of NaBH4 (1.59 mg, 0.042 mmol) in MeOH (0.25 mL). After 1 h, the mixture was quenched by addition of saturated ammonium chloride and the solution was concentrated to a solid. The residue was triturated with ethyl acetate to afford {3-[4-chloro-3-(2-fluoro-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-oxazol-2-yl-methanol (16 mg, 72.82%). MS: m/z 550 (M+H+).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][C:15]([OH:17])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:18][C:19]1[CH:20]=[C:21]([C:25]2NN=[N:27][N:26]=2)[CH:22]=[CH:23][CH:24]=1.C1(N=C=NC2CCCCC2)CCCCC1>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][C:15]1[O:17][C:25]([C:21]2[CH:22]=[CH:23][CH:24]=[C:19]([F:18])[CH:20]=2)=[N:26][N:27]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)N1CCCCC1CC(=O)O
Reactant: Fc1cccc(-c2nnn[nH]2)c1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Product: CC(C)(C)OC(=O)N1CCCCC1Cc1nnc(-c2cccc(F)c2)o1

Procedure:
The title compound ((1.28 g) was prepared from 2-carboxymethyl-piperidine-1-carboxylic acid tert butyl ester (1.48 g), 5-(3-fluorophenyl)tetrazole (1.0 g) and dicyclohexylcarbodiimide (1.25 g) according to the method of description 1.
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[S:3]([NH:6][CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([O:15]C)[CH:10]=1)(=[O:5])=[O:4].B(Br)(Br)Br.CO>C(Cl)Cl>[F:17][C:2]([F:1])([F:18])[S:3]([NH:6][CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([OH:15])[CH:10]=1)(=[O:4])=[O:5]
Reactant: COc1cccc(CCNS(=O)(=O)C(F)(F)F)c1
Agent: BrB(Br)Br
Solvent: ClCCl
Solvent: CO
Product: O=S(=O)(NCCc1cccc(O)c1)C(F)(F)F
Temperature: 25 °C
Yield: 99.6 %

Procedure:
A solution of 12.5 g (0.044 mol) of 1,1,1-trifluoro-N-[2-(3-methoxyphenyl)ethyl]methanesulfonamide in 150 ml of methylene chloride is cooled to -40° C. A solution of boron tribromide in methylene chloride (90 ml, 0.09 mol) is added from a dropping funnel and the mixture is allowed to warm to room temperature. The solution is concentrated in vacuo to obtain a residue, which is rapidly added to 50 ml of methanol. The solution is concentrated in vacuo to obtain 11.8 g (100%) of an oil, MS (CI) 270 (M+H). The product is used without further purification in the subsequent step.
Reaction SMILES: CC(C)([O-])C.[K+].[Br:7][C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][CH:9]=1.Cl.CO[NH2:20]>COCCOC.CN(C)C=O.C(OCC)(=O)C.[Cu]Cl>[Br:7][C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[C:10]([NH2:20])[CH:9]=1
Reactant: O=[N+]([O-])c1ccc(Br)cc1
Reactant: CON
Agent: Cl[Cu]
Agent: CC(C)(C)[O-]
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: COCCOC
Product: Nc1cc(Br)ccc1[N+](=O)[O-]
Yield: 75.2 %

Procedure:
To a solution of potassium tert-butoxide (14.5 g; 129.2 mmol) and copper(I) chloride (301 mg; 3.04 mmol) in ethyleneglycol dimethylether (120 mL), stirred at 0° C. under nitrogen, a solution of 1-bromo-4-nitro-benzene (1, 6.141 g; 30.4 mmol) and O-methyl-hydroxylamine hydrochloride (3.174 g; 38 mmol) in N,N-dimethylformamide (65 mL) was added drop wise over 103 min, the cooling bath was removed and the mixture was allowed to react at room temperature for 3 h, diluted with ethyl acetate (600 mL) and washed with saturated aqueous ammonium chloride. The organic layer was dried (MgSO4), filtered and concentrated. After purification by flash chromatography (eluent 25% ethyl acetate in hexane), 4.96 g (75% yield) of compound 2 were obtained.
Reaction SMILES: [Br:1][C:2]1[CH:21]=[CH:20][C:5]2[C:6]([C:12]3[C:17]([F:18])=[CH:16][CH:15]=[CH:14][C:13]=3[F:19])=[N:7][CH2:8][C:9](=S)[NH:10][C:4]=2[CH:3]=1.[CH3:22][O:23][CH2:24][C:25]([NH:27][NH2:28])=O>C(O)CCC>[Br:1][C:2]1[CH:21]=[CH:20][C:5]2[C:6]([C:12]3[C:17]([F:18])=[CH:16][CH:15]=[CH:14][C:13]=3[F:19])=[N:7][CH2:8][C:9]3[N:10]([C:25]([CH2:24][O:23][CH3:22])=[N:27][N:28]=3)[C:4]=2[CH:3]=1
Reactant: COCC(=O)NN
Reactant: Fc1cccc(F)c1C1=NCC(=S)Nc2cc(Br)ccc21
Solvent: CCCCO
Product: COCc1nnc2n1-c1cc(Br)ccc1C(c1c(F)cccc1F)=NC2

Procedure:
In the manner given in Example 1, a solution of 1,3-dihydro-8-bromo-5-(2,6-difluorophenyl)-2H-1,4-benzodiazepine-2-thione in n-butyl alcohol was heated to reflux with methoxyacetic acid hydrazide to give 9-bromo-1-(methoxymethyl)-6-(2,6-difluorophenyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine.
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][N:11]=1)[C:6](O)=[O:7].Cl.[CH3:15][NH:16][O:17][CH3:18].Cl.C(C(NCCCN(C)C)=N)C.CCN(CC)CC.[NH4+].[Cl-]>C(Cl)Cl>[CH3:18][O:17][N:16]([CH3:15])[C:6](=[O:7])[C:5]1[CH:9]=[CH:10][N:11]=[C:3]([C:2]([F:13])([F:12])[F:1])[CH:4]=1
Reactant: CNOC
Reactant: O=C(O)c1ccnc(C(F)(F)F)c1
Agent: CCC(=N)NCCCN(C)C
Agent: Cl
Agent: [Cl-]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CON(C)C(=O)c1ccnc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a suspension of 2-(trifluoromethyl)isonicotinic acid (1.03 g, 5.39 mmol), N,O-dimethylhydroxylamine hydrochloride (0.800 g, 8.20 mmol) and N′(ethylcarbonimidoyl)-N,N-dimethyl-1,3-propanediamine hydrochloride (EDCI, 1.35 g, 7.04 mmol) in CH2Cl2 (30 mL) was added Et3N (1.90 mL, 13.7 mmol), and the mixture immediately turned clear. After stirring at room temperature overnight, NH4Cl (aqueous) was added. The mixture was stirred vigorously for a while, and white solid was then filtered off. The organic layer was separated, and the aqueous layer was extracted with CH2Cl2. The combined organic phases were washed with brine, and the aqueous layer was back extracted with CH2Cl2. The organic phases were combined, dried (Na2SO4), filtered, concentrated, and purified by flash column chromatography (40 g silica gel column, 40-70% EtOAc in heptanes) to afford the title compound as a clear oil.