Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:26])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[CH:18][CH:17]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:25])[CH:11]=2)[CH:6]=1.C1COCC1.[Cl-].[NH4+].O>CO.[Zn]>[CH3:1][O:2][C:3](=[O:26])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([C:16]2[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:25])[CH:11]=2)[CH:6]=1
Reactant: COC(=O)Cc1cc2ccc(F)cc2c(-c2ccc([N+](=O)[O-])cc2)c1C
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: COC(=O)Cc1cc2ccc(F)cc2c(-c2ccc(N)cc2)c1C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 67.6 %

Procedure:
To a suspension of [6-fluoro-3-methyl-4-(4-nitro-phenyl)-naphthalen-2-yl]-acetic acid methyl ester (190 mg, 0.54 mmol) in methanol (3 mL) was added THF (2 mL). Then, zinc dust (287.1 mg, 4.4 mmol), and ammonium chloride (287.8 mg, 5.38 mmol) were added followed by water (1.3 mL). The reaction mixture was stirred at room temperature for 30 minutes. Solid was filtered and washed with ethyl acetate (20 mL). The solution was concentrated to remove organic solvent, and then diluted with water (25 mL). The mixture was extracted with ethyl acetate (2×20 mL). The combined organic extracts were washed with brine solution (30 mL) and dried over anhydrous magnesium sulfate. Filtration of the drying agent and concentration of the solvent under vacuum gave [4-(4-amino-phenyl)-6-fluoro-3-methyl-naphthalen-2-yl]-acetic acid methyl ester (118 mg, 67.7%) as a light brown solid. 1H NMR (300 MHz, CDCl3) δ ppm 7.71-7.83 (m, 1 H), 7.69 (s, 1 H), 7.27 (s, 1 H), 7.10-7.22 (m, 1 H), 6.93-7.09 (m, 3 H), 6.83 (d, J=7.8 Hz, 1H), 3.86 (s, 2 H), 3.78 (br. s, 2 H), 3.74 (s, 3 H), 2.19 (s, 3 H). HRMS calcd. for C20H19FNO2 [(M+H)+] 324.1395, obsd. 324.1392.
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:8]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C@@H:9]1[O:11][CH2:10]1>C(O)C.C(N(CC)CC)C>[CH2:13]([O:12][CH2:8][C@H:9]([OH:11])[CH2:10][O:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: c1ccc(COC[C@H]2CO2)cc1
Reactant: Oc1ccccc1
Solvent: CCO
Solvent: CCN(CC)CC
Product: O[C@@H](COCc1ccccc1)COc1ccccc1
Temperature: 60 °C
Reaction time: 2 h
Yield: 72.3 %

Procedure:
A solution of phenol (3.3 g; 35 mmol), benzyl(R)-(+)-glycidyl ether (5 g; 30.5 mmol) and triethylamine (300 μl; 2.15 mmol) in absolute ethanol (80 ml) was heated to reflux and stirred for 2 hours and then cooled to 60° C. and stirred overnight. The crude reaction mixture was concentrated under reduced pressure and the residues purified by silica gel chromatography using an eluant of hexanes and ethyl acetate (85:15 v/v) to afford 5.7 g (72.5%) of the pure product. m/z (ES) 281.1 (M+Na)+.
Reaction SMILES: [CH3:1][N:2]([CH2:26][CH:27]=[CH2:28])[S:3]([C:6]1[CH:11]=[C:10]([N:12]2[C:17](=[O:18])[CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[N:14]([CH3:23])[C:13]2=[O:24])[CH:9]=[CH:8][C:7]=1[Cl:25])(=[O:5])=[O:4].IC.[H][H]>[Pd].C(OCC)(=O)C>[CH3:1][N:2]([CH2:26][CH2:27][CH3:28])[S:3]([C:6]1[CH:11]=[C:10]([N:12]2[C:17](=[O:18])[CH:16]=[C:15]([C:19]([F:21])([F:22])[F:20])[N:14]([CH3:23])[C:13]2=[O:24])[CH:9]=[CH:8][C:7]=1[Cl:25])(=[O:4])=[O:5]
Reactant: C=CCN(C)S(=O)(=O)c1cc(-n2c(=O)cc(C(F)(F)F)n(C)c2=O)ccc1Cl
Reactant: [H][H]
Agent: [Pd]
Solvent: CI
Solvent: CCOC(C)=O
Product: CCCN(C)S(=O)(=O)c1cc(-n2c(=O)cc(C(F)(F)F)n(C)c2=O)ccc1Cl
Reaction time: 0.5 h
Yield: 87.1 %

Procedure:
A mixture of 1.6 g of N-methyl-N-(2-propenyl)-2-chloro -5-(3,6-dihydro-3-methyl-4-trifluoromethyl-2,6-dioxo-1(2H)-pyrimidinyl)benzenesulfonamide (Compound #29), prepared by process C from Compound #28 and iodomethane, 100 ml of ethyl acetate and 200 mg of 5% palladium/carbon catalyst was hydrogenated in a Paar® apparatus at 28 psi of hydrogen. After 30 minutes, the catalyst was filtered and solvent removed from the filtrate by rotary evaporation. The glassy residue was treated with ethanol to give 1.4 g of the title compound as a light gray powder, m.p. 143.5°-145° C.
Reaction SMILES: C([O:8][CH2:9][CH:10]=[O:11])C1C=CC=CC=1.P([O-])([O-])([O-])=O.[OH:17][CH2:18][C:19](=[O:21])[CH3:20].C(OCC1C=CC=CC=1)C1C=CC=CC=1>CO.[OH-].[OH-].[Pd+2].C(#N)C>[CH3:20][C:19]([C@@H:18]([C@H:9]([CH2:10][OH:11])[OH:8])[OH:17])=[O:21]
Reactant: CC(=O)CO
Reactant: O=CCOCc1ccccc1
Agent: [Pd+2]
Agent: O=P([O-])([O-])[O-]
Agent: [OH-]
Solvent: CC#N
Solvent: c1ccc(COCc2ccccc2)cc1
Solvent: CO
Product: CC(=O)[C@H](O)[C@@H](O)CO
Reaction time: 48 h
Yield: 81 %

Procedure:
Benzyloxyacetaldehyde (80 mg, 0.53 mmol) in ) in ) 0.5 mL of acetonitrile, was added to 9 mL of a solution of antibody 38C2 (35 mg, 0.23 mmol) in PBS (phosphate buffer saline, 100 mM), followed by the addition of of hydroxyacetone. (0.5 mL, 6.3 mmol). After 48 hr at room temperature the reaction reached 56% conversion and the mixture was freeze dried. The remaining residue was extracted with methylene chloride. The solvent was removed under reduced pressure and the crude product was purified by column chromatography (silica gel, ethyl acetate/hexane, 1/1) to give pure 2111α (39 mg, 0.17 mmol, 32%) in 97% ee. Benzyl ether 2111α (39 mg, 0.17 mmol) was dissolved in 1 mL of methanol and hydrogenated with a catalytic amount of palladium hydroxide on carbon. After two hr, the mixture was filtered through celite and the solvent was removed under reduced pressure to give pure 1-deoxy-L-xylulose 1111 (19 mg, 0.14 mmol, 81%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[CH:9][CH:8]=[C:7](F)[C:4]=1[C:5]#[N:6].N1C=[C-:15][N:14]=[N:13]1.[Na+].[CH3:18][N:19](C)C=O>>[CH3:1][O:2][C:3]1[CH:10]=[CH:9][CH:8]=[C:7]([N:14]2[CH:15]=[N:19][CH:18]=[N:13]2)[C:4]=1[C:5]#[N:6]
Reactant: CN(C)C=O
Reactant: COc1cccc(F)c1C#N
Reactant: [c-]1c[nH]nn1
Agent: [Na+]
Product: COc1cccc(-n2cncn2)c1C#N
Temperature: 0 °C
Reaction time: 2 h

Procedure:
A solution of 30.2 g (0.20 mol) of 2-methoxy-6-fluorobenzonitrile [preparation: J. Heterocycl. Chem. 25 (1988), 1173]in 50 ml of N,N-dimethylformamide is added dropwise at 45°-50° C., under nitrogen, to a solution of 0.21 mol of sodium triazolide (prepared from equimolar amounts of triazol and sodium hydride) in 100 ml of N,N-dimethylformamide, and the mixture is stirred for 2 h at 0° C. After the solvent has been evaporated under reduced pressure, the residue is stirred with 200 ml of ice water, the pH is brought to 6 with a little glacial acetic acid and the solid is filtered off under suction and dried. After the addition of a little ether, 35 g of the product of melting point 169°-171° C. (decomposition) are obtained.
Reaction SMILES: [H-].[Na+].[OH:3][C:4]([C:7]([C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)=[O:8])([CH3:6])[CH3:5].CS(C)=O.[CH2:20](Br)[CH:21]=[CH2:22]>O>[OH:3][C:4]([C:7]([C:9]1[CH:10]=[CH:11][C:12]([O:15][CH2:22][CH:21]=[CH2:20])=[CH:13][CH:14]=1)=[O:8])([CH3:5])[CH3:6]
Reactant: C=CCBr
Reactant: CC(C)(O)C(=O)c1ccc(O)cc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: C=CCOc1ccc(C(=O)C(C)(C)O)cc1
Reaction time: 0.25 h

Procedure:
6.6 g. (0.22 mol) of sodium hydride (80% strength in paraffin oil) are added in portions to 36.0 g (0.2 mol) of 4-hydroxyphenyl 2-hydroxy-2-propyl ketone in 450 ml. of dimethyl sulfoxide under an inert gas and the mixture is stirred for 15 minutes at room temperature. 26.8 g. (0.22mol) of allyl bromide in 40 ml. of dimethyl sulfoxide are then added dropwise at 30°-40° C., and the mixture is stirred for 15 minutes. The reaction mixture is poured into 2 l of water and then extracted with methyl t-butyl ether. By removing the solvent, 41.5 g. of compound IIh are obtained.
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH:13]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:26][CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)=[CH:16][CH:15]=2)[CH2:12][C:11]([C:27]([C:33]([F:36])([F:35])[F:34])([C:29]([F:32])([F:31])[F:30])[OH:28])=[N:10]1.C(N(CC)CC)C.[CH3:44][S:45](Cl)(=[O:47])=[O:46]>ClCCl>[Cl:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH:13]([C:14]2[CH:15]=[CH:16][C:17]([N:20]3[CH2:26][CH2:25][CH2:24][N:23]([S:45]([CH3:44])(=[O:47])=[O:46])[CH2:22][CH2:21]3)=[CH:18][CH:19]=2)[CH2:12][C:11]([C:27]([C:29]([F:31])([F:32])[F:30])([C:33]([F:34])([F:36])[F:35])[OH:28])=[N:10]1
Reactant: OC(C1=NN(c2ccccc2Cl)C(c2ccc(N3CCCNCC3)cc2)C1)(C(F)(F)F)C(F)(F)F
Reactant: CS(=O)(=O)Cl
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)N1CCCN(c2ccc(C3CC(C(O)(C(F)(F)F)C(F)(F)F)=NN3c3ccccc3Cl)cc2)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 27.8 %

Procedure:
1-(2-Chloro-phenyl)-5-[4-(homopiperazin-1-yl]-phenyl)-3-[di-(trifluoromethyl)-hydroxy-methyl]-4,5-dihydro-1H-pyrazole hydrochloride (30.0 mg, 0.06 mmol) prepared in Step 1, triethylamine (42.3 uL, 0.30 mmol) and methanesulfonyl chloride (10.4 mg, 0.09 mmol) were added to dichloromethane (1.0 mL). The reaction mixture was stirred at room temperature for 1 hour, washed with distilled water, 1N hydrochloride, a saturated solution of sodium hydrogen carbonate, and brine, dried on anhydrous magnesium sulfate, and then concentrated under reduced pressure to give a yellow liquid residue. The resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=2/1) to give 10.0 mg of the titled compound as a yellow liquid.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:30][C:31]([O:33]CC)=O)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][S:18]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[C:22]=4[Cl:28])(=[O:20])=[O:19])=[C:13]([F:29])[CH:12]=3)[C:3]=12.[CH3:36][N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1>>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:30][C:31]([N:40]3[CH2:41][CH2:42][N:37]([CH3:36])[CH2:38][CH2:39]3)=[O:33])[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][S:18]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[C:22]=4[Cl:28])(=[O:19])=[O:20])=[C:13]([F:29])[CH:12]=3)[C:3]=12
Reactant: CCOC(=O)Cn1nc(-c2ccc(NS(=O)(=O)c3cccc(Cl)c3Cl)c(F)c2)c2c(N)ncnc21
Reactant: CN1CCNCC1
Product: CN1CCN(C(=O)Cn2nc(-c3ccc(NS(=O)(=O)c4cccc(Cl)c4Cl)c(F)c3)c3c(N)ncnc32)CC1

Procedure:
Ethyl 2-[4-amino-3-(4-{[(2,3-dichlorophenyl)sulfonyl]amino}-3-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]acetate was treated with 1-methylpiperazine using the representative procedure for amide formation. Purification by preparative HPLC (25 to 100% CH3CN in 0.1 M aqueous ammonium acetate over 20 min at 21 mL/min using an 8 Hypersil HS C18, 250×21 mm column, Rt 6.4-7.0 min) afforded N1-(4-{4-amino-1-[2-(4-methylpiperazino)-2-oxoethyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-fluorophenyl)-2,3-dichloro-1-benzenesulfonamide as a white solid (0.005 g, 0.009 mmol): RP-HP (25 to 100% acetonitrile in 0.1 M aqueous ammonium acetate over 10 min at 1 mL/min using a Hypersil HS C18, 250×4.6 mm column) Rt 6.83 min. 1H NMR (DMSO-d6, 400 MHz) δ 8.20 (s, 1H), 7.96 (d, 1H), 7.88 (d, 1H), 7.50 (t, 1H), 7.36 (m, 3H), 5.31 (s, 2H), 3.45 (m, 4H), 2.50 (m, 4H), 2.30 (s, 3H), //MS: MH+ 593.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[S:12][C:13]([C:15]([OH:17])=O)=[CH:14][C:10]=3[CH2:9][CH2:8][O:7][C:6]=2[CH:18]=1.[NH2:19][C:20]1[CH:30]=[CH:29][C:23]([C:24]([N:26]([CH3:28])[CH3:27])=[O:25])=[CH:22][C:21]=1[Cl:31].N1C=CC=CC=1>O=S(Cl)Cl.C1COCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[S:12][C:13]([C:15]([NH:19][C:20]4[CH:30]=[CH:29][C:23]([C:24](=[O:25])[N:26]([CH3:27])[CH3:28])=[CH:22][C:21]=4[Cl:31])=[O:17])=[CH:14][C:10]=3[CH2:9][CH2:8][O:7][C:6]=2[CH:18]=1
Reactant: CN(C)C(=O)c1ccc(N)c(Cl)c1
Reactant: O=C(O)c1cc2c(s1)-c1ccc(Br)cc1OCC2
Solvent: c1ccncc1
Solvent: C1CCOC1
Solvent: O=S(Cl)Cl
Product: CN(C)C(=O)c1ccc(NC(=O)c2cc3c(s2)-c2ccc(Br)cc2OCC3)c(Cl)c1
Reaction time: 8 h
Yield: 76.8 %

Procedure:
A solution of 8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxylic acid (25.00 g, 76.9 mmol) in SOCl2 (200 mL) was heated at 90-100° C. for 3 h. Concentration of the reaction mixture gave the crude acid chloride. A suspension of the acid chloride in THF (600 mL) was treated with a solution of 4-amino-3-chloro-N,N-dimethylbenzamide (18.23 g, 92.3 mmol) and pyridine (14 mL) in THF (200 mL) at 0° C. The mixture was allowed to reach room temperature and stirred overnight. After concentration, water (200 mL) was added into the mixture. The resulting precipitate was collected by filtration, washed with water and dried to give 8-bromo-N-(2-chloro-4-(dimethylcarbamoyl)phenyl)-4,5-dihydro-benzo[b]thieno[2,3-d]oxepine-2-carboxamide (29.88 g, yield: 77%). ESI-MS: 504.99. 1H NMR (DMSO-d6, 400 MHz): δ10.14 (s, 1H, NH), 7.86 (s, 1H, ArH), 7.67-7.57 (m, 3H, ArH), 7.40-7.25 (m, 3H, ArH), 4.32 (t, J=5.2 Hz, 2H, CH2), 3.21 (t, J=5.2 Hz, 2H, CH2), 2.95 (s, 3H, CH3), 2.92 (s, 3H, CH3).
Reaction SMILES: CC1C=CC(S(O[CH2:12][CH:13]2[CH2:17][C:16]3[CH:18]=[C:19]([Cl:30])[CH:20]=[C:21]([C:22]4[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=4[Cl:29])[C:15]=3[O:14]2)(=O)=O)=CC=1.[CH3:31][NH2:32]>>[Cl:30][C:19]1[CH:20]=[C:21]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=2[Cl:29])[C:15]2[O:14][CH:13]([CH2:12][NH:32][CH3:31])[CH2:17][C:16]=2[CH:18]=1
Reactant: CN
Reactant: Cc1ccc(S(=O)(=O)OCC2Cc3cc(Cl)cc(-c4ccc(Cl)cc4Cl)c3O2)cc1
Product: CNCC1Cc2cc(Cl)cc(-c3ccc(Cl)cc3Cl)c2O1

Procedure:
The title compound was prepared (0.059 g, 57%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5-chloro-7-(2,4-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.135 g, 0.28 mmol) and methylamine (0.086 g, 2.8 mmol). mp 202-204° C.
Reaction SMILES: [CH:1]1([C:4]2[C:5]([O:14][CH2:15][CH:16]3[CH:21]([CH3:22])[CH2:20][CH2:19][CH2:18][CH:17]3[CH3:23])=[CH:6][C:7]([F:13])=[C:8]([CH:12]=2)[C:9](O)=[O:10])[CH2:3][CH2:2]1.C(N1C=CN=C1)(N1C=CN=C1)=O.N12CCCN=C1CCCCC2.[N:47]1([S:51]([NH2:54])(=[O:53])=[O:52])[CH2:50][CH2:49][CH2:48]1.Cl>O1CCCC1>[N:47]1([S:51]([NH:54][C:9](=[O:10])[C:8]2[CH:12]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[C:5]([O:14][CH2:15][CH:16]3[CH:21]([CH3:22])[CH2:20][CH2:19][CH2:18][CH:17]3[CH3:23])=[CH:6][C:7]=2[F:13])(=[O:53])=[O:52])[CH2:50][CH2:49][CH2:48]1
Reactant: CC1CCCC(C)C1COc1cc(F)c(C(=O)O)cc1C1CC1
Reactant: NS(=O)(=O)N1CCC1
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCC2=NCCCN2CC1
Solvent: C1CCOC1
Product: CC1CCCC(C)C1COc1cc(F)c(C(=O)NS(=O)(=O)N2CCC2)cc1C1CC1
Temperature: 70 °C
Reaction time: 1 h
Yield: 22.8 %

Procedure:
To a stirred solution of 5-cyclopropyl-4-((2,6-dimethylcyclohexyl)methoxy)-2-fluorobenzoic acid (0.07 g, 0.22 mmol) in tetrahydrofuran (2 mL) and under an atmosphere of nitrogen was added carbonyldiimidazole (0.053 g, 0.33 mmol) and the reaction mixture was stirred at 70° C. for 1 hour. The mixture was cooled down to ambient temperature and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.07 mL, 0.45 mmol) was added followed by azetidine-1-sulfonamide (0.051 g, 0.37 mmol) and the stirring continued at ambient temperature for 18 hours. 5% aqueous hydrochloric acid solution (0.15 mL) was added and the mixture was concentrated and directly purified by column chromatography (0 to 30% ethyl acetate in hexanes) to afford the title compound (0.022 g, 22%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ 8.75-8.55 (m, 1H), 7.57 (d, J=9.1 Hz, 1H), 6.62 (d, J=14.5 Hz, 1H), 4.23 (t, J=7.7 Hz, 4H), 4.01 (d, J=4.5 Hz, 2H), 2.35-2.17 (m, 2H), 2.07-1.95 (m, 2H), 1.86-0.56 (m, 20H); MS (ES+) m/z 439.1 (M+1); MS (ES−) m/z 437.2 (M−1).
Reaction SMILES: [O:1]=[Si]=O.[OH-].[Na+:5].[O-:6][Si:7]([O-:9])=[O:8].[Na+].[Na+]>O>[Si:7]([O-:1])([O-:9])([O-:6])[O-:8].[Na+:5].[Na+:5].[Na+:5].[Na+:5]
Reactant: O=[Si]([O-])[O-]
Reactant: O=[Si]=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: [O-][Si]([O-])([O-])[O-]

Procedure:
For producing crystalline sodium silicates having a layer structure, an SiO2 /Na2O molar ratio of (1.9 to 2.1):1 and a water content of less than 0.3% by weight from a waterglass solution containing at least 20% by weight of solids, the waterglass solution is obtained by reacting quartz sand with sodium hydroxide solution at an SiO2 /Na2O molar ratio of (2.0 to 2.3):1 at temperatures of 180° to 240° C. and pressures of 10 to 30 bar. This waterglass solution is treated in a spray-drying zone with hot air at 200° to 300° C. for a residence time of 10 to 25 seconds and at a temperature of the exit gas leaving the spray-drying zone of 90° to 130° C., to form a pulverulent amorphous sodium silicate having a water content (determined as the loss on ignition at 700° C.) of 15 to 23% by weight and a bulk density of more than 300 g/l. The pulverulent, amorphous, water-containing sodium silicate is introduced into an obliquely arranged rotary kiln fitted with devices for moving solids and treated therein with flue gas in countercurrent at temperatures from more than 500° up to 850° C. for 1 to 60 minutes to form crystalline soidium silicate. The rotary kiln is here insulated in such a way that its outside wall temperature is less than 60° C. Finally, the crystalline sodium silicate emerging from the rotary kiln is comminuted by means of a mechanical crusher to grain sizes of 0.1 to 12 mm.
Reaction SMILES: [CH2:1]([C:8]1[C:13]([Br:14])=[CH:12][CH:11]=[C:10]([OH:15])[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:22][O:23][CH2:24][CH2:25]Br>CN(C)C=O>[CH2:1]([C:8]1[C:13]([Br:14])=[CH:12][CH:11]=[C:10]([O:15][CH2:25][CH2:24][O:23][CH3:22])[N:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COCCBr
Reactant: Oc1ccc(Br)c(Cc2ccccc2)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COCCOc1ccc(Br)c(Cc2ccccc2)n1
Reaction time: 1 h

Procedure:
A mixture of 5 g of 2-benzyl-3-bromo-6-hydroxypyridine, 3.9 g of anhydrous potassium carbonate, 2.7 ml of 2-bromoethyl methyl ether and 20 ml of N,N-dimethylformamide was heated under stirring in an oil bat kept at 80° C. for one hour. After cooling as it was, the mixture was extracted with ethyl acetate-water. The organic phase was washed with water and brine, dried over anhydrous magnesium sulfate and evaporated. The residue was subjected to silica gel column chromatography and eluted with 1-3% ethyl acetate/hexane, to give 4.2 g of the target compound.
Reaction SMILES: [Br:1][C:2]1[S:3][C:4]2[CH2:10][CH2:9][CH2:8][CH:7]([OH:11])[C:5]=2[CH:6]=1.N1C=CN=C1.[C:17]([Si:21]([CH3:24])([CH3:23])Cl)([CH3:20])([CH3:19])[CH3:18].O>CN(C)C=O>[Br:1][C:2]1[S:3][C:4]2[CH2:10][CH2:9][CH2:8][CH:7]([O:11][Si:21]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:24])[CH3:23])[C:5]=2[CH:6]=1
Reactant: OC1CCCc2sc(Br)cc21
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OC1CCCc2sc(Br)cc21
Yield: 91 %

Procedure:
To a solution of 2-bromo-4,5,6,7-tetrahydro-1-benzothiophen-4-ol (5.0 g, 21 mmol) that was obtained in Example 8 (8a) in N,N-dimethylformamide (30 ml) were added successively imidazole (2.9 g, 43 mmol) and t-butyldimethylchlorosilane (3.5 g, 24 mmol) with stirring, and the resulting mixture was stirred for 2 hours. After stirring, the reaction mixture was poured into water (50 ml) to quench the reaction and extracted with ether. The extract was washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. After filtration, the filtrate was evaporated in vacuo, and the crude product of the title compound thus obtained was purified by chromatography on a silica gel column using a mixed solvent of ethyl acetate and hexane (1:9) as the eluent to afford the title compound (6.8 g) in a yield of 91% as a colourless oily product.
Reaction SMILES: Br[C:2]1[C:3]2[C:4]3[CH2:15][CH2:14][N:13]([C:16]([O:18]C(C)(C)C)=O)[CH2:12][CH2:11][C:5]=3[NH:6][C:7]=2[CH:8]=[CH:9][CH:10]=1.[CH2:23]([CH2:26][O:27][CH3:28])OC.C([O-])([O-])=O.[Na+].[Na+]>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.C(OCC)(=O)C.CCCCCC>[C:16]([N:13]1[CH2:14][CH2:15][C:4]2[C:3]3[C:2]([C:23]4[CH:11]=[CH:5][CH:4]=[CH:15][C:26]=4[O:27][CH3:28])=[CH:10][CH:9]=[CH:8][C:7]=3[NH:6][C:5]=2[CH2:11][CH2:12]1)(=[O:18])[C:2]1[CH:3]=[CH:7][CH:8]=[CH:9][CH:10]=1
Reactant: COCCOC
Reactant: CC(C)(C)OC(=O)N1CCc2[nH]c3cccc(Br)c3c2CC1
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: CCOC(C)=O
Solvent: CCCCCC
Product: COc1ccccc1-c1cccc2[nH]c3c(c12)CCN(C(=O)c1ccccc1)CC3
Temperature: 25 °C

Procedure:
tert-Butyl 10-bromo-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (4.40 g, 11.9 mmol), Pd(PPh3)4 (1.40 g, 1.21 mmol), and dimethoxyethane (60 mL) were stirred at room temperature for 15 minutes then treated with 2-methoxyboronic acid (2.18 g, 14.3 mmol) and a 2 M solution of Na2CO3 (36 mL). The reaction was heated to reflux for 17.0 hours then cooled to room temperature and partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate (2×) and the organic layers were combined, washed with brine, dried over MgSO4 and concentrated in vacuo to give a brown foam which was passed through a column of silica gel with 40% ethyl acetate/hexane to give 3.87 g (82%) of a white solid as the title compound: mp 218.9-221.6° C. 1H NMR (400 MHz, DMSO-d6) δ 10.95-10.85 (m, 1H), 7.43-7.38 (m, 4H), 7.27-7.23 (m, 2H), 7.17-6.97 (m, 4H), 6.67-6.61 (m, 1H), 3.82 (m, 1H), 3.66-3.53 (m, 5H), 3.27 (m, 1H), 3.09-3.06 (m, 1H), 2.85 (m, 1H), 2.39-2.32 (m, 1H), 2.17-2.13 (m, 1H); 13C NMR (100 MHz, DMSO-d6) δ 170.1, 169.8, 156.8, 156.7, 137.1, 135.7, 134.8, 134.6, 130.8, 130.5, 130.4, 130.2, 130.0, 128.9, 128.5, 128.3, 128.2, 126.1, 126.0, 120.5, 119.9, 119.8, 119.7, 111.2, 110.5, 110.2, 109.7, 109.5, 54.9, 54.7, 49.6, 48.3, 46.1, 44.2, 29.4, 27.5, 25.7, 24.6; IR (diffuse reflectance) 3202, 3181 (b), 1602 (s), 1500, 1489, 1466, 1434, 1299, 1266, 1249, 1241, 786, 759 (s), 748, 707 cm−1; HRMS (FAB) calcd for C26H24N2O2+H1 397.1916, found 397.1910. Anal. Calcd for C26H24N2O2: C, 78.76; H, 6.10; N, 7.07. Found: C, 78.40; H, 6.22; N, 6.97.
Reaction SMILES: [N:1]1[C:14]2[C:5](=[CH:6][CH:7]=[C:8]3[C:13]=2[N:12]=[CH:11][CH:10]=[CH:9]3)[CH:4]=[CH:3][CH:2]=1.[CH3:15][I:16]>[N+](C1C=CC=CC=1)([O-])=O>[I-:16].[CH3:15][N+:1]1[C:14]2[C:5](=[CH:6][CH:7]=[C:8]3[C:13]=2[N:12]=[CH:11][CH:10]=[CH:9]3)[CH:4]=[CH:3][CH:2]=1
Reactant: CI
Reactant: c1cnc2c(c1)ccc1cccnc12
Solvent: O=[N+]([O-])c1ccccc1
Product: C[n+]1cccc2ccc3cccnc3c21
Product: [I-]
Yield: 88 %

Procedure:
Under a stream of argon, 1,10-phenanthroline (23 g; 127 mmol) was dissolved in nitrobenzene (500 mL). To the reaction mixture, methyl iodide (45.29 g; 319 mmol) was 35° C. for 24 hours. The reaction mixture was cooled in an ice bath, filtered out. The resulting solids were sequentially washed with nitrobenzene, benzene, and ethanol, and evaporated under reduced pressure to give 36 g (yield: 88%) of the title compound (1).
Reaction SMILES: [CH3:1][NH:2][S:3]([C:6]1[CH:7]=[C:8]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:9]=[CH:10][CH:11]=1)(=[O:5])=[O:4].[N:19]([O-:21])=[O:20].[Na+]>C(O)(C(F)(F)F)=O>[CH3:1][NH:2][S:3]([C:6]1[CH:7]=[C:8]([O:12][C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][CH:14]=2)[CH:9]=[CH:10][CH:11]=1)(=[O:4])=[O:5]
Reactant: CNS(=O)(=O)c1cccc(Oc2ccccc2)c1
Reactant: O=N[O-]
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Product: CNS(=O)(=O)c1cccc(Oc2ccc([N+](=O)[O-])cc2)c1
Temperature: -10 °C
Reaction time: 1 h
Yield: 56.9 %

Procedure:
To a solution of 4-(3-(N-methylsulfamoyl)phenyloxy)benzene (0.30 g, 1.14 mmol) in TFA (6 mL) at −10° C. was added NaNO2 (0.097 g, 1.14 mmol) in portions over 5 min. The resulting solution was stirred at −10° C. for 1 h, then was allowed to warm to room temp., and was concentrated under reduced pressure. The residue was separated between EtOAc (10 mL) and water (10 mL). The organic phase was sequentially washed with water (10 mL) and a saturated NaCl solution (10 mL), dried (MgSO4) and concentrated under reduced pressure to give 4-(3-(N-methylsulfamoyl)phenyloxy)-1-nitrobenzene (0.20 g). This material carried on to the next step without further purification.