Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([N:11]2[CH2:14][CH:13]([OH:15])[CH2:12]2)[S:9][CH:10]=1)=[O:5])[CH3:2].[CH3:16][S:17](Cl)(=[O:19])=[O:18].C(N(CC)CC)C.C(O)C>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([N:11]2[CH2:12][CH:13]([O:15][S:17]([CH3:16])(=[O:19])=[O:18])[CH2:14]2)[S:9][CH:10]=1)=[O:5])[CH3:2]
Reactant: CS(=O)(=O)Cl
Reactant: CCOC(=O)c1csc(N2CC(O)C2)n1
Solvent: ClCCl
Solvent: CCO
Solvent: CCN(CC)CC
Product: CCOC(=O)c1csc(N2CC(OS(C)(=O)=O)C2)n1
Temperature: 25 °C
Reaction time: 2 h
Yield: 82.5 %

Procedure:
To a solution of 1-(4-ethoxycarbonyl-1,3-thiazol-2-yl)-3-hydroxyazetidine (676 mg, 2.96 mmol) (obtained as described in Reference Example 1(2)) in methylene chloride (20.5 ml) were added methanesulfonyl chloride (0.28 ml, 3.63 mmol) and triethylamine (0.495 ml, 3.56 mmol) in an ice bath. After stirring the mixture in the ice bath for 10 minutes, the mixture was stirred at room temperature for 2 hours. After checking the completion of the reaction, ethanol was added to the reaction mixture in an ice bath and the resulting mixture was stirred at room temperature for 30 minutes. The reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate solution. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using n-hexane:ethyl acetate (1:2) as the eluant to afford 1-(4-ethoxycarbonyl-1,3-thiazol-2-yl)-3-methanesulfonyloxyazetidine (748 mg, yield 82%) as a pale brown solid.
Reaction SMILES: [N:1]1[CH:2]=[C:3]([C:10]2[C:14](=[O:15])[NH:13][C:12](=[O:16])[C:11]=2[C:17]2[C:23]3[CH:24]=[C:25]([F:41])[CH:26]=[C:27]4[CH:28](CC[O-])[CH:29]([C:30]([N:32]5[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]5)=[O:31])[N:21]([C:22]=34)[CH2:20][CH2:19][N:18]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.Cl.[OH-:43].[Na+]>O>[OH2:15].[OH2:43].[N:1]1[CH:2]=[C:3]([C:10]2[C:14](=[O:15])[NH:13][C:12](=[O:16])[C:11]=2[C:17]2[C:23]3[CH:24]=[C:25]([F:41])[CH:26]=[C:27]4[CH2:28][CH:29]([C:30]([N:32]5[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37]5)=[O:31])[N:21]([C:22]=34)[CH2:20][CH2:19][N:18]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12
Reactant: [OH-]
Reactant: O=C1NC(=O)C(c2cnc3ccccn23)=C1C1=NCCN2c3c1cc(F)cc3C(CC[O-])C2C(=O)N1CCCCC1
Agent: Cl
Agent: [Na+]
Solvent: O
Product: O=C1NC(=O)C(c2cnc3ccccn23)=C1C1=NCCN2c3c(cc(F)cc31)CC2C(=O)N1CCCCC1
Temperature: 25 °C
Reaction time: 0.67 h

Procedure:
Heat a slurry of 7-(2,5-dihydro-4-imidazo[1,2-a]pyridine-3-yl-2,5-dioxo-1H-pyrrol-3-yl)-9-fluoro-1,2,3,4-tetrahydro-2-(1-piperidinyl-carbonyl)-pyrrolo[3,2,1-jk][1,4]benzodiazepine ethanolate (200.8 mg) in water (25 mL) to 75° C. for 0.67 hours. Add 0.72 mL of 1N HCl and continue to heat for 1.75 hours. Add 0.1N NaOH in 1 mL increments every 5 minutes until 7.2 mL have been added. After the last addition, allow the suspension to remain at 75° C. for 0.67 hours and then allow the suspension to cool to room temperature. Collect the solid using vacuum filtration through Whatman #1 paper, rinse with 20 mL deionized water and allow to dry loosely covered for 2 days. Powder X-ray Principal Peaks (Degrees 2 Theta, Intensity): 5.498°, 100%; 22.149°, 100%; 14.921°, 32.9%; 11.399°, 36.7%; and 11.019°, 20.5%.
Reaction SMILES: [CH3:1][C:2]1([CH3:25])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]2[CH:7]=[C:6]([C:14]3[CH:24]=[CH:23][CH:22]=[CH:21][C:15]=3[C:16](OCC)=[O:17])[CH:5]=[CH:4][C:3]1=2.[H-].C([Al+]CC(C)C)C(C)C>>[CH3:1][C:2]1([CH3:25])[CH2:11][CH2:10][C:9]([CH3:12])([CH3:13])[C:8]2[CH:7]=[C:6]([C:14]3[CH:24]=[CH:23][CH:22]=[CH:21][C:15]=3[CH2:16][OH:17])[CH:5]=[CH:4][C:3]1=2
Reactant: CCOC(=O)c1ccccc1-c1ccc2c(c1)C(C)(C)CCC2(C)C
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Product: CC1(C)CCC(C)(C)c2cc(-c3ccccc3CO)ccc21

Procedure:
Employing the same general procedure as used for the preparation of 3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl)but-2(Z)-en-1-ol (Compound C), but instead using 420 mgs (1.25 mmols) ethyl 2-[5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]benzoate (Compound H) and 6 mmols of diisobutylaluminiumhydride the title compound was obtained as a white solid.
Reaction SMILES: Cl.[CH2:2]([O:4][C:5]([C:7]1[N:8]([CH2:23][C:24]2[C:33]3[C:28](=[CH:29][CH:30]=[C:31]([F:34])[CH:32]=3)[CH:27]=[CH:26][CH:25]=2)[C:9]2[C:14]([C:15]=1[CH2:16][NH:17]S(C)(=O)=O)=[CH:13][C:12]([F:22])=[CH:11][CH:10]=2)=[O:6])[CH3:3]>>[CH2:2]([O:4][C:5]([C:7]1[N:8]([CH2:23][C:24]2[C:33]3[C:28](=[CH:29][CH:30]=[C:31]([F:34])[CH:32]=3)[CH:27]=[CH:26][CH:25]=2)[C:9]2[C:14]([C:15]=1[CH2:16][NH2:17])=[CH:13][C:12]([F:22])=[CH:11][CH:10]=2)=[O:6])[CH3:3]
Reactant: CCOC(=O)c1c(CNS(C)(=O)=O)c2cc(F)ccc2n1Cc1cccc2ccc(F)cc12
Agent: Cl
Product: CCOC(=O)c1c(CN)c2cc(F)ccc2n1Cc1cccc2ccc(F)cc12

Procedure:
salt with HCl (prepared according to Example 104.2.) was converted to 5-fluoro-1-(7-fluoro-naphthalen-1-ylmethyl)-3-(methanesulfonylamino-methyl)-1H-indole-2-carboxylic acid ethyl ester as described in Example 77.1. which was hydrolyzed as described in the general procedure B (Exp. 2.2) to give the title compound as a colorless solid. MS: 443.5 ([M−H]31 ).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([OH:9])=[CH:7][CH:6]=[CH:5][C:4]=1[C:10]1[NH:18][C:17]2[C:12](=[N:13][CH:14]=[N:15][CH:16]=2)[N:11]=1.[CH3:19][S:20](Cl)(=[O:22])=[O:21]>>[CH3:1][O:2][C:3]1[C:8]([O:9][S:20]([CH3:19])(=[O:22])=[O:21])=[CH:7][CH:6]=[CH:5][C:4]=1[C:10]1[NH:18][C:17]2[C:12](=[N:13][CH:14]=[N:15][CH:16]=2)[N:11]=1
Reactant: CS(=O)(=O)Cl
Reactant: COc1c(O)cccc1-c1nc2ncncc2[nH]1
Product: COc1c(OS(C)(=O)=O)cccc1-c1nc2ncncc2[nH]1

Procedure:
Prepared analogously to Example 1 from 8-(2'-methoxy-3'-hydroxy-phenyl)-purine and methanesulfonic acid chloride.
Reaction SMILES: [OH:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.[C:16]1(O)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC(N=NC(OC(C)(C)C)=O)=O)(C)(C)C>C1COCC1>[O:1]([CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: CC(C)(C)OC(=O)N1CCC(CO)CC1
Reactant: Oc1ccccc1
Agent: CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(COc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 18 h
Yield: 71.2 %

Procedure:
tert-Butyl 4-(hydroxymethyl)piperidine-1-carboxylate (0.300 g, 1.393 mmol), phenol (0.122 mL, 1.393 mmol), triphenylphosphine (0.440 g, 1.672 mmol) and N-{[(tert-butoxy)carbonyl]imino}(tert-butoxy)formamide (0.390 g, 1.672 mmol) were combined in THF (4 mL) and stirred at room temperature for 18 h. The reaction mixture was concentrated under reduced pressure and purified by FCC (EtOAc: heptane, 1:1) to afford a white solid. This was further purified by trituration with diethyl ether to afford the title compound (0.289 g, 71%). Method B HPLC-MS: MH+ requires m/z=292 Found: m/z=235 (MH+-tBu), Rt=2.44 min (71%).
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7](F)=[CH:6][CH:5]=1)=[O:3].[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1.C([O-])([O-])=O.[K+].[K+]>CS(C)=O>[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][C:7]2[CH:8]=[CH:9][C:4]([C:2](=[O:3])[CH3:1])=[CH:5][CH:6]=2)=[CH:15][CH:14]=1
Reactant: CC(=O)c1ccc(F)cc1
Reactant: COc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: COc1ccc(Oc2ccc(C(C)=O)cc2)cc1
Temperature: 80 °C
Reaction time: 8 h

Procedure:
138 mg (1 mmol) of 4-fluoroacetophenone were taken and 124 mg (1 mmol) of 4-methoxyphenol were dissolved in DMSO and added thereto, then 200 mg (1.45 mmol) of K2CO3 were added and the mixture was stirred for 8 h at 80° C., then for 6 h at 100° C., then for 3 h at 120° C. and for 3 h at 140° C. The reaction mixture was filtered through basic Alox, washed with DMF/methanol=9/1 and concentrated by rotary evaporation. The substance was purified by reversed-phase chromatography.
Reaction SMILES: [C:1]([O:5][C:6](=[O:31])[NH:7][CH2:8][C:9]1[N:10]([CH3:30])[C:11](=[O:29])[C:12]2[C:17]([C:18]=1[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([N+:25]([O-])=O)[CH:20]=1)=[CH:16][C:15]([Cl:28])=[CH:14][CH:13]=2)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].S(S([O-])=O)([O-])=O.[Na+].[Na+]>O>[C:1]([O:5][C:6](=[O:31])[NH:7][CH2:8][C:9]1[N:10]([CH3:30])[C:11](=[O:29])[C:12]2[C:17]([C:18]=1[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([NH2:25])[CH:20]=1)=[CH:16][C:15]([Cl:28])=[CH:14][CH:13]=2)([CH3:4])([CH3:3])[CH3:2]
Reactant: Cn1c(CNC(=O)OC(C)(C)C)c(-c2cccc([N+](=O)[O-])c2)c2cc(Cl)ccc2c1=O
Agent: O=C([O-])[O-]
Agent: O=S([O-])S(=O)[O-]
Agent: [K+]
Solvent: O
Product: Cn1c(CNC(=O)OC(C)(C)C)c(-c2cccc(N)c2)c2cc(Cl)ccc2c1=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 58.5 %

Procedure:
Tert-butyl{6-chloro-2-methyl-1-oxo-4-(3-nitrophenyl)-1,2-dihydro-3-isoquinolinyl}methylcarbamate (synthesized according to the method similar to that in Example 23 (6)) (0.89 g, 2 mmol) was added to an aqueous solution (10 ml) of potassium carbonate (2.90 g, 21 mmol) and sodium hydrosulfite (2.44 g, 14 mmol) and the mixture was stirred at room temperature for 1 h. The reaction mixture was poured into water and extracted with ethyl acetate. After washing the extract with water, the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give tert-butyl{4-(3-aminophenyl)-6-chloro-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl}methylcarbamate (0.48 g, 58.5%) as crystals.
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[C:6]1([CH:12]=[CH:13][C:14]([CH3:17])(O)[CH3:15])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[C:18]([O-:21])(=[O:20])C.[Na+]>CN(C)C=O.O>[CH3:15][C:14]([CH:13]=[CH:12][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[CH:17][C:18]([OH:21])=[O:20]
Reactant: CC(C)(O)C=Cc1ccccc1
Reactant: CC(=O)[O-]
Agent: [Na+]
Solvent: O=P(Cl)(Cl)Cl
Solvent: O
Solvent: CN(C)C=O
Product: CC(C=Cc1ccccc1)=CC(=O)O
Temperature: 25 °C
Reaction time: 3 h
Yield: 63.4 %

Procedure:
Dimethylformamide (DMF, anhydrous, 25 mL) was cooled to 0-5° C. and phosphorus oxychloride (16.4 mL) was added dropwise over a period of an hour. The resulting solution was added dropwise to a cooled (0-5° C.) solution of 4-phenyl-2-methyl-3-buten-2-ol (0.14 mol) in 60 mL of anhydrous DMF over a period of an hour. The reaction mixture was then warmed to room temperature, gradually heated up to 80° C., stirred at 80° C. for three hours and cooled to 0-5° C. To the cooled reaction solution was added dropwise a solution of sodium acetate (80 g) in deionized water (190 mL) over a period of two hours. The mixture was then reheated to 80° C., stirred at 80° C. for an additional 10 minutes, cooled down to room temperature and extracted with ether (300 mL) twice. The combined extract was washed with water (200 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuum to yield 16.7 g of the desired 3-methyl-5-phenyl-2,4-pentadienal as a liquid which was used in the next step without further purification.
Reaction SMILES: [NH2:1][C:2]1[CH:18]=[CH:17][CH:16]=[CH:15][C:3]=1[CH2:4][NH:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[O:13][CH3:14].[C:19](=S)=[S:20]>C(O)C>[CH3:14][O:13][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[CH2:6][N:5]1[CH2:4][C:3]2[C:2](=[CH:18][CH:17]=[CH:16][CH:15]=2)[NH:1][C:19]1=[S:20]
Reactant: COc1ccccc1CNCc1ccccc1N
Reactant: S=C=S
Solvent: CCO
Product: COc1ccccc1CN1Cc2ccccc2NC1=S

Procedure:
4.0 g (16.51 mmol) (2-aminobenzyl)(2-methoxybenzyl)amine in 100 mL ethanol was mixed with 40 mL CS2 and heated at reflux for 8 hours, forming a yellow precipitate. The mixture was evaluated and the resulting solids were recrystallized in ethanol; 4.24 g white solids.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:17][CH2:16][C:11]3([O:15][CH2:14][CH2:13][O:12]3)[CH2:10][CH2:9]2)[CH:5]=[CH:4][N:3]=1.[CH2:18]([NH2:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>O>[CH2:18]([NH:25][C:2]1[N:7]=[C:6]([N:8]2[CH2:17][CH2:16][C:11]3([O:15][CH2:14][CH2:13][O:12]3)[CH2:10][CH2:9]2)[CH:5]=[CH:4][N:3]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: NCc1ccccc1
Reactant: Clc1nccc(N2CCC3(CC2)OCCO3)n1
Solvent: O
Product: c1ccc(CNc2nccc(N3CCC4(CC3)OCCO4)n2)cc1
Temperature: 150 °C

Procedure:
A mixture of 8 g 8-(2-chloro-pyrimidin-4-yl)-1,4-dioxa-8-aza-spiro[4.5]decane 8a) and 7.2 ml benzylamine is heated for 2 hours at 150° C., then cooled, admixed with 20 ml water and the aqueous solution is extracted three times with 20 ml methylene chloride each time. After drying the combined organic phases over sodium sulfate and removing the solvent, the residue is washed with cold isohexane. In this way 9.6 g benzyl-[4-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-pyrimidin-2-yl]amine is obtained as a yellow powder. 1H-NMR (d6 -DMSO): δ=7.85 ppm (d, 1H); 7.40-7.18 (m, 5H) 7.15 (broad s, 1H, NH); 6.12 (d, 1H); 4.45 (d, 2H); 3.96 (s, 4H); 3.65 (m, 4H); 1.61 (m, 4H).
Reaction SMILES: [C:1]([N:11]1[CH2:18][C@@H:17]2[C@@H:13]([CH2:14][N:15]([C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:29][C@H:28]([CH2:30][NH2:31])[O:27][C:26]4=[O:32])=[CH:21][C:20]=3[F:33])[CH2:16]2)[CH2:12]1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].N1C=CC=CC=1.[C:40](OC(=O)C)(=[O:42])[CH3:41]>C(Cl)Cl>[C:1]([N:11]1[CH2:12][C@@H:13]2[C@@H:17]([CH2:16][N:15]([C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:29][C@H:28]([CH2:30][NH:31][C:40](=[O:42])[CH3:41])[O:27][C:26]4=[O:32])=[CH:21][C:20]=3[F:33])[CH2:14]2)[CH2:18]1)([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2]
Reactant: NC[C@H]1CN(c2ccc(N3C[C@H]4CN(C(=O)OCc5ccccc5)C[C@H]4C3)c(F)c2)C(=O)O1
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(=O)NC[C@H]1CN(c2ccc(N3C[C@H]4CN(C(=O)OCc5ccccc5)C[C@H]4C3)c(F)c2)C(=O)O1
Temperature: 0 °C
Reaction time: 15 h

Procedure:
To a flame dried flask equipped with a nitrogen inlet is introduced (R)-[3-[4-[cis-3-(carbobenzyloxy)-3,7-diazabicyclo[3.3.0]octan-7-yl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methanol (1.75 g, 3.84 mmol) and methylene chloride (100 mL) cooled to 0° C. Triethylamine (0.80 mL, 5.76 mmol) and methanesulfonyl chloride are added, stirred at 0° C. for 2 hours, and warmed to ambient temperature for 1 hour. The reaction is washed with water (30 mL), saturated sodium bicarbonate (30 mL), and saline (30 mL), dried over sodium sulfate, and concentrated in vacuo to give the crude (R)-[[3-[4-[cis-3-(carbobenzyloxy)-3,7-diazabicyclo[3.3.0]octan-7-yl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]methanesulfonate. (R)-[[3-[4-[cis-3-(Carbobenzyloxy)-3,7-diazabicyclo[3.3.0]octan-7-yl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]methanesulfonate is combined in a resealable tube with THF (5 mL), isopropanol (5 mL), and concentrated ammonium hydroxide (10 mL) and heated to 95° C. for 10 hours. The reaction is diluted with methylene chloride (50 mL) and washed with saline (30 mL), dried over sodium sulfate, concentrated in vacuo to give (S)-[[3-[4-[cis-3-(carbobenzyloxy)-3,7-diazabicyclo[3.3.0]octan-7-yl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]amine. The crude (S)-[[3-[4-[cis-3-(carbobenzyloxy)-3,7-diazabicyclo[3.3.0]octan-7-yl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]amine (1.67 g, 3.67 mmol) is dissolved in methylene chloride (20 mL), cooled to 0° C. under nitrogen, pyridine (0.89 mL, 11.02 mmol) and acetic anhydride (0.43 mL, 4.59 mmol) are added, and the reaction is stirred 15 hours at ambient temperature. The reaction is diluted with methylene chloride (50 mL), washed with 1N HCl (25 mL), saturated sodium bicarbonate (25 mL), saline (25 mL), dried over sodium sulfate, concentrated in vacuo, and chromatographed on silica gel (230-400 mesh, 200 mL), eluting with chloroform/methanol (98/2). The appropriate fractions are combined (Rf =0.15, TLC, chloroform/methanol, 95/5) and concentrated in vacuo to give the title compound, mp 165-168° C.
Reaction SMILES: C([O:4][CH2:5][C:6]1[CH:11]=[C:10]([O:12][CH2:13][CH:14]2[CH2:16][CH2:15]2)[CH:9]=[CH:8][N:7]=1)(=O)C>[OH-].[Na+]>[CH:14]1([CH2:13][O:12][C:10]2[CH:9]=[CH:8][N:7]=[C:6]([CH2:5][OH:4])[CH:11]=2)[CH2:15][CH2:16]1
Reactant: CC(=O)OCc1cc(OCC2CC2)ccn1
Agent: [Na+]
Agent: [OH-]
Product: OCc1cc(OCC2CC2)ccn1

Procedure:
To the crude 2-acetoxymethyl-4-cyclopropylmethoxy pyridine, NaOH (100 ml 2M) was added and the mixture was refluxed for 2 hours. The mixture was extracted with methylene chloride, and the phases were separated. The organic layer was dried with Na2SO4, filtered and the solvent was evaporated off, yielding 2.7 g of crude title compound. NMR data is given below. The crude product was used without any further purification.
Reaction SMILES: O.CS[C:4]1[NH:9][C:8]2[CH:10]=[CH:11][N:12]=[CH:13][C:7]=2[S:6](=[O:15])(=[O:14])[N:5]=1.O.[NH2:17][NH2:18]>CO>[NH:17]([C:4]1[NH:9][C:8]2[CH:10]=[CH:11][N:12]=[CH:13][C:7]=2[S:6](=[O:15])(=[O:14])[N:5]=1)[NH2:18]
Reactant: NN
Reactant: CSC1=NS(=O)(=O)c2cnccc2N1
Solvent: CO
Solvent: O
Product: NNC1=NS(=O)(=O)c2cnccc2N1
Temperature: 70 °C

Procedure:
3-Methylsulfanyl-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxide monohydrate (1.0 g) was added to hydrazine hydrate (0.8 ml) and the mixture was heated to 70° C. for 30 min. After cooling, the reaction mixture was supplemented with methanol (10 ml) and the solvents were removed by distillation under reduced pressure. The residue was dissolved in NaOH 2M (20 ml), treated with charcoal, filtered, and the filtrate was adjusted to pH 6-7 with HCl 1M. The precipitate so obtained was collected by filtration, washed with water an dried (yield: 0.8 g); m.p. 290°-292° C. (Compound 1).
Reaction SMILES: [CH3:1][C:2]1[C:19]([S:20][CH3:21])=[C:18]([C:22]([F:28])([F:27])[C:23]([F:26])([F:25])[F:24])[CH:17]=[CH:16][C:3]=1[C:4]([O:6][C:7]1[CH:8]2[CH2:15][CH:11]([C:12](=[O:14])[CH:13]=1)[CH2:10][CH2:9]2)=[O:5].ClC1C=CC=C(C(OO)=[O:37])C=1>ClCCl>[CH3:1][C:2]1[C:19]([S:20]([CH3:21])=[O:37])=[C:18]([C:22]([F:28])([F:27])[C:23]([F:25])([F:26])[F:24])[CH:17]=[CH:16][C:3]=1[C:4]([O:6][C:7]1[CH:8]2[CH2:15][CH:11]([C:12](=[O:14])[CH:13]=1)[CH2:10][CH2:9]2)=[O:5]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CSc1c(C(F)(F)C(F)(F)F)ccc(C(=O)OC2=CC(=O)C3CCC2C3)c1C
Solvent: ClCCl
Product: Cc1c(C(=O)OC2=CC(=O)C3CCC2C3)ccc(C(F)(F)C(F)(F)F)c1S(C)=O
Temperature: 25 °C

Procedure:
280 mg (90% by weight; 0.599 mmol) of 4-oxobicyclo[3.2.1]oct-2-en-2-yl 2-methyl-3-methylthio-4-pentafluoroethylbenzoate were introduced into 20 ml of dichloromethane and admixed with 134 mg (77% by weight; 0.599 mmol) of meta-chloroperbenzoic acid. The mixture was stirred at RT until monitoring of the reaction by thin-layer chromatography indicated complete conversion. For working up, the contents were washed once with 10% strength aqueous sodium hydrogensulfite solution, then twice with saturated aqueous sodium hydrogencarbonate solution. Finally, the organic phase was freed from the solvent. As the residue, 250 mg of product with a purity of 95% by weight were recovered.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=2)=[N:6][CH:7]=1.[Cu][C:15]#[N:16].[OH-].[Na+]>CN(C)C(=O)C>[C:15]([C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=2)=[N:6][CH:7]=1)#[N:16]
Reactant: N#C[Cu]
Reactant: Brc1ccc(-c2ccncc2)nc1
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)N(C)C
Product: N#Cc1ccc(-c2ccncc2)nc1
Yield: 83 %

Procedure:
By the same method as in Example 1,5-bromo-2,4′-bipyridine was prepared. The resulting 5-bromo-2,4′-bipyridine (7.0 g) was dissolved in N,N-dimethylacetamide (15 ml), followed by addition of copper (I) cyanide (2.8 g), for agitation at 140° C. for 3 hours. After the reaction solution was cooled, aqueous 25% NaOH solution (10 ml) was added to deposit a crystal, which was filtered and recovered, to obtain the object substance (4.5 g; yield of 83%).
Reaction SMILES: [C:1]1([NH2:12])[C:6]([F:7])=[C:5]([F:8])[C:4]([F:9])=[C:3]([NH2:10])[C:2]=1[F:11].[ClH:13].Cl.C([O-])([O-])=O.[Cs+].[Cs+].[Cl:21][CH2:22][C:23](N(CC)CC)=[O:24]>CN(C=O)C.CC#N.CCOC(C)=O>[ClH:21].[CH3:22][CH2:23][O:24][CH2:6][CH3:1].[C:1]1([NH2:12])[C:6]([F:7])=[C:5]([F:8])[C:4]([F:9])=[C:3]([NH2:10])[C:2]=1[F:11].[ClH:13].[ClH:21]
Reactant: CCN(CC)C(=O)CCl
Agent: Cl
Agent: Nc1c(F)c(N)c(F)c(F)c1F
Agent: O=C([O-])[O-]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CC#N
Product: CCOCC
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
To a solution of 17-7 dihydrochloride (0.145 g, 0.3 mmole) in dried DMF (5 ml) is added Cs2CO3 (1.95 g, 0.6 mmole). The resulting mixture is stirred at r.t. for 5 min, 2-chloro-N,N-diethylacetamide (0.090 g, 0.6 mmole) is added dropwise and the mixture is stirred overnight. The reaction was then diluted with CH3CN (50 m), the inorganics filtered and the filtrate concentrated to a viscous residue. Flash chromatography over silica gel (CHCl3 -MeOH 92.5=7.5) provided pure free base, Rf =0.52 (CHCl3 /MeOH, 9:1). Treatment of the free base in EtOAc with HCl/Ether provided the dihydrochloride salt 17-8.
Reaction SMILES: [H-].[Na+].[OH:3][C:4]1[CH:16]=[CH:15][C:7]2[O:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[C:6]=2[CH:5]=1.CS(O[CH2:22][CH2:23][F:24])(=O)=O>CN(C)C=O>[F:24][CH2:23][CH2:22][O:3][C:4]1[CH:16]=[CH:15][C:7]2[O:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[C:6]=2[CH:5]=1
Reactant: CS(=O)(=O)OCCF
Reactant: Oc1ccc2oc3ccccc3c2c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: FCCOc1ccc2oc3ccccc3c2c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 85.2 %

Procedure:
To a suspension of sodium hydride (60% oil dispersion; 4.0 g) in N,N-dimethylformamide (100 ml), 2-hydroxydibenzofuran (18.4 g) was added at a temperature of 0 to 5° C., and the resultant suspension was stirred at room temperature for 1 hour. 2-Fluoroethyl methanesulfonate (14.2 g) was added thereto. The resulting mixture was stirred at room temperature for 12 hours. The reaction mixture was poured into ice-water and extracted with ethyl acetate. The extract was washed with aqueous potassium carbonate solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was distilled under reduced pressure to give 2-(2-fluoroethoxy)-dibenzofuran (Compound No. 35) (19.6 g). b.p., 180°-185° C./5 mmHg.