Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CN1CCCC1=O.F[C:9]1[C:14]([F:15])=[C:13]([CH3:16])[C:12]([F:17])=[C:11]([F:18])[N:10]=1.[CH2:19]([NH2:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C(Cl)(Cl)Cl>[CH2:19]([NH:26][C:9]1[C:14]([F:15])=[C:13]([CH3:16])[C:12]([F:17])=[C:11]([F:18])[N:10]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: NCc1ccccc1
Reactant: Cc1c(F)c(F)nc(F)c1F
Solvent: CN1CCCC1=O
Solvent: ClC(Cl)Cl
Product: Cc1c(F)c(F)nc(NCc2ccccc2)c1F
Temperature: 80 °C
Reaction time: 2 h

Procedure:
To 2 ml of N-methylpyrrolidone were added 1.65 g of 2,3,5,6-tetrafluoro-4-methylpyridine and 2.30 g of benzylamine, and the mixture was stirred at 80° C. for 2 hours and allowed to cool. After adding 25 ml of chloroform, the mixture was washed three times with 300 ml of distilled water. The chloroform layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain the title compound in crude form.
Reaction SMILES: Cl[CH:2]([CH2:12][S:13]([F:18])([F:17])([F:16])([F:15])[F:14])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][S:8]([OH:11])(=[O:10])=[O:9].[OH-].[Na+:20]>O1CCCC1>[F:18][S:13]([F:14])([F:15])([F:16])([F:17])[CH:12]=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][S:8]([O-:11])(=[O:9])=[O:10].[Na+:20]
Reactant: O=S(=O)(O)CCCCCC(Cl)CS(F)(F)(F)(F)F
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: O=S(=O)([O-])CCCCCC=CS(F)(F)(F)(F)F
Temperature: 97 °C

Procedure:
10g (29.35 mmol; 1 eq) of sulfonic acid from Example 6b are suspended in 400 ml of tetrahydrofuran in a 500 ml flask, and 11.74 g (293.5 mmol; 10 eq) of sodium hydroxide are subsequently added. The reaction mixture is heated under reflux for 10 h, cooled and acidified, and the sulfonic acid is separated off from the aqueous phase by repeated extraction with methyl t-butyl ether. The organic phase is subsequently washed and evaporated to dryness. The crude sulfonic acid is suspended in 100 ml of ethanol, 1.4 g (35.22 mmol; 1.2 eq) of sodium hydroxide are added, and the mixture is heated at 97° C. for 1 h. After the suspension has been cooled, crystals deposit, which are filtered off and dried.
Reaction SMILES: C([O:3][C:4](=[O:21])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH2:15][C:16]1[NH:17][CH:18]=[CH:19][N:20]=1)C>O>[NH:17]1[CH:18]=[CH:19][N:20]=[C:16]1[CH2:15][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[O:8][CH2:7][CH2:6][CH2:5][C:4]([OH:21])=[O:3]
Reactant: CCOC(=O)CCCOc1ccccc1Cc1ncc[nH]1
Solvent: O
Product: O=C(O)CCCOc1ccccc1Cc1ncc[nH]1

Procedure:
Hydrolysis of 4-[2-(1-imidazolylmethyl)phenoxy]butyric acid ethyl ester by the method of Example 14 gave 4-[2-(1-imidazolylmethyl)phenoxy]butyric acid, m.p. 150°-152° C. (from water). Found: C, 64.27, H, 6.29, N, 10.71. C14H16N2O3 requires: C, 64.59, H, 6.19, N, 10.76%.
Reaction SMILES: [C:1]1(O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1.[CH2:34]([NH2:38])[CH2:35][CH2:36][CH3:37]>>[CH2:34]([NH:38][C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1)[CH2:35][CH2:36][CH3:37]
Reactant: CCCCN
Reactant: Oc1cccc2ccccc12
Agent: c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1
Product: CCCCNc1cccc2ccccc12
Yield: 87 %

Procedure:
288 parts of α-naphthol, 10 parts of triphenyl phosphite and 160 parts of n-butylamine are heated for 20 hours at 220° C in a pressure autoclave, whilst stirring. The further working up is carried out as described in Example 3. 346 parts of n-butyl-α-naphthylamine, boiling at 160° - 162° C/18 mm Hg, are obtained, corresponding to a yield of 87% of theory.
Reaction SMILES: N[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5]([Br:11])=[CH:4][N:3]=1.N([O-])=O.[Na+].N.C(OCC)C.[ClH:22]>O.[Cu]Cl>[Br:11][C:5]1[CH:6]=[C:7]([N+:8]([O-:10])=[O:9])[C:2]([Cl:22])=[N:3][CH:4]=1
Reactant: Cl
Reactant: Nc1ncc(Br)cc1[N+](=O)[O-]
Agent: Cl[Cu]
Agent: N
Agent: O=N[O-]
Solvent: CCOCC
Solvent: O
Product: O=[N+]([O-])c1cc(Br)cnc1Cl
Temperature: 0 °C
Reaction time: 1 h
Yield: 55 %

Procedure:
2-Amino-5-bromo-3-nitropyridine (21.8 g, 0.1 mol) was ground to a fine powder using a mortar and pestle and then suspended in 6M hydrochloric acid (250 ml). This mixture was cooled to 0° C. and treated with solid NaNO2 (8.3 g, 0.12 mol) at such a rate that the internal temperature remained below 5° C. (ca. 45 minutes). Following the addition, stirring at 0° C. was continued for a further 1 hour. To the resultant suspension was added a solution of freshly prepared copper(I) chloride (12.9 g. 0.13 mol) in degassed 38% hydrochloric acid and the reaction stirred to ambient temperature over 90 minutes before heating the reaction to 70° C. to complete the decomposition of the diazonium salt. The reaction was cooled, diluted with water (750 ml) and then air was passed through the mixture for 30 minutes before adding 0.88 ammonia to ca. pH 9. The blue mixture was shaken with diethyl ether (600 ml) and any remaining solids removed by filtration. The organic layer was then washed with 5% aqueous ammonia, water, brine and dried over anhydrous sodium sulphate. This solution was filtered and then pre-adsorbed on to silica. Purification by dry flash chromatography eluting with isohexane and a gradient of ethyl acetate from 5% to 20% gave 5-bromo-2-chloro-3-nitropyridine as a pale yellow solid (13.1 g, 55%) followed by recovered starting material (6.4 g); δH (400 MHz, CDCl3) 8.36 (1H, d, J 1, H-6), 8.69 (1H, d, J 1, H-4).
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[C:8]([C:11]([F:14])([F:13])[F:12])[C:7]([C:15]#[N:16])=[CH:6][CH:5]=2.Cl[CH2:18][C:19]1[N:20]=[C:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[Cl:30])[S:22][CH:23]=1>>[Cl:30][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[C:21]1[S:22][CH:23]=[C:19]([CH2:18][N:3]2[C:4]3[C:9](=[C:8]([C:11]([F:12])([F:14])[F:13])[C:7]([C:15]#[N:16])=[CH:6][CH:5]=3)[CH:10]=[C:2]2[CH3:1])[N:20]=1
Reactant: Cc1cc2c(C(F)(F)F)c(C#N)ccc2[nH]1
Reactant: ClCc1csc(-c2ccccc2Cl)n1
Product: Cc1cc2c(C(F)(F)F)c(C#N)ccc2n1Cc1csc(-c2ccccc2Cl)n1

Procedure:
Synthesized as described in Example 4 using 2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (Example 120) and 4-(chloromethyl)-2-(2-chlorophenyl)-1,3-thiazole: 1H NMR (400 MHz, CDCl3) δ 8.17 (m, 1H), 7.58 (d, J=8.3 Hz, 1H), 7.49 (m, 2H), 7.36 (m, 2H), 6.79 (s, 1H), 6.65 (s, 1H), 5.51 (s, 2H), 2.58 (s, 3H); MS (ES) m/z 432 (M+1) and 434 (M+1, isotope).
Reaction SMILES: C(N=C=NC(C)C)(C)C.[CH3:10][Si:11]([CH3:36])([CH2:30][CH2:31][C:32]([F:35])([F:34])[F:33])[CH2:12][CH2:13][CH2:14][CH2:15][O:16][C:17]1[CH:18]=[N:19][C:20]([C:23]2[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=2)=[N:21][CH:22]=1.[CH2:37]([C@H:42]1[CH2:47][CH2:46][C@H:45]([C:48](O)=[O:49])[CH2:44][CH2:43]1)[CH2:38][CH2:39][CH2:40][CH3:41].CN(C1C=CC=CN=1)C>C(OCC)(=O)C>[CH3:36][Si:11]([CH3:10])([CH2:30][CH2:31][C:32]([F:35])([F:33])[F:34])[CH2:12][CH2:13][CH2:14][CH2:15][O:16][C:17]1[CH:22]=[N:21][C:20]([C:23]2[CH:28]=[CH:27][C:26]([O:29][C:48]([C@H:45]3[CH2:46][CH2:47][C@H:42]([CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])[CH2:43][CH2:44]3)=[O:49])=[CH:25][CH:24]=2)=[N:19][CH:18]=1
Reactant: CCCCC[C@H]1CC[C@H](C(=O)O)CC1
Reactant: C[Si](C)(CCCCOc1cnc(-c2ccc(O)cc2)nc1)CCC(F)(F)F
Agent: CC(C)N=C=NC(C)C
Agent: CN(C)c1ccccn1
Solvent: CCOC(C)=O
Product: CCCCC[C@H]1CC[C@H](C(=O)Oc2ccc(-c3ncc(OCCCC[Si](C)(C)CCC(F)(F)F)cn3)cc2)CC1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
A solution of diisopropyl-carbodiimide (DIC) (0.0454 g, 0.360 mmol) in ethyl acetate (3.0 ml) was added dropwise to a stirred solution of compound 41 (0.119 g, 0.300 mmol), trans-4-pentylcyclohexanecarboxlic acid (0.0713 g, 0.369 mmol) and dimethylaminopyridine (DMAP) (3.66 mg, 0.03 mmol) in ethyl acetate (3.0 ml). The reaction mixture was stirred at room temperature for 24 h, the solvent removed in vacuo and the residues purified by column chromatography [silica gel, eluted with hexane/ethyl acetate (4:1)] to give a colorless solid, which recrystallized acetonitrile to yield colorless crystals.
Reaction SMILES: [CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[N:11]1[C:14](=[O:15])[C:13]([CH3:17])([CH3:16])[NH:12]1)[CH2:8]2.[CH3:18][S:19][C:20]1[CH:27]=[CH:26][CH:25]=[CH:24][C:21]=1[CH2:22]Br>>[CH3:16][C:13]1([CH3:17])[N:12]([CH2:22][C:21]2[CH:24]=[CH:25][CH:26]=[CH:27][C:20]=2[S:19][CH3:18])[N:11]([CH:2]2[CH:3]3[CH2:4][CH:5]4[CH2:6][CH:7]([CH2:8][CH:1]2[CH2:10]4)[CH2:9]3)[C:14]1=[O:15]
Reactant: CC1(C)NN(C2C3CC4CC(C3)CC2C4)C1=O
Reactant: CSc1ccccc1CBr
Product: CSc1ccccc1CN1N(C2C3CC4CC(C3)CC2C4)C(=O)C1(C)C

Procedure:
2-(Adamantan-2-yl)-4,4-dimethyl-1,2-diazetidin-3-one and 2-(methylthio)benzyl bromide were used for a similar reaction and treatment as Process 6 of Example 1, and the title compound was obtained as a white crystalline powder.
Reaction SMILES: [N:1]1[NH:2][CH:3]=[C:4]2[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6][C:5]=12.[Br:18][C:19]1[N:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1.N1C=CC=CC=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Br:18][C:19]1[N:24]=[CH:23][C:22]([N:2]2[CH:3]=[C:4]3[C:5]([CH2:6][CH2:7][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:9][CH2:10]3)=[N:1]2)=[CH:21][CH:20]=1
Reactant: CC(C)(C)OC(=O)N1CCc2c[nH]nc2CC1
Reactant: OB(O)c1ccc(Br)nc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(C)(C)OC(=O)N1CCc2cn(-c3ccc(Br)nc3)nc2CC1
Reaction time: 192 h

Procedure:
A mixture of 1,1-dimethylethyl 4,5,7,8-tetrahydropyrazolo[3,4-d]azepine-6(2H)-carboxylate (may be prepared as described in Description 9) (207 mg, 0.87 mmol), (6-bromo-3-pyridinyl)boronic acid (204 mg, 1.74 mmol), copper acetate (472 mg, 2.61 mmol), pyridine (140 μl, 1.74 mmol) and molecular sieves (4 Å, 750 mg) in dichloromethane (10 ml) was stirred open to the atmosphere for 8 days. Crude mixture was then filtered through a pad of celite and washed with dichloromethane and ammonia. After evaporation in vacuo, the residue was purified by SCX cartridge eluting with methanol first then 2M ammonia in methanol. The methanol fractions containing the product were combined and evaporated in vacuo. The residue was then purified by column chromatography on silica gel eluting with a mixture of hexane in ethyl acetate (10:1 to 1:1) to afford the title compound (D17). MS (ES+) m/e 393 and 395 [M+H]+.
Reaction SMILES: [CH3:1][N:2]([C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])[NH2:3].Cl[CH2:12]/[CH:13]=[CH:14]\[CH2:15]Cl>>[N:3]1([N:2]([CH3:1])[C:4](=[O:5])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8])[CH2:15][CH:14]=[CH:13][CH2:12]1
Reactant: CN(N)C(=O)OC(C)(C)C
Reactant: ClC/C=C\CCl
Product: CN(C(=O)OC(C)(C)C)N1CC=CC1
Yield: 86.3 %

Procedure:
Using tert-butyl 1-methylhydrazinecarboxylate (5.00 g, 34.2 mmol) and (2Z)-1,4-dichloro-2-butene (3.6 ml, 34.2 mmol), and according to the method of Reference Example 35, step A, the title compound (5.85 g, yield 86%) was obtained as a yellow oil.
Reaction SMILES: [C:1]1([CH3:8])[CH:6]=[CH:5][C:4]([SH:7])=[CH:3][CH:2]=1.C[O-].[Na+].CN(C=O)C.C1(C)C=CC(S(O[CH:27]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([C:36](=[O:43])[C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH:31]=2)[C:28]#[N:29])(=O)=O)=CC=1>CO.O>[C:1]1([CH3:8])[CH:6]=[CH:5][C:4]([S:7][CH:27]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([C:36](=[O:43])[C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH:31]=2)[C:28]#[N:29])=[CH:3][CH:2]=1
Reactant: Cc1ccc(S)cc1
Reactant: Cc1ccc(S(=O)(=O)OC(C#N)c2cccc(C(=O)c3ccccc3)c2)cc1
Agent: C[O-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CO
Product: Cc1ccc(SC(C#N)c2cccc(C(=O)c3ccccc3)c2)cc1
Temperature: -15 °C
Reaction time: 0.5 h
Yield: 81.5 %

Procedure:
p-Toluenethiol (372 mg) was dissolved in 2 ml of anhydrous methanol, and 1.20 ml of a 2.5 M methanol solution of sodium methoxide was added at room temperature in an atmosphere or argon. The mixture was cooled to -15° C., and stirred. Then, 4 ml of an anhhdrous DMF solution containing 1.170 g of O-(p-toluenesulfonyl)-m-benzoylmandelonitrile was added over 10 minutes. With continued stirring, the mixture was gradually warmed, and in 30 minutes, the temperature rose to 0° C. At this time, 30 ml of water was added to the reaction mixture, and the mixture was extracted with 20 ml of methylene chloride three times. The extract was washed with 20 ml of water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel; benzene) to afford 837 mg (yield 82%) of alpha-(p-tolylthio)(m-benzoylphenyl)acetonitrile as colorless crystals.
Reaction SMILES: C(OC([N:8]([C:10]1([C@@H:13]2[CH2:17][CH2:16][NH:15][CH2:14]2)[CH2:12][CH2:11]1)[CH3:9])=O)(C)(C)C.C(N(CC)CC)C.F[C:26]1[C:35]([O:36][CH3:37])=[C:34]2[C:29]([C:30](=[O:45])[C:31]([C:42]([OH:44])=[O:43])=[CH:32][N:33]2[C@@H:38]2[CH2:40][C@@H:39]2[F:41])=[CH:28][CH:27]=1>CS(C)=O>[F:41][C@H:39]1[CH2:40][C@H:38]1[N:33]1[C:34]2[C:29](=[CH:28][CH:27]=[C:26]([N:15]3[CH2:16][CH2:17][C@@H:13]([C:10]4([NH:8][CH3:9])[CH2:11][CH2:12]4)[CH2:14]3)[C:35]=2[O:36][CH3:37])[C:30](=[O:45])[C:31]([C:42]([OH:44])=[O:43])=[CH:32]1
Reactant: CN(C(=O)OC(C)(C)C)C1([C@@H]2CCNC2)CC1
Reactant: COc1c(F)ccc2c(=O)c(C(=O)O)cn([C@@H]3C[C@@H]3F)c12
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: CNC1([C@@H]2CCN(c3ccc4c(=O)c(C(=O)O)cn([C@@H]5C[C@@H]5F)c4c3OC)C2)CC1
Temperature: 100 °C
Yield: 49.7 %

Procedure:
After adding 3-(R)-[1-[N-(tert-butoxycarbonyl)-N-(methyl)amino]cyclopropyl]pyrrolidine (102 mg, 379 μmol) and triethylamine (0.50 ml) to dried dimethyl sulfoxide (1 ml, 7-fluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid (112 mg, 379 μmol) was added thereto and stirred while heating in an oil bath of 100° C. for 15 hours under a nitrogen atmosphere. After concentrating the reaction solution under a reduced pressure, the residue was dissolved in chloroform (100 ml). After washing the organic layer with a 10% aqueous citric acid solution (100 ml), the organic layer was dried over anhydrous sodium sulfate. After filtering, the filtrate was concentrated under a reduced pressure, and after adding dropwise concentrated hydrochloric acid (2 ml) to the residue while cooling with ice, it was stirred at room temperature for 30 minutes. After adding 1 mol/l hydrochloric acid (2 ml) to the reaction solution and washing the yellow acidic aqueous solution with chloroform (50 ml×4), the pH was adjusted to 12.0 with an aqueous sodium hydroxide solution. After adjusting the pH of the basic aqueous solution to 7.4 with 1 mol/l hydrochloric acid, extraction with chloroform (100 ml×3) was performed. After drying over anhydrous sodium sulfate, the solvent was evapolated under a reduced pressure. The residue thus obtained was then purified by a preparative chromatography (developed into the lower layer of a 7:3:1 mixture of chloroform:methanol:water), purified further by recrystallization from ethanol, and then dried under a reduced pressure. 78.3 mg (50%) of the title compound was thereby obtained in the form of yellow crystals.
Reaction SMILES: [F:1][C:2]1[C:3]([F:13])=[CH:4][C:5]2[O:9][C:8]([C:10]#[N:11])=[CH:7][C:6]=2[CH:12]=1.Cl.[NH2:15][OH:16].C(=O)([O-])[O-].[K+].[K+]>C(O)C>[F:1][C:2]1[C:3]([F:13])=[CH:4][C:5]2[O:9][C:8]([C:10](=[N:15][OH:16])[NH2:11])=[CH:7][C:6]=2[CH:12]=1
Reactant: NO
Reactant: N#Cc1cc2cc(F)c(F)cc2o1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: NC(=NO)c1cc2cc(F)c(F)cc2o1
Yield: 61.9 %

Procedure:
A mixture of 1.2 g (6.7 mmol) of 5,6-difluorobenzofuran-2-carbonitrile, 0.93 g (13.4 mmol) of hydroxylamine hydrochloride, 2.78 g (20.1 mmol) of potassium carbonate and 50 ml of anhydrous ethanol was heated under reflux over 16 hours while stirring. Subsequently, the solid was filtered off and the filtrate was concentrated in a vacuum. The crude product obtained was purified by column chromatography on silica gel (ethyl acetate/hexane 3:2). There was obtained 0.88 g (61%) of 5,6-difluorobenzofuran-2-carboxamidoxime as a light yellow solid with m.p. 184°.
Reaction SMILES: [SH:1][CH2:2][C:3]([O:5][CH3:6])=[O:4].[C:7]([C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]([CH3:19])[C:11]=1Cl)(=O)[CH3:8].C([O-])([O-])=O.[K+].[K+].O>CO>[CH3:8][C:7]1[C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]([CH3:19])[C:11]=2[S:1][C:2]=1[C:3]([O:5][CH3:6])=[O:4]
Reactant: CC(=O)c1c(Cl)n(C)c2ccccc12
Reactant: COC(=O)CS
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: COC(=O)c1sc2c(c1C)c1ccccc1n2C
Reaction time: 8 h

Procedure:
450 μl of methyl 2-mercaptoacetate was added to a slurry of 870 mg of (76) and 1.2 g of K2CO3 in 10 ml of MeOH. The reaction was stirred overnight. 30 ml of water was added, stirring continued for 1 hour, and the product filtered off giving 160 mg of product. Recrystallization from MeOH gave 30 mg of (77). M.p. 165.5°-166.8° C.
Reaction SMILES: [Si]([O:18][C:19]1[C:24]([CH3:25])=[C:23]([CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][O:36][C:37]([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)C(O)=[C:21]([O:57][CH3:58])[C:20]=1[O:59][CH3:60])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[C:61]([O:68][C:69]([O:71][C:72]([CH3:75])([CH3:74])[CH3:73])=[O:70])(OC(C)(C)C)=O.C(N(CC)CC)C>ClCCl>[C:72]([O:71][C:69]([O:68][C:61]1[C:23]([CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][O:36][C:37]([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)=[C:24]([CH3:25])[C:19]([OH:18])=[C:20]([O:59][CH3:60])[C:21]=1[O:57][CH3:58])=[O:70])([CH3:73])([CH3:74])[CH3:75]
Reactant: COc1c(O)c(CCCCCCCCCCOC(c2ccccc2)(c2ccccc2)c2ccccc2)c(C)c(O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)c1OC
Reactant: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1c(O)c(C)c(CCCCCCCCCCOC(c2ccccc2)(c2ccccc2)c2ccccc2)c(OC(=O)OC(C)(C)C)c1OC
Temperature: 40 °C
Reaction time: 16 h
Yield: 150.3 %

Procedure:
A mixture of 4-tert-butyldiphenylsilyloxy-2,3-dimethoxy-5-methyl-6-(10-trityloxydecyl)phenol (8 g), di-tert-butyl dicarbonate (3 g), triethylamine (1 g) and dichloromethane (20 ml) was stirred at 40° C. for 16 hours. After concentration under reduced pressure, the residue was dissolved in tetrahydrofuran (30 ml). Tetrabutylammonium fluoride trihydrate (2 g) was added, and the mixture was stirred at room temperature for 15 minutes. The solvent was distilled off under reduced pressure, and the residue was subjected to column chromatography on silica gel and eluted with hexane/ethyl acetate (7:3) to obtain the desired compound (10 g).
Reaction SMILES: [C:1]([N:4]1[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1)(=[O:3])[CH3:2].[CH3:11][OH:12]>F[B-](F)(F)F.C[N+](C)(C)C>[C:1]([N:4]1[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH:5]1[O:12][CH3:11])(=[O:3])[CH3:2]
Reactant: CC(=O)N1CCCCCC1
Reactant: CO
Agent: C[N+](C)(C)C
Agent: F[B-](F)(F)F
Product: COC1CCCCCN1C(C)=O
Yield: 90.3 %

Procedure:
In the same manner as indicated in Example 6 there are electrolyzed 23.2 g of N-acetylhexahydroazepine and 57.7 g of methanol in the presence of 0.26 g of tetramethylammonium tetrafluoroborate as conducting salt. After throughput of 2.5 Faraday per mol of N-acetylhexahydroazepine the current is switched off. The calculated mean cell voltage is 40.8 volts. Work-up of the electrolysis solution gives 25.4 g of 1-acetyl-2-methoxyhexahydroazepine (boiling point 53° C./0.06 mbar; nD25 = 1.4775), which corresponds to a product yield of 90.1% and a current efficiency of 71.5%.
Reaction SMILES: C1CCN2C(=NCCC2)CC1.[CH3:12]/[C:13](=[CH:16]\[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)/[CH:14]=[O:15].[N:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:24]>ClCCl>[OH:24][N:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:14](=[O:15])/[C:13](/[CH3:12])=[CH:16]/[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: O=Nc1ccccc1
Reactant: C/C(C=O)=C\c1ccccc1
Solvent: ClCCl
Solvent: C1CCC2=NCCCN2CC1
Product: C/C(=C\c1ccccc1)C(=O)N(O)c1ccccc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
DBU (15 mg, 0.1 mmol) was added under argon to a solution of (E)-2-methyl-3-phenylacrylaldehyde (146 mg, 1 mmol), nitrosobenzene (107 mg, 1 mmol) and catalyst (36.4 mg, 0.1 mmol) in dichloromethane (5 mL). The reaction mixture was stirred at room temperature for 10 min. The solvent was removed under vacuum, and the residue was purified by flash silica gel column chromatography using hexane and ethyl acetate as the eluents.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([NH:7]C(=O)OC(C)(C)C)[CH2:3][CH2:2]1.[CH3:15][C:16]([CH3:18])=O>>[CH3:15][CH:16]([N:1]1[CH2:2][CH2:3][CH:4]([NH2:7])[CH2:5][CH2:6]1)[CH3:18]
Reactant: CC(C)=O
Reactant: CC(C)(C)OC(=O)NC1CCNCC1
Product: CC(C)N1CCC(N)CC1

Procedure:
Synthesized according to the method of reagent preparation 9 by using acetone and 1,1-dimethylethyl piperidin-4-ylcarbamate. MS (EI) for C8H18N2: 143 (MH+).
Reaction SMILES: Cl.Cl.[CH2:3]([O:5][C:6](=[O:12])[CH2:7][NH:8][CH2:9][CH2:10][NH2:11])[CH3:4].[Cl:13][C:14]1[C:19]2[N:20]=[C:21]([S:23](Cl)(=[O:25])=[O:24])[S:22][C:18]=2[CH:17]=[CH:16][C:15]=1[O:27][CH3:28]>>[CH2:3]([O:5][C:6](=[O:12])[CH2:7][NH:8][CH2:9][CH2:10][NH:11][S:23]([C:21]1[S:22][C:18]2[CH:17]=[CH:16][C:15]([O:27][CH3:28])=[C:14]([Cl:13])[C:19]=2[N:20]=1)(=[O:25])=[O:24])[CH3:4]
Reactant: COc1ccc2sc(S(=O)(=O)Cl)nc2c1Cl
Reactant: CCOC(=O)CNCCN
Agent: Cl
Product: CCOC(=O)CNCCNS(=O)(=O)c1nc2c(Cl)c(OC)ccc2s1
Yield: 89 %

Procedure:
The title compound (726 mg, 89%) was synthesized by the reaction of N-(2-aminoethyl)-glycine ethyl ester 2HCl (398 mg, 2.0 mmol) with 4-chloro-5-methoxy-benzothiazole-2-sulfonyl chloride (596 mg, 2.0 mmol) as per the procedure of Example 1. 1H NMR (500 MHz; DMSO-d6) δ 8.18 (d, 1H), 7.57 (d, 1H), 4.00 (q, 2H), 3.97 (s, 3H), 3.22 (s, 2H), 3.14 (t, 2H), 2.62 (t, 2H), 1.13 (t, 3H).
Reaction SMILES: [CH3:1][CH:2]([CH3:15])[C:3]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([N+:12]([O-:14])=[O:13])[CH:7]=1)=[N:4][NH2:5].[CH2:16]([N:22]1[C:26](=[O:27])[CH:25]=[CH:24][C:23]1=[O:28])[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]>O1CCOCC1.[O-2].[O-2].[Mn+4]>[CH2:16]([N:22]1[C:23](=[O:28])[CH:24]2[CH:25]([N:5]=[N:4][C:3]2([CH:2]([CH3:15])[CH3:1])[C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([N+:12]([O-:14])=[O:13])[CH:7]=2)[C:26]1=[O:27])[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: CCCCCCN1C(=O)C=CC1=O
Reactant: CC(C)C(=NN)c1cccc([N+](=O)[O-])c1
Agent: [Mn+4]
Agent: [O-2]
Solvent: C1COCCO1
Product: CCCCCCN1C(=O)C2N=NC(c3cccc([N+](=O)[O-])c3)(C(C)C)C2C1=O
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
2-Methyl-1-(3-nitrophenyl)-1-propanone hydrazone (Preparation 57, 0.52 g, 2.5 mmol) was dissolved in dioxan (10 ml) and manganese dioxide (grade CMD-1 from Sumitomo, 5.2 g, 60.0 mmol) was added portionwise and the reaction mixture was stirred at room temperature for 20 minutes. This solution was filtered over a pad of Celite® dropwise, directly into a solution of 1-hexyl-1H-pyrrole-2,5-dione (Preparation 56, 0.54 g, 3.0 mmol) in dioxan (10 ml). The Celite® pad was washed with dioxan (40 ml) to ensure complete addition of the reactants and then the reaction mixture was stoppered and stirred for 72 h. The reaction mixture was purified by chromatography using a Biotage Flash 40S™ cartridge packed with silica gel (40 g), eluting with petroleum ether:ethyl acetate (4:1). The title compound was obtained as a yellow solid (0.65 g, 67%).