Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[S:11](Cl)(=[O:13])=[O:12])(=[O:4])=[O:3].[NH2:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[N:21]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[N:20]=[C:19]2[CH2:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>N1C=CC=CC=1.O>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[S:11]([NH:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[N:21]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:30])[CH3:31])[N:20]=[C:19]2[CH2:33][CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)(=[O:13])=[O:12])(=[O:4])=[O:3]
Reactant: CS(=O)(=O)c1ccccc1S(=O)(=O)Cl
Reactant: C[Si](C)(C)CCOCn1nc(CCc2ccccc2)c2cc(N)ccc21
Solvent: c1ccncc1
Solvent: O
Product: C[Si](C)(C)CCOCn1nc(CCc2ccccc2)c2cc(NS(=O)(=O)c3ccccc3S(C)(=O)=O)ccc21
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 42.3 %

Procedure:
2-Methylsulfonyl-N-[3-phenethyl-1-(2-trimethylsilanylethoxymethyl)-1H-indazol-5-yl]benzenesulfonamide can be obtained in the following way: 0.6 g 2-methylsulfonylbenzenesulfonyl chloride is added portionwise to a solution, at a temperature in the region of 0° C. and under argon, of 0.83 g of 5-amino-3-phenethyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazole in 13 ml of pyridine. The reaction mixture is then stirred for 0.5 hours at a temperature in the region of 0° C. then 2 hours at a temperature in the region of 20° C., and is then diluted with 13 ml of water. After settling out, the aqueous phase is extracted with 3 times 30 ml of ethyl acetate. The organic extracts are pooled, washed with 2 times 15 ml of a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue thus obtained is purified by chromatography under argon pressure (50 kPa), on a cartridge of 70 g of silice (particle size 20-40 μm), eluting successively with pure cyclohexane then with a cyclohexane/ethyl acetate (80/20 by volume) mixture. The fractions containing the expected product are pooled and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 25° C. 0.56 g of 2-methylsulfonyl-N-[3-phenethyl-1-(2-trimethylsilanylethoxymethyl)-1H-indazol-5-yl]benzenesulfonamide are obtained in the form of a brown-colored paste (Rf=0.32, silica gel thin layer chromatography, eluent: cyclohexane/ethyl acetate (70/30 by volume)).
Reaction SMILES: CO[C:3]1[CH:12]=[CH:11][C:6]([C:7](=[O:10])[CH2:8][Br:9])=[CH:5][CH:4]=1.C(Br)C(C1C=CC=CC=1)=O.[C:23]([C:26]1[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=1)(=[O:25])[CH3:24]>N1C=CC=CC=1>[Br-:9].[CH2:8]([N+:29]1[CH:30]=[CH:31][C:26]([C:23](=[O:25])[CH3:24])=[CH:27][CH:28]=1)[C:7]([C:6]1[CH:5]=[CH:4][CH:3]=[CH:12][CH:11]=1)=[O:10]
Reactant: COc1ccc(C(=O)CBr)cc1
Reactant: CC(=O)c1ccncc1
Agent: O=C(CBr)c1ccccc1
Solvent: c1ccncc1
Product: CC(=O)c1cc[n+](CC(=O)c2ccccc2)cc1
Product: [Br-]

Procedure:
Employing the procedure of Example I above but replacing 4-methoxyphenacyl bromide with a substantially equimolecular amount of phenacyl bromide and replacing pyridine with a substantially equimolecular amount of 4-acetylpyridine there is obtained N-(phenacyl) 4-acetylpyridinium bromide, a white solid melting at 214-215° C., and which is soluble in water.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH:10]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1.C([BH3-])#N.[Na+]>C(O)C.O>[CH2:1]([N:8]1[CH2:13][CH2:12][C@H:11]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[C@H:10]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C1COCCN1
Reactant: O=C1CCN(Cc2ccccc2)CC1c1ccccc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: c1ccc(CN2CC[C@H](N3CCOCC3)[C@H](c3ccccc3)C2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 54.2 %

Procedure:
To a mixture of 1-benzyl-3-phenyl-piperidin-4-one (2.07 g, 7.78 mmol) and morpholine (678 mg, 7.78 mmol) was added tetraisopropyl-orthotitanate (2.97 mL, 9.73 mmol) at room temperature. After stirring at room temperature overnight the reaction mixture was diluted with ethanol (8.0 mL) and sodium cyanoborohydride (369 mg, 5.37 mmol) was added. The reaction mixture was stirred at room temperature for 24 h and was diluted with water (2.0 mL). The inorganic precipitate was filtered off and washed with ethanol. The filtrate was evaporated and purified by flash chromatography on silica gel with toluene/ethyl acetate 6:1 to give rac-cis-4-(1-benzyl-3-phenyl-piperidin-4-yl)-morpholine (1.42 g, 54%) as a yellow solid, MS: m/e=337.3 (M+H+).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[O:13][CH3:14])[CH:6]=[CH:7][C:8]#[N:9].N[OH:16].[CH2:17]([OH:19])[CH3:18].O>N1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[O:13][CH3:14])[CH:6]=[CH:7][C:8]#[N:9].[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[O:13][CH3:14])[CH:6]=[O:19].[C:8]([CH2:18][C:17]([OH:16])=[O:19])#[N:9]
Reactant: NO
Reactant: CCO
Agent: COc1ccc(C=CC#N)cc1OC
Solvent: c1ccncc1
Solvent: O
Product: COc1ccc(C=O)cc1OC
Product: N#CCC(=O)O

Procedure:
3,4-Dimethoxy-cinnamic acid amidoxime used as starting material was prepared by the reaction of 3,4-dimethoxycinnamonitrile with hydroxylamine under the usual conditions in ethanol-water solution. The 3,4-dimethoxycinnamonitrile was obtained from 3,4-dimethoxybenzaldehyde with cyanoacetic acid in pyridine solution by literature method (J. Am. Chem. Soc. 65, 22(1943)).
Reaction SMILES: [F:1][CH:2]([F:22])[O:3][C:4]1[C:9]2[O:10][C:11]3[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][C:12]=3[C:8]=2[C:7]([CH:20]=[O:21])=[CH:6][CH:5]=1.S(=O)(=O)([OH:25])N.Cl([O-])=O.[Na+]>CC(C)=O.O>[F:22][CH:2]([F:1])[O:3][C:4]1[C:9]2[O:10][C:11]3[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][C:12]=3[C:8]=2[C:7]([C:20]([OH:25])=[O:21])=[CH:6][CH:5]=1
Reactant: O=Cc1ccc(OC(F)F)c2oc3ccc([N+](=O)[O-])cc3c12
Reactant: NS(=O)(=O)O
Agent: [Na+]
Agent: [O-][Cl+][O-]
Solvent: CC(C)=O
Solvent: O
Product: O=C(O)c1ccc(OC(F)F)c2oc3ccc([N+](=O)[O-])cc3c12
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 81.9 %

Procedure:
To a stirring solution of 4-(difluoromethoxy)-8-nitrodibenzo[b,d]furan-1-carbaldehyde (6.5 g, 0.021 mol) and sulphamic acid (3.7 g, 0.038 mol) in acetone (25 mL) was added sodium chlorite (3.0 g, 0.033 mol) in water (25 mL) dropwise at 5-10° C. After 15 minutes, the reaction slurry was allowed to stir at room temperature for 17 hours. The reaction slurry was poured into ice-cold water and filtered. The solid obtained was washed with hexane and dried. Yield—81.9%. 1H-NMR (DMSO-d6) δ: 7.44-7.64-7.80 (t, 2H), 8.09-8.16 (m, 2H), 8.53-8.55 (m, 1H), 9.80 (d, 1H), 13.75 (s, 1H); HPLC (purity): 87.6%; Mass calculated for C14H7F2NO6-323.2, observed—322.0; Rf—0.25 (Ethyl acetate:Hexane (1:1).
Reaction SMILES: [OH-:1].[O:2]=O.[NH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.CS(C)=O>O>[N:4]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[N:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[OH:1][OH:2]
Reactant: [OH-]
Reactant: O=O
Reactant: Nc1ccccc1
Solvent: O
Solvent: CS(C)=O
Product: OO
Product: c1ccc(N=Nc2ccccc2)cc1

Procedure:
The excess hydroxide ions (OH-), dissolved dioxygen (O2), and aniline (PhNH2) reacted in the dimethyl sulfoxide solution to form superoxide ions (O2-.), azobenzene (PhN=NPh), hydrogen peroxide (HOOH), and water (H2O). The dioxygen was introduced by bubbling gaseous dioxygen through the solution of other reactants for 20 minutes, and then purging with argon. The reaction yielded concentrations of 1.4 mM of superoxide ions and 2.5 mM of azobenzene.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][C:11]3[S:10][C:9]([C:15]4[N:16]([CH:20]([CH3:22])[CH3:21])[N:17]=[CH:18][N:19]=4)=[N:8][C:7]=3[C:6]=2[CH:23]=1.[N:24]1[CH:29]=[CH:28][CH:27]=[C:26](B(O)O)[CH:25]=1>>[CH:20]([N:16]1[C:15]([C:9]2[S:10][C:11]3[CH2:12][CH2:13][O:14][C:5]4[CH:4]=[CH:3][C:2]([C:26]5[CH:25]=[N:24][CH:29]=[CH:28][CH:27]=5)=[CH:23][C:6]=4[C:7]=3[N:8]=2)=[N:19][CH:18]=[N:17]1)([CH3:22])[CH3:21]
Reactant: OB(O)c1cccnc1
Reactant: CC(C)n1ncnc1-c1nc2c(s1)CCOc1ccc(Br)cc1-2
Product: CC(C)n1ncnc1-c1nc2c(s1)CCOc1ccc(-c3cccnc3)cc1-2
Yield: 22 %

Procedure:
Following the procedure for 128, 9-Bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene from Example 6 and pyridin-3-ylboronic acid were reacted to give 342 (0.120 g, 22%). 1H NMR (400 MHz, DMSO) δ 8.91 (d, J=1.7, 1H), 8.72 (d, J=2.3, 1H), 8.57 (dd, J=7.2, 3.7, 1H), 8.11 (s, 1H), 8.07 (d, J=8.0, 1H), 7.69 (dd, J=8.4, 2.3, 1H), 7.53 (dd, J=7.9, 4.8, 1H), 7.22 (d, J=8.4, 1H), 5.79 (dt, J=13.2, 6.6, 1H), 4.44 (t, J=4.9, 2H), 3.49 (t, J=4.9, 2H), 1.57 (d, J=6.6, 6H). MS (ESI(+)): m/z 390.1 (M+H)
Reaction SMILES: [Br:1][C:2]1[N:7]=[C:6]([NH:8][NH2:9])[CH:5]=[CH:4][CH:3]=1.[C:10](OC(OCC)OCC)(=O)C>CCCCC>[Br:1][C:2]1[N:7]2[CH:10]=[N:9][N:8]=[C:6]2[CH:5]=[CH:4][CH:3]=1
Reactant: NNc1cccc(Br)n1
Reactant: CCOC(OCC)OC(C)=O
Solvent: CCCCC
Product: Brc1cccc2nncn12
Yield: 78 %

Procedure:
A solution of (6-bromopyridin-2-yl)hydrazine (500 mg, 2.66 mmol) in diethoxymethyl acetate (2.5 mL) was stirred at room temperature for 18 hours. The reaction mixture was diluted with pentane and filtered. The precipitate was washed with pentane and dried at 50° C. under vacuum for 1 hour to give 5-bromo-[1,2,4]triazolo[4,3-a]pyridine as a beige solid (410 mg, 78%). 1H NMR (400 MHz, CHCl3-d): δ 8.98 (s, 1 H); 7.83 (dt, J=9.2, 0.9 Hz, 1 H); 7.22 (dd, J=9.2, 7.0 Hz, 1 H); 7.09 (dd, J=7.0, 0.9 Hz, 1 H).
Reaction SMILES: C([NH:4][C:5]1[CH:10]=[CH:9][C:8]([S:11]([N:14]2[CH:19]([CH3:20])[CH:18]=[C:17]([CH3:21])[CH:16]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH3:30])=[CH:24][CH:23]=3)[O:15]2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)(=O)C.[OH-].[K+]>CO.ClCCl>[NH2:4][C:5]1[CH:6]=[CH:7][C:8]([S:11]([N:14]2[CH:19]([CH3:20])[CH:18]=[C:17]([CH3:21])[CH:16]([C:22]3[CH:23]=[CH:24][C:25]([O:28][CH2:29][CH3:30])=[CH:26][CH:27]=3)[O:15]2)(=[O:12])=[O:13])=[CH:9][CH:10]=1
Reactant: CCOc1ccc(C2ON(S(=O)(=O)c3ccc(NC(C)=O)cc3)C(C)C=C2C)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: ClCCl
Product: CCOc1ccc(C2ON(S(=O)(=O)c3ccc(N)cc3)C(C)C=C2C)cc1

Procedure:
A stirred mixture of 2-(4-acetamidobenzenesulphonyl)-3, 6-dihydro-3,5-dimethyl-6-(4-ethoxyphenyl) -2H-1,2-oxazine (0.153 g) and powdered potassium hydroxide (40mg) in methanol (5 ml) was-heated under reflux for 24 h. The cooled mixture was diluted with dichloromethane and the solution washed with water. The dichloromethane solution was separated, dried over magnesium sulphate, filtered and evaporated to dryness. The residual oil was purified by chromatography on silica using ethyl acetate:n-hexane 3:2 as eluant to give 2-(4-aminobenzenesulphonyl)-3,6-dihydro-3,5-dimethyl-6-(4-ethoxyphenyl)-2H-1,2-oxazine as a colourless foam. 1H NMR (CDCl3) δ 1.44(9H, m), 4.02(2H, q), 4.13(2H, br s), 4.44 (1H, m), 5.02(1H, br s), 5.70(1H, m), 6.61(2H, d), 6.83(2H, d), 7.13(2H, d), 7.65(2H, d).
Reaction SMILES: [CH2:1]([S:3][S:4][CH2:5][CH3:6])[CH3:2].S(Cl)([Cl:10])(=O)=O.[CH3:12][NH:13][C:14]([NH:16][C:17]1[CH:22]=[CH:21][C:20]([Br:23])=[CH:19][CH:18]=1)=[O:15].Cl>N1C=CC=CC=1.O>[CH2:1]([S:3][Cl:10])[CH3:2].[CH3:12][N:13]([S:4][CH2:5][CH3:6])[C:14]([NH:16][C:17]1[CH:22]=[CH:21][C:20]([Br:23])=[CH:19][CH:18]=1)=[O:15]
Reactant: O=S(=O)(Cl)Cl
Reactant: CNC(=O)Nc1ccc(Br)cc1
Reactant: CCSSCC
Agent: Cl
Solvent: c1ccncc1
Solvent: O
Product: CCSCl
Product: CCSN(C)C(=O)Nc1ccc(Br)cc1
Temperature: -40 °C
Reaction time: 0.5 h
Yield: 43.6 %

Procedure:
Ethane sulfenyl chloride was prepared as in Example 9 from 68 g of diethyldisulfide and 67 g of sulfuryl chloride, cooled to -40° C. and a solution of 60 g of N-methyl-N'-(4-bromophenyl)-urea in 800 ml of pyridine was added thereto. After stirring the reaction mixture for 30 minutes at -40° C., the temperature was allowed to rise to -20° C. and the mixture was stirred for 11/2 hours at this temperature. The mixture was poured into a mixture of water, ice and hydrochloric acid and was extracted with methylene chloride. The organic phase was washed with water, dried and evaporated to dryness under reduced pressure. The residue was chromatographed over silica gel and eluted with a 7-3 benzene-ethyl acetate mixture. The product was dissolved in ethyl ether and the solution was treated with activated carbon, filtered and concentrated to dryness under reduced pressure. The residue was added to petroleum ether (b.p. = 65°-75° C.) and the precipitate formed was recovered by vacuum filtration to obtain 33 g of N-methyl-N-ethylthio-N'-(4-bromophenyl)-urea melting at <50° C.
Reaction SMILES: [CH3:1][C:2]1([CH3:13])[CH2:6][CH2:5][O:4][C:3]1=[CH:7][N:8]1[CH:12]=[N:11][CH:10]=[N:9]1.Cl.C[OH:16]>>[CH3:1][C:2]1([CH3:13])[CH2:6][CH2:5][O:4][C:3]1([OH:16])[CH2:7][N:8]1[CH:12]=[N:11][CH:10]=[N:9]1
Reactant: CO
Reactant: CC1(C)CCOC1=Cn1cncn1
Agent: Cl
Product: CC1(C)CCOC1(O)Cn1cncn1
Yield: 93 %

Procedure:
30 g (0.17 mole) of (3,3-dimethyl-tetrahydrofuran-2-ylidene)-(1,2,4-triazol-1-yl)-methane and 100 g of concentrated hydrochloric acid are stirred in 300 ml of methanol at room temperature for 4 hours. The reaction mixture is concentrated in vacuo, the residue is taken up in water, the pH value is adjusted to 7 to 8 with dilute sodium hydroxide solution and the mixture is extracted with methylene chloride. The organic phase is washed with water, dried over sodium sulphate and concentrated in vacuo. 30.7 g (93% of theory) of 3,3-dimethyl-2-hydroxy-2-(1,2,4-triazol-1-yl-methyl)-tetrahydrofuran of melting point 93°-95° C. are obtained. ##STR101##
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[N:3]=1.[F:18][C:19]1[C:32]([F:33])=[C:31]([F:34])[C:30]([F:35])=[C:29]([F:36])[C:20]=1[O:21][C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][CH:28]=1)[NH2:25]>>[F:18][C:19]1[C:32]([F:33])=[C:31]([F:34])[C:30]([F:35])=[C:29]([F:36])[C:20]=1[O:21][C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][CH:28]=1)[NH:25][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[N:3]=1
Reactant: FC(F)(F)c1cc(Cl)nc(-c2cccnc2)n1
Reactant: Nc1cccc(Oc2c(F)c(F)c(F)c(F)c2F)c1
Product: Fc1c(F)c(F)c(Oc2cccc(Nc3cc(C(F)(F)F)nc(-c4cccnc4)n3)c2)c(F)c1F

Procedure:
The title compound was prepared from a mixture of 4-chloro-2-(3-pyridinyl)-6-(trifluoromethyl)pyrimidine (50 mg, 0.193 mmol) and 3-(2,3,4,5,6-pentafluorophenoxy)aniline (106 mg, 0.386 mmol) similar to Example 58 and isolated as a yellow solid (65 mg, 68%). 1H NMR (DMSO-d6): 10.46 (s, 1H), 9.24 (s, 1H), 8.75 (dd, J=1.8, 4.8 Hz, 1H), 8.56-8.52 (m, 1H), 7.77 (s, 1H), 7.59-7.55 (m, 1H), 7.50-7.41 (m, 2H), 7.14 (s, 1H), 6.94-6.92 (m, 1H).
Reaction SMILES: [NH2:1][C@H:2]([C:5]([NH:7][C@H:8]([C:17]([NH:19][C@@H:20]([C:25]([NH:27][C@H:28]([C:35]([NH:37][C@H:38]([C:46]([N:48]1[CH2:57][CH2:56][CH2:55][C@H:49]1[C:50]([NH:52][CH2:53][CH3:54])=[O:51])=[O:47])[CH2:39][CH2:40][CH2:41][NH:42][C:43](=[NH:45])[NH2:44])=[O:36])[CH2:29][S:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:26])[CH2:21][CH:22]([CH3:24])[CH3:23])=[O:18])[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=1)=[O:6])[CH2:3][OH:4].[CH3:58][C:59]([CH2:61][C:62]([OH:64])=[O:63])=[O:60].[NH2:65][C@H:66]([C:72]([NH:74][C@H:75]([C:82]([NH:84][C@H:85]([C:96](NN)=[O:97])[CH2:86][C:87]1[C:95]2[C:90](=[CH:91][CH:92]=[CH:93][CH:94]=2)[NH:89][CH:88]=1)=[O:83])[CH2:76][C:77]1[N:81]=[CH:80][NH:79][CH:78]=1)=[O:73])[CH2:67][CH2:68][C:69](=[O:71])[OH:70]>>[NH2:65][C@H:66]([C:72]([NH:74][C@H:75]([C:82]([NH:84][C@H:85]([C:96]([NH:1][C@H:2]([C:5]([NH:7][C@H:8]([C:17]([NH:19][C@@H:20]([C:25]([NH:27][C@H:28]([C:35]([NH:37][C@H:38]([C:46]([N:48]1[CH2:57][CH2:56][CH2:55][C@H:49]1[C:50]([NH:52][CH2:53][CH3:54])=[O:51])=[O:47])[CH2:39][CH2:40][CH2:41][NH:42][C:43](=[NH:44])[NH2:45])=[O:36])[CH2:29][S:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:26])[CH2:21][CH:22]([CH3:24])[CH3:23])=[O:18])[CH2:9][C:10]1[CH:11]=[CH:12][C:13]([OH:16])=[CH:14][CH:15]=1)=[O:6])[CH2:3][OH:4])=[O:97])[CH2:86][C:87]1[C:95]2[C:90](=[CH:91][CH:92]=[CH:93][CH:94]=2)[NH:89][CH:88]=1)=[O:83])[CH2:76][C:77]1[N:81]=[CH:80][NH:79][CH:78]=1)=[O:73])[CH2:67][CH2:68][C:69](=[O:70])[OH:71].[CH3:58][C:59]([CH2:61][C:62]([OH:64])=[O:63])=[O:60]
Reactant: NNC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H](N)CCC(=O)O
Reactant: CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CSC(C)(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](N)CO
Agent: CC(=O)CC(=O)O
Product: CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CSC(C)(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H](N)CCC(=O)O

Procedure:
In analogy to Example 7(e) 469.5 mg (0.5 mol) of H-Ser-Tyr-D-Leu-Cys(But)-Arg-Pro-NH-C2H5 -diacetate were reacted with Glu-His-Trp-NH-NH2, worked up and purified over Dowex 1 × 2 (acetate form) and carboxymethyl cellulose. Since the substance was not yet completely pure it was purified in analogy to Example 1(a) on Sephadex LH 20.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]([Cl:12])[CH:9]=[CH:8][C:3]=1[NH:4][CH2:5][C:6]#[N:7].[C:13]1([CH3:23])[CH:18]=[CH:17][C:16]([S:19]([OH:22])(=[O:21])=[O:20])=[CH:15][CH:14]=1.[CH2:24](N)[CH2:25][NH2:26].ClC1C=CC=CC=1Cl>C(Cl)Cl>[C:13]1([CH3:23])[CH:14]=[CH:15][C:16]([S:19]([OH:22])(=[O:20])=[O:21])=[CH:17][CH:18]=1.[Cl:1][C:2]1[CH:11]=[C:10]([Cl:12])[CH:9]=[CH:8][C:3]=1[NH:4][CH2:5][C:6]1[NH:26][CH2:25][CH2:24][N:7]=1
Reactant: NCCN
Reactant: N#CCNc1ccc(Cl)cc1Cl
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCl
Solvent: Clc1ccccc1Cl
Product: Clc1ccc(NCC2=NCCN2)c(Cl)c1
Reaction time: 1.17 h
Yield: 84.1 %

Procedure:
A mixture of 21.5 grams (g) of 2,4-dichloroanilinoacetonitrile, 23.3 g of ethylenediamine p-toluenesulfonate and 75 milliliters (ml) of 1,2-dichlorobenzene was heated with stirring in a round-bottomed three-necked flask at from about 140°-170° C. for about 70 minutes under a small flow of nitrogen. The reaction mixture was cooled and then diluted with methylene chloride. The mixture was cooled and then filtered, which gave 35.1 g of 2-((2,4-dichloroanilino)methyl)-2-imidazoline p-toluenesulfonate as white crystals. The p-toluenesulfonate salt was slurried in water and CH2Cl2 and then basified. The CH2Cl2 layer was separated and the remaining aqueous portion extracted with CH2Cl2 and then CHCl3. The extracts were combined, treated with diatomaceous earth and activated charcoal, and then filtered. Concentrating the filtrate to dryness, left 17.0 g of crystals. Recrystallization from ethylene dichloride gave 14.0 g of purified 2-((2,4-dichloroanilino)methyl)-2-imidazoline as white crystals, having a melting point (m.p.) of 154°-156° C.
Reaction SMILES: C1(C)C=CC(S(Cl)(=O)=O)=CC=1.C(N(CC)CC)C.O[CH2:20][C:21]([NH:24][C:25]([C:27]1[CH:36]=[CH:35][C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[N:28]=1)=[O:26])([CH3:23])[CH3:22]>ClCCCl.C(Cl)Cl>[CH3:20][C:21]1([CH3:23])[CH2:22][O:26][C:25]([C:27]2[CH:36]=[CH:35][C:34]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[N:28]=2)=[N:24]1
Reactant: CC(C)(CO)NC(=O)c1ccc2ccccc2n1
Agent: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: ClCCCl
Product: CC1(C)COC(c2ccc3ccccc3n2)=N1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 47 %

Procedure:
To an oven dried 250 mL round bottomed flask was weighed p-Toluene sulfonyl chloride (1.049 g, 5.5 mmol) and N,N-dimethylaminopyridine (39.1 mg, 0.32 mmol). A magnetic stirbar was added and the flask was placed under N2 atmosphere. The flask was charged with DCE (20 mL) and triethylamine (3.2 mL, 23 mmol). The N-(1-hydroxy-2-methylpropan-2-yl)quinoline-2-carboxamide (1.112 g, 4.55 mmol) was dissolved in DCE (15 mL) and added to the flask dropwise via syringe. The reaction mixture was stirred at 0° C. for 15 min, before a reflux condenser was fitted to the flask and heated to reflux for 16 h. The reaction mixture was cooled to room temperature, transferred to a separatory funnel and diluted with DCM (70 mL). The organic phase was washed with saturated NaHCO3 solution (2×70 mL), H2O (2×70 mL), and Brine (1×70 mL). Dried over Na2SO4, filtered and concentrated under reduced pressure. The crude mixture was purified by flash chromatography eluting with 20%→30% acetone in hexanes to afford 4,4-dimethyl-2-(quinoline-2-yl)-oxazoline in 47% yield (484 mg, 2.14 mmol) according to the reaction
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[Mg]Br.FC1C=C(F)C=CC=1Br.[Mg].[C:21]([O:24][CH2:25][C:26]([CH2:28][O:29][C:30](=[O:32])[CH3:31])=[O:27])(=[O:23])[CH3:22].Cl>C1COCC1>[C:30]([O:29][CH2:28][C:26]([C:3]1[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=1[F:1])([OH:27])[CH2:25][O:24][C:21](=[O:23])[CH3:22])(=[O:32])[CH3:31]
Reactant: Fc1ccc([Mg]Br)c(F)c1
Reactant: CC(=O)OCC(=O)COC(C)=O
Agent: Cl
Agent: Fc1ccc(Br)c(F)c1
Agent: [Mg]
Solvent: C1CCOC1
Product: CC(=O)OCC(O)(COC(C)=O)c1ccc(F)cc1F
Temperature: -30 °C
Reaction time: 2 h

Procedure:
Under an atmosphere of argon, 850 ml of THF solution of 2,4-difluorophenylmagnesium bromide prepared from 202.6 g (1.05 mol) of 2,4-difluorobromobenzene and 26.7 g (1.1 mol) of magnesium turnings was added dropwise at -30° C. to 1.7 l of THF solution of 174 g (1.00 mol) of 1,3-diacetoxyacetone which was previously cooled to -30° C. After the resulting liquid was stirred at -60° C. for 2 hours, a temperature thereof was gradually raised to room temperature. Then, to the reaction mixture was added 1 l of 1.2 N aqueous solution of hydrochloric acid at 5° C. or below, and an aqueous layer was extracted twice with 1 l of ethyl acetate. The organic layer was washed with saturated aqueous solution of sodium chloride, dried and concentrated under reduced pressure to give 302 g of crude oil. The obtained oil was purified by means of column chromatography on silica gel (hexane:ethyl acetate=1:1) to give 125 g of the desired compound. The compound was recrystallized from toluene/hexane
Reaction SMILES: [C:1]([OH:9])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.S(Cl)(Cl)=O.[CH3:14][C:15]1[N:19](CCO)[C:18]([N+:23]([O-:25])=[O:24])=[CH:17][N:16]=1>>[CH3:14][C:15]1[NH:19][C:18]([N+:23]([O-:25])=[O:24])=[CH:17][N:16]=1.[C:1]([O:9][CH2:14][CH3:15])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1
Reactant: O=C(O)c1cccnc1
Reactant: Cc1ncc([N+](=O)[O-])n1CCO
Solvent: O=S(Cl)Cl
Product: CCOC(=O)c1cccnc1
Product: Cc1ncc([N+](=O)[O-])[nH]1
Temperature: 70 °C
Reaction time: 2 h
Yield: 171.5 %

Procedure:
The reaction mixture of nicotinic acid (1.23 g, 10 mmol) and thionyl chloride (3 ml) was refluxed for 2 h, the excessive thionyl chloride was evaporated under vacuum. The residue was dissolved in 5 ml of pyridine. To this solution, metronidazole (1.20 g, 7.0 mmol) was added. The mixture was stirred at 70° C. for 2 h. Pyridine was then removed under reduced pressure. The residue was dissolved in dichloromethane. The organic layer of CH2Cl2 was washed with saturated aqueous NaHCO3 solution, water, and brine, and then dried over MgSO4. The solvent was removed. The resulting pale yellow solid was recrystallized from ethyl alcohol to give 1.67 g (86.72%) 2-methyl-5-nitro-1H-imidazole-1-ethyl nicotinate. m.p.: 116-118° C.