Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]([CH3:20])[C:3]([N:5]1[CH2:11][CH2:10][C:9]2[CH:12]=[CH:13][C:14]([S:16]([NH2:19])(=[O:18])=[O:17])=[CH:15][C:8]=2[CH2:7][CH2:6]1)=[O:4].C(=O)([O-])[O-].[K+].[K+].[CH2:27]([O:29][C:30](Cl)=[O:31])[CH3:28].S(=O)(=O)(O)O>C(Cl)(Cl)Cl.O.CC(C)=O>[CH2:27]([O:29][C:30](=[O:31])[NH:19][S:16]([C:14]1[CH:13]=[CH:12][C:9]2[CH2:10][CH2:11][N:5]([C:3](=[O:4])[N:2]([CH3:20])[CH3:1])[CH2:6][CH2:7][C:8]=2[CH:15]=1)(=[O:18])=[O:17])[CH3:28]
Reactant: CCOC(=O)Cl
Reactant: CN(C)C(=O)N1CCc2ccc(S(N)(=O)=O)cc2CC1
Agent: O=C([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Solvent: ClC(Cl)Cl
Solvent: O
Solvent: CC(C)=O
Product: CCOC(=O)NS(=O)(=O)c1ccc2c(c1)CCN(C(=O)N(C)C)CC2
Temperature: 25 °C

Procedure:
A mixture of 7.5 g. of 3-dimethylcarbamoyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7-sulfonamide, 13.9 g. of potassium carbonate, 9.6 ml. of chloroformic acid ethyl ester and 150 ml. of acetone is heated to reflux for 16 hours while stirring, then cooled to 25° C. and poured on to a mixture of 500 ml. of water and 1000 ml. of chloroform. The pH of the aqueous phase is then brought to 2.0 with 6N sulfuric acid while stirring. The chloroform phase is subsequently separated, dried over sodium sulfate and evaporated in vacuo. The evaporation residue is crystallized by the addition of ether. There is obtained [(3-dimethylcarbamoyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)sulfonyl]carbamic acid ethyl ester of melting point 140°-141° C.
Reaction SMILES: CSC.[Cl:4][C:5]1[CH:6]=[C:7]([C:12]2[CH:17]=[CH:16][C:15]([CH2:18][C@@H:19]([NH:23][C:24]([C:26]3[CH:27]=[C:28]([C:34]4[CH:39]=[CH:38][C:37]([C:40]([F:43])([F:42])[F:41])=[CH:36][CH:35]=4)[CH:29]=[CH:30][C:31]=3[O:32]C)=[O:25])[CH2:20][O:21][CH3:22])=[CH:14][CH:13]=2)[CH:8]=[CH:9][C:10]=1[F:11].CO>C(Cl)Cl>[Cl:4][C:5]1[CH:6]=[C:7]([C:12]2[CH:17]=[CH:16][C:15]([CH2:18][C@@H:19]([NH:23][C:24]([C:26]3[CH:27]=[C:28]([C:34]4[CH:35]=[CH:36][C:37]([C:40]([F:43])([F:41])[F:42])=[CH:38][CH:39]=4)[CH:29]=[CH:30][C:31]=3[OH:32])=[O:25])[CH2:20][O:21][CH3:22])=[CH:14][CH:13]=2)[CH:8]=[CH:9][C:10]=1[F:11]
Reactant: COC[C@@H](Cc1ccc(-c2ccc(F)c(Cl)c2)cc1)NC(=O)c1cc(-c2ccc(C(F)(F)F)cc2)ccc1OC
Solvent: CSC
Solvent: ClCCl
Solvent: CO
Product: COC[C@@H](Cc1ccc(-c2ccc(F)c(Cl)c2)cc1)NC(=O)c1cc(-c2ccc(C(F)(F)F)cc2)ccc1O
Temperature: -78 °C
Reaction time: 2 h
Yield: 62.7 %

Procedure:
DMS (13 mg, 0.04 mmol) was added to a solution of 4-Methoxy-4′-trifluoromethyl-biphenyl-3-carboxylic acid [2-(3′-chloro-4′-fluoro-biphenyl-4-yl)-1-(R)-methoxymethyl-ethyl]-amide (24 mg, 0.04 mmol) in 3 mL of anhydrous CH2Cl2, at −78° C. and slowly allowed to come to room temperature and stirred for 2 h. After completion of the reaction, reaction was cooled to −78° C. and 0.5 mL of MeOH was added, solvent was removed under vacuum and the residue was taken in ethyl acetate (4 mL) and washed with aq NaHCO3 solution, water, brine and dried over Na2SO4. Solvent was removed under vacuum and silica gel column chromatography (Ethyl acetate: Hexanes) gave pure 4-Hydroxy-4′-trifluoromethyl-biphenyl-3-carboxylic acid [2-(3′-chloro-4′-fluoro-biphenyl-4-yl)-1-(R)-methoxymethyl-ethyl]-amide (14 mg).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[SH:10])([O-:3])=[O:2].Br[CH:12]([CH3:14])[CH3:13].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH:12]([S:10][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[N+:1]([O-:3])=[O:2])([CH3:14])[CH3:13]
Reactant: CC(C)Br
Reactant: O=[N+]([O-])c1ccccc1S
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CC(C)Sc1ccccc1[N+](=O)[O-]

Procedure:
2-Nitrothiophenol, 2-bromopropane, potassium carbonate and acetone were refluxed for several hours. The solvent then was removed by rotary evaporation. The crude product was partitioned between methylene chloride and a 10% sodium carbonate solution. The organic phase was distilled to yield 2-isopropylmercaptonitrobenzene.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[F:7][C:8]([F:46])([F:45])[C:9]1[CH:10]=[C:11]([CH:38]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:40]=1)[CH2:12][NH:13][CH2:14][C:15]1[CH:16]=[C:17]2[C:32]([CH3:33])=[N:31][N:30]([C:34]([CH3:37])([CH3:36])[CH3:35])[C:18]2=[N:19][C:20]=1[N:21]([CH2:26][CH:27]1[CH2:29][CH2:28]1)[CH2:22][CH:23]1[CH2:25][CH2:24]1.[Br:47][C:48]1[CH:49]=[N:50][C:51](Cl)=[N:52][CH:53]=1.O>CN(C=O)C>[F:46][C:8]([F:45])([F:7])[C:9]1[CH:10]=[C:11]([CH:38]=[C:39]([C:41]([F:43])([F:44])[F:42])[CH:40]=1)[CH2:12][N:13]([CH2:14][C:15]1[CH:16]=[C:17]2[C:32]([CH3:33])=[N:31][N:30]([C:34]([CH3:36])([CH3:37])[CH3:35])[C:18]2=[N:19][C:20]=1[N:21]([CH2:26][CH:27]1[CH2:29][CH2:28]1)[CH2:22][CH:23]1[CH2:24][CH2:25]1)[C:51]1[N:52]=[CH:53][C:48]([Br:47])=[CH:49][N:50]=1
Reactant: Cc1nn(C(C)(C)C)c2nc(N(CC3CC3)CC3CC3)c(CNCc3cc(C(F)(F)F)cc(C(F)(F)F)c3)cc12
Reactant: Clc1ncc(Br)cn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1nn(C(C)(C)C)c2nc(N(CC3CC3)CC3CC3)c(CN(Cc3cc(C(F)(F)F)cc(C(F)(F)F)c3)c3ncc(Br)cn3)cc12

Procedure:
Potassium carbonate (0.43 g, 3 mmol) was added to a mixture of 5-(((3,5-bis(trifluoromethyl)benzyl)amino)methyl)-1-(tert-butyl)-N,N-bis(cyclopropylmethyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-6-amine (0.6 g, 1 mmol) and 5-bromo-2-chloropyrimidine (0.6 g, 3 mmol) in DMF. The resultant mixture was stirred at 100° C. for 12-16 h. The reaction mixture was treated with water and extracted with ethylacetate (100 ml). The organic layer was washed with brine and dried over Na2SO4, concentrated under reduced pressure to obtain the crude product. This product was further purified by column chromatography using silica gel (60-120 mesh) and 5% ethyl acetate in petroleum ether as eluent.
Reaction SMILES: C(N(CC)CC)C.Cl.[CH3:9][O:10][C:11](=[O:18])[C@H:12]([CH2:14][CH:15]([CH3:17])[CH3:16])[NH2:13].[CH:19]1[C:32]2[NH:31][C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[S:24][C:23]=2[CH:22]=[CH:21][C:20]=1[C:33](O)=[O:34].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[CH3:16][CH:15]([CH3:17])[CH2:14][C@H:12]([NH:13][C:33]([C:20]1[CH:21]=[CH:22][C:23]2[S:24][C:25]3[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=3)[NH:31][C:32]=2[CH:19]=1)=[O:34])[C:11]([O:10][CH3:9])=[O:18]
Reactant: O=C(O)c1ccc2c(c1)Nc1ccccc1S2
Reactant: COC(=O)[C@@H](N)CC(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: COC(=O)[C@H](CC(C)C)NC(=O)c1ccc2c(c1)Nc1ccccc1S2
Reaction time: 15 h

Procedure:
4.6 ml (33 mmoles) of triethylamine is added to a solution of 1.82 g (10 mmoles) of L-Leucine methyl ester hydrochloride, 2.43 g (10 mmoles) of 10H-phenothiazine-2-carboxylic acid (J. Med. Chem.(1998) 41 (2), 148-156), 1.48 g (11 mmoles) of HOBT and 4.21 g (22 mmoles) of EDC in 30 ml of anhydrous DMF. The reaction mixture is stirred for 15 hours. After evaporation of the solvent under vacuum, the residue is divided between 100 ml of AcOEt and 50 ml of a 1M solution of HCl. The organic phase is decanted and washed successively with 50 ml of H2O, 50 ml of a saturated solution of NaHCO3 and 50 ml of salt water. The organic solution is dried over magnesium sulphate, filtered and concentrated to dryness under vacuum. The evaporation residue is taken up in Et2O and filtered. Yellow powder (71%). Melting point: 160.5-161° C.
Reaction SMILES: Cl[S:2]([C:5]1[S:9][C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH:16]([CH3:18])[CH3:17])=[CH:12][CH:11]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].[NH2:19][C:20]1[O:24][N:23]=[C:22]([CH3:25])[C:21]=1[Br:26]>CO.C(Cl)(Cl)Cl>[Br:26][C:21]1[C:22]([CH3:25])=[N:23][O:24][C:20]=1[NH:19][S:2]([C:5]1[S:9][C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH:16]([CH3:18])[CH3:17])=[CH:12][CH:11]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3]
Reactant: Cc1noc(N)c1Br
Reactant: CC(C)c1ccc(-c2ccc(S(=O)(=O)Cl)s2)cc1
Solvent: ClC(Cl)Cl
Solvent: CO
Product: Cc1noc(NS(=O)(=O)c2ccc(-c3ccc(C(C)C)cc3)s2)c1Br

Procedure:
N-(4-bromo-3-methyl-5-isoxazolyl)-5-(4-isopropylphenyl)thiophene-2-sulfonamide was prepared in the same manner as described in Example 2. Reaction of 5-chlorosulfonyl-2-(4-isopropylphenyl)thiophene (260 mg, 0.87 mmol) with 5-amino-4-bromo-3-methylisoxazole (161 mg, 0.91 mmol) yielded after flash chromatography using 10% MeOH/CHCl3 a pale brown solid (265 mg) which was further purified using preparative HPLC to give the pure sulfonamide as a light tan colored solid, m.p. 114-116° C.
Reaction SMILES: [CH3:1][S-:2].[Na+].[N+:4]([C:7]1[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][C:8]=1[C:14](=[O:17])[CH2:15]Br)([O-:6])=[O:5]>CO>[N+:4]([C:7]1[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][C:8]=1[C:14](=[O:17])[CH2:15][S:2][CH3:1])([O-:6])=[O:5]
Reactant: C[S-]
Reactant: O=C(CBr)c1cccc(Cl)c1[N+](=O)[O-]
Agent: [Na+]
Solvent: CO
Product: CSCC(=O)c1cccc(Cl)c1[N+](=O)[O-]
Yield: 36.3 %

Procedure:
1.5 g (0.0061 mol) of 2'-nitro-3'-chloro-2-(methylthio)acetophenone are prepared by addition at 0° C. of 1.3 g (0.018 mol) of sodium methanethiolate in solution in 10 ml of methanol to 4.7 g (0.0168 mol) of 2'-nitro-3'-chloro-2-bromoacetophenone obtained above.
Reaction SMILES: [NH2:1][C:2](=[N:21][OH:22])[C:3]1[CH:4]=[CH:5][C:6]([F:20])=[C:7]([CH:19]=1)[CH2:8][N:9]([CH3:18])[CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].[CH2:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:31]1[CH:36]=[CH:35][C:34]([C:37](O)=O)=[CH:33][C:32]=1[CH2:40][O:41][CH3:42])[CH3:24]>>[CH2:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:31]1[CH:36]=[CH:35][C:34]([C:37]2[O:22][N:21]=[C:2]([C:3]3[CH:4]=[CH:5][C:6]([F:20])=[C:7]([CH:19]=3)[CH2:8][N:9]([CH3:18])[CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[N:1]=2)=[CH:33][C:32]=1[CH2:40][O:41][CH3:42])[CH3:24]
Reactant: CCc1ccccc1-c1ccc(C(=O)O)cc1COC
Reactant: CN(CC(=O)OC(C)(C)C)Cc1cc(C(N)=NO)ccc1F
Product: CCc1ccccc1-c1ccc(-c2nc(-c3ccc(F)c(CN(C)CC(=O)OC(C)(C)C)c3)no2)cc1COC

Procedure:
The title compound was prepared following procedure described for example 4, step 1, but starting from Intermediate 60 (256.87 mg; 0.83 mmol) and Intermediate 36 (202.74 mg; 0.75 mmol). The reaction mixture was filtered through a SPE NH2 column (2 g) and rinsed with ACN. After evaporation of the solvents, the crude product was purified by flash chromatography (c-hex/(DCM/EtOAc 1:1) gradient from 1:0 to 1:1), affording the title compound as a pale yellow oil. 1H NMR (CDCl3) δ 8.42 (d, J=1.4 Hz, 1H), 8.26 (dd, J=7.0, 2.1 Hz, 1H), 8.18-8.09 (m, 2H), 7.41-7.34 (m, 3H), 7.29-7.23 (m, 1H), 7.19 (t, J=9.0 Hz, 1H), 7.12-7.10 (m, 1H), 4.27-4.17 (m, 2H), 3.90 (s, 2H), 3.38 (s, 3H), 3.28 (s, 2H), 2.47-2.29 (m, 5H), 1.51 (s, 9H), 1.05 (t, J=7.5 Hz, 3H). LC/MS (Method B): 546.3 (M+H)+. HPLC (Method A) Rt 5.04 min (Purity: 99.5%).
Reaction SMILES: S([CH2:11][CH2:12][CH:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15](=[O:22])[NH:14]1)(C1C=CC(C)=CC=1)(=O)=O.[CH3:23][C:24]1[CH:25]=[C:26]([N:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)[CH:27]=[CH:28][C:29]=1[CH3:30].C([O-])([O-])=O.[K+].[K+]>CC#N>[CH3:23][C:24]1[CH:25]=[C:26]([N:31]2[CH2:32][CH2:33][N:34]([CH2:11][CH2:12][CH:13]3[C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[C:15](=[O:22])[NH:14]3)[CH2:35][CH2:36]2)[CH:27]=[CH:28][C:29]=1[CH3:30]
Reactant: Cc1ccc(N2CCNCC2)cc1C
Reactant: Cc1ccc(S(=O)(=O)CCC2NC(=O)c3ccccc32)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: Cc1ccc(N2CCN(CCC3NC(=O)c4ccccc43)CC2)cc1C
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 60.8 %

Procedure:
A solution of 1,3-dihydro-3-(2-tosylethyl)-2H-isoindol-1-one (4.2 g, 12.7 mmol), 1-(3,4-dimethylphenyl)-piperazine (2.6 g, 13.9 mmol), and K2CO3 (8.8 g, 63.3 mmol) in 150 mL of CH3CN is warmed to reflux overnight under argon. After being cooled to room temperature, the solvent is evaporated, and the remaining solid is stirred in 100 mL of H2O for 20 minutes. The solid is collected, dried, and recrystallized from CH3CN to give 2.7 g (60% yield) of 3-{2-[4-(3,4-dimethyl-phenyl)-piperazin-1-yl]-ethyl}-2,3-dihydro-isoindol-1-one; mp=167-169° C.
Reaction SMILES: C([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:25][O:26][CH:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)[C:10]([NH:12][CH:13]2[C:23](=[O:24])[N:15]3[C:16]([C:20]([OH:22])=[O:21])=[CH:17][CH2:18][S:19][C@H:14]23)=[O:11])[N:8]=1)=O.Cl>CO.O1CCCC1>[NH2:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:25][O:26][CH:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)[C:10]([NH:12][CH:13]2[C:23](=[O:24])[N:15]3[C:16]([C:20]([OH:22])=[O:21])=[CH:17][CH2:18][S:19][C@H:14]23)=[O:11])[N:8]=1
Reactant: O=CNc1nc(C(=NOC2CCCC2)C(=O)NC2C(=O)N3C(C(=O)O)=CCS[C@H]23)cs1
Agent: Cl
Solvent: C1CCOC1
Solvent: CO
Product: Nc1nc(C(=NOC2CCCC2)C(=O)NC2C(=O)N3C(C(=O)O)=CCS[C@H]23)cs1
Yield: 81.4 %

Procedure:
7-[2-(2-formamidothiazol-4-yl)-2cyclopentyloxyiminoacetamido]-3-cephem-4-carboxylic acid (syn isomer, 1.7 g.) in methanol (17 ml.) and tetrahydrofuran (5 ml.), and conc. hydrochloric acid (1.5 g.) were treated in a similar manner to that of Example 15-(3) to give 7-[2-(2-aminothiazol-4-yl)-2cyclopentyloxyiminoacetamido]-3cephem-4-carboxylic acid (syn isomer, 1.3 g.).
Reaction SMILES: [NH2:1][C:2]1[CH:17]=[CH:16][C:5]2[N:6]([C:9]3[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][CH:10]=3)[CH:7]=[N:8][C:4]=2[CH:3]=1.[NH:18]1[C:26]2[C:21](=[CH:22][C:23]([C:27]([OH:29])=O)=[CH:24][CH:25]=2)[CH:20]=[CH:19]1>>[NH:18]1[C:26]2[C:21](=[CH:22][C:23]([C:27]([NH:1][C:2]3[CH:17]=[CH:16][C:5]4[N:6]([C:9]5[CH:10]=[CH:11][C:12]([NH:15][C:27]([C:23]6[CH:22]=[C:21]7[C:26](=[CH:25][CH:24]=6)[NH:18][CH:19]=[CH:20]7)=[O:29])=[CH:13][CH:14]=5)[CH:7]=[N:8][C:4]=4[CH:3]=3)=[O:29])=[CH:24][CH:25]=2)[CH:20]=[CH:19]1
Reactant: O=C(O)c1ccc2[nH]ccc2c1
Reactant: Nc1ccc(-n2cnc3cc(N)ccc32)cc1
Product: O=C(Nc1ccc(-n2cnc3cc(NC(=O)c4ccc5[nH]ccc5c4)ccc32)cc1)c1ccc2[nH]ccc2c1

Procedure:
Compound 564 was prepared according to the procedure described in Scheme IV from 5-amino-1-(4-aminophenyl)benzimidazole and indole-5-carboxylic acid. [M+H]+ calcd for C31H22N6O2: 511.19; found: 511.07.
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[O:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]([O:12]C)=[O:11])=[N:8][CH:9]=1.[OH-].[K+:17].CO>O>[F:15][C:2]([F:1])([F:14])[O:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]([O-:12])=[O:11])=[N:8][CH:9]=1.[K+:17]
Reactant: COC(=O)c1ccc(OC(F)(F)F)cn1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=C([O-])c1ccc(OC(F)(F)F)cn1
Temperature: 25 °C
Reaction time: 1 h
Yield: 122 %

Procedure:
A mixture of methyl 5-(trifluoromethoxy)pyridine-2-carboxylate (0.313 g, 1.41 mmol), potassium hydroxide (0.076 g, 1.35 mmol) in a 5:1 MeOH:water mixture (3 mL) was stirred at room temperature for 1 h. Additional potassium hydroxide (0.015 g, 0.267 mmol) in water (0.2 mL) was added and the mixture was stirred at room temperature for 1 h. The reaction mixture was evaporated to dryness and azeotroped twice with toluene to give the potassium 5-(trifluoromethoxy)pyridine-2-carboxylate intermediate (404 mg 100%). A fraction of this intermediate (0.173 g, 0.706 mmol) was dissolved in oxalyl chloride (4 mL) and the mixture was stirred at room temperature for 2 h before being evaporated to dryness and used without further purification in the next step.
Reaction SMILES: C1(N2C(=O)C3=CNC4C=C[C:16]([N:19]5[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]5)=NC=4C3=N2)C=CC=CC=1.F[C:28]1[CH:37]=[CH:36][C:35]2[NH:34][CH:33]=[C:32]3[C:38](=[O:47])[N:39]([C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][N:42]=4)[N:40]=[C:31]3[C:30]=2[N:29]=1.CN1CCNCC1.N1CCNCC1>>[CH3:16][N:19]1[CH2:24][CH2:23][N:22]([C:28]2[CH:37]=[CH:36][C:35]3[NH:34][CH:33]=[C:32]4[C:38](=[O:47])[N:39]([C:41]5[CH:46]=[CH:45][CH:44]=[CH:43][N:42]=5)[N:40]=[C:31]4[C:30]=3[N:29]=2)[CH2:21][CH2:20]1
Reactant: O=c1c2c[nH]c3ccc(F)nc3c-2nn1-c1ccccn1
Reactant: O=c1c2c[nH]c3ccc(N4CCNCC4)nc3c-2nn1-c1ccccc1
Agent: C1CNCCN1
Agent: CN1CCNCC1
Product: CN1CCN(c2ccc3[nH]cc4c(=O)n(-c5ccccn5)nc-4c3n2)CC1

Procedure:
The title compound was prepared following the procedure described for 6a using 5b and 1-methylpiperazine instead of 5a and piperazine respectively. 1H-NMR (DMSO-d6) δ (ppm): 2.55 (4H, br), 2.77 (3H, brs), 3.80 (4H, br), 7.20 (1H, m), 7.27 (6H, d, J=9.24 Hz), 7.87 (2H, m), 8.20 (1H, d, J=8.24 Hz), 8.48 (1H, m), 8.60 (1H, s). m/z 362.4 (MH+).
Reaction SMILES: [NH2:1][CH2:2][C:3]([C@@H:5]1[C@@H:10]([OH:11])[C@H:9]([OH:12])[C@@H:8]([CH2:13][OH:14])[O:7][C@@:6]1([NH2:43])[N:15]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[C:16](=[O:28])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])=[O:4].[C:44]([NH:54][C@H:55]([C:59](O)=[O:60])[CH:56]([CH3:58])[CH3:57])([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45]>ClCCl>[C:44]([NH:54][C@H:55]([C:59]([NH:1][CH2:2][C:3]([C@@H:5]1[C@@H:10]([OH:11])[C@H:9]([OH:12])[C@@H:8]([CH2:13][OH:14])[O:7][C@@:6]1([NH2:43])[N:15]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[C:16](=[O:28])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])=[O:4])=[O:60])[CH:56]([CH3:58])[CH3:57])([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45]
Reactant: CCCCCCCCCCCCCCN(C(=O)CCCCCCCCCCC)[C@]1(N)O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1C(=O)CN
Reactant: CC(C)[C@H](NC(=O)OCc1ccccc1)C(=O)O
Solvent: ClCCl
Product: CCCCCCCCCCCCCCN(C(=O)CCCCCCCCCCC)[C@]1(N)O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1C(=O)CNC(=O)[C@@H](NC(=O)OCc1ccccc1)C(C)C
Yield: 76 %

Procedure:
from N-(2-glycyl-amino-2-deoxy-β-D-glucopyranosyl)-N-tetradecyl-dodecanamide and N-carbobenzoxy-L-valine. Yield 76%. [α]D =+17.8° (c=1.09, dichloromethane). m.p. 85-86°.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[N:4][C:5]([CH2:11][S+:12]([O-:24])[C:13]2[NH:14][C:15]3[CH:16]=[CH:17][C:18]([O:22][CH3:23])=[CH:19][C:20]=3[N:21]=2)=[C:6]([CH3:10])[C:7]=1[O:8][CH3:9].C1(C(C2C=CC=CC=2)(O)[C@H](C2C=CC=CC=2)O)C=CC=CC=1>C(O)C>[CH3:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([CH3:10])[C:5]([CH2:11][S@@:12]([C:13]2[NH:21][C:20]3[CH:19]=[C:18]([O:22][CH3:23])[CH:17]=[CH:16][C:15]=3[N:14]=2)=[O:24])=[N:4][CH:3]=1
Reactant: COc1ccc2[nH]c([S+]([O-])Cc3ncc(C)c(OC)c3C)nc2c1
Agent: O[C@@H](c1ccccc1)C(O)(c1ccccc1)c1ccccc1
Solvent: CCO
Product: COc1ccc2nc([S@@](=O)Cc3ncc(C)c(OC)c3C)[nH]c2c1
Reaction time: 30 h

Procedure:
A suspension of omeprazole (20 g, 57.9 mmol) and (S)-1,1,2-triphenyl-1,2-ethanediol (25.2 g, 86.9 mmol) in ethanol (700 ml) at ambient temperature was stirred for 30 h. The solid was filtered, was washed with ethanol (2×150 ml) and was dried in vacuo to afford (S)-omeprazole.2[(S)-1,1,2-triphenyl-1,2-ethanediol] (24.1 g, 90%, 95.5% e.e.) as a white powder.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.C([Li])CCC.[CH2:11](Br)[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].O>O1CCCC1.ClCCl>[CH2:22]([C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH3:11]
Reactant: c1ccsc1
Reactant: CCCCCCCCCCCCBr
Agent: [Li]CCCC
Solvent: ClCCl
Solvent: O
Solvent: C1CCOC1
Product: CCCCCCCCCCCCc1cccs1
Temperature: 0 °C
Reaction time: 3 h
Yield: 54.2 %

Procedure:
8.0 g of thiophene was dissolved in 150 ml of tetrahydrofuran and cooled to 0° C. To this solution, 62 ml of n-butyllithium solution (1.6 mol/l hexane solution) was added dropwise, and stirred for 3 hours. 25.0 g of n-dodecylbromide was added dropwise to the solution, and was stirred at room temperature for 18 hours. 150 ml of water and 150 ml of dichloromethane were added to the resulting solution to separate the organic layer. The organic layer was washed with 300 ml of water and dried over anhydrous magnesium sulfate. The solvent was distilled off from the resulting solution under reduced pressure with a rotary evaporator and then the solution was distilled under reduced pressure to obtain 13 g of 2-n-dodecylthiophene.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:5]2.[H-].[Na+].Br.Br[CH2:20][C:21]1[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=1.C(OCC)C>CN(C)C=O>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:20][C:21]1[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=1)[C:6]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:5]2
Reactant: BrCc1ccncc1
Reactant: CCOC(=O)c1cc2cc(F)ccc2[nH]1
Agent: Br
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOCC
Product: CCOC(=O)c1cc2cc(F)ccc2n1Cc1ccncc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 51.9 %

Procedure:
A solution of 1 g (4.73 mmol) of ethyl 5-fluoro-1H-indole-2-carboxylate is added dropwise to a suspension of 0.38 g (9.45 mmol) of 60% sodium hydride in 10 ml of dimethylformamide, stirred at 0° C. under argon. The mixture is stirred for 30 minutes at 0° C. and then for 30 min at 20° C. The reaction mixture is cooled and 1.24 g (4.2 mmol) of 4-bromomethylpyridine hydrobromide are added portionwise. The mixture is stirred for 30 minutes at 0° C. and then for 30 minutes at 20° C. The reaction mixture is cooled again to 0° C. and a further 0.38 g (9.45 mmol) of 60% sodium hydride in 10 ml of dimethylformamide is added. After 30 minutes at 0° C., 1.24 g (4.2 mmol) of 4-bromomethylpyridine hydrobromide are added portionwise. The reaction mixture is then stirred for 20 hours at 20° C. After this time, the mixture is poured into a solution of 100 ml of ice-water and 100 ml of ethyl ether. The organic phase is separated out and the aqueous phase is re-extracted with 100 ml of ethyl ether. The organic phases are combined, washed with 50 ml of water and then dried over sodium sulfate, filtered and then concentrated under reduced pressure. The residue is purified by preparative chromatography (eluent: dichloromethane/acetone). 0.65 g of expected product is obtained in the form of an oil, which is used without further purification in the subsequent synthesis.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][N:16]2C(=O)C3=CC=CC=C3C2=O)(=[O:10])=[O:9])=[CH:4][CH:3]=1.C(O)C.O.NN>ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][NH2:16])(=[O:9])=[O:10])=[CH:6][CH:7]=1
Reactant: O=C1c2ccccc2C(=O)N1CCCCCS(=O)(=O)c1ccc(Cl)cc1
Agent: NN
Solvent: O
Solvent: CCO
Solvent: ClCCl
Product: NCCCCCS(=O)(=O)c1ccc(Cl)cc1
Yield: 119.8 %

Procedure:
Then, 4.0 g (10.2 mmol) of 1-(4-chlorophenylsulfonyl)-5-phthalimidopentane was dissolved in 120 ml of dichloromethane and 20 ml of ethanol and stirred together with 6 ml of 80% hydrazine hydrate at room temperature for 36 hours. The impurities were filtered out, and the filtrate was evaporated in vacuo to give 3.2 g of the title compound.
Reaction SMILES: [Br:1][C:2]1[C:8]([Cl:9])=[C:7]([F:10])[CH:6]=[C:5]([N+:11]([O-:13])=[O:12])[C:3]=1N.C(ON=O)(C)(C)C.[ClH:21]>C(#N)C>[Br:1][C:2]1[C:3]([Cl:21])=[C:5]([N+:11]([O-:13])=[O:12])[CH:6]=[C:7]([F:10])[C:8]=1[Cl:9]
Reactant: Nc1c([N+](=O)[O-])cc(F)c(Cl)c1Br
Reactant: Cl
Agent: CC(C)(C)ON=O
Solvent: CC#N
Product: O=[N+]([O-])c1cc(F)c(Cl)c(Br)c1Cl

Procedure:
To a mixture of anhydrous cupric chloride (147 g) and 2-bromo-3-chloro-4-fluoro-6-nitroaniline (235.6 g) in anhydrous acetonitrile (1.5 litter) was added tert-butylnitrite (135.2 g) at 60° C. during 70 minutes. The reaction mixture was poured into ice-chilled diluted hydrochloric acid (1.5 litter) and extracted with benzene. The organic layer was successively washed with ice-chilled diluted hydrochloric acid and water saturated with sodium chloride, dried over anhydrous sodium sulfate and concentrated. The resulting residue was purified by distillation to give the title compound (218.8 g), bp 78°-117° C./2 mmHg. The oil was crystallized from methanol to give yellow prisms, mp 65.5°-67.5° C.