Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1]N1C(=O)CCC1=O.CSC.O[CH2:13][CH:14]=[C:15]([CH2:17][CH2:18][CH:19]=[C:20]([CH2:22][CH2:23][CH:24]=[C:25]([CH3:27])[CH3:26])[CH3:21])[CH3:16].[Na+].[Cl-]>C(Cl)Cl.ClCl>[CH2:13]([Cl:1])[CH:14]=[C:15]([CH2:17][CH2:18][CH:19]=[C:20]([CH2:22][CH2:23][CH:24]=[C:25]([CH3:27])[CH3:26])[CH3:21])[CH3:16]
Reactant: O=C1CCC(=O)N1Cl
Reactant: CC(C)=CCCC(C)=CCCC(C)=CCO
Agent: ClCl
Agent: [Cl-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CSC
Product: CC(C)=CCCC(C)=CCCC(C)=CCCl
Temperature: -30 °C
Reaction time: 0.25 h
Yield: 89 %

Procedure:
N-Chlorosuccinimide (0.66 g, 4.95 mmol) was dissolved in 20 ml of dry CH2Cl2 under a nitrogen atmosphere. The solution was cooled to -30° C. and 0.37 ml dimethyl sulphide (5 mmol) was added. The mixture was allowed to warm to 0° C. before it was cooled to -40° C. Then farnesol (1 g, 4.5 mmol) dissolved in 2.5 ml CH2 Cl2 was added dropwise to the mixture over a period of 3 minutes. The reaction mixture was warmed to 0.C in 1 h, at which temperature it was maintained for another hour. After 15 minutes of stirring at room temperature the reaction mixture was poured into a separatory funnel which contained 12.5 ml of cold saturated NaCl. The aqueous layer was extracted with two 10 ml portions of pentane. The organic layers were combined with an additional 10 ml of pentane and washed with two 5 ml portions of cold saturated NaCl. The organic layer was dried over MgSO4 and concentrated to dryness in vacuo. Compound (b) was thus obtained in a yield of 89%.
Reaction SMILES: [CH2:1]([OH:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[I:10][C:11]1[C:19]([C:20]([NH:22][CH3:23])=[O:21])=[C:18]([I:24])[C:17]([NH:25][C:26](=[O:30])[CH2:27][O:28][CH3:29])=[C:16]([I:31])[C:12]=1[C:13](Cl)=[O:14]>>[I:10][C:11]1[C:19]([C:20]([NH:22][CH3:23])=[O:21])=[C:18]([I:24])[C:17]([NH:25][C:26](=[O:30])[CH2:27][O:28][CH3:29])=[C:16]([I:31])[C:12]=1[C:13]([O:3][CH2:1][CH3:2])=[O:14]
Reactant: CCO
Reactant: CNC(=O)c1c(I)c(NC(=O)COC)c(I)c(C(=O)Cl)c1I
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CCOC(=O)c1c(I)c(NC(=O)COC)c(I)c(C(=O)NC)c1I

Procedure:
A solution of 2,4,6-triiodo-5-methoxyacetamido-N-methylisophthalamoyl chloride in N,N-dimethylacetamide (prepared as in Example 3) is treated with absolute ethanol in the presence of potassium carbonate. After the reaction is complete, the inorganic salts are removed by filtration and the filtrate is evaporated to dryness to provide ethyl 2,4,6-triiodo-5-methoxyacetamido-N-methylisophthalamate.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([N:15]3[CH2:19][CH:18]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:17][C:16]3=[O:25])=[CH:11][C:10]=2[F:26])=[CH:5][CH:4]=1.[N:27]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:30]([CH:37]=O)=[CH:29][CH:28]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.CN(C=O)C>[F:26][C:10]1[CH:11]=[C:12]([N:15]2[CH2:19][CH:18]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:17][C:16]2=[O:25])[CH:13]=[CH:14][C:9]=1[C:6]1[CH:7]=[CH:8][C:3]([CH2:2][NH:1][CH2:37][C:30]2[C:31]3[C:36](=[CH:35][CH:34]=[CH:33][CH:32]=3)[N:27]=[CH:28][CH:29]=2)=[CH:4][CH:5]=1
Reactant: O=Cc1ccnc2ccccc12
Reactant: CC(=O)NCC1CN(c2ccc(-c3ccc(CN)cc3)c(F)c2)C(=O)O1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: CC(=O)NCC1CN(c2ccc(-c3ccc(CNCc4ccnc5ccccc45)cc3)c(F)c2)C(=O)O1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 66 %

Procedure:
A solution of amine 54 (36 mg, 0.1 mmol) in a mixture of THF and DMF (3:1, v/v) was treated with quinoline-4-carboxaldehyde (16 mg, 0.1 mmol, 1.0 equiv) at 25° C. under argon, and the resulting reaction mixture was stirred at 25° C. for 30 min before being treated with sodium triacetoxyborohydride (NaB(OAc)3H, 33 mg, 0.15 mmol, 1.5 equiv) at 25° C. The reaction mixture was subsequently stirred at 25° C. for 6 h. When TLC and HPLC showed the reductive amination reaction was complete, the reaction mixture was concentrated in vacuo. The residue was then directly purified by flash column chromatography (0-7% MeOH—CH2Cl2 gradient elution) to produce the desired N-[3-(2-fluoro-4′-{[(quinolin-4-ylmethyl)-amino]-methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide 4016 (32.9 mg, 66% yield) as pale-yellow oil, which solidified upon standing at room temperature in vacuo. 1H NMR (300 MHz, DMSO-d6) δ 1.85 (s, 3H, COCH3), 3.44 (t, 2H, J=5.4 Hz), 3.79 (dd, 1H, J=6.4, 9.2 Hz), 3.88 (s, 2H), 4.17 (t, 1H, J=9.1 Hz), 4.30 (s, 2H), 4.77 (m, 1H), 7.41 (dd, 1H, J=2.0, 8.0 Hz), 7.51-7.63 (m, 8H, aromatic-H), 7.74 (t, 1H, J=8.0 Hz), 8.04 (d, 1H, J=8.0 Hz), 8.18 (d, 1H, J=8.0 Hz), 8.27 (t, 1H, J=5.8 Hz, NHCOCH3), 8.87 (d, 1H, J=8.0 Hz). LCMS (ESI) m/e 499 (M+H)+.
Reaction SMILES: [CH3:1][O-:2].[Na+].[NH2:4][C:5]1[N:10]=[C:9](F)[CH:8]=[C:7]([O:12][C:13]([F:16])([F:15])[F:14])[N:6]=1>CO>[NH2:4][C:5]1[N:10]=[C:9]([O:2][CH3:1])[CH:8]=[C:7]([O:12][C:13]([F:16])([F:15])[F:14])[N:6]=1
Reactant: Nc1nc(F)cc(OC(F)(F)F)n1
Reactant: C[O-]
Agent: [Na+]
Solvent: CO
Product: COc1cc(OC(F)(F)F)nc(N)n1
Temperature: 25 °C

Procedure:
2.7 g (0.015 mol) of 30% strength sodium methylate were added to 2.95 g (0.015 mol) of 2-amino-4-fluoro-6-trifluoromethoxypyrimidine in 50 ml of methanol in the course of 15 minutes at from -5° to 0° C. while stirring. The reaction mixture was stirred for 1 hour at 0° C., warmed up to 25° C. and then evaporated down under reduced pressure, and the residue was stirred with water and extracted twice with methylene chloride. Drying and evaporating down under reduced pressure gave 3.1 g (98% of theory) of the title compound of nD25 =1.4770.
Reaction SMILES: [CH3:1][Si](C=[N+]=[N-])(C)C.[N+:8]([C:11]1[CH:12]=[C:13]([CH:36]=[CH:37][CH:38]=1)[CH2:14][C:15]1[C:16](=[O:35])[O:17][C:18]2[CH:28]=[C:27]([O:29][C:30](=[O:34])[N:31]([CH3:33])[CH3:32])[CH:26]=[CH:25][C:19]=2[C:20]=1[CH2:21][C:22]([OH:24])=[O:23])([O-:10])=[O:9].ClCCl>CO>[CH3:1][O:23][C:22](=[O:24])[CH2:21][C:20]1[C:19]2[CH:25]=[CH:26][C:27]([O:29][C:30](=[O:34])[N:31]([CH3:32])[CH3:33])=[CH:28][C:18]=2[O:17][C:16](=[O:35])[C:15]=1[CH2:14][C:13]1[CH:36]=[CH:37][CH:38]=[C:11]([N+:8]([O-:10])=[O:9])[CH:12]=1
Reactant: CN(C)C(=O)Oc1ccc2c(CC(=O)O)c(Cc3cccc([N+](=O)[O-])c3)c(=O)oc2c1
Reactant: C[Si](C)(C)C=[N+]=[N-]
Solvent: CO
Solvent: ClCCl
Product: COC(=O)Cc1c(Cc2cccc([N+](=O)[O-])c2)c(=O)oc2cc(OC(=O)N(C)C)ccc12
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 94 %

Procedure:
Trimethylsilyl diazomethane (0.82 mL, 2.0 M in hexane) was added to a solution of {3-(3-nitrobenzyl)-7-dimethylcarbamoyloxy-2-oxo-2H-1-benzopyran-4-yl}acetic acid (compound 7f-1-1COOH) (350 mg, 0.82 mmol) in methanol (5.0 mL)/dichloromethane (8.0 mL), and the mixture was stirred at room temperature for 10 minutes. Aacetic acid (2.0 mL) was added to the reaction mixture, and the title compound (338 mg, 94%) was obtained by vacuum concentration as a pale yellow powder.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[C:11]([C:15]([F:18])([F:17])[F:16])=[CH:10][C:9]=1[NH:19][C:20](=[O:37])[CH2:21][C:22]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([C:30]2[CH:35]=[CH:34][N:33]=[C:32]([CH3:36])[CH:31]=2)[CH:25]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:14][C:12]1[C:11]([C:15]([F:17])([F:16])[F:18])=[CH:10][C:9]2[NH:19][C:20](=[O:37])[CH2:21][C:22]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([C:30]4[CH:35]=[CH:34][N:33]=[C:32]([CH3:36])[CH:31]=4)[CH:25]=3)=[N:7][C:8]=2[CH:13]=1
Reactant: Cc1cc(-c2cccc(C(=O)CC(=O)Nc3cc(C(F)(F)F)c(C)cc3NC(=O)OC(C)(C)C)c2)ccn1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1cc(-c2cccc(C3=Nc4cc(C)c(C(F)(F)F)cc4NC(=O)C3)c2)ccn1

Procedure:
The title compound was prepared from (5-methyl-2-{3-[3-(2-methyl-pyridin-4-yl)-phenyl]-3-oxo-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example M68) (0.42 g, 0.80 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an off-white solid (242 mg, 74%).
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[C:19]2[C:14](=[CH:15][C:16]([Cl:20])=[CH:17][CH:18]=2)[C:13]([CH2:21]O)=[CH:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)([Cl:25])=O.CCCCCC>ClCCl>[CH2:1]([O:8][C:9]([N:11]1[C:19]2[C:14](=[CH:15][C:16]([Cl:20])=[CH:17][CH:18]=2)[C:13]([CH2:21][Cl:25])=[CH:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=S(Cl)Cl
Reactant: O=C(OCc1ccccc1)n1cc(CO)c2cc(Cl)ccc21
Solvent: CCCCCC
Solvent: ClCCl
Product: O=C(OCc1ccccc1)n1cc(CCl)c2cc(Cl)ccc21
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
To a solution of 1-benzyloxycarbonyl-5-chloro-3-hydroxymethylindole (1.45 g) in dichloromethane (23 ml) was added thionylchloride (0.797 μl) at −78° C. After the mixture was stirred for 1.5 hours at room temperature, the reaction mixture was concentrated under the reduced pressure to give a residue. Hexane was added to the residue. 1-benzyloxycarbonyl-5-chloro-3-chloromethylindole (1.43 g) was obtained as a crystal.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].S(Cl)([Cl:15])=O.CN(C=O)C>ClCCCl>[OH:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:3]=1[C:4]([Cl:15])=[O:5]
Reactant: O=S(Cl)Cl
Reactant: COc1ccc(C(=O)O)c(O)c1
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: COc1ccc(C(=O)Cl)c(O)c1
Temperature: 25 °C
Reaction time: 4.5 h
Yield: 99.1 %

Procedure:
To a solution of 2-hydroxy-p-anisic acid (0.2 g, 1.2 mmol) in DCE (8 mL) was added thionyl chloride (0.13 mL, 1.8 mmol) and a drop of DMF. After stirring at room temperature for 4.5 h the reaction mixture was concentrated and azeotroped several times with benzene to give the acid chloride 123 as a white solid (222 mg).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:4]=1[CH:11]([CH:13]=[CH2:14])[OH:12]>C(Cl)Cl.O=[Mn]=O>[CH:13]([C:11]([C:4]1[CH:5]=[C:6]([O:9][CH3:10])[CH:7]=[CH:8][C:3]=1[O:2][CH3:1])=[O:12])=[CH2:14]
Reactant: C=CC(O)c1cc(OC)ccc1OC
Agent: O=[Mn]=O
Solvent: ClCCl
Product: C=CC(=O)c1cc(OC)ccc1OC
Temperature: 25 °C
Reaction time: 24 h

Procedure:
Activated MnO2 (100 g) was added in portions to a mechanically stirred solution of 2,5-dimethoxyphenyl vinyl carbinol (12.5 g, 0.064 mole) in 250 ml of methylene chloride. The mixture was stirred at room temperature for 24 hours and then filtered through a patch of Celite. The filtrate was concentrated to give a brown oil which was purified by column chromatography on silica gel, using diethyl ether/hexane (1/1) as eluant. The compound was obtained as a light brown oil; 7.2 g; IR (neat) 1680 cm-1 ; NMR (CDCl3) δ6.85-7.1 (m,4H); 6.3 (d,1H); 5.8 (d,1H); 3.8 and 3.85 (two singlets,6H).
Reaction SMILES: [Br:1][C:2]1[CH:26]=[C:25]([Br:27])[CH:24]=[C:23]([Br:28])[C:3]=1[O:4][CH2:5][C:6]1([CH2:10][O:11][C:12]2[C:17]([Br:18])=[C:16]([Br:19])[C:15]([Br:20])=[C:14]([Br:21])[C:13]=2[Br:22])[CH2:9][O:8][CH2:7]1.O.S(=O)(=O)(O)[OH:31]>O1CCOCC1>[Br:18][C:17]1[C:12]([O:11][CH2:10][C:6]([CH2:5][O:4][C:3]2[C:2]([Br:1])=[CH:26][C:25]([Br:27])=[CH:24][C:23]=2[Br:28])([CH2:7][OH:8])[CH2:9][OH:31])=[C:13]([Br:22])[C:14]([Br:21])=[C:15]([Br:20])[C:16]=1[Br:19]
Reactant: O=S(=O)(O)O
Reactant: Brc1cc(Br)c(OCC2(COc3c(Br)c(Br)c(Br)c(Br)c3Br)COC2)c(Br)c1
Solvent: O
Solvent: C1COCCO1
Product: OCC(CO)(COc1c(Br)cc(Br)cc1Br)COc1c(Br)c(Br)c(Br)c(Br)c1Br

Procedure:
A mixture of the oxetane derivative of Example 2 (47.5 g., 0.053 moles), dioxane (290 ml.), water (10 ml.) and 1 g. of conc. sulfuric acid was stirred and refluxed 22 hours. The cooled reaction mixture was poured into 1.5 liters of water. A gummy solid formed which became crystalline when heated with dioxane. This product was recrystallized twice from dioxane, yielding 19.4 g. of the desired product which had a melting point of 184°-187° C.
Reaction SMILES: [CH:1]1([CH2:4][N:5]2[C:10](=[O:11])[C:9]([CH2:12][N:13]3[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]3)=[CH:8][C:7]([C:20]3[CH:21]=[CH:22][C:23]4[O:27][CH2:26][CH2:25][C:24]=4[CH:28]=3)=[N:6]2)[CH2:3][CH2:2]1.[Cl:29][C:30]1[CH:60]=[CH:59]C(C=CCN2C(=O)C(COS(C)(=O)=O)=CC(C3C=CC4OCCC=4C=3)=N2)=[CH:32][CH:31]=1>>[Cl:29][C:30]1[CH:60]=[CH:59][C:3]([CH:2]=[CH:1][CH2:4][N:5]2[C:10](=[O:11])[C:9]([CH2:12][N:13]3[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]3)=[CH:8][C:7]([C:20]3[CH:21]=[CH:22][C:23]4[O:27][CH2:26][CH2:25][C:24]=4[CH:28]=3)=[N:6]2)=[CH:32][CH:31]=1
Reactant: CS(=O)(=O)OCc1cc(-c2ccc3c(c2)CCO3)nn(CC=Cc2ccc(Cl)cc2)c1=O
Reactant: CN1CCN(Cc2cc(-c3ccc4c(c3)CCO4)nn(CC3CC3)c2=O)CC1
Product: CN1CCN(Cc2cc(-c3ccc4c(c3)CCO4)nn(CC=Cc3ccc(Cl)cc3)c2=O)CC1
Yield: 45.8 %

Procedure:
The general procedure of Example 1 (6) was carried out by use of 2-(4-chlorocinnamyl)-6-(2,3-dihydro-1-benzofuran-5-yl)-4-methanesulfonyloxymethyl-2H-pyridazin-3-one, to thereby yield the title compound as a faint brown powder (yield: 45.8%).
Reaction SMILES: [NH2:1][C:2]1[C:7]([NH2:8])=[CH:6][C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1.[N+:12]([C:15]1[CH:23]=[CH:22][C:18]([C:19](Cl)=[O:20])=[CH:17][CH:16]=1)([O-:14])=[O:13].O>N1C=CC=CC=1>[NH2:1][C:2]1[C:7]([NH:8][C:19](=[O:20])[C:18]2[CH:17]=[CH:16][C:15]([N+:12]([O-:14])=[O:13])=[CH:23][CH:22]=2)=[CH:6][C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1
Reactant: Nc1cc([N+](=O)[O-])cnc1N
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Solvent: O
Solvent: c1ccncc1
Product: Nc1ncc([N+](=O)[O-])cc1NC(=O)c1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 81 %

Procedure:
To a solution of 2,3-Diamino-5-nitropyridine (3) in dry pyridine (85 mL) was added 4-nitrobenzoylchloride (0.875 g, 4.7 mmol) and the mixture was stirred at room temperature for 20 h. The mixture was then poured into H2O (250 mL) and stirred for 30 minutes. The resulting yellow solid was collected by filtration and rinsed with H2O until no pyridine remained. The solid was dried in vacuuo at 80 C to give 6 as a yellow solid (1.15 g, 3.8 mmol, 81%). 1H NMR (500 MHz, DMSO-d6) δ10.12 (br s, 1H), 8.83 (d, J=2.55 Hz, 1H), 8.84 (d, J=8.5 Hz, 2H), 8.35 (d, J=2.45 Hz, 2H), 8.24 (d, J=8.7 Hz, 2H), 7.62 (br s, 2H). EIMS M−1 302.3.
Reaction SMILES: CO[C:3]([C:5]1[N:6]=[C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]3[CH2:17][C:18](=[O:32])[NH:19][C:20]4[CH:26]=[C:25]([N:27]5[CH:31]=[CH:30][CH:29]=[CH:28]5)[CH:24]=[CH:23][C:21]=4[N:22]=3)[CH:11]=2)[O:8][CH:9]=1)=[O:4]>NCCO>[OH:4][CH2:3][CH2:5][NH:6][C:3]([C:5]1[N:6]=[C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]3[CH2:17][C:18](=[O:32])[NH:19][C:20]4[CH:26]=[C:25]([N:27]5[CH:31]=[CH:30][CH:29]=[CH:28]5)[CH:24]=[CH:23][C:21]=4[N:22]=3)[CH:11]=2)[O:8][CH:9]=1)=[O:4]
Reactant: COC(=O)c1coc(-c2cccc(C3=Nc4ccc(-n5cccc5)cc4NC(=O)C3)c2)n1
Solvent: NCCO
Product: O=C1CC(c2cccc(-c3nc(C(=O)NCCO)co3)c2)=Nc2ccc(-n3cccc3)cc2N1
Yield: 42.6 %

Procedure:
A solution of 2-[3-(4-oxo-7-pyrrol-1-yl-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl)-phenyl]-oxazole-4-carboxylic acid methyl ester (Example 25) (88 mg) in 2-amino-ethanol (2 mL) was stirred at 50° C. for 2 h. The mixture was partitioned between EtOAc and H2O, the organic layer was dried and evaporated in vacuum. The residue was chromatographed on silicag gel using EtOAc/hexane (1:1) as eluent and the purified product was triturated with Et2O to give the title compound (20 mg) as light-yellow solid.
Reaction SMILES: [NH2:1][C:2]1[O:3][CH:4]([CH2:8][CH:9]([CH3:11])[CH3:10])[C:5](=[O:7])[N:6]=1.[CH:12]1(N)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1>>[CH:12]1([NH:1][C:2]2[O:3][CH:4]([CH2:8][CH:9]([CH3:11])[CH3:10])[C:5](=[O:7])[N:6]=2)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1
Reactant: CC(C)CC1OC(N)=NC1=O
Reactant: NC1CCCCCC1
Product: CC(C)CC1OC(NC2CCCCCC2)=NC1=O

Procedure:
Synthesis was performed from 2-amino-5-isobutyl-1,3-oxazol-4(5H)-one and cycloheptylamine according to Method G+H.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](/[CH:10]=[C:11]2\[O:12][C:13]3[C:20]([CH2:21][N:22]4[CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][CH2:23]4)=[C:19]([OH:35])[C:18]([Cl:36])=[CH:17][C:14]=3[C:15]\2=[O:16])=[CH:2]1.[ClH:37]>C(Cl)Cl.O1CCOCC1>[ClH:36].[ClH:37].[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](/[CH:10]=[C:11]2\[O:12][C:13]3[C:20]([CH2:21][N:22]4[CH2:23][CH2:24][NH:25][CH2:26][CH2:27]4)=[C:19]([OH:35])[C:18]([Cl:36])=[CH:17][C:14]=3[C:15]\2=[O:16])=[CH:2]1
Reactant: CC(C)(C)OC(=O)N1CCN(Cc2c(O)c(Cl)cc3c2O/C(=C\c2c[nH]c4ccccc24)C3=O)CC1
Agent: Cl
Solvent: ClCCl
Solvent: C1COCCO1
Product: O=C1/C(=C/c2c[nH]c3ccccc23)Oc2c1cc(Cl)c(O)c2CN1CCNCC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 73 %

Procedure:
A solution of tert-butyl (Z)-4-({2-[(1H-indol-3-yl)methylene]-5-chloro-6-hydroxy-3-oxo-2,3-dihydrobenzofuran-7-yl}methyl)piperazine-1-carboxylate (0.016 g, 0.031 mmol) in methylene chloride (2.0 mL) was added with a 4 M solution of hydrogen chloride in 1,4-dioxane (2.0 mL), and then the mixture was stirred at room temperature for 1 hour. The mixture was azeotroped twice with toluene under reduced pressure, and then the residual solid was suspended in methylene chloride and thereby washed to obtain (Z)-2-[(1H-indol-3-yl)methylene]-5-chloro-6-hydroxy-7-(piperazin-1-ylmethyl)benzofuran-3(2H)-one dihydrochloride (0.011 g, 73%).
Reaction SMILES: [C:1]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:6]=[CH:5][C:4]([C:7]([C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:13][CH:12]=2)=[CH:8][CH2:9][NH2:10])=[CH:3][CH:2]=1.[C:29](OC(=O)C)(=[O:31])[CH3:30]>C(O)(=O)C>[C:14]1([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:15]=[CH:16][C:11]([C:7]([C:4]2[CH:3]=[CH:2][C:1]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)=[CH:6][CH:5]=2)=[CH:8][CH2:9][NH:10][C:29](=[O:31])[CH3:30])=[CH:12][CH:13]=1
Reactant: CC(=O)OC(C)=O
Reactant: NCC=C(c1ccc(-c2ccccc2)cc1)c1ccc(-c2ccccc2)cc1
Solvent: CC(=O)O
Product: CC(=O)NCC=C(c1ccc(-c2ccccc2)cc1)c1ccc(-c2ccccc2)cc1

Procedure:
1, 1-di(4-biphenyl)-3 (1g) was added to a mixture of anhydrous sodium acetate (1g), acetic acid (10 ml.) and acetic anhydride (1 ml) and the mixture was refluxed for 1 hour then evaporated in vacuo. The residue was washed with water and dried and recrystallised from n- propanol to give 1, 1-di(4-biphenylyl)- 3 -acetamido-prop-1-ene. (m.p. 246° - 249° C). This compound was reduced in a similar manner to the method described in Example 43 to yield 1,1-di(4-biphenyly;0- 3 -ethylamino-prop-1-ene.
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[N:20][NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2F)[CH2:8][CH2:7]1)=[O:5])[CH3:2].CC(C)([O-])C.[K+].O>O1CCCC1>[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12]2[C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:21]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[N:20]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)N1CCN(C(=NNc2ccccc2)c2ccccc2F)CC1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: CCOC(=O)N1CCN(c2nn(-c3ccccc3)c3ccccc23)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 34.6 %

Procedure:
To a stirred solution, under nitrogen of 16.2 g of 4-[(phenylhydrazono)(2-fluorophenyl)methyl]-1-piperazine carboxylic acid ethyl ester in 150 ml of tetrahydrofuran was added, dropwise, a solution of 6.0 g of potassium t-butoxide in 60 ml of tetrahydrofuran. The reaction mixture was stirred at room temperature for 16 hrs., poured into water, and extracted with dichloromethane. The extract was washed with water, dried over anhydrous magnesium sulfate, filtered, and concentrated to an oil. The oil was purified on a Water's Model 500 Preparative High Pressure Liquid Chromatograph utilizing two silica gel columns and hexane/ethyl acetate (3:1 by volume) as the eluent. Concentration of the appropriate fractions yielded 5.3 g (51%) of 4-(1-phenyl-1H-indazol-3-yl)-1-piperazine carboxylic acid ethyl ester.
Reaction SMILES: [NH2:1][CH2:2][C:3]([N:5]([CH2:12][C:13]([N:15]1[CH2:20][CH2:19][S:18][C:17]([CH3:22])([CH3:21])[CH2:16]1)=[O:14])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:4].[CH3:23][C:24]1[CH:25]=[C:26]([N:30]=[C:31]=[O:32])[CH:27]=[CH:28][CH:29]=1>>[CH3:21][C:17]1([CH3:22])[CH2:16][N:15]([C:13](=[O:14])[CH2:12][N:5]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:3](=[O:4])[CH2:2][NH:1][C:31]([NH:30][C:26]2[CH:27]=[CH:28][CH:29]=[C:24]([CH3:23])[CH:25]=2)=[O:32])[CH2:20][CH2:19][S:18]1
Reactant: CC1(C)CN(C(=O)CN(C(=O)CN)c2ccccc2)CCS1
Reactant: Cc1cccc(N=C=O)c1
Product: Cc1cccc(NC(=O)NCC(=O)N(CC(=O)N2CCSC(C)(C)C2)c2ccccc2)c1
Yield: 62.8 %

Procedure:
The procedure is analogous to that described in Example 81, but 0.7 g of 2-amino-N-[2-(2,2-dimethylthiomorpholino)-2-oxoethyl]-N-phenylacetamide and 0.28 g of 3-methylphenyl isocyanate are used as the starting material. After recrystallization from an ethyl acetate/acetonitrile mixture (80/20 by volume), 0.6 g of N-[2-(2,2-dimethylthiomorpholino)-2-oxoethyl]-2-[3-(3-methylphenyl)ureido]-N-phenylacetamide melting at 186° C. is obtained.
Reaction SMILES: [H-].[Na+].[CH2:3]([C:5]1[N:6]([CH2:18][C:19]([CH3:22])([OH:21])[CH3:20])[C:7]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:17]=1)[CH3:4].[CH:23]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH2:24]>O1CCCC1.O>[CH2:3]([C:5]1[N:6]([CH2:18][C:19]([CH3:22])([O:21][CH2:24][CH2:23][S:25]([CH3:28])(=[O:27])=[O:26])[CH3:20])[C:7]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:17]=1)[CH3:4]
Reactant: CCc1nc2cnc3ccccc3c2n1CC(C)(C)O
Reactant: C=CS(C)(=O)=O
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CCc1nc2cnc3ccccc3c2n1CC(C)(C)OCCS(C)(=O)=O
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 68.1 %

Procedure:
Sodium hydride (60% dispersion in oil, 30 mg, 0.74 mmol) was added to a stirred solution of 1-(2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol (2.00 g, 7.43 mmol) in tetrahydrofuran (30 mL). After five minutes, methyl vinyl sulfone (1.60 g, 14.9 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 1.5 hours and a solid formed. A few drops of water were added to the mixture, which was then concentrated under reduced pressure to yield a solid that was purified by flash chromatography (silica gel, eluted with 5% methanol in dichloromethane) to provide 1.90 g of 2-ethyl-1-{2-methyl-2-[2-(methylsulfonyl)ethoxy]propyl}-1H-imidazo[4,5-c]quinoline as a white solid.
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([S:8]([C:11]2[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=2)(=[O:10])=[O:9])[CH:5]=[C:4]([Br:18])[N:3]=1.[CH3:19][NH2:20]>O1CCOCC1.C(O)C>[NH2:17][C:14]1[CH:15]=[CH:16][C:11]([S:8]([C:6]2[CH:5]=[C:4]([Br:18])[N:3]=[C:2]([NH:20][CH3:19])[CH:7]=2)(=[O:10])=[O:9])=[CH:12][CH:13]=1
Reactant: Nc1ccc(S(=O)(=O)c2cc(Br)nc(Br)c2)cc1
Reactant: CN
Solvent: CCO
Solvent: C1COCCO1
Product: CNc1cc(S(=O)(=O)c2ccc(N)cc2)cc(Br)n1
Temperature: 25 °C
Reaction time: 48 h
Yield: 69 %

Procedure:
1.45 g (0.0037 mol) of 4-(2,6-dibromopyridine-4-sulphonyl)-phenylamine were dissolved in 40 ml of dioxane and treated with 9.6 ml of 8M methylamine in ethanol. The mixture was stirred at room temperature for 48 hrs., the solvents were removed and the residue was chromatographed on silica gel with ethyl acetate/hexane 1:3 and 1:2. The product-containing fractions, after concentration, were suspended in 50 ml of diethyl ether, treated in an ultrasound bath for 1 hr., then treated with 75 ml of hexane and the precipitate which thereby resulted was filtered off under suction. After drying in a high vacuum there was obtained 0.87 g (69%) of [4-(4-aminobenzenesulphonyl)-6-bromopyridin-2-yl]-methylamine as pale beige crystals; m.p.: 171-173° C.