Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:5][C:6](=[O:25])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=1[CH2:16][O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21]C=1)(C)(C)C.[C:26]1(C2C=CC=CC=2)[CH:31]=[CH:30][C:29]([C:32]2[O:33][C:34]([CH3:50])=[C:35]([CH2:37][CH2:38]OS(C3C=CC(C)=CC=3)(=O)=O)[N:36]=2)=[CH:28][CH:27]=1.CN(C=O)C.C(=O)([O-])[O-].[Cs+].[Cs+]>CCOCC>[CH:29]1([C:32]2[O:33][C:34]([CH3:50])=[C:35]([CH2:37][CH2:38][O:15][C:12]3[CH:13]=[CH:14][C:9]([CH2:8][CH2:7][C:6]([OH:5])=[O:25])=[C:10]([CH2:16][O:17][C:18]4[CH:19]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH:11]=3)[N:36]=2)[CH2:28][CH2:27][CH2:26][CH2:31][CH2:30]1
Reactant: CC(C)(C)OC(=O)CCc1ccc(O)cc1COCc1ccccc1
Reactant: Cc1ccc(S(=O)(=O)OCCc2nc(-c3ccc(-c4ccccc4)cc3)oc2C)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOCC
Solvent: CN(C)C=O
Product: Cc1oc(C2CCCCC2)nc1CCOc1ccc(CCC(=O)O)c(COc2ccccc2)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 78.3 %

Procedure:
General procedure for the parallel synthesis of analogs using the DynaVac Carousel apparatus: A 50 mL glass tube with screw cap and nitrogen inlet was charged with 3-(2-benzyloxymethyl-4-hydroxy-phenyl)-propionic acid tert-butyl ester (0.050 g, 0.146 mmol), toluene-4-sulfonic acid 2-(2-biphenyl-4-yl-5-methyloxazol-4-yl)ethyl ester (0.078 g, 0.18 mmol), anhydrous DMF (0.5 mL), and then cesium carbonate (0.072 g, 0.22 mmol). The mixture was stirred at ambient temperature for 16 h. MS analysis of the reaction indicated that the intermediate ester was formed, MS (ES) m/e 534 (M+1). The crude reaction was poured into ether (30 mL), and washed with brine (2×), dried (Na2SO4), and concentrated in vacuo. The crude residue was dissolved in CH2Cl2 (2 mL) and trifluoroacetic acid was added (1.0 mL). The reaction mixture was stirred at ambient temperature for 2 h and was concentrated under a stream of N2. The crude product was purified by mass-directed reverse phase HPLC to provide 0.053 g (71%) of 3-{4-[2-(2-Cyclohexyl-5-methyloxazol-4-yl)ethoxy]-2-phenoxymethylphenyl}propionic acid. MS (ES) m/e 478 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[N:13]([CH3:14])[C:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)=[N:11][C:10]=2[C:21]2[CH:30]=[CH:29][C:24]([C:25]([NH:27][NH2:28])=[O:26])=[CH:23][CH:22]=2)=[CH:4][CH:3]=1.[C:31](Cl)(Cl)=[O:32]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[N:13]([CH3:14])[C:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)=[N:11][C:10]=2[C:21]2[CH:22]=[CH:23][C:24]([C:25]3[O:26][C:31](=[O:32])[NH:28][N:27]=3)=[CH:29][CH:30]=2)=[CH:4][CH:3]=1
Reactant: O=C(Cl)Cl
Reactant: Cn1c(-c2ccccn2)nc(-c2ccc(C(=O)NN)cc2)c1Sc1ccc(Cl)cc1
Solvent: C1CCOC1
Product: Cn1c(-c2ccccn2)nc(-c2ccc(-c3n[nH]c(=O)o3)cc2)c1Sc1ccc(Cl)cc1
Temperature: -78 °C
Reaction time: 1 h

Procedure:
To 4-{5-[(4-chlorophenyl)thio]-1-methyl-2-pyridin-2-yl-1H-imidazol-4-yl}benzohydrazide (Step 1 of Example 48, 120 mg, 0.27 mmol) in THF (1 mL) was added phosgene (PhMe solution, 0.55 mmol) at −78° C. After stirring at −78° C. for 60 min, the reaction was quenched with aq NaHCO3 and the product was extracted with EtOAc. The combined extracts were washed with water, brine, dried over MgSO4, filtered, and concentrated. The residue was re-crystallized in MeCN/MeOH to afford the title compound. 1H NMR (500 MHz, (CDCl3): 8.68 (d, 1H), 8.42 (broad d, 1H), 8.28 (d, 2H), 7.91 (d, 2H), 7.89 (m, 1H), 7.37 (m, 1H), 7.27 (d, 2H), 7.06 (d, 2H), 4.17 (s, 3H). LCMS: m/z 462 (M+H)+.
Reaction SMILES: [N:1]1(CCOC2C=C(CC#N)C=CC=2)CCOCC1.[C:19]1([N:25]([C:28]2[CH:33]=[CH:32]C=CC=2)C=N)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C1(C)C(C)=CC=CC=1.CCCCCC>[C:19]1([NH:25][CH:28]=[CH:33][C:32]#[N:1])[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
Reactant: N#CCc1cccc(OCCN2CCOCC2)c1
Reactant: N=CN(c1ccccc1)c1ccccc1
Solvent: CCCCCC
Solvent: Cc1ccccc1C
Product: N#CC=CNc1ccccc1
Temperature: 100 °C
Reaction time: 3 h
Yield: 170.8 %

Procedure:
A mixture of 2-[3-(2-morpholin-4-ylethoxy)phenyl]acetonitrile (5.0 g) and N,N-diphenylformamidine (5.0 g, 25.5 mmol) in xylene (150 ml). was heated at 100° C. under a nitrogen atmosphere. After 3 h, the reaction mixture was cooled to room temperature and diluted with hexane to give 2-|3-(2-morpholin-4-ylethoxy)benzoyl[-3-phenylaminoacrylonitrile (5.0 g) as a solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:27])[CH2:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)[CH:14]=2)[CH2:9][CH2:8]1)=[O:6].Cl.CCOCC.[N:34](OCCC(C)C)=[O:35]>CCOC(C)=O>[CH3:1][O:2][C:3](=[O:27])[C:4](=[N:34][OH:35])[C:5]([N:7]1[CH2:12][CH2:11][CH:10]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH:22]3[CH2:23][CH2:24][CH2:25][CH2:26]3)[CH:14]=2)[CH2:9][CH2:8]1)=[O:6]
Reactant: CC(C)CCON=O
Reactant: COC(=O)CC(=O)N1CCC(c2ccc(OC)c(OC3CCCC3)c2)CC1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CCOCC
Product: COC(=O)C(=NO)C(=O)N1CCC(c2ccc(OC)c(OC3CCCC3)c2)CC1
Reaction time: 0.17 h

Procedure:
To 3-[4-(3-cyclopentyloxy-4-methoxyphenyl)-piperidin-1-yl]-3-oxo-propionic acid methyl ester (5.3 mmol, 2.0 g) was added a solution of HCl/Et2O (1N, 55 mL) and isoamyl nitrite (6.36 mmol, 0.854 mL) at room temperature. After 10 minutes, the reaction mixture had become homogenous, and a white precipitate formed after and additional 30 minutes. After 3 hours, the reaction mixture was diluted with EtOAc and washed with H2O. The aqueous phase was extracted with EtOAc, the organics dried (Na2SO2) and concentrated in vacuo. The residue was triturated in Et2O/hexane to yield the title compound as a white solid, mp=159°-160° C. (4.7 mmol, 1.89 g, 88%).
Reaction SMILES: [OH:1][C:2]1[C:11]([C:12](=[O:15])[CH2:13][CH3:14])=[C:10]2[C:5]([C:6]([CH2:17][CH2:18][CH3:19])=[CH:7][C:8](=[O:16])[O:9]2)=[C:4]2[O:20][C:21]([CH3:25])([CH3:24])[CH:22]=[CH:23][C:3]=12.[H][H]>C1(C)C=CC=CC=1.C(O)(C)C.[Pt]>[OH:1][C:2]1[C:11]([C:12](=[O:15])[CH2:13][CH3:14])=[C:10]2[C:5]([C:6]([CH2:17][CH2:18][CH3:19])=[CH:7][C:8](=[O:16])[O:9]2)=[C:4]2[O:20][C:21]([CH3:25])([CH3:24])[CH2:22][CH2:23][C:3]=12
Reactant: CCCc1cc(=O)oc2c(C(=O)CC)c(O)c3c(c12)OC(C)(C)C=C3
Reactant: [H][H]
Agent: [Pt]
Solvent: Cc1ccccc1
Solvent: CC(C)O
Product: CCCc1cc(=O)oc2c(C(=O)CC)c(O)c3c(c12)OC(C)(C)CC3
Yield: 52.9 %

Procedure:
A mixture of 5-hydroxy-2,2-dimethyl-6-propionyl-10-propyl-2H-pyrano[2,3-f]chromen-8-one (30) (5 g, 14.60 mmol) and sulfided platinum (5% on carbon, 1 g) in toluene/isopropyl alcohol (200/50 mL) was hydrogenated 16 h at room temperature under atmospheric pressure of hydrogen. The catalyst was filtered off and the filtrate concentrated under vacuum. The solid residue was crystallized from ethanol and re-crystallized from acetone to provide 2.66 g of 44a (53% yield). 1H NMR (CDCl3): 1.03 (t, J=7.5 Hz, 3H), 1.23 (t, J=7.5 Hz, 3H), 1.42 (s, 6H), 1.64 (m, 2H), 1.84 (t, J=6.5 Hz, 2H), 2.70 (t, J=6.5 Hz, 2H), 2.90 (m, 2H), 3.34 (q, J=7.0 Hz, 2H), 5.98 (s, 1H), 14.61 (s, 1H); 13C NMR (CDCl3): 8.45, 13.89, 16.42, 23.37, 26.62, 31.20, 38.13, 39.38, 77.60, 102.77, 103.43, 105.30, 110.22, 156.41, 157.29, 158.94, 159.76, 165.77, 206.67; IR: 1730 cm−1; MS (ACPI+): 345 (M+1); Anal. Calcd. for C20H24O5: C 69.75, H 7.02; Found C 70.03, H 7.18.
Reaction SMILES: FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:20][CH2:19][CH2:18][CH:17]([CH2:21][CH2:22][O:23][CH2:24][C:25]2[CH:30]=[C:29]([Br:31])[CH:28]=[CH:27][C:26]=2[F:32])[CH2:16]1)=O)(C)(C)C>C(Cl)Cl>[F:32][C:26]1[CH:27]=[CH:28][C:29]([Br:31])=[CH:30][C:25]=1[CH2:24][O:23][CH2:22][CH2:21][CH:17]1[CH2:18][CH2:19][CH2:20][NH:15][CH2:16]1
Reactant: CC(C)(C)OC(=O)N1CCCC(CCOCc2cc(Br)ccc2F)C1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Fc1ccc(Br)cc1COCCC1CCCNC1
Temperature: 0 °C

Procedure:
In a 1-ml round bottom flask 1-(t-butoxycarbonyl)-3-[2-(2-fluoro-5-bromobenzyloxy)ethyl]piperidine (0.495 g) was dissolved in methylene chloride (4 ml) under a nitrogen atmosphere. The solution was cooled to 0° C. and trifluoroacetic acid (1 ml) was slowly added dropwise. The resulting mixture was stirred for thirty minutes at ambient temperature. The progress of the reaction was monitored by thin layer chromatography. The reaction mixture was partitioned between 1 M potassium carbonate and methylene chloride. The aqueous fraction was back extracted with methylene chloride. The organic fractions were combined, and dried over sodium sulfate. The solvents were removed in vacuo. The resulting residue was used as is.
Reaction SMILES: [C:1]12([CH2:11][CH2:12][N:13]([CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])[C:14]([NH:16][CH2:17][CH2:18][CH:19]([O:26][Si](C(C)(C)C)(C)C)[C:20]3[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=3)=[O:15])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2>Cl.CO>[C:1]12([CH2:11][CH2:12][N:13]([CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])[C:14]([NH:16][CH2:17][CH2:18][CH:19]([OH:26])[C:20]3[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=3)=[O:15])[CH2:8][CH:7]3[CH2:6][CH:5]([CH2:4][CH:3]([CH2:9]3)[CH2:2]1)[CH2:10]2
Reactant: CCCCCN(CCC12CC3CC(CC(C3)C1)C2)C(=O)NCCC(O[Si](C)(C)C(C)(C)C)c1ccncc1
Agent: Cl
Solvent: CO
Product: CCCCCN(CCC12CC3CC(CC(C3)C1)C2)C(=O)NCCC(O)c1ccncc1
Yield: 55.3 %

Procedure:
A solution of 1-[2-(1-adamantyl)ethyl]-3-[3-(t-butyldimethylsilyloxy)-3-(4-pyridyl)propyl]-1-pentylurea (Compound No. 1-138) (136 mg, 0.250 mmol) in 10% hydrogen chloride-methanol (2.3 ml) was stirred at room temperature for three days. The solvent was evaporated under reduced pressure, the residue was distributed with ethyl acetate (50 ml), water (30 ml) and a 1 N aqueous sodium hydroxide solution (20 ml), and the organic layer was washed with a saturated aqueous sodium chloride solution (40 ml). The organic layer was dried over anhydrous anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the titled compound (59.2 mg, colorless noncrystalline powder, 55.3%).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7]([OH:15])=[N:8][N:9]([CH:12]([CH3:14])[CH3:13])[C:10]=1[Br:11])=[O:5])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[CH2:22](Br)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.Cl>CN(C)C=O>[CH2:1]([O:3][C:4]([C:6]1[C:7]([O:15][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[N:8][N:9]([CH:12]([CH3:14])[CH3:13])[C:10]=1[Br:11])=[O:5])[CH3:2]
Reactant: BrCc1ccccc1
Reactant: CCOC(=O)c1c(O)nn(C(C)C)c1Br
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1c(OCc2ccccc2)nn(C(C)C)c1Br
Temperature: 25 °C
Reaction time: 6 h

Procedure:
5-Bromo-3-hydroxy-1-isopropylpyrazole-4-carboxylic acid ethyl ester (5.8 g) and potassium carbonate (3.5 g) were suspended in N,N-dimethylformamide (50 mL), and benzyl bromide (2.76 mL) was added to the suspension under ice cooling. The mixture was stirred at room temperature for 6 hours. The reaction mixture was poured into 1 mol/L hydrochloric acid (100 mL), and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the obtained residue was purified by column chromatography on silica gel (eluent: ethyl acetate/hexane=1/5) to give the title compound (7.7 g)
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([Br:12])[CH:6]=2.N1C=CC=CC=1.Cl[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26]>C(Cl)Cl>[CH2:28]([O:27][C:25]([NH:1][C:2]1[C:3]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([Br:12])[CH:6]=2)=[O:26])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: CCOC(=O)c1nc2cc(Br)ccc2cc1N
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCOC(=O)c1nc2cc(Br)ccc2cc1NC(=O)OCc1ccccc1
Temperature: -10 °C
Reaction time: 1 h
Yield: 86.1 %

Procedure:
DCM (20.0 mL) was added to a flask containing ethyl 3-amino-7-bromoquinoline-2-carboxylate (from commercial source, 1.38 g, 4.68 mmol) and pyridine (1.0 mL, 12 mmol). The reaction mixture was cooled to −10° C. Benzyl chloroformate (0.843 mL, 5.61 mmol) was added slowly. The mixture was then allowed to warm gradually to room temperature and stirred for an additional 1 h. The reaction mixture was concentrated under reduced pressure. The resulting residue was triturated with MeOH (10 mL) to form a precipitate that was collected by vacuum filtration and washed with cold MeOH to give the sub-title compound (1.73 g, 86%) as a white powder. LCMS calc. for C20H18BrN2O4(M+H)+: m/z=429.2. Found: 429.1.
Reaction SMILES: [NH2:1][C:2]([CH3:21])([CH2:5][N:6]1[C:14]([O:15][CH3:16])=[C:13]2[C:8]([CH:9]=[C:10]([C:17]([F:20])([F:19])[F:18])[CH:11]=[CH:12]2)=[N:7]1)[C:3]#[N:4].[F:22][C:23]([F:34])([F:33])[C:24]1[CH:32]=[CH:31][C:27]([C:28](Cl)=[S:29])=[CH:26][CH:25]=1>>[C:3]([C:2]([NH:1][C:28](=[S:29])[C:27]1[CH:26]=[CH:25][C:24]([C:23]([F:22])([F:33])[F:34])=[CH:32][CH:31]=1)([CH3:21])[CH2:5][N:6]1[C:14]([O:15][CH3:16])=[C:13]2[C:8]([CH:9]=[C:10]([C:17]([F:19])([F:20])[F:18])[CH:11]=[CH:12]2)=[N:7]1)#[N:4]
Reactant: COc1c2ccc(C(F)(F)F)cc2nn1CC(C)(N)C#N
Reactant: FC(F)(F)c1ccc(C(=S)Cl)cc1
Product: COc1c2ccc(C(F)(F)F)cc2nn1CC(C)(C#N)NC(=S)c1ccc(C(F)(F)F)cc1

Procedure:
Using a procedure similar to that described in Example 1, except using 2-amino-3-(3-methoxy-6-trifluoromethyl-2H-indazol-2-yl)-2-methylpropionitrile (50 mg, described in Example 120) and 4-trifluoromethylthiobenzoyl chloride, the title compound was isolated as a white solid (66 mg, 78%). MS (ES): M/Z [M+H]=503. 1H NMR: (400 MHz, DMSO-d6): 1.72 (s, 3H), 4.24 (s, 3H), 4.84 (d, J=13.8 Hz, 1H), 4.96 (d, J=13.9 Hz, 1H), 7.08 (dd, J=9.0, 1.4 Hz, 1H), 7.85 (s, 1H), 7.88 (d, J=8.2 Hz, 2H), 7.94-7.99 (m, 2H), 8.09 (d, J=9.0 Hz, 1H) and 8.99 (s, 1H). 19F NMR (376 MHz, DMSO-d6): −42.0 (s, 3F) and −61.8 (s, 3F).
Reaction SMILES: [H-].[Na+:2].[O:3]1[CH2:7][CH2:6][CH2:5][C:4]1=[O:8].[CH:9](OCC)=[O:10]>CCCCCC.CCOCC>[O:8]=[C:4]1[C:5](=[CH:9][O-:10])[CH2:6][CH2:7][O:3]1.[Na+:2]
Reactant: O=C1CCCO1
Reactant: CCOC=O
Agent: [H-]
Agent: [Na+]
Solvent: CCCCCC
Solvent: CCOCC
Product: O=C1OCCC1=C[O-]
Reaction time: 1 h
Yield: 102.9 %

Procedure:
Three-neck, round-bottomed flask equipped with mechanical stirrer, addition funnel, and reflux condenser was placed in a hood behind a shield. The condenser was fitted with a drying tube which was connected to a mineral oil bubble chamber so hydrogen evolution could be monitored. After NaH (4.4 g of 60% oil dispersion, 0.11 mol) was washed with n-C6H14 (2×50 mL), filtered with brief suction drying, and transferred to the flask, sufficient Et2O was added to cover the resulting solid. A catalytic amount of C2H5OH (ca. 2 drops) was added directly to the Et2O—NaH suspension and dropwise addition without stirring of a solution of dihydrofuran-2(3H)-one (8.61 g, 0.1 mol) and ethyl formate (7.41 g, 0.1 mol) in Et2O (10 mL) was started. As soon as the Et2O began to reflux, additional Et2O (50-60 mL) was rapidly added through the reflux condenser and stirring was started. Lactone-formate addition was complete in 1 hr, and stirring was continued for an additional 22 h. Filtration, washing with Et2O, and vacuum drying gave desired product (14.0 g) as a fine powdery solid.
Reaction SMILES: [F:1][C:2]1([F:31])[CH2:6][CH2:5][C@@H:4]([C@@:7]([OH:30])([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:8]([O:10][CH:11]2[CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][CH2:12]2)=[O:9])[CH2:3]1>Cl.CO>[F:31][C:2]1([F:1])[CH2:6][CH2:5][C@@H:4]([C@@:7]([OH:30])([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:8]([O:10][CH:11]2[CH2:12][CH2:13][NH:14][CH2:15][CH2:16]2)=[O:9])[CH2:3]1
Reactant: CC(C)(C)OC(=O)N1CCC(OC(=O)[C@](O)(c2ccccc2)[C@@H]2CCC(F)(F)C2)CC1
Agent: Cl
Solvent: CO
Product: O=C(OC1CCNCC1)[C@](O)(c1ccccc1)[C@@H]1CCC(F)(F)C1
Reaction time: 12 h

Procedure:
162 Milligrams of t-butyl 4-((2R)-2-((1R)-3,3-difluorocyclo-pentyl)-2-hydroxy-2-phenylethanoyloxy)tetrahydropyridine-1(2H)-carboxylate was dissolved in 5 ml of 10% hydrochloric acid-methanol, stirred for 12 hours, and the solvent was distilled off under reduced pressure. The residue was diluted with water, washed with diethyl ether and a saturated aqueous sodium hydrogencarbonate solution was added to the aqueous layer to render it alkaline. Following an extraction with ethyl acetate, the organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. Distilling the solvent off under reduced pressure, 104 mg of the title compound was obtained as a colorless, foamy substance.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[C:7]([NH2:9])=[NH:8])([O-:3])=[O:2].[N+:13]([C:16]1[CH:27]=[CH:26][C:19]([CH:20]=[CH:21][S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1)([O-:15])=[O:14]>>[N+:13]([C:16]1[CH:17]=[CH:18][C:19]([CH:20]=[CH:21][S:22]([NH:8][C:7](=[NH:9])[C:6]2[CH:10]=[CH:11][CH:12]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)(=[O:24])=[O:23])=[CH:26][CH:27]=1)([O-:15])=[O:14]
Reactant: N=C(N)c1cccc([N+](=O)[O-])c1
Reactant: O=[N+]([O-])c1ccc(C=CS(=O)(=O)Cl)cc1
Product: N=C(NS(=O)(=O)C=Cc1ccc([N+](=O)[O-])cc1)c1cccc([N+](=O)[O-])c1

Procedure:
Reaction of 3-nitrobenzamidine with 4-nitrostyrylsulfonyl chloride according to the above procedure provides N-(4-NITROSTYRYLSULFONYL)-3-NITROBENZAMIDINE, m.p. 230°-232° C.
Reaction SMILES: [Br:1][C:2]1[C:3]([C:12]2[O:13][CH:14]=[CH:15][CH:16]=2)=[N:4][C:5]([NH2:11])=[N:6][C:7]=1S(C)=O.[CH2:17]([NH2:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>O1CCOCC1>[CH2:17]([NH:24][C:7]1[C:2]([Br:1])=[C:3]([C:12]2[O:13][CH:14]=[CH:15][CH:16]=2)[N:4]=[C:5]([NH2:11])[N:6]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: NCc1ccccc1
Reactant: CS(=O)c1nc(N)nc(-c2ccco2)c1Br
Solvent: C1COCCO1
Product: Nc1nc(NCc2ccccc2)c(Br)c(-c2ccco2)n1
Temperature: 100 °C
Yield: 71.1 %

Procedure:
To a stirred suspension of 200 mg (0.66 mmol) 5-bromo-4-furan-2-yl-6-methanesulfinyl-pyrimidin-2-ylamine in 5 ml dioxane was added 0.16 ml (1.46 mmol) benzylamine and the mixture heated at 100° C. for 2 hour. The reaction mixture was then concentrated in vacuo. Chromatography (ethyl acetate) followed by trituration in ether/hexane afforded 162 mg (71%) N4-benzyl-5-bromo-6-furan-2-yl-pyrimidine-2,4-diamine as a white crystalline solid. EI-MS m/e (%): 346 (M{81Br}+, 50), 344 (M{79Br} +51), 265 (46), 106 (100), 91 (61).
Reaction SMILES: [CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[N:3]([C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9])[O:2]2>C(O)(=O)C.O.[Zn]>[OH:2][C@@H:1]1[CH2:6][CH2:5][C@H:4]([NH:3][C:8](=[O:9])[O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:7]1
Reactant: O=C(OCc1ccccc1)N1OC2CCC1C2
Agent: [Zn]
Solvent: O
Solvent: CC(=O)O
Product: O=C(N[C@H]1CC[C@@H](O)C1)OCc1ccccc1
Temperature: 25 °C
Reaction time: 7.5 h
Yield: 23.8 %

Procedure:
A solution 3-aza-2-oxabicyclo[2.2.1]heptane-3-carboxylic acid, (phenylmethyl) ester (0.5 g) in glacial acetic acid (0.5 ml) was added to a stirred suspension of powdered zinc (0.35 g) in a mixture of acetic acid and water (1:1; 4 ml), and the mixture was stirred at 60° for 7.5 h. Additional zinc powder (0.14 g) and acetic acid (1 ml) were added and stirring was continued for a further 16.5 h. After cooling to room temperature, the mixture was filtered and the excess of zinc washed with 2M hydrochloric acid (20 ml). The combined filtrate and washings were neutralised with 8% sodium carbonate and extracted into ethyl acetate (3×30 ml). The combined organic extracts were washed with brine (30 ml), dried and concentrated in vacuo. Purification by FCC eluting with ethyl acetate: cyclohexane (1:1) gave an oil (120 mg) which solidified upon standing and was recrystallised from cyclohexane to give the title compound (70 mg), m.p. 62°-63°.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:14]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)=[N:13][NH:12][C:11](=[O:23])[C:10]=2[C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:5][CH:4]=1.[CH2:29](Cl)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>>[CH2:29]([N:12]1[C:11](=[O:23])[C:10]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[C:9]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[C:14]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)=[N:13]1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1
Reactant: CCOC(=O)c1c(-c2ccc(OC)cc2)c(-c2ccc(OC)cc2)n[nH]c1=O
Reactant: ClCc1ccccc1
Product: CCOC(=O)c1c(-c2ccc(OC)cc2)c(-c2ccc(OC)cc2)nn(Cc2ccccc2)c1=O
Yield: 99.1 %

Procedure:
Using 5,6-bis(4-methoxyphenyl)-4-ethoxycarbonyl-2H-pyridazin-3-one and benzyl chloride as starting materials, the procedures of Example 19 were repeated likewise, whereby the title compound was obtained in a yield of 99.1%.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:9]([O:11][CH2:12][CH3:13])=[O:10].[Br:14]N1C(=O)CCC1=O>>[Br:14][CH2:8][C:4]1[C:3]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[C:2]([Cl:1])[CH:7]=[CH:6][CH:5]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: CCOC(=O)c1c(C)cccc1Cl
Product: CCOC(=O)c1c(Cl)cccc1CBr

Procedure:
Reaction of ethyl 3-chloro-o-toluate with N-bromosuccinimide as described in Example 1a provides ethyl α-bromo-3chloro-o-toluate as an oil.
Reaction SMILES: [C:1]([O-:4])([O-])=[O:2].[K+].[K+].[OH:7][CH2:8][CH:9]1[CH2:14][CH2:13][CH2:12][NH:11][CH2:10]1>CC(C)=O>[C:9]([O:4][C:1]([N:11]1[CH2:12][CH2:13][CH2:14][CH:9]([CH2:8][OH:7])[CH2:10]1)=[O:2])([CH3:14])([CH3:10])[CH3:8]
Reactant: O=C([O-])[O-]
Reactant: OCC1CCCNC1
Agent: [K+]
Solvent: CC(C)=O
Product: CC(C)(C)OC(=O)N1CCCC(CO)C1
Yield: 88 %

Procedure:
Using a procedure analogous to Example 1-C (K2CO3, acetone), 3-hydroxymethylpiperidine gave the title compound as a solid (34.2 g, 88%).
Reaction SMILES: [OH:1][CH2:2][CH2:3][NH2:4].[CH:5]1([CH2:12]Br)[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1>>[CH:5]1([CH2:12][NH:4][CH2:3][CH2:2][OH:1])[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1
Reactant: NCCO
Reactant: BrCC1CCCCCC1
Product: OCCNCC1CCCCCC1

Procedure:
2-Hydroxyethylamine was reacted with cycloheptylmethyl bromide according to Method B2a to give N-cycloheptylmethyl-N-(2-hydroxyethyl)amine. The alcohol was reacted with SOCl2 according to Method B7c to give N-cycloheptylmelthyl-N-(2-chloroethyl)ammonium chloride. The chloroethylamine was reacted with 4-cyanophenyl isothiocyanate to give 2-(4-cyanophenylimino)-3-(cycloheptylmethyl)-1,3-thiazolidine.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:12]3[C:13]([CH3:30])=[C:14]([NH:19][C:20](=O)[C:21]4[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=4)[C:15]([CH3:18])=[C:16]([CH3:17])[C:11]=3[O:10][C:9]2([CH3:32])[CH3:31])=[CH:4][CH:3]=1>CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[C:12]3[C:13]([CH3:30])=[C:14]([NH:19][CH2:20][C:21]4[CH:22]=[CH:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=4)[C:15]([CH3:18])=[C:16]([CH3:17])[C:11]=3[O:10][C:9]2([CH3:32])[CH3:31])=[CH:6][CH:7]=1
Reactant: COc1ccc(C(=O)Nc2c(C)c(C)c3c(c2C)C(c2ccc(F)cc2)C(C)(C)O3)cc1
Solvent: CO
Product: COc1ccc(CNc2c(C)c(C)c3c(c2C)C(c2ccc(F)cc2)C(C)(C)O3)cc1
Yield: 52 %

Procedure:
By using N-[3-(4-fluorophenyl)-2,2,4,6,7- pentamethyl-2,3-dihydro-1-benzofuran-5-yl]-4-methoxybenzamide, the title compound was synthesized according to Example 2b. Yield: 52%. Melting point: 114-115° C. (Methanol).