Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:7]([C:8]2[CH:12]=[CH:11][S:10][CH:9]=2)=[C:6](Cl)[N:5]2[N:14]=[CH:15][N:16]=[C:4]2[N:3]=1.[CH:17]1([NH2:22])[CH2:21][CH2:20][CH2:19][CH2:18]1.C(N(CC)CC)C>O1CCCC1>[Cl:1][C:2]1[C:7]([C:8]2[CH:12]=[CH:11][S:10][CH:9]=2)=[C:6]([NH:22][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[N:5]2[N:14]=[CH:15][N:16]=[C:4]2[N:3]=1
Reactant: Clc1nc2ncnn2c(Cl)c1-c1ccsc1
Reactant: NC1CCCC1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Clc1nc2ncnn2c(NC2CCCC2)c1-c1ccsc1
Yield: 70.4 %

Procedure:
5,7-Dichloro-6-thien-3-yl-1,2,4-triazolo[1,5-a]pyrimidine (0.54 g, 0.002 mol) was dissolved in tetrahydrofuran (20 ml). A mixture of cyclopentylamine (0.2 g, 0.002 mol), tetrahydrofuran (2 ml) and triethylamine (0.25 g, 0.002 mol) was then added with stirring and the stirring continued for a further hour after the addition was complete. The solvent was then distilled off in vacuo and the residue treated with ethyl acetate and water (50 ml each). The organic phase was separated, dried with sodium sulphate, filtered and the solvent removed in vacuo. The residue was purified by chromatography on silica gel using 8:2 ethyl acetate: petroleum ether (300 ml) as eluant to give 0.45 g 5-chloro-6-thien-3yl-7-cyclopentylamino-1,2,4-triazolo[1,5-a]-pyrimidine as colourless crystals, m.pt. 78° C. Yield: 71% of theoretical.
Reaction SMILES: [SH:1][C:2]1[O:3][C:4]2[CH:10]=[CH:9][C:8]([S:11]([NH2:14])(=[O:13])=[O:12])=[CH:7][C:5]=2[N:6]=1.[C:15]([O-])([O-])=O.[K+].[K+].CI>CN(C=O)C>[CH3:15][S:1][C:2]1[O:3][C:4]2[CH:10]=[CH:9][C:8]([S:11]([NH2:14])(=[O:12])=[O:13])=[CH:7][C:5]=2[N:6]=1
Reactant: NS(=O)(=O)c1ccc2oc(S)nc2c1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: CSc1nc2cc(S(N)(=O)=O)ccc2o1
Temperature: 25 °C
Reaction time: 3 h
Yield: 96.5 %

Procedure:
To a solution of 2-mercapto-benzooxazole-5-sulfonic acid amide (17.0 g, 73.8 mmol, 1.0 equiv) in anhydrous DMF (200 mL) was added anhydrous K2CO3 (51.0 g, 369.1 mmol, 5.0 equiv) and methyl iodide (16.1 mL, 36.7 g, 258.4 mmol, 3.5 equiv). After stirring for 3 h at rt, the K2CO3 was removed by filtration and the reaction mixture concentrated by evaporation under reduced pressure. The residue was washed with ethyl acetate (50 mL) give 17.4 g (97%) of the title compound. 1H NMR (300 MHz, DMSO): δ 2.80 (s, 3H), 7.47 (br s, 2H), 7.83 (s, 2H), 8.07 (s, 1H). 13C NMR (75 MHz, DMSO): δ 4.28, 110.47, 115.71, 122.04, 140.99, 141.37, 152.92, 167.84. MS (ISP): 244.9 [M+H]+.
Reaction SMILES: [CH3:1]NC(=[O:17])NC1(C2C=CC=CC=2)CCNCC1.C(O)(=O)C.O.O.[ClH:24].[C:25]([N:33]1[CH2:38][CH2:37][O:36][C:35]([C:57]2[CH:62]=[CH:61][C:60]([F:63])=[C:59]([F:64])[CH:58]=2)([CH2:39][CH2:40][N:41]2[CH2:46][CH2:45][C:44]([C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)([NH:47][C:48]([NH2:50])=[O:49])[CH2:43][CH2:42]2)[CH2:34]1)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C([BH3-])#N.[Na+]>CO>[OH2:17].[ClH:24].[C:25]([N:33]1[CH2:38][CH2:37][O:36][C:35]([C:57]2[CH:62]=[CH:61][C:60]([F:63])=[C:59]([F:64])[CH:58]=2)([CH2:39][CH2:40][N:41]2[CH2:46][CH2:45][C:44]([NH:47][C:48]([NH:50][CH3:1])=[O:49])([C:51]3[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=3)[CH2:43][CH2:42]2)[CH2:34]1)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: NC(=O)NC1(c2ccccc2)CCN(CCC2(c3ccc(F)c(F)c3)CN(C(=O)c3ccccc3)CCO2)CC1
Reactant: CNC(=O)NC1(c2ccccc2)CCNCC1
Agent: Cl
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: O
Solvent: CO
Solvent: CC(=O)O
Product: CNC(=O)NC1(c2ccccc2)CCN(CCC2(c3ccc(F)c(F)c3)CN(C(=O)c3ccccc3)CCO2)CC1
Yield: 73.2 %

Procedure:
This compound is prepared by the procedure described in step B of EXAMPLE 68 from 1.85 g of 4-(N'-methylureido)-4-phenylpiperidine (free base), 0.44 ml of acetic acid and 26 ml of MeOH, and then 2.75 g of the compound obtained in step A of EXAMPLE 68 in 26 ml of MeOH and 0.55 g of sodium cyanoborohydride in 26 ml of MeOH. This gives 2 g of the expected product.
Reaction SMILES: C([N:4]1[CH2:9][CH2:8][CH2:7][C:6]2([CH2:13][C:12]3[CH:14]=[C:15]([NH:18][S:19]([CH3:22])(=[O:21])=[O:20])[CH:16]=[CH:17][C:11]=3[O:10]2)[CH2:5]1)(=O)C.[ClH:23]>C(O)C>[ClH:23].[CH3:22][S:19]([NH:18][C:15]1[CH:16]=[CH:17][C:11]2[O:10][C:6]3([CH2:7][CH2:8][CH2:9][NH:4][CH2:5]3)[CH2:13][C:12]=2[CH:14]=1)(=[O:20])=[O:21]
Reactant: CC(=O)N1CCCC2(Cc3cc(NS(C)(=O)=O)ccc3O2)C1
Agent: Cl
Solvent: CCO
Product: CS(=O)(=O)Nc1ccc2c(c1)CC1(CCCNC1)O2

Procedure:
A solution of 3.6 g (11.09 mmole) of 1'-Acetyl-2,3-dihydro-5-methanesulfonamidospiro(benzofuran-2,3'-piperidine) in 100 mL ethanol was treated with 50 mL 6N hydrochloric acid and heated to reflux for 18 hours. The reaction was concentrated to dryness and the residue crystallized from ethanol to give 2.77 g of products mp=243°-244° C. 'H NMR (DMSO) δ9.6 (brs, 1H), 9.4 (s, 1H), 7.11 (d, J=1.6 Hz, 1H), 7.0 (dd, J=1.6, 8.5 Hz), 6.70 (d, J=8.5 Hz, 1H), 3.5-2.8 (m, 6H), 2.88 (s, 3H), 2.0-1.30 (m, 4H).
Reaction SMILES: [CH2:1](P(=O)(OCC)OCC)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].CC([N-]C(C)C)C.[CH2:24]([N:31]1[C:39]2[C:34](=[CH:35][C:36]([O:40][CH:41]3[CH2:46][CH2:45][CH2:44][CH2:43][O:42]3)=[CH:37][CH:38]=2)[C:33]([CH:47]=O)=[C:32]1[CH:49]([CH3:51])[CH3:50])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>C1COCC1.CCOC(C)=O>[CH2:24]([N:31]1[C:39]2[C:34](=[CH:35][C:36]([O:40][CH:41]3[CH2:46][CH2:45][CH2:44][CH2:43][O:42]3)=[CH:37][CH:38]=2)[C:33](/[CH:47]=[CH:1]/[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[C:32]1[CH:49]([CH3:51])[CH3:50])[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
Reactant: CC(C)c1c(C=O)c2cc(OC3CCCCO3)ccc2n1Cc1ccccc1
Reactant: CCOP(=O)(Cc1ccccc1)OCC
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)c1c(/C=C/c2ccccc2)c2cc(OC3CCCCO3)ccc2n1Cc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a −78° C. solution of diethyl benzylphoshonate (91 mg, 0.4 mmol) in THF (5 mL) was added a 2 M solution of LDA and THF (0.2 mL, 0.4 mmol), and the solution was warmed to RT over 20 min. A solution of 1-benzyl-2-isopropyl-5-(tetrahydropyran-2-yloxy)-1H-indole-3-carboxaldehyde (Compound 13, 100 mg, 0.27 mmol) and THF (2 mL) was added, and the solution was stirred for 1 h at ambient temperature. The solution was diluted with EtOAc (50 mL), and washed with brine (10 mL), and dried (Na2SO4), and the solvent was removed under vacuum. Silica gel flash chromatography using 20% EtOAc in hexane gave (E)-1-benzyl-2-isopropyl-3-(2-phenylethen-1-yl)-5-(tetrahydropyran-2-yloxy)-1H-indole (Compound 26) as a colorless oil.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=O)=[CH:15][CH:14]=3)=[CH:11][CH:10]=[N:9]2)=[CH:4][CH:3]=1.[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29]C#N)=[CH:25][CH:24]=1>>[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[O:21][N:19]=[C:16]3[CH:15]=[CH:14][C:13]([C:12]4[N:8]([C:5]5[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=5)[N:9]=[CH:10][CH:11]=4)=[CH:18][C:17]=23)=[CH:25][CH:24]=1
Reactant: N#CCc1ccc(Cl)cc1
Reactant: O=[N+]([O-])c1ccc(-c2ccnn2-c2ccc(Cl)cc2)cc1
Product: Clc1ccc(-c2onc3ccc(-c4ccnn4-c4ccc(Cl)cc4)cc23)cc1

Procedure:
The title compound, light green solid (111 mg, 82%), MS (ISP) m/z=406.2 [(M+H)+], mp 222° C., was prepared in accordance with the general method of example 1 from 1-(4-chloro-phenyl)-5-(4-nitro-phenyl)-1H-pyrazole (intermediate H) (100 mg, 353 μmol) and commercially available 2-(4-chloro-phenyl)-acetonitrile.
Reaction SMILES: CO[C:3](=[O:13])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([Cl:10])[C:5]=1[CH2:11]Br.[CH2:14]([NH2:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C([O-])([O-])=O.[K+].[K+].C(OCC)(=O)C>C1(C)C=CC=CC=1.CCCCCC>[CH2:14]([N:21]1[CH2:11][C:5]2[C:4](=[CH:9][CH:8]=[CH:7][C:6]=2[Cl:10])[C:3]1=[O:13])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: COC(=O)c1cccc(Cl)c1CBr
Reactant: NCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Solvent: CCCCCC
Product: O=C1c2cccc(Cl)c2CN1Cc1ccccc1
Temperature: 100 °C
Reaction time: 2 h
Yield: 100.1 %

Procedure:
A mixture of 2-bromomethyl-3-chloro-benzoic acid methyl ester (0.132 g, 0.5 mmol), benzylamine (0.065 mL, 0.6 mmol), and K2CO3 (0.207 g, 1.5 mmol) in toluene (5 mL) was heated with stirring at 100° C. for 2 h. Workup and silica gel column chromatography using 30% ethyl acetate in hexane afforded 2-benzyl-4-chloro-2,3-dihydro-isoindol-1-one (0.129 g, 100%). 1H NMR (300 MHz, CDCl3): δ (ppm) 4.24 (s, 2H), 4.70 (s, 2H), 7.27-7.48 (m, 7H), 7.80 (d, 1H). GC-MS: m/z 257 (M)+, 180 (M−77)+.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([OH:11])[CH:5]=[C:6]([CH3:10])[C:7]=1[N:8]=[O:9].[OH:12]O>C(O)(=O)C.N.N.N.N.N.N.O.O.O.O.O[Mo](O)(=O)=O.O[Mo](O)(=O)=O.O[Mo](O)(=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O>[CH3:10][C:6]1[CH:5]=[C:4]([OH:11])[CH:3]=[C:2]([CH3:1])[C:7]=1[N+:8]([O-:12])=[O:9]
Reactant: Cc1cc(O)cc(C)c1N=O
Reactant: OO
Agent: O=[Mo](=O)(O)O
Agent: O=[Mo](=O)=O
Agent: N
Solvent: CC(=O)O
Solvent: O
Product: Cc1cc(O)cc(C)c1[N+](=O)[O-]
Temperature: 100 °C

Procedure:
A mixture of 3,5-dimethyl-4-nitrosophenol (70.63 g) from above and (NH4)6Mo7O24.4H2O) (2.83g) in 770 ml of glacial acetic acid was warmed to 100° C. 30% H2O2 (84 ml) was added to the mixture in 10 ml portions until an exothermic reaction was observed. The reaction mixture was then stirred and the remainder of the H2O2 solution added in small portions. The reaction mixture was heated and stirred until a clear dark red solution results. A yellow-orange solid precipitated from the solution after stirring for another 20-30 minutes. The reaction mixture was stirred overnight and filtered to give a small amount of a yellow solid and a clear dark red filtrate. The red filtrate was concentrated in vacuo and partitioned between water and ether. The aqueous layer was washed with ether and the combined ether extracts washed with 10% sodium carbonate until the aqueous layer becomes basic. The ether extract was dried over anhydrous sodium sulfate, filtered, concentrated and allowed to cool overnight. After cooling in an ice bath the mixture was filtered to give 49.5 g of 3,5-dimethyl-4-nitrophenol as a yellow-green solid. Mp. 106-108° C.
Reaction SMILES: [C:1]1([NH2:11])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[H-].[Na+].F[C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1[S:22]([CH3:25])(=[O:24])=[O:23]>CN(C)C=O.O>[F:21][C:19]1[CH:20]=[CH:15][C:16]([S:22]([CH3:25])(=[O:24])=[O:23])=[C:17]([NH:11][C:1]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH:4]=[CH:3][CH:2]=2)[CH:18]=1
Reactant: CS(=O)(=O)c1ccc(F)cc1F
Reactant: Nc1cccc2ccccc12
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CS(=O)(=O)c1ccc(F)cc1Nc1cccc2ccccc12
Temperature: 25 °C
Reaction time: 16 h
Yield: 37.8 %

Procedure:
Naphthalen-1-amine (0.89 g, 4.7 mmol) and 60% NaH in oil (0.24 g, 6.1 mmol) were stirred in N,N-dimethylformamide (5 mL) for 15 min. at 0° C. and for 30 min. at room temperature. 2,4-Difluoro-1-(methylsulfonyl)benzene (0.67 g, 4.7 mmol), was added to the reaction as a solid. The reaction was allowed to stir at room temperature for 16 h. The reaction was poured in water and extracted with ether. After removal of solvent the crude was purified on silica chromatography in 10% ethyl acetate in hexanes to obtain 0.56 g of product (0.36 mg, 38% yield). 1H NMR (400 MHz, CDCl3): δ 8.30 (s, 1H), 7.89 (m, 3H), 7.54 (m, 5H), 6.79 (t, 1H), 6.48 (d, 1H), 3.22 (s, 3H).
Reaction SMILES: N[C:2]1[CH:19]=[CH:18][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][CH:10]=2)=[O:7])=[CH:4][CH:3]=1.NC1N=C(C)[CH:24]=[C:23](Cl)[N:22]=1.Cl.N.C([O:33]CCO)C>C(OCC)(=O)C.CO.O>[C:23]([NH:22][C:18]1[CH:19]=[CH:2][CH:3]=[CH:4][C:5]=1[C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][CH:10]=1)=[O:7])(=[O:33])[CH3:24]
Reactant: CCOCCO
Reactant: Nc1ccc(C(=O)Nc2ccc([N+](=O)[O-])cc2)cc1
Reactant: Cc1cc(Cl)nc(N)n1
Agent: Cl
Agent: N
Solvent: CO
Solvent: CCOC(C)=O
Solvent: O
Product: CC(=O)Nc1ccccc1C(=O)Nc1ccc([N+](=O)[O-])cc1
Temperature: 20 °C

Procedure:
4-Amino-N-(4-nitrophenyl)benzamide (C1) (730 mg, 2.84 mmol) and 4-chloro-6-methyl-2-pyrimidinylamine (A8) (416 mg, 2.84 mmol) were dissolved in warm 2-ethoxyethanol (20 mL), two drops c.HCl was then added to the reaction mixture was refluxed for 40 min. by which time TLC and MS showed the completion of the reaction. The reaction mixture was diluted with ethyl acetate and cooled to 20° C. The resulting precipitate was filtered and washed with more EtOAc to give a solid product. This was suspended in MeOH and basified with aqueous NH3 and diluted with water. The resulting precipitate was filtered and dried to give C2 (671 mg). The filtrate was concentrated to give a further 276 mg of C2 (92% overall): mp (MeOH)>300° C.; 1H NMR [(CD3)2SO] δ10.59 (s, 1 H, NH), 9.37 (s, 1 H, NH), 8.27-8.24 (m, 2 H, ArH), 8.09-8.06 (m, 2 H, ArH), 8.05-7.90 (m, 4 H, ArH), 6.25 (s, 2 H, NH2), 5.96 (s, 1 H, ArH), 2.16 (s, 3 H, CH3); Mass APCI+ 365.
Reaction SMILES: [K].Cl[C:3]1[CH:11]=[CH:10][CH:9]=[CH:8][C:4]=1[C:5]([OH:7])=[O:6].[F:12][C:13]1[CH:19]=[CH:18][C:16]([NH2:17])=[CH:15][CH:14]=1.[C:20](=O)([O-])[O-:21].[K+].[K+]>[Cu].CN(C)C=O>[F:12][C:13]1[CH:19]=[CH:18][C:16]([N:17]2[C:20](=[O:21])[O:7][C:5](=[O:6])[C:4]3=[CH:8][CH:9]=[CH:10][CH:11]=[C:3]23)=[CH:15][CH:14]=1
Reactant: O=C([O-])[O-]
Reactant: O=C(O)c1ccccc1Cl
Reactant: Nc1ccc(F)cc1
Agent: [Cu]
Agent: [K+]
Agent: [K]
Solvent: CN(C)C=O
Product: O=c1oc(=O)n(-c2ccc(F)cc2)c2ccccc12
Reaction time: 18 h

Procedure:
The potassium salt of o-chlorobenzoic acid (25 g), 25 g. of 4-fluoroaniline, 9 g. potassium carbonate and 2 g. of copper powder were heated under reflux in 200 ml. dimethylformamide. After cooling the solvent was evaporated, the residue dissolved in 500 ml. of absolute ethanol, the solution was filtered and the filtrate evaporated. The residue was suspended in 300 ml. of methylene chloride and filtered. The solid (on 10 filter) was dissolved in 100 ml. of water and 45 g. of potassium carbonate was added. To this solution 65 ml. phosgene (12.5% in benzene) was added under vigorous stirring. The stirring was continued for 18 hours at room temperature. The precipitate, which had formed, was filtered off and washed with water. After air drying the filter case was dissolved in chloroform (200 ml.) and the solution treated with solid sodium carbonate, aluminium oxide and activated charcoal. The solvent was then exchanged for ether and the material, which crystallized, was collected by filtration, m.p. 199°-201°.
Reaction SMILES: N1C(C)=CC=[CH:3][C:2]=1C.C(Cl)(=O)C(Cl)=O.CNC(=O)C.[OH:20][C:21]([CH3:49])([CH3:48])[CH2:22][C@@:23]1([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[O:28][C:27](=[O:29])[N:26]([C@H:30]([C:32]2[CH:41]=[CH:40][C:35]([C:36]([NH:38][NH2:39])=[O:37])=[CH:34][CH:33]=2)[CH3:31])[CH2:25][CH2:24]1>ClCCl>[OH:20][C:21]([CH3:48])([CH3:49])[CH2:22][C@@:23]1([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[O:28][C:27](=[O:29])[N:26]([C@H:30]([C:32]2[CH:41]=[CH:40][C:35]([C:36]3[O:37][C:2]([CH3:3])=[N:39][N:38]=3)=[CH:34][CH:33]=2)[CH3:31])[CH2:25][CH2:24]1
Reactant: Cc1cccc(C)n1
Reactant: C[C@@H](c1ccc(C(=O)NN)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
Agent: O=C(Cl)C(=O)Cl
Solvent: CNC(C)=O
Solvent: ClCCl
Product: Cc1nnc(-c2ccc([C@H](C)N3CC[C@](CC(C)(C)O)(c4ccccc4)OC3=O)cc2)o1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
2,6-Lutidine (88 μL) followed by oxalyl chloride (32 μL) was added to a solution of N-methyl-acetamide (28 mg) in dichloromethane (3 mL) chilled in an ice bath. After stirring the solution for 15 min, 4-{(S)-1-[(S)-6-(2-hydroxy-2-methyl-propyl)-2-oxo-6-phenyl-[1,3]oxazinan-3-yl]-ethyl}-benzoic acid hydrazide (154 mg) was added and then the cooling bath was removed. The solution was stirred for 1 h and then neutralized by the addition of saturated aqueous NaHCO3 solution. The resulting mixture was extracted twice with dichloromethane and the combined extracts were dried (MgSO4) and concentrated. The residue was taken up in acetic acid (1 mL) and stirred at 120° C. for 2.5 h. After cooling to ambient temperature, the solution was concentrated under reduced pressure and the residue was purified by chromatography on silica gel (CH2Cl2/MeOH 98:2->95:5) to afford pure Example 3 and a mixture containing Example 2. Example 2 was separated by a second chromatography on silica gel (CH2Cl2/MeOH 92:8).
Reaction SMILES: [C:1]([F:4])([F:3])=[CH2:2].[C:5]([O:12][CH3:13])(=[O:11])/[CH:6]=[CH:7]\[C:8]([O-:10])=[O:9].[OH2:14]>>[C:5]([O:11][O:12][C:5]([O:11][CH:1]([CH3:2])[CH3:2])=[O:14])([O:12][CH:13]([CH3:1])[CH3:13])=[O:14].[C:1]([F:4])([F:3])=[CH2:2].[C:5]([O:12][CH3:13])(=[O:11])/[CH:6]=[CH:7]\[C:8]([O-:10])=[O:9]
Reactant: O
Agent: C=C(F)F
Agent: COC(=O)/C=C\C(=O)[O-]
Product: CC(C)OC(=O)OOC(=O)OC(C)C

Procedure:
In a 2 liter-autoclave, 1040 g of deionized water, 0.8 g of methyl cellulose, 2 g of diisopropyl peroxydicarbonate (IPP), 396 g of vinylidene fluoride and 4 g of monomethyl maleate (giving a vinylidene fluoride/monomethyl maleate (mol ratio)=100/1.01) were charged and subjected to suspension polymerization at 28° C.
Reaction SMILES: [Cl:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[C:20]([C:22]4[O:23][C:24]([CH3:27])=[N:25][N:26]=4)[CH:19]=[CH:18][C:17]=3[CH3:28])=[CH:12][CH:11]=2)=[O:9])=[CH:4][CH:3]=1.[CH:31]1([CH2:34]Br)[CH2:33][CH2:32]1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]([CH2:34][CH:31]2[CH2:33][CH2:32]2)[C:8]([C:10]2[CH:11]=[CH:12][C:13]([C:16]3[CH:21]=[C:20]([C:22]4[O:23][C:24]([CH3:27])=[N:25][N:26]=4)[CH:19]=[CH:18][C:17]=3[CH3:28])=[CH:14][CH:15]=2)=[O:9])=[CH:29][CH:30]=1
Reactant: BrCC1CC1
Reactant: Cc1nnc(-c2ccc(C)c(-c3ccc(C(=O)NCc4ccc(Cl)cc4)cc3)c2)o1
Product: Cc1nnc(-c2ccc(C)c(-c3ccc(C(=O)N(Cc4ccc(Cl)cc4)CC4CC4)cc3)c2)o1

Procedure:
N-(4-Chlorobenzyl)-N-(cyclopropylmethyl)-2′-methyl-5′-(5-methyl-1,3,4-oxadiazol-2-yl)-1,1′-biphenyl-4-carboxamide was prepared from N-(4-chlorobenzyl)-2′-methyl-5′-(5-methyl-1,3,4-oxadiazol-2-yl)-1,1′-biphenyl-4-carboxamide and cyclopropylmethyl-bromide using method L. LCMS; retention time 3.89 min, MH+ 472/474.
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([C:17]2[N:21]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:20]3[CH:30]=[CH:31][CH:32]=[CH:33][C:19]=3[N:18]=2)[C:5](=[O:16])[N:6]([CH2:8][O:9][CH2:10][CH2:11][Si:12]([CH3:15])([CH3:14])[CH3:13])[N:7]=1.[S:34]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35]1.C(=O)([O-])[O-].[K+].[K+].O>C(COC)OC>[S:34]1[CH:38]=[CH:37][C:36]([C:2]2[CH:3]=[C:4]([C:17]3[N:21]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:27])[CH3:28])[C:20]4[CH:30]=[CH:31][CH:32]=[CH:33][C:19]=4[N:18]=3)[C:5](=[O:16])[N:6]([CH2:8][O:9][CH2:10][CH2:11][Si:12]([CH3:13])([CH3:14])[CH3:15])[N:7]=2)=[CH:35]1
Reactant: C[Si](C)(C)CCOCn1nc(Cl)cc(-c2nc3ccccc3n2COCC[Si](C)(C)C)c1=O
Reactant: OB(O)c1ccsc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: COCCOC
Product: C[Si](C)(C)CCOCn1nc(-c2ccsc2)cc(-c2nc3ccccc3n2COCC[Si](C)(C)C)c1=O
Temperature: 85 °C
Reaction time: 4 h

Procedure:
44 mg of 6-chloro-2-(2-trimethylsilanylethoxymethyl)-4-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzimidazol-2-yl]-2H-pyridazin-3-one, 14 mg of thiophene-3-boronic acid and 36 mg of potassium carbonate are dissolved 1.5 ml of a 1:2 mixture of water and dimethoxyethane, and argon is passed through the solution for degassing. Addition of 7 mg of (1,1′-bis(diphenylphosphine) -ferrocene)palladium(II) chloride-dichloromethane complex is followed by stirring at 85° C. for 4 hours. For workup, it is diluted with water and extracted several times with ethyl acetate. The combined organic phases are dried using a silica gel cartridge, and the solvent is distilled off. The crude product is purified by silica gel chromatography (n-heptane/ethyl acetate).
Reaction SMILES: [C:1](Cl)(=[O:5])[C:2]([CH3:4])=[CH2:3].[N+:7]([C:10]1[CH:16]=[CH:15][C:13]([NH2:14])=[CH:12][CH:11]=1)([O-:9])=[O:8].C([O-])([O-])=O.[Na+].[Na+]>CC(C)=O>[CH3:4][C:2](=[CH2:3])[C:1]([NH:14][C:13]1[CH:15]=[CH:16][C:10]([N+:7]([O-:9])=[O:8])=[CH:11][CH:12]=1)=[O:5]
Reactant: C=C(C)C(=O)Cl
Reactant: Nc1ccc([N+](=O)[O-])cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(C)=O
Product: C=C(C)C(=O)Nc1ccc([N+](=O)[O-])cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 92.4 %

Procedure:
275 ml of methacryloyl chloride (2.75 mol=1.1 equiv.) was added dropwise to a cooled suspension of 345 g of 4-nitro aniline (2.5 mol) and 290 g of Na2CO3 (2.75 mol =1.1 equiv.) in 2.5 liter acetone. After completing the addition, stirring was continued for 30 min at 30° C. After TLC inspection the reaction mixture was poured into 15 liter of ice-water under stirring. The precipitate was suction-filtered and washed 3 times with 2.5 liter of demineralised water. After drying at 50° C., 476.5 g of 2-methyl-N-(4-nitro phenyl) acrylamide was obtained.
Reaction SMILES: [C:1]1([C:7]2([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[O:11][C:10]3[CH:12]=[CH:13][C:14]([NH2:16])=[CH:15][C:9]=3[O:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(C(C)C)C(C)C)C.[C:32]1([S:38](Cl)(=[O:40])=[O:39])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>ClCCl>[C:17]1([C:7]2([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[O:11][C:10]3[CH:12]=[CH:13][C:14]([NH:16][S:38]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)(=[O:40])=[O:39])=[CH:15][C:9]=3[O:8]2)[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: Nc1ccc2c(c1)OC(c1ccccc1)(c1ccccc1)O2
Reactant: O=S(=O)(Cl)c1ccccc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: O=S(=O)(Nc1ccc2c(c1)OC(c1ccccc1)(c1ccccc1)O2)c1ccccc1
Temperature: 25 °C
Reaction time: 5 h
Yield: 6 %

Procedure:
2,2-Diphenyl-1,3-benzodioxol-5-amine was dissolved in dichloromethane (5 ml). N-ethyldiisopropyl amine (0.1 ml. 0.6 mmol) and benzenesulfonyl chloride (88 mg, 0.5 mmol) were added. The reaction was stirred for 5 hours at room temperature. The reaction was washed with cold 1N aqueous HCl, with 1N aqueous NaOH and with saturated aqueous sodium chloride solution. The organic layer was dried over sodium sulfate, filtered and the solvent was evaporated in vacuo. The residue was purified by column chromatography using dichloromethane as the eluant. The product was crystallized from hexane to yield the product as white crystals (12 mg, 6%).
Reaction SMILES: F[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[N+:12]([O-:14])=[O:13])[NH:8][C:7](=[O:15])[C:6](=[O:16])[NH:5]2.[CH3:17][C:18]1[NH:19][CH:20]=[CH:21][N:22]=1>CN(C=O)C>[CH3:17][C:18]1[NH:19][CH:20]=[C:21]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][C:11]=2[N+:12]([O-:14])=[O:13])[NH:8][C:7](=[O:15])[C:6](=[O:16])[NH:5]3)[N:22]=1
Reactant: O=c1[nH]c2cc(F)c([N+](=O)[O-])cc2[nH]c1=O
Reactant: Cc1ncc[nH]1
Solvent: CN(C)C=O
Product: Cc1nc(-c2cc3[nH]c(=O)c(=O)[nH]c3cc2[N+](=O)[O-])c[nH]1
Temperature: 130 °C
Yield: 42.3 %

Procedure:
In DMF, 1 g of 6-fluoro-7-nitroquinoxaline-2,3-(1H,4H)-dione and 1.8 g of 2-methylimidazole were stirred with heating at 130° C. for 8 hours. The reaction mixture was then concentrated and diluted with water, whereupon crystals separated out. The crystals were recrystallized from DMF-water to provide 540 mg of 6-(2-methylimidazolyl)-7-nitroquinoxaline-2,3-(1H,4H)-dione.