Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([OH:13])=O)=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[NH2:14][C:15]1[CH:16]=[C:17]([NH:22][C:23](=[O:32])[CH2:24][CH2:25][CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)[CH:18]=[CH:19][C:20]=1[CH3:21]>>[CH:26]1([CH2:25][CH2:24][C:23]([NH:22][C:17]2[CH:18]=[CH:19][C:20]([CH3:21])=[C:15]([NH:14][C:11]([C:7]3[CH:6]=[C:5]4[C:10](=[CH:9][CH:8]=3)[N:1]=[CH:2][CH:3]=[CH:4]4)=[O:13])[CH:16]=2)=[O:32])[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1
Reactant: Cc1ccc(NC(=O)CCC2CCCCC2)cc1N
Reactant: O=C(O)c1ccc2ncccc2c1
Product: Cc1ccc(NC(=O)CCC2CCCCC2)cc1NC(=O)c1ccc2ncccc2c1

Procedure:
Using an analogous procedure to that described in Example 5, quinoline-6-carboxylic acid was reacted with N-(3-amino-4-methylphenyl)-3-cyclohexylpropionamide to give the title compound; NMR Spectrum: (DMSOd6) 0.76-1.28 (m, 6H), 1.42-1.78 (m, 7H), 2.2 (s, 3H), 2.28 (t, 2H), 7.17 (d, 1H), 7.39 (d, 1H), 7.6 (m, 1H)), 7.69 (s, 1H), 8.12 (d, 1H), 8.24 (d, 1H), 8.49 (d, 1H), 8.63 (s, 1H), 9.0 (m, 1H), 9.82 (s, 1H), 10.09 (s, 1H); Mass Spectrum: M+H+ 437.
Reaction SMILES: [Br:1][C:2]1[CH:31]=[CH:30][C:5]([O:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[NH:13][S:14]([C:17]2[CH:29]=[CH:28][C:20]([C:21]([NH:23][CH2:24][C:25]([OH:27])=O)=[O:22])=[CH:19][CH:18]=2)(=[O:16])=[O:15])=[C:4]([Cl:32])[CH:3]=1.C(OC([N:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1)=O)(C)(C)C>>[ClH:32].[Br:1][C:2]1[CH:31]=[CH:30][C:5]([O:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[NH:13][S:14]([C:17]2[CH:18]=[CH:19][C:20]([C:21]([NH:23][CH2:24][C:25](=[O:27])[N:40]3[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]3)=[O:22])=[CH:28][CH:29]=2)(=[O:16])=[O:15])=[C:4]([Cl:32])[CH:3]=1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: O=C(O)CNC(=O)c1ccc(S(=O)(=O)Nc2ccccc2Oc2ccc(Br)cc2Cl)cc1
Product: Cl
Product: O=C(NCC(=O)N1CCNCC1)c1ccc(S(=O)(=O)Nc2ccccc2Oc2ccc(Br)cc2Cl)cc1

Procedure:
The title compound was prepared from {4-[2-(4-bromo-2-chloro-phenoxy)-phenylsulfamoyl]-benzoylamino}-acetic acid (Example 10.1/e) and piperazine-1-carboxylic acid tert-butyl ester (Aldrich) according to the method described in Example 11.1. MS (EI) 609.2 (MH+).
Reaction SMILES: [N:1]1([CH2:7][C:8]2[CH:9]=[C:10]([NH2:15])[C:11]([NH2:14])=[CH:12][CH:13]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH3:16][O:17][C:18]1[CH:35]=[CH:34][C:21]([CH2:22][N:23]2[CH:27]=[C:26]([N+:28]([O-:30])=[O:29])[C:25]([C:31](O)=O)=[N:24]2)=[CH:20][CH:19]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[CH3:16][O:17][C:18]1[CH:19]=[CH:20][C:21]([CH2:22][N:23]2[CH:27]=[C:26]([N+:28]([O-:30])=[O:29])[C:25]([C:31]3[NH:14][C:11]4[CH:12]=[CH:13][C:8]([CH2:7][N:1]5[CH2:6][CH2:5][O:4][CH2:3][CH2:2]5)=[CH:9][C:10]=4[N:15]=3)=[N:24]2)=[CH:34][CH:35]=1
Reactant: Nc1ccc(CN2CCOCC2)cc1N
Reactant: COc1ccc(Cn2cc([N+](=O)[O-])c(C(=O)O)n2)cc1
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: COc1ccc(Cn2cc([N+](=O)[O-])c(-c3nc4cc(CN5CCOCC5)ccc4[nH]3)n2)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 44.6 %

Procedure:
A mixture of 4-morpholin-4-ylmethyl-benzene-1,2-diamine (2.5 g, 12 mmol), 1-(4-methoxy-benzyl)-4-nitro-1H-pyrazole-3-carboxylic acid (2.91 g, 10 mmol), EDC (2.3 g, 12 mmol) and HOBt (1.62 g, 12 mmol) in dry DMF (40 ml) was stirred at ambient temperature for 24 h. The mixture was reduced in vacuo, the residue partitioned between EtOAc (100 ml) and water (50 ml) and the organic portion washed with saturated aqueous sodium hydrogen carbonate, dried (MgSO4) and reduced in vacuo. The residue was dissolved in AcOH (70 ml) and heated at reflux for 3 h. The solvent was removed in vacuo and the residue purified by flash column chromatography [SiO2, MeOH:DCM (5:95)] to give 2-[1-(4-methoxy-benzyl)-4-nitro-1H-pyrazol-3-yl]-5-morpholin-4-ylmethyl-1H-benzimidazole (2 g, 37%) as a yellow foam. (LC/MS: Rt 1.91, [M+H]+ 449).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:29])[CH2:4][C@H:5]1[C:9]2[CH:10]=[CH:11][C:12]([O:14][C@H:15]3[C:23]4[C:18](=[C:19](Br)[C:20]([C:24]([F:27])([F:26])[F:25])=[CH:21][CH:22]=4)[CH2:17][CH2:16]3)=[CH:13][C:8]=2[O:7][CH2:6]1.[Cl-].[F:31][C:32]1[CH:39]=[CH:38][C:35]([CH2:36][Zn+])=[CH:34][CH:33]=1>C(C1C=CC=C(C(C)C)C=1N1C=CN(C2C(C(C)C)=CC=CC=2C(C)C)C1=[Pd-3](Cl)(Cl)C1C(Cl)=CC=CN=1)(C)C>[CH3:1][O:2][C:3](=[O:29])[CH2:4][C@H:5]1[C:9]2[CH:10]=[CH:11][C:12]([O:14][C@H:15]3[C:23]4[C:18](=[C:19]([CH2:36][C:35]5[CH:38]=[CH:39][C:32]([F:31])=[CH:33][CH:34]=5)[C:20]([C:24]([F:27])([F:26])[F:25])=[CH:21][CH:22]=4)[CH2:17][CH2:16]3)=[CH:13][C:8]=2[O:7][CH2:6]1
Reactant: COC(=O)C[C@@H]1COc2cc(O[C@@H]3CCc4c3ccc(C(F)(F)F)c4Br)ccc21
Reactant: Fc1ccc(C[Zn+])cc1
Agent: CC(C)c1cccc(C(C)C)c1-n1ccn(-c2c(C(C)C)cccc2C(C)C)c1=[Pd-3](Cl)(Cl)c1ncccc1Cl
Agent: [Cl-]
Product: COC(=O)C[C@@H]1COc2cc(O[C@@H]3CCc4c3ccc(C(F)(F)F)c4Cc3ccc(F)cc3)ccc21

Procedure:
The title compound is prepared from {(S)-6-[(R)-4-bromo-5-trifluoromethyl-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester and 4-fluoro-benzylzinc chloride following a procedure analogous to that described in Step 6 of Intermediate 1; [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]-(3-chloropyridyl)-palladium(II) dichloride (Pd-PEPPSI-IPr) is used as catalyst. LC (method 6): tR=1.28 min; Mass spectrum (ESI+): m/z=501 [M+H]+.
Reaction SMILES: [CH2:1]([C:6]1[CH:11]=[CH:10][C:9](Br)=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH2:4][CH3:5].CCCCCC.C([Li:23])CCC>C1C=CC=CC=1>[CH2:1]([C:6]1[CH:11]=[CH:10][C:9]([Li:23])=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: CCCCCc1ccc(Br)cc1
Reactant: [Li]CCCC
Solvent: c1ccccc1
Solvent: CCCCCC
Product: [Li]c1ccc(CCCCC)cc1
Temperature: 25 °C

Procedure:
18.35g (0.081mol) of 4-pentylbromobenzene was dissolved in 30ml of benzene and the solution was stirred at room temperature in a stream of nitrogen. To the resulting solution was added drop-wise 50ml (0.081mol) of hexane solution including 15% butyllithium for 30 minutes and the solution was stirred for 2 hours. Then the produced precipitate gathered by the filtration in a stream of nitrogen was dried under reduced pressure to yield 9.2g of 4-pentylphenyllithium.
Reaction SMILES: [F:1][C:2]1[C:8]([N+:9]([O-:11])=[O:10])=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[C:12](OC(=O)C)(=[O:14])[CH3:13]>N1C=CC=CC=1>[F:1][C:2]1[C:8]([N+:9]([O-:11])=[O:10])=[CH:7][CH:6]=[CH:5][C:3]=1[NH:4][C:12](=[O:14])[CH3:13]
Reactant: CC(=O)OC(C)=O
Reactant: Nc1cccc([N+](=O)[O-])c1F
Solvent: c1ccncc1
Product: CC(=O)Nc1cccc([N+](=O)[O-])c1F
Reaction time: 16 h
Yield: 33.3 %

Procedure:
To a solution (233 mL) of 2-fluoro-3-nitroaniline (18.2 g, 116 mol) in pyridine was added acetic anhydride (27.4 mL, 291 mmol) and the mixture was stirrred at room temperature for 16 hrs. The reaction solution was concentrated under reduced pressure and the obtained residue was treated with isopropyl ether to give the title compound (19.2 g) as a powder.
Reaction SMILES: [C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].[C:14]([O:18][C:19](=[O:30])[NH:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27]Br)=[C:23]([CH3:29])[N:22]=1)([CH3:17])([CH3:16])[CH3:15].CCOC(C)=O>CN(C=O)C>[CH2:10]([O:9][C:1](=[O:8])[CH:2]([CH2:27][C:24]1[C:23]([CH3:29])=[N:22][C:21]([NH:20][C:19]([O:18][C:14]([CH3:16])([CH3:15])[CH3:17])=[O:30])=[CH:26][CH:25]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4])[CH3:11]
Reactant: CCOC(=O)CC(=O)OCC
Reactant: Cc1nc(NC(=O)OC(C)(C)C)ccc1CBr
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCOC(=O)C(Cc1ccc(NC(=O)OC(C)(C)C)nc1C)C(=O)OCC
Reaction time: 0.75 h
Yield: 74 %

Procedure:
A solution of diethyl malonate (1.21 mL, 7.97 mmol) in DMF (2 mL) was added dropwise to a suspention of NaH (348 mg, 7.97 mmol, 55% in mineral oil) in DMF (5 mL) at 0 ° C. under argon. The reaction mixture was stirred for 45 min and a solution of (5-bromomethyl-6-methyl-pyridin-2-yl)-carbamic acid tert-butyl ester (2.0 g, 6.64 mmol) in DMF (5 mL) was added dropwise. The mixture was stirred over night (0° C.→20° C.). EtOAc was added and the solution was washed with water and brine, dried and concentrated under reduced pressure. Flash chromatography (heptane/EtOAc, 4:1) gave 2-(6tert-butoxycarbonylamino-2-methyl-pyridin-3-ylmethyl)-malonic acid diethyl ester (1.87 g, 74%).
Reaction SMILES: [NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3]([C:10]([OH:12])=[O:11])=[N:2]1.[CH3:13]O>OS(O)(=O)=O>[NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3]([C:10]([O:12][CH3:13])=[O:11])=[N:2]1
Reactant: CO
Reactant: O=C(O)c1n[nH]c2ncccc12
Agent: O=S(=O)(O)O
Product: COC(=O)c1n[nH]c2ncccc12
Yield: 90 %

Procedure:
To a solution of 1H-pyrazole[3,4-b]pyridine-3-carboxylic acid (V) (0.39 g, 2.4 mmol) in dry MeOH (10 mL) was added concentrated H2SO4 (4 drops) and refluxed for 6 h under nitrogen. The solution was cooled and the solvent was evaporated under vacuum. The residue was partitioned between DCM and saturated NaHCO3 solution. The organic layer was separated, dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was purified on a flash silica gel column (100% DCM→100:3 DCM:MeOH) to produce methyl 1H-pyrazolo[3,4-b]pyridine-3-carboxylate (VI) as a white solid (382 mg, 2.16 mmol, 90% yield). 1H NMR (CDCl3) δ ppm 4.08 (s, 3 H), 7.38 (m, 1 H), 8.63 (dd, J=8.10, 1.51 Hz, 1 H), 8.72 (dd, J=4.62, 1.41 Hz, 1 H); ESIMS found for C8H7N3O2 m/z 178.2 (M+H).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([CH:10]=[CH:11][CH:12]=1)[CH:8]=O)=[O:4].[C:13]([O:19][CH2:20][CH2:21][N:22]1[CH2:27][CH2:26][N:25]([CH:28]([C:36]2[CH:41]=[CH:40][C:39]([CH3:42])=[CH:38][CH:37]=2)[C:29]2[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=2)[CH2:24][CH2:23]1)(=[O:18])[CH2:14][C:15]([CH3:17])=O.[NH2:43]/[C:44](/[CH3:51])=[CH:45]\[C:46]([O:48][CH2:49][CH3:50])=[O:47]>C(O)(C)C>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([CH:8]2[C:45]([C:46]([O:48][CH2:49][CH3:50])=[O:47])=[C:44]([CH3:51])[NH:43][C:15]([CH3:17])=[C:14]2[C:13]([O:19][CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][N:25]([CH:28]([C:29]3[CH:30]=[CH:31][C:32]([CH3:35])=[CH:33][CH:34]=3)[C:36]3[CH:37]=[CH:38][C:39]([CH3:42])=[CH:40][CH:41]=3)[CH2:24][CH2:23]2)=[O:18])[CH:10]=[CH:11][CH:12]=1)=[O:4]
Reactant: CC(=O)CC(=O)OCCN1CCN(C(c2ccc(C)cc2)c2ccc(C)cc2)CC1
Reactant: COC(=O)c1cccc(C=O)c1
Reactant: CCOC(=O)/C=C(/C)N
Solvent: CC(C)O
Product: CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCCN2CCN(C(c3ccc(C)cc3)c3ccc(C)cc3)CC2)C1c1cccc(C(=O)OC)c1
Yield: 47.5 %

Procedure:
A mixture of m-methoxycarbonylbenzaldehyde, 2-[4-(4,4'-dimethylbenzhydryl)-1-piperazinyl]ethyl acetoacetate and ethyl 3-aminocrotonate was worked up in isopropyl alcohol in the same manner as Example 1 to give 2-[4-(4,4'-dimethylbenzhydryl)-1-piperazinyl]ethyl ethy 4-(3-methoxycarbonylphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate as a light yellow powder, m.p. 80°-83° C. (sintering). Yield 47.5%. IR(Nujol)cm-1 : 3330, 1720, 1690. NMR(CDCl3) δ: 1.17(3H,t,J=7,--CH2CH3), 2.25(6H,s, ##STR49## 2.31(6H,s, ##STR50## 3.83(3H,s,--COOCH3), 4.03(2H, q,J=7,--CH2CH3), 4.10(1H,s,>N--CH<), 4.10(2H,t,J=6, --COOCH2CH2 --), 5.00(1H,s,C(4) --H), 5.78(1H,broad s, NH).
Reaction SMILES: [CH2:1]([C:4]1[CH:12]=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)[CH:2]=[CH2:3].CCC(OO)=[O:16]>CCC(Cl)Cl>[O:16]1[CH2:3][CH:2]1[CH2:1][C:4]1[CH:12]=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1
Reactant: CCC(=O)OO
Reactant: C=CCc1ccc2c(c1)OCO2
Agent: CCC(Cl)Cl
Product: c1cc2c(cc1CC1CO1)OCO2

Procedure:
48.82 g (0.3 mol) of 5-(2-propenyl)-1,3-benzodioxole were reacted with 45 g (0.1 mol) of a 20% strength solution of perpropionic acid in dichloropropane at 30° C. as described in Example 1. After a reaction time of 6 hours, the peracid conversion was 96%. 5-(Oxiranylmethyl)-1,3-benzodioxole was formed with a selectivity of 68%.
Reaction SMILES: N1C=CC=CC=1.Cl.[NH2:8][C:9]1[CH:36]=[CH:35][C:12]([CH2:13][N:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[N:16]([CH2:23][C:24]3[CH:29]=[CH:28][C:27]([C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:26][CH:25]=3)[C:15]2=[O:34])=[CH:11][CH:10]=1.[CH3:37][S:38](Cl)(=[O:40])=[O:39]>O.C1COCC1>[C:30]([C:27]1[CH:26]=[CH:25][C:24]([CH2:23][N:16]2[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:14]([CH2:13][C:12]3[CH:11]=[CH:10][C:9]([NH:8][S:38]([CH3:37])(=[O:40])=[O:39])=[CH:36][CH:35]=3)[C:15]2=[O:34])=[CH:29][CH:28]=1)([CH3:31])([CH3:32])[CH3:33]
Reactant: CC(C)(C)c1ccc(Cn2c(=O)n(Cc3ccc(N)cc3)c3ccccc32)cc1
Reactant: CS(=O)(=O)Cl
Agent: Cl
Solvent: c1ccncc1
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)c1ccc(Cn2c(=O)n(Cc3ccc(NS(C)(=O)=O)cc3)c3ccccc32)cc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
Pyridine (0.3 mL, 3.72 mmol) was added to a suspension of the hydrochloride of 1-(4-aminobenzyl)-3-(4-tert-butylbenzyl)-1,3-dihydrobenzimidazol-2-one (Q) (717 mg, 1.7 mmol) in abs. THF (20 mL). The reaction mixture was stirred at RT for 10 min, methanesulphonyl chloride (0.13 mL, 1.7 mmol, dissolved in abs. THF (1 mL)) was added within a period of 5 min, and the reaction mixture was again stirred at RT over a period of 17 h. To the reaction mixture there was then added H2O (10 mL) followed, after 10 min, by H2O (100 mL). After an hour the precipitated solid matter was separated through a frit and then dried in vacuo. The desired product N-{4-[3-(4-tert-Butyl-benzyl)-2-oxo-2,3-dihydrobenzoimidazol-1-ylmethyl]phenyl}methanesulfonamide (60) was obtained in a yield of 680 mg (86% of theory, mp: 228-230° C.).
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[CH3:5][C:6]1([CH3:13])[NH:10][C:9](=[O:11])[CH2:8][C:7]1=[O:12].C(N(CC)CC)C>C(Cl)Cl>[C:1]([O:12][C:7]1[C:6]([CH3:13])([CH3:5])[NH:10][C:9](=[O:11])[CH:8]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)Cl
Reactant: CC1(C)NC(=O)CC1=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)OC1=CC(=O)NC1(C)C
Reaction time: 24 h
Yield: 18.7 %

Procedure:
At 0 to 5° C., a solution of 4.08 g of acetyl chloride in 20 of methylene chloride is added dropwise to a solution of 6.36 g of 5,5-dimethylpyrrolidine-2,4-dione and 5.57 g of triethylamine in 50 ml of methylene chloride. The mixture is then left to reach room temperature over the course of approximately one hour and then stirred for a further 24 hours. The reaction mixture is then diluted with 50 ml of methylene chloride, and extracted by shaking twice with in each case 50 ml of water, twice with in each case 25 ml of 5% strength sodium hydroxide solution and once with 50 ml of saturated aqueous NaCl solution. Drying and concentration by evaporation gives 1.58 g of the title compound in a purity according to HPLC of 97%.
Reaction SMILES: N1CCCCC1.[N+:7]([C:10]1[CH:17]=[CH:16][C:13]([CH:14]=O)=[CH:12][CH:11]=1)([O-:9])=[O:8].[C:18]([O:24][CH2:25][CH3:26])(=[O:23])[CH2:19][C:20]([CH3:22])=[O:21]>C(OCC)C>[N+:7]([C:10]1[CH:17]=[CH:16][C:13](/[CH:14]=[C:19](/[C:20](=[O:21])[CH3:22])\[C:18]([O:24][CH2:25][CH3:26])=[O:23])=[CH:12][CH:11]=1)([O-:9])=[O:8]
Reactant: O=Cc1ccc([N+](=O)[O-])cc1
Reactant: CCOC(=O)CC(C)=O
Solvent: C1CCNCC1
Solvent: CCOCC
Product: CCOC(=O)/C(=C\c1ccc([N+](=O)[O-])cc1)C(C)=O
Temperature: 25 °C
Reaction time: 48 h

Procedure:
Piperidine (0.5ml) was added to a solution of paranitrobenzaldehyde (7.5g, 0.05 moles) and ethyl acetoacetate (6.5g, 0.05 moles) and stirred at room temperature for 48 hrs. Ethyl ether (50ml) was added and stirring continued for 7 days. After removal of the ethyl ether by rotary evaporator the titled products were separated and purified by silica gel chromatography. The structure assignments were supported by NMR, infrared and uv spectra and elemental analysis (263.2).
Reaction SMILES: [F:1][C:2]([F:32])([F:31])[C:3]1[CH:4]=[C:5]([NH:9][C:10]([N:12]2[C:20]3[C:15](=[CH:16][C:17]([O:21][C:22]4[N:27]=[CH:26][N:25]=[C:24]([C:28](O)=[O:29])[CH:23]=4)=[CH:18][CH:19]=3)[CH2:14][CH2:13]2)=[O:11])[CH:6]=[CH:7][CH:8]=1.C(OP(C#N)(=O)OCC)C.[NH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>CN(C=O)C.CCOC(C)=O.C([O-])(O)=O.[Na+]>[F:1][C:2]([F:32])([F:31])[C:3]1[CH:4]=[C:5]([NH:9][C:10]([N:12]2[C:20]3[C:15](=[CH:16][C:17]([O:21][C:22]4[CH:23]=[C:24]([C:28](=[O:29])[NH:43][C:44]5[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=5)[N:25]=[CH:26][N:27]=4)=[CH:18][CH:19]=3)[CH2:14][CH2:13]2)=[O:11])[CH:6]=[CH:7][CH:8]=1
Reactant: O=C(O)c1cc(Oc2ccc3c(c2)CCN3C(=O)Nc2cccc(C(F)(F)F)c2)ncn1
Reactant: Nc1ccccc1
Agent: CCOP(=O)(C#N)OCC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: O=C(Nc1ccccc1)c1cc(Oc2ccc3c(c2)CCN3C(=O)Nc2cccc(C(F)(F)F)c2)ncn1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To an ice-cooled solution of 400 mg (0.90 mMol) 6-[1-(3-trifluoromethyl-phenylcarbamoyl)-2,3-dihydro-1H-indol-5-yloxy]-pyrimidine-4-carboxylic acid in 4 ml DMF, 402 μl (2.7 mMol) diethyl-cyanophosphonate and 248 μl (2.7 mMol) aniline are added. After stirring the solution for 3 h at rt, another 402 μl diethyl-cyanophosphonate are added and stirring continued for 16 h. Then the mixture is diluted with EtOAc and sat. NaHCO3, the aqueous layer separeted off and extracted twice with EtOAc. The organic phases are washed with water and brine, dried (Na2SO4) and partially concentrated until crystals are formed. These are filtered and washed with EtOAC/DIPE, yielding the title compound: m.p.: 227-229° C.; MS: [M−1]=518; HPLC: AtRet=17.2.
Reaction SMILES: COC1C=C(C(Cl)=O)C=CC=1.[CH3:12][O:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][C:23]=1[O:24][CH3:25])[N:20]=[CH:19][CH:18]=[C:17]2[O:26][C:27]1[CH:33]=[CH:32][C:30]([NH2:31])=[CH:29][C:28]=1[F:34].[CH3:35][O:36][C:37]1[CH:38]=[C:39]([C:43]([N:45]=[C:46]=[S:47])=[O:44])[CH:40]=[CH:41][CH:42]=1>C1(C)C=CC=CC=1.C(O)C>[CH3:35][O:36][C:37]1[CH:38]=[C:39]([C:43]([N:45]=[C:46]=[S:47])=[O:44])[CH:40]=[CH:41][CH:42]=1.[CH3:12][O:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][C:23]=1[O:24][CH3:25])[N:20]=[CH:19][CH:18]=[C:17]2[O:26][C:27]1[CH:33]=[CH:32][C:30]([NH:31][C:46]([NH:45][C:43](=[O:44])[C:39]2[CH:40]=[CH:41][CH:42]=[C:37]([O:36][CH3:35])[CH:38]=2)=[S:47])=[CH:29][C:28]=1[F:34]
Reactant: COc1cc2nccc(Oc3ccc(N)cc3F)c2cc1OC
Agent: COc1cccc(C(=O)Cl)c1
Agent: COc1cccc(C(=O)N=C=S)c1
Solvent: Cc1ccccc1
Solvent: CCO
Product: COc1cccc(C(=O)NC(=S)Nc2ccc(Oc3ccnc4cc(OC)c(OC)cc34)c(F)c2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 90 %

Procedure:
3-Methoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-methoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-methoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (73 mg, yield 90%).
Reaction SMILES: [CH:1]([CH:3]([Cl:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[CH2:2].[CH2:11]([N:27]([CH3:29])[CH3:28])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]>C(C1C=C(C)C=C(C(C)(C)C)C=1O)(C)(C)C>[Cl-:10].[CH:1]([CH2:2][CH:14]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[CH2:13][CH2:12][CH2:11][NH+:27]([CH3:29])[CH3:28])=[CH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: CCCCCCCCCCCCCCCCN(C)C
Reactant: C=CC(Cl)c1ccccc1
Agent: Cc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Product: CCCCCCCCCCCCC(CC=Cc1ccccc1)CCC[NH+](C)C
Product: [Cl-]
Temperature: 50 °C
Yield: 74.6 %

Procedure:
In a 100 ml flask commercial vinylbenzyl chloride (3.05 g, 0.020 mol) was mixed with hexadecyldimethylamine (5.4 g, 0.020 mol) without any additional solvent. After addition of 2,6-di-tert-butyl-4-methylphenol (100 mg, 0.45 mmol) the mixture was heated overnight at 50° C. The solid product which formed was washed several times with dry ether, dried under vacuum at room temperature, and recrystallized from acetone/ether to give 6.3 g (75%) of 4-styrylmethyl (hexadecyl)dimethylammonium chloride. 1H NMR (CDCl3 /Me4Si): 0.88 (s, 3H), 1.24 (br s, 26H ), 1.78 (s, 2H), 3.30 (s, 6H), 3.53 (s, 2H), 5.08 (s, 2H), 5.32 (d, J=10.8 Hz, 1H), 5.84(d, J=18 Hz, 1H), 6.7 m, 1H), 7.51 (m, 4H). IR (KBr); 3020, 2920, 1640 cm-1. The critical micelle concentration (CMC) was 1.28× 10-2M at 25° C. determined conductometrically.
Reaction SMILES: [O:1]1[CH:11]2[CH:2]1[C:3](=[O:13])[C:4]1[C:9]([C:10]2=[O:12])=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH2:14]([N:21]([CH3:26])[CH2:22][CH2:23][NH:24][CH3:25])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C(O)C>[OH:1][C:11]1[C:10](=[O:12])[C:9]2[C:4]([C:3](=[O:13])[C:2]=1[N:24]([CH3:25])[CH2:23][CH2:22][N:21]([CH3:26])[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[CH:5][CH:6]=[CH:7][CH:8]=2
Reactant: CNCCN(C)Cc1ccccc1
Reactant: O=C1c2ccccc2C(=O)C2OC12
Solvent: CCO
Product: CN(CCN(C)C1=C(O)C(=O)c2ccccc2C1=O)Cc1ccccc1
Reaction time: 20 h

Procedure:
A mixture of 2.61 g of 2,3-epoxy-2, 3-dihydro-1,4-naphthoquinone, 2.67 g of N-benzyl-N,N'-dimethylethylene-diamine and 150 ml of absolute ethanol was stirred for 20 hours, then concentrated to one-half its original volume and refrigerated overnight. The solvent was removed, the residue dissolved in dichloromethane and passed through a pad of hydrous magnesium silicate and silica, eluting first with dichloromethane, then with 1% methanol in dichloromethane. The active fraction was flash chromatographed eluting with dichloromethane followed by 2% methanol in dichloromethane. The active fraction was evaporated and the residue triturated in dichloromethane/-hexane giving 900 mg of the desired product, mp 121°-123° C.
Reaction SMILES: [Br:1][CH2:2][C:3](Br)=[O:4].Cl.[CH3:7][C:8]([CH3:18])([CH3:17])[CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.C(N(CC)CC)C>ClCCl>[Br:1][CH2:2][C:3]([N:14]1[CH2:15][CH2:16][N:11]([CH2:10][CH2:9][C:8]([CH3:18])([CH3:17])[CH3:7])[CH2:12][CH2:13]1)=[O:4]
Reactant: CC(C)(C)CCN1CCNCC1
Reactant: O=C(Br)CBr
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)CCN1CCN(C(=O)CBr)CC1
Temperature: 25 °C
Reaction time: 20 h
Yield: 13.3 %

Procedure:
Bromoacetyl bromide (0.52 ml, 6.0 mmol) was added to a solution of 1-(3,3-dimethyl-butyl)-piperazine hydro-chloride from Example E4 (1.5 g, 5.7 mmol) in dichloromethane (20 ml) and triethylamine (3.57 ml, 25.6 mmol) at 0° C. The mixture was stirred for 20 h at room temperature, washed with saturated NaHCO3, dried and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 5% methanol:95% dichloromethane) to yield the title compound (220 mg, 13%).