Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=1.[Si](C=[N+]=[N-])(C)(C)[CH3:12]>C1C=CC=CC=1.CO>[OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([O:8][CH3:12])=[O:7])=[CH:4][N:3]=1
Reactant: O=C(O)c1ccc(O)nc1
Reactant: C[Si](C)(C)C=[N+]=[N-]
Solvent: c1ccccc1
Solvent: CO
Product: COC(=O)c1ccc(O)nc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 49 %

Procedure:
To a stirred solution of 6-hydroxynicotinic acid (500 mg, 3.594 mmol) in benzene (8 mL) and MeOH (2 mL) was added dropwise TMSCHN2 (1.97 mL, 3.953 mmol) at 0° C., and the mixture was stirred overnight at room temp. The reaction mixture was quenched by the addition of AcOH, and the resulting mixture was concentrated in vacuo. The residue was chromatographed on silica-gel with n-hexane-EtOAc (1:3, v/v) as eluent to give 269.8 mg (49%) methyl 2-hydroxypyridine-5-carboxylate as a white crystalline powder. IR (KBr) 3062, 1657, 1654, 1612, 1435, 1300, 1113,775, 642 cm−1; 1H-NMR (400 MHz, CDCl3) δ 3.87 (s, 3H), 6.58 (d, J=9.8 Hz, 1H), 7.99 (dd, J=2.4, 9.8 Hz, 1H), 8.19 (d, J=2.4 Hz, 1H); MS (FAB) m/z 154 (M++1); Anal. Calcd for C7H7NO3.1/4H2O: C, 53.33; H, 4.80; N, 8.89. Found: C, 53.58; H, 4.65; N, 8.87.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[C:7]2[CH2:11][NH:12][CH3:13].CNCC1C2C=CC=CC=2N2CCCC=12.[NH2:29][C:30]1[N:35]=[CH:34][C:33](/[CH:36]=[CH:37]/[C:38]([OH:40])=O)=[CH:32][CH:31]=1.Cl.O=C1NC2N=CC(/C=C/C(O)=O)=CC=2CC1>>[NH2:29][C:30]1[N:35]=[CH:34][C:33](/[CH:36]=[CH:37]/[C:38]([N:12]([CH2:11][C:7]2[C:6]3[C:10](=[C:2]([F:1])[CH:3]=[CH:4][CH:5]=3)[NH:9][CH:8]=2)[CH3:13])=[O:40])=[CH:32][CH:31]=1
Reactant: Nc1ccc(/C=C/C(=O)O)cn1
Reactant: CNCc1c[nH]c2c(F)cccc12
Agent: CNCc1c2n(c3ccccc13)CCC2
Agent: Cl
Agent: O=C(O)/C=C/c1cnc2c(c1)CCC(=O)N2
Product: CN(Cc1c[nH]c2c(F)cccc12)C(=O)/C=C/c1ccc(N)nc1
Yield: 17.7 %

Procedure:
According to the procedure of Example 24, except substituting 7-fluoro-3-(methylaminomethyl)-1H-indole (0.31 g, 1.74 mmole) for the 2,3-dihydro-8-(methylaminomethyl)-1H-3a-azacyclopenta[a]indene, and substituting (E)-3-(6-aminopyridin-3-yl)acrylic acid (0.285 g, 1.74 mmole) for the (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylic acid hydrochloride salt, the title compound (0.1 g, 18%) was prepared as a white powder: MS (ES) m/e 325 (M+H)+.
Reaction SMILES: [NH2:1][CH:2]([C:9]1[C:14]([O:15][CH3:16])=[CH:13][CH:12]=[CH:11][C:10]=1[O:17][CH3:18])[CH2:3][CH2:4][C:5]([O:7]C)=O.[N:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[C:21]([CH:29]=O)[CH:20]=1>>[CH3:18][O:17][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]([O:15][CH3:16])[C:9]=1[CH:2]1[N:1]([CH2:29][C:21]2[CH:20]=[N:19][C:28]3[C:23]([CH:22]=2)=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:5](=[O:7])[CH2:4][CH2:3]1
Reactant: COC(=O)CCC(N)c1c(OC)cccc1OC
Reactant: O=Cc1cnc2ccccc2c1
Product: COc1cccc(OC)c1C1CCC(=O)N1Cc1cnc2ccccc2c1

Procedure:
Prepared according to the described general procedure 1 (GP1) by reaction of methyl 4-amino-4-(2,6-dimethoxyphenyl)butanoate with commercially available quinoline-3-carbaldehyde. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions A): tR=0.55 min.; [M+H]+: 363.35 g/mol.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.Cl.[N:16]1([CH2:22][CH2:23][C:24]2[N:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]3=[C:26]([C:33](Cl)=[O:34])[N:25]=2)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1>C(Cl)Cl>[N:4]1[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][C:33]([C:26]2[N:25]=[C:24]([CH2:23][CH2:22][N:16]3[CH2:17][CH2:18][O:19][CH2:20][CH2:21]3)[N:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=23)=[O:34])[CH:3]=1
Reactant: Nc1cccnc1
Reactant: O=C(Cl)c1nc(CCN2CCOCC2)n2ccccc12
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(Nc1cccnc1)c1nc(CCN2CCOCC2)n2ccccc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 31.6 %

Procedure:
To a solution of 3-aminopyridine (0.051 g, 0.54 mmol) and triethylamine (0.16 mL, 1.14 mmol) in CH2Cl2 (10 mL) was added 3-(2-morpholin-4-yl-ethyl)-imidazo[1,5-a]pyridine-1-carbonyl chloride hydrochloride (150 mg, 0.45 mmol). The mixture was stirred at ambient temperature for 1 h then washed with sat. aq. NaHCO3 (20 mL). The organic layer was separated and the aqueous layer was extracted with dichloromethane (20 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was chromatographed on silica to yield the title compound (50 mg, 32%). 1H NMR (DMSO-d6) δ 10.05 (1H), 9.05 (1H), 8.45 (1H), 8.28 (2H), 8.15 (1H), 7.35 (1H), 7.20 (1H), 6.94 (1H), 3.58 (4H), 3.26 (2H), 2.80 (2H), 2.45 (4H); m/z (M+H)=352.17.
Reaction SMILES: Br.C(O[C:5](=O)[CH2:6][N:7]1[CH:12]=[C:11]([B:13]2[O:17][C:16]([CH3:19])([CH3:18])[C:15]([CH3:21])([CH3:20])[O:14]2)[CH:10]=[CH:9][C:8]1=[NH:22])C.O=P(Cl)(Cl)[Cl:26]>>[Cl:26][C:5]1[N:22]=[C:8]2[CH:9]=[CH:10][C:11]([B:13]3[O:17][C:16]([CH3:19])([CH3:18])[C:15]([CH3:21])([CH3:20])[O:14]3)=[CH:12][N:7]2[CH:6]=1
Reactant: CCOC(=O)Cn1cc(B2OC(C)(C)C(C)(C)O2)ccc1=N
Reactant: O=P(Cl)(Cl)Cl
Agent: Br
Product: CC1(C)OB(c2ccc3nc(Cl)cn3c2)OC1(C)C
Temperature: 105 °C

Procedure:
8.78 g of ethyl[2-imino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyridin-1-yl]acetate hydrobromide in 20 ml of POCl3 are placed in a round-bottomed flask. The reaction mixture is heated at 105° C. for 16 h, cooled to ambient temperature and concentrated under reduced pressure. The residue is taken up between dichloromethane and water at 0° C., and a 30% aqueous solution of NH4OH is added until a basic pH is obtained. The organic phase is separated, dried over magnesium sulphate and concentrated under reduced pressure. 4.3 g of compound are obtained.
Reaction SMILES: [CH2:1]([CH:3]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([CH:13]=[CH:14][C:15]3[CH:16]=[C:17]4[C:22](=[CH:23][CH:24]=3)[CH:21]=[C:20]([C:25]#[N:26])[CH:19]=[CH:18]4)[CH:11]=2)[CH2:6][NH:5][CH2:4]1)[CH3:2].[CH:27](=O)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClCCl>[CH2:27]([N:5]1[CH2:4][CH:3]([CH2:1][CH3:2])[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([CH:13]=[CH:14][C:15]3[CH:16]=[C:17]4[C:22](=[CH:23][CH:24]=3)[CH:21]=[C:20]([C:25]#[N:26])[CH:19]=[CH:18]4)[CH:11]=2)[CH2:6]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: O=Cc1ccccc1
Reactant: CCC1CNCc2ccc(C=Cc3ccc4cc(C#N)ccc4c3)cc21
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCl
Product: CCC1CN(Cc2ccccc2)Cc2ccc(C=Cc3ccc4cc(C#N)ccc4c3)cc21
Reaction time: 24 h

Procedure:
A solution of Example 49A (600 mg) in dichloromethane (25 mL) was treated sequentially with benzaldehyde (0.7 mL), sodium triacetoxyborohydride (1.3 g), and acetic acid (319 mg), stirred for 24 hours, diluted with dichloromethane, washed with 1M NaOH and brine, dried (MgSO4), filtered, and concentrated. The concentrate was crystallized from diethyl ether/hexanes to provide the desired product.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]=[N:10][C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][C:12]=2[O:18][CH3:19])=[CH:5][CH:4]=1.C([O-])([O-])=O.[K+].[K+].[CH3:26][O:27][C:28](=[O:31])[CH2:29]Br.C(COC1C=CC(N=NC2C=CC(CO)=CC=2)=CC=1)(OC)=O>CC(C)=O>[OH:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]=[N:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:29][C:28]([O:27][CH3:26])=[O:31])=[CH:13][C:12]=2[O:18][CH3:19])=[CH:7][CH:8]=1
Reactant: COC(=O)CBr
Reactant: COc1cc(O)ccc1N=Nc1ccc(CO)cc1
Agent: COC(=O)COc1ccc(N=Nc2ccc(CO)cc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: COC(=O)COc1ccc(N=Nc2ccc(CO)cc2)c(OC)c1
Reaction time: 12 h

Procedure:
Compound 2 (0.375 g, 1.45 mmol) was dissolved in 20 mL anhydrous acetone to which K2CO3 (0.6 g, 4.35 mmol) was added, followed by methyl-bromoacetate (0.15 mL, 1.59 mmol) at room temperature and reaction mixture stirred for 12 hours. The remaining procedure was followed as described for compound 3 to obtain compound 4. Yield: 0.41 g (86%). 1H NMR (500 MHz, CD3SOCD3) δ 3.71 (s, 3H, H, (OMe)), 3.94 (s, 3H, aromatic-OCH3), 4.56 (d, 2H, J=6.0 Hz, Hf), 4.93 (s, 2H, Hl), 5.34 (t, 1H, J=6.0 Hz, —OH), 6.54-6.64 (m, 1H, Hb), 6.78-6.82 (m, 1H, Hc), 7.45-7.49 (m, 2H, He), 7.57-7.61 (m, 1H, Ha), 7.73-7.78 (m, 2H, Hd). 13C NMR (125 MHz, CD3SOCD3) δ 51.96 (Cm), 52.2 (aromatic-OMe), 62.5 (Cf), 64.8 (Cl), 100.0 (Cc), 106.4 (Cb), 117.2 (Ci), 122.1 (Cd), 127.0 (Ce), 136.2 (Ca), 145.3 (Ck), 151.4 (Cj), 158.4 (Ch), 161.7 (Cg), 168.8 (CO). ESI-MS: [M+H]+ C17H19N2O5 calcd 331.1294, obsd 331.11.
Reaction SMILES: [C:1]([O:4][C:5]1[C:6]2[N:7]([CH:11]=[C:12]([CH3:14])[N:13]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:3])[CH3:2].[Br:15]N1C(=O)CCC1=O>C(O)C.C(OCC)(=O)C>[C:1]([O:4][C:5]1[C:6]2[N:7]([C:11]([Br:15])=[C:12]([CH3:14])[N:13]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:3])[CH3:2]
Reactant: O=C1CCC(=O)N1Br
Reactant: CC(=O)Oc1cccn2cc(C)nc12
Solvent: CCOC(C)=O
Solvent: CCO
Product: CC(=O)Oc1cccn2c(Br)c(C)nc12
Reaction time: 0.5 h
Yield: 86.9 %

Procedure:
To a solution of 8-acetoxy-2-methylimidazo[1,2-a]pyridine (100 mg) in ethanol (1 ml) was added N-bromosuccinimide (103 mg) under ice-cooling, and the mixture was stirred for 30 minutes at the same temperature. The mixture was diluted with ethyl acetate and washed with saturated sodium bicarbonate solution, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by preparative thin layer chromatography (ethyl acetate) to give 8-acetoxy-3-bromo-2-methylimidazo[1,2-a]pyridine (123 mg) as oil.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[F:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]2[O:30]C(=O)[O:28][C:27]2=O)=[CH:22][CH:21]=1>C1COCC1>[CH2:12]([O:11][C:9]1[CH:8]=[CH:7][C:3]([C:4]([NH2:6])=[O:5])=[C:2]([NH:1][C:27](=[O:28])[CH:26]([C:23]2[CH:24]=[CH:25][C:20]([F:19])=[CH:21][CH:22]=2)[OH:30])[CH:10]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: O=C1OC(=O)C(c2ccc(F)cc2)O1
Reactant: NC(=O)c1ccc(OCc2ccccc2)cc1N
Solvent: C1CCOC1
Product: NC(=O)c1ccc(OCc2ccccc2)cc1NC(=O)C(O)c1ccc(F)cc1
Temperature: 63 °C
Yield: 63 %

Procedure:
To a solution of 2-amino-4-(benzyloxy)benzamide (4.0 g, 16.5 mmol) in THF (60 mL) was added a solution of 5-(4-fluorophenyl)-1,3-dioxolane-2,4-dione (3.65 g, 18.6 mmol) from Example 16 in THF (20 mL) portionwise at rt. After heating to 63° C. for 18 h, the solution was cooled and concentrated. After addition of H2O, the solution was extracted twice with DCM. The combined organic phases were washed with brine and dried over sodium sulfate. Chromatography on silica gel eluting with 10 to 80% EtOAc/DCM afforded 4-(benzyloxy)-2-(2-(4-fluorophenyl)-2-hydroxyacetamido)benzamide as a foamy solid (4.1 g, 64%). 1H NMR (300 MHz, DMSO-d6) δ ppm 5.06 (m, 1H), 5.12 (s, 2H) 6.68-6.74 (m, 1H) 7.14-7.20 (m, 2H) 7.32-7.51 (m, 6H) 7.77 (d, J=8.85 Hz, 1H) 8.05 (br. s., 1H) 8.30 (d, J=2.64 Hz, 1H) 12.73 (s, 1H). LC-MS (ESI) m/z 392 (M−2).
Reaction SMILES: [Br:1][C:2]1[C:18]([O:19][CH3:20])=[CH:17][C:5]2[CH:6]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH2:7][NH:8][CH2:9][CH2:10][C:4]=2[CH:3]=1.[CH2:21]=O>C(O)=O>[Br:1][C:2]1[C:18]([O:19][CH3:20])=[CH:17][C:5]2[CH:6]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH2:7][N:8]([CH3:21])[CH2:9][CH2:10][C:4]=2[CH:3]=1
Reactant: C=O
Reactant: COc1cc2c(cc1Br)CCNCC2c1ccccc1
Solvent: O=CO
Product: COc1cc2c(cc1Br)CCN(C)CC2c1ccccc1

Procedure:
7-Bromo-8-methoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (9.6 g, 0.03 m), 37% formalin (27 ml) and 95% formic acid (38 ml) were mixed and heated to reflux for 16 hours. The mixture was concentrated in vacuo, treated with 10% hydrochloric acid (70 ml) and concentrated in vacuo. The residue was partitioned between ethyl acetate and ammonium hydroxide to give 7-bromo8-methoxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine.
Reaction SMILES: [OH:1][CH:2]([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH:28]=[CH:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[CH:3]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:4]([OH:6])=[O:5].[CH2:38](Br)[C:39]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:40].C(N(CC)CC)C>O1CCCC1>[OH:1][CH:2]([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH:28]=[CH:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[CH:3]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:4]([O:6][CH2:38][C:39]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:40])=[O:5]
Reactant: O=C(CBr)c1ccccc1
Reactant: CCCCCCCCC=CCCCCCCCC(O)C(CCCCCCCCCCCCCC)C(=O)O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CCCCCCCCC=CCCCCCCCC(O)C(CCCCCCCCCCCCCC)C(=O)OCC(=O)c1ccccc1
Temperature: 25 °C
Yield: 22.1 %

Procedure:
3-Hydroxy-2-n-tetradecyl-11-icosenoic acid (II)(3.68 g, 7.04 millimole) was dissolved in dry tetrahydrofuran (100 ml), and phenacyl bromide (2.10 g, 10.56 millimole) and triethyl amine (1.47 ml, 10.56 millimole) were successively added thereto with ice cooling. The reaction mixture was allowed to warm to room temperature, and to react for 13.5 hours. The insoluble matter in the reaction mixture was filtered off with suction and the solvent was distilled off from the filtrate. The residue was dissolved in methylene chloride and the obtained solution was successively washed with water and saturated aqueous sodium chloride solution, and dried over anhydrous sodium sulfate. The inorganic salt was filtered off and the solvent was distilled off from the filtrate. The obtained residue was purified over a silicagel column (benzene -→ benzene:ethyl acetate=8:2) to give phenacyl 3-hydroxy-2-n-tetradecyl-11-icosenoate (IV)(998.6 mg, yield 22.1%) in the form of white viscous solid. IR(νmaxKBr, cm-1); 3340, 2900, 2850, 1740, 1705
Reaction SMILES: Cl[C:2]1[C:3]([C:13]([NH2:15])=[O:14])=[N:4][C:5]([C:9]([OH:12])([CH3:11])[CH3:10])=[C:6]([Cl:8])[N:7]=1.[NH2:16][C:17]1[CH:18]=[N:19][N:20]([CH2:22][CH2:23][OH:24])[CH:21]=1.C(N(C(C)C)CC)(C)C.C(=O)([O-])O.[Na+]>O1CCOCC1>[Cl:8][C:6]1[N:7]=[C:2]([NH:16][C:17]2[CH:18]=[N:19][N:20]([CH2:22][CH2:23][OH:24])[CH:21]=2)[C:3]([C:13]([NH2:15])=[O:14])=[N:4][C:5]=1[C:9]([OH:12])([CH3:11])[CH3:10]
Reactant: CC(C)(O)c1nc(C(N)=O)c(Cl)nc1Cl
Reactant: Nc1cnn(CCO)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1COCCO1
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(O)c1nc(C(N)=O)c(Nc2cnn(CCO)c2)nc1Cl
Yield: 62 %

Procedure:
A mixture of 3,5-dichloro-6-(2-hydroxypropan-2-yl)pyrazine-2-carboxamide (2.0 g), 2-(4-amino-1H-pyrazol-1-yl)ethan-1-ol (1.12 g), diisopropylethylamine (2.79 mL), and dioxane (20 mL) was heated and refluxed for 2 hours. The reactant was cooled, and then a saturated aqueous sodium hydrogen carbonate solution was added thereto, followed by extraction with a mixture of chloroform:methanol (10:1). The organic phase was dried over anhydrous sodium sulfate, and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol=99:1-90:10) to obtain 5-chloro-3-{[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]amino}-6-(2-hydroxypropan-2-yl)pyrazine-2-carboxamide (1.69 g) as a yellow solid.
Reaction SMILES: [CH2:1]([O:3][C:4]1[N:8]=[C:7]([CH:9]2[CH2:14][CH:13]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=3)[CH2:12][N:11]([C:26]([N:28]3[CH2:33][CH2:32][S:31][CH2:30][CH2:29]3)=[O:27])[CH2:10]2)[O:6][N:5]=1)[CH3:2].ClC1C=CC=C(C(OO)=[O:42])C=1>>[CH2:1]([O:3][C:4]1[N:8]=[C:7]([CH:9]2[CH2:14][CH:13]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=3)[CH2:12][N:11]([C:26]([N:28]3[CH2:29][CH2:30][S:31](=[O:42])[CH2:32][CH2:33]3)=[O:27])[CH2:10]2)[O:6][N:5]=1)[CH3:2]
Reactant: CCOc1noc(C2CC(c3ccc(CC(F)(F)F)cc3)CN(C(=O)N3CCSCC3)C2)n1
Reactant: O=C(OO)c1cccc(Cl)c1
Product: CCOc1noc(C2CC(c3ccc(CC(F)(F)F)cc3)CN(C(=O)N3CCS(=O)CC3)C2)n1
Yield: 44.1 %

Procedure:
129 mg (0.266 mmol) of the compound from Example 64 were reacted according to General Method 2 with 82.7 mg (0.240 mmol) of meta-chloroperbenzoic acid. Enantiomer separation of 132 mg of the racemate according to Method 8D gave 51.0 mg of the title compound from Example 65 (enantiomer 1) and 53.0 mg of the title compound from Example 66 (enantiomer 2).
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([O:17][CH2:18][C:19]([OH:21])=O)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)([Cl:24])=O>C1C=CC=CC=1>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([O:17][CH2:18][C:19]([Cl:24])=[O:21])=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=S(Cl)Cl
Reactant: O=C(O)COc1nn(Cc2ccccc2)c2ccccc12
Solvent: c1ccccc1
Product: O=C(Cl)COc1nn(Cc2ccccc2)c2ccccc12
Yield: 90 %

Procedure:
[(1-BENZYL-1H-indazol-3-yl)-oxy]acetic acid (Bendazac) (50 g) are suspended in benzene (500 ml) and thionyl chloride (15 ml) is added. The solution is stirred under reflux for about half an hour, cooled, concentrated at room temperature under reduced pressure, the oily residue is treated with further benzene and concentrated again to dryness under vacuum. After addition of hexane, the acidic chloride precipitates as lightly coloured crystals. The solution is filtered and washed with hexane. The substance is colourless and shows m.p. 78°-9°. Yield: 90% of the calculated.
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[C:11]([OH:26])([CH2:20][N:21]1[CH:25]=[N:24][CH:23]=[N:22]1)[C:12]([F:19])([F:18])[S:13][CH2:14][CH2:15][O:16][CH3:17].[CH3:27]I.O>CN(C)C=O>[F:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[C:11]([O:26][CH3:27])([C:12]([F:18])([F:19])[S:13][CH2:14][CH2:15][O:16][CH3:17])[CH2:20][N:21]1[CH:25]=[N:24][CH:23]=[N:22]1
Reactant: CI
Reactant: COCCSC(F)(F)C(O)(Cn1cncn1)c1ccc(F)cc1F
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COCCSC(F)(F)C(Cn1cncn1)(OC)c1ccc(F)cc1F
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 86 %

Procedure:
To a solution of 60% sodium hydride (131 mg, 3.29 mmol) in N,N-dimethylformamide (50 ml), 2-(2,4-difluorophenyl)-1,1-difluoro-1-[(2-methoxyethyl)thio]-3-(1H-1,2,4-triazol-1-yl)-2-propanol (1.0 g, 2.74 mmol) was added dropwise under ice cooling. The resulting mixture was stirred at room temperature for 30 minutes. To the reaction mixture, methyl iodide (516 mg, 3.56 mmol) was added dropwise under ice cooling and the resulting mixture was stirred at room temperature for one hour. Water was added to the reaction mixture and the resulting mixture was extracted with ethyl acetate. The ethyl acetate solution was washed with water, dried over anhydrous sodium sulfate and then distilled off under reduced pressure. The residue was separated and purified by a silica gel column (chloroform:n-hexane=50:1), whereby 1-{2-(2,4-difluorophenyl)-3,3-difluoro-2-methoxy-3-[(2-methoxyethyl)thio]propyl}-1H-1,2,4-triazole (894 mg, yield: 86.0%) was obtained as a yellow oil.
Reaction SMILES: Br[CH:2]([C:4]1([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[CH:13][CH:14]=[C:15]([O:20][CH3:21])[CH:16]=3)[CH:11]=2)OCCCO1)C.[C:22]([O-:25])(=[O:24])C.[K+]>C(N)=O>[CH3:21][O:20][C:15]1[CH:16]=[C:17]2[C:12](=[CH:13][CH:14]=1)[CH:11]=[C:10]([CH:4]([CH3:2])[C:22]([OH:25])=[O:24])[CH:19]=[CH:18]2
Reactant: CC(=O)[O-]
Reactant: COc1ccc2cc(C3(C(C)Br)OCCCO3)ccc2c1
Agent: [K+]
Solvent: NC=O
Product: COc1ccc2cc(C(C)C(=O)O)ccc2c1
Temperature: 170 °C
Reaction time: 2.5 h
Yield: 53 %

Procedure:
A mixture of 2-(1-bromoethyl)-2-(6-methoxy-2-naphthyl)-1,3-dioxane (3.79 g; 10 mmol), potassium acetate (1.2 g; 12 mmol) and formamide (50 ml) is heated at 170° C. under stirring for 2.5 h. The reaction mixture is worked up as described in example 1a to provide 2-(6-methoxy-2-naphthyl)-propionic acid (yield 53%).
Reaction SMILES: [CH:1]1[C:6]([OH:7])=[CH:5][CH:4]=[CH:3][C:2]=1[CH3:8].[CH3:9][C:10]1[O:14][C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[N:12][C:11]=1[CH2:21][CH2:22]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[CH3:9][C:10]1[O:14][C:13]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)=[N:12][C:11]=1[CH2:21][CH2:22][O:7][C:6]1[CH:1]=[C:2]([CH3:8])[CH:3]=[CH:4][CH:5]=1
Reactant: Cc1oc(-c2ccccc2)nc1CCO
Reactant: Cc1cccc(O)c1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Cc1cccc(OCCc2nc(-c3ccccc3)oc2C)c1
Temperature: 22 °C
Reaction time: 24 h
Yield: 78.3 %

Procedure:
A solution of 3.50 g of m-cresol, 9.87 g of 2-(5-methyl-2-phenyl-oxazole-4yl)-ethanol and 12.73 g of triphenylphosphine in 190 ml of THF was treated at 0° C. with a solution of 8.45 g of diethyl azodicarboxylate (DEAD) in 75 ml of THF over 20 min and the brown solution was stirred at 22° C. for 24 h. The solution was evaporated and the residue partitioned between CH2Cl2 (300 ml) and 0.1 N aqueous NaOH (100 ml). The organic layer was washed twice with water (2×100 ml), dried, the organic solvent was evaporated and the residue was chromatographed on silica (n-hexane/AcOEt, 20:1) to give 7.43 g (78%) of the title compound as white crystals.
Reaction SMILES: [CH3:1][C:2]([CH3:49])([CH3:48])[C@H:3]([NH:43][C:44](=[O:47])[O:45][CH3:46])[C:4](=[O:42])[N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10](=[O:41])[NH:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][N:19]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:20][C:21]2[CH:26]=[CH:25][C:24]([NH:27][C:28]([C@@H:30]3[CH2:34][CH2:33][CH2:32][NH:31]3)=[O:29])=[CH:23][CH:22]=2)=[CH:14][CH:13]=1.[C:50]1([C@@H:56]([N:60]2[CH2:64][CH2:63][CH2:62][CH2:61]2)[C:57](O)=[O:58])[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1>>[CH3:46][O:45][C:44]([NH:43][C@H:3]([C:4]([N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]([NH:11][C:12]1[CH:13]=[CH:14][C:15]([CH2:18][N:19]([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH2:20][C:21]2[CH:26]=[CH:25][C:24]([NH:27][C:28](=[O:29])[C@@H:30]3[CH2:34][CH2:33][CH2:32][N:31]3[C:57](=[O:58])[C@@H:56]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[N:60]3[CH2:61][CH2:62][CH2:63][CH2:64]3)=[CH:23][CH:22]=2)=[CH:16][CH:17]=1)=[O:41])=[O:42])[C:2]([CH3:49])([CH3:48])[CH3:1])=[O:47]
Reactant: COC(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)Nc1ccc(CN(Cc2ccc(NC(=O)[C@@H]3CCCN3)cc2)c2ccccc2)cc1)C(C)(C)C
Reactant: O=C(O)[C@@H](c1ccccc1)N1CCCC1
Product: COC(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)Nc1ccc(CN(Cc2ccc(NC(=O)[C@@H]3CCCN3C(=O)[C@@H](c3ccccc3)N3CCCC3)cc2)c2ccccc2)cc1)C(C)(C)C
Yield: 60.4 %

Procedure:
The product from Example 10A (40 mg, 0.060 mmol) and the product of Example 55A (18.4 mg, 0.090 mmol) were processed using the method described in Example 43 to afford 31 mg (60%) of the title compound. 1H NMR (500 MHz, DMSO-D6) δ ppm 9.94 (bs, 1H), 9.90 (bs, 1H), 7.46 (m, 3H), 7.41 (m, 2H), 7.27 (m, 3H), 7.15 (m, 4H), 7.02 (m, 3H), 6.61 (d, J=8.2 Hz, 2H), 6.52 (t, J=7.3 Hz, 1H), 4.55 (bs, 4H), 4.38 (m, 1H), 4.27 (m, 1H), 4.17 (m, 2H), 3.79 (m, 1H), 3.72 (m, 1H), 3.58 (m, 1H), 3.49 (s, 3H), 3.40 (m, 1H), 2.43 (m, 3H), 2.29 (m, 2H), 2.09 (m, 1H), 1.95 (m, 3H), 1.89 (m, 4H), 1.57 (m, 3H), 0.91 (s, 9H).
Reaction SMILES: [NH2:1][C:2]1[C:3](=[O:14])[N:4]([CH2:12][CH3:13])[C:5](=[O:11])[N:6]([CH2:9][CH3:10])[C:7]=1[NH2:8].[CH3:15][O:16][C:17]1[C:27]([O:28][CH3:29])=[CH:26][C:20]([CH:21]=[CH:22][C:23](O)=O)=[C:19]([N+:30]([O-:32])=[O:31])[CH:18]=1>>[CH3:15][O:16][C:17]1[C:27]([O:28][CH3:29])=[CH:26][C:20](/[CH:21]=[CH:22]/[C:23]2[NH:1][C:2]3[C:3](=[O:14])[N:4]([CH2:12][CH3:13])[C:5](=[O:11])[N:6]([CH2:9][CH3:10])[C:7]=3[N:8]=2)=[C:19]([N+:30]([O-:32])=[O:31])[CH:18]=1
Reactant: CCn1c(N)c(N)c(=O)n(CC)c1=O
Reactant: COc1cc(C=CC(=O)O)c([N+](=O)[O-])cc1OC
Product: CCn1c(=O)c2[nH]c(/C=C/c3cc(OC)c(OC)cc3[N+](=O)[O-])nc2n(CC)c1=O
Yield: 38.8 %

Procedure:
Substantially the same procedure as in Example 7 was repeated using 1.50 g (7.57 mmol) of 5,6-diamino-1,3-diethyluracil and 2.11 g (8.33 mmol) of 4,5-dimethoxy-2-nitrocinnamic acid. Then, the resultant crude crystals were recrystallized from dioxane to give 1.22 g (yield 39%) of Compound 124 as orange needles.