Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:3]=1[CH2:4][CH:5]1[CH2:9][C:8](=[O:10])[NH:7][CH:6]12.[H-].[Na+].Cl[CH2:18][C:19]([NH2:21])=[O:20].Cl>CN(C)C=O>[Cl:1][C:2]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:3]=1[CH2:4][CH:5]1[CH2:9][C:8](=[O:10])[N:7]([CH2:18][C:19]([NH2:21])=[O:20])[CH:6]12
Reactant: NC(=O)CCl
Reactant: O=C1CC2Cc3c(Cl)cccc3C2N1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: NC(=O)CN1C(=O)CC2Cc3c(Cl)cccc3C21
Reaction time: 2 h
Yield: 40.7 %

Procedure:
To a solution of 2.7 g of 5-chloro-1,2,3,3a,4,8b-hexahydro-indeno[1,2-b]pyrrol-2-one in 80 ml of dimethylformamide is added 0.8 g of sodium hydride (60% dispersion in mineral oil). After the evolution of gas ceases, the mixture is heated at 50°-60° C. for 1 hour whereupon a solution of 1.8 g of monochloroacetamide in 30 ml of dimethylformamide is added dropwise, and the resulting mixture is stirred at the same temperature for 2 hours and then cooled. The reaction mixture is poured into ice-cold water, acidified with dilute hydrochloric acid and extracted with chloroform. The extract is dried over sodium sulfate, and the solvent is distilled off. The residue is crystallized with a mixture of acetone and ether. The crystalline product is collected by suction filtration and recrystallized from ether to give 1.4 g of [5-chloro-1,2,3,3a,4,8b-hexahydro-2-oxo-indeno[1,2-b]pyrrol-1-yl]acetamide, melting at 186°-188° C.
Reaction SMILES: [OH-].[K+].CS(C)=O.[CH:7]1[CH:12]=[C:11]([NH:13][C:14]2[N:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:10]=[CH:9][CH:8]=1.[CH3:20][C:21]1[N:26]=[C:25]([CH2:27]Br)[CH:24]=[CH:23][CH:22]=1>O>[CH3:27][C:25]1[N:26]=[C:21]([CH2:20][N:13]([C:11]2[CH:12]=[CH:7][CH:8]=[CH:9][N:10]=2)[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][N:19]=2)[CH:22]=[CH:23][CH:24]=1
Reactant: c1ccc(Nc2ccccn2)nc1
Reactant: Cc1cccc(CBr)n1
Agent: [K+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: O
Product: Cc1cccc(CN(c2ccccn2)c2ccccn2)n1
Reaction time: 0.75 h

Procedure:
To a flask were added 0.6 g pulverized potassium hydroxide and 15 ml dimethylsulfoxide. After adding 1.4 g of 2,2′-dipyridylamine, the mixture was stirred under nitrogen for 45 minutes, when 1.5 g 6-methyl-2-(bromomethyl)pyridine was added. After stirring for 1 hour, 35 ml of water was added and the product was extracted with 60 ml of 50% ethyl acetate, 50% hexane. The organic layer was washed with 30 ml water and the solvent was removed. The residue was purified by silica gel chromatography using 48% ethyl acetate, 48% hexane, and 4% methanol resulting in 2.0 g of an oil.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([F:11])[C:9]=1[F:10])[CH:5]=O.C1(P(C2C=CC=CC=2)(C2C=CC=CC=2)=[C:19]([CH3:25])[C:20]([O:22][CH2:23][CH3:24])=[O:21])C=CC=CC=1>CN(C=O)C.C(OC(C)C)(C)C>[CH3:25][C:19](=[CH:5][C:4]1[CH:3]=[C:2]([F:1])[C:9]([F:10])=[C:8]([F:11])[CH:7]=1)[C:20]([O:22][CH2:23][CH3:24])=[O:21]
Reactant: O=Cc1cc(F)c(F)c(F)c1
Reactant: CCOC(=O)C(C)=P(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Solvent: CC(C)OC(C)C
Product: CCOC(=O)C(C)=Cc1cc(F)c(F)c(F)c1

Procedure:
1.0 eq. of 3,4,5-trifluorobenzaldehyde is dissolved in DMF and stirred at room temperature with 1.1 eq. of ethyl 2-(triphenylphosphanylidene)propionate until complete conversion can be determined by means of thin-layer chromatography. The mixture is freed from the solvent and the residue is stirred in diisopropyl ether. The insoluble residue is filtered off, the filtrate is concentrated in vacuo and the residue is chromatographed on silica gel (EA/heptane 1:1), the title compound being obtained in the form of a colorless solid. (M.p.: 66-68° C.).
Reaction SMILES: CC(C)=O.[CH3:5][O:6][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][NH:16][CH2:17][CH:18]([OH:34])[CH2:19][O:20][C:21]1[CH:22]=[CH:23][CH:24]=[C:25]2[NH:33][C:32]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[C:26]=12.[C:35]([OH:43])(=[O:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>COC(C)(C)C>[CH3:5][O:6][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][NH:16][CH2:17][CH:18]([OH:34])[CH2:19][O:20][C:21]1[CH:22]=[CH:23][CH:24]=[C:25]2[NH:33][C:32]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[C:26]=12.[C:35]([O-:43])(=[O:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1
Reactant: O=C(O)c1ccccc1
Agent: COc1ccccc1OCCNCC(O)COc1cccc2[nH]c3ccccc3c12
Solvent: COC(C)(C)C
Solvent: CC(C)=O
Product: O=C([O-])c1ccccc1

Procedure:
A suitable reactor is charged with acetone. The solution is sequentially charged with carvedilol (4.1 grams, 0.1 moles), and benzoic acid solution. Upon addition of the benzoic acid (1.4 grams, 0.011 moles) solution, all material dissolves into the solution. To the stirred solution is added tert-butyl methyl ether (60 ml). The precipitate formed is stirred for a period of time, filtered and the collected cake is washed with water. The cake is dried under vacuum to a constant weight and stored in a polyethylene container.
Reaction SMILES: [N+:1]([C:4]1[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=1[NH2:6])([O-:3])=[O:2].[F:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[N+]([O-])=O.C(=O)([O-])[O-].[K+].[K+]>[Cu].C1(C)C(C)=CC=CC=1>[N+:1]([C:4]1[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=1[NH:6][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[F:11])([O-:3])=[O:2]
Reactant: Nc1ccccc1[N+](=O)[O-]
Reactant: O=[N+]([O-])c1ccccc1F
Agent: [Cu]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1C
Product: O=[N+]([O-])c1ccccc1Nc1ccccc1F
Yield: 71.9 %

Procedure:
2-Nitroaniline (14.9 g), 2-fluoronitrobenzene (29 g), potassium carbonate (14.9 g), copper powder (6.9 g) and xylene (100 ml) was mixed, the mixture was refluxed for 39 hours under argon atmosphere. The reaction mixture was allowed to cool, filtrated, and the filtrate was concentrated under reduced pressure. The residue was dissolved ethyl acetate, successively washed with water and saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=10:1), to thereby obtain 18.0 g of the titled compound as orange color crystals (Yield: 72%).
Reaction SMILES: [CH2:1]([NH:13][C:14]([NH:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])=[S:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[C:29]([C:34](O)=[O:35])#[C:30][C:31]([OH:33])=[O:32]>>[CH2:17]([N:16]1[C:34](=[O:35])[C:29](=[CH:30][C:31]([OH:33])=[O:32])[S:15][C:14]1=[N:13][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]
Reactant: O=C(O)C#CC(=O)O
Reactant: CCCCCCCCCCCCNC(=S)NCCCCCCCCCCCC
Product: CCCCCCCCCCCCN=C1SC(=CC(=O)O)C(=O)N1CCCCCCCCCCCC
Yield: 79.9 %

Procedure:
Prepared by the method described in Example 16 from N,N'-didodecylthiourea (25.0 g, 61 mmoles) and acetylenedicarboxylic acid (7.3 g, 61 mmoles). Recrystallization from 2-propanol, then ethyl acetate gave the product (24.8 g), mp 71°-72° C.
Reaction SMILES: [C:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][CH2:16][O:17][C:18]2[CH:22]=[C:21]([C:23]([OH:25])=O)[O:20][N:19]=2)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[NH2:26][CH2:27][C@H:28]([NH:33][S:34]([CH2:37][CH2:38][CH2:39][CH3:40])(=[O:36])=[O:35])[C:29]([O:31][CH3:32])=[O:30].C1C=CC2N(O)N=NC=2C=1.N(CC)(C(C)C)C(C)C.C(Cl)CCl>CN(C=O)C>[CH3:32][O:31][C:29](=[O:30])[C@@H:28]([NH:33][S:34]([CH2:37][CH2:38][CH2:39][CH3:40])(=[O:36])=[O:35])[CH2:27][NH:26][C:23]([C:21]1[O:20][N:19]=[C:18]([O:17][CH2:16][CH2:15][CH2:14][CH:11]2[CH2:10][CH2:9][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:5])[CH3:6])=[O:2])[CH2:13][CH2:12]2)[CH:22]=1)=[O:25]
Reactant: CC(C)(C)OC(=O)N1CCC(CCCOc2cc(C(=O)O)on2)CC1
Reactant: CCCCS(=O)(=O)N[C@@H](CN)C(=O)OC
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: ClCCCl
Product: CCCCS(=O)(=O)N[C@@H](CNC(=O)c1cc(OCCCC2CCN(C(=O)OC(C)(C)C)CC2)no1)C(=O)OC

Procedure:
A stirred solution of 3-7 (142 mg, 0.4 mmol), 2-9 (110 mg, 0.4 mmol), HOBT (61 mg, 0.4 mmol), N(i-Pr)2Et (216 μL, 1.2 mmol) and DMF (7 mL) at -15° C. was treated with EDC (77 mg, 0.4 mmol) followed by removal of the cooling bath. After 20 h. the reaction mixture concentrated followed by dilution with EtOAc. The EtOAc solution was washed with 1M NaHSO4, and brine, dried (MgSO4), and concentrated. Flash chromatography (silica, 10% to 20% acetone/CH2Cl2) to give 3-8 as a viscous gum. Rf 0.64 (silica, 20% acetone/CH2Cl2).
Reaction SMILES: Br[C:2](C)(C)C(Br)=O.[F:8][C:9]([F:23])([F:22])[C:10]([NH:12][CH2:13][C:14]1[CH:19]=C[C:17](OC)=[CH:16][CH:15]=1)=[O:11].[C:24]([CH:27]([CH:29]([C:31]([O-])=O)[OH:30])[OH:28])([O-])=O.[Na+].[K+].O>ClCCCl.[Fe](Cl)(Cl)Cl.CCOC(C)=O>[CH3:2][C:27]1([CH3:24])[C:29](=[O:30])[C:31]2[CH:19]=[C:14]([CH2:13][NH:12][C:10](=[O:11])[C:9]([F:8])([F:22])[F:23])[CH:15]=[CH:16][C:17]=2[O:28]1
Reactant: CC(C)(Br)C(=O)Br
Reactant: O=C([O-])C(O)C(O)C(=O)[O-]
Reactant: COc1ccc(CNC(=O)C(F)(F)F)cc1
Agent: Cl[Fe](Cl)Cl
Agent: [K+]
Agent: [Na+]
Solvent: ClCCCl
Solvent: CCOC(C)=O
Solvent: O
Product: CC1(C)Oc2ccc(CNC(=O)C(F)(F)F)cc2C1=O
Reaction time: 192 h
Yield: 17 %

Procedure:
Add 2-bromoisobutyryl bromide (1.724 g, 7.5 mmol) to a solution of 2,2,2-trifluoro-N-(4-methoxy-benzyl)-acetamide (1.166 g, 5.0 mmol) in 1,2-dichloroethane (8 mL) at 15° C., then add powdered anhydrous iron(III) chloride (973 mg, 6.0 mmol). Stir the reaction at 15° C. for 3 h and at ambient temperature for 8 days. Add dropwise saturated aqueous potassium sodium tartrate, then water and EtOAc, and stir for 1 h. Filter off the solid, separate the organic layer, and extract the aqueous layer three times with EtOAc. Combine the organic extracts, wash with brine, dry over Na2SO4, filter and concentrate in vacuo. Purify by chromatography on silica gel eluting with EtOAc/hexane (1:3) to give the desired intermediate (253 mg, 17%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:4]=1[CH2:11][C:12]([OH:14])=[O:13].[N+:15]([O-])([OH:17])=[O:16]>C(O)(=O)C.O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N+:15]([O-:17])=[O:16])[C:6]([O:9][CH3:10])=[CH:5][C:4]=1[CH2:11][C:12]([OH:14])=[O:13]
Reactant: COc1ccc(OC)c(CC(=O)O)c1
Reactant: O=[N+]([O-])O
Solvent: O
Solvent: CC(=O)O
Product: COc1cc([N+](=O)[O-])c(OC)cc1CC(=O)O
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 69 %

Procedure:
A solution of of 2,5-dimethoxyphenylacetic acid (1.00 g, 5.10 mmol) in 10 mL of acetic acid was added 6.5 mL of 1.0M HNO3 in acetic acid. The reaction was stirred at ambient temperature for 10 min, and diluted with 75 mL of water. The yellow precipitate was collected and washed with water (3×10 mL), then dried on the filter. Recrystallization from 20 mL of 2-propanol gave 846 mg (69%) of the titled compound as fine yellow crystals.
Reaction SMILES: C([O:3][C:4](=[O:32])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[NH:31][C:14]3[N:15]=[CH:16][N:17]=[C:18]([O:19][C:20]4[C:21]([F:30])=[C:22]5[C:26](=[CH:27][CH:28]=4)[NH:25][C:24]([CH3:29])=[CH:23]5)[C:13]=3[CH:12]=2)=[CH:7][CH:6]=1)C.O[Li:34].O>O1CCOCC1.O>[Li+:34].[F:30][C:21]1[C:20]([O:19][C:18]2[C:13]3[CH:12]=[C:11]([C:8]4[CH:7]=[CH:6][C:5]([C:4]([O-:32])=[O:3])=[CH:10][CH:9]=4)[NH:31][C:14]=3[N:15]=[CH:16][N:17]=2)=[CH:28][CH:27]=[C:26]2[C:22]=1[CH:23]=[C:24]([CH3:29])[NH:25]2
Reactant: CCOC(=O)c1ccc(-c2cc3c(Oc4ccc5[nH]c(C)cc5c4F)ncnc3[nH]2)cc1
Reactant: [Li]O
Solvent: O
Solvent: C1COCCO1
Product: Cc1cc2c(F)c(Oc3ncnc4[nH]c(-c5ccc(C(=O)[O-])cc5)cc34)ccc2[nH]1
Product: [Li+]
Temperature: 120 °C
Reaction time: 24 h

Procedure:
A suspension of 2.87 g (6.7 mMol) of 4-[4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-benzoic acid ethyl ester and 520 mg (12 mMol) LiOH.H2O in 240 ml of dioxane and 5 ml of water is stirred for 24 h at 120° C. The solid is dissolved first, then a new precipitate is formed. Filtration at RT and washing with dioxane and diethylether gives the title compound; HPLC (conditions see Examples 67-78) tR=13.5 min; MS-ES+: (M+H)+=403.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:10](=[O:37])[C:11]([CH2:32][C:33]([O:35]C)=[O:34])=[CH:12][N:13]([CH2:26][CH:27]([O:30][CH3:31])[O:28][CH3:29])[C:14]=1[C:15](=[O:25])[NH:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[CH:19]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO.[OH-].[Na+].Cl>O1CCCC1.O>[CH2:1]([O:8][C:9]1[C:10](=[O:37])[C:11]([CH2:32][C:33]([OH:35])=[O:34])=[CH:12][N:13]([CH2:26][CH:27]([O:28][CH3:29])[O:30][CH3:31])[C:14]=1[C:15](=[O:25])[NH:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[CH:19]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC(=O)Cc1cn(CC(OC)OC)c(C(=O)NCc2cccc(Cl)c2)c(OCc2ccccc2)c1=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: COC(Cn1cc(CC(=O)O)c(=O)c(OCc2ccccc2)c1C(=O)NCc1cccc(Cl)c1)OC
Temperature: 70 °C
Reaction time: 0.5 h
Yield: 79.4 %

Procedure:
To a solution of methyl [5-benzyloxy-6-(3-chlorobenzylcarbamoyl)-1-(2,2-dimethoxyethyl)-4-oxo-1,4-dihydropyridin-3-yl]acetate (150 mg) obtained in Example 187, Step 1 in tetrahydrofuran (1.5 ml)-methanol (1.5 ml) was added 4N aqueous sodium hydroxide solution (0.11 ml), and the mixture was stirred at 70° C. for 30 min. The reaction mixture was warmed to room temperature, 1N aqueous hydrochloric acid (0.5 ml) and water (15 ml) were added, and the mixture was extracted twice with ethyl acetate (30 ml each). The ethyl acetate layer was washed with water, dried, concentrated, and crystallized from ethyl acetate-diisopropyl ether to give [5-benzyloxy-6-(3-chlorobenzylcarbamoyl)-1-(2,2-dimethoxyethyl)-4-oxo-1,4-dihydropyridin-3-yl]acetic acid (116 mg).
Reaction SMILES: [NH2:1][C@H:2]([C:4]([OH:6])=[O:5])[CH3:3].[C:7]1([CH2:13][CH2:14][CH:15]=O)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C(Cl)(Cl)Cl.CO.[C-:23]#[N:24].[Na+]>>[C:23]([CH:15]([NH:1][C@H:2]([C:4]([OH:6])=[O:5])[CH3:3])[CH2:14][CH2:13][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)#[N:24]
Reactant: [C-]#N
Reactant: C[C@H](N)C(=O)O
Reactant: O=CCCc1ccccc1
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: CO
Product: C[C@H](NC(C#N)CCc1ccccc1)C(=O)O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
L-alanine (3.56 g) is dissolved in aqueous sodium cyanide (1.96 g/40 ml) and a methanolic solution of 3-phenylpropionaldehyde (5.63 g/25 ml) is added under vigorous stirring, bringing the total volume to 65 ml. The mixture is stirred at room temperature for 3 hours, extracted with chloroform, and acidified with 2NHCl (pH 3-4). The resulting precipitate is collected, washed, and dried, and used in the next reaction without further purification [m.p.=115° C. (decompose); TLC (Silica gel; CHCl3 /MeOH/HOAC=9:1:0.5); Rf=0.60].
Reaction SMILES: C([NH:4][C:5]1[C:10]([Cl:11])=[CH:9][C:8]([C:12](=[O:18])[CH2:13][CH2:14][CH2:15][CH2:16]Cl)=[C:7]([O:19][CH2:20][C:21]2[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[C:23]([O:29][CH3:30])[CH:22]=2)[CH:6]=1)(=O)C.N1CCCCC1.[NH2:37][C:38]([CH:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1)=[O:39]>>[ClH:11].[NH2:4][C:5]1[C:10]([Cl:11])=[CH:9][C:8]([C:12](=[O:18])[CH2:13][CH2:14][CH2:15][CH2:16][N:43]2[CH2:44][CH2:45][CH:40]([C:38]([NH2:37])=[O:39])[CH2:41][CH2:42]2)=[C:7]([O:19][CH2:20][C:21]2[CH:22]=[C:23]([O:29][CH3:30])[CH:24]=[C:25]([O:27][CH3:28])[CH:26]=2)[CH:6]=1
Reactant: NC(=O)C1CCNCC1
Reactant: COc1cc(COc2cc(NC(C)=O)c(Cl)cc2C(=O)CCCCCl)cc(OC)c1
Solvent: C1CCNCC1
Product: COc1cc(COc2cc(N)c(Cl)cc2C(=O)CCCCN2CCC(C(N)=O)CC2)cc(OC)c1
Product: Cl

Procedure:
Proceeding as in Example 4, Step (c), but replacing 1-(4-acetylamino-5-chloro-2-methoxyphenyl)-5-chloropentan-1-one with 1-[4-acetylamino-5-chloro-2-(3,5-dimethoxybenzyloxy)phenyl]-5-chloropentan-1-one and piperidine with 4-aminocarbonylpiperidine, gave 1-[4-amino-5-chloro-2-(3,5-dimethoxybenzyloxy)-phenyl]-5-(4-aminocarbonylpiperidin-1-yl)pentan-1-one hydrochloride, m.p. 207-209° C.
Reaction SMILES: C[CH2:2][CH2:3][CH2:4][C:5]([OH:20])([C:12]1[CH:13]=[CH:14][C:15](Cl)=[CH:16][C:17]=1Cl)[CH2:6][N:7]1[N:11]=[CH:10][N:9]=[CH:8]1.CC(C(O)(CN1N=CN=C1)CCC1C=C[C:31]([Cl:34])=CC=1)(C)C.CCCC1OC(C2C=CC(Cl)=CC=2[Cl:62])(CN2N=CN=C2)OC1>>[Cl:62][C:4]1([C:5]([OH:20])([CH2:6][N:7]2[CH:8]=[N:9][CH:10]=[N:11]2)[CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:31]=2[Cl:34])[CH2:3][CH2:2]1
Reactant: CCCCC(O)(Cn1cncn1)c1ccc(Cl)cc1Cl
Reactant: CC(C)(C)C(O)(CCc1ccc(Cl)cc1)Cn1cncn1
Reactant: CCCC1COC(Cn2cncn2)(c2ccc(Cl)cc2Cl)O1
Product: OC(Cc1ccccc1Cl)(Cn1cncn1)C1(Cl)CC1

Procedure:
Particularly preferred mixtures comprise as azoles, in addition to hexaconazole, tebuconazole, propiconazole, cycproconazole and/or 2-(1-chloro-cyclopropyl)-1-(2-chlorophenyl)-3-1H-(1,2,4-triazol-1-yl)-propan-2-ol, preferably in a ratio by weight to hexaconazole of 1:9 to 9:1.
Reaction SMILES: C([Li])CCC.[Br-].[CH2:7]([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].CN(P(N(C)C)N(C)C)C.[CH:44]([C:46]1[C:55]([CH3:56])=[C:54]([O:57][C:58](=[O:60])[CH3:59])[C:53]2[C:48](=[CH:49][CH:50]=[C:51]([F:61])[CH:52]=2)[N:47]=1)=O>O1CCCC1.O.CCCCCC>[CH:44](/[C:46]1[C:55]([CH3:56])=[C:54]([O:57][C:58](=[O:60])[CH3:59])[C:53]2[C:48](=[CH:49][CH:50]=[C:51]([F:61])[CH:52]=2)[N:47]=1)=[CH:7]\[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: CCCCCCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CC(=O)Oc1c(C)c(C=O)nc2ccc(F)cc12
Agent: CN(C)P(N(C)C)N(C)C
Agent: [Br-]
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: O
Solvent: CCCCCC
Product: CCCCCCC/C=C/c1nc2ccc(F)cc2c(OC(C)=O)c1C
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 10.2 %

Procedure:
0.29 ml of a hexane solution of 0.48 mmols of n-butyl lithium was added to a solution of 218 mg (0.48 mmols) of octyltriphenylphosphonium bromide in 3 ml of tetrahydrofuran and stirred at room temperature for 5 minutes. This solution was cooled to -78° C., after which 1.43 g (8 mmols) of hexamethylphosphorus triamide was added and stirred for 5 minutes, followed by further addition of 2 ml of a tetrahydrofuran solution of 98.8 mg (0.40 mmols) of 2-formyl-3-methyl-4-acetoxy-6-fluoroquinoline and stirring at -78° C. for 15 minutes and -42° C. for 30 minutes. The reaction solution was added to 20 ml of water and extracted with ethyl acetate, followed by washing with a saturated sodium chloride aqueous solution and drying with anhydrous sodium sulfate. After removal of the solvent by distillation under reduced pressure, the residue was purified by silica gel column chromatography (solvent n-hexane ethyl acetate=30:1 ) to obtain 14 mg (yield 10 %) of 2-(trans-1-nonenyl)-3-methyl-4-acetoxy-6-fluoroquinoline.
Reaction SMILES: [CH3:1][N:2]=[C:3]=[O:4].[NH2:5][C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH:16]=[CH:15][N:14]=[C:13]2[CH2:17][CH3:18])=[CH:8][CH:7]=1>ClCCl>[CH2:17]([C:13]1[N:12]([C:9]2[CH:8]=[CH:7][C:6]([NH:5][C:3]([NH:2][CH3:1])=[O:4])=[CH:11][CH:10]=2)[CH:16]=[CH:15][N:14]=1)[CH3:18]
Reactant: CCc1nccn1-c1ccc(N)cc1
Reactant: CN=C=O
Solvent: ClCCl
Product: CCc1nccn1-c1ccc(NC(=O)NC)cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
0.8 g of methyl isocyanate was added to a solution of 1.5 g of 1-(4-aminophenyl)-2-ethylimidazole in 20 ml of dichloromethane, and the mixture was stirred at room temperature for 3 hours and then refluxed with stirring for 3 hours. After completion of the reaction, the reaction mixture was naturally cooled and the solvent was removed by distillation under reduced pressure. Benzene was added to the residue, and the formed solid was recovered by filtration. The recovered solid was dissolved in a small quantity of methanol and recrystallized from an ethyl ether/benzene mixed solvent. The obtained compound was converted to a hydrochloride having a melting point of 228° to 232° C. according to customary procedures. Elementary analysis values as C13H16N4O.HCl were as follows.
Reaction SMILES: C(N(CC)CC)C.[Br:8][C:9]1[C:10]([CH2:19]Br)=[C:11]([CH:16]=[CH:17][CH:18]=1)[C:12]([O:14]C)=O.Cl.[C:22]([O:26][C:27](=[O:35])[C@H:28]([CH2:30][CH2:31][C:32](=[O:34])[NH2:33])[NH2:29])([CH3:25])([CH3:24])[CH3:23]>C1COCC1>[Br:8][C:9]1[CH:18]=[CH:17][CH:16]=[C:11]2[C:10]=1[CH2:19][N:29]([CH:28]([CH2:30][CH2:31][C:32](=[O:34])[NH2:33])[C:27]([O:26][C:22]([CH3:25])([CH3:23])[CH3:24])=[O:35])[C:12]2=[O:14]
Reactant: COC(=O)c1cccc(Br)c1CBr
Reactant: CC(C)(C)OC(=O)[C@@H](N)CCC(N)=O
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)C(CCC(N)=O)N1Cc2c(Br)cccc2C1=O
Temperature: 25 °C
Yield: 47.7 %

Procedure:
Triethylamine (4.66 g, 46.09 mmol) was added to a stirred suspension of methyl 3-bromo-2-bromomethylbenzoate (6.45 g, 20.95 mmol) and L-glutamine t-butyl ester hydrochloride (5.0 g, 20.95 mmol) in THF (100 mL). The mixture was heated to reflux for 18 hours. The mixture was cooled to room temperature and solvent was removed. The residue was dissolved in methylene chloride (100 mL) and washed with water (2×80 mL), brine (80 mL) and dried (MgSO4). Solvent was removed and the residue was purified by chromatography (CH2Cl2:CH3OH 97.5:2.5) to afford tert-butyl 2-(4-bromo-1-oxoisoindolin-2-yl)-4-carbamoylbutanoate (3.97 g, 48%): 1H NMR (CDCl3) δ 7.74 (d, J=7.1 Hz, 1H), 7.65 (d, J=7.9 Hz, 1H), 7.35 (t, J=7.8 Hz, 1H), 6.15 (s, 1H), 5.77 (s, 1H), 5.02–4.96 (m, 1H), 4.58 (d, J=17.4 Hz, 1H), 4.34 (d, J=17.4 Hz, 1H), 2.45–2.10 (m, 4H), 1.46 (s, 9H); 13C NMR (CDCl3) δ 173.83, 169.42, 168.74, 142.28, 134.70, 133.65, 129.80, 122.70, 117.75, 82.66, 54.29, 47.80, 32.27, 27.95, 25.54.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:18])[CH2:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH3:16])[CH:13]=2)[NH:8][C:7]=1[CH3:17])[CH3:2].[H-].[Na+].I[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]>>[CH2:1]([O:3][C:4](=[O:18])[CH2:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH3:16])[CH:13]=2)[N:8]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[C:7]=1[CH3:17])[CH3:2]
Reactant: CCOC(=O)Cc1c(C)[nH]c2ccc(OC)cc12
Reactant: CCCCCCCCI
Agent: [H-]
Agent: [Na+]
Product: CCCCCCCCn1c(C)c(CC(=O)OCC)c2cc(OC)ccc21
Yield: 51.5 %

Procedure:
Using the procedure described in Example 50, Part A, 2.47 g (0.01 mol) of 5-methoxy-2-methyl-1H-indole-3-acetic acid ethyl ester was reacted with 0.48 g (0.012 mol) of 60% NaH/mineral oil and then 2.17 mL (0.012 mol of iodooctane. The product was chromatographed on silica gel and eluted with 5% EtOAc/toluene to give 1.85 g (51% yield) of 5-methoxy-2-methyl-1-octyl-1H-indole-3-acetic acid ethyl ester as an oil.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[CH3:8].[CH3:9][I:10]>CC(C)=O>[I-:10].[CH3:9][N+:4]1[CH:5]=[CH:6][C:7]([CH3:8])=[C:2]([CH3:1])[CH:3]=1
Reactant: Cc1ccncc1C
Reactant: CI
Solvent: CC(C)=O
Product: Cc1cc[n+](C)cc1C
Product: [I-]
Temperature: 25 °C
Reaction time: 18 h

Procedure:
As shown in Scheme 2 (in FIG. 2), a solution of 100 g of 3,4-dimethylpyridine in 800 ml of acetone was added dropwise to 57.27 mL of methyl iodide. The reaction mixture was stirred at room temperature for 18 hrs. The solid was collected by filtration and washed with cold ether. After drying under vacuum, there was obtained 202 g of 1,3,4-trimethylpyridinium iodide. The subsequent Grignard reaction was conducted under standard conditions to afford an unstable intermediate that was utilized immediately.