Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH-].[Na+].[CH2:3]([O:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH3:28])[CH:22]=1)[C:15]([C:29]([O:31]CC)=[O:30])=[C:14]2[C:34]1[CH:39]=[CH:38][C:37]([O:40][CH2:41][CH:42]2[CH2:44][CH2:43]2)=[CH:36][CH:35]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl>CO.O>[CH2:3]([O:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH3:28])[CH:22]=1)[C:15]([C:29]([OH:31])=[O:30])=[C:14]2[C:34]1[CH:39]=[CH:38][C:37]([O:40][CH2:41][CH:42]2[CH2:43][CH2:44]2)=[CH:36][CH:35]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: CCOC(=O)c1c(-c2ccc(OCC3CC3)cc2)c2cc(OCc3ccccc3)ccc2n1Cc1cccc(OC)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: COc1cccc(Cn2c(C(=O)O)c(-c3ccc(OCC4CC4)cc3)c3cc(OCc4ccccc4)ccc32)c1
Temperature: 50 °C
Reaction time: 18 h
Yield: 40.4 %

Procedure:
1 M Aqueous sodium hydroxide (1 mL) was added to a stirred solution of ethyl 5-(benzyloxy)-3-[4-(cyclopropylmethoxy)phenyl]-1-(3-methoxybenzyl)-1H-indole-2-carboxylate (Example 61, 100 mg, 0.178 mmol) in methanol (1 mL). The reaction was warmed (50° C.) and stirring was continued for 18 h. After cooling the reaction was diluted with water (20 mL) and then the solution was adjusted to pH=2 using 1 M hydrochloric acid. The product was extracted with ethyl acetate (3×20 mL) and then the combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. Flash chromatography of the residue over silica gel using 50% ethyl acetate/hexane gave 38.4 mg (40%) of the desired product as a pure white solid (mp=185-187° C.). The product had: 1H NMR (300 MHz, CDCl3) δ 7.25-7.48 (m, 8 H), 6.89-7.17 (m, 3 H), 6.65-6.78 (m, 2 H), 5.83 (s, 2 H), 5.05 (s, 2 H), 3.84 (d, 2 H), 3.68 (s, 3 H), 1.25-1.35 (m, 1 H), 0.57-0.67 (m, 2 H), 0.31-0.41 (m, 2 H); mass spectroscopy gave MH+=534.1 (calcd exact mass for C34H31NO5=533.22).
Reaction SMILES: N.[C:2]([CH2:5][C:6]12[CH2:18][CH2:17][CH2:16][CH2:15][CH:14]1[C:13]1[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=1)[CH:7]2O)([OH:4])=[O:3].[Li].C(O)C>C1COCC1>[C:2]([CH2:5][C:6]12[CH2:18][CH2:17][CH2:16][CH2:15][CH:14]1[C:13]1[CH2:12][CH:11]=[CH:10][CH2:9][C:8]=1[CH2:7]2)([OH:4])=[O:3]
Reactant: O=C(O)CC12CCCCC1c1ccccc1C2O
Agent: N
Agent: [Li]
Solvent: CCO
Solvent: C1CCOC1
Product: O=C(O)CC12CCCCC1C1=C(CC=CC1)C2

Procedure:
To 500 ml of liquid NH3 is added a solution of 9.84 g (0.04 mole) of 9a-carboxymethyl-1,2,3,4,4a,9a-hexahydrofluoren-9-ol (JACS 82 2561 (1960)) in 100 ml of THF. The mixture is then treated portionwise with 7 g of lithium cut in small pieces followed dropwise by sufficient absolute ethanol to discharge the blue color. After NH3 has evaporated, the cooled mixture is treated with water and carefully acidified. The desired 9a-carboxymethyl-1,2,3,4,5,8,4a,9a-octahydrofluorene is isolated by extraction with ether, drying and solvent removal.
Reaction SMILES: [ClH:1].[F:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[CH2:14][CH2:13][NH:12][CH2:11][C@H:10]2[CH2:15][O:16][C:17]2[CH:22]=[CH:21][C:20]3[O:23][CH2:24][O:25][C:19]=3[CH:18]=2)=[CH:5][CH:4]=1.Br[CH2:27][CH2:28][CH2:29][CH2:30][CH3:31].C(=O)([O-])[O-].[K+].[K+].CC(C)=O>C(O)C.C(OCC)C>[ClH:1].[F:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[CH2:14][CH2:13][N:12]([CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[CH2:11][C@H:10]2[CH2:15][O:16][C:17]2[CH:22]=[CH:21][C:20]3[O:23][CH2:24][O:25][C:19]=3[CH:18]=2)=[CH:5][CH:4]=1
Reactant: CCCCCBr
Reactant: Fc1ccc([C@@H]2CCNC[C@H]2COc2ccc3c(c2)OCO3)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: CC(C)=O
Solvent: CCOCC
Product: CCCCCN1CC[C@@H](c2ccc(F)cc2)[C@H](COc2ccc3c(c2)OCO3)C1
Temperature: 25 °C

Procedure:
10g of (-)-trans-4-(-4-fluorophenyl)-3-(3,4-methylenedioxy-phenoxymethyl)-piperidine hydrochloride in 250 ml 99.9% ethanol was mixed with 50 ml 1-bromopentane and 20 g potassium carbonate. The mixture was refluxed for 3 hours and was subsequently cooled to room temperature. 25 ml acetone and 25 ml diethylether was added to the solution. The precipitate was filtered off and the filtrate was evaporated in vacuo. 20 ml 4N NaOH was added to the residue, and the resulting mixture was extracted 3 times with diethyl ether. The combined ether phases were dried over potassium carbonate, filtered, the filtrate was acidified with conc. hydrochloric acid to pH 2, and the filtrate was evaporated in vacuo. The resulting oil was dissolved in acetone and crystals precipitated by addition of ether and after cooling at 4° C. over night. The title compound was filtered off and dried giving 10.1 g of the title compound. M.p. 153.6° C.
Reaction SMILES: [C:1]([O-:5])(=[O:4])[CH2:2][OH:3].[K+].[C:7]([O:10][CH2:11]Br)(=[O:9])[CH3:8].C(OCC)C>C(#N)C>[C:1]([O:5][CH2:11][O:10][C:7](=[O:9])[CH3:8])(=[O:4])[CH2:2][OH:3]
Reactant: CC(=O)OCBr
Reactant: O=C([O-])CO
Agent: [K+]
Solvent: CCOCC
Solvent: CC#N
Product: CC(=O)OCOC(=O)CO
Temperature: 50 °C
Reaction time: 6 h
Yield: 54.1 %

Procedure:
To a suspension of potassium glycolate (11.4 g) in acetonitrile (30 ml) KI (0.5 g) and acetoxymethyl bromide (19 g) were added. The mixture was stirred at 50° C. for 6 hours, and then cooled to room temperature. Diethyl ether was added and the solid filtered off. The solution was evaporated in vacuo and the oily residue was purified by column chromatography to yield 8 g of acetoxymethyl glycolate as a colourless oil.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:39])[NH:15][C:16]2[CH:17]=[N:18][C:19]([O:22][C:23]3[CH:24]=[C:25]4[C:30](=[CH:31][CH:32]=3)[O:29][CH:28]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:27][CH2:26]4)=[CH:20][CH:21]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl>C(OCC)C>[C:33]1([CH:28]2[CH2:27][CH2:26][C:25]3[C:30](=[CH:31][CH:32]=[C:23]([O:22][C:19]4[N:18]=[CH:17][C:16]([NH:15][C:14]([CH:11]5[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]5)=[O:39])=[CH:21][CH:20]=4)[CH:24]=3)[O:29]2)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1
Reactant: CC(C)(C)OC(=O)N1CCC(C(=O)Nc2ccc(Oc3ccc4c(c3)CCC(c3ccccc3)O4)nc2)CC1
Agent: Cl
Solvent: CCOCC
Product: O=C(Nc1ccc(Oc2ccc3c(c2)CCC(c2ccccc2)O3)nc1)C1CCNCC1

Procedure:
Mixture of 4-[6-(2-Phenyl-chroman-6-yloxy)-pyridin-3-ylcarbamoyl]-piperidine-1-carboxylic acid tert-butyl ester (860 mg) and of 1 M HCl in diethyl ether (13 ml) was stirred at room temperature for 24 hours. Precipitate was filtered and washed with ether. 1H-NMR (300 MHz; d6-DMSO) δ: 10.3 (s, 1H), 8.97 (bs, 1H), 8.65 (bs, 1H), 8.34 (d, 1H, J 2.7 Hz), 8.04 (dd, 1H, J 2.7, 8.8 Hz), 7.47-7.33 (m, 5H), 6.94 (d, 1H, J 8.8 Hz), 6.86-6.84 (m, 3H), 5.11 (dd, 1H, J 2.3, 10.0 Hz), 3.35-3.29 (m, 2H), 2.97-2.89 (m, 3H), 2.74-2.66 (m, 2H), 2.19-2.13 (m, 1H), 2.00-1.74 (m, 5H), 1.50-1.35 (m, 11H).
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=1[O:4][CH2:5][CH2:6][OH:7].[H-].[Na+].[Cl:14][C:15]1[C:24](Cl)=[N:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]=1>O1CCOCC1>[Cl:14][C:15]1[C:24]([O:7][CH2:6][CH2:5][O:4][C:3]2[CH:8]=[CH:9][CH:10]=[CH:11][C:2]=2[Cl:1])=[N:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]=1
Reactant: Clc1nc2ccccc2nc1Cl
Reactant: OCCOc1ccccc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1COCCO1
Product: Clc1ccccc1OCCOc1nc2ccccc2nc1Cl
Temperature: 25 °C
Reaction time: 3 h

Procedure:
2-(2-Chlorophenoxy)ethanol (0.229 g, 1.33 mmol) was treated with NaH (55% dispersion in mineral oil; 0.058 g, 1.33 mmol) in dioxane (2 mL). After stirring at room temperature for 3 h, the mixture was added dropwise to a slurry of 2.3-dichloroquinoxaline (0 320 g, 1.60 mmol) in dioxane (1 mL). The resulting mixture was stirred at room temperature for 15 h to produce the intermediate 2-chloro-3-[2-(2-chlorophenoxy)ethoxy]quinoxaline which was used directly in the next step.
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[CH3:5][N:6]1[CH2:11][CH2:10][CH:9]([C:12](Cl)=[O:13])[CH2:8][CH2:7]1.[CH:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>>[CH3:5][N:6]1[CH2:11][CH2:10][CH:9]([C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:13])[CH2:8][CH2:7]1
Reactant: CN1CCC(C(=O)Cl)CC1
Reactant: c1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Product: CN1CCC(C(=O)c2ccccc2)CC1
Temperature: 0 °C
Yield: 84 %

Procedure:
To a cooled suspension of anhydrous aluminum chloride (20 g, 75 mmol) in benzene 30 ml at 0° C. was added 1-methylpiperidine-4-carboxylic acid chloride in small portions and the resulted mixture was refluxed for 3 hours. The reaction mixture was cooled down, poured into ice water. The organic phase was discarded. The aqueous solution was washed with 2×50 ml ethyl ether, basified with potassium hydroxide pellet slowly to pH>10 and extracted with ethyl ether 4×50 ml. The combined ethereal solution was dried over sodium sulfate and concentrated to give 9.5 g of the title compound in 84% yield.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[CH:10]=O.[CH3:12][N:13]([CH3:17])[CH2:14][CH2:15][NH2:16]>>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[CH:10]=[N:16][CH2:15][CH2:14][N:13]([CH3:17])[CH3:12]
Reactant: CN(C)CCN
Reactant: O=Cc1cc2ccccc2[nH]1
Product: CN(C)CCN=Cc1cc2ccccc2[nH]1
Yield: 96.1 %

Procedure:
Replicate the preparation of the ligand used in Ex. 7 except use 0.200 g (1.378 mmol) of 1H-indole-2-carbaldehyde instead of pyrrole-2-carbaldehyde and use 0.158 mL (1.447 mmol) of the N1,N1-dimethylethane-1,2-diamine to give 0.285 g (96%) of N1-((1H-indol-2-yl)methylene)-N2,N2-dimethylethane-1,2-diamine as an off-white solid, which is analytically pure by GC-MS and 1H-NMR: 1H NMR (400 MHz, CDCl3) δ 9.11 (s, br, 1H), 8.19 (s, br, 1H), 7.53 (d, J=7.8 Hz, 1H), 7.23 (d, J=8.0 Hz, 1H), 7.14 (t, J=8.0 Hz, 1H), 7.00 (t, J=7.4 Hz, 1H), 6.65 (s, br, 1H), 3.64 (t, J=6.3 Hz, 2H), 2.53 (t, J=6.7 Hz, 2H), 2.22 (s, 6H).
Reaction SMILES: [C:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][CH2:18][C:19](OC)=[O:20])=[CH:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CC(C[AlH]CC(C)C)C>C1(C)C=CC=CC=1>[C:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][CH2:18][CH:19]=[O:20])=[CH:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]
Reactant: COC(=O)CCc1cn(C(=O)OC(C)(C)C)c2ccccc12
Agent: CC(C)C[AlH]CC(C)C
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)n1cc(CCC=O)c2ccccc21
Reaction time: 2 h
Yield: 77.6 %

Procedure:
To a solution of methyl 1-Boc-indole-3-propionate(2.0 g, 6.6 mmol) in toluene(20 ml) cooled at −78° C. was added a 1.5M toluene solution of DIBAL-H slowly so that the internal temperature was kept below −65° C. After addition, stirring was continued at −78° C. for additional 2 hrs. After quenched with 3 ml of MeOH, the mixture was poured into a NaCl solution and extrated with EtOAc. The combined organic solution was washed with a queous acid , NaHCO3 and bine, then dried over Na2SO4. Flush chromatography gave 1.4 g of oily product. 1H NMR(300 MHz, CDCl3) δ1.68(s, 9H), 2.84(t, 2H), 3.04(t, 2H), 7.20-7.40(m, 3H), 7.52(d, 1H), 8.14(d, 1H), 9.90(s, 1H); MS(ESI) Calc. for (M+1)+: 274. Found: 274.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7](F)=[CH:6][CH:5]=1)=[O:3].[CH2:11]([O:18][C:19]1[CH:20]=[C:21]2[C:26](=[CH:27][CH:28]=1)[CH:25]=[C:24]([OH:29])[CH:23]=[CH:22]2)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(=O)([O-])[O-].[K+].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C(=O)C>[CH2:11]([O:18][C:19]1[CH:20]=[C:21]2[C:26](=[CH:27][CH:28]=1)[CH:25]=[C:24]([O:29][C:7]1[CH:8]=[CH:9][C:4]([C:2](=[O:3])[CH3:1])=[CH:5][CH:6]=1)[CH:23]=[CH:22]2)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: CC(=O)c1ccc(F)cc1
Reactant: Oc1ccc2cc(OCc3ccccc3)ccc2c1
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Product: CC(=O)c1ccc(Oc2ccc3cc(OCc4ccccc4)ccc3c2)cc1
Temperature: 150 °C
Reaction time: 5 h
Yield: 96 %

Procedure:
4-Fluoroacetophenone (969 μl, 8.00 mmol) was added to dry N,N-dimethylacetamide (12 ml) solution of 6-benzyloxy-2-naphthol (500 mg, 2.00 mmol) and potassium carbonate (553 mg, 4.00 mmol) in nitrogen atmosphere and stirred at 150° C. for 5 hours. After completing the reaction, 10% citric acid was added to the reaction liquid, extracted with methylene chloride, washed with water, dried with magnesium sulfate and concentrated. The obtained residue was purified by silica gel chromatography to obtain the subject compound (707 mg, 1.92 mmol). The result of 1H-NMR was consistent with the above structure.
Reaction SMILES: [NH2:1][C:2]1[C:3]([CH3:19])=[C:4](/[CH:9]=[C:10](\[CH3:18])/[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8].NC1C(C)=C(C=CC=1Cl)CC(=C)C(OC(C)(C)C)=O.[Mg].II.Cl.[OH-].[Na+]>CO>[NH2:1][C:2]1[C:3]([CH3:19])=[C:4]([CH2:9][CH:10]([CH3:18])[C:11]([O:13][C:14]([CH3:16])([CH3:15])[CH3:17])=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: C/C(=C\c1ccc(Cl)c(N)c1C)C(=O)OC(C)(C)C
Agent: C=C(Cc1ccc(Cl)c(N)c1C)C(=O)OC(C)(C)C
Agent: Cl
Agent: II
Solvent: CO
Product: Cc1c(CC(C)C(=O)OC(C)(C)C)ccc(Cl)c1N
Temperature: 25 °C

Procedure:
A solution of 1.58 g (5.61 mmol) of a mixture of tert-butyl (2E)-3-(3-amino-4-chloro-2-methylphenyl)-2-methylacrylate and tert-butyl 2-(3-amino-4-chloro-2-methylbenzyl)acrylate (Example 135A) in 5.0 ml of methanol was added to 354 mg (14.6 mmol) of magnesium turnings and a few grains of iodine. The mixture was stirred at RT (initially with cooling) overnight. 50 ml of 1 N hydrochloric acid were then added with ice-cooling. By addition of 10% strength aqueous sodium hydroxide solution, the pH of the mixture was then adjusted to about 10. The mixture was extracted three times with ethyl acetate. The combined organic phases were dried over magnesium sulphate and concentrated under reduced pressure. The crude product gave, after chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 50:1 to 40:1), 962 mg of the target product (60.5% of theory).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][CH:3]=1.[O:9]1[C:13]2([CH2:18][CH2:17][C:16](=[O:19])[CH2:15][CH2:14]2)[O:12][CH2:11][CH2:10]1>>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([C:16]2([OH:19])[CH2:17][CH2:18][C:13]3([O:12][CH2:11][CH2:10][O:9]3)[CH2:14][CH2:15]2)=[CH:3][CH:4]=1
Reactant: Clc1ccc(Br)cc1
Reactant: O=C1CCC2(CC1)OCCO2
Product: OC1(c2ccc(Cl)cc2)CCC2(CC1)OCCO2

Procedure:
The title compound was prepared as a white solid from 4-bromochlorobenzene (Aldrich) and 1,4-dioxa-spiro[4.5]decan-8-one using the procedure described in Step A of Example 1.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:11](=O)[C:12]2[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=2)[C:9]#[N:10])=[CH:4][CH:3]=1.O.[NH2:20][NH2:21].C(O)(=O)C>C1C=CC=CC=1>[NH2:10][C:9]1[NH:21][N:20]=[C:11]([C:12]2[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=2)[C:8]=1[C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1
Reactant: N#CC(C(=O)c1ccncc1)c1ccc(F)cc1
Reactant: NN
Solvent: CC(=O)O
Solvent: c1ccccc1
Solvent: O
Product: Nc1[nH]nc(-c2ccncc2)c1-c1ccc(F)cc1

Procedure:
A mixture of 2-(4-fluorophenyl)-3-oxo-3-(pyridin-4-yl)propanenitrile (10 g), hydrazine monohydrate (2.4 ml) and acetic acid (5.2 ml) in dry benzene (100 ml) was refluxed for 4 hours. The reaction mixture was cooled and extracted with 3N-hydrochloric acid (80 ml×3). The extracts were concentrated in vacuo to 100 ml of the volume and the solution was neutralized with aqueous ammonia solution. The separated solid was collected, washed with water and dried to give 5-amino-4-(4-fluorophenyl)-3-(pyridin-4-yl)pyrazole (2.02 g).
Reaction SMILES: [CH3:1][S:2]([CH:5]([CH2:15][CH2:16][CH2:17][CH:18]([OH:24])[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH2:6][CH2:7][CH2:8][CH2:9]CCC(O)=O)(=[O:4])=[O:3].CSC(CCCC(O)CCCCC)CCCC[O:32][CH2:33][C:34]([OH:36])=[O:35]>>[CH3:1][S:2]([CH:5]([CH2:15][CH2:16][CH2:17][CH:18]([OH:24])[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH2:6][CH2:7][CH2:8][CH2:9][O:32][CH2:33][C:34]([OH:36])=[O:35])(=[O:3])=[O:4]
Reactant: CCCCCC(O)CCCC(CCCCCCC(=O)O)S(C)(=O)=O
Reactant: CCCCCC(O)CCCC(CCCCOCC(=O)O)SC
Product: CCCCCC(O)CCCC(CCCCOCC(=O)O)S(C)(=O)=O

Procedure:
This compound is prepared essentially by the method described in Example 2 except that the 8-methylthio-12-hydroxyheptadecanoic acid of Example 2 is replaced by 5-methylthio-9-hydroxytetradecyloxyacetic acid. The product is purified by chromatography on silica gel and is obtained as a very viscous yellowish oil.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1C=CN=C1.[I:25]I.[F:27][C:28]([F:37])([C:33]([F:36])([F:35])[F:34])[CH:29]=[CH:30][CH2:31]O>C(Cl)Cl>[F:27][C:28]([F:37])([C:33]([F:36])([F:35])[F:34])[CH2:29][CH2:30][CH2:31][I:25]
Reactant: II
Reactant: OCC=CC(F)(F)C(F)(F)F
Agent: c1c[nH]cn1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: FC(F)(F)C(F)(F)CCCI
Temperature: 10 °C
Reaction time: 0.25 h

Procedure:
446 mg of triphenylphosphine is dissolved in 2 cm3 of methylene chloride, cooled down to 10° C., 116 mg of imidazole is added, agitation is carried out for 15 minutes, 431 mg of iodine is added, agitation is carried out for 30 minutes, 0.21 cm3 of 4,4,5,5,5-pentafluoro 2-penten 1-ol is added, agitation is carried out for 4 hours at ambient temperature, the organic phase is washed with a saturated aqueous solution of sodium thiosulphate and a chloromethylenic solution of 4,4,5,5,5-pentafluoro iodopentane is obtained which is used as it is in the continuation of the synthesis. The operation is carried out as indicated in Example 8 Stage F, starting with 618 mg of the thioacetate prepared below in 7 cm3 of methanol and the chloromethylenic solution of the iodated derivative prepared above. 1.2 g of expected product is obtained.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]([N:20]2[CH:24]=[N:23][CH:22]=[N:21]2)[CH2:10][CH:11]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)O)=[CH:5][CH:4]=1)#[N:2].S([O-])(O)(=O)=O.[K+]>CO>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]([N:20]2[CH:24]=[N:23][CH:22]=[N:21]2)[CH:10]=[CH:11][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)=[CH:5][CH:4]=1)#[N:2]
Reactant: N#Cc1ccc(C(CC(O)c2ccc(F)cc2)n2cncn2)cc1
Agent: O=S(=O)([O-])O
Agent: [K+]
Solvent: CO
Product: N#Cc1ccc(C(C=Cc2ccc(F)cc2)n2cncn2)cc1

Procedure:
1-[1-(4cyanophenyl)-3-(4-fluorophenyl)-3-hydroxypropyl]-1,2,4-triazole (100 mg) is heated with potassium hydrogen sulfate (400 mg) on oil bath at 140° C. for 2 hours. Methanol is added and the inorganic material is filtered off. Methanol is evaporated to give the product as a mixture of cis and trans isomers.
Reaction SMILES: Cl[C:2]1[C:7]([O:8][CH2:9][CH2:10][O:11]C2CCCCO2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:18]1[CH2:23][CH2:22][CH2:21][CH:20]([CH2:24][OH:25])[CH2:19]1.CC(C)([O-])C.[K+].C(O)(C)(C)C>C1(C)C=CC=CC=1>[NH:18]1[CH2:23][CH2:22][CH2:21][CH:20]([CH2:24][O:25][C:2]2[C:7]([O:8][CH2:9][CH2:10][OH:11])=[CH:6][CH:5]=[CH:4][N:3]=2)[CH2:19]1
Reactant: OCC1CCCNC1
Reactant: Clc1ncccc1OCCOC1CCCCO1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CC(C)(C)O
Solvent: Cc1ccccc1
Product: OCCOc1cccnc1OCC1CCCNC1
Temperature: 50 °C
Reaction time: 48 h
Yield: 53.8 %

Procedure:
A solution of 2-chloro-3-[2-(tetrahydro-2H-pyran-2-yloxy)ethoxy]pyridine (from Example 4; 100 mg, 0.39 mmol), 3-piperidinemethanol (65 μl, 0.58 mmol) and 1.0 M potassium tert-butoxide in tert-butanol (0.8 mL, 0.80 mmol) in 4 mL of toluene was heated at 100° C. for 1 day. The organic phase was washed with 3×2 mL of water and 2 mL of brine. The organic phase was shaken at 50° C. with 4 mL of 2.0 M acetic acid for 2 days. The aqueous phase was washed with 3×3 mL of ethyl acetate, made basic by addition of potassium hydroxide, saturated with sodium chloride and extracted with 3×2 mL of ethyl acetate. The organic phase was dried (MgSO4) and concentrated under reduced pressure to give 52 mg (0.21 mmol, 53%) of the title compound as a colorless oil. LC-UV purity 95%. MS m/z 253 (M+1)+, calc. 253 (M+1)+.
Reaction SMILES: [CH2:1]([C:8]1([CH3:25])[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[CH:18]=3)[CH:15]=2)[NH:10][C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:35])=CC=1>C1(C)C=CC=CC=1>[CH2:1]([C:8]1([CH3:25])[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[CH:18]=3)[CH:15]=2)[NH:10][C:9]1=[S:35])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC1(Cc2ccccc2)C(=O)Nc2ccc(-c3cccc(Cl)c3)cc21
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: Cc1ccccc1
Product: CC1(Cc2ccccc2)C(=S)Nc2ccc(-c3cccc(Cl)c3)cc21
Yield: 21 %

Procedure:
The title compound was prepared from 3-benzyl-5-(3-chloro-phenyl)-3-methyl-1,3-dihydro-indol-2-one (100 mg) and Lawesson's reagent (120 mg) in toluene (10 ml) at reflux, according to General Procedure A, to afford the title compound (0.022 g) as an off white solid: mp. 168-170° C.; 1H NMR (CDCl3) δ 9.23 (br s, 1H), 7.49 (s, 1H), 7.49-7.30 (m, 4H), 7.21 (s, 1H), 7.15-7.09 (m, 3H), 6.96-6.94 (m, 2H), 6.89 (d, 1H, J=8.0 Hz), 3.19 (dd, 2H, J=40.5 and 13 Hz) and 1.57 (s, 3H); MS (EI) m/z 363/365 [M]+.
Reaction SMILES: C(NC(C)C)(C)C.[F:8][C:9]1[CH:10]=[C:11]([CH:13]=[CH:14][CH:15]=1)[NH2:12].[CH3:16][Si:17](Cl)([CH2:19][CH2:20][Si:21](Cl)([CH3:23])[CH3:22])[CH3:18]>O1CCCC1>[F:8][C:9]1[CH:10]=[C:11]([N:12]2[Si:21]([CH3:23])([CH3:22])[CH2:20][CH2:19][Si:17]2([CH3:18])[CH3:16])[CH:13]=[CH:14][CH:15]=1
Reactant: Nc1cccc(F)c1
Reactant: C[Si](C)(Cl)CC[Si](C)(C)Cl
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: C[Si]1(C)CC[Si](C)(C)N1c1cccc(F)c1
Temperature: -78 °C
Reaction time: 0.75 h

Procedure:
A solution of freshly distilled diisopropylamine (22.9 mL) in dry tetrahydrofuran (175 mL) at -78° C. under N2 is treated with n-butylithium (1.6 M in hexanes, 109 mL) dropwise over 15 minutes, and the resulting mixture is stirred at -78° C. for 45 minutes and is then added over ten minutes via cannula to a solution of 3-fluoroaniline (8.00 mL) in dry tetrahydrofuran (166 mL) at -78° C. under N2. The resulting reaction mixture is stirred at -78° C. for 50 minutes and is then treated with a solution of 1,1,4,4-tetramethyl-1,4-dichlorodisilethylene (18.3 g) in dry tetrahydrofuran (85 mL). The mixture is allowed to slowly warm to ambient temperature over four hours with stirring and is then washed with water (2×200 mL) and saline (100 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound, NMR (CDCl3, 400 MHz) 7.12, 6.65, 6.58, 0.86, 0.24 δ.