Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]#[C:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].CN(P(N(C)C)(N(C)C)=O)C.I[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][O:27][CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][O:29]1>C1COCC1.[Li]CCCC>[CH2:26]([O:27][CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][O:29]1)[CH2:25][CH2:24][CH2:23][CH2:22][C:1]#[C:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: ICCCCCOC1CCCCO1
Reactant: C#CCCCCCCC
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: CCCCCCCC#CCCCCCOC1CCCCO1
Reaction time: 0.25 h
Yield: 67.4 %

Procedure:
1-Nonyne 11 (1.0 g, 8.06 mmol) in THF (20 ml) was treated with n-BuLi (1.7 M in hexanes, 6.6 ml, 0.011 mmol) at 0° C. and the resulting pale yellow solution stirred for a 15 min. HMPA (15 ml) was then added and the mixture stirred for a further 15 min at 0° C. To the resultant dark yellow/orange solution was then added 10 (3.6 g, 0.0121 mol) at 0° C. which resulted in a immediate colour change in the solution to light yellow. This light yellow solution was stirred at r.t. overnight at which stage it was triturated with water and extracted with hexanes. The hexane extract were well washed with water, dried (MgSO4) and concentrated invacuo to afford a light yellow residue which was purified by flash column chromatography (eluent—8.5% EtOAc in hexanes) to yield a the pure 12 (1.6 g, 70%); δH(270 MHz, CDCl3); 0.86 (3H, t, J 6.2), 1.15-1.85 (13H, m), 2.11 (4H, m), 3.30-3.55 (2H, m), 3.69-3.90 (2H, m) and 4.56 (1H, m); δC(67.5 MHz, CDCl3) 14.17, 18.82, 18.82, 19.74, 22.71, 25.57, 25.57, 28.91, 28.91, 29.08, 29.24, 29.38, 30.49, 30.84, 31.84, 62.40, 62.40, 67.57, 67.57, 98.90. MS (EI) 295 (M+H)+; HRMS: Found 295.2616 [M+H]+. Calc. for C19H35O2: 295.263706 [M+H]+.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[CH:28]1([CH2:33]/[CH:34]=[C:35](\[C:39]2[CH:44]=[CH:43][C:42]([S:45]([CH3:48])(=[O:47])=[O:46])=[CH:41][CH:40]=2)/[C:36]([OH:38])=O)[CH2:32][CH2:31][CH2:30][CH2:29]1.[NH2:49][C:50]1[S:51][CH:52]=[CH:53][N:54]=1>C(Cl)Cl>[S:51]1[CH:52]=[CH:53][N:54]=[C:50]1[NH:49][C:36](=[O:38])/[C:35](/[C:39]1[CH:44]=[CH:43][C:42]([S:45]([CH3:48])(=[O:47])=[O:46])=[CH:41][CH:40]=1)=[CH:34]/[CH2:33][CH:28]1[CH2:29][CH2:30][CH2:31][CH2:32]1
Reactant: CS(=O)(=O)c1ccc(/C(=C\CC2CCCC2)C(=O)O)cc1
Reactant: Nc1nccs1
Agent: O=C1CCC(=O)N1Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CS(=O)(=O)c1ccc(/C(=C\CC2CCCC2)C(=O)Nc2nccs2)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 34.8 %

Procedure:
A solution of triphenylphosphine (672 mg, 2.56 mmol) in methylene chloride (7.5 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (456 mg, 2.56 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with a solution of (E)-4-cyclopentyl-2-(4-methanesulfonyl-phenyl)-but-2-enoic acid (545.5 mg, 1.47 mmol) in methylene chloride (4 mL). The clear solution was stirred for 10 min at 0° C. and then allowed to warm to 25° C. where it was stirred for 1 h. The reaction mixture was then treated with 2-aminothiazole (378 mg, 3.76 mmol), and the resulting suspension was stirred at 25° C. over the weekend. The reaction mixture was concentrated in vacuo to remove methylene chloride, and the residue was diluted with ethyl acetate (75 mL) and a 1N aqueous hydrochloric acid solution (100 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×50 mL). The combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (2×50 mL) and a saturated aqueous sodium chloride solution (1×100 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 4/1 to 1/1 hexanes/ethyl acetate) afforded (E)-4-cyclopentyl-2-(4-methanesulfonyl-phenyl)-but-2-enoic acid thiazol-2-ylamide (200 mg, 35%) as a white solid: mp 173-176° C.; EI-HRMS m/e calcd for C19H22N2O3S2 (M+) 390.1071, found 390.1072.
Reaction SMILES: [NH2:1][C@@H:2]([CH3:17])[C@@H:3]([C:5]1[CH:6]=[CH:7][C:8]([OH:16])=[C:9]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])[CH:10]=1)[OH:4].[Cl:18][C:19]1[CH:20]=[C:21]([CH:24]=[C:25]([Cl:27])[CH:26]=1)[CH:22]=O.O>CO>[Cl:18][C:19]1[CH:20]=[C:21]([CH:24]=[C:25]([Cl:27])[CH:26]=1)[CH2:22][NH:1][C@@H:2]([CH3:17])[C@@H:3]([C:5]1[CH:6]=[CH:7][C:8]([OH:16])=[C:9]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])[CH:10]=1)[OH:4]
Reactant: O=Cc1cc(Cl)cc(Cl)c1
Reactant: C[C@H](N)[C@H](O)c1ccc(O)c(NS(C)(=O)=O)c1
Solvent: O
Solvent: CO
Product: C[C@H](NCc1cc(Cl)cc(Cl)c1)[C@H](O)c1ccc(O)c(NS(C)(=O)=O)c1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 45.3 %

Procedure:
To a solution of the amine (4) (105 mg, 0.40 mmol) and 3,5-dichlorobenzaldehyde (95 mg, 0.52 mmol) in methanol (4 mL) was added borane-pyridine complex (130 μL, 1.21 mmol) at 40° C. and the resulting mixture was stirred for 1.5 hours. The reaction mixture was cooled to room temperature and water was added thereto, followed by extraction with a mixed solvent (ethyl acetate:methanol=10:1) and subsequent washing of the organic layer with saturated brine. The organic layer was dried and concentrated and the obtained crude product was purified by amine silica gel column chromatography (eluent; chloroform:methanol=7:1) to obtain the desired amine (7) as a white solid (76 mg, Yield: 45%).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[CH:8]=[O:9].[OH:10]O>Cl>[OH:10][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[CH:8]=[O:9]
Reactant: O=Cc1cnccc1Cl
Reactant: OO
Agent: Cl
Product: O=Cc1cnccc1O
Yield: 80 %

Procedure:
Following the procedure described in MARSAIS et al. (J. Het. Chem., vol. 25, p. 81-87, 1988), compound 2 is heated for 6 h in an aqueous solution of 3 N HCl containing several drops of 3% H2O2, in order to obtain 4-hydroxypyridine-3-carboxaldehyde 4 as a colorless solid (>80%).
Reaction SMILES: [NH2:1][OH:2].[O:3]1[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][N:11]2[CH:16]3[CH2:17][CH2:18][CH:12]2[CH2:13][C:14](=O)[CH2:15]3)[CH2:5][CH2:4]1>C(O)C>[O:3]1[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][N:11]2[CH:16]3[CH2:17][CH2:18][CH:12]2[CH2:13][C:14](=[N:1][OH:2])[CH2:15]3)[CH2:5][CH2:4]1
Reactant: NO
Reactant: O=C1CC2CCC(C1)N2CCN1CCOCC1
Solvent: CCO
Product: ON=C1CC2CCC(C1)N2CCN1CCOCC1
Temperature: 25 °C

Procedure:
After 22.2 ml of 50% hydroxylamine aqueous solution was added to a solution of 40.0 g of 8-(2-morpholinoethyl)-8-azabicyclo[3.2.1]octan-3-one in 200 ml of ethanol, the mixture was stirred at room temperature for an hour. The solvent was distilled off and toluene was added followed by azeotropic distillation. After the solvent was distilled off, the residue was purified by silica gel column chromatography (chloroform:NH3 -saturated methanol=20:1) to give 32.8 g of 8-(2-morpholinoethyl)-8-azabicyclo[3.2.1]octan-3-one oxime.
Reaction SMILES: C([O:3][C:4](=[O:29])[CH:5]=[CH:6][CH:7]1[CH2:13][CH2:12][CH2:11][CH2:10][N:9]([S:14]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[CH:8]1[C:25](=[O:28])[NH:26][OH:27])C.[OH-].[Li+]>C1COCC1.O>[OH:27][NH:26][C:25]([CH:8]1[CH:7]([CH:6]=[CH:5][C:4]([OH:29])=[O:3])[CH2:13][CH2:12][CH2:11][CH2:10][N:9]1[S:14]([C:17]1[CH:18]=[CH:19][C:20]([O:23][CH3:24])=[CH:21][CH:22]=1)(=[O:16])=[O:15])=[O:28]
Reactant: CCOC(=O)C=CC1CCCCN(S(=O)(=O)c2ccc(OC)cc2)C1C(=O)NO
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: COc1ccc(S(=O)(=O)N2CCCCC(C=CC(=O)O)C2C(=O)NO)cc1

Procedure:
To a solution of 3-(2-Hydroxycarbamoyl-1-(4-methoxy-benzenesulfonyl)-azepan-3-yl)-acrylic acid ethyl ester (41 mg, 0.096 mmoL) in 0.96 mL THF and 1.1 mL water was added lithium hydroxide (12 mg, 0.288 mmoL) at ambient temperature. After 3.5 hours the reaction solvent was evaporated under reduced pressure, and the residue was diluted with water and washed twice with diethyl ether. The water layer was acidified to pH=1 and extracted twice with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate, filtered, and the solvent evaporated under reduced pressure. The residue was freeze dried to yield 3-(2-Hydroxycarbamoyl-1-(4-methoxy-benzenesulfonyl)-azepan-3-yl)-acrylic acid; MS: (M+H)+ =399, (M+NH4)+ =416, (M-H)- =397.
Reaction SMILES: [NH2:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([C:13]3[NH:17][CH:16]=[C:15]([C:18]([O:20][CH3:21])=[O:19])[CH:14]=3)[CH:8]=2)=[CH:4][CH:3]=1.[F:24][C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][C:26]=1[N:32]=[C:33]=[O:34].Cl>C1COCC1>[F:24][C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][C:26]=1[NH:32][C:33]([NH:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([C:13]3[NH:17][CH:16]=[C:15]([C:18]([O:20][CH3:21])=[O:19])[CH:14]=3)[CH:8]=2)=[CH:4][CH:3]=1)=[O:34]
Reactant: COC(=O)c1c[nH]c(-c2cc(Oc3ccc(N)cc3)ccn2)c1
Reactant: Cc1ccc(F)c(N=C=O)c1
Agent: Cl
Solvent: C1CCOC1
Product: COC(=O)c1c[nH]c(-c2cc(Oc3ccc(NC(=O)Nc4cc(C)ccc4F)cc3)ccn2)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirred solution of methyl 5-[4-(4-aminophenoxy)pyridin-2-yl]-1H-pyrrole-3-carboxylate (1.0 g, 3.23 mmol) in anhydrous THF (10 ml) was added 2-fluoro-5-methyl-phenylisocyanate (488 mg, 3.23 mmol). The mixture was stirred at room temperature for one hour and poured into 200 ml of 0.02M HCl solution with vigorous stirring. The resulting precipitates were filtered, washed with water, and dried in vacuo to give methyl 5-{4-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrole-3-carboxylate as white solid. Yield: 1.38 g, 93%.
Reaction SMILES: [O:1]([C:8]1[N:13]=[C:12]([CH:14]([C:16]([F:19])([F:18])[F:17])[OH:15])[CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:20][C:21]([Cl:31])=[CH:22][C@@H:23]1[C@H:25]([C:26](Cl)=[O:27])[C:24]1([CH3:30])[CH3:29].C(N(CC)CC)C>O1CCCC1>[O:1]([C:8]1[N:13]=[C:12]([CH:14]([O:15][C:26]([C@H:25]2[C@@H:23]([CH:22]=[C:21]([Cl:20])[Cl:31])[C:24]2([CH3:30])[CH3:29])=[O:27])[C:16]([F:19])([F:17])[F:18])[CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OC(c1cccc(Oc2ccccc2)n1)C(F)(F)F
Reactant: CC1(C)[C@H](C=C(Cl)Cl)[C@@H]1C(=O)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC1(C)[C@H](C=C(Cl)Cl)[C@@H]1C(=O)OC(c1cccc(Oc2ccccc2)n1)C(F)(F)F
Reaction time: 72 h
Yield: 74.6 %

Procedure:
To a solution of 2.04 g (7.6 mmol) of the 6-phenoxy-α-(trifluoromethyl)-2-pyridinemethanol of Step C and 1.72 g (7.6 mmol) of cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarbonyl chloride in 30 ml of dry tetrahydrofuran was added 2.0 ml (14.2 mmol) of triethylamine. The reaction was stirred for 72 hours. The precipitated triethylamine hydrochloride was then filtered off and the filtrate was concentrated under vacuum. The residue was chromatographed through silica gel and then distilled bulb to bulb (bp 155° C., 0.2 mm) to afford 2.61 g (74%) of the title compound as a clear, colorless oil, which was obtained as a mixture of diastereomers as indicated by the 1H NMR spectrum: 1H NMR (CDCl3) δ 1.14, 1.24, 1.26, 1.29 (4×s, 6H), 2.0-2.2 (m, 2H), 6.0-6.2 (m, 2H), 6.90 (d, 1H), 7.1-7.5 (m, 6H), 7.75 (t, 1H); IR (neat) 1742 cm-1.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[N+:4]([O-])[C:3]=1[C:10]1[N+:11]([O-:16])=[CH:12][CH:13]=[CH:14][CH:15]=1.[C:17]([O:20]C(=O)C)(=[O:19])[CH3:18]>C(Cl)(Cl)Cl>[CH3:1][C:2]1[C:3]([C:10]2[N+:11]([O-:16])=[CH:12][CH:13]=[CH:14][CH:15]=2)=[N:4][C:5]([CH2:8][O:20][C:17](=[O:19])[CH3:18])=[CH:6][CH:7]=1
Reactant: CC(=O)OC(C)=O
Reactant: Cc1ccc(C)[n+]([O-])c1-c1cccc[n+]1[O-]
Solvent: ClC(Cl)Cl
Product: CC(=O)OCc1ccc(C)c(-c2cccc[n+]2[O-])n1
Reaction time: 20 h

Procedure:
A solution of 4 g (0.018 mol) of 3,6-dimethyl-2,2'-bipyridine 1,1'-dioxide in 20 ml chloroform is added dropwise, at 60° C. and under a nitrogen atmosphere, to 20 ml of acetic anhydride. The mixture is stirred for 20 hours at 60°-65° C. and then concentrated in vacuo. After the addition of 50 ml of water and 50 ml of ethyl acetate, the mixture is rendered alkaline with potassium carbonate. The water phase is separated off and washed with four times 50 ml of ethyl acetate/THF (ratio about 2:1 by volume). The combined organic phases are dried over sodium sulfate. After the solvent has been distilled off in vacuo, 4.44 g (96% of theory) of a brown crude product are obtained, which can be caused to crystallise at 0° C. The crude product can be employed direct for further reactions. After recrystallisation from diethyl ether, 73% of pure 3-methyl-6-acetoxymethyl-2,2'-bipyridine 1' -oxide are obtained; melting point 105°-107° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH:15](/[CH:16]=[CH:17]/[C:18]([O:20][CH2:21][CH3:22])=[O:19])[O:14][CH2:13][CH2:12][N:11]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH:15]([CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[O:14][CH2:13][CH2:12][N:11]([C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: CCOC(=O)/C=C/C1OCCN(C(=O)OC(C)(C)C)CC1c1ccc(Cl)c(Cl)c1
Solvent: CCO
Product: CCOC(=O)CCC1OCCN(C(=O)OC(C)(C)C)CC1c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 71.1 %

Procedure:
To a solution of tert-butyl (6SR,7RS)-6-(3,4-dichlorophenyl)-7-[(1E)-3-ethoxy-3-oxoprop-1-en-1-yl]-1,4-oxazepane-4-carboxylate (630 mg) in ethanol (5 ml) was added 3% Pt/sulfided carbon (100 mg), and the mixture was stirred under a hydrogen atmosphere at room temperature overnight. The catalyst was removed by filtration. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound (450 mg).
Reaction SMILES: [N:1]([C:4]([O:6][CH2:7][CH3:8])=[O:5])=[C:2]=[S:3].[NH:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1>C1COCC1>[CH2:7]([O:6][C:4](=[O:5])[NH:1][C:2]([N:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)=[S:3])[CH3:8]
Reactant: C1COCCN1
Reactant: CCOC(=O)N=C=S
Solvent: C1CCOC1
Product: CCOC(=O)NC(=S)N1CCOCC1
Temperature: 0 °C
Reaction time: 3 h
Yield: 99.5 %

Procedure:
Ethyl isothiocyanatoformate (5 g, 38.2 mmol) was dissolved in THF (50 mL) and cooled to 0° C. Morpholine (3.99 mL, 45.8 mmol) was added dropwise over 2 min. The reaction mixture was stirred for 3 h. The solvent was evaporated to give (morpholin-4-yl-carbothioyl)carbamic acid ethyl ester (8.3 g, 38 mmol) as a white solid.
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[OH:10].[O:11]1[CH:15]=[CH:14][CH:13]=[C:12]1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC.O>[O:11]1[CH:15]=[CH:14][CH:13]=[C:12]1[C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[OH:10]
Reactant: OB(O)c1ccco1
Reactant: Cc1cc(C)c(O)c(Br)c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: Cc1cc(C)c(O)c(-c2ccco2)c1
Temperature: 120 °C
Reaction time: 0.33 h
Yield: 49.3 %

Procedure:
2-Bromo-4,6-dimethylphenol (500 mg, 2.49 mmol), furan-2-ylboronic acid (88 mg, 2.99 mmol), sodium carbonate (791 mg, 7.47 mmol) and Pd2(dppf)2Cl2 (406 mg, 0.49 mmol) were dissolved in dimethoxyethane/water 6 mL/3 mL, followed by stirring in microwave at 120° C. for 20 minutes. After the completion of the reaction, the reaction mixture was filtered using Celite. The filtrate was added with water, and extracted with ethyl acetate. The obtained organic layer was dried over magnesium sulfate, and purified by column chromatography (ethyl acetate:hexane=1:3) to obtain 2-(furan-2-yl)-4,6-dimethylphenol (231 mg, 45%).
Reaction SMILES: [Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1.[OH: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][CH2:26][CH2:27][C:28]([O:30][CH3:31])=[O:29].C(OCC)C>C(Cl)Cl>[CH: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][CH2:26][CH2:27][C:28]([O:30][CH3:31])=[O:29])=[O:12]
Reactant: COC(=O)CCCCCCCCCCCCCCCO
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: CCOCC
Solvent: ClCCl
Product: COC(=O)CCCCCCCCCCCCCCC=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 79.8 %

Procedure:
65.6 gm of pyridinium chlorochromate was dissolved into 400 ml of methylene chloride. To the solution was added 55 gm of methyl 16-hydroxyhexadecanoate which had been dissolved in 40 ml of methylene chloride in advance. After stirring for 2 hours at room temperature, 400 ml of anhydrous diethyl ether was added. The supernatant was removed and the insolbles were washed three times with 100 ml of anhydrous diethyl ether. The supernatant and the washing were combined together and passed through 40 gm of a silica gel column, and the eluent was concentrated under reduced pressure. The crude crystals thus obtained were purified by flash column chromatography (chloroform:hexane=4:l) to obtain 43.6 gm of methyl 15-formylpentadecanoate.
Reaction SMILES: [C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:10][C:11]1[C:16]([CH3:17])=[CH:15][N:14]=[C:13](Cl)[CH:12]=1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC=CC=1.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:10][C:11]1[C:16]([CH3:17])=[CH:15][N:14]=[C:13]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:12]=1
Reactant: OB(O)c1ccccc1
Reactant: Cc1cnc(Cl)cc1N
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: c1ccccc1
Solvent: CCOC(C)=O
Product: Cc1cnc(-c2ccccc2)cc1N
Yield: 62.1 %

Procedure:
Phenylboronic acid (188 mg, 1.5 mmol, 1.1 equiv.) and 11 (200 mg, 1.4 mmol, 1.0 equiv.) were dissolved in benzene (5 mL). Aqueous Na2CO3 (1 mL) was then added, followed by Pd(PPh3)4 (324 mg, 0.28 mmol, 0.2 equiv.). The resulting mixture was refluxed for 16 hours. The reaction mixture was dissolved in ethyl acetate and washed with water. The organic extract was dried over Na2SO4 and the solvent evaporated. The crude material was purified by reverse phase HPLC (Acetonitrile/water/TFA), to give 12 as a colorless solid (160 mg, 0.87 mmol, HPLC Rt3.373 minutes; FIA ES+ 185.1, ES− not observed).
Reaction SMILES: [F:1][C:2]([F:16])([F:15])[C:3](=[O:14])[CH2:4][C:5]([C:7]1[CH:12]=[CH:11][C:10](Br)=[CH:9][CH:8]=1)=[O:6].[O:17]1[CH:21]=[CH:20][CH:19]=[C:18]1B(O)O.C([O-])(O)=O.[Na+]>COCCOC>[F:1][C:2]([F:16])([F:15])[C:3](=[O:14])[CH2:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([C:18]2[O:17][CH:21]=[CH:20][CH:19]=2)=[CH:9][CH:8]=1)=[O:6]
Reactant: OB(O)c1ccco1
Reactant: O=C(CC(=O)C(F)(F)F)c1ccc(Br)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: COCCOC
Product: O=C(CC(=O)C(F)(F)F)c1ccc(-c2ccco2)cc1
Temperature: 25 °C
Yield: 61.3 %

Procedure:
To a stirred solution of 4,4,4-trifluoro-1-(4-bromophenyl)butane-1,3-dione (1 g, 3.39 mmol, J.Med.Chem., 1997, 40, 1347) in DME.(40 mL) was added furan-2-boronic acid (0.455 g, 4.07 mmol), bis(triphenylphosphine) palladium(.)chloride (0.271 g, 0.386 mmol) and saturated NaHCO3 solution (12 mL) at room temperature under nitrogen. The mixture was heated at reflux temperature for 5 hours, and cooled down to room temperature. The reaction mixture was filtered through celite, the filtrate was poured into water and the whole was extracted with ethyl acetate (30 mL×3). The organic layer was washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by flash chromatography eluting with hexane/ethyl acetate (3/1) to give the subtitle compound (0.586 g, 61.2% yield). MS (EI): m/z 282 (M+).
Reaction SMILES: [F: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]([F: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(F)cc2)cc1
Product: Fc1ccc(-n2nccc2-c2ccc3noc(-c4ccc(Cl)cc4)c3c2)cc1

Procedure:
The title compound, yellow solid (81 mg, 59%), MS (ISP) m/z=390.2 [(M+H)+], mp 188° C., was prepared in accordance with the general method of example 1 from 1-(4-fluoro-phenyl)-5-(4-nitro-phenyl)-1H-pyrazole (intermediate C) (100 mg, 353 μmol) and commercially available 2-(4-chloro-phenyl)-acetonitrile.
Reaction SMILES: [ClH:1].C(OC([N:9]1[CH2:14][CH2:13][CH:12]([CH2:15][CH:16]([N:31]([CH3:33])[CH3:32])[CH2:17][CH:18]2[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][CH2:19]2)[CH2:11][CH2:10]1)=O)(C)(C)C>C(OCC)(=O)C>[ClH:1].[ClH:1].[ClH:1].[NH:9]1[CH2:14][CH2:13][CH:12]([CH2:15][CH:16]([N:31]([CH3:33])[CH3:32])[CH2:17][CH:18]2[CH2:19][CH2:20][NH:21][CH2:22][CH2:23]2)[CH2:11][CH2:10]1
Reactant: CN(C)C(CC1CCN(C(=O)OC(C)(C)C)CC1)CC1CCN(C(=O)OC(C)(C)C)CC1
Agent: Cl
Solvent: CCOC(C)=O
Product: CN(C)C(CC1CCNCC1)CC1CCNCC1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A 4N hydrogen chloride in ethyl acetate (1 ml; 4 mmol) was added to a solution in ethyl acetate (0.5 ml) of 1,3-bis(1-tert-butoxycarbonyl-4-piperidinyl)-2-(dimethylamino)propane (84 mg; 0.19 mmol) synthesized by the process described in Referential Example 4, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure to obtain crude crystals of 1,3-bis(4-piperidinyl)-2-(dimethylamino)propane trihydrochoride.
Reaction SMILES: [F:1][C:2]([F:32])([C:28]([F:31])([F:30])[F:29])[C:3]([F:27])([F:26])[C:4]([F:25])([F:24])[O:5][C:6]([F:23])([F:22])[C:7]([F:21])([F:20])[O:8][C:9]([F:19])([F:18])[CH2:10][O:11][CH2:12][CH2:13][O:14][CH2:15][CH2:16]Br.[CH2:33]([O:39][C:40]1[CH:41]=[N:42][C:43]([C:46]2[CH:51]=[CH:50][C:49]([OH:52])=[CH:48][CH:47]=2)=[N:44][CH:45]=1)[CH2:34][CH2:35][CH2:36][CH2:37][CH3:38]>O>[CH2:33]([O:39][C:40]1[CH:45]=[N:44][C:43]([C:46]2[CH:47]=[CH:48][C:49]([O:52][CH2:16][CH2:15][O:14][CH2:13][CH2:12][O:11][CH2:10][C:9]([O:8][C:7]([F:21])([F:20])[C:6]([F:23])([F:22])[O:5][C:4]([F:25])([F:24])[C:3]([F:27])([F:26])[C:2]([F:32])([F:1])[C:28]([F:31])([F:30])[F:29])([F:19])[F:18])=[CH:50][CH:51]=2)=[N:42][CH:41]=1)[CH2:34][CH2:35][CH2:36][CH2:37][CH3:38]
Reactant: CCCCCCOc1cnc(-c2ccc(O)cc2)nc1
Reactant: FC(F)(COCCOCCBr)OC(F)(F)C(F)(F)OC(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Solvent: O
Product: CCCCCCOc1cnc(-c2ccc(OCCOCCOCC(F)(F)OC(F)(F)C(F)(F)OC(F)(F)C(F)(F)C(F)(F)C(F)(F)F)cc2)nc1

Procedure:
The title compound was prepared essentially as in Example 1 by combining 2-(2-(2-(2-(nonafluorobutoxy)tetrafluoroethoxy)-2,2-difluoroethoxy)ethoxy)ethyl bromide (7.7 g of 90% purity by gas chromatography 11.8 mmol) with 5-hexyloxy-2-(4-hydroxyphenyl)pyrimidine (3.0 g, 11.0 mmol). The resulting product was isolated by addition of water (50 mL) to the reaction mixture, followed by filtration and recrystallization from ethanol. The recrystallized precipitate was dried at about 130° C., and the resulting product was further purified by distillation using a Kugelrohr apparatus (b.p. 185-210° C. at 0.01 torr; yield 5.6 g).