Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:16])[CH:4]=[CH:5][CH:6]=[CH:7][CH2:8][S:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.I([O-])(=O)(=O)=[O:18].[Na+]>CO.O.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:16])[CH:4]=[CH:5][CH:6]=[CH:7][CH2:8][S:9]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:18]
Reactant: COC(=O)C=CC=CCSc1ccccc1
Reactant: [O-][I+3]([O-])([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CO
Solvent: CCOC(C)=O
Product: COC(=O)C=CC=CCS(=O)c1ccccc1
Temperature: 20 °C
Yield: 81 %

Procedure:
To a solution of 6-phenylsulfanyl-hexa-2,4-dienoic acid methyl ester (0.336 g, 1.43 mmol) in methanol (17 mL) was added dropwise at 0° C. a solution of sodium metaperiodate (0.37 g, 1.72 mmol) in distilled water (6 mL). The mixture was allowed to warm to 20° C. and then heated at reflux for 5 hours. The solution was concentrated under reduced pressure to give an oil that was dissolved in ethyl acetate (20 mL). The organic layer was washed with saturated aqueous sodium hydrogen carbonate (10 mL), distilled water (10 mL) and then brine. The organic layer was dried over anhydrous MgSO4, filtered and concentrated under reduced pressure to give an oil that was purified by flash chromatography (1:2 to 1:1 to 2:1 ethyl acetate:60-80 ° C. petroleum ether). The resulting powder was recrystallised from diethyl ether to give the title compound (0.29 g, 81%) as a white solid, mp 82-84° C.
Reaction SMILES: [CH2:1]([NH2:4])[C:2]#[CH:3].C(N(CC)CC)C.[CH2:12]([C:14]1[CH:19]=[CH:18][C:17]([CH:20]2[CH2:25][N:24]([C:26]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)=[O:27])[CH2:23][CH:22]([C:34](Cl)=[O:35])[CH2:21]2)=[CH:16][CH:15]=1)[CH3:13].O>ClCCl>[CH2:12]([C:14]1[CH:19]=[CH:18][C:17]([CH:20]2[CH2:25][N:24]([C:26]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)=[O:27])[CH2:23][CH:22]([C:34]([NH:4][CH2:1][C:2]#[CH:3])=[O:35])[CH2:21]2)=[CH:16][CH:15]=1)[CH3:13]
Reactant: C#CCN
Reactant: CCc1ccc(C2CC(C(=O)Cl)CN(C(=O)N3CCOCC3)C2)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O
Product: C#CCNC(=O)C1CC(c2ccc(CC)cc2)CN(C(=O)N2CCOCC2)C1
Temperature: 0 °C
Reaction time: 16 h

Procedure:
18 μl (16 mg, 0.29 mmol) of propargylamine, 40 μl (29 mg, 0.29 mmol) of triethylamine and 1 mg (0.01 mmol) of N,N-dimethylaminopyridine were initially charged in 0.5 ml of dichloromethane, and 105 mg (0.29 mmol) of 5-(4-ethylphenyl)-1-(morpholin-4-ylcarbonyl)piperidine-3-carbonyl chloride, dissolved in 1 ml of dichloromethane, were added. The reaction mixture was stirred at 0° C. for 30 minutes and at RT for 16 h. For work-up, water was added and the reaction mixture was extracted with ethyl acetate. The combined organic extracts were dried over magnesium sulphate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (mobile phase dichloromethane/methanol 100:5). Yield: 108 mg (98% of theory.)
Reaction SMILES: [C:1]([O:5][C:6](=[O:19])[N:7]([CH2:9][CH2:10][C@H:11]1[CH2:16][CH2:15][C@H:14]([CH2:17][OH:18])[CH2:13][CH2:12]1)[CH3:8])([CH3:4])([CH3:3])[CH3:2].I([O-])(=O)(=O)=[O:21].[Na+]>C(Cl)(Cl)(Cl)Cl.O.C(#N)C>[C:1]([O:5][C:6]([N:7]([CH3:8])[CH2:9][CH2:10][C@H:11]1[CH2:12][CH2:13][C@H:14]([C:17]([OH:21])=[O:18])[CH2:15][CH2:16]1)=[O:19])([CH3:3])([CH3:2])[CH3:4]
Reactant: [O-][I+3]([O-])([O-])[O-]
Reactant: CN(CC[C@H]1CC[C@H](CO)CC1)C(=O)OC(C)(C)C
Agent: [Na+]
Solvent: ClC(Cl)(Cl)Cl
Solvent: CC#N
Solvent: O
Product: CN(CC[C@H]1CC[C@H](C(=O)O)CC1)C(=O)OC(C)(C)C

Procedure:
A solution of 17.1 g (63.1 mmol) of trans-[2-(4-hydroxymethyl-cyclohexyl)-ethyl]-methyl-carbamic acid tert-butyl ester in 60 mL of CCl4, 60 mL of water and 90 mL of acetonitrile were treated with 0.075 g (0.33mmol, 0.05 eq) of ruthenium (III) chloride•hydrate and 55.4 g (259 mmol, 4.1 eq) of sodium metaperiodate within 30 min. After 6 h the reaction was decanted and washed with CH2Cl2 (×3). The decanted phase was partitioned between CH2Cl2 (×3)/H2O, dried over Na2SO4 and evaporated to yield 17.24 g (96%) of trans-4-[2-(tert-butoxycarbonyl-methyl-amino)-ethyl]-cyclohexanecarboxylic acid, MS: 284 (M−H−).
Reaction SMILES: [CH3:1][N:2]([CH3:12])[C:3]1[S:4][CH:5]=[C:6]([Sn](C)(C)C)[N:7]=1.[Br:13]C1SC=C(Br)N=1.O>CN(C=O)C>[CH3:1][N:2]([CH3:12])[C:3]1[S:4][CH:5]=[C:6]([Br:13])[N:7]=1
Reactant: CN(C)c1nc([Sn](C)(C)C)cs1
Reactant: Brc1csc(Br)n1
Solvent: O
Solvent: CN(C)C=O
Product: CN(C)c1nc(Br)cs1
Temperature: 155 °C
Yield: 89 %

Procedure:
Synthesis of 2-Dimethylamino-4-trimethylstannylthiazole 386 as illustrated in FIG. 53. 2,4-Dibromothiazole (358; 1.0 equiv) was dissolved in DMF (0.1 M) and heated at 150-160° C. for 8 h, upon which completion of the reaction was indicated by TLC. The mixture was poured into water and extracted with ether (2×). Drying (MgSO4) and evaporation of the solvents gave 2-dimethylamino-4-bromothiazole 385, which was isolated after flash column chromatography (silica gel, 5% EtOAc in hexanes) in 89% yield.
Reaction SMILES: [CH2:1]([S:8][C:9]1[CH:10]=[C:11]([C:15](=[O:31])[CH:16]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH3:30])[CH2:17][CH2:18][C:19]([O:21]CC)=[O:20])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>O1CCOCC1>[OH2:20].[CH2:1]([S:8][C:9]1[CH:10]=[C:11]([C:15](=[O:31])[CH:16]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH3:30])[CH2:17][CH2:18][C:19]([OH:21])=[O:20])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1.[CH2:1]([S:8][C:9]1[CH:10]=[C:11]([C:15](=[O:31])[CH:16]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH3:30])[CH2:17][CH2:18][C:19]([OH:21])=[O:20])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)CCC(C(=O)c1cccc(SCc2ccccc2)c1)c1ccccc1C
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: Cc1ccccc1C(CCC(=O)O)C(=O)c1cccc(SCc2ccccc2)c1
Product: O
Yield: 103.7 %

Procedure:
A stirred solution of ethyl (RS)-5-(3-benzylthiophenyl)-4-(2-methylphenyl)-5-oxopentanoate (0.56 g) and 1 N sodium hydroxide (3.4 mL) in dioxan (11 mL) is heated at 70° C. for 1.5 hours. The reaction mixture is evaporated and the residue dissolved in water (6 mL). The pH of the solution is adjusted to pH 1 by addition of 2 N hydrochloric acid and the mixture extracted with ether (20 mL). The organic phase is washed twice with water (6 mL), dried over magnesium sulphate and evaporated. The residual orange oil (0.59 g) is triturated with pentane and crystallised from cyclohexane to give (RS)-5-(3-benzylthiophenyl)-4-(2-methylphenyl)-5-oxopentanoic acid hemihydrate as a pale yellow solid (0.37 g), m.p.105-107° C. [Elemental analysis:- C,72.4; H,5.94%. Calculated for C25H24O3S.0.5H2O:- C,72.4; H,5.91%].
Reaction SMILES: [CH2:1]([C:3]1[NH:4][C:5]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:6]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:7]=1)[CH3:2].[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>>[CH2:18]([N:4]1[C:5]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:6]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:7]=[C:3]1[CH2:1][CH3:2])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: BrCc1ccccc1
Reactant: CCOC(=O)c1nc(CC)[nH]c1C(=O)OCC
Product: CCOC(=O)c1nc(CC)n(Cc2ccccc2)c1C(=O)OCC

Procedure:
Following a procedure similar to that described in Preparation 42(i), 4.00 g of diethyl 2-ethylimidazole-4,5-dicarboxylate were benzylated, using 2.20 ml of benzyl bromide. The product was purified by column chromatography through silica gel, using a 1:1 by volume mixture of methylene chloride and ethyl acetate as the eluent, to give 5.19 g of the title compound as a syrup.
Reaction SMILES: [NH2:1][C:2]1[NH:3][C:4]2[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[C:7]([C:15]([F:18])([F:17])[F:16])[C:5]=2[N:6]=1.[Cl:19][CH2:20][S:21][C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=1[Br:29]>>[Cl-:19].[NH2:1][C:2]1[N:6]([CH2:20][S:21][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=2[Br:29])[C:5]2[C:7]([C:15]([F:18])([F:16])[F:17])=[CH:8][C:9]([C:11]([F:12])([F:13])[F:14])=[CH:10][C:4]=2[N+:3]=1[CH2:20][S:21][C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=1[Br:29]
Reactant: Fc1ccc(SCCl)c(Br)c1
Reactant: Nc1nc2c(C(F)(F)F)cc(C(F)(F)F)cc2[nH]1
Product: Nc1n(CSc2ccc(F)cc2Br)c2c(C(F)(F)F)cc(C(F)(F)F)cc2[n+]1CSc1ccc(F)cc1Br
Product: [Cl-]

Procedure:
Following the procedure of Example 2 and replacing 2-aminobenzimidazole with 2-amino-5,7-bis-trifluoromethylbenzimidazole and replacing 2-bromo-4-chlorophenyl chloromethyl ether with 2-bromo-4-fluorophenyl chloromethyl sulfide, the title compound is obtained.
Reaction SMILES: [C:1]([N:4]([CH:23]1[C:31]2[C:26](=[C:27]([O:32][CH3:33])[CH:28]=[CH:29][CH:30]=2)[CH2:25][CH2:24]1)[CH2:5][C:6]1[O:7][C:8]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:10]=1)(=O)[CH3:2].Cl>C1COCC1>[CH2:1]([N:4]([CH:23]1[C:31]2[C:26](=[C:27]([O:32][CH3:33])[CH:28]=[CH:29][CH:30]=2)[CH2:25][CH2:24]1)[CH2:5][C:6]1[O:7][C:8]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:9]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:10]=1)[CH3:2]
Reactant: COc1cccc2c1CCC2N(Cc1nc(-c2ccccc2)c(-c2ccccc2)o1)C(C)=O
Agent: Cl
Solvent: C1CCOC1
Product: CCN(Cc1nc(-c2ccccc2)c(-c2ccccc2)o1)C1CCc2c(OC)cccc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 121.4 %

Procedure:
To a solution of 1-[N-acetyl-N-[(4,5-diphenyloxazol-2-yl)methyl]amino]-2,3-dihydro-4-methoxy-1H-indene (0.40 g) in THF (10 ml) was added 1M solution of borane-THF complex in THF (9 ml) at room temperature. The reaction mixture was refluxed for 8 hours and cooled down to room temperature. 1N aqueous HCl solution (25 ml) was added to the reaction mixture. After being stirred for 1 hour at room temperature, the mixture was partitioned between ethyl acetate and 1N aqueous NaOH solution. The organic layer was washed with brine. The dried solvent was evaporated in vacuo to give 1-[N-ethyl-N-[(4,5-diphenyloxazol-2-yl)methyl]amino]-2,3-dihydro-4-methoxy-1H-indene (0.47 g). MS (m/z): 425 (M+ +1) NMR (CDCl3, δ): 7.66-7.58 (4H, m), 7.39-7.08 (8H, m), 6.70 (1H, d, J=7.7 Hz), 4.67 (1H, t, J=7.6 Hz), 3.81 (3H, s), 3.18-2.80 (2H, m), 2.73 (2H, q, J=7.2 Hz), 2.35-1.84 (2H, m), 1.14 (3H, t, J=7.2 Hz)
Reaction SMILES: [C:1]1(C)C=[CH:5][C:4](S(O)(=O)=O)=[CH:3][CH:2]=1.[Br:12][C:13]1[CH:18]=[CH:17][C:16]([SH:19])=[CH:15][CH:14]=1.C(N(CC)CC)C.C(=O)(O)[O-:28].[Na+]>O1C=CCCC1.O1CCCC1>[Br:12][C:13]1[CH:18]=[CH:17][C:16]([S:19][CH:5]2[CH2:4][CH2:3][CH2:2][CH2:1][O:28]2)=[CH:15][CH:14]=1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: O=C([O-])O
Reactant: Sc1ccc(Br)cc1
Agent: C1=COCCC1
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Brc1ccc(SC2CCCCO2)cc1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
2.3 mg of p-toluene sulfonic acid were added to a solution of 1 g of 4-bromo thiophenol in 1 ml of 3,4-dihydro-[2H]-pyran and 1 ml of tetrahydrofuran and the mixture was stirred for 20 hours at ambient temperature. 0.1 ml of triethylamine were added and the mixture was poured into a saturated solution of sodium bicarbonate and extracted with ethyl acetate. The extracts were washed with a saturated aqueous solution of sodium chloride, dried and evaporated to dryness under reduced pressure. The 1,603 g of residue were chromatographed on silica (eluant: cyclohexane-ethyl acetate 97.5-2.5) to obtain 1.246 g of the expected product.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12](=[O:14])[CH3:13])=[C:5]2[NH:15][C@H:16]1[CH2:21][CH2:20][C@H:19]([CH2:22][N:23]([CH3:25])[CH3:24])[CH2:18][CH2:17]1.[Cl:26][C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[C:31]([Cl:35])[C:32]=1[O:33][CH3:34].C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl>>[ClH:1].[ClH:26].[Cl:26][C:27]1[CH:28]=[C:29]([C:2]2[N:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[CH:7][C:6]([C:12](=[O:14])[CH3:13])=[C:5]3[NH:15][C@H:16]2[CH2:21][CH2:20][C@H:19]([CH2:22][N:23]([CH3:25])[CH3:24])[CH2:18][CH2:17]2)[CH:30]=[C:31]([Cl:35])[C:32]=1[O:33][CH3:34]
Reactant: CC(=O)c1cnc2ccc(Cl)nc2c1N[C@H]1CC[C@H](CN(C)C)CC1
Reactant: COc1c(Cl)cc(B(O)O)cc1Cl
Agent: Cl
Agent: Nc1c(F)c(N)c(F)c(F)c1F
Product: COc1c(Cl)cc(-c2ccc3ncc(C(C)=O)c(N[C@H]4CC[C@H](CN(C)C)CC4)c3n2)cc1Cl

Procedure:
Following general procedure II, 1-(6-chloro-4-{trans-4-[(dimethylamino)methyl]-cyclohexylamino}-1,5-naphthyridin-3-yl)ethanone (77 g, 0.21 mmol) was reacted with (3,5-dichloro-4-methoxyphenyl)boronic acid (70 g, 0.32 mmol) followed by formation of the dihydrochloride salt to afford the desired product (80 g, 66%) as a brown solid: 1H NMR (300 MHz, CD3OD) δ 9.18 (s, 1H), 8.52 (d, J=9.0 Hz, 1H), 8.39 (d, J=9.0 Hz, 1H), 8.20 (s, 2H), 5.74-5.59 (m, 1H), 3.99 (s, 3H), 3.09 (d, J=6.6 Hz, 2H), 2.94 (s, 6H), 2.76 (s, 3H), 2.48-2.40 (m, 2H), 2.10-2.00 (m, 3H), 1.79-1.61 (m, 2H), 1.50-1.31 (m, 2H);
Reaction SMILES: [NH2:1]C(CC)C(O)=O.[CH2:8]([OH:15])[C:9]1C=CC=[CH:11][CH:10]=1.[C:16]1([CH3:26])[CH:21]=[CH:20][C:19]([S:22]([OH:25])(=[O:24])=[O:23])=[CH:18][CH:17]=1.[OH2:27]>C1C=CC=CC=1>[CH2:26]([O:27][C:8](=[O:15])[CH2:9][CH:10]([NH2:1])[CH3:11])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[CH3:26][C:16]1[CH:21]=[CH:20][C:19]([S:22]([OH:25])(=[O:24])=[O:23])=[CH:18][CH:17]=1
Reactant: OCc1ccccc1
Reactant: O
Reactant: CCC(N)C(=O)O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccccc1
Product: CC(N)CC(=O)OCc1ccccc1

Procedure:
According to the above synthetic scheme, first, 18.1 g of aminobutyric acid, 87.5 ml of benzyl alcohol and 40.0 g of p-toluenesulfonic acid were dissolved in 175 ml of benzene and refluxed. The water formed was removed as the azeotrope with benzene. To the reaction solution were added 280 ml of diethyl ether and 280 ml of hexane to form a precipitate. This precipitate was separated by filtration and recystallized in an ether/ethanol mixed solution to effect purification. As a result, 53.8 mg of β-aminobutyric acid benzyl ester·p-toluenesulfonate were obtained as a white crystal. From the results of 1H-NMR spectrometry the synthesis of β-aminobutyric acid benzyl ester·p-toluenesulfonate was confirmed. The results of the 1H-NMR spectrometry are set forth below. The underlined portion shows the position of the corresponding proton in the compound. Further, in the NMR data, “Φ-” shows a phenyl group.
Reaction SMILES: [NH2:1][C:2]1[N:3]([CH3:24])[C:4](=[O:23])[C:5]2([C:15]3[C:10](=[CH:11][CH:12]=[C:13](Br)[CH:14]=3)[O:9][CH:8]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:7]2)[N:6]=1.[C:25]([C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1)#[N:26]>C1(C)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+].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>[NH2:1][C:2]1[N:3]([CH3:24])[C:4](=[O:23])[C:5]2([C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:29]4[CH:28]=[C:27]([CH:32]=[CH:31][CH:30]=4)[C:25]#[N:26])[CH:14]=3)[O:9][CH:8]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:7]2)[N:6]=1
Reactant: N#Cc1ccc(B(O)O)cc1
Reactant: CN1C(=O)C2(CC(c3ccccc3)Oc3ccc(Br)cc32)N=C1N
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: Cc1ccccc1
Product: CN1C(=O)C2(CC(c3ccccc3)Oc3ccc(-c4cccc(C#N)c4)cc32)N=C1N
Yield: 8.7 %

Procedure:
Pd(PPh3)4 (28 mg, 0.073 mmol) in a 10 mL flask under Ar was treated sequentially with 2′-amino-6-bromo-1′-methyl-2-phenylspiro[chroman-4,4′-imidazol]-5′(1′H)-one (28 mg, 0.073 mmol) in toluene (4.4 mL), Na2CO3 (2 N, 2.2 mL) and 4-cyanophenylboronic acid (12.9 mg, 0.088 mmol). The mixture was refluxed under Ar for 3-5 h. The reaction mixture was concentrated in vacuo to give the residue, which was purified by preparative TLC followed by preparative HPLC to give pure 3-(2′-amino-1′-methyl-5′-oxo-2-phenyl-1′,5′-dihydrospiro[chroman-4,4′-imidazole]-6-yl)benzonitrile (2.58 mg, 9%). 1H-NMR (CDCl3): 0.92 (m, 1H), 1.07 (m, 1H), 1.75 (s, 3H), 4.32 (d, 1H), 5.62 (d, 1H), 5.82-5.98 (m, 5H), 6.06 (m, 2H), 6.15 (m, 2H), 6.47 (d, 1H), 6.46 (s, 1H).
Reaction SMILES: C[O-].[Na+].CO.C(O[C:9](=[O:17])[CH2:10][CH2:11][C:12](=[O:16])[CH2:13][CH2:14][CH3:15])C>C1(C)C(C)=CC=CC=1>[CH2:14]([CH:13]1[C:9](=[O:17])[CH2:10][CH2:11][C:12]1=[O:16])[CH3:15]
Reactant: CCCC(=O)CCC(=O)OCC
Agent: C[O-]
Agent: [Na+]
Solvent: Cc1ccccc1C
Solvent: CO
Product: CCC1C(=O)CCC1=O
Temperature: 25 °C
Yield: 46 %

Procedure:
A 1 l. three-necked flask, equipped with a dropping funnel, mechanical stirrer and a distillation head with thermometer and Liebig condenser was charged with 515 ml of xylene (b.p. 138°-140°), stirred and heated to boiling. 65.9 g of a 24% (wt/wt) sodium methoxide solution (prepared as in Example 1) in methyl alcohol (15.8 g = 0.293 moles) was added over 10 min., distilling off continuously the methyl alcohol. 300 ml of additional xylene were added and distillation was continued until the vapor temperature reached 135°. After the addition of 6.6 ml of dimethylsulfoxide, a solution of 40 g (0.232 moles) of 4-oxoheptanoic acid ethyl ester in 80 ml of xylene was added over 25 min. to the vigorously stirred sodium methoxide suspension while keeping the vapor temperature at ca. 135°C by continuous distillation of xylene. The orange-colored mixture was stirred and heated for an additional 5 min. and then allowed to cool to room temperature. Water was added, the mixture was acidified and the product filtered, washed, dried and recrystallized from water to afford 13.45 g (46%) of 2-ethyl-cyclopentan-1,3-dione, m.p. (uncorr.): 171°-172°C.
Reaction SMILES: [C:1]1([P:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:20][CH2:21][C:22]1[C:23]([CH3:29])=[N:24][C:25]([CH3:28])=[CH:26][CH:27]=1>CC#N>[Cl-:20].[CH3:29][C:23]1[C:22]([CH2:21][P+:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[CH:27][CH:26]=[C:25]([CH3:28])[N:24]=1
Reactant: Cc1ccc(CCl)c(C)n1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC#N
Product: Cc1ccc(C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)c(C)n1
Product: [Cl-]
Yield: 78.9 %

Procedure:
A mixture of triphenylphosphine (885 mg), 3-(chloromethyl)-2,6-dimethylpyridine (500 mg) and CH3CN (20 mL) was refluxed for 24 h. The mixture was concentrated in vacuo. The residual solid was washed with IPE to give the title compound (1060 mg).
Reaction SMILES: CO.[CH2:3]([O:6][C:7]([CH2:9][N:10]1[C@H:13]([S:14]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[C@@H:12]([CH:34]([OH:36])[CH3:35])[C:11]1=[O:37])=[O:8])[CH:4]=[CH2:5].[N+]([O-])([O-])=O.[Ag+:42]>N1C=CC=CC=1>[OH:36][CH:34]([C@@H:12]1[C@@H:13]([S-:14])[N:10]([CH2:9][C:7]([O:6][CH2:3][CH:4]=[CH2:5])=[O:8])[C:11]1=[O:37])[CH3:35].[Ag+:42]
Reactant: C=CCOC(=O)CN1C(=O)[C@H](C(C)O)[C@H]1SC(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Ag+]
Agent: O=[N+]([O-])[O-]
Solvent: c1ccncc1
Solvent: CO
Product: C=CCOC(=O)CN1C(=O)[C@H](C(C)O)[C@H]1[S-]
Temperature: 20 °C
Reaction time: 1 h

Procedure:
To a 50 ml flask equipped with a nitrogen atmosphere add 10 ml of methanol and 460 mg of (3S,4R)-1-(allyloxycarbonylmethyl)-3-(1-hydroxyethyl)-4-(triphenylmethylthio)azetidin-2-one. To this system add 160 mg silver nitrate and 0.15 ml of pyridine. Stir the system at 20° C. for 1 hour. Stop the reaction and remove the methanol by stripping to give the title compound.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[O:25][CH3:26])=[C:6]([CH:16]=1)[C:7]([NH:9][C:10]1[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=1)=[O:8].[CH3:27][N:28]1[CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:30]=[N:29]1.C(=O)([O-])[O-].[Na+].[Na+]>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.COCCOC>[CH3:26][O:25][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[CH2:18][O:17][C:5]1[CH:4]=[CH:3][C:2]([C:31]2[CH:30]=[N:29][N:28]([CH3:27])[CH:32]=2)=[CH:16][C:6]=1[C:7]([NH:9][C:10]1[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=1)=[O:8]
Reactant: COc1ccccc1COc1ccc(Br)cc1C(=O)Nc1cccnc1
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
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: COCCOC
Product: COc1ccccc1COc1ccc(-c2cnn(C)c2)cc1C(=O)Nc1cccnc1
Temperature: 120 °C

Procedure:
To a microwave vial was added 5-bromo-2-({[2-(methyloxy)phenyl]methyl}oxy)-N-3-pyridinylbenzamide (may be prepared as described in example 21; 115 mg, 0.28 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (63.7 mg, 0.31 mmol), 1,2-dimethoxyethane (2 ml), 1M sodium carbonate (0.56 ml, 0.56 mmol) and tetrakis(triphenylphosphine)palladium(0) (19.29 mg, 0.02 mmol). The vial was sealed and heated to 120° C. for 1 hr under microwave conditions. The mixture was evaporated under reduced pressure. Water (5 ml) was added to the residue and the mixture was extracted with ethyl acetate (3×10 ml). The organics were combined, evaporated under reduced pressure and the residue was purified using MDAP to yield the title compound. 10 mg.
Reaction SMILES: Cl.[O:2]1[CH:6]=[CH:5][C:4]([C:7]([CH2:9][NH2:10])=[O:8])=[CH:3]1.C(=O)(O)[O-].[Na+].[F:16][C:17]1[CH:25]=[CH:24][C:20]([C:21](Cl)=[O:22])=[CH:19][CH:18]=1>>[F:16][C:17]1[CH:25]=[CH:24][C:20]([C:21]([NH:10][CH2:9][C:7]([C:4]2[CH:5]=[CH:6][O:2][CH:3]=2)=[O:8])=[O:22])=[CH:19][CH:18]=1
Reactant: NCC(=O)c1ccoc1
Reactant: O=C(Cl)c1ccc(F)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Product: O=C(CNC(=O)c1ccc(F)cc1)c1ccoc1
Yield: 92.6 %

Procedure:
6.0 g of (3-furylcarbonyl)methylamine hydrochloride, 7.8 g of sodium bicarbonate and 6.4 g of 4-fluorobenzoyl chloride are treated in the same manner as described in Preparation 1-(1). 8.5 g of N-(4-fluorobenzoyl)-(3-furylcarbonyl)methylamine are thereby obtained. Yield: 92.4%
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([NH:8][CH2:9][C:10]([OH:12])=[O:11])=O.[CH3:13][O:14][C:15]1[CH:16]=[C:17]([CH:21]=O)[CH:18]=[N:19][CH:20]=1.C([O-])(=O)C.[Na+].C(OC(=O)C)(=O)C>O>[CH3:13][O:14][C:15]1[CH:16]=[C:17]([CH:21]=[C:9]2[C:10](=[O:11])[O:12][C:6]([C:2]3[S:1][CH:5]=[CH:4][CH:3]=3)=[N:8]2)[CH:18]=[N:19][CH:20]=1
Reactant: COc1cncc(C=O)c1
Reactant: O=C(O)CNC(=O)c1cccs1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)OC(C)=O
Solvent: O
Product: COc1cncc(C=C2N=C(c3cccs3)OC2=O)c1
Temperature: 90 °C
Yield: 46.6 %

Procedure:
To a screw-capped test tube, N-(2-thienylcarbonyl)glycine (56 mg, 0.3 mmol), 5-methoxy-3-pyridinecarboxaldehyde (45 mg, 0.3 mmol), sodium acetate (25 mg, 0.3 mmol) and acetic anhydride (0.3 mL) were added. The test tube was sealed, and it was then stirred at an external temperature of 90° C. Three hours later, the temperature of the reaction solution was returned to room temperature, and water (1.5 mL) was then added thereto. The obtained mixture was stirred at the same temperature as described above for 1.5 hours. Thereafter, the precipitated crystal was collected by filtration, and it was washed with water (5 mL) and was then dried under reduced pressure, so as to obtain 40 mg of the above-captioned compound.
Reaction SMILES: [Br:1]Br.[C:3]([C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][N:8]=1)(=[O:6])[CH2:4][CH3:5].O>C(Cl)(Cl)Cl>[Br:1][CH:4]([CH3:5])[C:3]([C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:14])[F:15])=[CH:9][N:8]=1)=[O:6]
Reactant: BrBr
Reactant: CCC(=O)c1ccc(C(F)(F)F)cn1
Solvent: O
Solvent: ClC(Cl)Cl
Product: CC(Br)C(=O)c1ccc(C(F)(F)F)cn1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
Bromine (0.52 ml.) in chloroform (50 ml.) was added to solution of 2-propionyl 5-trifluoromethylpyridine (2.03 g.) in chloroform (20 ml.) over 1 hour under photoflood illumination. After addition was complete the reaction was stirred for 16 hours at room temperature. The reaction was then poured into water, and the organic phase was separated, washed with water, dried over magnesium sulphate and concentrated to dryness to give 2-(2-bromopropionyl)-5-trifluoromethylpyridine as an oil which was used without further purification.