Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([NH:7][C:8]([C:10]2[C:14]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][OH:22])[CH:16]=3)=[CH:13][N:12](CC3C=CC(OC)=CC=3)[N:11]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(OC)C=CC=CC=1>FC(F)(F)C(O)=O>[C:1]1([NH:7][C:8]([C:10]2[C:14]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][OH:22])[CH:16]=3)=[CH:13][NH:12][N:11]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COc1ccc(Cn2cc(-c3cccc(CO)c3)c(C(=O)Nc3ccccc3)n2)cc1
Solvent: COc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: O=C(Nc1ccccc1)c1n[nH]cc1-c1cccc(CO)c1
Temperature: 120 °C
Yield: 35.2 %

Procedure:
A mixture of 4-(3-hydroxymethyl-phenyl)-1-(4-methoxy-benzyl)-1H-pyrazole-3-carboxylic acid phenylamide (20 mg) and anisole (20 μl) in trifluoroacetic acid (1 ml) was heated at 120° C. (50 W) for 15 minutes in a CEM Discover microwave synthesiser. The reaction was evaporated then purified by flash column chromatography eluting with 2:1 ethyl acetate/hexane. Product containing fractions were combined and evaporated to give 5 mg of product. (LC/MS: Rt 2.55 [M+H]+ 294).
Reaction SMILES: [CH3:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[NH:12][C:13](=[O:15])[CH3:14].C(O)(=O)C.[Br:20]Br.C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C>[Br:20][C:6]1[CH:5]=[CH:4][C:3]([NH:12][C:13](=[O:15])[CH3:14])=[C:2]([CH3:1])[C:7]=1[C:8]([F:10])([F:11])[F:9]
Reactant: BrBr
Reactant: CC(=O)Nc1cccc(C(F)(F)F)c1C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: CC(=O)Nc1ccc(Br)c(C(F)(F)F)c1C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a mixture of N-[2-methyl-3-(trifluoromethyl)phenyl]acetamide (6.2 g) and acetic acid (40 ml) was added an acetic acid solution (10 ml) of bromine (1.8 ml) under water-cooling. The reaction liquid was stirred at room temperature overnight and then at 50° C. for 2 hours. In addition, to the reaction liquid was added bromine (1.5 ml) under water-cooling, followed by stirring at 50° C. for 1 day. In addition, to the reaction liquid was added bromine (2.0 ml) under water-cooling, followed by stirring at 50° C. for 1 day. In addition, to the reaction liquid was added bromine (2.0 ml) under water-cooling, followed by stirring at 50° C. for 1 day. In addition, to the reaction liquid was added bromine (2.0 ml) under water-cooling, followed by stirring at 50° C. for 4 days. The reaction liquid was poured into ice water (about 200 g), ethyl acetate was added thereto, followed by neutralization with potassium carbonate. A liquid-separation operation was carried out, and the organic layer was washed with an aqueous sodium thiosulfate solution and saturated brine in this order, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to obtain N-[4-bromo-2-methyl-3-(trifluoromethyl)phenyl]acetamide (9.0 g).
Reaction SMILES: [N+](=[CH2:3])=[N-].[OH:4][CH:5]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])/[CH:6]=[CH:7]/[CH:8]=[CH:9]/[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH2:16][CH2:17][CH2:18][CH2:19][C:20]([OH:22])=[O:21]>C(Cl)Cl>[CH3:3][O:21][C:20](=[O:22])[CH2:19][CH2:18][CH2:17][CH2:16][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1/[CH:9]=[CH:8]/[CH:7]=[CH:6]/[CH:5]([OH:4])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]
Reactant: C=[N+]=[N-]
Reactant: CCCCCCCCC(O)/C=C/C=C/c1ccccc1CCCCC(=O)O
Solvent: ClCCl
Product: CCCCCCCCC(O)/C=C/C=C/c1ccccc1CCCCC(=O)OC
Temperature: 0 °C
Reaction time: 0.08 h

Procedure:
An ethereal diazomethane solution is added to a solution of 5 mg of 5-[2-[(1E,3E)-(5RS)-5-hydroxy-1,3-tridecadienyl]-phenyl]-pentanoic acid (produced in example 9) in 0.5 ml of methylene chloride at 0° C. until permanent yellow dyeing and stirred for 5 minutes at 0° C. Then, it is concentrated by evaporation in a vacuum and the residue is chromatographed on silica gel. With hexane/0-80% of ether, 2.6 mg of the title compound is obtained as a colorless oil.
Reaction SMILES: [Br:1][C:2]1[C:7]([OH:8])=[C:6]([O:9][CH3:10])[C:5]([O:11][CH:12]([F:14])[F:13])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:21](Br)[CH2:22][CH3:23]>C(#N)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH:12]([F:13])[F:14])=[C:6]([O:9][CH3:10])[C:7]=1[O:8][CH2:21][CH2:22][CH3:23]
Reactant: CCCBr
Reactant: COc1c(OC(F)F)ccc(Br)c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCCOc1c(Br)ccc(OC(F)F)c1OC
Temperature: 80 °C
Yield: 86.5 %

Procedure:
To a stirring solution of 6-bromo-3-(difluoromethoxy)-2-methoxyphenol (300 mg, 1.115 mmol) in acetonitrile (10 mL) was added potassium carbonate (495 mg, 2.334 mmol) and propyl bromide (411 mg, 3.34 mmol) and the resultant reaction mixture was heated to 80° C. for 3 h. The reaction mixture was cooled to RT, filtered through celite and the filtrate was concentrated under reduced pressure to afford 300 mg of 1-Bromo-4-(difluoromethoxy)-3-methoxy-2-propoxybenzene (Int14-F2) as a solid. A stirring solution of 1-bromo-4-(difluoromethoxy)-3-methoxy-2-propoxybenzene (300 mg, 0.964 mmol) in dimethylformamide (5 mL) was purged with argon for 1 h, to this cesium carbonate (625 mg, 1.926 mmol), tetrakis(triphenylphosphine) palladium(0) (37 mg, 0.032 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (199 mg, 0.771 mmol) were added and the resultant reaction mixture was heated to 80-90° C. for 3 h. The reaction mixture was cooled to RT, filtered and the filtrate was diluted with water and extracted with ethyl acetate (3×). The combined ethyl acetate layer was washed with brine and dried over anhydrous sodium sulphate and concentrated under reduced pressure. Purification of the residue by column chromatography (silica gel, 0-20% ethyl acetate in pet ether) afforded the title compound as a solid (40 mg, 11%).
Reaction SMILES: [C:1]1([C:7]2[C:8]([C:16]3[CH:23]=[CH:22][C:19]([CH:20]=O)=[CH:18][CH:17]=3)=[N:9][C:10]3[N:11]([CH:13]=[CH:14][N:15]=3)[CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[F:25][C:26]1[CH:27]=[CH:28][C:29]2[N:33]=[C:32]([CH:34]3[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]3)[NH:31][C:30]=2[CH:40]=1>>[F:25][C:26]1[CH:27]=[CH:28][C:29]2[N:33]=[C:32]([CH:34]3[CH2:35][CH2:36][N:37]([CH2:20][C:19]4[CH:22]=[CH:23][C:16]([C:8]5[C:7]([C:1]6[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=6)=[CH:12][N:11]6[CH:13]=[CH:14][N:15]=[C:10]6[N:9]=5)=[CH:17][CH:18]=4)[CH2:38][CH2:39]3)[NH:31][C:30]=2[CH:40]=1
Reactant: O=Cc1ccc(-c2nc3nccn3cc2-c2ccccc2)cc1
Reactant: Fc1ccc2nc(C3CCNCC3)[nH]c2c1
Agent: Cl
Product: Fc1ccc2nc(C3CCN(Cc4ccc(-c5nc6nccn6cc5-c5ccccc5)cc4)CC3)[nH]c2c1
Yield: 65.7 %

Procedure:
150 mg (0.5 mmol) 4-(6-phenylimidazo[1,2-a]pyrimidin-7-yl)benzaldehyde were reacted with 132 mg (0.6 mmol) 6-fluoro-2-piperidine-4-yl-1H-benzimidazole hydrochloride salt in analogy as described in example 6.0. The desired compound (165 mg) was obtained after purification on silicagel.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][S:4][CH2:3][CH2:2]1.[CH:7]1([NH:10][C:11]([C:13]2[CH:14]=[CH:15][C:16]([CH3:32])=[C:17]([NH:19][C:20](=[O:31])[C:21]3[CH:26]=[C:25](F)[CH:24]=[CH:23][C:22]=3[N+:28]([O-:30])=[O:29])[CH:18]=2)=[O:12])[CH2:9][CH2:8]1>>[CH:7]1([NH:10][C:11]([C:13]2[CH:14]=[CH:15][C:16]([CH3:32])=[C:17]([NH:19][C:20](=[O:31])[C:21]3[CH:26]=[C:25]([N:1]4[CH2:6][CH2:5][S:4][CH2:3][CH2:2]4)[CH:24]=[CH:23][C:22]=3[N+:28]([O-:30])=[O:29])[CH:18]=2)=[O:12])[CH2:9][CH2:8]1
Reactant: C1CSCCN1
Reactant: Cc1ccc(C(=O)NC2CC2)cc1NC(=O)c1cc(F)ccc1[N+](=O)[O-]
Product: Cc1ccc(C(=O)NC2CC2)cc1NC(=O)c1cc(N2CCSCC2)ccc1[N+](=O)[O-]

Procedure:
Using an analogous procedure to that described paragraph (A) in the portion of Example 13 which is concerned with the preparation of starting materials thiomorpholine was reacted with N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-5-fluoro-2-nitrobenzamide to give N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-nitro-5-thiomorpholin-4-ylbenzamide; NMR Spectrum: (DMSOd6) 0.56 (m, 2H), 0.67 (m, 2H), 2.30 (s, 3H), 2.67 (m, 4H), 2.82 (m, 1H), 3.91 (m, 4H), 7.06 (m, 2H), 7.27 (d, 1H), 7.55 (d, 1H), 7.97 (s, 1H), 8.04 (d, 1H), 8.37 (s, 1H), 9.90 (s, 1H); Mass Spectrum: M+Na+ 463.
Reaction SMILES: C[Al](C)C.[CH:5]1([CH2:8][NH2:9])[CH2:7][CH2:6]1.C[O:11][C:12](=O)[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]2[C:22]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[N:23][O:24][C:25]=2[C:26]([F:29])([F:28])[F:27])=[N:15][CH:14]=1.O>O1CCOCC1>[CH:5]1([CH2:8][NH:9][C:12](=[O:11])[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]3[C:22]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[N:23][O:24][C:25]=3[C:26]([F:29])([F:28])[F:27])=[N:15][CH:14]=2)[CH2:7][CH2:6]1
Reactant: NCC1CC1
Reactant: COC(=O)c1ccc(OCc2c(-c3ccccc3)noc2C(F)(F)F)nc1
Agent: C[Al](C)C
Solvent: O
Solvent: C1COCCO1
Product: O=C(NCC1CC1)c1ccc(OCc2c(-c3ccccc3)noc2C(F)(F)F)nc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 84.8 %

Procedure:
A solution of trimethylaluminium (2 M in toluene, 529 μL, 1.1 mmol) was added dropwise (exothermic) to a solution of cyclopropanemethylamine (75 mg, 91 μL, 1.1 mmol) in dioxane (7 mL) and the resulting mixture was stirred at room temperature for 1 h. Then a solution of 6-(3-phenyl-5-trifluoromethyl-isoxazol-4-ylmethoxy)-nicotinic acid methyl ester (100 mg, 0.26 mmol) in dioxane (4 mL) was added. The resulting mixture was then heated at 85-95° C. for 6 h and then cooled to room temperature and then poured into water and extracted with ethyl acetate which was then washed with brine, dried over sodium sulfate and evaporated. Purification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 1:1) afforded the title compound (92 mg, 83%) which was obtained as an off white solid. MS: m/e=418.3 [M+H]+.
Reaction SMILES: [F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([C@H:9]([O:11][C:12](=[O:27])[NH:13][C:14]2[C:15]([CH3:26])=[N:16][O:17][C:18]=2[C:19]2[CH:24]=[CH:23][C:22](Br)=[CH:21][CH:20]=2)[CH3:10])[CH:6]=[CH:7][CH:8]=1.CC1(C)C(C)(C)OB([C:38]2[CH:43]=[CH:42][C:41]([C:44]3([C:47]([NH:49][S:50]([CH3:53])(=[O:52])=[O:51])=[O:48])[CH2:46][CH2:45]3)=[CH:40][CH:39]=2)O1>>[F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([C@H:9]([O:11][C:12](=[O:27])[NH:13][C:14]2[C:15]([CH3:26])=[N:16][O:17][C:18]=2[C:19]2[CH:24]=[CH:23][C:22]([C:38]3[CH:39]=[CH:40][C:41]([C:44]4([C:47]([NH:49][S:50]([CH3:53])(=[O:52])=[O:51])=[O:48])[CH2:46][CH2:45]4)=[CH:42][CH:43]=3)=[CH:21][CH:20]=2)[CH3:10])[CH:6]=[CH:7][CH:8]=1
Reactant: Cc1noc(-c2ccc(Br)cc2)c1NC(=O)O[C@H](C)c1cccc(C(F)(F)F)c1
Reactant: CC1(C)OB(c2ccc(C3(C(=O)NS(C)(=O)=O)CC3)cc2)OC1(C)C
Product: Cc1noc(-c2ccc(-c3ccc(C4(C(=O)NS(C)(=O)=O)CC4)cc3)cc2)c1NC(=O)O[C@H](C)c1cccc(C(F)(F)F)c1

Procedure:
Prepared according to the procedure described in Example 1, Step 6 using [5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-carbamic acid (R)-1-(3-trifluoromethyl-phenyl)-ethyl ester and N-{1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarbonyl}-methanesulfonamide.
Reaction SMILES: [CH3:1][O:2][CH:3]=[CH:4][C:5]([O:7][Si](C)(C)C)=[CH2:6].[C:12]([O:16][CH2:17][CH3:18])(=[O:15])C=O.O.FC(F)(F)C(O)=O>C1COCC1.C1(C)C=CC=CC=1>[CH2:17]([O:16][C:12]([CH:1]1[CH2:6][C:5](=[O:7])[CH:4]=[CH:3][O:2]1)=[O:15])[CH3:18]
Reactant: CCOC(=O)C=O
Reactant: C=C(C=COC)O[Si](C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: CCOC(=O)C1CC(=O)C=CO1
Reaction time: 0.5 h
Yield: 102.2 %

Procedure:
ZnCl (0.63 g, 4.6 mmol) was dissolved in anhydrous THF (15 mL) and added to a solution of 1-methoxy-3-(trimethylsilyloxy)-1,3-butadiene (7.94 g, 46.0 mmol) and ethyl glyoxalate (7.05 g, 69.0 mmol) in toluene (30 mL) at room temperature. After stirring for 30 minutes, water (30 mL) and TFA (trifluoracetic acid) (2 mL) were added and the mixture was stirred vigorously for 20 min. After concentration, the residue was partitioned between EtOAc (200 mL) and water (100 mL). The separated organic layer was washed with brine, dried over sodium sulfate, and concentrated to give 8.0 g (100%) of brown oil which was carried to the next step without further purification. 1H NMR (CDCl3) δ 1.30 (t, 3H), 2.85 (d, 2H), 4.26 (q, 2H), 5.00 (t, 1H), 5.48 (d, 1H), 7.39 (d, 1H).
Reaction SMILES: [CH3:1][C:2]1([CH3:29])[CH:11]([OH:12])[CH:10]([C:13]2[C:14](=[O:26])[N:15]([CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:16]=[CH:17][CH:18]=2)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:27]#[N:28])[CH:8]=2)[O:3]1.P(=O)(O)(O)[OH:31]>>[CH3:1][C:2]1([CH3:29])[CH:11]([OH:12])[CH:10]([C:13]2[C:14](=[O:26])[N:15]([CH2:19][C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:16]=[CH:17][CH:18]=2)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:27](=[O:31])[NH2:28])[CH:8]=2)[O:3]1
Reactant: O=P(O)(O)O
Reactant: CC1(C)Oc2ccc(C#N)cc2C(c2cccn(Cc3ccccc3)c2=O)C1O
Product: CC1(C)Oc2ccc(C(N)=O)cc2C(c2cccn(Cc3ccccc3)c2=O)C1O

Procedure:
A mixture of 1 g of 2,2-dimethyl-4-(1-benzyl-1,2-dihydro-2-oxo-3-pyridyl)-6-cyano-3-chromanol and 10 ml of 85 percent phosphoric acid is warmed to 100° for 2 hours. After cooling and working up in the customary manner, there is obtained 2,2-dimethyl-4- (1-benzyl-1,2-dihydro-2-oxo-3-pyridyl)-6-carbamoyl -3-chromanol, m.p. 230°-235°.
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1.[O:15]([C:17]1[CH:25]=[CH:24][C:20]([C:21](O)=[O:22])=[CH:19][CH:18]=1)[CH3:16]>>[Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:21](=[O:22])[C:20]2[CH:24]=[CH:25][C:17]([O:15][CH3:16])=[CH:18][CH:19]=2)=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1
Reactant: COc1ccc(C(=O)O)cc1
Reactant: Nc1ccc(Cl)c(-c2ccccn2)c1
Product: COc1ccc(C(=O)Nc2ccc(Cl)c(-c3ccccn3)c2)cc1

Procedure:
Procedure G was used to couple 4-chloro-3-(pyridin-2-yl)aniline and 4-methoxylbenzoic acid to produce N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-methoxybenzamide. MS (Q1) 341.2 (M)+.
Reaction SMILES: [BH4-].[Na+].[Br:3][C:4]1[C:13]([O:14][CH3:15])=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8]([CH:16]=[O:17])=[CH:9]2.O>CO.C1COCC1>[Br:3][C:4]1[C:13]([O:14][CH3:15])=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8]([CH2:16][OH:17])=[CH:9]2
Reactant: COc1ccc2cc(C=O)ccc2c1Br
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: COc1ccc2cc(CO)ccc2c1Br
Reaction time: 0.5 h
Yield: 89 %

Procedure:
Step d) Sodium borohydride (4.78 g, 128.3 mmol) was added portionwise in to a cold (0° C.) mixture of 5-bromo-6-methoxy-2-naphthldehyde (34.0 g, 128.3 mmol) in methanol (300 ml) and THF (200 mL). After stirring for 30 minutes the mixture was poured in to water and extracted with EtOAc. The organic extracts were dried over MgSO4. Evaporation and purification by flash chromatography (hexane/EtOAc 2/1 ) gave a yellow solid (30.5 g, 90% yield, m.p. 85°-87° C.).
Reaction SMILES: [CH:1]([O:4][C:5]1[C:10]([N+:11]([O-])=O)=[CH:9][CH:8]=[CH:7][N:6]=1)([CH3:3])[CH3:2].C([O-])=O.[NH4+]>C(O)C.[OH-].[OH-].[Pd+2]>[CH:1]([O:4][C:5]1[C:10]([NH2:11])=[CH:9][CH:8]=[CH:7][N:6]=1)([CH3:3])[CH3:2]
Reactant: CC(C)Oc1ncccc1[N+](=O)[O-]
Agent: [Pd+2]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CCO
Product: CC(C)Oc1ncccc1N
Temperature: 90 °C
Reaction time: 2 h

Procedure:
Palladium hydroxide on carbon (20%, 0.076 g, 0.54 mmol) was added into a solution of 2-iso-propoxy-3-nitro-pyridine (1.97 g, 10.8 mmol) and ammonium formate (3.40 g, 54.0 mmol) in ethanol (100 mL) at ambient temperature. The solution was stirred for 2 hours at 90° C., cooled to ambient temperature, filtered through Celite and washed with MeOH. The filtrate was concentrated in vacuo and triturated from diethyl ether to yield brown oil which was used in the next step without further purification.
Reaction SMILES: [O:1]=[C:2]([NH:14][NH:15][C:16]([N:18]1[CH2:24][C:23]2[CH:25]=[CH:26][CH:27]=[CH:28][C:22]=2[S:21][C:20]2[CH:29]=[CH:30][C:31]([Cl:33])=[CH:32][C:19]1=2)=[O:17])[CH2:3][CH2:4][NH:5][C:6](=[O:13])[CH2:7][C:8]1[S:9][CH:10]=[CH:11][CH:12]=1.[OH:34]O>CC(O)=O>[O:1]=[C:2]([NH:14][NH:15][C:16]([N:18]1[CH2:24][C:23]2[CH:25]=[CH:26][CH:27]=[CH:28][C:22]=2[S:21](=[O:34])[C:20]2[CH:29]=[CH:30][C:31]([Cl:33])=[CH:32][C:19]1=2)=[O:17])[CH2:3][CH2:4][NH:5][C:6](=[O:13])[CH2:7][C:8]1[S:9][CH:10]=[CH:11][CH:12]=1
Reactant: OO
Reactant: O=C(Cc1cccs1)NCCC(=O)NNC(=O)N1Cc2ccccc2Sc2ccc(Cl)cc21
Solvent: CC(=O)O
Product: O=C(Cc1cccs1)NCCC(=O)NNC(=O)N1Cc2ccccc2S(=O)c2ccc(Cl)cc21
Reaction time: 1 h

Procedure:
To a stirring solution of 0.7 g (1.5 mmol) of 8-chlorodibenzo[b,f][1,4]thiazepine-10(11H)-carboxylic acid, 2-[1- oxo-3-[(2-thienylacetyl)amino]propyl]hydrazide (37), prepared in the manner described above in Example 37, in 5 mL of HOAc is added 0.13 mL (1.5 mmol) of 30% H2O2. After stirring for 1 hour, the reaction mixture is lyophilized to obtain the product.
Reaction SMILES: [C:1]([OH:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11]/[CH:12]=[CH:13]\[CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].C(O)(=O)CCCC/C=C\C/C=C\C/C=C\CCCCC.CC/C=C\C/C=C\C/C=C\CCCCCCCC(O)=O>>[C:1]([OH:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5]/[CH:6]=[CH:7]\[CH2:8]/[CH:9]=[CH:10]\[CH2:11]/[CH:12]=[CH:13]\[CH2:14]/[CH:15]=[CH:16]\[CH2:17][CH3:18]
Reactant: CCCCC/C=C\C/C=C\CCCCCCCC(=O)O
Agent: CC/C=C\C/C=C\C/C=C\CCCCCCCC(=O)O
Agent: CCCCC/C=C\C/C=C\C/C=C\CCCCC(=O)O
Product: CC/C=C\C/C=C\C/C=C\C/C=C\CCCCC(=O)O

Procedure:
FIG. 23 shows the results of the feeding experiments with the yeast cells which comprise plasmid pYES52Dest-MaLPAAT (MaB4_AT). In FIG. 23, A/B, the yeast cultures were fed linoleic acid (18:2 Δ9,12). In comparison with the control culture (FIG. 23, A), the yeast cells with the MaLPAAT showed a markedly higher conversion (increased 4-fold) of 18:2 into γ-linolenic acid (18:3 Δ6,9,12), and a 3.5-fold increase of the fatty acid 20:2 Δ11,14 elongated from 18:2. Analogously, when feeding linolenic acid (18:3 Δ9, 12, 15), a markedly higher conversion rate to give stearidonic acid (18:4 Δ6, 9, 12, 15) and isoarachidonic acid (20:4 Δ8, 11, 14, 17) was observed in comparison with the controls (FIG. 24).
Reaction SMILES: [Cl:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][NH:7][C:8](=[O:17])[C:9](=[CH:13][O:14][CH2:15][CH3:16])[C:10](=[O:12])[CH3:11])=[CH:4][CH:3]=1.[CH2:20]([O:22][C:23]([O:26][CH2:27][CH3:28])=[CH:24][CH3:25])[CH3:21]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:9]2[C@H:13]([O:14][CH2:15][CH3:16])[C@H:24]([CH3:25])[C:23]([O:26][CH2:27][CH3:28])([O:22][CH2:20][CH3:21])[O:12][C:10]=2[CH3:11])=[O:17])=[CH:18][CH:19]=1
Reactant: CCOC=C(C(C)=O)C(=O)NCc1ccc(Cl)cc1
Reactant: CC=C(OCC)OCC
Solvent: Cc1ccccc1
Product: CCO[C@H]1C(C(=O)NCc2ccc(Cl)cc2)=C(C)OC(OCC)(OCC)[C@H]1C
Temperature: 25 °C
Reaction time: 72 h
Yield: 44 %

Procedure:
N-(4'-chlorobenzyl)-2-ethoxymethylene-3-oxobutanamide (1.4 g) and tris (6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedianato)ytterbium (0.26 g) were stirred in toluene (10 ml) whilst 1,1-diethoxyprop-1-ene (4 g) was added dropwise. The mixture was stirred at room temperature for 3 days and evaporated to dryness. The residual gum was triturated with petroleum ether b.p. 60°-80° C. to give a solid which was recrystallised from a mixture of toluene and petroleum ether b.p. 60°-80° C. to give cis-N-(4'-chlorobenzyl)-2,2-diethoxy-3,6-dimethyl-4-ethoxy-3,4-dihydro-2H-pyran-5-carboxamide (0.9 g) m.p. 97°-100° C.
Reaction SMILES: C(O)C.[Na:4].[CH:5]1[CH2:9][CH:8]=[CH:7][CH:6]=1.O.[CH3:11][CH2:12][CH2:13][CH2:14][CH3:15]>>[Na:4].[CH2:14]([CH:15]=[C:6]1[CH:5]=[CH:9][CH:8]=[CH:7]1)[CH2:13][CH:12]=[CH2:11]
Reactant: CCCCC
Reactant: C1=CCC=C1
Agent: [Na]
Solvent: CCO
Solvent: O
Product: C=CCCC=C1C=CC=C1
Temperature: 0 °C
Reaction time: 4 h

Procedure:
Then a sodium solution of ethanol was prepared by combining 4.3 g of sodium with 150 mL of ethanol. The solution was cooled to 0° C. and then 30 g of the phenyl alkenyl ketone was added. Then 30 mL of cyclopentadiene was slowly added to the solution and the mixture stirred for 4 hrs. Then 100 mL of water and 100 mL of pentane were added. The ethanol-water layer was then extracted twice with pentane. The organic layer was dried over filtered silica and the solvent removed in a vacuum to yield 6-phenyl, 6-(but-3-enyl) fulvene.
Reaction SMILES: [OH:1][CH2:2][C:3]([N:5]1[CH2:10][CH2:9][N:8]([CH2:11][CH2:12][CH2:13][C:14]2[C:22]3[CH2:21][CH2:20][CH2:19][CH2:18][C:17]=3[NH:16][C:15]=2[CH:23]=O)[CH2:7][CH2:6]1)=[O:4].[CH2:25]([S:27]([C:30]1[CH:31]=[C:32]2[C:36](=[CH:37][CH:38]=1)[NH:35][C:34](=[O:39])[CH2:33]2)(=[O:29])=[O:28])[CH3:26]>>[CH2:25]([S:27]([C:30]1[CH:31]=[C:32]2[C:36](=[CH:37][CH:38]=1)[NH:35][C:34](=[O:39])/[C:33]/2=[CH:23]\[C:15]1[NH:16][C:17]2[CH2:18][CH2:19][CH2:20][CH2:21][C:22]=2[C:14]=1[CH2:13][CH2:12][CH2:11][N:8]1[CH2:9][CH2:10][N:5]([C:3](=[O:4])[CH2:2][OH:1])[CH2:6][CH2:7]1)(=[O:28])=[O:29])[CH3:26]
Reactant: CCS(=O)(=O)c1ccc2c(c1)CC(=O)N2
Reactant: O=Cc1[nH]c2c(c1CCCN1CCN(C(=O)CO)CC1)CCCC2
Product: CCS(=O)(=O)c1ccc2c(c1)/C(=C/c1[nH]c3c(c1CCCN1CCN(C(=O)CO)CC1)CCCC3)C(=O)N2
Yield: 28.4 %

Procedure:
3-{3-[4-(2-Hydroxy-acetyl)-piperazin-1-yl]-propyl}-4,5,6,7-tetrahydro-1H-indole-2-carbaldehyde (134 mg, 0.3 mmol), prepared as described in Example 13, was condensed with 5-ethylsulfonyloxindole (102 mg, 72% pure) following the procedure used in Example 1. Dark solid was precipitated out and purified by flash chromatography, eluting with (dichloromethane/methanol 10/1) to give 46 mg of the desired product.
Reaction SMILES: [O:1]1[C:5]([NH:6][C:7](=[O:14])OCC(Cl)(Cl)Cl)=[CH:4][CH:3]=[N:2]1.[C:15]1([C:21]2[N:25]=[C:24]([N:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)[S:23][N:22]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(N(C(C)C)CC)(C)C.CS(C)=O>O>[O:1]1[C:5]([NH:6][C:7]([N:29]2[CH2:30][CH2:31][N:26]([C:24]3[S:23][N:22]=[C:21]([C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)[N:25]=3)[CH2:27][CH2:28]2)=[O:14])=[CH:4][CH:3]=[N:2]1
Reactant: c1ccc(-c2nsc(N3CCNCC3)n2)cc1
Reactant: O=C(Nc1ccno1)OCC(Cl)(Cl)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CS(C)=O
Solvent: O
Product: O=C(Nc1ccno1)N1CCN(c2nc(-c3ccccc3)ns2)CC1

Procedure:
A solution of 2,2,2-trichloroethyl isoxazol-5-ylcarbamate (200 mg, 0.771 mmol), 1-(3-phenyl-1,2,4-thiadiazol-5-yl)piperazine (190 mg, 0.771 mmol), diisopropylethylamine (0.134 ml, 0.771 mmol) and dimethylsulfoxide (7 ml) was stirred at 70° C. for 12 hours, the reaction mixture was poured into water and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate) to obtain the desired product as a solid. This was recrystallized from a mixed solvent of tetrahydrofuran, ethyl acetate and hexane to obtain the desired product (61.5 mg, 22.4%) as a solid.