Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].S(Cl)([Cl:19])=O>>[F:1][C:2]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4]([Cl:19])=[O:5]
Reactant: O=S(Cl)Cl
Reactant: O=C(O)c1ccc(-c2ccccn2)cc1F
Product: O=C(Cl)c1ccc(-c2ccccn2)cc1F
Temperature: 70 °C
Reaction time: 8 h

Procedure:
Thionyl chloride (20 ml) was added to 2-fluoro-4-(pyridine-2-yl)benzoic acid (1.91 g, 8.66 mmol) and the mixture was stirred at 70° C. overnight. The solvent was evaporated under reduced pressure and the residue was dried in vacuum to yield 2-fluoro-4-(pyridin-2-yl)benzoyl chloride.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][C:21]([F:24])([F:23])[F:22])(=[O:12])=[O:11])=[CH:6][CH:5]=1)([O-])=O.[Sn](Cl)Cl>CCO>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([S:10]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][C:21]([F:24])([F:22])[F:23])(=[O:11])=[O:12])=[CH:8][CH:9]=1
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)Nc2ccccc2OC(F)(F)F)cc1
Agent: Cl[Sn]Cl
Solvent: CCO
Product: Nc1ccc(S(=O)(=O)Nc2ccccc2OC(F)(F)F)cc1
Temperature: 80 °C
Reaction time: 4 h
Yield: 51.2 %

Procedure:
To a mixture of 4-nitro-N-(2-(trifluoromethoxy)phenyl)benzenesulfonamide (2.62 g, 7.23 mmol) in EtOH (60 mL) was added Tin (II) chloride dehydrate (8.16 g, 36.2 mmol). The reaction mixture was stirred for 4 h at 80° C. LC-MS and TLC analyses indicated that the reaction was completed. The mixture was cooled down to room temperature. The EtOH was removed via vacuo and the residual was taken up in EtOAc (100 mL), followed by the addition of 2N NaOH (40 mL to make basic). After stirring vigorously for 1 h, the precipitates were filtered through celite and washed with EtOAc. The filtrate layers were separated. The organic layer was washed with 1N NaOH (optional), then water and brine, dried (Na2SO4), filtered, and concentrated. The crude product (brown residue, 1.42 g) was subjected a column purification on BioTage (0-6% MeOH in DCM) to yield a desired product (1.23 g, 51% yield).
Reaction SMILES: [CH:1]1([CH2:4][N:5]2[C:10](=[O:11])[C:9]([CH2:12][O:13][S:14]([CH3:17])(=[O:16])=[O:15])=[CH:8][C:7]([C:18]3[CH:19]=[CH:20][C:21]4[O:25][CH2:24][CH2:23][C:22]=4[CH:26]=3)=[N:6]2)[CH2:3][CH2:2]1.[F:27][C:28]1C=CC(CN2C(=O)C(CO)=CC(C3C=CC4OCCC=4C=3)=N2)=[CH:30][CH:29]=1>>[F:27][C:28]1[CH:3]=[CH:2][C:1]([CH2:4][N:5]2[C:10](=[O:11])[C:9]([CH2:12][O:13][S:14]([CH3:17])(=[O:16])=[O:15])=[CH:8][C:7]([C:18]3[CH:19]=[CH:20][C:21]4[O:25][CH2:24][CH2:23][C:22]=4[CH:26]=3)=[N:6]2)=[CH:30][CH:29]=1
Reactant: CS(=O)(=O)OCc1cc(-c2ccc3c(c2)CCO3)nn(CC2CC2)c1=O
Reactant: O=c1c(CO)cc(-c2ccc3c(c2)CCO3)nn1Cc1ccc(F)cc1
Product: CS(=O)(=O)OCc1cc(-c2ccc3c(c2)CCO3)nn(Cc2ccc(F)cc2)c1=O
Yield: 78.6 %

Procedure:
The general procedure of Example 1 (5) was carried out by use of 2-(4-fluorobenzyl)-6-(2,3-dihydro-1-benzofuran-5-yl)-4-hydroxymethyl-2H-pyridazin-3-one, to thereby yield the title compound as a yellow oil (yield: 78.6%).
Reaction SMILES: C(OC(=O)[NH:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]2[CH2:25][C:24](=[O:26])[N:23]([CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[S:22]2(=[O:34])=[O:33])=[C:17]([O:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH:16]=1)(C)(C)C>C(O)(C(F)(F)F)=O.C(Cl)Cl>[NH2:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]2[S:22](=[O:34])(=[O:33])[N:23]([CH2:27][CH2:28][Si:29]([CH3:31])([CH3:32])[CH3:30])[C:24](=[O:26])[CH2:25]2)=[C:17]([O:35][CH2:36][C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH:16]=1
Reactant: CC(C)(C)OC(=O)N[C@@H]1CCCC[C@H]1Cc1ccc(N2CC(=O)N(CC[Si](C)(C)C)S2(=O)=O)c(OCc2ccccc2)c1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: C[Si](C)(C)CCN1C(=O)CN(c2ccc(C[C@@H]3CCCC[C@H]3N)cc2OCc2ccccc2)S1(=O)=O

Procedure:
A solution of ((1R*,2S*)-2-{3-benzyloxy-4-[1,1,4-trioxo-5-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-2-yl]-benzyl}-cyclohexyl)-carbamic acid tert-butyl ester (Example 66, step C) (150 mg, 0.238 mmol) in 2 mL of TFA/methylene chloride (1:1) is stirred at RT for 15 min. The solvent is removed under reduced pressure to give the title compound which is used directly in the next step.
Reaction SMILES: Cl([O-])=O.[Na+].[CH2:5]([O:12][C:13]([N:15]1[C@@H:20]([CH3:21])[C:19](=[O:22])[N:18]2[C@@H:23]([CH2:26][CH2:27][OH:28])[CH2:24][O:25][CH:17]2[CH2:16]1)=[O:14])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.S([O-])([O-])(=[O:31])=S.[Na+].[Na+].Cl>P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(#N)C.O.CCOC(C)=O.Cl[O-].[Na+].CC1(C)N([O])C(C)(C)CCC1>[CH2:5]([O:12][C:13]([N:15]1[C@@H:20]([CH3:21])[C:19](=[O:22])[N:18]2[C@@H:23]([CH2:26][C:27]([OH:31])=[O:28])[CH2:24][O:25][CH:17]2[CH2:16]1)=[O:14])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: O=S([O-])([O-])=S
Reactant: C[C@H]1C(=O)N2C(CN1C(=O)OCc1ccccc1)OC[C@@H]2CCO
Agent: CC1(C)CCCC(C)(C)N1[O]
Agent: Cl
Agent: O=P([O-])([O-])[O-]
Solvent: CCOC(C)=O
Solvent: CC#N
Solvent: O
Product: C[C@H]1C(=O)N2C(CN1C(=O)OCc1ccccc1)OC[C@@H]2CC(=O)O
Temperature: 45 °C
Yield: 82 %

Procedure:
Solutions of sodium chlorite (66 mg, 0.58 mmol in 0.5 mL water) and 10% aq. sodium hypochlorite (4 μL, 6 μmol in 0.2 mL water) were added simultaneously at 35° C. to a mixture of (3S,6S)-3-(2-hydroxy-ethyl)-6-methyl-5-oxo-hexahydro-oxazolo[3,2-a]pyrazine-7-carboxylic acid benzyl ester (98 mg, 0.29 mmol), 2,2,6,6-tetramethylpiperidine-1-oxyl radical (3 mg, 20 μmol) in 1 M aq. potassium phosphate buffer (pH 6.85; 0.75 mL) and acetonitrile (1 mL). The reaction mixture was heated at 45° C. for 16 h, then cooled to 0° C., diluted with water and EtOAc and treated with 1 M sodium thiosulfate solution. The pH was then set to 3-4 by addition of 2 M aq. hydrochloric acid solution. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and evaporated. Chromatography (SiO2; DCM→DCM/MeOH/25% aq. ammonia solution 90:10:0.25) afforded the title compound (84 mg, 82%). Colourless gum, MS: 347.1 (M−H)−.
Reaction SMILES: [Cl:1][SiH:2]([Cl:4])[Cl:3].[C:5]([O:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]=[CH2:14])=[CH:11][CH:10]=1)(=[O:7])[CH3:6]>O.Cl.Cl.Cl[Pt](Cl)(Cl)Cl.CCCCCCC>[C:5]([O:8][C:9]1[CH:16]=[CH:15][C:12]([CH2:13][CH2:14][Si:2]([Cl:4])([Cl:3])[Cl:1])=[CH:11][CH:10]=1)(=[O:7])[CH3:6]
Reactant: C=Cc1ccc(OC(C)=O)cc1
Reactant: Cl[SiH](Cl)Cl
Agent: Cl[Pt](Cl)(Cl)Cl
Agent: Cl
Solvent: CCCCCCC
Solvent: O
Product: CC(=O)Oc1ccc(CC[Si](Cl)(Cl)Cl)cc1

Procedure:
Trichlorosilane (56.9 grams, 0.42 mole), 4-acetoxystyrene (64.6 grams, 0.40 mole), and 200 ml heptane were placed in a round bottom flask equipped with a water condenser and nitrogen inlet. Hydrogen hexachloroplatinate(IV) hydrate (20 mg) was added to this solution and heated to reflux for 18 hours. Afterwards, the solution was filtered hot through a frit funnel. The solvent and the unreacted reagents were distilled off at atmospheric pressure and the residue was purified by distillation under reduced pressure. 4-acetoxyphenylethyl trichlorosilane (91.2 grams) was collected between 105-125° C. at 1 mm Hg pressure as a waxy solid.
Reaction SMILES: [OH:1][C:2]1[C:3]([F:30])=[C:4]([C:22]([F:29])=[C:23]([F:28])[C:24]=1[N+:25]([O-])=O)[O:5][C:6]1[C:11]([F:12])=[C:10]([F:13])[C:9]([N+:14]([O-])=O)=[C:8]([O:17]CC=C)[C:7]=1[F:21]>O1CCCC1.C(OCC)(=O)C.[Pd]>[OH:17][C:8]1[C:7]([F:21])=[C:6]([O:5][C:4]2[C:22]([F:29])=[C:23]([F:28])[C:24]([NH2:25])=[C:2]([OH:1])[C:3]=2[F:30])[C:11]([F:12])=[C:10]([F:13])[C:9]=1[NH2:14]
Reactant: C=CCOc1c(F)c(Oc2c(F)c(O)c([N+](=O)[O-])c(F)c2F)c(F)c(F)c1[N+](=O)[O-]
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Nc1c(O)c(F)c(Oc2c(F)c(O)c(N)c(F)c2F)c(F)c1F
Temperature: 25 °C
Reaction time: 6 h

Procedure:
44 g of 1-(3-hydroxy-4-nitro-2,5,6-trifluorophenoxy)-3-(prop-2-enyloxy)-4-nitro-2,5,6-tri-fluorobenzene prepared as described in Example 10 (0.1 mol) are dissolved in 400 ml of a mixture of tetrahydrofuran and ethyl acetate (volume ratio 1:1), and 4.4 g of Pd/C (palladium/carbon) are added to the solution. The solution is then stirred vigorously for 6 hours at room temperature in an autoclave in order to remove the allyl protecting group. Hydrogen is then passed in, and the mixture is hydrogenated at a pressure of 1 bar; after 3 days, the reaction is terminated. The yellow solution is evaporated to half in a rotary evaporator and left to stand at room temperature overnight, during which the reaction product precipitates in crystalline form. The reaction product is then separated off and dried for 48 hours under nitrogen at 40° C./10 mbar in a vacuum drying cabinet.
Reaction SMILES: ClC1C=C(C(Cl)=O)C=C(Cl)C=1.[Cl:12][C:13]1[CH:14]=[C:15]([CH:17]=[CH:18][C:19]=1[O:20][C:21]1[C:30]2[C:25](=[CH:26][C:27]([O:33][CH3:34])=[C:28]([O:31][CH3:32])[CH:29]=2)[N:24]=[CH:23][CH:22]=1)[NH2:16].[Cl:35][C:36]1[CH:37]=[C:38]([C:43]([N:45]=[C:46]=[S:47])=[O:44])[CH:39]=[C:40]([Cl:42])[CH:41]=1>C1(C)C=CC=CC=1.C(O)C>[Cl:35][C:36]1[CH:37]=[C:38]([C:43]([N:45]=[C:46]=[S:47])=[O:44])[CH:39]=[C:40]([Cl:42])[CH:41]=1.[Cl:12][C:13]1[CH:14]=[C:15]([NH:16][C:46]([NH:45][C:43](=[O:44])[C:38]2[CH:39]=[C:40]([Cl:42])[CH:41]=[C:36]([Cl:35])[CH:37]=2)=[S:47])[CH:17]=[CH:18][C:19]=1[O:20][C:21]1[C:30]2[C:25](=[CH:26][C:27]([O:33][CH3:34])=[C:28]([O:31][CH3:32])[CH:29]=2)[N:24]=[CH:23][CH:22]=1
Reactant: COc1cc2nccc(Oc3ccc(N)cc3Cl)c2cc1OC
Agent: O=C(Cl)c1cc(Cl)cc(Cl)c1
Agent: O=C(N=C=S)c1cc(Cl)cc(Cl)c1
Solvent: CCO
Solvent: Cc1ccccc1
Product: COc1cc2nccc(Oc3ccc(NC(=S)NC(=O)c4cc(Cl)cc(Cl)c4)cc3Cl)c2cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 63 %

Procedure:
3,5-Dichloro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3,5-dichloro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3,5-dichloro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (55 mg, yield 63%).
Reaction SMILES: [ClH:1].[Br:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][C@H:6]([C:17]([O:19]C)=[O:18])[N:7](C(OC)=O)[CH2:8]2.BrC1C=CC=C2C=1C[C@H](C(O)=O)N(C(OC)=O)C2>O>[ClH:1].[Br:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][C@H:6]([C:17]([OH:19])=[O:18])[NH:7][CH2:8]2
Reactant: COC(=O)[C@H]1Cc2c(Br)cccc2CN1C(=O)OC
Agent: COC(=O)N1Cc2cccc(Br)c2C[C@@H]1C(=O)O
Agent: Cl
Solvent: O
Product: O=C(O)[C@H]1Cc2c(Br)cccc2CN1
Temperature: 95 °C

Procedure:
Add water (1.3 L) and 36.5% hydrochloric acid (9.07 Kg, 90.81 moles) to a mixture of dimethyl (3R)-5-bromo-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylate and (3R)-5-bromo-2-methoxycarbonyl-3,4-dihydro-1H-isoquinoline-3-carboxylic acid (Preparation 3a) (520 g, 1.27 moles) in an appropriate vessel and stir the mixture at 95° C. After 12 hours cool the mixture to 10° C. and stir for 15 minutes. Filter the mixture and dry the solid under vacuum at 40° C. give the title compound (332 g, 1.13 moles). MS (m/z): 256.1 (M-Cl (79Br)), 258 (M-Cl (81Br)).
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:5]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:4][C:3]=1[N+:18]([O-])=O>C(O)(=O)C.[Fe]>[NH2:18][C:3]1[CH: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][C:2]=1[CH3:1]
Reactant: CCOC(=O)c1cc([N+](=O)[O-])c(C)nc1C(=O)OCC
Agent: [Fe]
Solvent: CC(=O)O
Product: CCOC(=O)c1cc(N)c(C)nc1C(=O)OCC
Temperature: 70 °C
Reaction time: 2 h

Procedure:
56.9 g (1.065 mol) of iron powder in 200 ml of glacial acetic acid were initially taken and were heated to 70° C. while stirring, and a solution of 100 g (0.355 mol) of diethyl 6-methyl-5-nitropyridine-2,3-dicarboxylate (EP 277 932) in 700 ml of glacial acetic acid was added in the course of 20 minutes. Stirring was carried out for 2 hours, after which a further 25.2 g (0.45 mol) of iron powder in 200 ml of glacial acetic acid were added and stirring was continued for a further hour at 70° C. The mixture was cooled to 25° C., the precipitate was filtered off with suction and the filtrate was evaporated down under reduced pressure, after which the residue was taken up in methylene chloride, extracted in succession with water, saturated sodium bicarbonate solution and sodium chloride solution, dried over magnesium sulfate and filtered off with suction over a suction filter containing silica gel. 49 g (55% of theory) of the title compound were isolated as a yellow resin from fractions 3 and 4 after they had been evaporated down.
Reaction SMILES: Cl[C:2]1[O:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[NH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1>ClCCl>[N:11]1([C:2]2[O:3][C:4]3[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=3[N:6]=2)[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1
Reactant: Clc1nc2ccccc2o1
Reactant: C1CNCCN1
Solvent: ClCCl
Product: c1ccc2oc(N3CCNCC3)nc2c1

Procedure:
A 3.07 g portion of 2-chlorobenzoxazole was dissolved in 10 ml of dichloromethane. Under cooling with ice, to this was added dropwise 3.45 g of anhydrous piperazine which has been dissolved in 30 ml of dichloromethane, followed by 1 hour of reaction. The reaction solution was concentrated under a reduced pressure, and the resulting residue was purified by a silica gel column chromatography (dichloromethane:methanol=20:1), followed by concentration of the eluate under a reduced pressure. Thereafter, the resulting residue was dissolved in 30 ml of water, neutralized with 1N hydrochloric acid, extracted with dichloromethane, washed with water, dehydrated with Na2SO4 and then concentrated under a reduced pressure to obtain 1.77 g of 2-(1-piperazinyl)benzoxazole.
Reaction SMILES: B.[CH3:2][O:3][C:4]1[CH:5]=[CH:6][C:7]([N+:13]([O-:15])=[O:14])=[C:8]([CH2:10][C:11]#[N:12])[CH:9]=1.CO.Cl>C1COCC1>[CH3:2][O:3][C:4]1[CH:5]=[CH:6][C:7]([N+:13]([O-:15])=[O:14])=[C:8]([CH2:10][CH2:11][NH2:12])[CH:9]=1
Reactant: COc1ccc([N+](=O)[O-])c(CC#N)c1
Agent: B
Agent: Cl
Solvent: CO
Solvent: C1CCOC1
Product: COc1ccc([N+](=O)[O-])c(CCN)c1
Reaction time: 0.5 h

Procedure:
Under a nitrogen atmosphere, 200 mL (200 mmol) of a 1M borane in THF solution were slowly added dropwise at RT to 12.6 g (65.7 mmol) (5-methoxy-2-nitrophenyl)-acetonitrile in 380 mL THF. The reaction mixture was refluxed for 2 h. After cooling 30 mL methanol were added dropwise within 20 min. During this time the temperature was maintained at 10° C. to 20° C. with an ice bath. The reaction mixture was left for 30 min at RT with stirring and then within 30 min 45 mL of a 2M aqueous HCl solution were added dropwise thereto. The reaction mixture was concentrated by rotary evaporation i. vac. The residue was diluted with water to approx. 200 mL and extracted with 200 mL EtOAc. The aqueous phase was made alkaline with a 15% (w/v) aqueous potassium carbonate solution and continuously extracted overnight with diethyl ether using a rotary perforator according to Ludwig (Messrs Normag). The organic extract was evaporated to dryness by rotary evaporation.
Reaction SMILES: C([O:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9]CC/C=C/C=C\CCCC)(=O)C.[CH2:20]([OH:29])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][OH:28].O1C=CCCC1.Cl>ClCCl>[O:4]1[CH2:5][CH2:6][CH2:7][CH2:8][CH:9]1[O:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][OH:29]
Reactant: OCCCCCCCCO
Reactant: CCCC/C=C\C=C\CCCCCCCOC(C)=O
Agent: C1=COCCC1
Agent: Cl
Solvent: ClCCl
Product: OCCCCCCCCOC1CCCCO1

Procedure:
The synthesis of compound I, the major component of the attractant composition of the invention is illustrated in FIG. 1. In brief, 1,8-octanediol is reacted with dihydropyran in dichloromethane catalyzed by hydrochloric acid to give 8-[(tetrahydro-2H-pyran-2-yl)oxy]-1-octanol, which is reacted with pyridinium chlorochromate to give 8-[(tetrahydro-2H-pyran-2-yl)oxy]octanal (A). The octanal (A) is then reacted with diethylcyanomethylphosphate and sodium hydride to produce 10-[(tetrahydro-2H-pyran-2-yl)oxy]-2-decenitrile (B). Diisobutylaluminum hydride reduces the nitrile (B) to an imine which upon hydrolysis yields the aldehyde (C). Wittig coupling of (C) with n-pentyl triphenylphosphorane gives the mixture of conjugated dienes (D) which upon hydrolysis and acetylation give the two isomeric pentadecadien-1-ol acetates (E). The (E,E)-8,10-isomer is removed by Diels-Alder reaction with tetracyanoethylene to give pure (E,Z)-8,10-pentadecadien- 1-ol acetate (I). A detailed description of the synthesis of I is given in Example 4, below.
Reaction SMILES: [CH:1]([C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[CH:16]=[CH:15][C:11]([C:12]([NH2:14])=[O:13])=[CH:10][N:9]=2)=[C:5]([O:19][CH3:20])[CH:4]=1)=O.[F:21][C:22]1[CH:30]=[CH:29][C:25]([CH2:26][CH2:27][NH2:28])=[CH:24][CH:23]=1>>[F:21][C:22]1[CH:30]=[CH:29][C:25]([CH2:26][CH2:27][NH:28][CH2:1][C:3]2[CH:18]=[CH:17][C:6]([O:7][C:8]3[CH:16]=[CH:15][C:11]([C:12]([NH2:14])=[O:13])=[CH:10][N:9]=3)=[C:5]([O:19][CH3:20])[CH:4]=2)=[CH:24][CH:23]=1
Reactant: COc1cc(C=O)ccc1Oc1ccc(C(N)=O)cn1
Reactant: NCCc1ccc(F)cc1
Product: COc1cc(CNCCc2ccc(F)cc2)ccc1Oc1ccc(C(N)=O)cn1
Yield: 94.7 %

Procedure:
Using a method similar to Example 405, a reaction of 6-(4-formyl-2-methoxyphenoxy)nicotinamide (Example 414, Part B) (0.050 g, 0.184 mmol) and 4-fluorophenethylamine (0.0256 g, 0.184 mmol) gives the title compound (0.0689 g, 94.9%): TOF MS ES− 396.2 (M+H)+, HRMS calcd for C22H23N3O3F 396.1723 (M+H)+, found 396.1714, time 0.41 min; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), 0.1% TFA/acetonitrile in 0.1% TFA/water at 1.0 mL/min, 20-99% over 23 min], tR=7.1 ml, 100% purity.
Reaction SMILES: [I:1][C:2]1[C:7]([I:8])=[CH:6][C:5]([NH2:9])=[C:4]([NH2:10])[CH:3]=1.O=[C:12]([C:18](OCC)=[O:19])[C:13]([O:15][CH2:16][CH3:17])=[O:14]>C(O)C>[I:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:6][C:7]=1[I:8])[N:9]=[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:18](=[O:19])[NH:10]2
Reactant: CCOC(=O)C(=O)C(=O)OCC
Reactant: Nc1cc(I)c(I)cc1N
Solvent: CCO
Product: CCOC(=O)c1nc2cc(I)c(I)cc2[nH]c1=O
Reaction time: 8 h

Procedure:
A solution was prepared from 0.9 g. of 4,5-di-iodo-o-phenylenediamine and 25 ml. of ethanol. Five grams of diethyl ketomalonate were added and the resulting mixture was heated to refluxing temperature with stirring overnight. The reaction mixture was then cooled. Ethyl 6,7-di-iodo-3,4-dihydro-3-oxo-2-quinoxaline carboxylate formed in the above reaction precipitated and was collected by filtration; yield=0.8 g.; mp=275°-276° C.
Reaction SMILES: [O:1]=[C:2]1[C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:6][NH:5][C:4](/[CH:16]=[CH:17]/[C:18]([O:20]CC)=[O:19])=[CH:3]1.[OH-].[K+]>C(O)C>[O:1]=[C:2]1[C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:6][NH:5][C:4](/[CH:16]=[CH:17]/[C:18]([OH:20])=[O:19])=[CH:3]1
Reactant: CCOC(=O)/C=C/c1cc(=O)c(OCc2ccccc2)c[nH]1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)/C=C/c1cc(=O)c(OCc2ccccc2)c[nH]1

Procedure:
(E)-3-[1,4-Dihydro-4-oxo-5-(phenylmethoxy)-2-pyridinyl]-2-propenoic acid, ethyl ester (1.5 g) and 0.29 g of potassium hydroxide were stirred in 30 ml of ethanol for two hours at 50° C. After evaporating the solvent, the residue was dissolved in 100 ml of water and filtered. Hydrochloric acid (2N) was added to the filtrate until pH 5 was reached; crystals of the title compound separated. The crystals were filtered and washed with water and dried in vacuo (yield: 1.14 g).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([O:15][CH2:16][C:17]#[CH:18])[C:10]=1[O:11][CH2:12][C:13]#[CH:14])[C:5](Cl)=[O:6].O.[NH3:20]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([O:15][CH2:16][C:17]#[CH:18])[C:10]=1[O:11][CH2:12][C:13]#[CH:14])[C:5]([NH2:20])=[O:6]
Reactant: C#CCOc1cc(C(=O)Cl)cc(Cl)c1OCC#C
Reactant: N
Solvent: Cc1ccccc1
Solvent: O
Product: C#CCOc1cc(C(N)=O)cc(Cl)c1OCC#C
Temperature: 0 °C

Procedure:
A solution of 3-choro-4,5-dipropargyloxybenzoyl chloride (1.00 g) in 30% ammonia water (20 ml) and toluene (10 ml) was stirred under reflux for 10 minutes, poured into ice-water and extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate and concentrated under reduced pressure to give a residue. The residue was further washed with hexane to give 3-chloro-4,5-dipropargyloxybenzamide (0.88 g). m.p. 122°-125° C.
Reaction SMILES: [O:1]1[CH2:5][CH2:4][CH:3]([CH2:6][N:7]2[CH2:12][CH2:11][CH2:10][NH:9][C:8]2=[N:13][N+:14]([O-:16])=[O:15])[CH2:2]1.[H-].[Na+].[C:19](Cl)(=[O:22])[CH2:20][CH3:21]>C(#N)C>[C:19]([N:9]1[CH2:10][CH2:11][CH2:12][N:7]([CH2:6][CH:3]2[CH2:4][CH2:5][O:1][CH2:2]2)[C:8]1=[N:13][N+:14]([O-:16])=[O:15])(=[O:22])[CH2:20][CH3:21]
Reactant: CCC(=O)Cl
Reactant: O=[N+]([O-])N=C1NCCCN1CC1CCOC1
Agent: [H-]
Agent: [Na+]
Solvent: CC#N
Product: CCC(=O)N1CCCN(CC2CCOC2)C1=N[N+](=O)[O-]
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 21.4 %

Procedure:
A mixture of 3.0 g of 1-[(tetrahydro-3-furanyl)methyl]-2-(nitroimino)hexahydropyrimidine, 0.70 g of sodium hydride (60%) and 100 ml of acetonitrile was stirred at 50° C. for 30 minutes. After this mixture was cooled on ice, 1.60 g of propionyl chloride was added dropwise thereto over 30 minutes, and the solution was then stirred at room temperature for 2 hours. After the completion of reaction, insolubles were removed by filtration, and the filtrate was then concentrated under a reduced pressure. The resultant residue was purified by silica gel column chromatography (2:1 ethyl acetate/acetone) to obtain 0.80 g of 1-propionyl-2-(nitroimino)-3-[(tetrahydro-3-furanyl)methyl]hexahydropyrimidine.
Reaction SMILES: [OH-].[K+].Br[CH2:4][CH2:5]Br.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH3:26][N:27]1[CH2:32][CH2:31][N:30]([C:33]2[CH:38]=[CH:37][C:36](B3OC(C)(C)C(C)(C)O3)=[CH:35][N:34]=2)[CH2:29][CH2:28]1>C1COCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:26][N:27]1[CH2:28][CH2:29][N:30]([C:33]2[CH:38]=[CH:37][C:36]([CH:4]=[CH2:5])=[CH:35][N:34]=2)[CH2:31][CH2:32]1
Reactant: BrCCBr
Reactant: CN1CCN(c2ccc(B3OC(C)(C)C(C)(C)O3)cn2)CC1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: C=Cc1ccc(N2CCN(C)CC2)nc1
Temperature: 95 °C

Procedure:
A sealed, degassed mixture of powdered KOH (123 mg, 2.2 mmol) and 1,2-dibromoethane (0.05 mL, 0.6 mmol) in anh THF (2 mL) under Ar was heated under microwave irradiation at 95° C. for 70 min. The reaction mixture was then cooled to rt and treated with Pd(OAc)2 (5.0 mg, 0.022 mmol), PPh3 (11.5 mg, 0.044 mmol), 1-methyl-4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine (120 mg, 0.39 mmol) and degassed MeOH (2 mL). The sealed reaction mixture was heated again under microwave irradiation at 95° C. for 60 min. The crude mixture was concentrated under reduced pressure and purified by prepTLC (SiO2 10% MeOH/DCM) to provide the title compound a colorless gum (0.18 g, quantitative): 1H NMR (400 MHz, CD3OD) δ ppm 8.07 (d, J=2.26 Hz, 1 H), 7.73 (dd, J=8.91, 2.38 Hz, 1 H), 6.82 (d, J=9.03 Hz, 1 H), 6.62 (dd, J=17.82, 11.04 Hz, 1 H), 5.63 (d, 1 H), 5.12 (d, J=10.79 Hz, 4 H), 3.52-3.66 (m, 4 H), 2.50-2.61 (m, 4 H), 2.35 (s, 3H); MS ESI 204.0 [M+H]+, calcd for [C12H17N3+H]+ 204.3.