Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH2:12]O)[C:5]2[O:10][CH2:9][CH2:8][O:7][C:6]=2[CH:11]=1.C(N(CC)CC)C.S(Cl)([Cl:23])=O>ClCCl>[Cl:23][CH2:12][C:4]1[C:5]2[O:10][CH2:9][CH2:8][O:7][C:6]=2[CH:11]=[C:2]([F:1])[CH:3]=1
Reactant: OCc1cc(F)cc2c1OCCO2
Reactant: O=S(Cl)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Fc1cc(CCl)c2c(c1)OCCO2

Procedure:
A solution of (7-fluoro-2,3-dihydro-1,4-benzodioxine-5-yl)methanol (436 mg, 2.36 mmol) and triethylamine (400 μL, 2.83 mmol) in dichloromethane (20 mL) was cooled to 0° C. and then slowly added thionyl chloride (260 μL, 3.55 mmol) and stirred for 45 min. The reaction mixture was partitioned with water (100 mL) and ethyl acetate (100 mL). The organic layer was washed with aqueous saturated sodium bicarbonate, brine, and then dried over anhydrous magnesium sulfate and concentrated to give crude 5-(chloromethyl)-7-fluoro-2,3-dihydro-1,4-benzodioxine as a colorless oil. The crude residue was taken up in N,N-dimethylformamide (10 mL) and was added potassium cyanide (460 mg, 7.08 mmol). The reaction mixture was heated to 60° C. and stirred for 5 h, at which time it was cooled to room temperature and partitioned with water (100 mL) and ethyl acetate (150 mL). The organic layer was washed with 10% citric acid (3×100 mL) and then aqueous saturated sodium bicarbonate (2×100 mL). The organic solution was further washed with brine, dried over anhydrous magnesium sulfate and concentrated to give 430 mg (94% over 2 steps) of (7-fluoro-2,3-dihydro-1,4-benzodioxin-5-yl)acetonitrile as an off-white powder. GCMS for C10H8FNO2: 193 (M+).
Reaction SMILES: [O-][CH2:2]C.[Na+].[Br:5][C:6]1[C:7]([CH2:14][C:15]#[N:16])=[C:8]([CH:11]=[CH:12][CH:13]=1)[C:9]#[N:10].IC>C(O)C.O1CCCC1>[Br:5][C:6]1[C:7]([CH:14]([C:15]#[N:16])[CH3:2])=[C:8]([CH:11]=[CH:12][CH:13]=1)[C:9]#[N:10]
Reactant: N#CCc1c(Br)cccc1C#N
Reactant: CC[O-]
Agent: [Na+]
Solvent: CI
Solvent: CCO
Solvent: C1CCOC1
Product: CC(C#N)c1c(Br)cccc1C#N
Temperature: 25 °C
Reaction time: 6.5 h
Yield: 67.5 %

Procedure:
A solution of sodium ethoxide (8.76 mL, 23.5 mmol, 21 wt % ethanol solution) in ethanol (10 mL) was cooled to 0° C. under argon atmosphere, and thereto was added dropwise a solution of 3-bromo-2-(cyanomethyl)benzonitrile (4.33 g, 19.6 mmol) and iodomethane (1.46 mL, 23.5 mmol) in tetrahydrofuran (10 mL) over 30 minutes, and then the mixture was stirred at room temperature for 6.5 hours. The mixture was concentrated under reduced pressure, and then the residue was neutralized by 2 mol/L hydrochloric acid, and extracted with ethyl acetate three times. The organic layer was combined, washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane=10%→40%) to give 3-bromo-2-(1-cyanoethyl)benzonitrile (3.11 g, 67%) as a yellow viscous material.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].[Na].[OH:8][C:9]([CH:14]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[O:22][CH3:23])=[CH:10][N+:11]([O-])=O.O.[OH-].[Na+]>O1CCCC1>[OH:8][CH:9]([CH:14]([O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[O:22][CH3:23])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH2:10][NH2:11]
Reactant: COc1ccccc1OC(C(O)=C[N+](=O)[O-])c1ccccc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: COc1ccccc1OC(c1ccccc1)C(O)CN
Yield: 47.5 %

Procedure:
To a suspension of 0.55 g of LiAlH4 in 18 ml of anhydrous tetrahydrofuran there was added dropwise at 30° C. over 4 hours 1 g of 2-hydroxy-1-nitro-3-phenyl-3-(2-methoxy-phenoxy)-propene sodium salt in 70 ml of anhydrous tetrahydrofuran. After the addition, the mixture was cooled and decomposed with water, 15% NaOH, water. It was then filtered; the solid was washed with tetrahydrofuran and the solvent evaporated to dryness. The residue was dissolved in ethyl ether and extracted with 3% HCl, made alkaline with 20% NaOH NaOH and re-extracted with ethyl ether. The organic solution was then washed with water, dried over Na2SO4, filtered and evaporated to dryness. A small quantity of isopropyl ether was then used to ground it to obtain 2-hydroxy-3-(2-methoxy-phenoxy)-3-phenyl-propylamine (0.4 g); melting point 84°-110° C. (R=47.2%) as mixture of two diastereoisomers. The mixture was separated by column chromatography on silica gel (phase: CHCl3 /CH 3 OH/32% NH4OH-150/50/2) to obtain two distinct diastereoisomers having melting point of 126°-129° C. (diastereoisomer with Rf<) and 105°-110° C. respectively (diastereoisomer with Rf>)
Reaction SMILES: [CH3:1][C:2]([CH3:6])([CH3:5])[CH:3]=O.Cl.[Cl:8][C:9]1[CH:22]=[C:21]([O:23][CH2:24][CH:25]=[C:26]([Cl:28])[Cl:27])[CH:20]=[C:19]([Cl:29])[C:10]=1[O:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][O:17][NH2:18].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>N1C=CC=CC=1>[Cl:8][C:9]1[CH:22]=[C:21]([O:23][CH2:24][CH:25]=[C:26]([Cl:28])[Cl:27])[CH:20]=[C:19]([Cl:29])[C:10]=1[O:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][O:17][N:18]=[CH:3][C:2]([CH3:6])([CH3:5])[CH3:1]
Reactant: NOCCCCCOc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl
Reactant: CC(C)(C)C=O
Agent: Cl
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Solvent: c1ccncc1
Product: CC(C)(C)C=NOCCCCCOc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl
Temperature: 25 °C
Reaction time: 1 h
Yield: 96.2 %

Procedure:
To a mixture of 0.07 g of trimethylacetaldehyde and 5 ml of pyridine was added 0.30 g of O-(5-(2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)pentyl)hydroxylamine hydrochloride. After stirring at room temperature for 1 hour, the reaction mixture was poured into 5% aqueous citric acid solution, and extracted twice with ethyl acetate. The ethyl acetate layers were combined, washed with water, dried over anhydrous magnesium sulfate, and concentrated to give a crude product. This crude product was subjected to silica gel chromatography, which afforded 0.31 g (yield, 96.8%) of trimethylacetaldehyde O-(5-(2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)pentyl)oxime, nD23.0 1.5178.
Reaction SMILES: C([O:3][C:4](=[O:19])[CH2:5][O:6][C:7]1[C:16]2[CH2:15][CH2:14][CH:13](Br)[C:12](=O)[C:11]=2[CH:10]=[CH:9][CH:8]=1)C.[C:20]1([CH:26]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:27][C:28]([NH2:30])=[S:29])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>>[C:20]1([CH:26]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:27][C:28]2[S:29][C:13]3[CH2:14][CH2:15][C:16]4[C:11](=[CH:10][CH:9]=[CH:8][C:7]=4[O:6][CH2:5][C:4]([OH:3])=[O:19])[C:12]=3[N:30]=2)[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: NC(=S)CC(c1ccccc1)c1ccccc1
Reactant: CCOC(=O)COc1cccc2c1CCC(Br)C2=O
Product: O=C(O)COc1cccc2c1CCc1sc(CC(c3ccccc3)c3ccccc3)nc1-2
Yield: 19 %

Procedure:
Using ethyl[(6-bromo-5,6,7,8-tetrahydro-5-oxo-1-naphthalenyl)oxy]acetate and 3,3-diphenylthiopropionamide, the procedure of Example 52 was otherwise repeated to synthesize the title compound. Yield 19%. Amorphous solid.
Reaction SMILES: [CH:1]1([NH:4][C:5](=[O:8])[CH2:6][SH:7])[CH2:3][CH2:2]1.C[O-].[Na+].Cl[C:13]1[N:20]=[C:19]([O:21][CH2:22][CH2:23][O:24][CH3:25])[C:18]([Cl:26])=[C:17]([CH3:27])[C:14]=1[C:15]#[N:16].ClC1C(Cl)=NC(OCCOC)=C(C=1C)C#N>CO.CCOC(C)=O.CCCCCC.O>[CH:1]1([NH:4][C:5]([C:6]2[S:7][C:13]3=[N:20][C:19]([O:21][CH2:22][CH2:23][O:24][CH3:25])=[C:18]([Cl:26])[C:17]([CH3:27])=[C:14]3[C:15]=2[NH2:16])=[O:8])[CH2:3][CH2:2]1
Reactant: COCCOc1nc(Cl)c(C#N)c(C)c1Cl
Reactant: O=C(CS)NC1CC1
Agent: COCCOc1nc(Cl)c(Cl)c(C)c1C#N
Agent: C[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CO
Solvent: CCCCCC
Product: COCCOc1nc2sc(C(=O)NC3CC3)c(N)c2c(C)c1Cl
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 10 %

Procedure:
To a solution of N-cyclopropyl-2-mercapto-acetamide (0.452 g, 3.45 mmol) in MeOH (5 ml) is added sodium methoxide solution (25% wt. in MeOH)(0.589 ml, 2.58 mmol). The resulting solution is stirred at room temperature for 30 minutes, then treated with a 1:1 mixture of 2,5-dichloro-6-(2-methoxy-ethoxy)-4-methyl-nicotinonitrile and 5,6-dichloro-2-(2-methoxy-ethoxy)-4-methyl-nicotinonitrile (0.450 g, 1.72 mmol). The reaction vessel is sealed, heated at 100° C. for 2.5 hours, and cooled to room temperature. The reaction mixture is poured over water (60 ml), then extracted with EtOAc (2×40 ml). The combined organic layers are washed with brine (50 ml), dried (anhydrous magnesium sulfate), filtered, and concentrated to give a yellow-brown solid. Flash chromatography (1.5:1 hexane:EtOAc) affords the title compound as a cream colored solid (53 mg, 10%). Mass (m/z): 356.1 (M++1).
Reaction SMILES: [CH2:1]([C:8]1[S:12][C:11]([NH2:13])=[N:10][C:9]=1[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:22][O:23][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][C:32]=1[O:33][CH3:34])[C:27](Cl)=[O:28]>>[CH2:1]([C:8]1[S:12][C:11]([NH:13][C:27](=[O:28])[C:26]2[CH:30]=[CH:31][C:32]([O:33][CH3:34])=[C:24]([O:23][CH3:22])[CH:25]=2)=[N:10][C:9]=1[C:14]1[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc(C(=O)Cl)cc1OC
Reactant: COc1ccc(-c2nc(N)sc2Cc2ccccc2)cc1
Product: COc1ccc(-c2nc(NC(=O)c3ccc(OC)c(OC)c3)sc2Cc2ccccc2)cc1
Yield: 46.5 %

Procedure:
A procedure similar to that in Example 4 was used. 5-benzyl-4-(4-methoxy-phenyl)-thiazol-2-ylamine prepared in Example 1 and 3,4-dimethoxy-benzoyl chloride prepared in the step 1 were used as starting materials, allowed to react at room temperature overnight, followed by post-treatment to obtain a crude product, which was purified by a silica gel column chromatography eluted with petroleum ether and ethyl acetate (10:1) to obtain a product as a white solid in a yield of 46.5%, mp: 179-180└. 1H-NMR (CDCl3, 400 MHz) δ: 3.79 (3H, s, OCH3), 3.83 (3H, s, OCH3), 3.89 (3H, s, OCH3), 4.22 (2H, s, CH2), 6.73 (1H, d, J=8.40 Hz, ArH), 6.78 (2H, d, J=8.40 Hz, ArH), 7.26˜7.35 (9H, m, ArH), 11.03 (1H, br, CONH); EI-MS m/e (%): 460.1 (M+, 99), 164.9 (100); HREI-MS Calcd. for C26H24N2O4S: 460.1457. found: 460.1463. Anal. Calcd. for C26H24N2O4S: C, 67.81; H, 5.25; N, 6.08. found: C, 67.62; H, 5.20; N, 6.50.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[C:5]2[CH:17]=[O:18].I[CH2:20][CH:21]([CH3:23])[CH3:22].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH2:20]([O:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[C:5]2[CH:17]=[O:18])[CH:21]([CH3:23])[CH3:22]
Reactant: CC(C)CI
Reactant: O=Cc1nn(C2CCCCO2)c2ccc(O)cc12
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CC(C)COc1ccc2c(c1)c(C=O)nn2C1CCCCO1
Temperature: 60 °C
Reaction time: 8 h
Yield: 34.5 %

Procedure:
A mixture of (R/S) 5-hydroxy-1-(oxan-2-yl)-1H-indazole-3-carbaldehyde (590 mg, 2.40 mmol, 1.00 equiv), 1-iodo-2-methylpropane (882.6 mg, 4.80 mmol, 2.00 equiv) and cesium carbonate (782 mg, 2.39 mmol, 1.00 equiv) and N,N-dimethylformamide (15 mL) was stirred under nitrogen overnight at 60° C. The reaction was cooled to room temperature then quenched by the addition of 50 mL of water/ice. The resulting mixture was extracted with 3×50 mL of ethyl acetate. The combined organic layers was washed with 3×50 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eluted with 15-35% of ethyl acetate in petroleum ether to give 250 mg (35%) of (R/S) 5-iso-butoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carbaldehyde as a yellow solid. 1H NMR (300 MHz, CDCL3): δ 10.25 (s, 1H), 7.65 (d, J=2.1 Hz, 1H), 7.59 (d, J=9.0 Hz, 1H), 7.16 (dd, J=9.0 Hz, 2.1 Hz, 1H), 5.83 (d, J=6.9 Hz, 1H), 4.05 (m, 1H), 3.83 (d, J=6.6 Hz, 2H), 3.80 (m, 1H), 2.60 (m, 1H), 2.15 (m, 3H), 1.80 (m, 3H), 1.08 (d, J=6.9 Hz, 6H) ppm. LCMS (method D, ESI): RT=1.77 min, m/z=303.1 [M+H]+.
Reaction SMILES: C([O:3][C:4](=[O:26])[CH2:5][CH2:6][NH:7][C:8]([NH:10][CH2:11][CH2:12][CH2:13][N:14]1[CH2:19][CH2:18][N:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:16][CH2:15]1)=[O:9])C.[OH-].[Na+].Cl>CC(C)=O>[C:20]1([N:17]2[CH2:18][CH2:19][N:14]([CH2:13][CH2:12][CH2:11][NH:10][C:8](=[O:9])[NH:7][CH2:6][CH2:5][C:4]([OH:26])=[O:3])[CH2:15][CH2:16]2)[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: CCOC(=O)CCNC(=O)NCCCN1CCN(c2ccccc2)CC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)=O
Product: O=C(O)CCNC(=O)NCCCN1CCN(c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
19.0 g (0.0524 mol) of this ester are dissolved in 250 ml of acetone and mixed with 52.4 ml of N sodium hydroxide solution. The mixture is stirred at room temperature for 18 hours, 52.4 ml of N hydrochloric acid are added, the mixture is evaporated and the residue is re-crystallised from methanol, to yield 3-{3-[3-(4-phenyl-1-piperazinyl)-propyl]-ureido}propionic acid. Yield: 15.9 g (90% of theory). Melting range: 169°-171° C. ##STR27##
Reaction SMILES: [CH:1]1([N:5]2[CH2:10][CH2:9][N:8]([C:11]([C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][C:17]([C:22]([N:24]3[CH2:29][CH2:28][C:27]([F:31])([F:30])[CH2:26][CH2:25]3)=[O:23])=[CH:16]4)=[O:12])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[H-].[Na+].CS(O[CH2:39][C:40]([F:43])([F:42])[F:41])(=O)=O>CN(C)C=O>[CH:1]1([N:5]2[CH2:6][CH2:7][N:8]([C:11]([C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[N:18]([CH2:39][C:40]([F:43])([F:42])[F:41])[C:17]([C:22]([N:24]3[CH2:25][CH2:26][C:27]([F:30])([F:31])[CH2:28][CH2:29]3)=[O:23])=[CH:16]4)=[O:12])[CH2:9][CH2:10]2)[CH2:2][CH2:3][CH2:4]1
Reactant: O=C(c1ccc2[nH]c(C(=O)N3CCC(F)(F)CC3)cc2c1)N1CCN(C2CCC2)CC1
Reactant: CS(=O)(=O)OCC(F)(F)F
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C(c1ccc2c(c1)cc(C(=O)N1CCC(F)(F)CC1)n2CC(F)(F)F)N1CCN(C2CCC2)CC1
Yield: 50 %

Procedure:
The title compound was synthesized in analogy to example 51, from [5-(4-cyclobutyl-piperazine-1-carbonyl)-1H-indol-2-yl]-(4,4-difluoro-piperidin-1-yl)-methanone (example 41), sodium hydride and 2,2,2-trifluoroethyl methanesulfonate in N,N-dimethylformamide, to give the desired product as a colorless foam (50%).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[CH:11]1[C:16]([OH:17])=[CH:15][CH:14]=[C:13]([CH3:18])[CH:12]=1.C([O-])([O-])=O.[K+].[K+].CN(C=O)C>O>[CH3:18][C:13]1[CH:12]=[CH:11][C:16]([O:17][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][CH:6]=[CH:5]3)=[CH:15][CH:14]=1
Reactant: Brc1ccc2[nH]ccc2c1
Reactant: Cc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1ccc(Oc2ccc3[nH]ccc3c2)cc1
Temperature: 160 °C
Yield: 51.5 %

Procedure:
A mixture of 5-bromo-1H-indole (98.0 mg, 0.500 mmol), p-cresol (108 mg, 1.00 mmol), Cu (32.0 mg, 0.500 mmol), K2CO3 (138 mg, 1.00 mL) and DMF (1.00 mL) was heated at 160° C. for 12 h. The resulting crude mixture was diluted with water (40 ML), the aqueous layer was extracted with CH2Cl2 (3×20 mL). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by preparative TLC using hexane:EtOAc (4:1) to give the desired product 5-(4-methylphenoxy)-1H-indole (57.5 mg, 51.5%): ESMS m/e: 224.0 (M+H)+.
Reaction SMILES: [C:1]1([S:7]([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)(=[NH:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:16]([N:18]([CH2:22][CH3:23])[CH2:19][CH2:20]Cl)[CH3:17]>>[CH2:16]([N:18]([CH2:22][CH3:23])[CH2:19][CH2:20][N:9]=[S:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)([C:10]1[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=1)=[O:8])[CH3:17]
Reactant: CCN(CC)CCCl
Reactant: N=S(=O)(c1ccccc1)c1cccnc1
Product: CCN(CC)CCN=S(=O)(c1ccccc1)c1cccnc1
Yield: 46 %

Procedure:
In a manner analogous to that described in Example 1, Stage 3, from S-phenyl-S-(3-pyridyl)-sulphoximide and 2-diethylaminoethyl chloride, there is obtained, in a yield of 46% of theory, N-(2-diethylaminoethyl)-S-phenyl-S-(3-pyridyl)-sulphoximide. The corresponding dibenzoyltartrate, after recrystallisation from isoporopanol, melts at 130° C.
Reaction SMILES: [CH2:1]([NH2:5])[CH2:2][CH2:3][CH3:4].[C:6]1(=O)[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1>C1(C)C=CC=CC=1>[CH2:1]([N:5]=[C:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCN
Reactant: O=C1CCCCC1
Solvent: Cc1ccccc1
Product: CCCCN=C1CCCCC1
Temperature: 25 °C
Yield: 83.5 %

Procedure:
1-Butylamine (9.88 mL, 0.1 mol) and toluene (15 mL) was added to cyclohexanone (10.36 mL, 0.1 mol) and the reaction mixture was heated under reflux for 24 h under dehydration condition by using Dienstark reflux condenser packing molecular sieves 4A. After the reaction mixture was cooled to room temperature, evaporated under reduced pressure. The residue was distilled under reduced pressure (2 mmHg) at 64° C. to give butyl-cyclohexylideneamine (1-015-01) (12.8 g, 84%) as a colorless oil.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:13]2[N:17]([C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)[N:16]=[C:15]([C:24]([OH:26])=O)[CH:14]=2)[CH:5]=[C:6]([O:8][C:9]([F:12])([F:11])[F:10])[CH:7]=1.ClC1C=C(C2N(C3C=CC=CN=3)N=C(C(N3CC(=O)NC3)=O)C=2)C=C(F)C=1.[S:54]1[CH2:58][CH2:57][NH:56][CH2:55]1>>[F:1][C:2]1[CH:3]=[C:4]([C:13]2[N:17]([C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)[N:16]=[C:15]([C:24]([N:56]3[CH2:57][CH2:58][S:54][CH2:55]3)=[O:26])[CH:14]=2)[CH:5]=[C:6]([O:8][C:9]([F:12])([F:11])[F:10])[CH:7]=1
Reactant: O=C(O)c1cc(-c2cc(F)cc(OC(F)(F)F)c2)n(-c2cccnc2)n1
Reactant: C1CSCN1
Agent: O=C1CN(C(=O)c2cc(-c3cc(F)cc(Cl)c3)n(-c3ccccn3)n2)CN1
Product: O=C(c1cc(-c2cc(F)cc(OC(F)(F)F)c2)n(-c2cccnc2)n1)N1CCSC1

Procedure:
200 mg (0.55 mmol) of the compound of Example 34A is reacted analogously to the synthesis of the compound of Example 1 with 0.05 ml (0.60 mmol) of thiazolidine. 193 mg (80% of theory) of the title compound is obtained.
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7]Br)=[CH:5][CH:4]=1.[CH2:11]1[C:16](=[O:17])[S:15][CH2:14][C:12]1=[O:13].[OH-].[K+].Cl>O1CCOCC1>[OH:13][C:12]1[CH2:14][S:15][C:16](=[O:17])[C:11]=1[CH2:7][C:6]1[CH:9]=[CH:10][C:3]([S:2][CH3:1])=[CH:4][CH:5]=1
Reactant: O=C1CSC(=O)C1
Reactant: CSc1ccc(CBr)cc1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: C1COCCO1
Product: CSc1ccc(CC2=C(O)CSC2=O)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 26.4 %

Procedure:
To a suspension of 4-methylthiobenzyl bromide (5.6 g. 25.8 mmol), thiotetronic acid (3.0 g, 25.8 mmol) in dioxane (50 ml), was added aqueous potassium hydroxide (25.8 mL). The mixture was stirred at temperatures in the range of 65°-70° C. for 3 hours. Then, the mixture was cooled to room temperature, poured into H20, acidified with HCl (2N) and extracted with EtOAc. The organic extracts were dried over MgSO4. Evaporation and purification by flash chromatography on acid washed (5% H3PO4 in MeOH) silica gel (eluting solvent hexane/EtOAc 1/3) gave a white solid (1.72 g, 26.5%): m.p. 206°-208° C.
Reaction SMILES: [H-].[Na+].[C:3]1([C:9]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:10][CH2:11][C@@H:12]([OH:16])[CH2:13][CH:14]=[CH2:15])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:29](Br)[CH:30]=[CH2:31].[Cl-].[NH4+]>C1COCC1>[CH2:31]([O:16][C@@H:12]([CH2:13][CH:14]=[CH2:15])[CH2:11][O:10][C:9]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1)[CH:30]=[CH2:29]
Reactant: C=CC[C@H](O)COC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: C=CCBr
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: C=CCO[C@@H](CC=C)COC(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 45 °C
Yield: 98 %

Procedure:
A 60% suspension of sodium hydride in mineral oil (268.9 g, 6.72 mole, 1.5 eq.) was suspended in 2.8 L of dry THF under N2 and a solution (S)-1-(triphenylmethoxy)-4-penten-2-ol (1543 g, 4.48 mole) in 5.6 L of dry THF was added at room temperature. The resultant mixture was stirred at room temperature for 1.5 hours and then 770 mL (8.89 mole, 2.0 eq.) of freshly distilled allyl bromide was added over 20 minutes. The reaction was heated to 45° C. for 1-2 hours. The reaction mixture was cooled to 15°-20° C. and 2 L of an aqueous saturated solution of ammonium chloride was slowly added to quench the excess base. The resultant mixture was diluted with 1 L of ethyl acetate and 1 L of water and the organic layer was isolated. The aqueous layer was back-extracted with 500 mL of ethyl acetate and the combined organic layers were dried (MgSO4) and evaporated in vacuo to give 1867 g (98%) of (S)-1,1',1"-[[[2-(2-propenyloxy)-4-pentenyl]oxy]methylidyne]tris[benzene] as a yellow oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH2:9].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].CO/[CH:22]=[C:23](\[C:30]([O:32][CH3:33])=[O:31])/[CH:24]=[CH:25]/[C:26](OC)=[O:27]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:26](=[O:27])[CH:25]=[CH:24][C:23]([C:30]([O:32][CH3:33])=[O:31])=[CH:22]1
Reactant: CO/C=C(/C=C/C(=O)OC)C(=O)OC
Reactant: Nc1c(F)cccc1F
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COC(=O)c1ccc(=O)n(-c2c(F)cccc2F)c1
Reaction time: 0.5 h
Yield: 20.2 %

Procedure:
To a solution of (2,6-difluorophenyl)amine (15.5 g) in THF (140 mL) was added dropwise an 1 M THF solution of lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide (120 mL) at 0° C. under a nitrogen atmosphere, and the mixture was stirred at the same temperature for 30 min. To the solution was added a solution of dimethyl (2E,4Z)-4-(methoxymethylene)-2-pentenedioate (20 g) in THF (60 mL) at 0° C., and the resulting mixture was stirred at the same temperature for 2 hr. The reaction was quenched with a mixture of EtOAc (200 mL) and 0.5 M HCl (200 mL). The aqueous layer was extracted with EtOAc (200 mL). The organic layers were combined, washed with brine, dried over MgSO4, filtered and evaporated in vacuo. The residue was diluted with MeOH (100 mL), and to the resulting solution was added 28% sodium methoxide in MeOH (38.6 mL). The resulted mixture was heated to reflux for 6 hr under a nitrogen atmosphere. The reaction mixture was concentrated under reduced pressure and the residue was partitioned between EtOAc (200 mL) and 1 M HCl (300 mL). The aqueous layer was separated and extracted with EtOAc (200 mL). The organic layers were combined, washed with saturated aqueous NaHCO3 (300 mL) and brine successively, dried over MgSO4 and evaporated in vacuo. The residue was triturated with IPE, and the precipitates produced were collected by filtration to give methyl 1-(2,6-difluorophenyl)-6-oxo-1,6-dihydro-3-pyridinecarboxylate (5.34 g).
Reaction SMILES: Cl[CH2:2][C:3]1[N:4]=[C:5]([C:9]2[CH:10]=[C:11]([CH:16]=[CH:17][CH:18]=2)[C:12]([O:14][CH3:15])=[O:13])[O:6][C:7]=1[CH3:8].[OH:19][C:20]1[CH:27]=[CH:26][C:23]([CH:24]=[O:25])=[CH:22][CH:21]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH:24]([C:23]1[CH:26]=[CH:27][C:20]([O:19][CH2:2][C:3]2[N:4]=[C:5]([C:9]3[CH:10]=[C:11]([CH:16]=[CH:17][CH:18]=3)[C:12]([O:14][CH3:15])=[O:13])[O:6][C:7]=2[CH3:8])=[CH:21][CH:22]=1)=[O:25]
Reactant: COC(=O)c1cccc(-c2nc(CCl)c(C)o2)c1
Reactant: O=Cc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)c1cccc(-c2nc(COc3ccc(C=O)cc3)c(C)o2)c1
Temperature: 90 °C
Reaction time: 2 h
Yield: 93.1 %

Procedure:
A mixture of methyl 3-(4-chloromethyl-5-methyl-1,3-oxazol-2-yl)benzoate (2.0 g), 4-hydroxybenzaldehyde (0.87 g), potassium carbonate (0.98 g) and N,N-dimethylformamide (50 mL) was stirred at 90° C. for 2 hrs. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated to give methyl 3-{4-[(4-formylphenoxy)methyl]-5-methyl-1,3-oxazol-2-yl}benzoate as colorless crystals (2.33 g, yield 94%). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 103-104° C.