Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[C:6]2[N:14]([CH3:15])[CH:13]=[CH:12][C:7]=2[C:8](Cl)=[N:9][CH:10]=1)=[O:4].[Cl:16][C:17]1[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=1)[NH:20][CH3:21].CS(O)(=O)=O>O1CCOCC1>[CH3:1][O:2][C:3]([C:5]1[C:6]2[N:14]([CH3:15])[CH:13]=[CH:12][C:7]=2[C:8]([N:20]([C:19]2[CH:22]=[CH:23][CH:24]=[C:17]([Cl:16])[CH:18]=2)[CH3:21])=[N:9][CH:10]=1)=[O:4]
Reactant: CNc1cccc(Cl)c1
Reactant: COC(=O)c1cnc(Cl)c2ccn(C)c12
Agent: CS(=O)(=O)O
Solvent: C1COCCO1
Product: COC(=O)c1cnc(N(C)c2cccc(Cl)c2)c2ccn(C)c12
Yield: 47.7 %

Procedure:
To a solution of 4-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-carboxylic acid methyl ester (0.5 g) in 1,4-dioxane (5 ml) was added 3-chloro-N-methyl aniline (0.629 g) and methanesulfonic acid (0.289 ml). The mixture was irradiated under microwave conditions at 180° C. for 30 min. 1,4-dioxane was removed in vacuo and the residue purified by MDAP to give the title compound (350 mg).
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[N:7]=[C:8]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[S:9][C:10]=1[C:11]([C:13]#[C:14][CH2:15][O:16][CH3:17])=[O:12].[H][H]>C(O)C.[C].[Pd]>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[N:7]=[C:8]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:23])([CH3:22])[CH3:24])[S:9][C:10]=1[C:11]([CH2:13][CH2:14][CH2:15][O:16][CH3:17])=[O:12]
Reactant: [H][H]
Reactant: COCC#CC(=O)c1sc(NC(=O)OC(C)(C)C)nc1-c1ccco1
Agent: [Pd]
Solvent: CCO
Product: COCCCC(=O)c1sc(NC(=O)OC(C)(C)C)nc1-c1ccco1
Yield: 99.9 %

Procedure:
Compound 414 (92.3 mg, 0.255 mmol) was dissolved in ethanol (5 mL), and 10% palladium-carbon (15.8 mg) was added thereto, followed by stirring in an atmosphere of hydrogen at room temperature for 1.5 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to afford the entitled Compound 415 (93.3 mg, 100%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=O)[CH2:10][N:11]2[C:15]([C:16]([O:18]C)=O)=[CH:14][C:13]3[CH:20]=[CH:21][S:22][C:12]2=3)=[CH:5][CH:4]=1.[CH2:24]([NH2:27])[CH2:25][NH2:26]>O1CCOCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]23[NH:27][CH2:24][CH2:25][N:26]2[C:16](=[O:18])[C:15]2[N:11]([C:12]4[S:22][CH:21]=[CH:20][C:13]=4[CH:14]=2)[CH2:10]3)=[CH:7][CH:8]=1
Reactant: NCCN
Reactant: COC(=O)c1cc2ccsc2n1CC(=O)c1ccc(OC)cc1
Solvent: C1COCCO1
Product: COc1ccc(C23Cn4c(cc5ccsc54)C(=O)N2CCN3)cc1
Yield: 73.7 %

Procedure:
To a solution of methyl 6-[2-(4-methoxyphenyl)-2-oxoethyl]-6H-thieno[2,3-b]pyrrole-5-carboxylate (100 mg, 0.30 mmol) in 1,4-dioxane (10 mL) was added ethylenediamine (0.78 mL, 12 mmol) and the mixture heated at reflux. The reaction was monitored by LCMS. Upon completion, the reaction mixture was concentrated in vacuo and the residue purified by flash chromatography (1 to 6% methanol-dichloromethane) to yield 11a-(4-methoxyphenyl)-2,3,11,11a-tetrahydro-1H,5H-imidazo[1,2-a]thieno[3′,2′:4,5]pyrrolo[1,2-d]pyrazin-5-one (75 mg, 73% yield) as a white solid. ESI-MI m/z [M+H]+ 340.25. 1H NMR (400 MHz, CDCl3) δ 7.31 (d, J=8.7 Hz, 2H), 7.14 (s, 1H), 6.96 (d, J=5.3 Hz, 1H), 6.82 (d, J=5.3 Hz, 1H), 6.78 (d, J=8.7 Hz, 2H), 4.52 (d, J=11.7 Hz, 1H), 4.25 (d, J=11.7 Hz, 1H), 4.02-3.89 (m, 1H), 3.73 (s, 3H), 3.64-3.51 (m, 1H), 3.37-3.26 (m, 1H), 3.08-2.94 (m, 1H).
Reaction SMILES: [Br:1][C:2]1[C:7](=[O:8])[N:6]([C:9]2[CH:10]=[C:11]([CH:18]=[CH:19][C:20]=2[CH3:21])[C:12](N(OC)C)=[O:13])[C:5]([CH3:22])=[N:4][C:3]=1[O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([CH3:31])[N:26]=1.[C:32]([Mg]Cl)#[CH:33]>O1CCCC1>[Br:1][C:2]1[C:7](=[O:8])[N:6]([C:9]2[CH:10]=[C:11]([C:12](=[O:13])[C:32]#[CH:33])[CH:18]=[CH:19][C:20]=2[CH3:21])[C:5]([CH3:22])=[N:4][C:3]=1[O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([CH3:31])[N:26]=1
Reactant: CON(C)C(=O)c1ccc(C)c(-n2c(C)nc(OCc3cccc(C)n3)c(Br)c2=O)c1
Reactant: C#C[Mg]Cl
Solvent: C1CCOC1
Product: C#CC(=O)c1ccc(C)c(-n2c(C)nc(OCc3cccc(C)n3)c(Br)c2=O)c1

Procedure:
To a solution of 3-[5-bromo-2-methyl-4-(6-methyl-pyridin-2-ylmethoxy)-6-oxo-6H-pyrimidin-1-yl]-N-methoxy-4,N-dimethyl-benzamide from Step C (60 mg, 0.12 mmol) in tetrahydrofuran (2 mL), cooled using an ice water bath, was added ethynylmagnesium chloride, 0.5M in tetrahydrofuran, (0.5 mL, 0.25 mmol) in a drop-wise manner. Additional Grignard reagent was added as necessary to ensure full product formation. After thirty minutes, the reaction was quenched into ice cold water and extracted with ethyl acetate. The organic layer was washed with saturated ammonium chloride, water and brine and dried over magnesium sulfate. The slurry was filtered and concentrated. The crude material was used without any additional purification.
Reaction SMILES: [CH2:1]([NH:8][C:9](=O)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].B.CSC.Cl>C1COCC1>[C:11]1([CH2:10][CH2:9][NH:8][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: CCCCCCCNC(=O)Cc1ccccc1
Agent: B
Agent: Cl
Solvent: C1CCOC1
Solvent: CSC
Product: CCCCCCCNCCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 70.1 %

Procedure:
N-Heptyl-2-phenylacetamide (0.886 g, 3.797 mmol) was dissolved in THF (10 ml) and was cooled to zero degrees under argon atmosphere. (Methylthio)methane compound with borane (1:1) (0.721 g, 9.492 mmol) was added and the mixture was refluxed for 5 hours. After the mixture was cooled to room temperature, 5 ml HCl (10%) was gently added and was stirred overnight. The solvent was removed by evaporation. EtOAc (20 ml) was added and the organic phase was washed with K2CO3 (2M, 2×20 ml). The crude was purified by flash chromatography (started with isocratic heptane/EtOAc 50/50 and then the EtOAc concentration was increased to 100%, (silica gel 60 0.004-0.063 mm). The product containing fractions were pooled and the EtOAc was removed by evaporation to give 0.584 g of N-(2-phenylethyl)heptan-1-amine (yield 70.1%).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][NH:9][C:10](SC)=[CH:11][C:12](=[O:17])[C:13]([F:16])([F:15])[F:14])=[CH:4][CH:3]=1.[CH3:20][NH:21][CH3:22]>C(O)C>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]([N:21]([CH3:22])[CH3:20])=[CH:11][C:12](=[O:17])[C:13]([F:16])([F:15])[F:14])=[CH:4][CH:3]=1
Reactant: CSC(=CC(=O)C(F)(F)F)NCc1ccc(Cl)nc1
Reactant: CNC
Solvent: CCO
Product: CN(C)C(=CC(=O)C(F)(F)F)NCc1ccc(Cl)nc1
Temperature: 20 °C

Procedure:
The product of Example 6, 1-(6-chloro-3-pyridylmethyl) amino-1-methylthio-4,4,4-trifluoro-1-buten-3-one, (2.0 g, 0.0065 mol) and dimethylamine (1.5 ml) were dissolved in ethanol (15 ml). The resulting solution was heated under reflux for 2 hours. The resulting mixture was cooled to ambient temperature (20° C.) and solvent removed by evaporation under reduced pressure. The solid residue was recrystallized from ether to give the product, 1-(6-chloro-3-pyridylmethyl)amino-1-dimethylamino-4,4,4-trifluoro-1-buten-3-one, in a yield of 0.3 g (16%), melting point 85° C.
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([O:9][CH3:10])[CH:5]=[CH:4][C:3]=1[C:11](=[O:16])[CH2:12][CH:13]([CH3:15])[CH3:14].C=O.Cl.[CH3:20]NC.C(O)(=O)C>C1C=CC=CC=1.CN(C=O)C>[CH2:20]=[C:12]([CH:13]([CH3:14])[CH3:15])[C:11]([C:3]1[CH:4]=[CH:5][C:6]([O:9][CH3:10])=[C:7]([Cl:8])[C:2]=1[Cl:1])=[O:16]
Reactant: CNC
Reactant: COc1ccc(C(=O)CC(C)C)c(Cl)c1Cl
Agent: C=O
Agent: Cl
Solvent: c1ccccc1
Solvent: CN(C)C=O
Solvent: CC(=O)O
Product: C=C(C(=O)c1ccc(OC)c(Cl)c1Cl)C(C)C
Temperature: 0 °C

Procedure:
A stirred mixture of 2',3'-dichloro-4'-methoxyisovalerophenone (261.6 g., 1.0 mole), paraformaldehyde (75.0 g., 2.5 mole), dimethylamine hydrochloride (327 g., 4.0 mole) and acetic acid (26 ml.) is heated on a steam bath for 18 hours, treated with DMF (500 ml.), heated an additional three hours, then poured into ice water (1.7 l.). The crude product which separates is dissolved in benzene (600 ml.) and dried over sodium sulfate. Evaporation of the benzene affords 237 g. of 2-methylene-2',3'-dichloro-4'-methoxyisovalerophenone which melts at 46°-51° C. and is used in Step C without further purification.
Reaction SMILES: [Mg].[CH2:2](Br)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9]/[CH:10]=[CH:11]\[CH2:12]/[CH:13]=[CH:14]\[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].CN([CH:24]=[O:25])C>CCOCC>[CH:24](=[O:25])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9]/[CH:10]=[CH:11]\[CH2:12]/[CH:13]=[CH:14]\[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]
Reactant: CCCCC/C=C\C/C=C\CCCCCCCCBr
Reactant: CN(C)C=O
Agent: [Mg]
Solvent: CCOCC
Product: CCCCC/C=C\C/C=C\CCCCCCCCC=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 218.2 %

Procedure:
A 100 mL round bottom flask charged with magnesium turnings (462 mg, 19.0 mmol) and a stir bar was dried with a high temperature heat gun for 5 minutes. The flask was cooled to room temperature under nitrogen then charged with THF (25 mL). Linoleyl bromide (1.9 g, 5.76 mmol) was added drop wise and the solution was heated to 45° C. for 3 hours under nitrogen. Upon completion, DMF (1.3 mL, 16.7 mmol) was added slowly and the solution was stirred for 1 hour at room temperature. The solution was diluted with ether (75 mL) and washed with 5% HCl (3×50 mL). The ether solution was dried on magnesium sulfate, filtered and concentrated in vacuo to dryness. The residue was purified by column chromatography (column: 2″×10″; eluted with 2% ether/hexanes) to afford the title compound as a colorless oil (3.5 g, 83%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[CH2:6]Br.[C:11]1([C:17]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[N:18][CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[OH-].[Na+].C1COCC1>O>[C:11]1([C:17]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[N:18][C@H:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:6][C:5]2[CH:8]=[CH:9][CH:10]=[C:3]([O:2][CH3:1])[CH:4]=2)[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: COc1cccc(CBr)c1
Reactant: CCOC(=O)CN=C(c1ccccc1)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)[C@H](Cc1cccc(OC)c1)N=C(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 48 h
Yield: 77.1 %

Procedure:
To a 100-mL round-bottomed flask was added 3-methoxybenzyl bromide (0.73 mL, 5.22 mmol, Sigma-Aldrich, St. Louis, Mo.), ethyl N-(diphenylmethylene)glycinate (1.40 g, 5.22 mmol, Acros, Pittsburgh, Pa.), 5 M sodium hydroxide (5.22 mL, 26.1 mmol) and THF (20 mL). The reaction mixture was stirred at room temperature for 2 d. After that time, the mixture was diluted with water (30 mL) and extracted with EtOAc (2×60 mL). The organic extracts were washed with saturated NaCl (30 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as light-yellow oil. Purification by silica gel chromatography, eluting with 20% EtOAc in hexanes gave ethyl N-(diphenylmethylidene)-3-methoxyphenylalaninate (1.56 g).
Reaction SMILES: [CH:1]1([NH:6][C:7]2[CH:8]=[CH:9][CH:10]=[C:11]3[C:15]=2[NH:14][C:13]([C:16]2[S:17][CH2:18][C@@H:19]([CH2:21]O)[N:20]=2)=[CH:12]3)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1>>[CH:1]1([NH:6][C:7]2[CH:8]=[CH:9][CH:10]=[C:11]3[C:15]=2[NH:14][C:13]([C:16]2[S:17][CH2:18][C@@H:19]([CH2:21][N:23]4[CH2:27][CH2:26][CH2:25][CH2:24]4)[N:20]=2)=[CH:12]3)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: OC[C@@H]1CSC(c2cc3cccc(NC4CCCC4)c3[nH]2)=N1
Reactant: C1CCNC1
Product: c1cc(NC2CCCC2)c2[nH]c(C3=N[C@H](CN4CCCC4)CS3)cc2c1

Procedure:
[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol prepared in Example 2 and pyrrolidine were reacted according to the same procedure as Example 156 to give the title compound.
Reaction SMILES: N(C(C)(C)C#N)=NC(C)(C)C#N.[Br:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=1[CH3:22].CC1(C)N([Br:29])C(=O)N(Br)C1=O.S([O-])([O-])(=O)=S.[Na+].[Na+]>ClC1C=CC=CC=1>[Br:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=1[CH2:22][Br:29]
Reactant: COc1ccc(Br)c(C)c1
Reactant: CC1(C)C(=O)N(Br)C(=O)N1Br
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: Clc1ccccc1
Product: COc1ccc(Br)c(CBr)c1
Temperature: 70 °C
Reaction time: 2 h

Procedure:
Azobisisobutyronitrile (0.60 g) was added to a mixture of 2-bromo-5-methoxytoluene (77.38 g, 384 mmol), 5,5-dimethy-1,3-dibromohydantoin (57.5 g, 200 mmol) and chlorobenzene (1500 mL), followed by stirring at 70° C. for 2 hours. Azobisisobutyronitrile (0.60 g) was added thereto again and stirred for another 1 hour. A 10% aqueous sodium thiosulfate solution (500 mL) was added to the reaction mixture, and the resulting mixture was washed with a saturated aqueous sodium chloride solution. The mixture washed was dried over anhydrous magnesium sulfate and then concentrated to dryness to obtain a crude product of 2-bromo-5-methoxybenzyl bromide. Thereto was added 100 mL of ice-cooled hexane to obtain a homogeneous slurry, which was filtered. The residue was washed with 100 mL of ice-cooled hexane and then dried under reduced pressure to obtain 65.75 g (235 mmol, 61.1%) of 2-bromo-5-methoxybenzyl bromide.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH:16]([OH:22])[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23]([C:27]1[CH:32]=[CH:31][C:30](O)=[CH:29][CH:28]=1)([CH3:26])([CH3:25])[CH3:24].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH:16]([O:22][C:30]2[CH:31]=[CH:32][C:27]([C:23]([CH3:26])([CH3:25])[CH3:24])=[CH:28][CH:29]=2)[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)c1ccc(O)cc1
Reactant: CCOC(=O)C(O)Cc1ccc(OCc2ccccc2)cc1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: CCOC(=O)C(Cc1ccc(OCc2ccccc2)cc1)Oc1ccc(C(C)(C)C)cc1
Yield: 41.7 %

Procedure:
In a similar manner to that described in Example 122, a reaction was carried out using ethyl 3-(4-benzyloxyphenyl)lactate (5.00 g), which is the product of Reference example 1(b), 4-t-butylphenol (2.50 g), triphenylphosphine (5.24 g) and a solution of diethylazodicarboxylate in toluene (40%, 8.80 ml) and the reaction mixture was treated to afford the desired compound (3.00 g) as a colorless oil.
Reaction SMILES: [NH2:1][O:2]C1CCCCO1.[C:9]1([S:15]([N:18]2[C:26]3[C:21](=[CH:22][C:23]([CH:27]=[CH:28][C:29]([OH:31])=O)=[CH:24][CH:25]=3)[CH2:20][CH2:19]2)(=[O:17])=[O:16])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.C(O)(C(F)(F)F)=O>CN(C=O)C.CO>[C:9]1([S:15]([N:18]2[C:26]3[C:21](=[CH:22][C:23]([CH:27]=[CH:28][C:29]([NH:1][OH:2])=[O:31])=[CH:24][CH:25]=3)[CH2:20][CH2:19]2)(=[O:17])=[O:16])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: O=C(O)C=Cc1ccc2c(c1)CCN2S(=O)(=O)c1ccccc1
Reactant: NOC1CCCCO1
Agent: F[P-](F)(F)(F)(F)F
Agent: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Solvent: CCN(CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: CN(C)C=O
Product: O=C(C=Cc1ccc2c(c1)CCN2S(=O)(=O)c1ccccc1)NO
Temperature: 25 °C
Reaction time: 1 h
Yield: 94.2 %

Procedure:
NH2OTHP (0.05 g, 0.44 mmol) was added to a solution of 15 (0.12 g, 0.37 mmol), PyBOP (0.20 g, 0.39 mmol), triethylamine (0.12 ml, 0.88 mmol) in DMF (1.5 mL). The reaction mixture was stirred at room temperature for 1 h before it was quenched with water, followed by extraction with EtOAc (15 mL×3). The combined organic layer was dried over anhydrous MgSO4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography (CH2Cl2:CH3OH=30:1:1% NH3(aq)) to give a white solid, which was treated with TFA (1.13 ml, 15.21 mmol) in the presence of CH3OH (25 mL) and stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure to give a white residue, which was recrystallized by CH3OH to afford Compound 12 (0.12 g). 1H NMR (500 MHz, CD3OD): δ 2.91 (t, J=8.5 Hz, 2H), 3.96 (t, J=8.4 Hz, 2H), 6.32 (d, J=15.8 Hz, 1H), 7.32 (s, 1H), 7.37-7.39 (m, 1H), 7.46 (d, J=15.7 Hz, 1H), 7.50-7.53 (m, 2H), 7.58-7.64 (m, 2H), 7.82 (d, J=7.8 Hz, 2H). MS (EI) m/z: 170 (100%), 344 (M+, 3.21%). HRMS (EI) for C17H16N2O4S (M+): calcd, 344.0831. found, 344.0829.
Reaction SMILES: [CH:1]1[CH2:8][CH2:7][CH:6]=[CH:5][CH2:4][CH2:3][CH:2]=1>CCCCCC>[CH2:8]=[CH:1][CH2:2][CH2:3][CH:4]=[CH:5][CH2:1][CH2:8][CH:7]=[CH:6][CH2:5][CH2:4][CH2:3][CH3:2]
Reactant: C1=CCCC=CCC1
Solvent: CCCCCC
Product: C=CCCC=CCCC=CCCCC

Procedure:
disproportionating 1,5-cyclooctadiene and 1-hexane in the presence of a disproportionation catalyst under disproportionation conditions suitable to produce 1,5,9-tetradecatriene;
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:35]2[CH:40]=[CH:39][C:38](Br)=[CH:37][CH:36]=2)([O:14][CH2:15][C:16]2[N:20]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:19]3[CH:29]=[C:30]([F:34])[C:31]([F:33])=[CH:32][C:18]=3[N:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:42]([C:44]1[CH:45]=[C:46](B(O)O)[CH:47]=[CH:48][CH:49]=1)#[N:43].C1(C)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:35]2[CH:40]=[CH:39][C:38]([C:48]3[CH:47]=[CH:46][CH:45]=[C:44]([C:42]#[N:43])[CH:49]=3)=[CH:37][CH:36]=2)([O:14][CH2:15][C:16]2[N:20]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:19]3[CH:29]=[C:30]([F:34])[C:31]([F:33])=[CH:32][C:18]=3[N:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: N#Cc1cccc(B(O)O)c1
Reactant: CC(C)(C)OC(=O)N1CCC(OCc2nc3cc(F)c(F)cc3n2COCC[Si](C)(C)C)(c2ccc(Br)cc2)CC1
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: CCOC(C)=O
Solvent: CCO
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N1CCC(OCc2nc3cc(F)c(F)cc3n2COCC[Si](C)(C)C)(c2ccc(-c3cccc(C#N)c3)cc2)CC1
Temperature: 80 °C
Yield: 34.6 %

Procedure:
A mixture of 0.116 g of 4-(4-bromo-phenyl)-4-[5,6-difluoro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-ylmethoxy]-piperidine-1-carboxylic acid tert-butyl ester 61 (˜0.18 mmol, 1 eq), 0.032 g of 3-cyanophenylboronic acid (0.215 mmol, 1.2 eq), and 0.040 g of Pd(PPh3)4 (0.036 mmol, 20 mol %) with 3 mL of toluene, 2 mL of ethanol and 1 mL of 2M aqueous Na2CO3 was heated at 80° C. for 20 h. The reaction was allowed to cool to room temperature, diluted with 25 mL of ethyl acetate and washed with 25 mL of saturated brine. The organic layer was dried over Na2SO4, filtered and concentrated by rotary evaporation to give the crude product which was purified by flash silica gel chromatography eluting with a gradient of 5-50% ethyl acetate in hexane to give 0.042 g of 4-(3′-cyano-biphenyl-4-yl)-4-[5,6-difluoro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-ylmethoxy]-piperidine-1-carboxylic acid tert-butyl ester 62 as a pale foam.
Reaction SMILES: [CH3:1][Si:2]([CH3:13])([CH3:12])[C:3]1[O:4][CH:5]=[C:6](CCC=O)[CH:7]=1.C(C(CCCCCCCC)(C([O-])=O)C([O-])=O)CCCCCCC.C(O)(=O)C.N1CCCCC1>O1CCCC1>[CH3:1][Si:2]([CH3:13])([CH3:12])[C:3]1[O:4][CH:5]=[CH:6][CH:7]=1
Reactant: C[Si](C)(C)c1cc(CCC=O)co1
Agent: CCCCCCCCC(CCCCCCCC)(C(=O)[O-])C(=O)[O-]
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: C1CCNCC1
Product: C[Si](C)(C)c1ccco1

Procedure:
3-(2-Trimethylsilyl-4-furyl)propan-1-al is reacted with dioctylmalonate in tetrahydrofuran in the presence of acetic acid and piperidine to give 3-[4,4-di (carbooctanoxy)-3-butenyl]- 5-trimethylsilylfuran which is treated with cold aqueous potassium hydroxide to give 3-(4-carboxy-4-carbooctanoxy-3-butenyl)-5-trimethylsilylfuran.
Reaction SMILES: [N:1]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[N:4]([C:10]1[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][CH:11]=1)[CH2:3][CH2:2]2.[C:17]1([S:23](Cl)(=[O:25])=[O:24])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[N:1]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[N:4]([C:10]1[CH:15]=[CH:14][C:13]([NH:16][S:23]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)(=[O:25])=[O:24])=[CH:12][CH:11]=1)[CH2:3][CH2:2]2
Reactant: Nc1ccc(N2CCN3CCC2CC3)cc1
Reactant: O=S(=O)(Cl)c1ccccc1
Product: O=S(=O)(Nc1ccc(N2CCN3CCC2CC3)cc1)c1ccccc1

Procedure:
Was prepared by Method G from 4-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-phenylamine and phenylsulfonyl chloride. Mp. 267° C.
Reaction SMILES: Cl.[CH:2]12[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:10][CH:4]([CH2:5]3)[CH:3]1[CH2:12][NH2:13])[CH2:9]2.[CH3:14][C:15]1([CH3:40])[CH2:20][CH:19]([CH2:21][N:22]2[CH2:27][CH2:26][N:25]([C:28]3[CH:38]=[CH:37][C:31]([C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:30][CH:29]=3)[CH2:24][CH2:23]2)[C:18](=O)[CH2:17][CH2:16]1.C([O-])(=O)C.[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[CH:2]12[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:10][CH:4]([CH2:5]3)[CH:3]1[CH2:12][NH:13][CH:18]1[CH2:17][CH2:16][C:15]([CH3:40])([CH3:14])[CH2:20][CH:19]1[CH2:21][N:22]1[CH2:23][CH2:24][N:25]([C:28]3[CH:38]=[CH:37][C:31]([C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:30][CH:29]=3)[CH2:26][CH2:27]1)[CH2:9]2
Reactant: NCC1C2CC3CC(C2)CC1C3
Reactant: CCOC(=O)c1ccc(N2CCN(CC3CC(C)(C)CCC3=O)CC2)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: CC(=O)[O-]
Agent: Cl
Solvent: CC(Cl)Cl
Product: CCOC(=O)c1ccc(N2CCN(CC3CC(C)(C)CCC3NCC3C4CC5CC(C4)CC3C5)CC2)cc1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
(2-Adamantylmethyl)amine hydrochloride salt (195 mg), ethyl 4-(4-((5,5-dimethyl-2-oxocyclohexyl)methyl)piperazin-1-yl)benzoate (200 mg) and sodium acetate (44 mg) were suspended in anhydrous dichloroethane. The reaction mixture was stirred at room temperature for 20 minutes, followed by the addition of sodium triacetoxyborohydride (228 mg). The reaction mixture was stirred at room temperature overnight. The reaction was quenched with saturated NaHCO3 aqueous solution. The reaction mixture was extracted with ethyl acetate, and washed with water and brine. The organic phase was dried over Na2SO4, filtered, and concentrated. The residue was purified by flash column purification with 0-5% methanol/dichloromethane to afford the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:3]=1[CH2:4][C:5]([C:13]([O:15][CH3:16])=[CH2:14])([C:7]1[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=1)[OH:6]>[Pd].C(O)(=O)C>[Cl:1][C:2]1[CH:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:3]=1[CH2:4][C:5]([CH:13]([O:15][CH3:16])[CH3:14])([C:7]1[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=1)[OH:6]
Reactant: C=C(OC)C(O)(Cc1ccc(Cl)cc1Cl)c1cccnc1
Agent: [Pd]
Solvent: CC(=O)O
Product: COC(C)C(O)(Cc1ccc(Cl)cc1Cl)c1cccnc1
Reaction time: 7 h

Procedure:
A mixture of 2.0 g of α-(2,4-dichlorobenzyl)-α-(1-methoxyvinyl)-3-pyridinemethanol (see Example 3, 2nd end product), 0.2 g of hydrogenation catalyst (5% palladium on carbon) and 40 ml of acetic acid is stirred for 7 hours at room temprature under a hydrogen atmosphere at normal pressure. Thereafter, the hydrogenation catalyst is removed by filtration, the filtrate is freed from solvent under reduced pressure, the residue is taken up in a saturated sodium bicarbonate solution and the solution is extracted with ethyl acetate. The organic phase is evaporated and the residue is crystallized from methylene chloride/n-hexane. In this manner there is obtained α-(2,4-dichlorobenzyl)-α-(1-methoxyethyl)-3-pyridinemethanol as colorless crystals, m.p. 94°-95° C.