Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6](I)[C:5]([F:9])=[C:4]([Cl:10])[C:3]=1[F:11].C([Mg]Cl)(C)C.[F:17][C:18]([F:25])([F:24])[C:19](OCC)=[O:20]>O1CCCC1.COC(C)(C)C>[Cl:10][C:4]1[C:5]([F:9])=[C:6]([C:19](=[O:20])[C:18]([F:25])([F:24])[F:17])[CH:7]=[C:2]([Cl:1])[C:3]=1[F:11]
Reactant: Fc1c(Cl)cc(I)c(F)c1Cl
Reactant: CCOC(=O)C(F)(F)F
Agent: CC(C)[Mg]Cl
Solvent: COC(C)(C)C
Solvent: C1CCOC1
Product: O=C(c1cc(Cl)c(F)c(Cl)c1F)C(F)(F)F
Temperature: 25 °C
Reaction time: 1 h
Yield: 69.2 %

Procedure:
1,3-Dichloro-2,4-difluoro-5-iodobenzene (4.0 g) was dissolved in tetrahydrofuran and cooled to −10 degree. A 2.0 M solution of isopropylmagnesium chloride in tetrahydrofuran (10 ml) was added dropwise via a dropping funnel. The reaction mixture was stirred for 1 hour at same temperature. A solution of ethyl trifluoroacetate (2.76 g) in tetrahydrofuran (6 ml) was added dropwise and the reaction mixture was allowed to warm to ambient temperature. The reaction mixture was diluted with t-butyl methyl ether and washed with 1 N NaOH and then brine. The combined extracts were dried over magnesium sulfate. After filtered off, the filtrate was concentrated in vacuo to give crude product which was purified with Kugel-Rohr to give 1-(3,5-dichloro-2,4-difluorophenyl)-2,2,2-trifluoroethanone (2.5 g).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:9]2[C:13]([CH:14]=[C:15]3[S:19][C:18](=[O:20])[NH:17][C:16]3=[O:21])=[CH:12][N:11]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[N:10]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH2:34](Br)[CH3:35].O>CN(C)C=O>[F:8][C:6]1[CH:5]=[C:4]([C:9]2[C:13]([CH:14]=[C:15]3[S:19][C:18](=[O:20])[N:17]([CH2:34][CH3:35])[C:16]3=[O:21])=[CH:12][N:11]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[N:10]=2)[CH:3]=[C:2]([F:1])[CH:7]=1
Reactant: O=C1NC(=O)C(=Cc2cn(-c3ccccc3)nc2-c2cc(F)cc(F)c2)S1
Reactant: CCBr
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCN1C(=O)SC(=Cc2cn(-c3ccccc3)nc2-c2cc(F)cc(F)c2)C1=O
Temperature: 25 °C
Reaction time: 4 h
Yield: 98.7 %

Procedure:
5-[3-(3,5-Difluoro-phenyl)-1-phenyl-1H-pyrazol-4-ylmethylene]-thiazolidine-2,4-dione (Compound No. 58, 0.10 g, 0.21 mmol) was dissolved in 1.0 mL of anhydrous dimethylformamide. Sodium carbonate (26.5 mg, 0.25 mmol) was added under nitrogen atmosphere and ethyl bromide (23.90 μL, 0.32 mmol) was added 10 minutes later. The mixture was stirred for 4 hours at room temperature. Water was added after the reaction was completed. The resultant solid was washed with water (10 mL×3 times). The solid was dried to obtain 85.3 mg (80%) of the target product.
Reaction SMILES: [N:1]1[N:2]=[C:3]([C:19]2[CH:24]=[CH:23][C:22]([CH2:25][OH:26])=[CH:21][CH:20]=2)[N:4]2[C:10]=1[C:9]1[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=1[NH:7][C:6]1[N:15]=[CH:16][CH:17]=[CH:18][C:5]2=1.C(N(C(C)C)CC)(C)C.[CH3:36][S:37](Cl)(=[O:39])=[O:38]>ClCCl>[CH3:36][S:37]([O:26][CH2:25][C:22]1[CH:23]=[CH:24][C:19]([C:3]2[N:4]3[C:5]4[CH:18]=[CH:17][CH:16]=[N:15][C:6]=4[NH:7][C:8]4[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=4[C:10]3=[N:1][N:2]=2)=[CH:20][CH:21]=1)(=[O:39])=[O:38]
Reactant: CS(=O)(=O)Cl
Reactant: OCc1ccc(-c2nnc3n2-c2cccnc2Nc2ccccc2-3)cc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CS(=O)(=O)OCc1ccc(-c2nnc3n2-c2cccnc2Nc2ccccc2-3)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a suspension of (4-(9H-benzo[f]pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]diazepin-3-yl)phenyl)methanol (1.35 g, 3.95 mmol) in dichloromethane (70 mL) was added diisopropylethylamine (1.72 mL, 9.89 mmol) and methanesulfonyl chloride (0.767 mL, 9.89 mmol). The reaction mixture was stirred at room temperature for 30 minutes. The mixture was washed with water (50 mL), saturated aqueous sodium bicarbonate solution (50 mL) and water (3×50 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo, yielding the 4-(9H-benzo[f]pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]diazepin-3-yl)benzyl methanesulfonate as a light yellow solid (1.7 g, quantitative). M.p.=252-253° C.; 400 MHz 1H NMR (DMSO-d6) δ: 8.82 (br.s, 1H), 8.22 (dd, J=4.8, 1.6 Hz, 1H), 7.97 (dd, J=7.6, 1.6 Hz, 1H), 7.6-7.4 (m, 5H), 7.36 (dd, J=8.0, 1.2 Hz, 1H), 7.2-7.1 (m, 2H), 6.92 (dd, J=7.6, 4.4 Hz, 1H), 5.33 (s, 2H), 3.28 (s, 3H); LCMS [M+H]: 420.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH2:11][CH:12]([CH3:14])[CH3:13])[C:5]([OH:7])=O.O[NH:16][C:17](=[NH:26])[C:18]1[CH:23]=[CH:22][C:21]([CH2:24][OH:25])=[CH:20][CH:19]=1.O.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[O:7][N:26]=[C:17]([C:18]3[CH:23]=[CH:22][C:21]([CH2:24][OH:25])=[CH:20][CH:19]=3)[N:16]=2)[CH:8]=[CH:9][C:10]=1[CH2:11][CH:12]([CH3:14])[CH3:13]
Reactant: CC(C)Cc1ccc(C(=O)O)cc1Cl
Reactant: N=C(NO)c1ccc(CO)cc1
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)Cc1ccc(-c2nc(-c3ccc(CO)cc3)no2)cc1Cl
Temperature: 122.5 °C

Procedure:
N,N-Dicyclohexylcarbodiimide (1.07 g, 0.0052 mol) is added to a solution of 3-chloro-4-isobutylbenzoic acid (0.74 g, 0.0035 mol), N-hydroxy-4-hydroxymethylbenzamidine (0.867 g, 0.0052 mol) and N-hydroxybenzotriazole monohydrate (0.798 g, 0.0052 mol) in N,N-dimethylformamide (15 mL). The reaction mixture is heated at 120-125° C. for 2 hrs. It is then cooled to 0-5° C., filtered and washed with dichloromethane (2×20 mL). The filtrate is evaporated under reduced pressure and the residue is treated with demineralized water (20 mL). It is extracted with ethyl acetate (2×30 mL) and the combined extract is dried over sodium sulfate. Removal of solvent under reduced pressure gives a crude residue which is purified by column chromatography (silica gel 230-400, ethyl acetate:toluene, 15:85) to give {4-[5-(3-chloro-4-isobutylphenyl)-[1,2,4]-oxadiazol-3-yl]-phenyl}methanol.
Reaction SMILES: [CH3:1][C:2]1([CH3:13])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=[O:12])[CH2:4][CH2:3]1.[Br:14]Br>C(Cl)Cl>[CH3:1][C:2]1([CH3:13])[C:11]2[C:6](=[CH:7][C:8]([Br:14])=[CH:9][CH:10]=2)[C:5](=[O:12])[CH2:4][CH2:3]1
Reactant: BrBr
Reactant: CC1(C)CCC(=O)c2ccccc21
Solvent: ClCCl
Product: CC1(C)CCC(=O)c2cc(Br)ccc21
Temperature: 70 °C
Yield: 80 %

Procedure:
A 100 ml three-necked flask, fitted with an efficient reflux condenser and drying tube, and addition funnel, was charged with a mixture of AlC3 9.5 g (71.4 mmol) and 3 ml of CH2Cl2. The 3,4-dihydro-4,4-dimethyl-1(2H)-naphthalenone (5.0 g, 28.7 mmol), was added dropwise with stirring (Caution: Exothermic Reaction!) to the mixture at room temperature. Bromine, 5.5 g (34.5 mmol), was then added very slowly, and the resulting mixture stirred for 2 hours at room temperature. (Note: if stirring stops, the mixture can be warmed to 70° C. until stirring resumes.) The reaction was then quenched by the slow addition of ice-cold 6M HCl. The mixture was extracted with Et2O and the combined organic layers washed with water, saturated aqueous NaHCO3, and saturated NaCl, before being dried over MgSO4. Removal of the solvent under reduced pressure, and distillation of the residue afforded 5.8 g (80%) of the product as a pale-yellow oil which solidified on standing, bp: 140° C./0.4 mm Hg. 1H NMR (CDCl3): δ 8.11 (1H, d, J=3.0 Hz), 7.61 (1H, dd, J=3.0, 9.0 Hz), 7.31 (1H, d, J=9.0 Hz), 2.72 (2H, t, J=6.0 Hz), 2.01 (2H, t, J=6.0 Hz), 1.28 (6H, s).
Reaction SMILES: [OH:1][CH2:2]/[C:3](/[CH2:13][CH2:14]/[CH:15]=[C:16](\[CH3:23])/[CH2:17][CH2:18][CH:19]=[C:20]([CH3:22])[CH3:21])=[CH:4]/[CH2:5][CH2:6]/[C:7](/[CH3:12])=[CH:8]\[C:9]([OH:11])=O.[NH2:24][CH2:25][CH2:26][N:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1>CN(C)C=O>[N:27]1([CH2:26][CH2:25][NH:24][C:9](=[O:11])/[CH:8]=[C:7](/[CH3:12])\[CH2:6][CH2:5]/[CH:4]=[C:3](/[CH2:2][OH:1])\[CH2:13][CH2:14]/[CH:15]=[C:16](\[CH3:23])/[CH2:17][CH2:18][CH:19]=[C:20]([CH3:22])[CH3:21])[CH2:31][CH2:30][CH2:29][CH2:28]1
Reactant: NCCN1CCCC1
Reactant: CC(C)=CCC/C(C)=C/CC/C(=C\CC/C(C)=C\C(=O)O)CO
Solvent: CN(C)C=O
Product: CC(C)=CCC/C(C)=C/CC/C(=C\CC/C(C)=C\C(=O)NCCN1CCCC1)CO

Procedure:
Following the same manner as in Example 9, the reaction was conducted using 1.0 g of (E,Z,E), (E,E,E), (Z,Z,E) and (Z,E,E)-7-hydroxymethyl-3,11,15-trimethyl-2,6,10,14-hexadecatetraenoic acid and 450 mg of 1-(2-aminoethyl)pyrrolidine in 6.0 ml of N,N-dimethylformamide and the reaction mixture was extracted with chloroform. The chloroform layer was washed with aqueous sodium hydrogencarbonate and extracted with dilute hydrochloric acid. The hydrochloric acid layer was neutralized with sodium hydrogencarbonate and extracted with chloroform. The chloroform layer was washed with water, dried and the solvent was distilled off. The residue was purified by a column chromatography using alumina (20 g) to afford 1.0 g of the end product.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:20]3[CH2:21][C:7]4([CH2:11][N:10]([CH2:12][CH:13]5[CH2:17][CH2:16][CH2:15][CH2:14]5)[CH2:9][CH:8]4[C:18]4[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=43)[C:6]=2[CH:26]=1.C(N(CC)CC)C.[C:34](Cl)(=[O:36])[CH3:35].[OH-].[Na+]>C(Cl)(Cl)Cl>[C:34]([NH:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:20]3[CH2:21][C:7]4([CH2:11][N:10]([CH2:12][CH:13]5[CH2:14][CH2:15][CH2:16][CH2:17]5)[CH2:9][CH:8]4[C:18]4[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=43)[C:6]=2[CH:26]=1)(=[O:36])[CH3:35]
Reactant: CC(=O)Cl
Reactant: Nc1ccc2c(c1)C13CC2c2ccccc2C1CN(CC1CCCC1)C3
Agent: [Na+]
Agent: [OH-]
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: CC(=O)Nc1ccc2c(c1)C13CC2c2ccccc2C1CN(CC1CCCC1)C3
Temperature: 25 °C
Reaction time: 8 h
Yield: 38.7 %

Procedure:
To a solution of 3.0 g (8.7 mmoles) of 5amino-2-cyclopentylmethyl-2,3,8,12b-tetrahydro-1H-3a, 8-methanodibenzo[3,4:6,7]cyclohepta[1,2-c]pyrrole and 10 ml of triethylamine in 25 ml of chloroform, cooled to 0°, was added dropwise 2.5 g (31.8 mmoles) of acetyl chloride. The reaction mixture was stirred overnight at room temperature and then for 30 minutes with 2.5 N aqueous sodium hydroxide. The organic layer was separated and the aqueous layer was extracted with methylene chloride. The combined organic extracts were washed with water, dried over potassium carbonate, and concentrated under vacuum. The residue was chromatographed on silica gel CC No. 7 with 57% methanol in chloroform to give 1.3 g of 5-acetamido-2-cyclopentylmethyl- 2,3,8,12b-tetrahydro1H-3a,8-methanodibenzo[3,4:6,7]cyclohepta[1,2-c]pyrrole as an oil; nmr spectrum: δ 1.0-4.0 (m, 19); 2.1 (s, 3); 6.8-7.8 (m, 7).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[CH:13]=[C:12]([C:14]([C:21]3[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:23][CH:22]=3)=[CH:15][CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[N:11](S(C3C=CC=CC=3)(=O)=O)[C:8]2=[N:9][CH:10]=1)=[O:4].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.C(OCC)(=O)C>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[CH:13]=[C:12]([C:14]([C:21]3[CH:22]=[CH:23][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:25][CH:26]=3)=[CH:15][CH:16]3[CH2:17][CH2:18][CH2:19][CH2:20]3)[NH:11][C:8]2=[N:9][CH:10]=1)=[O:4]
Reactant: COC(=O)c1cnc2c(c1)cc(C(=CC1CCCC1)c1ccc(S(C)(=O)=O)cc1)n2S(=O)(=O)c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COC(=O)c1cnc2[nH]c(C(=CC3CCCC3)c3ccc(S(C)(=O)=O)cc3)cc2c1
Yield: 82.9 %

Procedure:
A mixture of 1-benzenesulfonyl-2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-vinyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methyl ester (prepared as in Example 3, 4 g, 7.1 mmol) in tetrahydrofuran (5 mL) and a tetrabutylammonium fluoride solution in tetrahydrofuran (1 M, 15 mL, 15 mmol) was stirred at room temperature for 12 h. The mixture was diluted with ethyl acetate (150 mL), washed with a saturated aqueous ammonium chloride solution and brine, dried over anhydrous sodium sulfate and then concentrated in vacuo to afford 2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-vinyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methyl ester (2.5 g, 83.3%) as a white solid: LC/MS m/e calcd for C23H24N2O4S [M+H]+ 425.52, observed 424.9.
Reaction SMILES: [CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][C:9]([CH2:11][CH2:12][NH:13][CH3:14])=[CH:10][C:5]=2[S:4](=[O:15])[CH2:3]1.[Cl:16][CH2:17][CH2:18]Br.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1>[CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][C:9]([CH2:11][CH2:12][N:13]([CH3:14])[CH2:18][CH2:17][Cl:16])=[CH:10][C:5]=2[S:4](=[O:15])[CH2:3]1
Reactant: CNCCc1ccc2c(c1)S(=O)CN2C
Reactant: ClCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Product: CN(CCCl)CCc1ccc2c(c1)S(=O)CN2C
Temperature: 60 °C
Reaction time: 48 h

Procedure:
In a ground-necked flask, 6 mmol of 3-methyl-6-(2-(N-methylamino)ethyl]benzothiazolinone are dissolved in 50 ml of dioxane, 20 mmol of 1-chloro-2-bromoethane and 20 mmol of potassium carbonate. The mixture is stirred for 48 hours at a temperature of 60° C. After cooling, the mixture is evaporated and the reaction medium is extracted with chloroform after adding water. After washing, drying and evaporation of the organic phase, 3 -methyl-6-{2-[N-methyl-N-(2-chloroethyl) amino]ethyl}benzothiazolinone is obtained, which product is transferred to a ground-necked flask. A catalytic amount of potassium iodide, 25 cm3 of methanol and 10 cm3 of chloroform are added. A stream of gaseous ammonia is bubbled into the solution to the point of saturation and a reflux condenser is then fitted. The temperature is stabilized at 50° C. with an oil bath and the mixture is then left stirring magnetically for 72 hours. After cooling, the reaction mixture is evaporated on a water bath under vacuum. The residue is ground with distilled water acidified with 5% HCl solution, and then drained. The filtrate is recovered, washed with ethyl acetate and then alkalinized with 10% sodium hydroxide solution. It is extracted with chloroform, leaving the 2 phases agitating for 1/2 hour, and the organic phase is washed with distilled water and then dried over calcium chloride. The organic phase is evaporated on a water bath under vacuum, the residue is then taken up in absolute ethanol, a stream of gaseous HCl is bubbled through and the mixture is then evaporated to dryness on a water bath under vacuum. The product is dried and then recrystallized.
Reaction SMILES: N12CCCN=C1CCCCC2.[Br:12][C:13]1[N:18]([CH3:19])[C:17](=[O:20])[NH:16][C:15](=[O:21])[C:14]=1[CH3:22].Cl[CH2:24][O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C(#N)C>[CH2:26]([O:25][CH2:24][N:16]1[C:15](=[O:21])[C:14]([CH3:22])=[C:13]([Br:12])[N:18]([CH3:19])[C:17]1=[O:20])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: Cc1c(Br)n(C)c(=O)[nH]c1=O
Reactant: ClCOCc1ccccc1
Solvent: CC#N
Solvent: C1CCC2=NCCCN2CC1
Product: Cc1c(Br)n(C)c(=O)n(COCc2ccccc2)c1=O
Reaction time: 90 h

Procedure:
1,8-Diazabicyclo[5.4.0]undec-7-ene (6.00 mL, 40.2 mmol) was added to a suspension of C2 (8.00 g, 36.5 mmol) and benzyl chloromethyl ether (95%, 5.86 mL, 40.2 mmol) in acetonitrile (100 mL). After 90 hours at room temperature, the reaction mixture was concentrated in vacuo, diluted with water, and extracted several times with ethyl acetate. The combined organic layers were washed sequentially with water and with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Silica gel chromatography (Gradient: 10% to 25% ethyl acetate in heptane) afforded the product as a white solid. Yield: 10.1 g, 29.8 mmol, 82%. 1H NMR (400 MHz, CDCl3) δ 7.24-7.39 (m, 5H), 5.52 (s, 2H), 4.71 (s, 2H), 3.63 (s, 3H), 2.11 (s, 3H).
Reaction SMILES: [N:1]1([C:6]2[CH:11]=[CH:10][C:9]([C:12]([CH:14]3[CH2:19][CH2:18][N:17]([CH2:20][C:21]4[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=4)[CH2:16][CH2:15]3)=[O:13])=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.[BH4-].[Na+].O>CO>[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([CH:12]([CH:14]3[CH2:19][CH2:18][N:17]([CH2:20][C:21]4[CH:22]=[CH:23][N:24]=[CH:25][CH:26]=4)[CH2:16][CH2:15]3)[OH:13])=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: O=C(c1ccc(-n2ccnc2)cc1)C1CCN(Cc2ccncc2)CC1
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: OC(c1ccc(-n2ccnc2)cc1)C1CCN(Cc2ccncc2)CC1
Yield: 43.5 %

Procedure:
To a stirred solution of [4-(1H-imidazol-1-yl)phenyl][1-(4-pyridylmethyl)-4-piperidinyl]methanone (5.70 g, 16.5 mmol) in methanol (100 ml) at 0° C. was added sodium borohydride (2.1 g, 56 mmol) in three equal portions over a 24 hour period. Water was added and the solution was concentrated to a white suspension. This aqueous suspension was extracted three times with dichloromethane. The combined organic layers were dried (MgSO4), and filtered through a pad of silica gel (eluting with acetone). The eluent was concentrated and the resulting solid was recrystallized from tetrahydrofuran to afford the desired product, α-[4-(1H-imidazol-1-yl)phenyl]-1-(4-pyridylmethyl)-4-piperidine methanol (2.5 g, 43%): m.p. 174°-175° C.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[CH:11][CH:10]=1)#[N:2]>C(O)C.C(OCC)(=O)C.[Pd]>[NH2:15][C:12]1[CH:11]=[CH:10][C:9]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[C:1]#[N:2])=[CH:14][CH:13]=1
Reactant: N#Cc1ccccc1-c1ccc([N+](=O)[O-])cc1
Agent: [Pd]
Solvent: CCO
Solvent: CCOC(C)=O
Product: N#Cc1ccccc1-c1ccc(N)cc1
Reaction time: 2.5 h

Procedure:
6.0 g (26.8 mmol) of 2'-cyano-4-nitrobiphenyl (prepared according to B. Sain, J. S. Sandhu, J. Org. Chem. 1990, 55, 2545) were dissolved in a mixture of 60 ml ethanol and 60 ml ethyl acetate, and the solution was filled into an autoclave. After addition of 660 mg 10% Pd on charcoal the mixture was set under an atmosphere of hydrogen (2-3 bar). The reduction was carried out at room temperature, the course of the reaction monitored by thin layer chromatography, and it had completed after 2.5 h. The catalyst was filtered and the solvent distilled off in vacuo. The title amine was obtained by crystallization from hexane as a white powder,
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH2:26][CH2:25][C:24](=[O:27])[CH2:23][CH2:22]3)=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:28][C:29]([Si](C)(C)C)([F:31])[F:30].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1>C([O-])(=O)C.C([N+](CCCC)(CCCC)CCCC)CCC.O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH2:26][CH2:25][C:24]([C:29]([F:31])([F:30])[F:28])([OH:27])[CH2:23][CH2:22]3)=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1CCN(c2ccc(-c3ccc(OCc4ccccc4)cc3)cc2)CC1
Reactant: C[Si](C)(C)C(F)(F)F
Agent: CC(=O)[O-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: O
Product: OC1(C(F)(F)F)CCN(c2ccc(-c3ccc(OCc4ccccc4)cc3)cc2)CC1
Temperature: 25 °C
Yield: 89.3 %

Procedure:
1-(4′-Benzyloxybiphenyl-4-yl)piperidin-4-one (7.1 g, 19.9 mmol), tetrabutylammonium acetate (0.3 g, 1.0 mmol) and 1,2-dimethoxethane (100 ml) were mixed. While stirring the mixture under ice cooling, trifluoromethyltrimethylsilane (4.11 ml, 27.8 mmol) was added to the mixture and warmed to room temperature, followed by stirring for 6 hours. The residue obtained by distilling off the solvent was dissolved in tetrahydrofuran (100 ml). While stirring at room temperature, 1 mol/l tetrabutylammonium fluoride in tetrahydrofuran (23.8 ml, 23.8 mmol) was added thereto and stirred at room temperature overnight. Water was added to the residue obtained by distilling off the solvent, followed by extraction with dichloromethane. The organic layer was washed with water and dried over sodium sulfate. After filtering, the filtrate was concentrated under reduced pressure. The resulting crude crystal was washed with diethylether to afford the title compound as a white powder (7.6 g, yield 90%).
Reaction SMILES: [CH2:1]([CH:3]1[C:12]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[C:6]2[S:13][C:14]([C:16]3[CH:20]=[CH:19][S:18][CH:17]=3)=[CH:15][C:5]=2[N:4]1[S:21]([C:24]1[CH:29]=[CH:28][C:27]([O:30]C)=[CH:26][CH:25]=1)(=[O:23])=[O:22])[CH3:2].C(=O)(O)[O-].[Na+].B(Br)(Br)Br.C(Cl)Cl>C1CCCCC=1>[CH2:1]([CH:3]1[C:12]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[C:6]2[S:13][C:14]([C:16]3[CH:20]=[CH:19][S:18][CH:17]=3)=[CH:15][C:5]=2[N:4]1[S:21]([C:24]1[CH:25]=[CH:26][C:27]([OH:30])=[CH:28][CH:29]=1)(=[O:23])=[O:22])[CH3:2]
Reactant: CCC1c2ccccc2-c2sc(-c3ccsc3)cc2N1S(=O)(=O)c1ccc(OC)cc1
Agent: BrB(Br)Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1=CCCCC1
Solvent: ClCCl
Product: CCC1c2ccccc2-c2sc(-c3ccsc3)cc2N1S(=O)(=O)c1ccc(O)cc1
Temperature: -78 °C
Yield: 289.4 %

Procedure:
A suspension of 5-ethyl-4-[(4-methoxyphenyl)sulfonyl]-2-thien-3-yl-4,5-dihydrothieno[3,2-c]isoquinoline (0.73 g, 1.6 mmol) in cyclohexene (11 mL) was treated with sodium bicarbonate (4.0 g, 48 mmol) and the mixture was cooled to −78° C. A solution of boron tribromide in methylene chloride (1.0 M, 6.4 mL, 6.4 mmol) was added dropwise during ca. 10 min. At this time the cooling bath was removed and the reaction mixture was warmed to 23° C. After 4 h the mixture was poured into saturated aqueous sodium bicarbonate (75 mL) and extracted with ethyl acetate (50 mL). The extract was washed with brine (75 mL), dried (Na2SO4), and concentrated in vacuo to give a dark oil (2.1 g) which was taken up in methylene chloride (ca. 5 mL) and pre-adsorbed on silica gel (5 g). Flash chromatography on silica (50 g) eluting 1.25-, and then 2.5% ethyl acetate-benzene gave the product (0.26 g) as a yellow solid. Recrystallization from hot ethyl acetate-hexane gave the title compound (0.15 g, 21%, m.p. 195-96° C.) as shiny tan needles.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[Br:15][CH2:16][CH2:17][CH2:18]Br.O>CN(C=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:18][CH2:17][CH2:16][Br:15])=[CH:4][CH:3]=1
Reactant: Oc1ccc(Br)cc1
Reactant: BrCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: BrCCCOc1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 69.1 %

Procedure:
To a suspension of 4-bromophenol (2.00 g, 11.56 mmol) and potassium carbonate (4.79 g, 34.68 mmol) in DMF (12 mL) was added 1,3-dibromopropane (7.00 g, 37.3 mmol). The mixture was stirred at room temperature overnight. Water was added, and the mixture was extracted with ethyl acetate (4×30 mL). The combined organic layers were washed with brine (3×20 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to give the crude product. The crude product was purified by flash chromatography (0-5% ethyl acetate/petroleum ether to afford the title compound (2.35 g, 69%) as a colorless oil. 1H NMR (400 MHz, CDCl3) ppm 7.39 (d, 2H), 6.80 (d, 2H), 4.16-4.01 (m, 2H), 3.55-3.53 (m, 2H), 2.41-2.26 (m, 2H).