Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[C:9]2[C:8](=[O:19])[N:7]([CH2:20][CH2:21][CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[C:6](=[O:31])[N:5]([CH3:32])[C:4]=2[N:3]=1.[CH2:33]([NH2:36])[CH2:34][CH3:35]>C(O)C.O>[Si:24]([O:23][CH2:22][CH2:21][CH2:20][N:7]1[C:8](=[O:19])[C:9]2[N:10]([CH2:11][C:12]3[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=3)[C:2]([NH:36][CH2:33][CH2:34][CH3:35])=[N:3][C:4]=2[N:5]([CH3:32])[C:6]1=[O:31])([C:27]([CH3:29])([CH3:28])[CH3:30])([CH3:25])[CH3:26]
Reactant: CCCN
Reactant: Cn1c(=O)n(CCCO[Si](C)(C)C(C)(C)C)c(=O)c2c1nc(Br)n2Cc1ccc(Cl)cc1
Solvent: CCO
Solvent: O
Product: CCCNc1nc2c(c(=O)n(CCCO[Si](C)(C)C(C)(C)C)c(=O)n2C)n1Cc1ccc(Cl)cc1
Temperature: 25 °C
Yield: 62.7 %

Procedure:
Step 1 8-Bromo-1-(3-((tert-butyldimethylsilyl)oxy)propyl)-7-(4-chlorobenzyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (0.25 g, 0.46 mmol, intermediate 77) and propan-1-amine (1.44 mL, 9.2 mmol) were combined in ethanol (5 mL) and heated at reflux for 24 h. The reaction was cooled to room temperature, diluted with water (75 mL) and extracted with ethyl acetate (3×75 mL). The combined organic extracts were dried with magnesium sulfate, filtered and the solvent evaporated under reduced pressure to yield a light golden oil. The oil was purified using a 25 g silica gel column eluted with 20% ethyl acetate/hexanes to give 1-(3-((tert-butyldimethylsilyl)oxy)propyl-7-(4-chlorobenzyl)-3-methyl-8-(propylamino)-1H-purine-2,6(3H,7H)-dione (0.15 g, 63% yield) as a white solid. LCMS retention time=5.013 min and 97% purity, LCMS MH+ 520.
Reaction SMILES: [CH:1]1([C:4]2[C:5]([N:24]([C:29]3[CH:34]=[CH:33][C:32]([B:35]4[O:39]C(C)(C)C(C)(C)[O:36]4)=[C:31]([F:44])[CH:30]=3)[S:25]([CH3:28])(=[O:27])=[O:26])=[CH:6][C:7]3[O:11][C:10]([C:12]4[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=4)=[C:9]([C:19]([NH:21][CH3:22])=[O:20])[C:8]=3[CH:23]=2)[CH2:3][CH2:2]1.Cl.C1(B(O)O)C=CC=CC=1>C1COCC1>[CH:1]1([C:4]2[C:5]([N:24]([C:29]3[CH:34]=[CH:33][C:32]([B:35]([OH:36])[OH:39])=[C:31]([F:44])[CH:30]=3)[S:25]([CH3:28])(=[O:26])=[O:27])=[CH:6][C:7]3[O:11][C:10]([C:12]4[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=4)=[C:9]([C:19](=[O:20])[NH:21][CH3:22])[C:8]=3[CH:23]=2)[CH2:3][CH2:2]1
Reactant: CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(c3ccc(B4OC(C)(C)C(C)(C)O4)c(F)c3)S(C)(=O)=O)c(C3CC3)cc12
Agent: Cl
Agent: OB(O)c1ccccc1
Solvent: C1CCOC1
Product: CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(c3ccc(B(O)O)c(F)c3)S(C)(=O)=O)c(C3CC3)cc12
Temperature: 25 °C
Reaction time: 24 h
Yield: 41.8 %

Procedure:
A solution of 5-cyclopropyl-6-(N-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methylsulfonamido)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (140 mg, 0.22 mmol) and 1N aqueous HCl (2 mL) in anhydrous THF (10 mL) was treated with polymer-supported benzeneboronic acid (5000 mg) and stirred at room temperature for 24 hours. The mixture was partitioned between ethyl acetate and water. The organic layer was separated, dried over sodium sulfate, filtered, concentrated to dryness, and purified by reverse phase HPLC to afford 4-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)-2-fluorophenylboronic acid (50 mg, 0.092 mmol, 42% yield) as a white solid. 1H NMR (300 MHz, METHANOL-d4) δ 7.96 (dd, 2H), 7.83 (s, 1H), 7.45-7.15 (m, 6H), 3.43 (s, 3H), 2.96 (s, 3H), 2.12 (m, 1H), 1.01-0.52 (m, 4H). LCMS (m/z, ES+)=541 (M+H+)
Reaction SMILES: [CH:1]([O:4][C:5]1[N:10]=[C:9]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][CH:15]=[C:14]3[C:20]2[O:24][C:23]([N:25]3[CH2:30][CH2:29][CH:28]([NH:31]C(=O)OC(C)(C)C)[CH2:27][CH2:26]3)=[N:22][N:21]=2)[CH:8]=[N:7][CH:6]=1)([CH3:3])[CH3:2].Cl>CO>[CH:1]([O:4][C:5]1[N:10]=[C:9]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][CH:15]=[C:14]3[C:20]2[O:24][C:23]([N:25]3[CH2:26][CH2:27][CH:28]([NH2:31])[CH2:29][CH2:30]3)=[N:22][N:21]=2)[CH:8]=[N:7][CH:6]=1)([CH3:3])[CH3:2]
Reactant: CC(C)Oc1cncc(-c2ccc3[nH]cc(-c4nnc(N5CCC(NC(=O)OC(C)(C)C)CC5)o4)c3c2)n1
Agent: Cl
Solvent: CO
Product: CC(C)Oc1cncc(-c2ccc3[nH]cc(-c4nnc(N5CCC(N)CC5)o4)c3c2)n1
Temperature: 25 °C
Reaction time: 4 h
Yield: 31.8 %

Procedure:
To a solution of tert-butyl (1-(5-(5-(6-isopropoxypyrazin-2-yl)-1H-indol-3-yl)-1,3,4-oxadiazol-2-yl)piperidin-4-yl)carbamate (80 mg, 0.15 mmol) in MeOH (1 mL) was added HCl in MeOH (2 mL) and the reaction was stirred for 4 h at RT. The suspension was filtered and the filtrate was washed with Et2O and basified with saturated NaHCO3 solution. The mixture was extracted in EtOAc (2×3 mL). The combined organic layer were dried over anhydrous Na2SO4, filtered and concentrated. The residue was triturated with 10% EtOAc in petroleum ether to give 1-(5-(5-(6-isopropoxypyrazin-2-yl)-1H-indol-3-yl)-1,3,4-oxadiazol-2-yl)piperidin-4-amine (20 mg, 31.2%) as a solid. MS (ESI, pos. ion) m/z: 420.3 (M+1); 1H NMR (400 MHz, DMSO-d6): δ ppm 8.73 (s, 1H), 7.96-8.13 (m, 3H), 7.63 (d, J=7.6 Hz, 1H), 5.42 (brs, 1H), 3.90 (d, J=10.8 Hz, 3H), 3.13-3.18 (m, 2H), 2.80 (brs, 2H), 1.82 (d, J=10.4 Hz, 3H), 1.23-1.50 (s, 8H).
Reaction SMILES: [C:1]([C@@H:6]([NH:10][C@H:11]([C:13]([OH:15])=[O:14])[CH3:12])[CH2:7][CH2:8][CH3:9])([O:3][CH2:4][CH3:5])=[O:2].F[P-](F)(F)(F)(F)F.[N:23]1(OC(N(C)C)=[N+](C)C)[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2N=N1>C(#N)C.[Cl-].[Na+].O>[CH2:4]([O:3][C:1]([C@@H:6]([NH:10][C@@H:11]([CH3:12])[C:13]([O:15][C:1]([CH:6]1[CH2:7][CH:26]2[CH:27]([CH2:28][CH2:29][CH2:30][CH2:31]2)[NH:23]1)=[O:2])=[O:14])[CH2:7][CH2:8][CH3:9])=[O:2])[CH3:5]
Reactant: CCC[C@H](N[C@@H](C)C(=O)O)C(=O)OCC
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CC#N
Product: CCC[C@H](N[C@@H](C)C(=O)OC(=O)C1CC2CCCCC2N1)C(=O)OCC
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A mixture of 9.54 g of (2S,3aS,7aS)-2-carboxyperhydroindole benzyl ester, 7.26 g of N-((S)-1-carbetoxybutyl)-(S)-alanine and 12.7 g of O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate in 225 ml of acetonitrile is stirred at room temperature for 30 min, then 560 ml of brine is added. The product is extracted twice with 400 ml of ethyl acetate, combined extracts are washed first with 800 ml of water, acidified with concentrated hydrochloric acid and then with 1.5 l of water. Organic phase is dried over anhydrous sodium sulphate and evaporated at 40° C. in vacuo to yield 13.5 g (88%) of benzyl (2S,3aS,7aS)-((2-(1-(ethoxycarbonyl)-(S)-butylamino)-(S)-propionyl)octahydroindole-2-carboxylate (benzyl ester of perindopril).
Reaction SMILES: [CH3:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:15][C:16]1[CH:21]=[C:20]([N+:22]([O-:24])=[O:23])[CH:19]=[CH:18][C:17]=1F>CC(C)=O.CCOC(C)=O>[Cl:15][C:16]1[CH:21]=[C:20]([N+:22]([O-:24])=[O:23])[CH:19]=[CH:18][C:17]=1[O:8][C:5]1[CH:4]=[CH:3][C:2]([CH3:1])=[N:7][CH:6]=1
Reactant: Cc1ccc(O)cn1
Reactant: O=[N+]([O-])c1ccc(F)c(Cl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CC(C)=O
Product: Cc1ccc(Oc2ccc([N+](=O)[O-])cc2Cl)cn1
Temperature: 25 °C

Procedure:
6-methyl-pyridin-3-ol Compound 80b (3.10 g, 28.4 mmol) and potassium carbonate (7.80 g, 56.8 mmol) were added to a solution of 2-chloro-1-fluoro-4-nitro-benzene Compound 80a (5.0 g, 28.4 mmol) in acetone (50 mL). The suspension was refluxed for 20 hrs and then cooled to 25° C. The reaction mixture was diluted with EtOAc and washed with water and brine. The organic solution was dried over Na2SO4, then filtered and concentrated to yield 5-(2-chloro-4-nitro-phenoxy)-2-methyl-pyridine Compound 80c (5.6 g, 80%). MS 350 (M−).
Reaction SMILES: [C:1](O)(=[O:10])[CH:2]=[CH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH:12]1[C:17]([OH:18])=[CH:16][CH:15]=[C:14]([CH3:19])[CH:13]=1.O>C1(C)C=CC=CC=1>[CH3:19][C:14]1[CH:13]=[C:12]2[C:17](=[CH:16][CH:15]=1)[O:18][C:1](=[O:10])[CH2:2][CH:3]2[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: O=C(O)C=Cc1ccccc1
Reactant: Cc1ccc(O)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: Cc1ccc2c(c1)C(c1ccccc1)CC(=O)O2
Temperature: 60 °C

Procedure:
Cinnamic acid (100 gms) and p-cresol (76.6 gms) were charged to a clean and dry flask under nitrogen and stirred. Concentrated sulphuric acid was slowly charged and the reaction mixture heated to 125° C.-130° C. for 6 hours. After completion of reaction the mixture was cooled to about 60° C. and about 50 ml water and about 300 ml toluene were charged under stirring. The layers were separated. The toluene layer was washed with aqueous saturated solution of sodium bicarbonate and water. The organic layer was dried over sodium sulfate and concentrated under vacuum, at a temperature below 50° C. The residue was stripped with 2×100 ml IPA. The residue was dissolved in 200 ml isopropanol, chilled to 5° C. and stirred for 2 hours. The solids obtained were filtered and dried at about 60° C. for 4-5 hours to give about 135 to 137 gms of the title product.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:12]=[CH:11][C:10]2[NH:9][C:8]3[CH2:13][CH2:14][N:15]([CH3:17])[CH2:16][C:7]=3[C:6]=2[CH:5]=1.Br[CH2:19][CH2:20][CH2:21][C:22]1[CH:23]=[CH:24][C:25]([C:28]([F:31])([F:30])[F:29])=[N:26][CH:27]=1.O>CN(C=O)C>[Cl:3][C:4]1[CH:12]=[CH:11][C:10]2[N:9]([CH2:19][CH2:20][CH2:21][C:22]3[CH:27]=[N:26][C:25]([C:28]([F:31])([F:29])[F:30])=[CH:24][CH:23]=3)[C:8]3[CH2:13][CH2:14][N:15]([CH3:17])[CH2:16][C:7]=3[C:6]=2[CH:5]=1
Reactant: CN1CCc2[nH]c3ccc(Cl)cc3c2C1
Reactant: FC(F)(F)c1ccc(CCCBr)cn1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CN1CCc2c(c3cc(Cl)ccc3n2CCCc2ccc(C(F)(F)F)nc2)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 32.7 %

Procedure:
To a suspension of sodium hydride (0.014 g, 0.00054 mol) in dry DMF (3 mL), 8-Chloro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.1 g, 0.00045 mol) was added at ice cold temp and stirred for 2 h at room temperature. Reaction mix was cooled to −20° C. and 5-(3-Bromo-propyl)-2-trifluoromethyl-pyridine (0.183 g, 0.00068 mol) was added, stirred for 1 h at 15° C., Reaction was monitor by TLC. After completion (TLC), reaction mix was cooled to 0° C. and water (10 mL) was added, extracted with ethyl acetate (3×100 mL). The organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure using rotary evaporator. The crude was purified through column chromatography (4% Methanol:DCM in silica 100-200 mesh, Diameter of column—2.5 cm, Height of silica—approx. 5 inch) to provide desired compound as brown oil (0.06 g, 32% yield). 8-Chloro-2-methyl-5-[3-(6-trifluoromethyl-pyridin-3-yl)-propyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.06 g, 0.000147 mol) was dissolved in THF (1.0 mL), A solution of oxalic acid dihydrate (0.016 g, 0.000126 mol) in THF (1.0 mL) was added and stirred for 30 min at RT. The precipitate was filtered and dried to give oxalate salt as off white solid (0.050 g, 68% yield).
Reaction SMILES: [NH2:1][CH2:2][CH:3]1[CH2:7][N:6]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:5](=[O:15])[CH2:4]1.[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]=[C:24]=[O:25])=[CH:19][CH:18]=1>O1CCOCC1>[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([NH:23][C:24]([NH:1][CH2:2][CH:3]2[CH2:7][N:6]([CH2:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[C:5](=[O:15])[CH2:4]2)=[O:25])=[CH:19][CH:18]=1
Reactant: NCC1CC(=O)N(Cc2ccccc2)C1
Reactant: O=C=Nc1ccc(Cl)cc1
Solvent: C1COCCO1
Product: O=C(NCC1CC(=O)N(Cc2ccccc2)C1)Nc1ccc(Cl)cc1
Yield: 74.9 %

Procedure:
52 g (0.25 mol) of 4-aminomethyl-1-benzylpyrrolidin-2-one are stirred for 2 hours at ambient temperature in 70 ml of dioxane with 38 g (0.25 mol) of p-chlorophenylisocyanate and the solution is then evaporated in vacuo. The residue crystallizes out of ethyl acetate to yield 67 g of the title compound, m.p. 139°-140° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:14]([CH2:16][C:17](OCC)=[O:18])#[N:15]>C1(C)C=CC=CC=1>[C:14]([CH2:16][C:17]([N:11]1[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]1)=[O:18])#[N:15]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: CCOC(=O)CC#N
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N1CCN(C(=O)CC#N)CC1
Yield: 36.3 %

Procedure:
A mixture of 1-tert-butoxycarbonylpiperazine (7.44 g, 40 mmol) and ethyl cyanoacetate (8.53 mL, 80 mmol) was gently stirred in 20 mL of toluene at 90° C. for 2 days. The mixture was concentrated and purified by silica gel column chromatography, eluting with 30% ethyl acetate in n-hexane to provide the title compound (3.68 g). MS (ESI(−)) m/e 252 (M−H)−; 1H NMR (300 MHz, DMSO-d6) δ 3.41 (m, 4H), 3.27-3.35 (m, 4H), 2.72 (m, 2H), 2.38 (m, 2H), 1.41 (s, 9H).
Reaction SMILES: [CH3:1][N:2]([CH2:13][CH:14]=[O:15])[C:3]([NH:5][C:6]1[S:7][C:8]([CH2:11][Cl:12])=[N:9][N:10]=1)=[O:4].Cl>O>[Cl:12][CH2:11][C:8]1[S:7][C:6]([N:5]2[CH:14]([OH:15])[CH2:13][N:2]([CH3:1])[C:3]2=[O:4])=[N:10][N:9]=1
Reactant: CN(CC=O)C(=O)Nc1nnc(CCl)s1
Agent: Cl
Solvent: O
Product: CN1CC(O)N(c2nnc(CCl)s2)C1=O

Procedure:
The dimethyl acetal of 2-[1-methyl-3-(5-chloromethyl-1,3,4-thiadiazol-2-yl)ureido]acetaldehyde (15 grams), water (400 ml) and hydrochloric acid (4 ml) are charged into a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux condenser. The reaction mixture is heated at reflux for a period of about 15 minutes. The reaction mixture is then filtered while hot, and the filtrate is cooled, resulting in the formation of a precipitate. The precipitate is recovered by filtration, is dried and is recrystallized from an ethyl acetate-hexane mixture to yield the desired product 1-(5-chloromethyl-1,3,4-thiadiazol-2-yl)-3-methyl-5-hydroxy-1,3-imidazolidin-2-one.
Reaction SMILES: [C:1]([O:5][C:6]([CH:8]([CH2:18][O:19][CH2:20][CH2:21][O:22][CH3:23])[CH2:9][C:10]1([C:15]([OH:17])=[O:16])[CH2:14][CH2:13][CH2:12][CH2:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][C@H:25]([NH:34][CH3:35])[C@@H:26]([OH:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CCCCCC>[CH3:24][C@H:25]([NH:34][CH3:35])[C@@H:26]([OH:33])[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1.[C:1]([O:5][C:6]([C@H:8]([CH2:18][O:19][CH2:20][CH2:21][O:22][CH3:23])[CH2:9][C:10]1([C:15]([OH:17])=[O:16])[CH2:14][CH2:13][CH2:12][CH2:11]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]
Reactant: COCCOCC(CC1(C(=O)O)CCCC1)C(=O)OC(C)(C)C
Agent: CN[C@@H](C)[C@@H](O)c1ccccc1
Solvent: CCCCCC
Product: COCCOC[C@H](CC1(C(=O)O)CCCC1)C(=O)OC(C)(C)C
Temperature: 5 °C
Reaction time: 1 h

Procedure:
A solution of 1-[2-(tert-butoxycarbonyl)-3-(2-methoxyethoxy)propyl]-1-cyclopentanecarboxylic acid (110.1 g, 0.333 mole) in hexane (550 ml) was treated with (+) pseudoephedrine (55.1 g, 0.333 mole) and the mixture was heated to reflux. The resulting solution was cooled to induce crystallisation, and stirred at 5° C. for 1 hour to granulate the crystals. After overnight refrigeration at 5° C., filtration, washing with hexane (200 ml) and drying gave the crude (+) pseudoephedrine salt of the (S) acid (89.9 g, 54.4%) as a white solid m.p. 76°-80° C. Recrystallisation of 30 g of this material twice from hexane (225 ml) gave the (+) pseudoephedrine salt of the title compound (21.45 g, 71.5% recovery) as white crystals m.p. 86°-7° C., [α]D +34.9° (c=1, MeOH). Found: C,65.21; H,9.23; N,2.91. C27H45NO7 requires C,65.42; H,9.15; N,2.82%.
Reaction SMILES: [F:1][C:2]([F:32])([F:31])[C:3]([N:5]([C:22]1[CH:30]=[CH:29][C:25]([C:26]([OH:28])=[O:27])=[CH:24][CH:23]=1)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])=[O:4].O1CCOCC1.O[N:40]1[C:44](=[O:45])[CH2:43][CH2:42][C:41]1=[O:46].C1(N=C=NC2CCCCC2)CCCCC1>O.CCCCCC>[F:1][C:2]([F:31])([F:32])[C:3]([N:5]([C:22]1[CH:30]=[CH:29][C:25]([C:26]([O:28][N:40]2[C:44](=[O:45])[CH2:43][CH2:42][C:41]2=[O:46])=[O:27])=[CH:24][CH:23]=1)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])=[O:4]
Reactant: O=C1CCC(=O)N1O
Reactant: CCCCCCCCCCCCCCCCN(C(=O)C(F)(F)F)c1ccc(C(=O)O)cc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: O
Solvent: CCCCCC
Solvent: C1COCCO1
Product: CCCCCCCCCCCCCCCCN(C(=O)C(F)(F)F)c1ccc(C(=O)ON2C(=O)CCC2=O)cc1

Procedure:
To stirred ice-cold solution of 18.3 g. of p-(2,2,2-trifluoro-N-hexadecylacetamido)benzoic acid in 80 ml. of dioxane is added successively 4.84 g. of N-hydroxysuccinimide and 9.16 g. of dicyclohexylcarbodiimide. After 18 hours at 0°-5° C. the mixture is stirred vigorously for one hour with hexane and water and filtered. The hexane layer is washed with water, dried over magnesium sulfate, and concentrated to give an oil.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][CH2:8][O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][OH:16].[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>ClCCl.CCOCC>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][CH2:8][O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH:15]=[O:16]
Reactant: OCCCCCCOCCc1ccccn1
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Solvent: CCOCC
Product: O=CCCCCCOCCc1ccccn1
Temperature: 25 °C
Reaction time: 4 h
Yield: 49.4 %

Procedure:
A solution of 6-[2-(2-pyridinyl)ethoxy]hexanol (1.0 g) in dichloromethane (8 ml) was added dropwise over 15 min to a stirred suspension of pyridinium chlorochromate (1.83 g) and silica (Merck 7734, 2.9 g) in dichloromethane (30 ml). The mixture was stirred at room temperature under nitrogen for 4 h, diluted with ether (100 ml) and filtered through silica (Merck 9385, 200 ml), eluting with dichloromethane followed by methanol to give a brown oil. Purification by FCC eluting with ether gave the title compound as a yellow oil (0.49 g), t.l.c. (System A 40:10:1) Rf 0.42.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH:14](O)[CH2:15][N:16]3[CH:20]=[N:19][CH:18]=[N:17]3)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.S(Cl)([Cl:24])=O.C1(C)C=CC=CC=1.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl>[Cl:24][CH:14]([C:11]1[CH:12]=[CH:13][C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)=[CH:9][CH:10]=1)[CH2:15][N:16]1[CH:20]=[N:19][CH:18]=[N:17]1
Reactant: O=S(Cl)Cl
Reactant: OC(Cn1cncn1)c1ccc(-c2ccc(Cl)cc2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: Cc1ccccc1
Product: Clc1ccc(-c2ccc(C(Cl)Cn3cncn3)cc2)cc1
Yield: 92 %

Procedure:
150 g (0.5 mole) of 1-(2-[4"-chloro-4'-biphenylyl]-2-hydroxy-ethyl)-1,2,4-triazole were dissolved in 2 liters of chloroform and heated to the boil, while stirring. 90g (0.75 mole) of thionyl chloride were slowly added dropwise thereto. The reaction mixture was heated for 12 hours under reflux and after cooling, 1.5 liters of toluene were added. The hydrochloride of 1-(2-chloro-2-[4'(4"-chlorophenyl)-phenyl]-ethyl)-1,2,4-triazole, which thereupon precipitated, was filtered off and taken up in 2 liters of water. The free base was obtained by adding sodium bicarbonate, and was taken up in chloroform. After drying over sodium sulfate, the solvent was distilled off and the residue soldified to crystals. 148 g (92% of theory) of 1-(2-chloro-2-[4"-chloro-4'-biphenylyl]ethyl)-1,2,4-triazole of melting point 118° C. were obtained.
Reaction SMILES: [Br:1][C:2]1[C:15]2[C:16]3=[C:17]4[C:12](=[CH:13][CH:14]=2)[CH:11]=[CH:10][C:9](Br)=[C:8]4[CH:7]=[CH:6][C:5]3=[CH:4][CH:3]=1.[C:19]1(B(O)O)[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][CH:20]=1.C([O-])([O-])=O.[Na+].[Na+].CCO>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(C)C=CC=CC=1>[Br:1][C:2]1[C:15]2[C:16]3=[C:17]4[C:12](=[CH:13][CH:14]=2)[CH:11]=[CH:10][C:9]([C:27]2[C:28]5[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=5)[CH:24]=[CH:25][CH:26]=2)=[C:8]4[CH:7]=[CH:6][C:5]3=[CH:4][CH:3]=1
Reactant: Brc1ccc2ccc3c(Br)ccc4ccc1c2c43
Reactant: OB(O)c1cccc2ccccc12
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: Brc1ccc2ccc3c(-c4cccc5ccccc45)ccc4ccc1c2c43
Temperature: 90 °C
Yield: 39.3 %

Procedure:
A mixture of 18 g (50 mmol) of 1,6-dibromopyrene, 8.6 g (50 mmol) of naphthalen-1-ylboronic acid, 0.6 g (0.5 mmol) of tetrakis(triphenylphosphine) palladium, 38 ml of 2M Na2CO3, 100 ml of EtOH and 200 ml toluene was degassed and placed under nitrogen, and then heated at 90° C. for 24 h. After finishing the reaction, the mixture was allowed to cool to room temperature. The organic layer was extracted with ethyl acetate and water, dried with anhydrous magnesium sulfate, the solvent was removed and the residue was purified by column chromatography on silica (hexane-dichloromethane) to give product 8 g (40%) as a white solid.
Reaction SMILES: OCCCCCCCCN[C:11]([C:13]1[CH:14]=[C:15]([S:19]([C:22]2[CH:23]=[C:24]3[C:29](=[C:30]([CH3:32])[CH:31]=2)[N:28]=[CH:27][C:26]([C:33]([NH2:35])=[O:34])=[C:25]3[NH:36][C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([O:43][CH3:44])[CH:38]=2)(=[O:21])=[O:20])[CH:16]=[CH:17][CH:18]=1)=[O:12].[NH2:45][C:46]1[CH:51]=[CH:50][C:49]([C:52]#[C:53][CH2:54][CH2:55][CH2:56][N:57]([CH3:80])[CH2:58][C@@H:59]([C:68]2[CH:77]=[CH:76][C:75]([OH:78])=[C:74]3[C:69]=2[CH:70]=[CH:71][C:72](=[O:79])[NH:73]3)[O:60][Si:61]([C:64]([CH3:67])([CH3:66])[CH3:65])([CH3:63])[CH3:62])=[CH:48][CH:47]=1>>[Si:61]([O:60][C@H:59]([C:68]1[CH:77]=[CH:76][C:75]([OH:78])=[C:74]2[C:69]=1[CH:70]=[CH:71][C:72](=[O:79])[NH:73]2)[CH2:58][N:57]([CH3:80])[CH2:56][CH2:55][CH2:54][C:53]#[C:52][C:49]1[CH:50]=[CH:51][C:46]([NH:45][C:11]([C:13]2[CH:14]=[C:15]([S:19]([C:22]3[CH:23]=[C:24]4[C:29](=[C:30]([CH3:32])[CH:31]=3)[N:28]=[CH:27][C:26]([C:33]([NH2:35])=[O:34])=[C:25]4[NH:36][C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([O:43][CH3:44])[CH:38]=3)(=[O:20])=[O:21])[CH:16]=[CH:17][CH:18]=2)=[O:12])=[CH:47][CH:48]=1)([C:64]([CH3:67])([CH3:66])[CH3:65])([CH3:62])[CH3:63]
Reactant: COc1cccc(Nc2c(C(N)=O)cnc3c(C)cc(S(=O)(=O)c4cccc(C(=O)NCCCCCCCCO)c4)cc23)c1
Reactant: CN(CCCC#Cc1ccc(N)cc1)C[C@H](O[Si](C)(C)C(C)(C)C)c1ccc(O)c2[nH]c(=O)ccc12
Product: COc1cccc(Nc2c(C(N)=O)cnc3c(C)cc(S(=O)(=O)c4cccc(C(=O)Nc5ccc(C#CCCCN(C)C[C@H](O[Si](C)(C)C(C)(C)C)c6ccc(O)c7[nH]c(=O)ccc67)cc5)c4)cc23)c1

Procedure:
The title compound was synthesized in a manner analogous to that described for Intermediate 70, using Intermediate 103 in place of 8-aminooctanol. ES/MS calcd. for C54H59N6O8SSi+ 979.4. Found m/z=979.6 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[CH3:9])[CH:5]=[CH:4][N:3]=1.[OH:12]O>FC(F)(F)C(O)=O>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:10])([F:11])[CH3:9])[CH:5]=[CH:4][N+:3]=1[O-:12]
Reactant: CC(F)(F)c1ccnc(Cl)c1
Reactant: OO
Solvent: O=C(O)C(F)(F)F
Product: CC(F)(F)c1cc[n+]([O-])c(Cl)c1

Procedure:
To a solution of 2-chloro-4-(1,1-difluoro)ethylpyridine (1.27 g, 7 mmol) in trifluoroacetic acid was added 30% hydrogen peroxide (6 mL) and the solution was heated at reflux 2.5 h. The reaction was concentrated in vacuo and the residue poured into ice-cold water. The mixture was neutralized with Na2CO3 and then extracted with EtOAc and CH2Cl2. The pooled organic layers were filtered and concentrated in vacuo to give 2-chloro-4-(1,1-difluoroethyl)-pyridine 1-oxide (1.00 g) as a brown oil. 1H NMR (CDCl3): δ 8.39 (d, J=6.6 Hz, 1H), 7.63 (d, J=2.4 Hz, 1H), 7.33 (dd, J=6.6, 2.4 Hz, 1H), 1.94 (t, J=18 Hz, 3H). GC/MS: m/z 193 [M+].
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10](=[O:12])[CH3:11])=[CH:4][CH:3]=1.[OH-].[K+].Br[CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].[OH-].[Na+]>O>[CH2:16]([O:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][C:10](=[O:12])[CH3:11])=[CH:6][CH:7]=1)[CH2:17][CH2:18][CH2:19][CH3:20]
Reactant: CC(=O)CCc1ccc(O)cc1
Reactant: CCCCCBr
Agent: [K+]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCCCCOc1ccc(CCC(C)=O)cc1
Yield: 90.1 %

Procedure:
4-(4-Hydroxyphenyl)-2-butanone (49 g) was added by portions while warming to a stirred solution of potassium hydroxide (0.33 m) in 15 ml of water. To this was added dropwise, 49.8 g of 1-bromopentane and the resultant mixture was stirred at reflux temperature overnight. The mixture was allowed to cool after which 500 ml of 20% sodium hydroxide was added and the resultant mixture was stirred an additional 30 minutes followed by extraction with ethylacetate. The organic extracts were dried and evaporated to yield approximately 63 g of the desired 4-(4-pentoxyphenyl)-2-butanone which was used to prepare the title compound as follows.