Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:20])([S:13]([CH2:16][CH2:17][CH2:18][OH:19])(=[O:15])=[O:14])[C:3]([F:12])([F:11])[C:4]([F:10])([F:9])[C:5]([F:8])([F:7])[F:6].C(N(CC)CC)C.[Cl-].[Ca+2].[Cl-].[C:31](Cl)(=[O:34])[CH:32]=[CH2:33]>C(C1C=C(O)C(=CC=1)O)(C)(C)C.ClCCl>[C:31]([O:19][CH2:18][CH2:17][CH2:16][S:13]([C:2]([F:1])([F:20])[C:3]([F:11])([F:12])[C:4]([F:10])([F:9])[C:5]([F:8])([F:7])[F:6])(=[O:15])=[O:14])(=[O:34])[CH:32]=[CH2:33]
Reactant: C=CC(=O)Cl
Reactant: O=S(=O)(CCCO)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Agent: CC(C)(C)c1ccc(O)c(O)c1
Agent: [Ca+2]
Agent: [Cl-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C=CC(=O)OCCCS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Temperature: 25 °C
Reaction time: 1 h
Yield: 95.2 %

Procedure:
A solution of 3-(perfluorobutylsulfonyl)propanol (54.4 g, 159 mmol), triethylamine (33 ml, 238 mmol), 4-t-butylcatechol (0.14 g) and dichloromethane (520 ml) was cooled to 0° C. in a state of being equipped with a calcium chloride, and then acryloyl chloride (15.5 ml, 191 mmol) was slowly added dropwise over 40 minutes. After stirring at room temperature for one hour and washing the mixture with 15% citric acid (600 ml) water and saturated saline, the mixture was dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure to obtain a crude acrylate ester. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=6:1) and the transparent liquid was vacuum-dried after concentration to obtain 60.0 g of 3-(perfluorobutylsulfonyl)propyl acrylate. Yield was 95.3%.
Reaction SMILES: [C:1]([C:4]([C@@H:17]1[CH2:21][CH2:20][NH:19][CH2:18]1)([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)(=[O:3])[NH2:2].[OH:22][C:23]1[CH:31]=[CH:30][C:26]([CH2:27][CH2:28]Br)=[CH:25][CH:24]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[C:1]([C:4]([C@@H:17]1[CH2:21][CH2:20][N:19]([CH2:28][CH2:27][C:26]2[CH:30]=[CH:31][C:23]([OH:22])=[CH:24][CH:25]=2)[CH2:18]1)([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)(=[O:3])[NH2:2]
Reactant: NC(=O)C(c1ccccc1)(c1ccccc1)[C@@H]1CCNC1
Reactant: Oc1ccc(CCBr)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: NC(=O)C(c1ccccc1)(c1ccccc1)[C@@H]1CCN(CCc2ccc(O)cc2)C1

Procedure:
A mixture containing 3-(S)-(1-carbamoyl-1,1-diphenylmethyl)pyrrolidine (0.1 g--see Preparation 10B), 4-hydroxyphenethyl bromide (0.072 g), anhydrous potassium carbonate (0.15 g) and acetonitrile (2 ml) was heated under reflux for 45 minutes. On cooling, the mixture was partitioned between dichloromethane (5 ml) and 10% aqueous potassium carbonate (10 ml). The layers were separated, and the aqueous layer was further extracted with dichloromethane (2×5 m]). The combined dichloromethane extracts were dried (MgSO4) and concentrated in vacuo to give a foam which was purified by column chromatography on silica eluting with dichloromethane containing methanol (5%). The product-containing fractions were combined and concentrated in vacuo to give the title compound as a colourless foam, yield 0.035 g.
Reaction SMILES: [CH2:1](OC(=O)C(C)=C)[CH2:2][CH2:3][CH3:4].[CH2:11]=[CH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C.C(Cl)Cl.CO>C1(C)C=CC=CC=1>[CH2:1]=[CH:2][CH:3]=[CH2:4].[CH2:11]=[CH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: C=C(C)C(=O)OCCCC
Agent: C
Solvent: ClCCl
Solvent: Cc1ccccc1
Solvent: C=Cc1ccccc1
Product: C=CC=C

Procedure:
The above semicrystalline polyolefins, 25 percent, (polypentene of Example I, polyhexadecene of Example II, polyoctadecene of Example II, and polyeicosene of Example III, and 75 percent by weight of styrene n-butyl methacrylate) (the aforesaid resin blend present in an amount of 70 weight percent) were admixed with 10 weight percent of Black Pearls L or 10 weight percent of Regal® 330 carbon black, which carbon black was allowed to dissolve with heating between 40° and 60° C. in toluene or methylene choride at 10 weight percent solids. The resultant slurries were then allowed to cool while the polymers were vigorously stirred using a Waring blender, a large Kady mill, and a ball mill or an attritor equipped with steel shot. The resultant slurried particles were then, in each instance, added to methanol, isolated by filtration, and then vacuum dried. Very small toner particles from submicron 0.5 micron to about 20 microns average diameter were obtained for the two prepared toners. Subsequent to classification, there resulted toner compositions with an average diameter of about 10 microns. These particles were then heat spheroidized by gentle warming of a vigorously stirred aqueous suspension of the dried toner particles in the presence of Alkanox soap followed by a rapid quench with ice water. The toner particles were then isolated in each instance by filtration and dried in vacuo.
Reaction SMILES: [CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br:9][C:10]1[CH:15]=[CH:14][C:13]([C:16](Cl)=[O:17])=[C:12]([O:19][CH3:20])[CH:11]=1.C(N(CC)CC)C>ClCCl>[CH2:1]([NH:8][C:16](=[O:17])[C:13]1[CH:14]=[CH:15][C:10]([Br:9])=[CH:11][C:12]=1[O:19][CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NCc1ccccc1
Reactant: COc1cc(Br)ccc1C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1cc(Br)ccc1C(=O)NCc1ccccc1
Reaction time: 3 h
Yield: 86 %

Procedure:
Benzylamine (0.69 mL, 6.31 mmol) was added slowly to a mixture of 4-Bromo-2-methoxy-1-benzenecarbonyl chloride (1.5 g, 6.01 mmol) and triethylamine (1.3 mL, 9.02 mmol) in dichloromethane (60 mL). After 3 hours, solvent was removed under reduced pressure. Ethyl acetate was added and the mixture was filtered. The filtrate was concentrated under reduced pressure and the residue was re-crystallized from ethyl acetate/heptane to give N1-benzyl-4-bromo-2-methoxybenzamide (1.654 g, 86%). 1H NMR (DMSO-d6) δ 3.92 (s, 3H), 4.67 (d, J=5.67 Hz, 32H), 7.31 (m, 7H), 8.03 (bs, 1H), 8.13 (d, J=8.41, 1H).
Reaction SMILES: [CH3:1][C:2]1([CH3:18])[CH2:6][C:5]2[CH:7]=[C:8]([CH:11]3[CH2:16][CH2:15][C:14](=[O:17])[CH2:13][CH2:12]3)[CH:9]=[CH:10][C:4]=2[O:3]1>[Pd].C(O)C>[CH3:1][C:2]1([CH3:18])[CH2:6][C:5]2[CH:7]=[C:8]([C:11]3[CH2:16][CH2:15][C:14](=[O:17])[CH2:13][CH:12]=3)[CH:9]=[CH:10][C:4]=2[O:3]1
Reactant: CC1(C)Cc2cc(C3CCC(=O)CC3)ccc2O1
Agent: [Pd]
Solvent: CCO
Product: CC1(C)Cc2cc(C3=CCC(=O)CC3)ccc2O1

Procedure:
This compound is prepared in a manner analogous to that of Step C of Example 2, by the hydrogenation of 6.3 grams (0.026 mole) of 1-(2,3-dihydro-2,2-dimethylbenzofuran-5-yl)-1-cyclohexen-4-one in the presence of 0.4 gram (catalyst) of 10% palladium on charcoal in 50 mL of ethanol, yielding 4-(2,3-dihydro-2,2-dimethylbenzofuran-5-yl)-1-cyclohexanone.
Reaction SMILES: C([O:5][C:6](=[O:30])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=1[C:18](=[O:29])[NH:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([Br:27])=[CH:23][C:22]=1[F:28])(C)(C)C.FC(F)(F)C(O)=O>ClCCl.O>[Br:27][C:24]1[CH:25]=[CH:26][C:21]([CH2:20][NH:19][C:18]([C:10]2[CH:11]=[C:12]([N+:15]([O-:17])=[O:16])[CH:13]=[CH:14][C:9]=2[O:8][CH2:7][C:6]([OH:30])=[O:5])=[O:29])=[C:22]([F:28])[CH:23]=1
Reactant: CC(C)(C)OC(=O)COc1ccc([N+](=O)[O-])cc1C(=O)NCc1ccc(Br)cc1F
Solvent: ClCCl
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: O=C(O)COc1ccc([N+](=O)[O-])cc1C(=O)NCc1ccc(Br)cc1F
Reaction time: 24 h
Yield: 92 %

Procedure:
A solution of (2-(4-bromo-2-fluoro-benzylcarbamoyl)-4-nitro-phenoxy]-acetic acid tert-butyl ester in dichloromethane (11 mL, 0.2 M) was treated with trifluoroacetic acid (3.0 mL, 4.44 g. 39.0 mmol) and stirred for 24 h. The reaction was diluted with H2O and extracted with ethyl acetate (3×). The combined organic extracts were washed with H2O (2×), saturated aq NaCl, dried over MgSO4, filtered and concentrated to a crude solid that was recrystallized from heptane and ethyl acetate to give (2-(4-bromo-2-fluoro-benzylcarbamoyl)-4-nitro-phenoxy]-acetic acid as a white crystalline solid (0.98 g, 92%); Rf 0.10 (10% ethyl acetate in dichloromethane); 1H NMR (DMSO-d6, 300 MHz) δ 9.14 (br t, J=6.0 Hz, 1 H), 8.58 (d, J=3.3 Hz, 1 H), 8.34 (dd, J1=9.0 Hz, J2=3.0 Hz, 1 H), 7.52 (br dd, J, =9.3 Hz, J2=3.0 Hz, 1 H), 7.43–7.32 (m, 3 H), 5.02 (s, 2 H), 4.52 (d, J=6.0 Hz, 2H). ESI-LC/MS m/z calcd for C16H12BrFN2O6: 426.0 found 427.0 (M+1)+. Anal. calcd for C16H12BrFN2O6: C, 44.99; H, 2.83; N, 6.56. Found C, 44.97; H, 2.83; N, 6.47.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.Br[C:12]1[CH:19]=[CH:18][C:15]([CH:16]=[O:17])=[CH:14][CH:13]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(COC)OC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:12]2[CH:19]=[CH:18][C:15]([CH:16]=[O:17])=[CH:14][CH:13]=2)=[CH:4][CH:3]=1
Reactant: O=Cc1ccc(Br)cc1
Reactant: OB(O)c1ccc(Cl)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Solvent: COCCOC
Product: O=Cc1ccc(-c2ccc(Cl)cc2)cc1
Yield: 94 %

Procedure:
A mixture of 4-chlorobenzeneboronic acid (19.4 g, 1 equiv), 4-bromobenzaldehyde (22.9 g, 1 equiv), palladium(II) acetate (1.4 g, 0.05 equiv) aqueous sodium carbonate (30.3 g in 144 ml solution, 2 equiv) and dimethoxyethane (500 ml) was stirred at reflux under argon for 2.5 h, then evaporated to low volume and diluted with dichloromethane. Workup continued as in (a) above to give identical material (25.2 g, 94%). 1H-NMR (CDCl3) δ 10.05 (1H, s), 7.96 (2H, d), 7.73 (2H, d), 7.57 (2H, d), 7.46 (2H, d); MS (AP+) found (M+1)=217, C13H935ClO requires 216.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[C:9]([Br:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].Cl.N([O-])=O.[Na+].[N-:17]=[N+:18]=[N-].[Na+].CC([O-])=O.[Na+]>O>[N:1]([C:2]1[CH:10]=[C:9]([Br:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5])=[N+:17]=[N-:18]
Reactant: [N-]=[N+]=[N-]
Reactant: Nc1cc(Br)ccc1C(=O)O
Agent: CC(=O)[O-]
Agent: Cl
Agent: O=N[O-]
Solvent: O
Product: [N-]=[N+]=Nc1cc(Br)ccc1C(=O)O
Reaction time: 0.25 h
Yield: 67.8 %

Procedure:
To a solution of 2-amino-4-bromobenzoic acid (8.4 g, 0.039 mol) in a mixture of concentrated HCl (70 mL) and H2O (100 mL) was added a solution of NaNO2 (2.8 g, 0.044 mol) in H2O (40 mL) such that the reaction temperature did not rise above 5° C. After addition was complete the resulting slurry was stirred for 15 min and the cold mixture added in aliquots to a solution of NaN3 (2.5 g, 0.039 mol) and NaOAc (38 g, 0.47 mol) in H2O (80 mL) at room temperature. The resulting slurry was stirred for 30 min and the solid collected by filtration giving 6.4 g (68% yield) of product as a tan powder. 1H NMR (360 MHz, DMSO): 7.46 (1H, dd, J 1.4 and 7.5 Hz), 7.57 (1H, d, J 1.4 Hz), 7.70 (1H, d, J 7.5 Hz).
Reaction SMILES: [NH2:1][C:2]1[C:7]([CH2:8][NH:9][C:10]([NH:12][CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)=[O:11])=[C:6]([CH:19]2[CH2:24][CH2:23][CH2:22][N:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:20]2)[CH:5]=[C:4]([C:32]2[C:37]([OH:38])=[CH:36][CH:35]=[CH:34][C:33]=2[O:39][CH2:40][CH:41]2[CH2:43][CH2:42]2)[N:3]=1.C(N(CC)CC)C.Cl[C:52](Cl)([O:54]C(=O)OC(Cl)(Cl)Cl)Cl>O1CCCC1>[CH:13]1([NH:12][C:10]([N:9]2[CH2:8][C:7]3[C:6]([CH:19]4[CH2:24][CH2:23][CH2:22][N:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:20]4)=[CH:5][C:4]([C:32]4[C:37]([OH:38])=[CH:36][CH:35]=[CH:34][C:33]=4[O:39][CH2:40][CH:41]4[CH2:43][CH2:42]4)=[N:3][C:2]=3[NH:1][C:52]2=[O:54])=[O:11])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1
Reactant: CC(C)(C)OC(=O)N1CCCC(c2cc(-c3c(O)cccc3OCC3CC3)nc(N)c2CNC(=O)NC2CCCCC2)C1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCCC(c2cc(-c3c(O)cccc3OCC3CC3)nc3c2CN(C(=O)NC2CCCCC2)C(=O)N3)C1
Temperature: 0 °C
Reaction time: 2 h
Yield: 52.1 %

Procedure:
To a cooled (0° C.) solution of tert-butyl 3-{2-amino-3-({[(cyclohexylamino)-carbonyl]amino}methyl)-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-pyridinyl}-1-piperidinecarboxylate(0.039 g, 0.065 mmol), which was obtained in the step (1) of Example 23-3, and triethylamine (15.0 mL, 0.389 mmol) in tetrahydrofuran (10.0 mL) was added dropwise a solution of triphosgene (0.019 g, 0.065 mmol) in tetrahydrofuran (5.0 mL) under an argon atmosphere. The mixture was stirred at 0° C. for 2 hrs. After quenched by water, the mixture was extracted with ethyl acetate. The separated organic phase was washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The resulting residue (white solid) was triturated with diisopropyl ether, collected by filtration, washed with diisopropyl ether, and dried under reduced pressure to give tert-butyl 3-{3-[(cyclohexylamino)carbonyl]-7-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-2-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-5-yl}-1-piperidinecarboxylate (0.021 g, yield; 52%).
Reaction SMILES: [CH2:1]([NH:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[C:16]([CH2:17][O:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=3)=[C:15]([C:26]([NH:28][CH2:29][CH2:30][OH:31])=[O:27])[N:14]=[N:13]2)=[CH:8][CH:7]=1)=[O:5])[CH3:2].[C:32](Cl)(=[O:36])[O:33][CH2:34][CH3:35].N1C=CC=CC=1.O>C1COCC1>[C:32](=[O:36])([O:33][CH2:34][CH3:35])[O:31][CH2:30][CH2:29][NH:28][C:26]([C:15]1[N:14]=[N:13][N:12]([C:9]2[CH:8]=[CH:7][C:6]([C:4]([NH:3][CH2:1][CH3:2])=[O:5])=[CH:11][CH:10]=2)[C:16]=1[CH2:17][O:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=1)=[O:27]
Reactant: CCOC(=O)Cl
Reactant: CCNC(=O)c1ccc(-n2nnc(C(=O)NCCO)c2COc2cccc(F)c2)cc1
Solvent: O
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: CCNC(=O)c1ccc(-n2nnc(C(=O)NCCOC(=O)OCC)c2COc2cccc(F)c2)cc1

Procedure:
To a solution of 1-{4-[(ethylamino)carbonyl]phenyl}-5-[(3-fluorophenoxy)methyl]-N-(2-hydroxyethyl)-1H-1,2,3-triazole-4-carboxamide (600 mg) obtained in Example 498 in THF (15 ml) were added ethyl chlorocarbonate (0.15 ml) and pyridine (0.17 ml), and the mixture was stirred under ice-cooling for 4 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate and washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column (ethyl acetate/hexane=3/1 to ethyl acetate) and recrystallized from ethyl acetate to give the title compound as a colorless powder (520 mg).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][O:4][C:5]1[C:10]([CH3:11])=[CH:9][C:8]([C:12]2[NH:21][C:20](=[O:22])[C:19]3[C:14](=[CH:15][C:16]([O:25][CH3:26])=[CH:17][C:18]=3[O:23][CH3:24])[N:13]=2)=[CH:7][C:6]=1[CH3:27].[CH3:28][N:29]=[C:30]=[O:31].CCN(CC)CC>C1COCC1>[CH3:24][O:23][C:18]1[CH:17]=[C:16]([O:25][CH3:26])[CH:15]=[C:14]2[C:19]=1[C:20](=[O:22])[NH:21][C:12]([C:8]1[CH:9]=[C:10]([CH3:11])[C:5]([O:4][CH2:3][CH2:2][NH:1][C:30]([NH:29][CH3:28])=[O:31])=[C:6]([CH3:27])[CH:7]=1)=[N:13]2
Reactant: COc1cc(OC)c2c(=O)[nH]c(-c3cc(C)c(OCCN)c(C)c3)nc2c1
Reactant: CN=C=O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CNC(=O)NCCOc1c(C)cc(-c2nc3cc(OC)cc(OC)c3c(=O)[nH]2)cc1C
Temperature: 25 °C
Reaction time: 16 h
Yield: 71.2 %

Procedure:
A mixture of compound 2-(4-(2-aminoethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one (0.10 g, 0.27 mmol), methylisocyanate (0.020 g, 0.35 mmol), and Et3N (0.034 g, 0.35 mmol) in THF (4.0 mL) was stirred at room temperature for 16 hours. The mixture was filtered, washed with CH2Cl2 and the solvent was removed under reduced pressure. The resulting residue was chromatographed on silica gel to yield the title compound (0.082 g, 71%) as a white solid: MS (APCI) m/z 449 [M+Na]+.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)=[O:9])=[CH:4][CH:3]=1.[CH3:18][N:19]([CH2:21][C:22]#[CH:23])[CH3:20]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.CCN(CC)CC>[CH3:18][N:19]([CH3:20])[CH2:21][C:22]#[C:23][C:2]1[N:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)=[O:9])=[CH:4][CH:3]=1
Reactant: COc1ccc(C(=O)c2ccc(Cl)nc2)cc1
Reactant: C#CCN(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCN(CC)CC
Product: COc1ccc(C(=O)c2ccc(C#CCN(C)C)nc2)cc1
Temperature: 80 °C
Reaction time: 24 h
Yield: 80.2 %

Procedure:
A 25 ml Schlenk flask was charged with (6-chloropyridin-3-yl)(4-methoxy-phenyl)methanone (124 mg, 0.5 mmol), Pd(PPh3)2Cl2 (18 mg, 0.0 25 mmol), CuI (10 mg, 0.05 mmol), Et3N (10 mL), and N,N-dimethylpropargylamine (83 mg, 1.0 mmol). The flask was flushed with argon three times and the mixture was stirred at 80° C. for 24 h. The solvent was evaporated under vacuum and the residue was purified by column chromatography to give the product (118 mg, 80% yield).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8]Cl>C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[CH3:1]
Reactant: Cc1ccccc1CCl
Solvent: Cc1ccccc1
Product: Cc1ccccc1Cc1ccccc1C
Yield: 81 %

Procedure:
A German patent, Ger.Offen 2,547,030 (1977), disclosed the preparation of o-benzyl toluenes by the reaction of o-methylbenzyl halides with substituted benzenes in the presence of Al-silicate. The 2-CH3C6H4CH2Cl was stirred with toluene and Al-silicate (25% Al2O3) at 110° C. to give 81% 2-methylbenzyltoluene. According to a Japanese patent, JP 59,186,937 (1984), o-benzylphenol was prepared by the liquid phase reaction of benzyl alcohol with phenol in the presence of γ-Al2O3. For example 7.5 g γ-Al2O3 was added to a mixture of 32.5 g benzyl alcohol and 47 g phenol at 190° C. under stirring to give a product-containing 49.9% o-benzylphenol. A German Patent, Ger. Offen DE 3,700,917 (1988), disclosed the preparation of p-substituted o-benzylphenols by alkylation of p-substituted phenols with benzylalcohol in the presence of Na—Y type zeolite. A mixture of 0.5 mole 4-ClC6H4OH, 0.1 mole C6H5CH2OH and 0.6 g of Na—Y type zeolite was heated at 200° C. for 3 hrs to give 25.4% 2-benzyl-4-chlorophenol.
Reaction SMILES: [C:1]1([CH2:7][S:8]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][C:15](=[O:20])[CH2:14]3)(=[O:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:21][C:22]1[C:26]([CH2:27][C:28]([N:30]2[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]2)=[O:29])=[C:25]([CH3:37])[NH:24][C:23]=1[CH:38]=O.N1CCCCC1>C(O)C>[CH3:21][C:22]1[C:26]([CH2:27][C:28]([N:30]2[CH2:31][CH2:32][N:33]([CH3:36])[CH2:34][CH2:35]2)=[O:29])=[C:25]([CH3:37])[NH:24][C:23]=1/[CH:38]=[C:14]1\[C:15](=[O:20])[NH:16][C:17]2[C:13]\1=[CH:12][C:11]([S:8]([CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)(=[O:10])=[O:9])=[CH:19][CH:18]=2
Reactant: Cc1[nH]c(C=O)c(C)c1CC(=O)N1CCN(C)CC1
Reactant: O=C1Cc2cc(S(=O)(=O)Cc3ccccc3)ccc2N1
Solvent: CCO
Solvent: C1CCNCC1
Product: Cc1[nH]c(/C=C2\C(=O)Nc3ccc(S(=O)(=O)Cc4ccccc4)cc32)c(C)c1CC(=O)N1CCN(C)CC1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
A mixture of 5-phenylmethanesulfonyl-1,3-dihydro-indol-2-one (100 mg, 0.35 mmol), 3,5-dimethyl-4-[2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl]-1H-pyrrole-2-carbaldehyde (174 mg, 0.68 mmol) and piperidine (0.5 eq.) in ethanol (2 mL) was stirred at rt for 48 hours. The reaction was concentrated and triturated with acetone to give the titled compound as a pale orange solid.
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[N:9][C:10]3[C:15]([C:16]=2[C:17]2[CH:18]=[C:19]([NH2:23])[CH:20]=[CH:21][CH:22]=2)=[CH:14][CH:13]=[CH:12][C:11]=3[C:24]([F:27])([F:26])[F:25])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:28]1([N:34]=[C:35]=[O:36])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C(N(CC)CC)C>[C:28]1([NH:34][C:35]([NH:23][C:19]2[CH:20]=[CH:21][CH:22]=[C:17]([C:16]3[C:15]4[C:10](=[C:11]([C:24]([F:27])([F:25])[F:26])[CH:12]=[CH:13][CH:14]=4)[N:9]=[CH:8][C:7]=3[C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH:18]=2)=[O:36])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: Nc1cccc(-c2c(-c3ccccc3)cnc3c(C(F)(F)F)cccc23)c1
Reactant: O=C=Nc1ccccc1
Solvent: CCN(CC)CC
Product: O=C(Nc1ccccc1)Nc1cccc(-c2c(-c3ccccc3)cnc3c(C(F)(F)F)cccc23)c1

Procedure:
The title compound was prepared from {3-[3-phenyl-8-(trifluoromethyl)quinolin-4-yl]phenyl}amine and phenyl isocyanate in substantially the same manner as described in Example 61 with one change: no triethylamine was used; off-white solid: mp 202-205° C.; MS (ES) m/z 481.8.
Reaction SMILES: [CH2:1]([O:11][C:12]1[CH:13]=[C:14]([CH:19]=[C:20]([O:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[CH:21]=1)[CH2:15][N:16]=[N+]=[N-])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].ClCCl.[N-]=[N+]=[N-]>[Pd].CCOCC.CO>[CH2:23]([O:22][C:20]1[CH:19]=[C:14]([CH:13]=[C:12]([O:11][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])[CH:21]=1)[CH2:15][NH2:16])[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]
Reactant: CCCCCCCCCCOc1cc(CN=[N+]=[N-])cc(OCCCCCCCCCC)c1
Agent: [Pd]
Agent: [N-]=[N+]=[N-]
Solvent: ClCCl
Solvent: CO
Solvent: CCOCC
Product: CCCCCCCCCCOc1cc(CN)cc(OCCCCCCCCCC)c1
Reaction time: 1 h
Yield: 97.9 %

Procedure:
Catalytic (5% by mass) palladium on carbon (0.51 g) was placed into a hydrogenation bottle. The bottle was then placed under N2. To the bottle, 50/50 ether methanol (10 mL) was added. 3,5-didecoxybenzyl azide (5.0 g, 11.2 mmol) was dissolved in 50/50 ether/methanol (60 mL) and transferred to the bottle. The bottle was attached to a hydrogenator with H2 pressure at 40 psi and left for 1 hour. Thin layer chromatography of the dichloromethane/10% hexanes showed the presence of an azide. The bottle was left on a hydrogenator with H2 at 40 psi for an additional hour after which time, thin layer chromatography then showed no evidence of the starting material. The contents of the bottle were then vacuum filtered over celite. The filtrate was then concentrated using rotary evaporation and then placed under high vacuum for 4 or more hours. The resulting viscous liquid was dark yellow. This produced a 4.6 g yield or a 97.9% yield of the derivative. The NMR characterization data for this derivative is as follows. 1NMR (300 MHz, CDCl3): 0.88 (t, J=6.6, 6H, CH2CH3), 1.27-1.46 (m, 28H, CH2(CH2)7), 1.77 (p, J=6.6, 4H, OCH2CH2), 3.92 (t, J=6.6, 4H, OCH2), 3.78 (s, 2H, ArCH2NH2), 6.33 (t, J=2.2, 1H, ArH), 6.44 (d, J=2.2, 2H, ArH). 13C NMR (75 MHZ, CDCl3): 14.23, 22.79, 26.16, 29.39, 29.45, 29.50, 29.69, 29.72, 32.01, 46.80, 69.04, 99.61, 105.35, 145.79, 160.58.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]([CH3:12])[CH3:11])[C:5]=1[NH:13][S:14]([CH2:17][C:18](NC1N=NN(CCCCCCCCCCCC)N=1)=[O:19])(=[O:16])=[O:15])([CH3:3])[CH3:2].[CH2:38]([OH:50])[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49]>>[CH2:38]([O:50][C:18](=[O:19])[CH2:17][S:14](=[O:15])(=[O:16])[NH:13][C:5]1[C:6]([CH:10]([CH3:12])[CH3:11])=[CH:7][CH:8]=[CH:9][C:4]=1[CH:1]([CH3:2])[CH3:3])[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49]
Reactant: CCCCCCCCCCCCO
Reactant: CCCCCCCCCCCCn1nnc(NC(=O)CS(=O)(=O)Nc2c(C(C)C)cccc2C(C)C)n1
Product: CCCCCCCCCCCCOC(=O)CS(=O)(=O)Nc1c(C(C)C)cccc1C(C)C

Procedure:
This compound was prepared in the same manner as for the title compound of Example 2, except that 2-DAT was replaced with dodecanol, mp 58°-59° C.