Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-:10])=[O:9])[C:3]=1F.[CH:12]1([NH2:15])[CH2:14][CH2:13]1>C1COCC1.CCOC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-:10])=[O:9])[C:3]=1[NH:15][CH:12]1[CH2:14][CH2:13]1
Reactant: O=[N+]([O-])c1cccc(Br)c1F
Reactant: NC1CC1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: O=[N+]([O-])c1cccc(Br)c1NC1CC1
Temperature: 60 °C
Reaction time: 18 h

Procedure:
A mixture of 1-bromo-2-fluoro-3-nitrobenzene (4.1 g, 18.6 mmol) and cyclopropanamine (1.29 mL, 18.6 mmol) in THF (10 mL) was stirred under N2 at 60° C. for 18 h. The reaction mixture was diluted with EtOAc, washed with water, filtered on a pad of Celite™, washed with brine and dried over magnesium sulfate. The solution was concentrated in vacuo. Purification of the residue by flash chromatography on a silica gel column using 30 to 50% gradient of DCM in hexane as eluent gave 2-bromo-N-cyclopropyl-6-nitroaniline: LC-MS (ESI) m/z 259.0 [M+H]+.
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:27])[CH2:10][C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:13]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br:28]N1C(=O)CCC1=O.C(O[C:44](=[O:55])CC1C2C(=CC=CC=2)NC=1)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[CH2:1]([O:8][C:9](=[O:27])[CH2:10][C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:55][CH3:44])[CH:18]=2)[N:13]([CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:12]=1[Br:28])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(Cc1cn(Cc2ccccc2)c2ccccc12)OCc1ccccc1
Reactant: O=C1CCC(=O)N1Br
Reactant: O=C(Cc1c[nH]c2ccccc12)OCc1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: COc1ccc2c(c1)c(CC(=O)OCc1ccccc1)c(Br)n2Cc1ccccc1
Reaction time: 0.5 h
Yield: 67 %

Procedure:
2-Bromo-5-methoxy-!-(phenylmethyl)-1H-indole-3-acetic acid benzyl ester. N-Bromosuccinimide (450 mg, 2.5 mmol) was added to 910 mg (2.5 mmol) of 5-methoxy-1-phenylmethyl)-1H-indole-3-acetic acid benzyl ester in 75 mL of carbon tetrachloride and the mixture stirred for 0.5 hour. After washing with Na2S2O3 solution, water and saturated NaCl solution and drying (Na2SO4), the CCl4 was removed at reduced pressure. The residue was chromatographed on silica (eluted with methylene chloride) and crystallized from ether/hexane to give 765 mg (67% yield) of 2-bromo-5-methoxy-1-(phenylmethyl)-1H-indole-3-acetic acid benzyl ester, mp, 89-90° C.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([C:9]([N:11]2[CH2:16][CH2:15][N:14]([S:17]([C:20]3[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][C:21]=3[CH3:28])(=[O:19])=[O:18])[CH2:13][C@@H:12]2[CH3:29])=[O:10])=[CH:4][CH:3]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>C(O)(C)C>[ClH:1].[CH3:28][C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][C:20]=1[S:17]([N:14]1[CH2:15][CH2:16][N:11]([C:9]([C:5]2[C:6]([CH3:8])=[N:7][C:2]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)=[CH:3][CH:4]=2)=[O:10])[C@@H:12]([CH3:29])[CH2:13]1)(=[O:19])=[O:18])[C:24]#[N:25]
Reactant: Cc1cc(C#N)ccc1S(=O)(=O)N1CCN(C(=O)c2ccc(Cl)nc2C)[C@@H](C)C1
Reactant: C1COCCN1
Solvent: CC(C)O
Product: Cc1cc(C#N)ccc1S(=O)(=O)N1CCN(C(=O)c2ccc(N3CCOCC3)nc2C)[C@@H](C)C1
Product: Cl
Temperature: 120 °C
Yield: 45.9 %

Procedure:
4-({(3S)-4-[(6-Chloro-2-methyl-3-pyridinyl)carbonyl]-3-methyl-1-piperazinyl}sulfonyl)-3-methylbenzonitrile (may be prepared as described in Example 25) (55 mg, 0.13 mmol) was weighed into a microwave vial, and suspended in isopropanol (1.3 ml). Morpholine (0.221 ml, 2.54 mmol) was added and the mixture was heated in the microwave to 120° C. for 12 h with stirring. LCMS analysis indicated >65% conversion. The reaction mixture was concentrated to give the crude material as a pale yellow gum (78 mg). This was purified by MDAP to give the free base of the title compound as a colourless gum (31 mg).
Reaction SMILES: [CH:1]([O:4][CH2:5][CH2:6][CH:7]=[CH:8][CH2:9][SH:10])([CH3:3])[CH3:2].[OH-].[Na+].[Cl:13][C:14]1[CH:21]=[CH:20][C:17]([CH2:18]Cl)=[CH:16][CH:15]=1>C(O)C>[CH:1]([O:4][CH2:5][CH2:6][CH:7]=[CH:8][CH2:9][S:10][CH2:18][C:17]1[CH:20]=[CH:21][C:14]([Cl:13])=[CH:15][CH:16]=1)([CH3:3])[CH3:2]
Reactant: CC(C)OCCC=CCS
Reactant: ClCc1ccc(Cl)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CC(C)OCCC=CCSCc1ccc(Cl)cc1

Procedure:
A solution of 8.0 g (0.05 mol) of 5-isopropoxy-2-penten-1-thiol and 2 g (0.05 mol) of sodium hydroxide in 30 cc of ethanol are added dropwise at 50° during the course of 45 minutes to a solution of 8.05 g (0.05 mol) of p-chloro-benzylchloride in 25 cc of ethanol, the temperature not exceeding 55°. After the addition is complete the mixture is heated to 60° during 10 minutes. The reaction mixture is filtered, the ethanol is distilled off and the residue is chromatographed on silica gel with chloroform, whereby 4-[(5-isopropoxy-2-pentenylthio)-methyl]-chlorobenzol is obtained which is identical with the compound produced in accordance with Example 40.
Reaction SMILES: C[Mg]Cl.[CH2:4]([N:11]1[CH2:15][CH:14]=[CH:13][CH2:12]1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH2:16]([N:23]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH:24]=O)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C1([Mg]Br)CCCCC1>O1CCCC1.C(O[Ti](OC(C)C)(OC(C)C)OC(C)C)(C)C.O>[CH2:4]([N:11]1[CH2:15][CH:14]2[CH:13]([CH:24]2[N:23]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:12]1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: O=CN(Cc1ccccc1)Cc1ccccc1
Reactant: C1=CCN(Cc2ccccc2)C1
Agent: CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C
Agent: Br[Mg]C1CCCCC1
Agent: C[Mg]Cl
Solvent: C1CCOC1
Solvent: O
Product: c1ccc(CN2CC3C(C2)C3N(Cc2ccccc2)Cc2ccccc2)cc1
Reaction time: 0.17 h
Yield: 69 %

Procedure:
At room temperature, a solution of methylmagnesium chloride (3.4 ml, 3 M in tetrahydrofuran) was added dropwise over a period of 10 min to a mixture of N-benzyl-3-pyrroline (1.48 g) and tetraisopropoxytitanium (2.72 ml, 9.3 mmol) tetrahydrofuran. After the solution had stirred for a further 10 min, a solution of dibenzylformamide (2.1 g) in 5 ml of tetrahydrofuran was added at room temperature over a period of 30 seconds. A solution of cyclohexylmagnesium bromide (5.2 ml, 1.95 M in diethyl ether) was then added dropwise over a period of 2 hours, and the mixture was heated under reflux for another 4 hours. The hot reaction mixture was admixed with water (5 ml) (careful, exothermic reaction), and the resulting precipitate was collected on a filter and washed with 20 ml of diethyl ether. The combined filtrates were concentrated under reduced pressure. Unreacted N-benzyl-3-pyrroline. Dibenzylformamide and unidentified compounds were distilled off from the residue under reduced pressure 1.3×10-4 mbar, bath temperature 150° C.). Further distillation (bath temperature 180-200° C.) gave 3-benzyl-6-(dibenzylamino)-3-azabicyclo[3.1.0]hexane (2.62 g, 90% pure according to 1H NMR, corresponding to a yield of 69%), contaminated by dibenzylformamide, as a slightly yellowish viscous oil.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3]1.C([Li])(C)(C)C.CCCCC.[CH3:21][N:22]([CH3:36])[C:23]1([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:28][CH2:27][C:26](=[O:29])[CH2:25][CH2:24]1>C1COCC1>[CH3:21][N:22]([CH3:36])[C:23]1([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:28][CH2:27][C:26]([C:3]2[N:2]([CH3:1])[C:10]3[C:5]([CH:4]=2)=[CH:6][CH:7]=[CH:8][CH:9]=3)([OH:29])[CH2:25][CH2:24]1
Reactant: CN(C)C1(c2ccccc2)CCC(=O)CC1
Reactant: Cn1ccc2ccccc21
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Solvent: CCCCC
Product: CN(C)C1(c2ccccc2)CCC(O)(c2cc3ccccc3n2C)CC1
Temperature: 0 °C
Reaction time: 2 h
Yield: 29.9 %

Procedure:
A solution of N-methylindol (400 mg, 3.05 mmol) in dry THF (20 ml) was cooled to −5° C. under a stream of argon. Tert-butyllithium (3.65 mmol, 2.15 ml of a 1.7 molar pentane solution) was added dropwise in such a way that a reaction temperature of 0° C. was not exceeded. Once all the substance had been added, the reaction mixture was stirred for 2 hours at 0° C. A solution of 4-dimethylamino-4-phenylcyclohexanone (662 mg, 3.05 mmol) in dry THF (5 ml) was added dropwise at 0° C. The mixture was stirred for 15 minutes at 0° C. and then 4 hours at ambient temperature. The reaction mixture was quenched with saturated ammonium chloride solution (20 ml), the organic phase was separated and the aqueous phase extracted four times with dichloromethane (20 ml). The combined organic phases were dried over sodium sulfate, filtered and the solvent removed under vacuum. Purification was carried out by flash chromatography with cyclohexane/ethylacetate (V:V=7:3) over silica gel. 318 mg 4-dimethylamino-1-(1-methyl-1H-indol-2-yl)-4-phenylcyclohexanol with a melting point of 163–165° C. were obtained.
Reaction SMILES: [C:1](Cl)(Cl)=[S:2].O.C(COC)OC.[Cl:12][C:13]1[N:18]=[C:17]([O:19][C:20]2[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][CH:21]=2)[CH:16]=[CH:15][CH:14]=1>CCCCCC>[Cl:12][C:13]1[N:18]=[C:17]([O:19][C:20]2[CH:25]=[CH:24][C:23]([N:26]=[C:1]=[S:2])=[CH:22][CH:21]=2)[CH:16]=[CH:15][CH:14]=1
Reactant: S=C(Cl)Cl
Reactant: Nc1ccc(Oc2cccc(Cl)n2)cc1
Solvent: COCCOC
Solvent: CCCCCC
Solvent: O
Product: S=C=Nc1ccc(Oc2cccc(Cl)n2)cc1

Procedure:
Thiophosgene (10.5 grams; 0.091 mole) was added to an agitated solution of water (170 ml.) and dimethoxyethane (25 ml.) 4-((6-Chloro-2-pyridinyl)oxy)benzenamine (20 grams; 0.0906 mole) was added in small portions (the dimethoxyethane aids in suspending the amine in the aqueous thiosphosgene solution) to the stirred thiophosgene solution over a 20 minute period. The reactive temperature during the addition was 25°-30° C. Following the addition of the amine reactant, the reaction mixture was filtered to recover the product precipitate which formed during the reaction. The precipitate was then dissolved in boiling hexane and the resulting solution dried and cooled to give the desired 4-((6-chloro-2-pyridinyl)oxy)phenyl isothiocyanate product as a light yellow crystalline solid having a melting point of 59°-62° C. The product was found to have carbon, hydrogen, nitrogen, chlorine and sulfur contents of 55.5, 2.3, 10.9, 13.36 and 12.34 percent, respectively, as compared with the theoretical contents of 54.82, 2.69, 10.66, 13.5 and 12.2 percent, respectively, calculated for the named structure.
Reaction SMILES: [NH2:1][C@@H:2]1[CH2:11][CH2:10][C:9]2[C:4](=[C:5]([N:12]3[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]3)[CH:6]=[CH:7][CH:8]=2)[CH2:3]1.C(N(CC)CC)C.[Br:26][C:27]1[CH:35]=[CH:34][C:30]([C:31](Cl)=[O:32])=[CH:29][CH:28]=1>C(Cl)Cl>[CH3:18][N:15]1[CH2:16][CH2:17][N:12]([C:5]2[CH:6]=[CH:7][CH:8]=[C:9]3[C:4]=2[CH2:3][C@H:2]([NH:1][C:31](=[O:32])[C:30]2[CH:34]=[CH:35][C:27]([Br:26])=[CH:28][CH:29]=2)[CH2:11][CH2:10]3)[CH2:13][CH2:14]1
Reactant: O=C(Cl)c1ccc(Br)cc1
Reactant: CN1CCN(c2cccc3c2C[C@H](N)CC3)CC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CN1CCN(c2cccc3c2C[C@H](NC(=O)c2ccc(Br)cc2)CC3)CC1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To an ice-cooled solution of (R)-2-amino-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalene (130 mg, 0.53 mmol) and triethylamine (110 μL, 0.79 mmol) in methylene chloride (25 mL) was added dropwise 4bromobenzoyl chloride (122 mg, 0.56 mmol) in methylene chloride (5 mL). After the addition, the reaction was allowed to stir at ambient temperature for 15 min and was then washed with dilute aqueous sodium hydrogen carbonate. The phases were separated and the organic phase was dried (Na2SO4), filtered and evaporated in vacuo to give a crude product which was purified on a silica gel column using chloroform/ethanol saturated with NH3 (100:4) as the eluent. Yield: 120 mg (51%) of the title compound as white crystals: mp 200-201° C.; [α]21D -32° (c 1.0, chloroform); EIMS (70 eV) m/z (relative intensity) 427 and 429 (3, M+).
Reaction SMILES: Br[C:2]1[C:7]([CH3:8])=[CH:6][N:5]=[C:4]([CH3:9])[CH:3]=1.C([Li])CCC.[Si]([O:22][C:23]1[CH:24]=[C:25]([CH:41]=[CH:42][CH:43]=1)[C:26]([C:28]1[CH:40]=[CH:39][C:31]([C:32]([N:34]([CH2:37][CH3:38])[CH2:35][CH3:36])=[O:33])=[CH:30][CH:29]=1)=[O:27])(C(C)(C)C)(C)C.N1C=CC=CC=1>C(OCC)C>[CH3:9][C:4]1[CH:3]=[C:2]([C:26]([C:28]2[CH:40]=[CH:39][C:31]([C:32]([N:34]([CH2:35][CH3:36])[CH2:37][CH3:38])=[O:33])=[CH:30][CH:29]=2)([OH:27])[C:25]2[CH:41]=[CH:42][CH:43]=[C:23]([OH:22])[CH:24]=2)[C:7]([CH3:8])=[CH:6][N:5]=1
Reactant: Cc1cc(Br)c(C)cn1
Reactant: CCN(CC)C(=O)c1ccc(C(=O)c2cccc(O[Si](C)(C)C(C)(C)C)c2)cc1
Agent: [Li]CCCC
Solvent: c1ccncc1
Solvent: CCOCC
Product: CCN(CC)C(=O)c1ccc(C(O)(c2cccc(O)c2)c2cc(C)ncc2C)cc1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 48.8 %

Procedure:
A portion of the 4-bromo-2,5-dimethylpyridine (15.4 g, 83.0 mmol) was dissolved in 500 mL of anhydrous diethyl ether and chilled to -78° C. n-Butyllithium (52 mL, 1.6M in hexanes) was added dropwise and the resulting slurry was stirred for 30 minutes. 4-(3-((tert-butyldimethylsilyl)oxy)benzoyl)-N,N-diethylbenzamide (34.2 g, 83.0 mmol) was dissolved in 250 mL of anhydrous diethyl ether and chilled to -78° C. The lithiated pyridine was slowly transferred via cannula to the diarylketone solution. The temperature was allowed to rise to -40° C. for 4.5 hours. The reaction was quenched with saturated aqueous ammonium chloride. The diethyl ether layer was separated, the solvent was removed, and the residue was redissolved in 300 mL acetonitrile. Tetraethylammonium fluoride hydrate (19.8 g) was added, and the reaction was stirred overnight. The solvent was removed, and the residue was redissolved in 500 mL 1M hydrochloric acid and washed with 500 mL of diethyl ether. The pH of the aqueous solution was adjusted to 8 and the solution was extracted with dichloromethane. The solvent was removed and the residue was crystallized from acetonitrile to give 16.4 g (48%) of (±)-4-(α-(2,5-dimethyl-4-pyridyl)-α,3-dihydroxybenzyl)-N,N-diethylbenzamide.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[C:22]([CH3:23])=[CH:21][C:19]([NH2:20])=[C:18]([CH3:24])[CH:17]=1.Cl[C:26](Cl)([O:28]C(=O)OC(Cl)(Cl)Cl)Cl.[NH2:37][C:38]1[C:39]([O:46][CH3:47])=[N:40][C:41]([O:44][CH3:45])=[CH:42][CH:43]=1.C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.C(N(CC)CC)C.ClCCl>[CH3:47][O:46][C:39]1[C:38]([NH:37][C:26]([NH:20][C:19]2[CH:21]=[C:22]([CH3:23])[C:16]([O:15][C:6]3[C:5]4[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=4)[N:9]=[CH:8][CH:7]=3)=[CH:17][C:18]=2[CH3:24])=[O:28])=[CH:43][CH:42]=[C:41]([O:44][CH3:45])[N:40]=1
Reactant: COc1ccc(N)c(OC)n1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: COc1cc2nccc(Oc3cc(C)c(N)cc3C)c2cc1OC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Product: COc1ccc(NC(=O)Nc2cc(C)c(Oc3ccnc4cc(OC)c(OC)cc34)cc2C)c(OC)n1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 79.7 %

Procedure:
4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethyl-aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml), and a solution of triphosgene (92 mg) in dichloromethane was then added to the solution. The mixture was stirred at room temperature for 30 min. Next, 3-amino-2,6-dimethoxypyridine (70 mg) was added to the reaction solution, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was dried over sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was dissolved in a minor amount of chloroform, and a large amount of ether was added to the solution to precipitate a crystal which was then collected by filtration to give 124 mg (yield 79%) of the title compound.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[C:10]1([C:16]2[CH:21]=[CH:20]C=C(C3C=CC=CC=3)N=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[Cl:28]([OH:32])(=[O:31])(=[O:30])=[O:29]>>[Cl:28]([O-:32])(=[O:31])(=[O:30])=[O:29].[C:4]1([C:1]2[CH:2]=[CH:20][CH:21]=[C:16]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[O+:3]=2)[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: c1ccc(-c2cccc(-c3ccccc3)n2)cc1
Reactant: CC(=O)c1ccccc1
Reactant: [O-][Cl+3]([O-])([O-])O
Product: [O-][Cl+3]([O-])([O-])[O-]
Product: c1ccc(-c2cccc(-c3ccccc3)[o+]2)cc1

Procedure:
It is known that 2,6-diphenyl pyridine is formed when diphenyl pyridone dicarboxylic acid ester is distilled in the presence of zinc dust. The ester is recovered by dehydrogenation of the diphenyl piperidone dicarboxylic acid ester formed in the reaction of acetone dicarboxylic acid ester with benzaldehyde and ammonia (Berichte Vol. 42 (1910) pages 2020-2025). It is also known to start from acetophenone in production of the 2,6-diphenyl pyridine. For this purpose acetophenone is condensed with phenyl propargyl aldehyde to 1,5-diphenylpentin-(1)-en-(3)-one-(5), this reacted with perchloric acid to form 2,6-diphenyl pyrylium perchlorate and this finally converted by means of ammonia into the 2,6-diphenyl pyridine (Berichte Vol. 93 (1960) pages 1253-1256). There is also obtained 2,6-diphenyl pyridine from acetophenone and N,N,N-trimethyl-hydrazonium tetrafluoroborate or in a corresponding manner from 4-methyl acetophenone there is formed 2,6-diphenyl-3,5-dimethyl pyridine or from propiophenone there is formed 2,6-di-p-tolyl pyridine (J. Amer. Chem. Soc. Vol. 88 (1966) pages 3654-3655). It is further known to recover 2,6-diphenyl pyridine and various substituted 2,6-diphenyl pyridine by dehydrogenation of the corresponding piperidines by means of sulfur. The piperidines are produced by reduction of the corresponding 4-piperidone (J. Indian Chem. Soc. Vol. 32 (1955) pages 274-278).
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:5]2[N:6]=[CH:7][NH:8][C:4]=2[CH:3]=1.[Cl:11][C:12]1[CH:19]=[CH:18][CH:17]=[CH:16][C:13]=1[CH:14]=O.[Si](C#N)(C)(C)C.[N:26]1([C:31](N2C=CN=C2)=[O:32])C=CN=[CH:27]1>>[NH:6]1[C:5]2[CH:9]=[CH:10][C:2]([N:1]3[CH:14]([C:13]4[CH:16]=[CH:17][CH:18]=[CH:19][C:12]=4[Cl:11])[CH2:27][NH:26][C:31]3=[O:32])=[CH:3][C:4]=2[N:8]=[CH:7]1
Reactant: O=Cc1ccccc1Cl
Reactant: Nc1ccc2nc[nH]c2c1
Reactant: O=C(n1ccnc1)n1ccnc1
Agent: C[Si](C)(C)C#N
Product: O=C1NCC(c2ccccc2Cl)N1c1ccc2[nH]cnc2c1

Procedure:
The compound was synthesized starting from 5-aminobenzimidazole (0.585 g, 4.4 mmol), 2-chloro benzaldehyde (0.448 mL, 4 mmol), TMSCN (0.5 mL, 4 mmol), PdC (10%, 0.02 g), TEA (1.15 mL, 8.25 mmol), di-(imidazol-1-yl)methanone (0.700 g, 4.32 mmol) as described in method 2.
Reaction SMILES: [C:1]1([CH3:14])[CH:6]=[CH:5][CH:4]=[C:3]([N:7]2[N:11]=[N:10][C:9]([CH2:12][OH:13])=[N:8]2)[CH:2]=1.[H-].[Na+].[CH:17]1([N:20]2[C:24](S(C)(=O)=O)=[N:23][N:22]=[C:21]2[C:29]2[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=2)[CH2:19][CH2:18]1>>[CH:17]1([N:20]2[C:24]([O:13][CH2:12][C:9]3[N:10]=[N:11][N:7]([C:3]4[CH:2]=[C:1]([CH3:14])[CH:6]=[CH:5][CH:4]=4)[N:8]=3)=[N:23][N:22]=[C:21]2[C:29]2[CH:30]=[CH:31][N:32]=[CH:33][CH:34]=2)[CH2:19][CH2:18]1
Reactant: CS(=O)(=O)c1nnc(-c2ccncc2)n1C1CC1
Reactant: Cc1cccc(-n2nnc(CO)n2)c1
Agent: [H-]
Agent: [Na+]
Product: Cc1cccc(-n2nnc(COc3nnc(-c4ccncc4)n3C3CC3)n2)c1
Yield: 1.2 %

Procedure:
The title compound (4.6 mg, 11%, yellow solid) was prepared from (2-m-tolyl-2H-tetrazol-5-yl)-methanol (1 mmol), sodium hydride (1.5 mmol) and 4-(4-cyclopropyl-5-methanesulfonyl-4H-[1,2,4]triazol-3-yl)-pyridine (1.25 mmol). 1H NMR (CDCl3) δ (ppm): 8.77 (s br, 2H), 7.97 (m, 2H), 7.79 (d, 2H), 7.47 (t, 1H), 7.35 (d, 1H), 5.94 (s, 2H), 3.21 (m, 1H), 2.50 (s, 3H), 1.12 (m, 2H), 0.86 (m, 2H).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1N.C[N+:8]([CH3:11])(C)C.C1C=C2C(C=C(C([S-])=S)C=C2)=CC=1.C([Li])CCC.[CH2:30]1[CH2:34][O:33][CH2:32][CH2:31]1>>[CH:30]1([CH:34]([C:2]2[S:1][C:5]([CH2:11][NH2:8])=[CH:4][CH:3]=2)[OH:33])[CH2:31][CH2:32]1
Reactant: C[N+](C)(C)C
Reactant: C1CCOC1
Reactant: Nc1cccs1
Agent: S=C([S-])c1ccc2ccccc2c1
Agent: [Li]CCCC
Product: NCc1ccc(C(O)C2CC2)s1
Temperature: 0 °C

Procedure:
Thienylamine of formula SS-1 (0.95 mL) is dissolved in dry THF under a nitrogen atmosphere and cooled to -78° C. n-Butyllithium (Aldrich, 1.6M in hexane, 13.4 mL) is added and the reaction turned a deep purple color. The reaction is allowed to warm to 0° C. for 10 min, then recooled to -78° C. for the addition of the aldehyde (0.82 mL). A thick slurry forms and stirring becomes difficult. The reaction is allowed to warm to 0° C., then quenched with ammonium chloride solution (10 mL). The reaction is extracted with EtOAc (200 mL) and washed with water (2×40 mL) and brine. The organic phase is dried over MgSO4, filtered and concentrated in vacuo. Chromatography over silica gel (300 g) eluting with 5% MeOH in CH2Cl2 gives the title product (356 mg) as a colorless oil.
Reaction SMILES: [C:1]1(=[O:6])[O:5][CH2:4][CH2:3][CH2:2]1.C(O)CCCO.[H][H]>>[C:1]1(=[O:6])[O:5][CH2:4][CH2:3][CH2:2]1.[CH:1]([OH:6])([OH:5])[CH2:2][CH2:3][CH3:4]
Reactant: [H][H]
Solvent: OCCCCO
Solvent: O=C1CCCO1
Product: CCCC(O)O

Procedure:
Example 2 was repeated using this catalyst, except that the liquid feed to the vaporizer was a 1:1 mixture of butyrolactone and 1,4-butanediol, the hydrogen pressure was maintained at 900 psig. and the LHSV was 0.1. A 98% conversion of butyrolactone with 97% selectivity to butanediol was obtained.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([S:17]([N:20]([CH2:22][C:23]([O:25][CH3:26])=[O:24])[CH3:21])(=[O:19])=[O:18])=[CH:13][C:12]=2[CH3:27])=[O:9])[CH:3]=1.C(NC(C)C)(C)C.[CH:35]1([CH2:38][NH:39][CH2:40][CH2:41][CH3:42])[CH2:37][CH2:36]1>CO>[CH:35]1([CH2:38][N:39]([CH2:40][CH2:41][CH3:42])[C:2]2[N:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][C:11]3[CH:16]=[CH:15][C:14]([S:17]([N:20]([CH2:22][C:23]([O:25][CH3:26])=[O:24])[CH3:21])(=[O:19])=[O:18])=[CH:13][C:12]=3[CH3:27])=[O:9])[CH:3]=2)[CH2:37][CH2:36]1
Reactant: CCCNCC1CC1
Reactant: COC(=O)CN(C)S(=O)(=O)c1ccc(NC(=O)c2cc(Cl)ncn2)c(C)c1
Solvent: CO
Solvent: CC(C)NC(C)C
Product: CCCN(CC1CC1)c1cc(C(=O)Nc2ccc(S(=O)(=O)N(C)CC(=O)OC)cc2C)ncn1
Temperature: 160 °C

Procedure:
A solution of methyl 2-(4-(6-chloropyrimidine-4-carboxamido)-N,3-dimethylphenylsulfonamido)acetate (Intermediate 36, 123 mg; 0.30 mmol) and diisopropylamine (105.5 mL; 0.61 mmol) in methanol (4 ml) was treated with N-(cyclopropylmethyl)propan-1-amine (45.3 mg; 0.4 mmol). The mixture was heated to 160° C. in a microwave for 1 hour and then the solvent removed in vacuo. The residue was purified by column chromatography (silica) eluting with petroleum ether containing increasing amounts of EtOAc to give methyl 2-(4-(6-((cyclopropylmethyl)(propyl)amino)pyrimidine-4-carboxamido)-N,3-dimethylphenylsulfonamido)acetate which was used directly without any further purification. The residue was redissolved in methanol (10 ml) and THF (10 ml) and treated with 5 N NaOH (1 ml). After stirring at RT for 5 hours the solvent was removed in vacuo. The residue was redissolved in water (10 ml) and acidified with conc. HCl. The aqueous phase was extracted with EtOAc and the organic extracts passed through a hydrophobic frit and the solvent removed in vacuo. The residue was triturated with petroleum ether to yield the title compound as an off-white solid.
Reaction SMILES: [CH2:1]=[CH:2][CH3:3].[CH:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>>[C:4]1([CH:2]([CH3:3])[CH3:1])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: c1ccccc1
Reactant: C=CC
Product: CC(C)c1ccccc1

Procedure:
alkylating benzene with propene to obtain cumene;
Reaction SMILES: Br[CH2:2][C:3]1[N:4]=[C:5]([CH3:8])[O:6][CH:7]=1.[CH2:9]([NH2:11])[CH3:10]>C1COCC1>[CH2:9]([NH:11][CH2:2][C:3]1[N:4]=[C:5]([CH3:8])[O:6][CH:7]=1)[CH3:10]
Reactant: CCN
Reactant: Cc1nc(CBr)co1
Solvent: C1CCOC1
Product: CCNCc1coc(C)n1

Procedure:
prepared by reaction of 4-bromomethyl-2-methyl-oxazole (prepared according to Pattenden G. et al, Org. & Biomolecular Chem., 2003, 1, 23, 4173-4208) with 2M ethylamine in THF.