Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[Sn](C)C.C[Sn](C)C.[Cl:9][C:10]1[CH:11]=[CH:12][C:13](Br)=[N:14][CH:15]=1.Br[C:18]1[O:22][C:21]([C:23]2[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=2)[C:26]#[N:27])=[CH:20][CH:19]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([C:18]2[O:22][C:21]([C:23]3[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=3)[C:26]#[N:27])=[CH:20][CH:19]=2)=[N:14][CH:15]=1
Reactant: Clc1ccc(Br)nc1
Reactant: N#Cc1cccc(-c2ccc(Br)o2)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: C[Sn](C)C
Product: N#Cc1cccc(-c2ccc(-c3ccc(Cl)cn3)o2)c1
Temperature: 80 °C
Reaction time: 16 h
Yield: 17.5 %

Procedure:
Pd(PPh3)4 (5 mg, 0.004 mmol) was added to a solution of hexamethylditin (160 mg, 0.49 mmol) and 5-chloro-2-bromopyridine (76 mg, 0.395 mmol) in toulene (1 mL) under argon. The resulting solution was stirred at 80° C. for 16 h. After cooling to room temperature, a second portion of Pd(PPh3)4 (20 mg, 0.019 mmol) and 3-(5-bromofuran-2-yl)-benzonitrile (79 mg, 0.32 mmol) were added and the resulting solution was stirred at 110° C. for 14 h. After cooling to room temperature, the solvent was removed in vacuo. Chromatography (5g silica gel SPE tube, 25-50% chloroform in hexane to 2% ethyl acetate in 1:1 chloroform:hexane) followed by triturating with hexanes and purification by preparative TLC (90% dichloromethane in hexane) afforded 15.7 mg (17%) of 3-(5-(5-choro-2-pyridyl)-2-furyl)-benzonitrile (97.5% pure by GC/MS, contaminated with 2.5% dimer). 1H-NMR (CDCl3), δ (ppm): 8.55 (d, 1H), 8.03 (s, 1H), 7.94 (dd, 1H), 7.73 (s, 2H), 7.54 (m, 12), 7.16 (d, 1H), 6.88 (d, 1H).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:21])[CH2:5][N:6]([S:8]([C:11]1[CH:15]=[CH:14][S:13][C:12]=1[CH:16]1OCCO1)(=[O:10])=[O:9])[CH3:7])[CH3:2].FC(F)(F)C(O)=O.C1CN2C(=NCCC2)C1.Cl>CC(C)=O.C(OCC)(=O)C.O>[CH3:7][N:6]1[C:5]([C:4]([O:3][CH2:1][CH3:2])=[O:21])=[CH:16][C:12]2[S:13][CH:14]=[CH:15][C:11]=2[S:8]1(=[O:10])=[O:9]
Reactant: CCOC(=O)CN(C)S(=O)(=O)c1ccsc1C1OCCO1
Agent: C1CN=C2CCCN2C1
Agent: Cl
Solvent: O
Solvent: CC(C)=O
Solvent: CCOC(C)=O
Product: CCOC(=O)C1=Cc2sccc2S(=O)(=O)N1C
Yield: 79.8 %

Procedure:
A mixture of the product from Step C (5.86 g, 16.5 mmol) and trifluoroacetic acid (8 mL) in acetone (50 mL) was heated at reflux temperature for 1 h, cooled, and poured into water (100 mL). Acetone was evaporated and the aqueous was combined with a saturated aqueous solution of sodium bicarbonate (50 mL) and this mixture was extracted with ethyl acetate (2×150 mL). The combined extracts were dried (MgSO4) and evaporated to give a crude aldehyde which was dissolved in ethyl acetate (100 mL) followed by the addition of DBN (1 mL) and molecular sieves (5 g). This mixture was heated at reflux temperature for 15 min, cooled, and poured into 2N HCl (50 mL). The organic layer was separated, dried (MgSO4), and evaporated to dryness. Column chromatography (silica, 30% ethyl acetate/hexane) gave 3.60 g (79%) of an off-white solid: mp 87°-89° C.
Reaction SMILES: N1C2C(=CC=CC=2)C=C1.C([N:17]1[C:29]2[C:28]([O:30][CH2:31][CH2:32][CH2:33][CH2:34]Br)=[C:27]3[N:36](C(OC(C)(C)C)=O)[C:37]4[CH:38]=[CH:39][C:40]([Br:43])=[CH:41][C:42]=4[C:26]3=[CH:25][C:24]=2[C:23]2[C:18]1=[CH:19][CH:20]=[C:21]([Br:51])[CH:22]=2)(OC(C)(C)C)=O.[NH:52]1[CH2:57][CH2:56][O:55][CH2:54][CH2:53]1>>[Br:43][C:40]1[CH:41]=[C:42]2[C:37](=[CH:38][CH:39]=1)[NH:36][C:27]1[C:28]([O:30][CH2:31][CH2:32][CH2:33][CH2:34][N:52]3[CH2:57][CH2:56][O:55][CH2:54][CH2:53]3)=[C:29]3[NH:17][C:18]4[CH:19]=[CH:20][C:21]([Br:51])=[CH:22][C:23]=4[C:24]3=[CH:25][C:26]2=1
Reactant: C1COCCN1
Reactant: CC(C)(C)OC(=O)n1c2ccc(Br)cc2c2cc3c4cc(Br)ccc4n(C(=O)OC(C)(C)C)c3c(OCCCCBr)c21
Agent: c1ccc2[nH]ccc2c1
Product: Brc1ccc2[nH]c3c(OCCCCN4CCOCC4)c4[nH]c5ccc(Br)cc5c4cc3c2c1

Procedure:
The title compound was prepared in a manner analogous to Example 70 except the starting indole is 5,7-diBOC-2,10-dibromo-6-(4-bromobutoxy)indolo[2,3-b]carbazole and the reagent is morpholine. 1H-NMR (400 MHz, DMSO-d6) δ ppm 11.22 (s, 2H), 8.64 (s, 1H), 8.25 (d, J=1.6 Hz, 2H), 7.44 (dd, J=8.4, 2.0 Hz, 2H), 7.41 (d, J=8.4 Hz, 2H), 4.26 (t, J=6.8 Hz, 2H), 3.57-3.40 (m, 6H), 2.32-2.18 (m, 4H), 1.92-1.80 (m, 2H), 1.65-1.50 (m, 2H); MS (ESI) m/z 570.0 (M−H)−
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[C:7]([CH3:9])[C:5](N)=[C:4]([CH3:10])[CH:3]=1.N([O-])=O.[Na+].S(=O)(=O)(O)N.[BrH:20]>O>[Cl:1][C:2]1[CH:8]=[C:7]([CH3:9])[C:5]([Br:20])=[C:4]([CH3:10])[CH:3]=1
Reactant: Cc1cc(Cl)cc(C)c1N
Reactant: Br
Agent: NS(=O)(=O)O
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Product: Cc1cc(Cl)cc(C)c1Br
Temperature: 80 °C
Reaction time: 0.25 h

Procedure:
To an initial charge of 75 ml of 48% aqueous HBr are added, in portions, 19.67 g [0.12 mol] of 4-chloro-2,6-dimethylaniline. The resulting thick suspension is stirred at 80° C. for 15 minutes. Then the mixture is cooled to −10° C., and a solution of 9.6 g [0.139 mol] of NaNO2 in 45 ml of water is added dropwise within approx. 1 h at such a rate that the temperature does not exceed −5° C. 100 mg of sulphamic acid are added. Then the suspension of the diazonium salt, cooled to −10° C., is metered within about 35 minutes into a solution, heated to 80° C., of 17.93 g [0.125 mol] of Cu(I)Br in 75 ml of 62% aqueous HBr. The reaction mixture is then stirred at 80° C. for another 1 hour, allowed to cool to room temperature and admixed with 125 ml of water, the phases are separated and the aqueous phase is extracted three times with 50 ml each time of methylene chloride. The combined organic phases are washed twice with 25 ml each time of water, dried and concentrated under reduced pressure. This gives 20.2 g of an oil which, according to GC, contains 95.5% 4-chloro-2,6-dimethylbromobenzene (73% of theory).
Reaction SMILES: CI.O1CCC[CH2:4]1.[CH3:8][CH:9]1[C:18](=[O:19])[C:17]2[C:12](=[CH:13][C:14]([O:20][CH3:21])=[CH:15][CH:16]=2)[O:11][CH2:10]1.[K]>O>[CH3:8][C:9]1([CH3:4])[C:18](=[O:19])[C:17]2[C:12](=[CH:13][C:14]([O:20][CH3:21])=[CH:15][CH:16]=2)[O:11][CH2:10]1
Reactant: COc1ccc2c(c1)OCC(C)C2=O
Reactant: C1CCOC1
Agent: [K]
Solvent: CI
Solvent: O
Product: COc1ccc2c(c1)OCC(C)(C)C2=O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Under nitrogen atmosphere, 0.4 ml of methyl iodide was added to 10 ml solution tetrahydrofuran with 240 mg of 3-methyl-7-methoxychroman-4-one, 100 mg of potassium hydrogenate was added and the mixture was stirred at room temperature for 3 hours. Water was added to the reaction solution, extracted with chloroform. Chloroform layer was washed with saturated saline solution and dried with anhydrous sodium sulfate. After distilling out the solvents under reduced pressure, residues were separated and purified by silicagel chromatography (hexane/ethyl acetate=5/1) to obtain 145 mg of the above compound as a white solid.
Reaction SMILES: CN(C)P(N(C)C)N(C)C.Br[C:12](Br)([F:14])[F:13].[CH3:16][C:17]([CH3:37])([CH2:20][O:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([F:29])=[C:25]([O:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:24]=1)[CH:18]=O.C(OCC)C>COCCOCCOCCOC>[CH3:16][C:17]([CH3:37])([CH:18]=[C:12]([F:14])[F:13])[CH2:20][O:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([F:29])=[C:25]([O:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:24]=1
Reactant: FC(F)(Br)Br
Reactant: CC(C)(C=O)COCc1ccc(F)c(Oc2ccccc2)c1
Agent: CN(C)P(N(C)C)N(C)C
Solvent: CCOCC
Solvent: COCCOCCOCCOC
Product: CC(C)(C=C(F)F)COCc1ccc(F)c(Oc2ccccc2)c1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 13.5 %

Procedure:
Hexamethylphosphorous triamide (0.65 g) was added portionwise to a stirred solution of dibromodifluoromethane (0.42 g) in triglyme (3 cm3) whilst being maintained at 0° C. under an atmosphere of nitrogen. After a period of 10 minutes a pale yellow colouration was observed and a solution of 2,2-dimethyl-3-(4-fluoro-3-phenoxybenzyloxy)propan-1-al (0.3 g) in triglyme (2 cm3) was added. After stirring for a further two hours, whilst being maintained at 0° C., the reaction mixture was allowed to warm to the ambient temperature. When GLC examination of a worked-up portion of the reaction mixture showed an absence of further reaction, the reaction mixture was poured into diethylether and sequentially washed with water and brine. The solvent was removed by evaporation under reduced pressure to give a pale yellow liquid which was subjected to short-path distillation (boiling point 75° C./0.01 mm Hg). The residue was then subjected to column chromatography on silica gel using petroleum ether (boiling range 40°-60° C.) containing 5% by volume diethyl ether as eluent to give 2,2-dimethyl-1-(4-fluoro-3-phenoxybenzyloxy)-4,4-difluorobut-3-ene (0.045 g).
Reaction SMILES: O=[C:2]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=1)[CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7].[C:21]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])(=[O:24])[NH:22][NH2:23].C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>C1COCC1.C(O)(=O)C.C(OCC)C>[C:26]([O:25][C:21]([NH:22][NH:23][CH:2]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=1)[CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])=[O:24])([CH3:29])([CH3:28])[CH3:27]
Reactant: CCOC(=O)CCCC(=O)c1cccc(C(F)(F)F)c1
Reactant: CC(C)(C)OC(=O)NN
Agent: O=C([O-])O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CCOCC
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CCOC(=O)CCCC(NNC(=O)OC(C)(C)C)c1cccc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 0.42 h

Procedure:
Ethyl 5-oxo-5-(3-trifluoromethylphenyl)pentanoate (CAS No. 898777-75-8, 330 mg) and tert-butyl carbazate (227 mg) were dissolved in a mixed solvent of THF (6 mL) and acetic acid (3 mL). After stirring at room temperature for 25 minutes, sodium cyanoborohydride (108 mg) was added. After further one hour and 30 minutes, sodium cyanoborohydride (108 mg) was added and the mixture was stirred at room temperature for one hour. A saturated sodium bicarbonate solution and diethyl ether were added to the reaction solution, and the organic layer was separated. The resulting organic layer was washed with a saturated sodium bicarbonate solution and then dried over anhydrous sodium sulfate. The drying agent was separated by filtration and then the organic layer was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (324 mg). The property values of the compound are as follows.
Reaction SMILES: C(N(CC)CC)C.[Cl:8][C:9]1[C:10]([F:40])=[C:11]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:38][CH3:39])=[C:23]([CH2:26][N:27]([CH3:37])[C:28]4([C:34]([NH2:36])=[O:35])[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]4)[CH:24]=3)[N:19]=[CH:18][N:17]=2)[CH:12]=[CH:13][CH:14]=1.[C:41]([O:44][CH2:45][C:46](Cl)=[O:47])(=[O:43])[CH3:42]>CN1C(=O)CCC1>[C:41]([O:44][CH2:45][C:46]([N:31]1[CH2:32][CH2:33][C:28]([C:34]([NH2:36])=[O:35])([N:27]([CH2:26][C:23]2[CH:24]=[C:25]3[C:20](=[CH:21][C:22]=2[O:38][CH3:39])[N:19]=[CH:18][N:17]=[C:16]3[NH:15][C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([Cl:8])[C:10]=2[F:40])[CH3:37])[CH2:29][CH2:30]1)=[O:47])(=[O:43])[CH3:42]
Reactant: COc1cc2ncnc(Nc3cccc(Cl)c3F)c2cc1CN(C)C1(C(N)=O)CCNCC1
Reactant: CC(=O)OCC(=O)Cl
Solvent: CN1CCCC1=O
Solvent: CCN(CC)CC
Product: COc1cc2ncnc(Nc3cccc(Cl)c3F)c2cc1CN(C)C1(C(N)=O)CCN(C(=O)COC(C)=O)CC1
Temperature: 25 °C

Procedure:
Triethylamine (360 μl, 2.58 mmol) was added to a stirred, cooled (0° C.) suspension of 4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-4-carboxamide (300 mg, 0.63 mmol) (Example 16) in NMP (5 ml). Acetoxyacetyl chloride (100 μl 0.93 mmol) was then added drop wise and the reaction mixture left to warm to room temperature over a period of 2 hours. This was then partitioned between saturated aqueous sodium hydrogen carbonate solution and ethyl acetate. The organic phase was washed with saturated aqueous ammonium chloride solution followed by brine, dried over magnesium sulfate, filtered and evaporated to give 2-{4-(aminocarbonyl)-4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidin-1-yl}-2-oxoethyl acetate as a dry film (250 mg). Mass spectrum: (M+H)+ 573.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH3:10])=[CH:4][C:3]=1[N:11]1[CH2:16][CH2:15][C:14]([CH2:18][C:19](OCC)=[O:20])([OH:17])[CH2:13][CH2:12]1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH3:10])=[CH:4][C:3]=1[N:11]1[CH2:16][CH2:15][C:14]([CH2:18][CH2:19][OH:20])([OH:17])[CH2:13][CH2:12]1
Reactant: CCOC(=O)CC1(O)CCN(c2cc(OC)c(Cl)cc2Cl)CC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1cc(N2CCC(O)(CCO)CC2)c(Cl)cc1Cl
Temperature: 25 °C
Reaction time: 2 h
Yield: 70.1 %

Procedure:
To a solution of ethyl 2-(1-(2,4-dichloro-5-methoxyphenyl)-4-hydroxypiperidin-4-yl)acetate (1 g, 2.76 mmol) in THF (10 mL) was added LiAlH4 (0.210 g, 5.52 mmol). The reaction mixture was stirred at RT for 2 h, quenched with minimum water and then treated with EtOAc and solid NaHCO3. The mixture was stirred and filtered. The filtrate was concentrated to give 1-(2,4-dichloro-5-methoxyphenyl)-4-(2-hydroxyethyl)piperidin-4-ol (0.62 g, 1.936 mmol, 70% yield) as a yellow oil.
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]2[C:5]([N:6]=[CH:7][C:8]3[N:9]2[C:12]([CH3:15])=[N:13][N:14]=3)=[CH:4][CH:3]=1.[CH3:16][O:17][C:18]1[C:23]([NH2:24])=[CH:22][C:21](B2OC(C)(C)C(C)(C)O2)=[CH:20][N:19]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:16][O:17][C:18]1[C:23]([NH2:24])=[CH:22][C:21]([C:2]2[CH:11]=[C:10]3[C:5]([N:6]=[CH:7][C:8]4[N:9]3[C:12]([CH3:15])=[N:13][N:14]=4)=[CH:4][CH:3]=2)=[CH:20][N:19]=1
Reactant: COc1ncc(B2OC(C)(C)C(C)(C)O2)cc1N
Reactant: Cc1nnc2cnc3ccc(Br)cc3n12
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: CN(C)C=O
Product: COc1ncc(-c2ccc3ncc4nnc(C)n4c3c2)cc1N
Temperature: 100 °C
Reaction time: 8 h
Yield: 77.6 %

Procedure:
A mixture of crude 8-bromo-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline (809 mg, 3.07 mmol), PdCl2(dppf)2 (132.6 mg, 0.153 mmol), 2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-amine (1 g, 4.3 mmol) and K2CO3 (1.7 g, 12.28 mmol) in DMF (40 mL) and water (15 mL) was stirred at 100° C. overnight. Half of solvent was removed. After cooling to room temperature, the resulting mixture was poured into ice-water. The precipitate was collected, washed with water three times, and dried in vacuo to afford crude 2-methoxy-5-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-8-yl)pyridin-3-amine as grey solid (730 mg, yield 77%) which was used in next step without further purification. MS (m/z): 307 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[N:11]=[C:12]([C:24]3[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=3)[N:13](S(C3C=CC=CC=3)(=O)=O)[CH:14]=2)=[O:9])=[CH:4][CH:3]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(O)=O.[Na+]>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([C:10]2[N:11]=[C:12]([C:24]3[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=3)[NH:13][CH:14]=2)=[O:9])=[CH:6][CH:7]=1
Reactant: COc1ccc(-c2nc(C(=O)c3ccc(F)cc3)cn2S(=O)(=O)c2ccccc2)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])O
Agent: [F-]
Solvent: C1CCOC1
Product: COc1ccc(-c2nc(C(=O)c3ccc(F)cc3)c[nH]2)cc1
Reaction time: 8 h
Yield: 90 %

Procedure:
To a solution of (4-fluorophenyl)(2-(4-methoxyphenyl)-1-(phenylsulfonyl)-1H-imidazol-4-yl)methanone (11cb, 872 mg, 2.0 mmol) in THF (20.0 mL) was added 1.0M tetrabutyl ammonium fluoride (4.0 mL, 4.0 mmol) and stirred overnight. The reaction mixture was diluted by 50 mL of saturated NaHCO3 solution (aqueous) and extracted by ethyl acetate (100 mL). The organic layer was dried over magnesium sulfate and concentrated. The residue was recrystallized from water and methanol to give a white solid. Yield: 90%; mp 245-247° C.
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]([CH:27]=O)=[C:5]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[N+:19]([O-:21])=[O:20])[C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].[NH2:29][CH2:30][CH2:31][OH:32].C1(C)C=CC(S(O)(=O)=O)=CC=1.O>C1C=CC=CC=1>[CH3:1][C:2]1[NH:3][C:4]([CH:27]=[N:29][CH2:30][CH2:31][OH:32])=[C:5]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[N+:19]([O-:21])=[O:20])[C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9]
Reactant: CCOC(=O)C1=C(C)NC(C=O)=C(C(=O)OCC)C1c1ccccc1[N+](=O)[O-]
Reactant: NCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccccc1
Solvent: O
Product: CCOC(=O)C1=C(C)NC(C=NCCO)=C(C(=O)OCC)C1c1ccccc1[N+](=O)[O-]
Temperature: 25 °C
Yield: 95.8 %

Procedure:
A mixture of diethyl 2-methyl- 4-(2-nitrophenyl)-6-formyl-1,4-dihydropyridine-3,5-dicarboxylate (1.1651 g), 2-aminoethanol (185 mg) and p-toluenesulfonic acid (catalytic amount) in dried benzene (20 ml) was refluxed under azeotropic dehydration for 1.5 hours. After cooling to room temperature, water was added to the resultant solution. The mixture was washed twice with water. The aqueous layer was extracted with diethyl ether and the extract was combined with the benzene solution. The mixed solution was dried over magnesium sulfate and then the solvent was removed from the solution to give viscous oil (1.2397 g) of diethyl 2-methyl-4-(2-nitrophenyl)-6-(2-hydroxyethyl)iminomethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Reaction SMILES: [CH2:1]([Mg]Br)[CH3:2].C(O[CH2:9]/[CH:10]=[CH:11]/[C@H:12]1[CH2:17][CH2:16][C@H:15]([C:18]2[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=2)[CH2:14][CH2:13]1)(=O)C.[Cl-].[NH4+]>O1CCCC1.[Li+].[Li+].[Cl-].[Cl-].[Cl-].[Cl-].[Cu+2]>[CH:11](/[C@H:12]1[CH2:13][CH2:14][C@H:15]([C:18]2[CH:19]=[CH:20][C:21]([C:22]#[N:23])=[CH:24][CH:25]=2)[CH2:16][CH2:17]1)=[CH:10]\[CH2:9][CH2:1][CH3:2]
Reactant: CC(=O)OC/C=C/[C@H]1CC[C@H](c2ccc(C#N)cc2)CC1
Reactant: CC[Mg]Br
Agent: [Cu+2]
Agent: [Cl-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CCC/C=C/[C@H]1CC[C@H](c2ccc(C#N)cc2)CC1
Temperature: -15 °C
Reaction time: 1.5 h

Procedure:
A solution of 7.1 mmol of ethylmagnesium bromide (prepared from 172 mg of magnesium and 530 μl of ethyl bromide) in 20 ml of absolute tetrahydrofuran was placed at -78° C. while gassing with argon in a sulphonation flask provided with a thermometer, dropping funnel and serum cap and treated in sequence with 3.6 ml of a 0.48M solution of dilithium tetrachlorocuprate in absolute tetrahydrofuran and with a solution of 500 mg of p-[trans-4-(3-acetoxy-trans-1-propenyl)cyclohexyl]benzonitrile in 10 ml of absolute tetrahydrofuran. After completion of the addition, the mixture was warmed to -15° C., stirred at this temperature for 1.5 hours, subsequently treated with 20 ml of saturated ammonium chloride solution and stirred at room temperature for a further 1 hour. The aqueous phase, which was now deep blue, was separated and extracted twice with 50 ml of diethyl ether each time. The organic phases were washed twice with 50 ml of water each time, dried over magnesium sulphate and concentrated. Low-pressure chromatography (0.5 bar) of the residue (0.4 g) on silica gel with ethyl acetate/petroleum ether (vol. 3:97) gave 375 mg of crude p-[trans-4-(trans-1-pentenyl)cyclohexyl]benzonitrile which, according to analysis by gas chromatography, was contaminated to 8.5% with p-[trans-4-(trans-1-pentenyl)cyclohexyl]propiophenone and to 4.0% with p-[trans-4-(1-vinylpropyl)cyclohexyl]benzonitrile. Treatment of this crude product with an excess of sodium borohydride in methanol at 0° C. (in order to reduce the propiophenone), working-up, low-pressure chromatography (0.5 bar) on silica gel with ethyl acetate/petroleum ether (vol. 1:9) and finally recrystallization from methanol at -78° C. gave p-[trans-4-(trans-1-pentenyl)cyclohexyl]benzonitrile in a purity of 98.6%; m.p. (C-N) 15.5° C., cl.p. (N-I) 57.0° C.
Reaction SMILES: [NH2:1][N:2]1[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=[O:19].[C:20]1([CH2:26][C:27](Cl)=[O:28])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([C:10]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3](=[O:19])[N:2]([NH:1][C:27](=[O:28])[CH2:26][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:11]=2)=[CH:13][CH:14]=1
Reactant: O=C(Cl)Cc1ccccc1
Reactant: Nn1nc(-c2ccc(Cl)cc2)c2ccccc2c1=O
Product: O=C(Cc1ccccc1)Nn1nc(-c2ccc(Cl)cc2)c2ccccc2c1=O

Procedure:
The product of Example 86A and 2-phenylacetyl chloride were treated as in Example 53 to give the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 11.70 (s, 1H), 8.39-8.44 (m, 1H), 7.85-8.05 (m, 2H), 7.69-7.76 (m, 1H), 7.59-7.66 (m, 4H), 7.21-7.41 (m, 5H), 3.69 (s, 2H); MS (ESI+) M/Z 390 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[C:5]2I.C([Sn](CCCC)(CCCC)[C:18]1[CH:23]=[CH:22][N:21]=[N:20][CH:19]=1)CCC.CCOC(C)=O>O1CCOCC1.[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[C:5]2[C:18]1[CH:23]=[CH:22][N:21]=[N:20][CH:19]=1
Reactant: Brc1ccc2nccc(I)c2c1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccnnc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: ClCCl
Solvent: C1COCCO1
Product: Brc1ccc2nccc(-c3ccnnc3)c2c1
Temperature: 105 °C
Reaction time: 3 h
Yield: 38.8 %

Procedure:
Dissolved 6-bromo-4-iodoquinoline (17.43 g, 52.2 mmol), 4-(tributylstannanyl)pyridazine (19.27 g, 52.2 mmol), and PdCl2(dppf)-CH2Cl2 (2.132 g, 2.61 mmol) in 1,4-dioxane (200 mL) and heated to 105° C. After 3 h, added more palladium catalyst and heated for 6 h. Concentrated and dissolved in methylene chloride/methanol. Purified by column chromatography (combiflash) with 2% MeOH/EtOAc to 5% MeOH/EtOAc to give the crude title compound. Trituration with EtOAc furnished 6-bromo-4-(4-pyridazinyl)quinoline (5.8 g, 20.27 mmol, 38.8% yield). MS (ES)+ m/e 285.9, 287.9 [M+H]+.
Reaction SMILES: [CH3:1][O:2][SiH:3]([O:6][CH3:7])[O:4][CH3:5].[CH2:8]([Cl:11])[CH:9]=[CH2:10]>>[Cl:11][CH2:8][CH2:9][CH2:10][Si:3]([O:6][CH3:7])([O:4][CH3:5])[O:2][CH3:1]
Reactant: CO[SiH](OC)OC
Reactant: C=CCCl
Product: CO[Si](CCCCl)(OC)OC
Yield: 73.6 %

Procedure:
The same researchers also report the results of directly hydrosilating allyl chloride with trimethoxysilane in the presence of several ruthenium complexes. A maximum yield of 73.6% of chloropropyltrimethoxysilane is reported in Table 2 for the reaction between trimethoxysilane and allyl chloride at a 4/l molar ratio. Assuming the use of the "typical reaction procedure," the process may have employed a ruthenium carbonyl catalyst in an amount to provide at least about 155 parts per million by weight of ruthenium metal in the reaction mixture. Apparently, the reaction also was conducted in a sealed reactor under autogenous pressure in the presence of at least 13.3% by weight of toluene solvent for 16 hours at 80° C. The conversion of limiting allyl chloride was complete, and thus the yields of by-products such as propyltrimethoxysilane, tetramethoxysilane and hydrogen, were not insignificant. The same reaction, at a 2/1 molar ratio of trimethoxysilane to allyl chloride, in the presence of the same absolute weights of ruthenium catalyst and toluene solvent, provided a 72.2% yield of chloropropyltrimethoxysilane on a molar basis, with similar by-product yields at complete conversion of limiting allyl chloride. At a 1/1 molar ratio, the conversion of allyl chloride was not complete. At this mole ratio, a maximum yield of only 52.4% was obtained after 16 hours at 50° C., while at 80° C. the yield was only 26.4%. (Table 2).