Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:4][C:5]1([CH2:10][N:11]2[CH:15]=[C:14]([C:16]([CH3:19])([CH3:18])[CH3:17])[S:13]/[C:12]/2=[N:20]\[C:21]([C:23]2[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:24]=2[O:30][CH3:31])=S)[CH2:9][CH2:8][CH2:7][CH2:6]1)(=[O:3])[CH3:2].C(N(CC)CC)C.[N:39]#[C:40][NH2:41]>C(#N)C.[Hg](OC(C)=O)OC(C)=O>[C:1]([O:4][C:5]1([CH2:10][N:11]2[CH:15]=[C:14]([C:16]([CH3:19])([CH3:18])[CH3:17])[S:13]/[C:12]/2=[N:20]\[C:21]([C:23]2[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:24]=2[O:30][CH3:31])=[N:41][C:40]#[N:39])[CH2:9][CH2:8][CH2:7][CH2:6]1)(=[O:3])[CH3:2]
Reactant: N#CN
Reactant: COc1ccc(Cl)cc1C(=S)/N=c1\sc(C(C)(C)C)cn1CC1(OC(C)=O)CCCC1
Agent: CC(=O)O[Hg]OC(C)=O
Solvent: CC#N
Solvent: CCN(CC)CC
Product: COc1ccc(Cl)cc1C(=NC#N)/N=c1\sc(C(C)(C)C)cn1CC1(OC(C)=O)CCCC1
Yield: 75 %

Procedure:
The product of Example 24D (1.6 g, 3.2 mmol), triethylamine (1.8 mL, 13 mmol), cyanamide (0.40 g, 9.7 mmol) and Hg(OAc)2 (2.0 g, 6.5 mmol) in acetonitrile (20 mL) were processed as described in Example 16E to provide the title compound (1.2 g, 2.4 mmol, 74% yield). 1H NMR (300 MHz, CDCl3) δ ppm 1.34-1.40 (m, 9H), 1.65-1.84 (m, 4H), 1.86-2.09 (m, 4H), 2.00-2.02 (m, 3H), 3.91 (s, 3H), 4.72 (s, 2H), 6.70 (s, 1H), 6.94 (d, J=9.1 Hz, 1H), 7.28 (d, J=2.4 Hz, 1H), 7.35 (dd, J=8.7, 2.8 Hz, 1H); MS (DCI/NH3) m/z 489 (M+H)+. Anal. calculated for C24H29ClN4O3S: C, 58.94; H, 5.98; N, 11.46. Found: C, 58.88; H, 5.86; N, 11.32.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([CH:14]=O)=[CH:10][CH:11]=[CH:12][CH:13]=2)=[CH:4][CH:3]=1.C([O-])(=O)C.[NH4+].C(O)(=O)C.[N+:25]([CH3:28])([O-:27])=[O:26]>>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[CH:14]=[CH:28][N+:25]([O-:27])=[O:26])=[CH:4][CH:3]=1
Reactant: C[N+](=O)[O-]
Reactant: Cc1ccc(-c2ccccc2C=O)cc1
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CC(=O)O
Product: Cc1ccc(-c2ccccc2C=C[N+](=O)[O-])cc1
Temperature: 0 °C

Procedure:
4'-Methylbiphenyl-2-carboxaldehyde (13.21 g, 67.3 mmol (1.0 eq), nitromethane (4.74 mL, 87.5 mmol, 1.3 eq), ammonium acetate (2.07 g, 26.0 mmol, 0.4 eq) and glacial acetic acid (30 mL) were mixed and refluxed for 2 days, at which time more nitromethane (4.74 mL) and ammonium acetate (2.07 g) were added and the reaction was refluxed for an additional 5 hours. The reaction mixture was poured into ice water (300 mL) and extracted with ethyl acetate (300 mL). The ethyl acetate layer was washed with water (3×200 mL), the organic layer dried (MgSO4), the solvent removed in vacuo and the residue chromatographed in 1:1 hexane/toluene to yield 11.22 g of a light yellow oil which crystallized. The product was recrystallized from methylcyclohexane to yield 8.47 g of yellow crystals; m.p. 64.0°-65.0°. NMR (200 MHz, CDCl3)δ8.04 (d, 1H, J= 13 Hz); 7.69 (d, 1H, J=9 Hz) 7.59-7.37 (m, 4H); 7.50 (d, 1H, J=13 Hz); 7.27 (d, 2H, J=7 Hz); 7.19 (d, 2H, J=7 Hz); 2.41 (s, 3H). Anal. Calcd. for C15H13NO2 : C, 75.30; H, 5.48; N, 5.85. Found: C, 75.32; H, 5.56; N, 5.58.
Reaction SMILES: [NH:1]1[CH2:4][CH:3]([N:5]2[CH2:10][CH2:9][N:8]([C:11]([C:13]3[S:14][CH:15]=[CH:16][N:17]=3)=[O:12])[CH2:7][CH2:6]2)[CH2:2]1.[F:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]2[C:33]3[C:28](=[CH:29][C:30]([C:34](O)=[O:35])=[CH:31][CH:32]=3)[CH2:27][CH2:26]2)=[CH:21][CH:20]=1.CCN(CC)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[F:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]2[C:33]3[C:28](=[CH:29][C:30]([C:34]([N:1]4[CH2:2][CH:3]([N:5]5[CH2:6][CH2:7][N:8]([C:11]([C:13]6[S:14][CH:15]=[CH:16][N:17]=6)=[O:12])[CH2:9][CH2:10]5)[CH2:4]4)=[O:35])=[CH:31][CH:32]=3)[CH2:27][CH2:26]2)=[CH:21][CH:20]=1
Reactant: O=C(O)c1ccc2c(c1)CCN2c1ccc(F)cc1
Reactant: O=C(c1nccs1)N1CCN(C2CNC2)CC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(c1ccc2c(c1)CCN2c1ccc(F)cc1)N1CC(N2CCN(C(=O)c3nccs3)CC2)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 75.3 %

Procedure:
To a mixture of compound 5e (42.9 mg, 0.132 mmol), compound 55d (30.9 mg, 0.12 mmol), and Et3N (0.084 mL, 0.6 mmol) in CH2Cl2 (1 mL) at room temperature was added HATU (70 mg, 0.168 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was diluted with CH2Cl2 and washed with H2O, aqueous NaHCO3 and brine, and then dried over Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, 2-4% MeOH/EtOAc) to give compound Cpd 885 (44.4 mg). 1H NMR (400 MHz, CDCl3): δ 7.89 (d, J=3.2 Hz, 1H), 7.55 (d, J=3.2 Hz, 1H), 7.51 (d, J=1.2 Hz, 1H), 7.38 (dd, J=8.3, 1.7 Hz, 1H), 7.16-7.25 (m, 2H), 7.03-7.12 (m, 2H), 6.88 (d, J=8.3 Hz, 1H), 4.05-4.67 (m, 6H), 3.99 (t, J=8.6 Hz, 2H), 3.76-3.94 (m, 2H), 3.20-3.30 (m, 1H), 3.16 (t, J=8.6 Hz, 2H), 2.37-2.64 (m, 4H); MS m/z (M+H+) 492.1.
Reaction SMILES: [C:1]1([N:7]2[CH2:12][CH2:11][CH:10]([NH2:13])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:14]([C:16]1[CH:23]=[CH:22][C:19]([CH:20]=O)=[CH:18][CH:17]=1)#[N:15].C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[C:14]([C:16]1[CH:23]=[CH:22][C:19]([CH2:20][NH:13][CH:10]2[CH2:9][CH2:8][N:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:12][CH2:11]2)=[CH:18][CH:17]=1)#[N:15]
Reactant: NC1CCN(c2ccccc2)CC1
Reactant: N#Cc1ccc(C=O)cc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: N#Cc1ccc(CNC2CCN(c3ccccc3)CC2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
1-Phenylpiperidin-4-ylamine (0.50 g, 2.84 mmol) (from Example 123) and 4-cyanobenzaldehyde (0.74 g, 5.64 mmol) were dissolved in anhydrous methanol (10 mL) and acetic acid (0.97 mL, 17 mmol) was added. The mixture was stirred for 2 hrs at room temperature, then cooled to 0° C. (ice-water) and sodium cyanoborohydride (0.267 g, 4.25 mmol) was added, then the reaction mixture was stirred at room temperature for 2 hrs. The solvent was evaporated under reduced pressure and the residue was partitioned between sat. NaHCO3(aq) (50 mL) and dichloromethane (25 mL), and the organic layer was extracted. The aqueous phase was extracted with dichloromethane (2×25 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. The residue was chromatographed on silica gel, eluting with hexane—30% ethyl acetate to give the product as a white solid.
Reaction SMILES: [C:1](Cl)(=[O:4])[CH2:2][CH3:3].[NH2:6][C:7]1[CH:8]=[N:9][C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][CH:11]=2.C(N(CC)CC)C>ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>[C:1]([NH:6][C:7]1[CH:8]=[N:9][C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][CH:11]=2)(=[O:4])[CH2:2][CH3:3]
Reactant: Nc1cnc2ccccc2c1
Reactant: CCC(=O)Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCC(=O)Nc1cnc2ccccc2c1
Yield: 100.5 %

Procedure:
Propionic acid chloride (17 g, 184 mmol) was added at ambient temperature to a solution of 25 g (174 mmol) 3-aminoquinoline and 26 ml triethyl amine in 400 ml dichloromethane. After stirring for 2 hours in 200 ml 10% sodium carbonate was added and the mixture was shaken and separated. The aqueous phase was extracted 3 times with dichloromethane and 3 times with ethyl acetate. The combined organic phases where dried (magnesium sulfate), filtered and evaporated to yield 35.0 g (100%) of the desired product.
Reaction SMILES: [Cl:1]Cl.[N+]([C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1)([O-])=O>>[Cl:1][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=1
Reactant: ClCl
Reactant: O=[N+]([O-])c1ccc(OC(F)(F)F)cc1
Product: FC(F)(F)Oc1ccc(Cl)cc1
Yield: 83 %

Procedure:
Chlorine and p-nitrotrifluoromethoxybenzene (10.7 parts) were fed simultaneously at a molar ratio of 3:1, Cl2 : organic reactant, into a vapor phase reactor maintained at 300° to 320° C. over a 30 minute period to yield 8.2 parts of p-chlorotrifluoromethoxybenzene (83% yield). The structure of the product was confirmed by gas chromatographic-mass spectrum and F19 nuclear magnetic resonance analysis.
Reaction SMILES: [CH2:1]([NH:8][C:9](=[O:18])[C:10]1[CH:15]=[CH:14][C:13]([NH:16][NH2:17])=[N:12][CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C)[CH:21]=[C:22]([N:28]1[CH:33]=[CH:32][C:31](=[O:34])[CH:30]=[CH:29]1)[C:23](OCC)=[O:24]>>[CH2:1]([NH:8][C:9](=[O:18])[C:10]1[CH:15]=[CH:14][C:13]([N:16]2[C:23]([OH:24])=[C:22]([N:28]3[CH:29]=[CH:30][C:31](=[O:34])[CH:32]=[CH:33]3)[CH:21]=[N:17]2)=[N:12][CH:11]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: NNc1ccc(C(=O)NCc2ccccc2)cn1
Reactant: CCOC(=O)C(=CN(C)C)n1ccc(=O)cc1
Product: O=C(NCc1ccccc1)c1ccc(-n2ncc(-n3ccc(=O)cc3)c2O)nc1

Procedure:
The title compound was prepared in a manner similar to Example 188 using N-benzyl-6-hydrazinylnicotinamide and ethyl 3-(dimethylamino)-2-(4-oxopyridin-1(4H)-yl)acrylate. MS m/z 388 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 4.53 (d, J=5.6 Hz, 2H) 6.68 (br. s., 2H) 7.27 (dq, J=8.5, 4.2 Hz, 1H) 7.30-7.41 (m, 4H) 8.29 (br. s., 2H) 8.37-8.54 (m, 3H) 8.97 (s, 1H) 9.27 (t, J=5.8 Hz, 1H).
Reaction SMILES: [Br:1]Br.[S:3]1[CH:7]=[CH:6][N:5]=[C:4]1[N:8]1[CH2:13][CH2:12][CH:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:10][CH2:9]1>C(O)(=O)C.C(OCC)(=O)C>[Br:1][C:7]1[S:3][C:4]([N:8]2[CH2:13][CH2:12][CH:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:10][CH2:9]2)=[N:5][CH:6]=1
Reactant: CCOC(=O)C1CCN(c2nccs2)CC1
Reactant: BrBr
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: CCOC(=O)C1CCN(c2ncc(Br)s2)CC1
Yield: 97.4 %

Procedure:
Bromine (0.14 mL, 2.7 mmol) was weighed into a vial and then diluted with acetic acid (1 mL). This solution was added dropwise (over 10 minutes) to a solution of ethyl 1-(1,3-thiazol-2-yl)piperidine-4-carboxylate (650 mg, 2.7 mmol) in acetic acid (12.5 mL). The mixture was then diluted with ethyl acetate (100 mL) and washed with water (100 mL) and brine (100 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo to provide 840 mg (2.63 mmol, 97% yield) of ethyl 1-(5-bromo-1,3-thiazol-2-yl)piperidine-4-carboxylate as a green oil.
Reaction SMILES: [NH2:1][C:2]1[N:23]=[C:22](Cl)[CH:21]=[CH:20][C:3]=1[C:4]([NH:6][CH2:7][C:8]1[S:9][C:10]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:11][CH:12]=1)=[O:5].C1C=CC(CC(NCN[C@H](C(O)=O)CC2C=CC([N+]([O-])=O)=CC=2)=O)=CC=1.[S:51]1[CH:55]=[CH:54][N:53]=[CH:52]1>C1(C)C(C)=CC=CC=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>[NH2:1][C:2]1[N:23]=[C:22]([C:52]2[S:51][CH:55]=[CH:54][N:53]=2)[CH:21]=[CH:20][C:3]=1[C:4]([NH:6][CH2:7][C:8]1[S:9][C:10]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:11][CH:12]=1)=[O:5]
Reactant: Nc1nc(Cl)ccc1C(=O)NCc1ccc(Oc2ccccc2)s1
Reactant: c1cscn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C(Cc1ccccc1)NCN[C@@H](Cc1ccc([N+](=O)[O-])cc1)C(=O)O
Solvent: Cc1ccccc1C
Product: Nc1nc(-c2nccs2)ccc1C(=O)NCc1ccc(Oc2ccccc2)s1
Temperature: 120 °C
Reaction time: 12 h
Yield: 19 %

Procedure:
To a solution of 2-amino-6-chloro-N-(5-phenoxy-thiophen-2-ylmethyl)-nicotinamide described in Example A-101 (101 mg, 0.281 mmol) in xylene (7 mL) were added 2-tributylstanyl thiazole (137 mg, 0.365 mmol) and tetrakis(triphenylphosphine)palladium(0) (81 mg, 0.070 mmol) under nitrogen atmosphere, and the solution was stirred for 12 hours at 120° C. The reaction mixture was concentrated, the obtained residue was purified by silica gel chromatography (toluene-ethyl acetate), then, the obtained residue was washed by hexane-ethyl acetate (20:1), and the title compound (22 mg, 0.054 mmol, 19%) was obtained.
Reaction SMILES: [CH2:1]([CH:3]1[CH:20]([OH:21])[CH:19]([CH3:22])[CH:18]=[C:17]([CH3:23])[CH:16]=[C:15]([O:24][CH3:25])[C:14](=[O:26])[O:13][CH:12]([CH:27]([CH:29]([OH:48])[CH:30]([CH3:47])/[C:31](=[N:41]\[O:42][CH2:43][C:44](O)=[O:45])/[CH:32]=[CH:33]/[CH:34]([CH3:40])[CH:35]([OH:39])/[CH:36]=[CH:37]/[CH3:38])[CH3:28])[CH:11]([O:49][CH3:50])[CH:10]=[CH:9][CH:8]=[C:7]([CH3:51])[CH2:6][CH:5]([CH3:52])[CH:4]1[OH:53])[CH3:2].C1C=CC2N(O)N=NC=2C=1.[N:64]1([CH:70]2[CH2:75][CH2:74][NH:73][CH2:72][CH2:71]2)[CH2:69][CH2:68][CH2:67][CH2:66][CH2:65]1.O>ClCCl>[N:64]1([CH:70]2[CH2:75][CH2:74][N:73]([C:44](=[O:45])[CH2:43][O:42]/[N:41]=[C:31](/[CH:32]=[CH:33]/[CH:34]([CH3:40])[CH:35]([OH:39])/[CH:36]=[CH:37]/[CH3:38])\[CH:30]([CH3:47])[CH:29]([OH:48])[CH:27]([CH:12]3[O:13][C:14](=[O:26])[C:15]([O:24][CH3:25])=[CH:16][C:17]([CH3:23])=[CH:18][CH:19]([CH3:22])[CH:20]([OH:21])[CH:3]([CH2:1][CH3:2])[CH:4]([OH:53])[CH:5]([CH3:52])[CH2:6][C:7]([CH3:51])=[CH:8][CH:9]=[CH:10][CH:11]3[O:49][CH3:50])[CH3:28])[CH2:72][CH2:71]2)[CH2:69][CH2:68][CH2:67][CH2:66][CH2:65]1
Reactant: C1CCN(C2CCNCC2)CC1
Reactant: C/C=C/C(O)C(C)/C=C/C(=N/OCC(=O)O)C(C)C(O)C(C)C1OC(=O)C(OC)=CC(C)=CC(C)C(O)C(CC)C(O)C(C)CC(C)=CC=CC1OC
Agent: C/C=C/C(O)C(C)/C=C/C(=N/OCC(=O)N1CCC(N2CCCCC2)CC1)C(C)C(O)C(C)C1OC(=O)/C(OC)=C/C(C)=C/C(C)C(O)C(CC)C(O)C(C)C/C(C)=C/C=C/C1OC
Agent: C/C=C/C(O)C(C)/C=C/C(=N/OCC(=O)O)C(C)C(O)C(C)C1OC(=O)/C(OC)=C/C(C)=C/C(C)C(O)C(CC)C(O)C(C)C/C(C)=C/C=C/C1OC
Agent: On1nnc2ccccc21
Solvent: O
Solvent: ClCCl
Product: C/C=C/C(O)C(C)/C=C/C(=N/OCC(=O)N1CCC(N2CCCCC2)CC1)C(C)C(O)C(C)C1OC(=O)C(OC)=CC(C)=CC(C)C(O)C(CC)C(O)C(C)CC(C)=CC=CC1OC
Reaction time: 0.33 h

Procedure:
To a solution of compound of example 10 (10 mg) in dichloromethane (2 mL) dicyclohexylcarbodiimide (3 mg), and HOBT (2 mg) were added. After 20 min, 4-piperidino-piperidine 2.5 mg) was added. The reaction mixture was stirred for 18 h under nitrogen atmosphere. Cold water was added to the reaction mixture, the organic layer was separated; Reaction mixture was extracted with dichloromethane (3×5 mL). The combined organic layer was washed with water (2×5 mL). The organic layer was dried over sodium sulphate, and was concentrated. The crude product was purified by preparative HPLC [Eurospere-100, C18 column (250 mm×8 mm), mobile phase: acetonitrile-water (1:1 isocratic)] to obtain the title compound.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:12](/[CH:13]=[CH:14]/[C:15]3[S:16][C:17]([C:20]([OH:22])=O)=[CH:18][N:19]=3)=[C:11]([CH3:23])[O:10][N:9]=2)=[N:6][CH:7]=1.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:12](/[CH:13]=[CH:14]/[C:15]3[S:16][C:17]([C:20]([N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[O:22])=[CH:18][N:19]=3)=[C:11]([CH3:23])[O:10][N:9]=2)=[N:6][CH:7]=1
Reactant: C1COCCN1
Reactant: Cc1onc(-c2ccc(F)cn2)c1/C=C/c1ncc(C(=O)O)s1
Product: Cc1onc(-c2ccc(F)cn2)c1/C=C/c1ncc(C(=O)N2CCOCC2)s1
Yield: 83 %

Procedure:
As described for example 77c, 2-{(E)-2-[3-(5-fluoro-pyridin-2-yl)-5-methyl-isoxazol-4-yl]-vinyl}-thiazole-5-carboxylic acid (83 mg, 0.25 mmol) was converted, using morpholine instead of 4-aminotetrahydropyran, to the title compound (83 mg, 83%) which was obtained as a yellow solid after purification by chromatography (silica, 0 to 100% ethyl acetate in heptane). MS: m/e=401.2 [M+H]+.
Reaction SMILES: [C:1]([O:5][C:6](=[O:31])[CH2:7][N:8]([S:14]([C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:19][CH:18]=1)(=[O:16])=[O:15])[CH2:9][CH2:10][CH2:11][CH:12]=[CH2:13])([CH3:4])([CH3:3])[CH3:2].CN(C)C=[O:35].O.O=O>Cl.[Pd](Cl)Cl>[C:1]([O:5][C:6](=[O:31])[CH2:7][N:8]([S:14]([C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:19][CH:18]=1)(=[O:16])=[O:15])[CH2:9][CH2:10][CH2:11][C:12](=[O:35])[CH3:13])([CH3:2])([CH3:3])[CH3:4]
Reactant: CN(C)C=O
Reactant: C=CCCCN(CC(=O)OC(C)(C)C)S(=O)(=O)c1ccc(OCc2ccccc2)cc1
Agent: Cl[Pd]Cl
Agent: Cl
Agent: O=O
Solvent: O
Product: CC(=O)CCCN(CC(=O)OC(C)(C)C)S(=O)(=O)c1ccc(OCc2ccccc2)cc1
Reaction time: 24 h

Procedure:
A mixture of [(4-benzyloxy-benzenesulfonyl)-pent-4-enyl-amino]-acetic acid tert-butyl ester (compound of formula XVI, 89 g, 200 mmol), cuprous chloride (19.8 g, 200 mmol), palladium (II) chloride (6.9 g, 39 mmol), dimethylformamide (541 ml) and water (293 ml) was treated with oxygen gas under vigorous stirring. After about 24 hours, an additional 4 g of cuprous chloride and 2 g of palladium (II) chloride were added, and stirring was continued for 2 days. The mixture was diluted with 1M hydrochloric acid, extracted 3 times with ethyl acetate, and the organic phase was washed 5 times with water, dried over sodium sulfate, filtered and concentrated, giving 83 g of [(4-benzyloxy-benzenesulfonyl)-(4-oxo-pentyl)-amino]-acetic acid tert-butyl ester (compound of formula XVII) as a colorless syrup.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10]Cl)[C:5]=1[NH:12][C:13](=[O:29])[CH2:14][CH:15]1[C:28]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[O:22][C:21]2[C:16]1=[CH:17][CH:18]=[CH:19][CH:20]=2)([CH3:3])[CH3:2].[O:30]1CCCC1.O>CC(C)=O.[N+]([O-])([O-])=O.[Ag+]>[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][OH:30])[C:5]=1[NH:12][C:13](=[O:29])[CH2:14][CH:15]1[C:28]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[O:22][C:21]2[C:16]1=[CH:17][CH:18]=[CH:19][CH:20]=2)([CH3:3])[CH3:2]
Reactant: CC(C)c1cccc(CCl)c1NC(=O)CC1c2ccccc2Oc2ccccc21
Reactant: C1CCOC1
Agent: [Ag+]
Agent: O=[N+]([O-])[O-]
Solvent: CC(C)=O
Solvent: O
Product: CC(C)c1cccc(CO)c1NC(=O)CC1c2ccccc2Oc2ccccc21
Temperature: 60 °C
Reaction time: 7 h
Yield: 66 %

Procedure:
4.24 g (25 mmol) of silver nitrate were added to a solution of 10.14 g (25.0 mmol) N-(2-isopropyl-6-chloromethylphenyl)-2-(9H-xanthen-9-yl)acetamide [prepared as described in step (iv) above] in a mixture of 500 ml of acetone, 100 ml of tetrahydrofuran and 200 ml of water, and the resulting mixture was stirred for 7 hours at 60° C. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure, and the concentrate was diluted with ethyl acetate. The diluted mixture was washed with water and with a saturated aqueous solution of sodium chloride, in that order. The organic phase was then dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through silica gel, using a 3:1 by volume mixture of methylene chloride and ethyl acetate as the eluent, to give 6.41 g (yield 66%) of the title compound as crystals.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[C:12]([O:14][CH3:15])[C:11]([O:16][CH3:17])=[C:10]([O:18][CH3:19])[CH:9]=2)[N:5]=[CH:4][N:3]=1.[Se](=O)=[O:21].O>O1CCOCC1>[CH3:15][O:14][C:12]1[CH:13]=[C:8]([C:6]2[N:5]=[CH:4][N:3]=[C:2]([CH:1]=[O:21])[CH:7]=2)[CH:9]=[C:10]([O:18][CH3:19])[C:11]=1[O:16][CH3:17]
Reactant: O=[Se]=O
Reactant: COc1cc(-c2cc(C)ncn2)cc(OC)c1OC
Solvent: O
Solvent: C1COCCO1
Product: COc1cc(-c2cc(C=O)ncn2)cc(OC)c1OC
Temperature: 105 °C
Reaction time: 8 h

Procedure:
4-Methyl-6-(3,4,5-trimethoxyphenyl)pyrimidine (920 mg) was dissolved in dioxane (100 mL), and to the solution selenium dioxide (784 mg) was added, and the mixture was stirred overnight at 105° C. Water was added to the reaction mixture to conduct extraction with ethyl acetate, and the resultant organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1) to obtain the title compound.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:17])[C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[C:7]([S:12][CH2:13][C:14](=O)[CH3:15])[CH:6]=1)[CH3:2].Cl.[Cl:19][C:20]1[CH:21]=[C:22]([NH:26]N)[CH:23]=[CH:24][CH:25]=1>>[CH2:1]([O:3][C:4](=[O:17])[C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[C:7]([S:12][C:13]2[C:23]3[C:22](=[CH:21][C:20]([Cl:19])=[CH:25][CH:24]=3)[NH:26][C:14]=2[CH3:15])[CH:6]=1)[CH3:2]
Reactant: CCOC(=O)c1ccc(C)c(SCC(C)=O)c1
Reactant: NNc1cccc(Cl)c1
Agent: Cl
Product: CCOC(=O)c1ccc(C)c(Sc2c(C)[nH]c3cc(Cl)ccc23)c1

Procedure:
Prepared according to the procedure described in Example 2, Step 1, using the following starting materials: 4-Methyl-3-(2-oxo-propylsulfanyl)-benzoic acid ethyl ester and 3-chlorophenylhydrazine hydrochloride.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([O:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([OH:28])=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][CH:17]=2)[C:5]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)=[N:6][C:7]=1[CH3:8].C(=O)([O-])[O-].[K+].[K+].Br[CH2:36][CH2:37][CH2:38][CH2:39][OH:40].O>CN(C)C=O>[CH3:1][C:2]1[CH:3]=[C:4]([O:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:28][CH2:36][CH2:37][CH2:38][CH2:39][OH:40])=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][CH:17]=2)[C:5]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)=[N:6][C:7]=1[CH3:8]
Reactant: COc1cc2c(Oc3cc(C)c(C)nc3-c3cccnc3)ccnc2cc1O
Reactant: OCCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1cc2c(Oc3cc(C)c(C)nc3-c3cccnc3)ccnc2cc1OCCCCO
Temperature: 25 °C
Reaction time: 8 h
Yield: 35.4 %

Procedure:
4-(5,6-Dimethyl-[2,3′]bipyridin-3-yloxy)-6-methoxy-quinolin-7-ol (compound 345) (45 mg) was dissolved in N,N-dimethylformamide (2 ml) to prepare a solution. Potassium carbonate (50 mg) and 4-bromo-1-butanol (55 mg) were added to the solution, and the mixture was stirred at room temperature overnight. Water was added to the reaction solution, the mixture was extracted with ethyl acetate, and the ethyl acetate layer was then washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography using chloroform-acetone to give the title compound (19 mg, yield 35%).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7](Br)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[CH2:15]([O:19][C:20]1[CH:21]=[C:22]([CH2:38][CH2:39][C:40]([O:42][CH3:43])=[O:41])[CH:23]=[CH:24][C:25]=1[CH2:26][CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][C:32]([OH:35])=[C:31]([O:36][CH3:37])[CH:30]=1)[CH2:16][CH2:17][CH3:18]>C(C(C)=O)C.C(OCC)(=O)C>[CH2:7]([O:35][C:32]1[CH:33]=[CH:34][C:29]([CH2:28][CH2:27][CH2:26][C:25]2[CH:24]=[CH:23][C:22]([CH2:38][CH2:39][C:40]([O:42][CH3:43])=[O:41])=[CH:21][C:20]=2[O:19][CH2:15][CH2:16][CH2:17][CH3:18])=[CH:30][C:31]=1[O:36][CH3:37])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: BrCc1ccccc1
Reactant: CCCCOc1cc(CCC(=O)OC)ccc1CCCc1ccc(O)c(OC)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Solvent: CCOC(C)=O
Product: CCCCOc1cc(CCC(=O)OC)ccc1CCCc1ccc(OCc2ccccc2)c(OC)c1
Temperature: 70 °C
Yield: 90.7 %

Procedure:
0.2 g (0.75 mmol) of potassium carbonate and then 0.2 ml (0.75 mmol) of benzyl bromide are added to a solution of 0.25 g (0.62 mmol) of methyl 3-{3-butoxy-4-[3-(4-hydroxy-3-methoxyphenyl)propyl]phenyl}propanoate in 25 ml of methyl ethyl ketone. The reaction mixture is heated at 70° C. for 24 hours and then cooled, diluted with ethyl acetate and washed with saturated aqueous sodium chloride solution. The organic phase is dried over sodium sulfate, filtered and evaporated. The residue obtained is purified by chromatography on a column of silica eluted with an 80/20 heptane/ethyl acetate mixture. 276 mg (93%) of methyl 3-{4-[3-(4-benzyloxy-3-methoxyphenyl)propyl]-3-butoxyphenyl}propanoate are obtained in the form of a colorless oil.
Reaction SMILES: C[O:2][C:3]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[NH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=1.ClC1C=CC(C(O)=O)=CC=1.[O-:28][C:29]#[N:30].[Na+]>C1(C)C=CC=CC=1>[CH:7]1[CH:8]=[CH:9][C:10]2[N:11]([C:29]([NH2:30])=[O:28])[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=3[C:3](=[O:2])[CH2:4][C:5]=2[CH:6]=1
Reactant: N#C[O-]
Reactant: COC1=Cc2ccccc2Nc2ccccc21
Agent: O=C(O)c1ccc(Cl)cc1
Agent: [Na+]
Solvent: Cc1ccccc1
Product: NC(=O)N1c2ccccc2CC(=O)c2ccccc21
Temperature: 25 °C
Yield: 38.9 %

Procedure:
A mixture of 100 gms of 10-methoxyiminostilbene in 1000 mL of toluene containing 351 gms of para-chlorobenzoic acid and 370 gms of sodium cyanate were heated to reflux and refluxed for 12 hours. The reaction mixture was then cooled to room temperature and filtered. The clear toluene filtrate was then washed with 5% sodium carbonate solution followed by water. The toluene layer was then added to 1000 mL of 2N hydrochloric acid and the mixture was heated at 75-80° C. for a period of 2 hours under good agitation. It was then cooled to 0-5° C., maintained for 2 hours and the product oxcarbazepine was separated by filtration. This was then purified once in a dichloromethane methanol mixture to furnish 44 gms of pure oxcarbazepine.