Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:4][C:5](=[O:55])[CH2:6][C@H:7]([OH:54])[C@H:8]([NH:12][C:13](=[O:53])[C@H:14]([NH:16][C:17](=[O:52])[C@H:18]([NH:22][C:23](=[O:51])[CH2:24][C@H:25]([OH:50])/[CH:26]=[CH:27]/[CH2:28][CH2:29][S:30][C:31]([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH:19]([CH3:21])[CH3:20])[CH3:15])[CH:9]([CH3:11])[CH3:10])C=C.N1CCOCC1>CO.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>[OH:54][C@H:7]([C@H:8]([NH:12][C:13](=[O:53])[C@H:14]([NH:16][C:17](=[O:52])[C@H:18]([NH:22][C:23](=[O:51])[CH2:24][C@H:25]([OH:50])/[CH:26]=[CH:27]/[CH2:28][CH2:29][S:30][C:31]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[CH:19]([CH3:20])[CH3:21])[CH3:15])[CH:9]([CH3:11])[CH3:10])[CH2:6][C:5]([OH:55])=[O:4]
Reactant: C=CCOC(=O)C[C@H](O)[C@H](NC(=O)[C@@H](C)NC(=O)[C@H](NC(=O)C[C@H](O)/C=C/CCSC(c1ccccc1)(c1ccccc1)c1ccccc1)C(C)C)C(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CO
Solvent: C1COCCN1
Product: CC(C)[C@@H](NC(=O)[C@@H](C)NC(=O)[C@H](NC(=O)C[C@H](O)/C=C/CCSC(c1ccccc1)(c1ccccc1)c1ccccc1)C(C)C)[C@@H](O)CC(=O)O
Reaction time: 2 h
Yield: 90 %

Procedure:
To a solution of 7 (152.2 mg, 0.2 mmol), Pd(PPh3)4 (23.2 mg, 0.02 mmol) in dry methanol (6 mL) under argon was added morpholine (35 μL, 0.40 mmol) which was allowed to stir for 2 h. The reaction mixture was concentrated in vacuo, purification by column chromatography on silica (eluent 0:1-5:95-10:90-10:90+0.5% AcOH MeOH/CH2Cl2) to give a yellow solid 8 (137 mg, 0.18 mmol, 100%): Rf 0.19 MeOH/CH2Cl2 (1:9+0.5% AcOH); IR (thin film) 3271 (b), 2962 (m), 2926 (m), 1624 (s), 1536 (m) cm−1.
Reaction SMILES: [CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]2[C:11](=[O:42])[N:12]([CH:15]([C:17]3[N:18]=[CH:19][N:20](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[C:21]=3[CH3:22])[CH3:16])[CH2:13][CH2:14][C:3]=12>C(O)(=O)C.O>[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]2[C:11](=[O:42])[N:12]([CH:15]([C:17]3[N:18]=[CH:19][NH:20][C:21]=3[CH3:22])[CH3:16])[CH2:13][CH2:14][C:3]=12
Reactant: Cc1c2n(c3ccccc13)C(=O)N(C(C)c1ncn(C(c3ccccc3)(c3ccccc3)c3ccccc3)c1C)CC2
Solvent: O
Solvent: CC(=O)O
Product: Cc1[nH]cnc1C(C)N1CCc2c(C)c3ccccc3n2C1=O
Temperature: 60 °C
Reaction time: 2 h

Procedure:
A mixture of 3,4-dihydro-5-methyl-2-[1-(5-methyl-1-trityl-1H-imidazol-4-yl)ethyl]pyrimido[1,6-a]indol-1(2H)-one (60 mg) in 70% acetic acid in water (2.6 ml) was stirred at 60° C. for 2 hours. After evaporation of the solvent, the residue was dissolved in 10% methanol in chloroform. The mixture was washed with aqueous sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography (10% methanol-chloroform) to give 3,4-dihydro-5-methyl-2-[1-(5-methyl-1H-imidazol-4-yl)ethyl]pyrimido[1,6-a]-indol-1(2H)-one as a powder. The powder was dissolved in 9N hydrogen chloride in ethanol (1 ml) and evaporated in vacuo. The residue was triturated with ether to give 3,4-dihydro-5-methyl-2-[1-(5-methyl-1H-imidazol-4-yl)ethyl]pyrimido[1,6-a[indol-1(2H)-one hydrochloride (36.8 mg).
Reaction SMILES: [F:1][C:2]([F:19])([F:18])[C:3]1[CH:17]=[CH:16][C:6]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.[CH3:20][O:21][C:22](=[O:27])[CH2:23][C:24](Cl)=[O:25]>>[CH3:20][O:21][C:22](=[O:27])[CH2:23][C:24]([NH:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:7][C:6]2[CH:16]=[CH:17][C:3]([C:2]([F:18])([F:19])[F:1])=[CH:4][CH:5]=2)=[CH:10][CH:11]=1)=[O:25]
Reactant: Nc1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
Reactant: COC(=O)CC(=O)Cl
Product: COC(=O)CC(=O)Nc1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
Yield: 71 %

Procedure:
In analogy to example 1, the title compound is prepared from 4-(4-trifluoromethyl-benzyloxy)-phenylamine and chlorocarbonyl-acetic acid methyl ester. Yield: 71%. Colorless solid. MS: m/e=368.1 (M++H).
Reaction SMILES: [CH2:1]([O:3][N:4]=[C:5]([C:10]([O:12][CH3:13])=[O:11])[C:6](OC)=[O:7])[CH3:2].[OH-].[NH4+:15].Cl>CO>[C:6]([C:5](=[N:4][O:3][CH2:1][CH3:2])[C:10]([O:12][CH3:13])=[O:11])(=[O:7])[NH2:15]
Reactant: CCON=C(C(=O)OC)C(=O)OC
Reactant: [NH4+]
Agent: Cl
Agent: [OH-]
Solvent: CO
Product: CCON=C(C(N)=O)C(=O)OC
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
A mixture of dimethyl ethoxyiminomalonate (57.4 g) and conc. ammonium hydroxide (50 ml) in methanol (150 ml) was stirred for 2.5 hours at room temperature. The mixture was adjusted to pH 4 with conc. hydrochloric acid under cooling and concentrated to 70 ml under reduced pressure. The aqueous solution was stood in a refrigerator for one hour and the resulting precipitates were collected by filtration, washed with cold water and dried to give methyl 2-carbamoyl-2-ethoxyiminoacetate (syn isomer) (31 g), mp 68° to 71° C.
Reaction SMILES: [Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([N:12]=[C:13]=S)=[CH:4][CH:3]=1.[C:15]1([NH2:22])[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[NH2:21].N=C=N.O>C1COCC1>[Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([NH:12][C:13]2[NH:22][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[N:21]=2)=[CH:4][CH:3]=1
Reactant: S=C=Nc1ccc(Br)c2ccccc12
Reactant: Nc1ccccc1N
Agent: N=C=N
Solvent: O
Solvent: C1CCOC1
Product: Brc1ccc(Nc2nc3ccccc3[nH]2)c2ccccc12

Procedure:
A slurry of 1-bromo-4-isothiocyanatonaphthalene (1.0 g, 3.8 mmol), o-phenylene diamine (0.45 g, 4.2 mmol), and polymer-supported carbodiimide (9.0 g, 11 mmol, 1.27 mmol/g) in 72 mL THF was heated to 70° C. with a water-cooled reflux condenser for 3 h. The reaction was filtered, rinsing with dichloromethane. The solution was concentrated to a yellow solid, suspended in dichloromethane, and filtered, rinsing with a small quantity of diethyl ether to give N-(4-bromonaphthalen-1-yl)-1H-benzo[d]imidazol-2-amine as a white solid. MS m/z=338 [M+1]+. Calc'd for C17H12BrN3: 337
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:10][C:11]2[C:19]3[N:18]=[N:17][NH:16][C:15]=3[CH:14]=[CH:13][C:12]=2[Cl:20])[CH:9]=1)[C:5]#[N:6].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:28][C:29]([C:31]1[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=1)=[O:30]>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:10][C:11]2[C:19]3[N:18]=[N:17][N:16]([CH2:28][C:29](=[O:30])[C:31]4[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=4)[C:15]=3[CH:14]=[CH:13][C:12]=2[Cl:20])[CH:9]=1)[C:5]#[N:6]
Reactant: O=C(CBr)c1cccnc1
Reactant: N#Cc1cc(Cl)cc(Oc2c(Cl)ccc3[nH]nnc23)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: N#Cc1cc(Cl)cc(Oc2c(Cl)ccc3c2nnn3CC(=O)c2cccnc2)c1
Reaction time: 16 h

Procedure:
3-chloro-5-[(5-chloro-1H-1,2,3-benzotriazol-4-yl)oxy]benzonitrile (50 mg, 0.164 mmol) and cesium carbonate (160 mg, 0.492 mmol) were suspended in DMF (1 μL) at room temperature under N2. To this was added 2-bromo-1-pyridin-3-ylethanone (48.3 mg, 0.172 mmol) as a solid. The resulting mixture was stirred under N2 for 16 hours. The reaction mixture was then diluted with water (2 mL) and extracted with EtOAc (2×15 mL). The combined organic fractions were washed with water (3×10 mL), dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The resulting residue was purified by reverse phase chromatography eluting with 30-95% MeCN/H2O+0.1% TFA. The product was lyophilized to afford the title compound. 1H NMR (DMSO-d6) δ 9.30 (s, 1H), 8.90 (m, 1H), 8.44 (d, J=7.8 Hz, 1H), 7.88 (d, J=8.8 Hz, 1H), 7.85 (m, 1H), 7.79 (d, J=8.8 Hz, 1H), 7.68 (m, 1H), 7.60 (m, 1H), 7.57 (m, 1H), 6.68 (s, 2H). HRMS (M+1)=424.0395
Reaction SMILES: [C:1]1([Li])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[Br:12][C:13]1[CH:26]=[CH:25][C:24]2[C:23](=O)[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([Br:28])[CH:21]=3)[C:16](=O)[C:15]=2[CH:14]=1>CCOCC.CC(O)=O>[Br:12][C:13]1[CH:26]=[CH:25][C:24]2[C:15](=[C:16]([C:9]3[C:10]4[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=4)[CH:6]=[CH:7][CH:8]=3)[C:17]3[C:22]([C:23]=2[C:1]2[C:10]4[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=4)[CH:4]=[CH:3][CH:2]=2)=[CH:21][C:20]([Br:28])=[CH:19][CH:18]=3)[CH:14]=1
Reactant: O=C1c2ccc(Br)cc2C(=O)c2ccc(Br)cc21
Reactant: [Li]c1cccc2ccccc12
Solvent: CC(=O)O
Solvent: CCOCC
Product: Brc1ccc2c(-c3cccc4ccccc34)c3cc(Br)ccc3c(-c3cccc4ccccc34)c2c1
Temperature: 130 °C
Reaction time: 24 h
Yield: 49.8 %

Procedure:
5 g of 1-naphthyl lithium was dissolved in Et2O, and the resulting solution was gradually added dropwise to a solution containing 5 g of 2,6-dibromoanthraquinone dissolved in Et2O. This reaction was carried out on a dry ice bath. Then, the temperature of the reaction material was elevated to room temperature, thereby obtaining an intermediate product. The obtained intermediate product was filtered, thereby obtaining white solids. The white solids thus obtained were dissolved in 100 mL of AcOH, followed by addition of KI and NaH2PO2 and the mixture was stirred at 130° C. for 24 hours. When the reaction was complete, the reaction material was filtered with addition of water. The filtrate was recrystallized from MC and MeOH, thereby obtaining 4 g of 2,6-dibromo-9,10-di-1-naphthylanthracene.
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH3:8])=[C:6]([OH:9])[C:5]([CH3:10])=[CH:4][C:3]=1[OH:11].N1C=CC=CC=1.[C:18](Cl)(=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20]>ClCCl>[Cl:1][C:2]1[C:7]([CH3:8])=[C:6]([OH:9])[C:5]([CH3:10])=[CH:4][C:3]=1[O:11][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20]
Reactant: Cc1cc(O)c(Cl)c(C)c1O
Reactant: CC(C)(C)C(=O)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cc1cc(OC(=O)C(C)(C)C)c(Cl)c(C)c1O
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 91.2 %

Procedure:
To a mixture of 5.91 g of 2-chloro-3,5-dimethylbenzene-1,4-diol, 8.13 g of pyridine and 30 ml of dichloromethane, 10 ml of a dichloromethane solution containing 4.54 g of pivaloyl chloride were added dropwise under ice cooling, followed by stirring at the same temperature for one hour and at room temperature for 90 minutes. The reaction mixture was concentrated by evaporation. Water was added to the concentrate and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by chromatography through a silica gel column (eluting solvent: n-hexane/ethyl acetate=10/1), whereby 8.02 g of the title compound were obtained.
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]23[CH:14]([CH:15]=[N:16][O:17][CH3:18])[CH:13]2[CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10]3)=[CH:5][CH:4]=1.CCCCCC>C(Cl)Cl>[ClH:2].[CH3:18][O:17][N:16]=[CH:15][CH:14]1[C:9]2([C:6]3[CH:7]=[CH:8][C:3]([Cl:2])=[CH:4][CH:5]=3)[CH:13]1[CH2:12][NH:11][CH2:10]2
Reactant: CON=CC1C2CN(C(=O)OC(C)(C)C)CC12c1ccc(Cl)cc1
Agent: Cl
Solvent: ClCCl
Solvent: CCCCCC
Product: CON=CC1C2CNCC12c1ccc(Cl)cc1
Yield: 186.8 %

Procedure:
HCl (g) was bubbled through a solution of tert-butyl 1-(4-chlorophenyl)-6-((methoxyimino)methyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate (210 mg, 0.598 mmol) obtained in step-1 of example 5 in dry DCM (10 mL). After the completion of the reaction as confirmed by TLC, the reaction mixture was purged with excess of nitrogen. The solvent was removed in vacuo to afford a gummy solid which was titurated with hexane to afford hydrochloric acid salt of 1-(4-chlorophenyl)-3-azabicyclo[3.1.0]hexane-6-carbaldehyde O-methyl oxime (140 mg, 81%) as white solid as mixture of isomers.
Reaction SMILES: [CH2:1]([Sn:5](Cl)([CH2:10][CH2:11][CH2:12][CH3:13])[CH2:6][CH2:7][CH2:8][CH3:9])[CH2:2][CH2:3][CH3:4].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1.[CH3:30][O:31][C:32]([CH:34]=[CH:35][C:36]1[N:37]=[CH:38][N:39]2[CH:43]=[CH:42][S:41][C:40]=12)=[O:33].O>C1COCC1>[CH3:30][O:31][C:32]([CH:34]=[CH:35][C:36]1[N:37]=[CH:38][N:39]2[CH:43]=[C:42]([Sn:5]([CH2:10][CH2:11][CH2:12][CH3:13])([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:1][CH2:2][CH2:3][CH3:4])[S:41][C:40]=12)=[O:33]
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Reactant: COC(=O)C=Cc1ncn2ccsc12
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: CCCC[Sn](CCCC)(CCCC)c1cn2cnc(C=CC(=O)OC)c2s1
Reaction time: 0.25 h

Procedure:
Tri-n-butylstannyl chloride (250 μl) and 2.1 ml of a 1.0 N lithiumbis(trimethylsilyl)amide/THF solution were added in that order to a solution of 7-(2-methoxycarbonylvinyl)imidazo[5,1-b]thiazole (a mixture of geometrical isomers) in dry THF in an argon atmosphere at −78° C. The mixture was stirred at the same temperature for 15 min. Water was added thereto. The mixture was extracted with ethyl acetate, followed by washing with saturated brine. The extract was dried over anhydrous magnesium sulfate and then filtered. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=4:1) to give 408 mg of the title compound.
Reaction SMILES: B(Br)(Br)Br.C[O:6][C:7]1[C:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:11]([O:19]C)[CH:10]=[CH:9][C:8]=1[CH2:21][CH2:22][C:23]([OH:25])=[O:24].[CH2:26](Cl)Cl>>[OH:6][C:7]1[C:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:11]([OH:19])[CH:10]=[CH:9][C:8]=1[CH2:21][CH2:22][C:23]([O:25][CH3:26])=[O:24]
Reactant: ClCCl
Reactant: COc1ccc(CCC(=O)O)c(OC)c1-c1ccccc1
Agent: BrB(Br)Br
Product: COC(=O)CCc1ccc(O)c(-c2ccccc2)c1O
Reaction time: 8 h
Yield: 94 %

Procedure:
BBr3 (4.72 g, 1.78 ml, 18.9 mmol) was carefully added through a syringe over 5 min to a stirred solution of dimethoxy acid 4c (1.35 g, 4.7 mmol) in anhydrous CH2Cl2 (20 ml). Resulted mixture was magnetically stirred for 8 h and concentrated under vacuum. The residue was co-evaporated with toluene (2×20 ml), dissolved in methanol (20 ml) and HCl gas was bubbled into the solution for 2 min. The material obtained after evaporation of the solvent was partitioned between cold water (30 ml) and ethyl acetate (100 ml). The organic phase was washed with saturated NaHCO3 (2×10 ml), brine (20 ml), dried over MgSO4 and concentrated. The resultant crude product was chromatographed on a short silica gel column eluting with ethyl acetate. Pure product fractions were concentrated to afford 1.2 g (94%) of 5c as a tan oil. 1H NMR(DMSO-d6): δ 8.95 (s, 1H), 7.82 (s, 1H), 7.24-7.36 (m, 5H), 6.83 (d, J=8.2 Hz, 1H), 6.38 (d, J=8.2 Hz, 1H), 3.59 (s, 3H), 2.75 (t, J=8.0 Hz, 2H), 2.52 (t, J=8.0 Hz, 2).
Reaction SMILES: [OH:1][C@H:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C@H:11]([OH:14])[CH2:12][CH3:13])[CH2:3][CH3:4].N1C=CC=CC=1.[C:21]1([P:27](Cl)(Cl)=[O:28])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.Cl.[NH+]1C=CC=CC=1.Cl>>[CH2:3]([C@@H:2]1[C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[C@H:11]([CH2:12][CH3:13])[O:14][P:27](=[O:28])([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:1]1)[CH3:4]
Reactant: O=P(Cl)(Cl)c1ccccc1
Reactant: CC[C@@H](O)c1ccccc1[C@@H](O)CC
Agent: Cl
Agent: c1cc[nH+]cc1
Solvent: c1ccncc1
Product: CC[C@@H]1OP(=O)(c2ccccc2)O[C@H](CC)c2ccccc21

Procedure:
To a solution of (R,S)-1-[2-(1-Hydroxy-propyl)-phenyl]-propan-1-ol (1.0 g, 5.15 mmol) in pyridine (1.22 g, 15.4 mmol) was added under exclusion of moisture phenyl phosphonic acid dichloride (1.0 g, 5.15 mmol). There is an exotherm and instant formation of pyridinium hydrochloride. The mixture was stirred over night. By 31P-NMR of the crude mixture there was complete conversion, and only one of two possible diastereoisomers present. After addition of HCl (5 ml of 4 N solution) the product was extracted with TBME (20 ml).
Reaction SMILES: [CH2:1]([SH:3])[CH3:2].C[O-].[Na+].[Cl:7][C:8]1[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=1[CH:15]=[C:16]([N:24]1[CH:28]=[N:27][CH:26]=[N:25]1)[C:17](=[O:23])[C:18]([CH3:22])([CH3:21])[CH2:19][F:20]>C(OCC)C>[Cl:7][C:8]1[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=1[CH:15]([S:3][CH2:1][CH3:2])[CH:16]([N:24]1[CH:28]=[N:27][CH:26]=[N:25]1)[C:17](=[O:23])[C:18]([CH3:22])([CH3:21])[CH2:19][F:20]
Reactant: CC(C)(CF)C(=O)C(=Cc1ccc(Cl)cc1Cl)n1cncn1
Reactant: CCS
Agent: C[O-]
Agent: [Na+]
Solvent: CCOCC
Product: CCSC(c1ccc(Cl)cc1Cl)C(C(=O)C(C)(C)CF)n1cncn1
Temperature: 25 °C
Reaction time: 2 h
Yield: 54.5 %

Procedure:
4.4 ml (0.059 mol) of ethylmercaptan were added to a suspension of 3.19 g (0.059 mol) of sodium methylate in 200 ml of diethyl ether. After 2 hours, 20.2 g (0.059 mol) of 1-(2,4-dichlorophenyl)-4,4-dimethyl-5-fluoro-2-(1,2,4-triazol-1-yl)-pent-1-en-3-one (E isomer) were introduced. The mixture was stirred for 18 hours at 25° C. and was then evaporated down in vacuo. The residue was introduced into water and the mixture was extracted with methylene chloride. The methylene chloride solution was dried over sodium sulphate, filtered and evaporated down in vacuo. The oil which remained was caused to crystallize by stirring with diisopropyl ether. 13 g (54.6% of theory) of 1-(2,4-dichlorophenyl)-4,4-dimethyl-1-ethylthio-5-fluoro-2-(1,2,4-triazol-1-yl)-pentan-3-one, of melting point 130° C., were obtained.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]#[C:8][CH2:9][CH2:10][C:11]1[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][CH:12]=1.CC(N(C)C)=O>C(OCC)(=O)C.Cl[Cu]>[CH:7]1[CH:8]=[C:9]([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([C:15]#[N:16])=[CH:17][CH:18]=2)[N:1]2[C:2]=1[CH:3]=[CH:4][CH:5]=[CH:6]2
Reactant: N#Cc1ccc(CCC#Cc2ccccn2)cc1
Agent: Cl[Cu]
Solvent: CCOC(C)=O
Solvent: CC(=O)N(C)C
Product: N#Cc1ccc(Cc2ccc3ccccn23)cc1
Temperature: 130 °C
Yield: 92.8 %

Procedure:
A dried 1 L of three-neck round-bottom flask was flushed with N2, connected to a N2 inlet, equipped with a thermometer and a magnetic stirrer. 4-(4-Pyridin-2-yl-but-3-ynyl)-benzonitrile (58.73 g, 0.25 mol), DMA (490 mL) and TEA (70 mL) were successively added to the flask, resulting in a light brown solution. CuCl (25.05 g, 0.25 mol) was then added, after which the reaction turned dark brown. The reaction mixture was kept stirring at 130° C. After stirring for 3 h at 130° C., the reaction was complete, and cooled to room temperature. The reaction was then quenched with water (300 mL), and ethyl acetate (400 mL) was added. The resulting dark brown mixture was then filtered through a celite cake to give a clear two-layer mixture. After separation, drying, and concentration, a dark oil was obtained. The dark oil was dissolved in 250 mL of ethyl acetate, applied to 15 g of decoloring carbon, and stirred for 20 minutes. After filtration through a celite cake, the filtrate was washed with water (100 mL) twice, dried over sodium sulfate. Concentration gave 53.89 g (89%) of 4-indolizin-3-ylmethyl-benzonitrile. 1H NMR (CDCl3): δ (ppm) 7.55 (d, J=8.1 Hz, 2H); 7.50 (d, J=9.0 Hz, 1H); 7.39 (d, J=9.0 Hz, 1H); 7.23 (d, J=7.8 Hz, 2H); 6.64 (m, 2H), 6.44 (m, 2H); 4.27 (s, 2H). ESMS calcd. (C16H12N2): 232.1. found: 233.1 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][C:5](C#N)=[CH:4][N:3]=1.C[Mg]Br.C(=O)(O)[O-].[Na+].CC[O:20][CH2:21][CH3:22]>C1COCC1>[F:1][C:2]1[N:3]=[CH:4][C:5]([C:21](=[O:20])[CH3:22])=[CH:8][CH:9]=1
Reactant: N#Cc1ccc(F)nc1
Reactant: CCOCC
Agent: C[Mg]Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(=O)c1ccc(F)nc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 14.9 %

Procedure:
To a solution of 6-fluoronicotinonitrile (5.00 g, 41.0 mmol) in THF (50 mL) was added 1 N methylmagnesium bromide (16.4 mL, 49.1 mmol) in THF at 0° C. After addition, the mixture was warmed to ambient temperature and stirred at ambient temperature for 4 hours. Saturated sodium bicarbonate solution (50 mL) and ether (100 mL) were added. The organic layer was separated, washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (5:1 hexane/ethyl acetate) to give 1-(6-fluoropyridin-3-yl)ethanone (0.85 g, 14.9%) as solid.
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][CH:6]1[N:24]=[C:25]=[S:26])(=[O:3])[CH3:2].[NH2:27][C:28]1[S:29][C:30]2[CH:36]=[CH:35][CH:34]=[CH:33][C:31]=2[N:32]=1>C1(C)C(C)=CC=CC=1>[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@H:6]1[NH:24][C:25]([NH:27][C:28]1[S:29][C:30]2[CH:36]=[CH:35][CH:34]=[CH:33][C:31]=2[N:32]=1)=[S:26])(=[O:3])[CH3:2]
Reactant: CC(=O)OC[C@H]1OC(N=C=S)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: Nc1nc2ccccc2s1
Solvent: Cc1ccccc1C
Product: CC(=O)OC[C@H]1O[C@@H](NC(=S)Nc2nc3ccccc3s2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: 110 °C

Procedure:
To 10 ml of anhydrous xylene were added 390 mg (1 mmol) of 2,3,4,6-tetra-O-acetyl-D-glucopyranosyl isothiocyanate and 150 mg (1 mmol) of 2-aminobenzothiazole (MW 150) and the mixture was heated at 110° C. for 40 minutes and allowed to cool to room temperature. Crystals formed were filtered off and recrystallized from methanol to give colourless needles melting between 179° and 181° C. (uncorrected). Yield: 230 mg (42%).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].Br[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29].[OH:30][C:31]1[CH:32]=[C:33]([CH:38]=[C:39]([OH:41])[CH:40]=1)[C:34]([O:36][CH3:37])=[O:35]>CN(C)C=O>[CH2:8]([O:30][C:31]1[CH:32]=[C:33]([CH:38]=[C:39]([O:41][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH3:8])[CH:40]=1)[C:34]([O:36][CH3:37])=[O:35])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]
Reactant: COC(=O)c1cc(O)cc(O)c1
Reactant: CCCCCCCCCCCCCCCCCCCCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCCCCCCCCCCCOc1cc(OCCCCCCCCCCCCCCCCCCCCCC)cc(C(=O)OC)c1
Temperature: 90 °C
Reaction time: 8 h
Yield: 82.7 %

Procedure:
Potassium carbonate (19.9 g, 144 mmol) was suspended in dehydrating N,N-dimethylformamide (200 mL), 1-bromodocosane (15.6 g, 46.7 mmol) and methyl (3,5-dihydroxy)benzoate (3.60 g, 21.4 mmol) were added, and the mixture was stirred at 90° C. overnight. After completion of the reaction, the reaction mixture was poured into purified water (800 mL), the mixture was stirred for 1 hr, and the precipitated solid was collected by filtration. The obtained solid was dissolved again in dichloromethane (800 mL), and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and acetone was added again to precipitate a solid. The solid was collected by filtration and slurry-washed in methanol. After filtration, the obtained solid was dried under reduced pressure to give the title compound (13.9 g, 96.5%) as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[NH:7][C:6]2[CH:14]=[CH:15][CH:16]=[CH:17][C:5]=2[CH:4]=1.C(O)(=O)C1C=CC=CC=1.[O-:27][C:28]#[N:29].[Na+]>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[NH:7][C:6]2[CH:14]=[CH:15][CH:16]=[C:17]([C:28]([NH2:29])=[O:27])[C:5]=2[CH:4]=1
Reactant: COC1=Cc2ccccc2Nc2ccccc21
Reactant: N#C[O-]
Agent: O=C(O)c1ccccc1
Agent: [Na+]
Solvent: Cc1ccccc1
Product: COC1=Cc2c(cccc2C(N)=O)Nc2ccccc21

Procedure:
An especially preferred method according to this invention comprises reaction of 10-methoxy-5H-dibenz[b,f]azepine with benzoic acid and sodium cyanate in toluene at reflux temperature to give 10-methoxy-5H-dibenz[b,f]azepine carboxamide as a major product (such as about 75%), along with 10-oxo-iminodibenzyl and other impurities. The reaction mixture is thereafter filtered and washed with water, and the toluene layer taken as such for hydrolysis in a biphasic system (aqueous hydrochloric acid/toluene) to furnish oxcarbazepine, which is purified just once (whereas twice at least is needed when the prior art process is carried out) in a mixture of methanol and dichloromethane (Scheme-5).