Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([Cl:9])[C:3]=1[N:10]1[C:14](=[O:15])[CH:13]([C:16]2[CH:20]=[CH:19][NH:18][N:17]=2)[C:12]([NH:21][C:22](=[O:32])[C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([N+:29]([O-])=O)[CH:24]=2)=[N:11]1.O.NN>[Ni].CO>[Cl:9][C:4]1[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[C:3]=1[N:10]1[C:14](=[O:15])[CH:13]([C:16]2[CH:20]=[CH:19][NH:18][N:17]=2)[C:12]([NH:21][C:22](=[O:32])[C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([NH2:29])[CH:24]=2)=[N:11]1
Reactant: O=C(NC1=NN(c2c(Cl)cc(Cl)cc2Cl)C(=O)C1c1cc[nH]n1)c1cccc([N+](=O)[O-])c1
Agent: [Ni]
Agent: NN
Solvent: CO
Solvent: O
Product: Nc1cccc(C(=O)NC2=NN(c3c(Cl)cc(Cl)cc3Cl)C(=O)C2c2cc[nH]n2)c1
Reaction time: 1.5 h
Yield: 68.6 %

Procedure:
Next, 197.5 g (0.4 mol) of the 1-(2,4,6-trichlorophenyl)-3-(3-nitrobenzamido)-4-pyrazolyl-5-oxo-2-pyrazoline was added to 2l of methanol, to which was added a small amount of Raney nickel. Then 120 ml of hydrazine hydrate was slowly added dropwise with heating and stirring, the mixture rcacted for about 1.5 hours, after which the insolubles were filtered out (while the mixture was hot). The filtrate was poured into water, and the deposited crystals were then filtered and washed with methanol to obtain 127.2 g (68%) of 1-(2,4,6-trichlorophenyl)-3-(3-aminobenzamido)-4-pyrazolyl-5-oxo-2-pyrazoline.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[Na].CN(C)[CH:14]=[O:15]>CO.[Cu]Br>[CH3:14][O:15][C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1
Reactant: Brc1cnc2[nH]ccc2c1
Reactant: CN(C)C=O
Agent: [Cu]Br
Agent: [Na]
Solvent: CO
Product: COc1cnc2[nH]ccc2c1
Yield: 77.3 %

Procedure:
To a solution of 5-bromo-1H-pyrrolo[2,3-b]pyridine (prepared as in Example 7, 10 g, 50.8 mmol) in N,N-dimethylformamide (200 mL) and methanol (150 mL) at 25° C. was added sodium (100 g, 185.1 mmol) and copper(I) bromide (14.56 g, 101.5 mmol) under a nitrogen atmosphere. The mixture was then heated at reflux for 5 h. After cooling, the solvent was removed under reduced pressure and the residue was extracted with ethyl acetate (3×300 mL), and washed with a saturated aqueous ammonium chloride solution, brine, and dried over anhydrous sodium sulfate. The solvent was evaporated in vacuo to afford 5-methoxy-1H-pyrrolo[2,3-b]pyridine (5.8 g, 77.3%) as a light yellow solid: LC/MS m/e calcd for C8H8N2O [M+H]+ 149.17, observed 149.3.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][O:17][C:18]3[NH:19][CH:20]=[C:21]([CH2:25][C:26]4[CH:27]=[N:28][CH:29]=[N:30][CH:31]=4)[C:22](=[O:24])[N:23]=3)=[CH:11][CH:10]=2)=[CH:4][C:3]=1[C:32]([F:35])([F:34])[F:33].[CH3:36]CN(C(C)C)C(C)C.CI>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][O:17][C:18]3[N:19]([CH3:36])[CH:20]=[C:21]([CH2:25][C:26]4[CH:31]=[N:30][CH:29]=[N:28][CH:27]=4)[C:22](=[O:24])[N:23]=3)=[CH:11][CH:10]=2)=[CH:4][C:3]=1[C:32]([F:35])([F:33])[F:34]
Reactant: O=c1nc(OCCc2ccc(Oc3ccc(Cl)c(C(F)(F)F)c3)cc2)[nH]cc1Cc1cncnc1
Reactant: CCN(C(C)C)C(C)C
Solvent: CI
Solvent: ClCCl
Product: Cn1cc(Cc2cncnc2)c(=O)nc1OCCc1ccc(Oc2ccc(Cl)c(C(F)(F)F)c2)cc1
Yield: 43.8 %

Procedure:
To a solution of 2-{[2-(4-{[4-chloro-3-(trifluoromethyl)phenyl]oxy}phenyl)ethyl]oxy}-5-(5-pyrimidinylmethyl)-4(1H)-pyrimidinone (45 mg, 0.089 mmol) in dichloromethane (DCM) (2 mL) was added DIPEA (0.031 mL, 0.179 mmol) and MeI (8.39 μL, 0.134 mmol). The mixture was purified by reverse phase biotage affording 2-{[2-(4-{[4-chloro-3-(trifluoromethyl)phenyl]oxy}phenyl)ethyl]oxy}-1-methyl-5-(5-pyrimidinylmethyl)-4(1H)-pyrimidinone (20 mg, 0.039 mmol, 43.2% yield) LCMS: rt=3.37 min, [M+H+]=517
Reaction SMILES: [OH-].[Na+].C([O:10][C:11](=[O:30])[C@H:12]([CH2:21][C:22]1[CH:27]=[CH:26][N:25]=[C:24]([C:28]#[N:29])[CH:23]=1)[NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])C1C=CC=CC=1.Cl>O1CCOCC1>[C:17]([O:16][C:14]([NH:13][C@H:12]([C:11]([OH:30])=[O:10])[CH2:21][C:22]1[CH:27]=[CH:26][N:25]=[C:24]([C:28]#[N:29])[CH:23]=1)=[O:15])([CH3:20])([CH3:18])[CH3:19]
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccnc(C#N)c1)C(=O)OCc1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: CC(C)(C)OC(=O)N[C@@H](Cc1ccnc(C#N)c1)C(=O)O
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 77.4 %

Procedure:
1M Aqueous sodium hydroxide solution (10.8 ml, 10.8 mmol) was added dropwise over 5 minutes to a stirred, ice-cooled solution of N-t-butoxycarbonyl-3-(2-cyano-4-pyridyl)-(S)-alanine benzyl ester (Preparation 12; 2.73 g, 7.1 mmol) in 1,4-dioxan and the resulting solution allowed to warm to room temperature. After 1.5 hours, the pH of the solution was adjusted to 9 using 2M hydrochloric acid and the bulk of the organic solvent removed under reduced pressure. The residual aqueous solution was washed with ethyl acetate, acidified with solid citric acid and extracted with ethyl acetate, then the latter extracts dried (MgSO4) and evaporated under reduced pressure to furnish the title compound (1.6 g) as a white solid. Rf 0.67 (SS 13). Found: C,57.86; H,5.99; N,13.52. C14H17N3O4 requires C,57.72; H,5.88; N,14.42%.
Reaction SMILES: [C:1]1([N:7]2[CH2:12][CH2:11][CH:10]([NH:13][C:14](=[O:22])OC3C=CC=CC=3)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[CH3:24][S:25]([N:28]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:30]2([CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[CH2:29]1)(=[O:27])=[O:26]>>[CH3:24][S:25]([N:28]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:30]2([CH2:31][CH2:32][N:33]([C:14]([NH:13][CH:10]3[CH2:9][CH2:8][N:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[CH2:12][CH2:11]3)=[O:22])[CH2:34][CH2:35]2)[CH2:29]1)(=[O:26])=[O:27]
Reactant: CS(=O)(=O)N1CC2(CCNCC2)c2ccccc21
Reactant: O=C(NC1CCN(c2ccccc2)CC1)Oc1ccccc1
Agent: Cl
Product: CS(=O)(=O)N1CC2(CCN(C(=O)NC3CCN(c4ccccc4)CC3)CC2)c2ccccc21

Procedure:
Compounds of Examples 78 to 83 were obtained by following the same procedure as in Example 77-(2), except that phenyl N-(1-phenyl-4-piperidyl)carbamate and 1-methanesulfonylspiro[indoline-3,4′-piperidine]hydrochloride used in Example 77-(2) were replaced with the corresponding starting material of each desired compound.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][C:6](I)=[CH:7][N:8]=2)[N:3]=1.[N:13]1([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.O>[Cl:1][C:2]1[N:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([N:16]1[CH2:15][CH2:14][N:13]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:18][CH2:17]1)=[CH:5]2
Reactant: Clc1ccc2ncc(I)cc2n1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: C1COCCO1
Product: CC(C)(C)OC(=O)N1CCN(c2cnc3ccc(Cl)nc3c2)CC1
Temperature: 25 °C
Yield: 29.7 %

Procedure:
To a solution of 2-chloro-7-iodo-1,5-naphthyridine (D-17) (586 mg, 2.02 mmol, 1.0 eq) in 1,4-dioxane (20 mL), tert-butyl piperazine-1-carboxylate (372 mg, 2.00 mmol, 1.0 eq), cesium carbonate (922 mg, 2.83 mmol, 1.4 eq), tris(benzylideneacetone)dipalladium (37 mg, 0.04 mmol, 0.02 eq) and Xantphos (35 mg, 0.06 mmol, 0.03 eq) were added. The mixture was stirred at reflux for 16 h under an argon atmosphere. After the reaction mixture was cooled to RT, it was diluted with water (50 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layer was washed with brine (50 mL), dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo. The resultant residue was purified by silica gel column chromatography (15% ethyl acetate/petroether) to afford the desired product, tert-butyl 4-(6-chloro-1,5-naphthyridin-3-yl)piperazine-1-carboxylate (D-18) (207 mg, 29.4% yield) as a yellow oil. 1H NMR (300 MHz, CDCl3-d6) δ: 8.79 (d, J=2.7 Hz, 1H), 8.16 (d, J=8.7 Hz, 1H), 7.43 (d, J=2.7 Hz, 1H), 7.36 (d, J=8.7 Hz, 1H), 3.64 (m, 4H), 3.34 (m, 4H), 1.49 (s, 9H); EST-MS m/z: 349.13[M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([O:16][CH3:17])=[CH:5][C:6]2[NH:12][C:11](=[O:13])[CH2:10][NH:9][C:8](=[O:14])[C:7]=2[CH:15]=1.[H-].[Na+].[CH2:20](I)[CH2:21][CH3:22]>CN(C=O)C>[CH3:1][O:2][C:3]1[C:4]([O:16][CH3:17])=[CH:5][C:6]2[N:12]([CH2:20][CH2:21][CH3:22])[C:11](=[O:13])[CH2:10][NH:9][C:8](=[O:14])[C:7]=2[CH:15]=1
Reactant: COc1cc2c(cc1OC)C(=O)NCC(=O)N2
Reactant: CCCI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCN1C(=O)CNC(=O)c2cc(OC)c(OC)cc21
Reaction time: 0.17 h
Yield: 37.6 %

Procedure:
To a solution of 723 mg (3.06 mmol) of 7,8-dimethoxy-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione (XVIIab), in 6 ml of anhydrous DMF, add under an inert atmosphere 134 mg (3.37 mmol) of 60% NaH in oil. After 10 minutes at room temperature, add dropwise 328 μl (3.37 mmol) of n-PrI. Allow to stand at room temperature for 3 hours. Add 40 ml of a water-ice mixture. Filter the precipitate and wash twice with 1 ml of EtOH and 3 ml of Et2O. One obtains 320 mg of the abovenamed product in the form of a white powder. Yield: 65%. 1H-NMR (DMSO, 200 MHz): d 0.66–0.73 (m, 3H, CH2CH3), 1.27–1.39 (m, 2H, CH2CH3), 3.30–4.22 (m, 10H, CH2+CH2+2×OCH3), 6.97 (s, 1H Ar), 7.13 (s, 1H Ar), 8.56 (s, 1H, NH).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([F:58])[C:5]([S:52]([CH:55]([CH3:57])[CH3:56])(=[O:54])=[O:53])=[C:6]([CH2:8][N:9]([CH3:51])[C:10]([CH:12]([NH:24][C:25]2[CH:26]=[C:27]3[C:32](=[CH:33][C:34]=2[F:35])[C:31]([N:36]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C:37](=[O:43])[O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[N:30][CH:29]=[CH:28]3)[C:13]2[CH:18]=[CH:17][C:16]([C@@H:19]([CH3:22])[CH2:20][OH:21])=[C:15]([CH3:23])[CH:14]=2)=[O:11])[CH:7]=1.[C:59](Cl)(Cl)=[O:60]>C(#N)C.ClCCl>[C:39]([O:38][C:37]([N:36]([C:31]1[C:32]2[C:27](=[CH:26][C:25]([NH:24][C@H:12]3[C:10](=[O:11])[N:9]([CH3:51])[CH2:8][C:6]4[CH:7]=[C:2]([CH:3]=[C:4]([F:58])[C:5]=4[S:52]([CH:55]([CH3:57])[CH3:56])(=[O:53])=[O:54])[NH:1][C:59](=[O:60])[O:21][CH2:20][C@H:19]([CH3:22])[C:16]4[CH:17]=[CH:18][C:13]3=[CH:14][C:15]=4[CH3:23])=[C:34]([F:35])[CH:33]=2)[CH:28]=[CH:29][N:30]=1)[C:44](=[O:45])[O:46][C:47]([CH3:48])([CH3:49])[CH3:50])=[O:43])([CH3:42])([CH3:40])[CH3:41]
Reactant: Cc1cc(C(Nc2cc3ccnc(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)c3cc2F)C(=O)N(C)Cc2cc(N)cc(F)c2S(=O)(=O)C(C)C)ccc1[C@@H](C)CO
Reactant: O=C(Cl)Cl
Solvent: ClCCl
Solvent: CC#N
Product: Cc1cc2ccc1[C@@H](C)COC(=O)Nc1cc(F)c(S(=O)(=O)C(C)C)c(c1)CN(C)C(=O)[C@@H]2Nc1cc2ccnc(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)c2cc1F
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 21.8 %

Procedure:
A solution of 34A (170 mg, 0.206 mmol) in acetonitrile (3 mL) and dichloromethane (6 mL) was cooled to 0° C. To this solution, was added phosgene (20% in toluene, 0.112 mL, 0.226 mmol). The mixture was stirred at 0° C. for 5 min, and rt for 1 h. The mixture was bubbled with Ar for 10 min to remove excess phosgene. The resulting solution was added dropwise over 3 h via syringe pump into a solution of TEA (0.287 mL, 2.058 mmol) in CH2Cl2 (260 mL). The solution was stirred for 16 h, and then concentrated and purified by flash chromatography to give a mixture of diastereoisomers (98 mg, 0.115 mmol, 55.9% yield). The diastereomers were separated by a prep chiral HPLC equipped with a OD column to give 34B (38 mg, 0.045 mmol, 38.8% yield). MS (ESI) m/z: 852.3 [M+1]+. 1H NMR (500 MHz, methanol-d4) δ ppm 8.10 (1H, d, J=5.8 Hz), 7.78 (1H, dd, J=7.8, 1.5 Hz), 7.55 (1H, d, J=5.8 Hz), 7.51 (1H, d, J=8.0 Hz), 7.41 (1H, d, J=12.1 Hz), 7.06 (1H, d, J=8.3 Hz), 7.04 (1H, d, J=1.7 Hz), 6.61 (1H, dd, J=12.0, 2.1 Hz), 6.27 (1H, d, J=1.1 Hz), 5.67-5.78 (2H, m), 4.63 (1H, t, J=11.0 Hz), 4.24 (1H, d, J=17.9 Hz), 3.98 (1H, dd, J=10.7, 4.4 Hz), 3.45-3.57 (2H, m), 3.34-3.41 (3H, m), 2.28 (3H, s), 1.38 (3H, d, J=6.9 Hz), 1.35 (3H, d, J=6.9 Hz), 1.33 (3H, d, J=6.9 Hz), 1.28 (18H, s).
Reaction SMILES: [C:1]1([C:7]2([C:10]#[N:11])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:18](OCC)C>>[CH:9]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:10][NH2:11])[CH2:8][CH2:18]1
Reactant: N#CC1(c2ccccc2)CC1
Reactant: CCOCC
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Product: NCC(c1ccccc1)C1CC1
Temperature: 0 °C

Procedure:
1-Phenyl-1-cyclopropanecarbonitrile (1.0 g, 6.98 mmol) was added to a stirred suspension of lithium aluminum hydride in anhydrous diethyl ether (25 mL). The suspension was refluxed for 2 h, then cooled to 0° C., and the excess hydride was destroyed by careful addition of water. After treatment with sodium hydroxide (1 N), the mixture was filtered and the filtrate extracted with diethyl ether. After drying of the organic phase with and evaporation 2 (719 mg, 70% ) was obtained as a clear liquid and used without further purification. 1H NMR (DMSO-d6): δ 7.28 (m, 4 H), 7.17 (m, 1 H), 2.70 (s, 2 H), 1.45 (bs, 2 H); 0.78 (dd, J=6.2, 3.8 Hz, 2 H); 0.67 (dd, J=6.2 Hz, 3.8 Hz, 2 H). MS: (m/z) 148 (M+1)+.
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.CN(C)C=O.[CH2:14]([C:21]1[C:22]2[CH2:29][CH2:28][CH:27]([CH2:30][OH:31])[CH2:26][C:23]=2[S:24][CH:25]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>O>[Br:1][C:25]1[S:24][C:23]2[CH2:26][CH:27]([CH2:30][OH:31])[CH2:28][CH2:29][C:22]=2[C:21]=1[CH2:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: OCC1CCc2c(Cc3ccccc3)csc2C1
Reactant: O=C1CCC(=O)N1Br
Solvent: O
Solvent: CN(C)C=O
Product: OCC1CCc2c(sc(Br)c2Cc2ccccc2)C1
Reaction time: 1 h

Procedure:
103 mg of N-bromosuccinimide was added little by little to a solution of 5.0 ml of N,N-dimethylformamide containing 136 mg of 3-benzyl-6-(hydroxymethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene under ice-cooling. After stirring for one hour, water was added to the reaction solution and the mixture was extracted with ethyl acetate. The organic phase was washed with water and brine, and the solvent was removed. Then, the residue was subjected to silica gel column chromatography and eluted with hexane and then with hexane/ethyl acetate (2:1), to give 164 mg of the target compound.
Reaction SMILES: C([O:8][C:9]1[CH:10]=[C:11]([NH:24]C(=O)OCC2C=CC=CC=2)[CH:12]=[CH:13][C:14]=1[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][CH3:23])=[CH:18][CH:17]=1)C1C=CC=CC=1>CO.[C].[Pd]>[NH2:24][C:11]1[CH:12]=[CH:13][C:14]([CH2:15][C:16]2[CH:17]=[CH:18][C:19]([CH2:22][CH3:23])=[CH:20][CH:21]=2)=[C:9]([OH:8])[CH:10]=1
Reactant: CCc1ccc(Cc2ccc(NC(=O)OCc3ccccc3)cc2OCc2ccccc2)cc1
Agent: [Pd]
Solvent: CO
Product: CCc1ccc(Cc2ccc(N)cc2O)cc1
Reaction time: 11 h
Yield: 76.6 %

Procedure:
To a solution of 3-benzyloxy-4-(4-ethylbenzyl)benzoic acid (1.4 g) and triethylamine (1.3 mL) in 1,4-dioxane (10 mL) was added a solution of diphenylphosphoryl azide (1.3 g) in 1,4-dioxane (10 mL), and the mixture was stirred at 100° C. for 1 hour. Benzyl alcohol (1.6 mL) was added to the reaction mixture, and the mixture was stirred at the same temperature for 7 hours. The solvent of the reaction mixture was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=4/1) to give benzyl N-[3-benzyloxy-4-(4-ethylbenzyl)phenyl]carbamate (1.4 g). To a solution of obtained benzyl N-[3-benzyloxy-4-(4-ethylbenzyl)phenyl]carbamate (1.4 g) in methanol (15 mL) was added 10% palladium-carbon powder (0.28 g), and the mixture was stirred under a hydrogen atmosphere for 11 hours. An insoluble material was removed by filtration, and the solvent of the filtrate was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=1/1) to give 5-amino-2-(4-ethylbenzyl)phenol (0.54 g).
Reaction SMILES: C(O[C:5](=[O:7])[CH3:6])(=O)C.[CH:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[C:10]([NH2:18])[N:9]=1.C(N(CC)CC)C>C(Cl)Cl>[CH:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[C:10]([NH:18][C:5](=[O:7])[CH3:6])[N:9]=1
Reactant: CC(=O)OC(C)=O
Reactant: Nc1cc2ccccc2cn1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)Nc1cc2ccccc2cn1
Reaction time: 3.5 h
Yield: 100 %

Procedure:
Acetic anhydride (5.92 mL, 62.6 mmol) was added to a suspension of isoquinolin-3-amine (3.01 g, 20.9 mmol) and triethylamine (3.18 mL, 23.0 mmol) in CH2Cl2 (80 mL) at ambient temperature. The mixture was stirred 3.5 hours, then the volatiles were evaporated in vacuo. The residue was chased with toluene and concentrated in vacuo (3×25 mL) to provide the title compound (3.89 g) as a yellow solid. This material, which was found to also contain small quantities of acetic acid, was used without further purification. 1H NMR (300 MHz, DMSO-d6) δ 10.58 (s, 1H), 9.13 (s, 1H), 8.45 (s, 1H), 8.04 (d, J=7.8 Hz, 1H), 7.88 (d, J=8.2 Hz, 1H), 7.69 (ddd, J=8.2, 6.8, 1.2 Hz, 1H), 7.52 (ddd, J=7.9, 6.9, 1.0 Hz, 1H), 2.13 (s, 3H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[CH3:9][S:10](Cl)=[O:11]>>[Cl:8][C:5]1[N:6]=[CH:7][C:2]([NH:1][S:10]([CH3:9])=[O:11])=[CH:3][N:4]=1
Reactant: CS(=O)Cl
Reactant: Nc1cnc(Cl)nc1
Product: CS(=O)Nc1cnc(Cl)nc1

Procedure:
The title compound is prepared from 5-amino-2-chloropyrimidine and methanesulfinyl chloride following a procedure analogous to that described for Intermediate 3 (Step 1). The reaction mixture is cooled in an ice bath for the entire reaction time. LC (method 1): tR=0.49 min; Mass spectrum (ESI+): m/z=192 [M+H]+.
Reaction SMILES: [N:1]1([C:7]2[N:12]=[CH:11][NH:10][C:9](=[O:13])[CH:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[Cl:14][C:15]1[C:22]([Cl:23])=[CH:21][CH:20]=[C:19]([Cl:24])[C:16]=1[CH:17]=O>>[Cl:14][C:15]1[C:22]([Cl:23])=[CH:21][CH:20]=[C:19]([Cl:24])[C:16]=1[CH2:17][N:4]1[CH2:5][CH2:6][N:1]([C:7]2[N:12]=[CH:11][NH:10][C:9](=[O:13])[CH:8]=2)[CH2:2][CH2:3]1
Reactant: O=Cc1c(Cl)ccc(Cl)c1Cl
Reactant: O=c1cc(N2CCNCC2)nc[nH]1
Product: O=c1cc(N2CCN(Cc3c(Cl)ccc(Cl)c3Cl)CC2)nc[nH]1

Procedure:
6-[4-(2,3,6-Trichloro-benzyl)-piperazin-1-yl]-3H-pyrimidin -4-one was prepared using Procedure A from 6-piperazin-1-yl-3H-pyrimidin-4-one (Intermediate 4) and 2,3,6-trichlorobenzaldehyde. Mass spectrum (ES) MH+=373.
Reaction SMILES: [CH3:1][N:2]1[CH2:8][CH2:7][CH:6]([OH:9])[C:5]2[CH:10]=[CH:11][O:12][C:4]=2[CH2:3]1.[Br:13][C:14]1[C:15]([Cl:21])=[C:16](F)[CH:17]=[CH:18][CH:19]=1>>[Br:13][C:14]1[C:15]([Cl:21])=[C:16]([O:9][CH:6]2[CH2:7][CH2:8][N:2]([CH3:1])[CH2:3][C:4]3[O:12][CH:11]=[CH:10][C:5]2=3)[CH:17]=[CH:18][CH:19]=1
Reactant: Fc1cccc(Br)c1Cl
Reactant: CN1CCC(O)c2ccoc2C1
Product: CN1CCC(Oc2cccc(Br)c2Cl)c2ccoc2C1

Procedure:
The same method as in Example 1 was conducted using 7-methyl-5,6,7,8-tetrahydro-4H-furo[2,3-c]azepin-4-ol (Reference Example 19) instead of 6-methyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-4-ol (Reference Example 6) and was conducted using 3-bromo-2-chloro-1-fluorobenzene instead of 1-fluoronaphthalene to give the objective compound.
Reaction SMILES: [Si]([O:8][CH2:9][C@H:10]([CH3:39])[O:11][C:12]1[CH:13]=[C:14]([CH:27]=[C:28]([C:30]([NH:32][C:33]2[CH:37]=[CH:36][N:35]([CH3:38])[N:34]=2)=[O:31])[CH:29]=1)[O:15][C:16]1[CH:26]=[CH:25][C:19]([C:20]([O:22]CC)=[O:21])=[CH:18][CH:17]=1)(C(C)(C)C)(C)C.O.[OH-].[Li+].Cl>C1COCC1.O>[OH:8][CH2:9][C@H:10]([CH3:39])[O:11][C:12]1[CH:13]=[C:14]([CH:27]=[C:28]([C:30]([NH:32][C:33]2[CH:37]=[CH:36][N:35]([CH3:38])[N:34]=2)=[O:31])[CH:29]=1)[O:15][C:16]1[CH:17]=[CH:18][C:19]([C:20]([OH:22])=[O:21])=[CH:25][CH:26]=1
Reactant: CCOC(=O)c1ccc(Oc2cc(O[C@@H](C)CO[Si](C)(C)C(C)(C)C)cc(C(=O)Nc3ccn(C)n3)c2)cc1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: C[C@@H](CO)Oc1cc(Oc2ccc(C(=O)O)cc2)cc(C(=O)Nc2ccn(C)n2)c1
Temperature: 25 °C
Reaction time: 72 h
Yield: 108.7 %

Procedure:
A solution of ethyl 4-(3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenoxy)benzoate (3.78 g, 6.84 mmol) in THF (100 mL) was added to a solution of lithium hydroxide monohydrate (1.44 g, 33 mmol) in water (50 mL). The mixture was stirred at ambient temperature for 72 hours. 1M Hydrochloric acid was added until pH=2 and the mixture stirred for a further 1 hour. The THF was removed in vacuo and the solid precipitate filtered off, washed with water and dried in vacuo to give the desired compound (3.06 g).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[O:11][CH3:12])[C:7](=O)[CH2:6][CH2:5]2.[C:14]([CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])#[N:15].CC(O)=O.C([O-])(=O)C.[NH4+]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[O:11][CH3:12])/[C:7](=[C:16](\[C:14]#[N:15])/[C:17]([O:19][CH2:20][CH3:21])=[O:18])/[CH2:6][CH2:5]2
Reactant: CCOC(=O)CC#N
Reactant: COc1cc2c(cc1Cl)CCC2=O
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: Cc1ccccc1
Solvent: CC(=O)O
Product: CCOC(=O)/C(C#N)=C1\CCc2cc(Cl)c(OC)cc21
Temperature: 120 °C
Reaction time: 12 h
Yield: 61.6 %

Procedure:
To the solution of 5-chloro-6-methoxy-2,3-dihydro-1H-inden-1-one (Prep15, 12 g, 61.2 mmol) in toluene (240 ml) was added ethyl cyanoacetate (8.3 g, 73.46 mmol), AcOH (48 ml, 0.8 mol) and ammonium acetate (12 g, 0.16 mol). The mixture was stirred for 12 hours at 120° C., checked by TLC, concentrated, filtered and washed with water and ethanol twice and purified by FC to afford 11 g of title compound (y=62%).
Reaction SMILES: [N:1]1([C:5](=[O:22])[CH2:6][C:7]2[CH:12]=[CH:11][C:10]([O:13]CC3C=CC=CC=3)=[CH:9][C:8]=2[CH3:21])[CH2:4][CH2:3][CH2:2]1>C(O)C.[OH-].[OH-].[Pd+2]>[N:1]1([C:5](=[O:22])[CH2:6][C:7]2[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][C:8]=2[CH3:21])[CH2:4][CH2:3][CH2:2]1
Reactant: Cc1cc(OCc2ccccc2)ccc1CC(=O)N1CCC1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CCO
Product: Cc1cc(O)ccc1CC(=O)N1CCC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
1-(azetidin-1-yl)-2-[4-(benzyloxy)-2-methylphenyl]ethanone (440 mg, 1.490 mmol) was dissolved in ethanol (3 ml) and palladium hydroxide on carbon (20%) (105 mg, 0.149 mmol) added. The mixture was stirred under an atmosphere of hydrogen gas at RT overnight. The mixture was filtered and the filtrate concentrated under reduced pressure to afford the title compound. LC/MS (m/z): 206 (M+H)+.
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.C(O)(=O)C1C=CC=CC=1.[O-:27][C:28]#[N:29].[Na+]>C1(C)C=CC=CC=1>[CH:7]1[CH:8]=[CH:9][C:10]2[N:11]([C:28]([NH2:29])=[O:27])[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)c1ccccc1
Agent: [Na+]
Solvent: Cc1ccccc1
Product: NC(=O)N1c2ccccc2CC(=O)c2ccccc21
Temperature: 25 °C
Yield: 40.7 %

Procedure:
A mixture of 100 gms of 10-methoxyiminostilbene in 2000 mL of toluene containing 274 gms of benzoic acid and 370 gms of sodium cyanate were heated to reflux temperature under stirring and maintained for 12 hours. The reaction mixture was then cooled to room temperature and filtered. The clear toluene filtrate was 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 75-90° 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 46 gms of pure oxcarbazepine. Purity was determined by HPLC to be 99.45%.