Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Li]CCCC.CN(CCN(C)C)C.[CH:14]([Si:17]([CH:30]([CH3:32])[CH3:31])([CH:27]([CH3:29])[CH3:28])[O:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[O:25][CH3:26])([CH3:16])[CH3:15].C1C[O:36][CH2:35]C1>CCOC(C)=O>[CH3:26][O:25][C:20]1[C:19]([O:18][Si:17]([CH:14]([CH3:16])[CH3:15])([CH:27]([CH3:29])[CH3:28])[CH:30]([CH3:32])[CH3:31])=[C:24]([CH:23]=[CH:22][CH:21]=1)[CH:35]=[O:36]
Reactant: COc1ccccc1O[Si](C(C)C)(C(C)C)C(C)C
Reactant: C1CCOC1
Agent: CN(C)CCN(C)C
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Product: COc1cccc(C=O)c1O[Si](C(C)C)(C(C)C)C(C)C
Temperature: 0 °C
Reaction time: 8 h

Procedure:
nBuLi (2.5 M in hexanes) (36 mmol) is mixed with TMEDA (36 mmol) at 0° C. in a dry round bottom flask for 10 minutes. A solution of triisopropyl-(2-methoxy-phenoxy)-silane (24 mmol) in 25 mL of dry THF is added to the above mixture. The mixture is warmed up to room temperature in 2 hours by removal of the ice bath. The slightly yellow solution is then transferred to another dry flask containing dry 7.5 mL of DMF at room temperature. The mixture is stirred overnight. HCl (1 M) is added to the mixture to quench the reaction. The mixture is diluted with EtOAc (100 mL), washed with HCl (1 M) (2×100 mL) and brine (50 mL) and finally dried over anhydrous Na2SO4. Purification is accomplished by silica flash chromatography (5% EtOAc/hexane) to yield 3-methoxy-2-triisopropylsilanyloxy-benzaldehyde as a colorless oil which needs to be stored at low temperatures: 1H NMR (400 MHz, CDCl3) δ 10.4 (s, 1H), 7.42 (dd, J1=7.7 Hz, J2=1.7 Hz, 1H), 7.67 (d, J1=8 Hz, J2=1.7 Hz, 1H), 7.04 (t, J=8.4 Hz, 1H), 3.96 (s, 3H), 1.26-1.35 (m, 3H), 1.13 (s, 9H), 1.12 (s, 9H). LC/MS (ES+): (M+1) 309.2. Rf=0.4 (5% EtOAc/hexane).
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C([O:29][CH2:30][CH3:31])=O)=O.[C:32]1([CH2:38][N:39]2[CH2:44][CH2:43][CH:42]([CH2:45][CH2:46][OH:47])[CH2:41][CH2:40]2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.[OH:48][C:49]1[CH:59]=[CH:58][C:52]([C:53]([O:55][CH2:56][CH3:57])=[O:54])=[CH:51][CH:50]=1>O1CCCC1>[C:30]([OH:29])(=[O:47])/[CH:31]=[CH:52]\[C:53]([OH:55])=[O:54].[C:32]1([CH2:38][N:39]2[CH2:44][CH2:43][CH:42]([CH2:45][CH2:46][O:48][C:49]3[CH:50]=[CH:51][C:52]([C:53]([O:55][CH2:56][CH3:57])=[O:54])=[CH:58][CH:59]=3)[CH2:41][CH2:40]2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1
Reactant: OCCC1CCN(Cc2ccccc2)CC1
Reactant: CCOC(=O)c1ccc(O)cc1
Reactant: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCOC(=O)c1ccc(OCCC2CCN(Cc3ccccc3)CC2)cc1
Product: O=C(O)/C=C\C(=O)O
Reaction time: 0.25 h
Yield: 42 %

Procedure:
To a stirred and cooled (-10° C.) mixture of 19.6 parts of triphenyl phosphine and 54 parts of tetrahydrofuran were added portionwise 13.7 parts of diethyl diazenedicarboxylate (exothermic reaction). Upon completion, stirring was continued for 15 minutes and then a solution of 16.5 parts of 1-(phenylmethyl)-4-piperidineethanol and 12.5 parts of ethyl 4-hydroxybenzoate in 54 parts of tetrahydrofuran was added dropwise at a temperature between 0° and -5° C. After complete addition, the whole was stirred overnight at room temperature and then evaporated. Water was added to the residue and the product was extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was dissolved in 2,2'-oxybispropane and allowed to crystallize. The precipitate was filtered off and the filtrate was evaporated. The residue was converted into the (Z)-2-butenedioate salt in 280 parts of 2-propanol. The salt was filtered off and dried, yielding 15 parts (42%) of ethyl 4-[2-[ 1-(phenylmethyl)-4-piperidinyl]ethoxy]benzoate (Z)-2-butenedioate(1:1); mp. 142.0° C. (int. 50).
Reaction SMILES: [F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C:13]([CH3:34])([CH3:33])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21](Cl)=[CH:22][C:23]=2[C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[CH3:31])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[NH2:37][CH2:38][C@H:39]1[CH2:43][CH2:42][CH2:41][N:40]1C(OC(C)(C)C)=O.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.ClCCl>[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C:13]([CH3:34])([CH3:33])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21]([NH:37][CH2:38][C@@H:39]3[CH2:43][CH2:42][CH2:41][NH:40]3)=[CH:22][C:23]=2[C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[CH3:31])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1
Reactant: Cc1cc(F)ccc1-c1cc(Cl)ncc1N(C)C(=O)C(C)(C)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H]1CN
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: ClCCl
Product: Cc1cc(F)ccc1-c1cc(NC[C@@H]2CCCN2)ncc1N(C)C(=O)C(C)(C)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Temperature: 138 °C
Yield: 24.5 %

Procedure:
A suspension of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide [WO 2005/002577] (1.5 g, 2.81 mmol) 1,1-dimethylethyl (2R)-2-(aminomethyl)-1-pyrrolidinecarboxylate (N-Boc prolinamine) (1.41 g, 7.025 mmol) and potassium carbonate (777 mg, 5.62 mmol) in 6 mL of DMSO was heated for 18 h at 150° C. (temperature detected 138° C.). A HPLC/MS check showed a 50% conversion with partial loss of the Boc protecting group. The reaction was heated under microwave irradiation to 160° C. for 1 h and to 180° C. for two cycles of 1 h and 1.5 h, respectively. The suspension was diluted with dichloromethane and extracted with sat. NaHCO3 and the organics were dried (Na2SO4) and the solution was loaded on a SCX cartridge, washed with dichloromethane (100 mL) and methanol (200 mL, this wash allowed the recovery of the unreacted chloropyridine) and eluted with 2M NH3 in MeOH. The crude thus obtained, which contained both the Boc-protected and unprotected compounds, was purified by flash chromatography (silica, cyclohexane:EtOAc 80:20 to EtOAc). Isolated 350 mg of Boc-protected amine and 410 mg of the title compound. This last compound was purified further by a boc-protection, flash chromatography, TFA deprotection and SCX isolation procedure. Final yield: 165 mg. O.A.HPLC, peak @ 5.20 min, >99% purity (UV).
Reaction SMILES: [C:1]1([C:7]2[CH:15]=[C:14]3[C:10]([CH2:11][CH:12]([Br:17])[C:13]3=[O:16])=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O1CCCC1.Cl>C(O)C>[C:1]1([C:7]2[CH:15]=[C:14]3[C:10]([CH2:11][CH:12]([Br:17])[CH:13]3[OH:16])=[CH:9][CH:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C1c2cc(-c3ccccc3)ccc2CC1Br
Agent: Cl
Solvent: C1CCOC1
Solvent: CCO
Product: OC1c2cc(-c3ccccc3)ccc2CC1Br
Temperature: 25 °C
Reaction time: 15 h
Yield: 71.7 %

Procedure:
To a three-necked flask of 250 ml, fitted with a condenser, was added 3.55 g (12.4 mmol) of 6-phenyl-2-bromo-1-indanone, 100 ml of tetrahydrofuran (THF) and 100 ml of absolute ethanol. A dark red solution was formed and 0.40 g (10 mmol) of sodiumboronhydride was added in small portions. The mixture was stirred for 15 hours at room temperature. The mixture was poured onto ice and a 5% hydrochloric acid solution was added. The water layer was extracted 3 times with ether and the combined ether layer washed 2 times with a saturated NaCl solution. The ether was evaporated under reduced pressure yielding 2.57 g (8.89 mmol) of 6-phenyl-2-bromoindanol (72%).
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][C@H:2]1[CH:6]=[CH:7][C:8]1[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=1.[O:14]=[C:15]([OH:27])[C@@H:16]([C@H:18]([C@H:20]([C@@H:22]([C:24]([OH:26])=[O:25])[OH:23])[OH:21])[OH:19])[OH:17]>C(O)C.O>[O:14]=[C:15]([OH:27])[C@@H:16]([C@H:18]([C@H:20]([C@@H:22]([C:24]([OH:26])=[O:25])[OH:23])[OH:21])[OH:19])[OH:17].[NH:1]1[CH2:5][CH2:4][CH2:3][C@H:2]1/[CH:6]=[CH:7]/[C:8]1[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=1.[NH:1]1[CH2:5][CH2:4][CH2:3][C@H:2]1/[CH:6]=[CH:7]/[C:8]1[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=1
Reactant: C(=C[C@@H]1CCCN1)c1cccnc1
Agent: O=C(O)[C@@H](O)[C@H](O)[C@H](O)[C@@H](O)C(=O)O
Solvent: CCO
Solvent: O
Product: C(=C/[C@@H]1CCCN1)\c1cccnc1
Temperature: 70 °C

Procedure:
To a stirred solution of (2S)-3-(2-pyrrolidin-2-ylvinyl)pyridine (120 mg, 0.689 mmol) in ethanol (2 mL), galactaric acid (72.4 mg, 0.344 mmol) was added. The mixture was heated at 70° C., sonicated and then water (1–2 drops) was added; this process was repeated until most of the solid dissolved. The remaining insoluble material was removed by filtration. To the filtrate anhydrous diethyl ether was added dropwise until it became cloudy. After 16 h at 4° C. a precipitate was formed; this was filtered and vacuum dried to give 120 mg (61.9% yield) of product as a light brown solid.
Reaction SMILES: [CH2:1]([NH:3][C:4]1[C:5](=[CH:9][C:10]([CH3:13])=[CH:11][CH:12]=1)[C:6](O)=[O:7])[CH3:2].[C:14](OC(=O)C)(=O)[CH3:15].C(O)(=[O:23])C>>[CH2:14]([N:3]1[C:4]2[C:5](=[CH:9][C:10]([CH3:13])=[CH:11][CH:12]=2)[C:6]([OH:7])=[CH:2][C:1]1=[O:23])[CH3:15]
Reactant: CCNc1ccc(C)cc1C(=O)O
Reactant: CC(=O)OC(C)=O
Reactant: CC(=O)O
Product: CCn1c(=O)cc(O)c2cc(C)ccc21

Procedure:
N-Ethyl-5-methyl anthranilic acid (17.6g- 0.098 mole, m.p. 159°C) was refluxed in acetic acid (43 ml) and acetic anhydride (43 ml) for 12 hrs. The dark red solution was cooled and poured onto crushed ice. The mixture was made alkaline filtered off tarry material and neutrallised with hydrochloric acid. The yellow crystalline product was filtered off, washed well with water and recrystallised from ethanol, m.p. 275°-280° (Found- C, 70,87, H, 6.34, N, 7.17 C12H13NO2 requires; C, 70.88; H, 6.44; N, 6.89%).
Reaction SMILES: O[C:2]([CH3:30])([CH3:29])[CH2:3][N:4]1[CH:12](C)[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:14]3[N:15]=[N:16][N:17]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=4[F:27])[C:18]=3[CH3:19])[CH:10]=2)[C:5]1=[O:28].[CH3:31][S:32](Cl)(=[O:34])=[O:33].C([N:38](CC)CC)C>C(Cl)(Cl)Cl>[CH3:31][S:32]([NH:38][C:2]([CH3:30])([CH3:29])[CH2:3][N:4]1[CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:14]3[N:15]=[N:16][N:17]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=4[F:27])[C:18]=3[CH3:19])[CH:10]=2)[C:5]1=[O:28])(=[O:34])=[O:33]
Reactant: Cc1c(-c2ccc3c(c2)C(C)N(CC(C)(C)O)C3=O)nnn1-c1ccc(F)cc1F
Reactant: CCN(CC)CC
Reactant: CS(=O)(=O)Cl
Solvent: ClC(Cl)Cl
Product: Cc1c(-c2ccc3c(c2)CN(CC(C)(C)NS(C)(=O)=O)C3=O)nnn1-c1ccc(F)cc1F
Reaction time: 0.5 h

Procedure:
10 mg of the compound obtained in Example 217 was dissolved in 2 ml of chloroform, 20 μl of methanesulfonylchloride and 20 μl of triethylamine were added, and after 30 min at room temperature, the solvents were distilled outunder reduced pressure. The obtained residues were purified by silicagel thin-layer chromatography (ethyl acetate) to obtain 12.3 mg of the above compound as a white solid.
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH:12]=O)[CH:8]=2)[O:3]1.[CH3:15][CH:16]([CH3:32])[C:17]([NH:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[CH:21]=1)=[O:18]>>[CH3:1][C:2]1([CH3:14])[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH2:12][N:29]3[CH2:30][CH2:31][CH:26]([C:22]4[CH:21]=[C:20]([NH:19][C:17](=[O:18])[CH:16]([CH3:15])[CH3:32])[CH:25]=[CH:24][CH:23]=4)[CH2:27][CH2:28]3)[CH:8]=2)[O:3]1
Reactant: CC1(C)CCc2cc(C=O)ccc2O1
Reactant: CC(C)C(=O)Nc1cccc(C2CCNCC2)c1
Product: CC(C)C(=O)Nc1cccc(C2CCN(Cc3ccc4c(c3)CCC(C)(C)O4)CC2)c1

Procedure:
Prepared by Procedure F and Scheme R using 2,2-dimethyl-6-chromanecarbaldehyde and 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide: ESMS m/e: 421.2 (M+H)+.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[N:2]1.I[C:7]1[CH:12]=[CH:11][C:10](OC(F)(F)F)=[CH:9][CH:8]=1.C([O-])([O-])=O.[Cs+].[Cs+].O[C:25]1[CH:26]=[CH:27][CH:28]=[C:29]2[C:34]=1N=CC=C2>[Cu]I.CN(C=O)C.O>[C:7]1([N:1]2[CH:5]=[CH:4][N:3]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:34]=3)[NH:2]2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: FC(F)(F)Oc1ccc(I)cc1
Reactant: Oc1cccc2cccnc12
Reactant: c1c[nH]nn1
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: C1=CN(c2ccccc2)NN1c1ccccc1
Yield: 671.8 %

Procedure:
The triazole (70 mg, 0.41 mmol), 1-iodo-4-trifluoromethoxybenzene (142 mg, 0.493 mmol), Cs2CO3 (535 mg, 1.644 mmol), CuI (3 mg, 0.012 mmol), 8-hydroxyquinoline (2 mg, 0.012 mmol), and DMF/H2O (2 mL; 10:1 solution) were combined in a 10 mL CEM Microwave reaction vessel fitted with magnetic stir bar and subjected to microwave irradiation at 150° C. for 30 min. The contents were then filtered and concentrated to dryness affording the 1,3-diphenyl triazole intermediate (18 mg, 13%).
Reaction SMILES: [OH-:1].[Cu+2:2].[OH-].[CH:4]([OH:6])=[O:5]>>[OH2:5].[OH2:1].[OH2:5].[OH2:5].[CH:4]([O-:6])=[O:5].[Cu+2:2].[CH:4]([O-:6])=[O:5]
Reactant: O=CO
Reactant: [OH-]
Agent: [Cu+2]
Product: O
Product: O=C[O-]
Reaction time: 1 h

Procedure:
To 1.62 kg of copper hydroxide powder was added 4.8 kg of a 80% aqueous solution of formic acid, and this mixture was stirred for 1 hour. Upon filtration of the resulting mixture, copper formate tetrahydrate was obtained, which was then dehydrated at 100° C. under vacuum to obtain anhydrous copper formate.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH:17]=[O:18])=[C:9]2[C:4]=1[CH:5]=[CH:6][CH:7]=[CH:8]2.[CH3:19]C[O-].[Na+].CCO.ClC1C2C(=CC=CC=2)C(C=O)=C2C=1C=CC=C2>C(Cl)Cl.CCCCCC>[CH2:1]([O:2][C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[C:10]([CH:17]=[O:18])=[C:11]2[C:16]=1[CH:15]=[CH:14][CH:13]=[CH:12]2)[CH3:19]
Reactant: CC[O-]
Reactant: COc1c2ccccc2c(C=O)c2ccccc12
Agent: O=Cc1c2ccccc2c(Cl)c2ccccc12
Agent: [Na+]
Solvent: CCO
Solvent: CCCCCC
Solvent: ClCCl
Product: CCOc1c2ccccc2c(C=O)c2ccccc12

Procedure:
Using the procedure outlined in 13A, except that NaOEt (Aldrich)/EtOH was used instead of NaOCH3 /CH3OH, 10-chloro-9-anthraldehyde (Aldrich) gave 10-ethoxy-9-anthracenecarbaldehyde mp 88°-90°, (CH2Cl2 /hexane) (C, H).
Reaction SMILES: [CH3:1][C:2]1[NH:6][NH:5][C:4](=[O:7])[CH:3]=1.[C:8]12(O)[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:16][CH:10]([CH2:11]3)[CH2:9]1)[CH2:15]2>>[C:8]12([C:3]3[C:4](=[O:7])[NH:5][NH:6][C:2]=3[CH3:1])[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:16][CH:10]([CH2:11]3)[CH2:9]1)[CH2:15]2
Reactant: Cc1cc(=O)[nH][nH]1
Reactant: OC12CC3CC(CC(C3)C1)C2
Product: Cc1[nH][nH]c(=O)c1C12CC3CC(CC(C3)C1)C2
Temperature: 0 °C
Reaction time: 24 h
Yield: 107.7 %

Procedure:
A suspension of 5-methyl-1,2-dihydro-pyrazol-3-one (4.0 g) and adamantan-1-ol (5.6 g) in a round bottom flask was cooled to 0° C. with an ice/water bath. To the cooled suspension was added borontrifluoride ethyl etherate (9.2 mL) over 10 minutes. The reaction mixture was then allowed to warm up to ambient temperature and stirred for 24 hours. The suspension was then re-cooled to 0° C. and quenched with 50% KOH solution. The mixture was then acidified with 2 N aqueous HCl solution and diluted with EtOAc. The resultant white precipitate was then collected by filtration and the solid was washed with ether. The white solid was dried in a dessicator to give the desired 4-adamantan-1-yl-5-methyl-1,2-dihydro-pyrazol-3-one (9.2 g) as a white solid. MS (ESI+): 233.3 [M+H]+).
Reaction SMILES: Cl[CH2:2][CH2:3][C:4]([S:17][C:18]1[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=1)([C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[C:9]([O:15][CH3:16])[CH:8]=1)[C:5]#[N:6].Cl.[CH3:26][O:27][C:28]1[CH:29]=[C:30]2[C:35](=[CH:36][C:37]=1[O:38][CH3:39])[CH2:34][NH:33][CH2:32][CH2:31]2>>[CH3:16][O:15][C:9]1[CH:8]=[C:7]([C:4]([S:17][C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)([CH2:3][CH2:2][N:33]2[CH2:32][CH2:31][C:30]3[C:35](=[CH:36][C:37]([O:38][CH3:39])=[C:28]([O:27][CH3:26])[CH:29]=3)[CH2:34]2)[C:5]#[N:6])[CH:12]=[CH:11][C:10]=1[O:13][CH3:14]
Reactant: COc1cc2c(cc1OC)CNCC2
Reactant: COc1ccc(C(C#N)(CCCl)Sc2ccc(C)cc2)cc1OC
Agent: Cl
Product: COc1ccc(C(C#N)(CCN2CCc3cc(OC)c(OC)cc3C2)Sc2ccc(C)cc2)cc1OC
Yield: 12.1 %

Procedure:
The procedure of Example 3 is repeated using 3.3 g of α-(2-chloroethyl)-3,4-dimethoxy-α-[(4-methylphenyl)thio]benzeneacetonitrile and 1.14 g of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride. This affords 0.311 g of the desired product as a brown oil.
Reaction SMILES: C=C[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C[N+]1([O-])[CH2:15][CH2:14][O:13]CC1.O.CC(C)=[O:20].C(#N)C>>[C:3]1([CH:14]([OH:13])[CH2:15][OH:20])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: C=Cc1ccccc1
Reactant: C[N+]1([O-])CCOCC1
Reactant: CC(C)=O
Solvent: O
Solvent: CC#N
Product: OCC(O)c1ccccc1
Yield: 86.2 %

Procedure:
To 9 mL of a solvent consisting of water-acetone-acetonitrile (1:1:1) were added 1 g of styrene, 1.5 g of N-methylmorpholine-N-oxide and 1.24 g of the metal oxide carried on the cross-linked polymer compound which was obtained in Example 2, followed by allowing a reaction to take place at room temperature for 5 hours with stirring. After the reaction, the metal oxide carried on the cross-linked polymer compound was recovered by filtration from the reaction solution, and the reaction solution was extracted with ethyl acetate and the organic layer was washed with water, concentrated and purified by column chromatography to give 1.2 g of 1-phenyl-1,2-ethanediol (yield: 86.2%).
Reaction SMILES: [CH2:1]([N:8]1[N:17]=[C:16](Cl)[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]1=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:20][O:21][C:22]1[CH:23]=[C:24]([CH:26]=[C:27]([O:31][CH3:32])[C:28]=1[O:29][CH3:30])[NH2:25].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[K+]>C1(C)C=CC=CC=1>[CH2:1]([N:8]1[N:17]=[C:16]([NH:25][C:24]2[CH:26]=[C:27]([O:31][CH3:32])[C:28]([O:29][CH3:30])=[C:22]([O:21][CH3:20])[CH:23]=2)[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]1=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=c1c2ccccc2c(Cl)nn1Cc1ccccc1
Reactant: COc1cc(N)cc(OC)c1OC
Agent: CC(C)(C)[O-]
Agent: [K+]
Agent: c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1
Solvent: Cc1ccccc1
Product: COc1cc(Nc2nn(Cc3ccccc3)c(=O)c3ccccc23)cc(OC)c1OC
Temperature: 25 °C
Reaction time: 19 h
Yield: 28.6 %

Procedure:
A mixture of 2-benzyl-4-chloro-2H-phthalazin-1-one (1.35 g, 5 mmol), 3,4,5-trimethoxyaniline (1.10 g, 6 mmol), bis(dibenzylideneacetone)palladium(II) (0.46 g, 0.5 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphtyl (0.62 g, 1 mmol) and potassium tert-butoxide (0.84 g, 7.5 mmol) in anhydrous toluene (20 mL) was degassed and heated to reflux with stirring for 19 h. After that time, the mixture was cooled to rt and quenched with saturated aqueous NH4Cl (20 mL). Ethyl acetate (20 mL) and water (20 mL) were added and the organic phase was separated, washed with brine (20 mL), dried over MgSO4 and concentrated under reduced pressure. The product was purified by flash column chromatography (silica gel, 60:40 hexanes/ethyl acetate) followed by recrystallization from CHCl3/hexanes to give 2-benzyl-4-((3,4,5-trimethoxyphenyl)amino)phthalazin-1(2H)-one (0.598 g, 29%) as a white solid: mp 206-207° C.; 1H H NMR (400 MHz, CDCl3) δ 8.57-8.55 (m, 1H), 7.84-7.76 (m, 3H), 7.41 (d, J=6.8 Hz, 2H), 7.32-7.22 (m, 3H), 6.69 (s, 2H), 6.40 (s, 1H), 5.38 (s, 2H), 3.81 (s, 3H), 3.70 (s, 6H); ESI MS m/z 418 [M+1]+.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:18][C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=[CH:21][CH:20]=2)[C:8]2[C:13]([C:14]=1[CH:15]=O)=[CH:12][C:11]([F:17])=[CH:10][CH:9]=2)=[O:5])[CH3:2].N1C=CC=CC=1.Cl.[NH2:36][OH:37]>CCO>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:18][C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=[CH:21][CH:20]=2)[C:8]2[C:13]([C:14]=1[CH:15]=[N:36][OH:37])=[CH:12][C:11]([F:17])=[CH:10][CH:9]=2)=[O:5])[CH3:2]
Reactant: NO
Reactant: CCOC(=O)c1c(C=O)c2cc(F)ccc2n1Cc1cccc2ccccc12
Agent: Cl
Solvent: CCO
Solvent: c1ccncc1
Product: CCOC(=O)c1c(C=NO)c2cc(F)ccc2n1Cc1cccc2ccccc12

Procedure:
To a suspension of 5-fluoro-3-formyl-1-naphthalen-1-ylmethyl-1H-indole-2-carboxylic acid ethyl ester (1.16 g) in EtOH (35 ml) was added at 22° C. pyridine (8.0 ml) and hydroxylamine hydrochloride (0.54 g) and the mixture was heated to reflux temperature for 2 h. The mixture was evaporated and the residue partitioned between 1 N HCl and t-butylmethyl ether. The organic layer was dried and evaporated to give 5-fluoro-3-(hydroxyimino-methyl)-1-naphthalen-1-ylmethyl-1H-indole-2-carboxylic acid ethyl ester as a colorless foam. MS: 391.1 ([M+H]+).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([Cl:9])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19].O>CN(C=O)C>[CH2:21]([O:20][C:18](=[O:19])[CH2:17][O:8][C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=1[Cl:9])[CH3:22]
Reactant: Oc1ccc(Br)cc1Cl
Reactant: CCOC(=O)CCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)COc1ccc(Br)cc1Cl
Temperature: 60 °C
Reaction time: 8 h
Yield: 100 %

Procedure:
A mixture of 4-bromo-2-chloro-phenol (2.0 g, 9.64 mmol) and anhydrous potassium carbonate (4.0 g, 28.92 mmol) in dry DMF (30 ml) was heated at 60° C. for 1 h under Ar atmosphere. The mixture was then cooled to room temperature and ethyl chloroacetate (1.24 ml, 11.57 mmol) was added through septum using syringe. The mixture was stirred overnight at room temperature and poured into water with stirring. Stirring continued for 10 min, and then partitioned between ethyl acetate and water. The organic phase washed with brine, dried (anhydrous MgSO4), and concentrated. The residue was purified by silica gel column chromatography (n-Hexane:Ethyl acetate:MeOH=15:3:1) to give (4-Bromo-2-chloro-phenoxy)-acetic acid ethyl ester as a colorless oil (2.98 (2.83) g, >100% yield). To (4-bromo-2-chloro-phenoxy)-acetic acid (132.8 mg, 0.5 mmol), 3-amino-benzamide (102.2 mg, 0.75 mmol), N-(3-dimethylaminopropyl)-N′-ethyl carbodiimide HCl (EDC) (143.8 mg, 0.75 mmol) and 1-hydroxybenzotriazole (HOBt) (101.4 mg, 0.75 mmol) in DMF (5 ml) was added N,N-diisopropylethylamine, redistilled (DIPEA) (0.13 ml, 0.75 mmol). The mixture was stirred overnight, and then partitioned between ethyl acetate and water. The organic phase was washed with brine, dried (MgSO4 anh), and concentrated. The residue was purified by silica gel flash column chromatography (CH2CH2:MeOH=10:1) to give 3-[2-(4-bromo-2-chloro-phenoxy)acetyl-amino]-benzamide as a white solid (181.4 mg, 94.6% yield).
Reaction SMILES: [CH3:1][N:2]1[C:6]([C:7]([NH:9][C:10]2[CH:11]=[C:12]([C:16]#[C:17][C:18]3[CH:19]=[C:20]([C:24]([N:26]=[S:27]([C:30]4[CH:35]=[CH:34][C:33]([CH2:36][CH2:37][C:38]([O:40]C)=[O:39])=[CH:32][CH:31]=4)([CH3:29])=[O:28])=[O:25])[CH:21]=[N:22][CH:23]=3)[CH:13]=[CH:14][CH:15]=2)=[O:8])=[CH:5][C:4]([CH3:42])=[N:3]1.[OH-].[Na+].C(O)(=O)C>C1COCC1>[CH3:1][N:2]1[C:6]([C:7]([NH:9][C:10]2[CH:11]=[C:12]([C:16]#[C:17][C:18]3[CH:19]=[C:20]([C:24]([N:26]=[S:27]([C:30]4[CH:35]=[CH:34][C:33]([CH2:36][CH2:37][C:38]([OH:40])=[O:39])=[CH:32][CH:31]=4)([CH3:29])=[O:28])=[O:25])[CH:21]=[N:22][CH:23]=3)[CH:13]=[CH:14][CH:15]=2)=[O:8])=[CH:5][C:4]([CH3:42])=[N:3]1
Reactant: COC(=O)CCc1ccc(S(C)(=O)=NC(=O)c2cncc(C#Cc3cccc(NC(=O)c4cc(C)nn4C)c3)c2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: Cc1cc(C(=O)Nc2cccc(C#Cc3cncc(C(=O)N=S(C)(=O)c4ccc(CCC(=O)O)cc4)c3)c2)n(C)n1
Yield: 70.8 %

Procedure:
A solution of Methyl 3-{4-[N-({5-[(3-{[(1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]amino}-phenyl)ethynyl]pyridin-3-yl}carbonyl)-S-methylsulfonimidoyl]phenyl}propanoate (0.075 g, 0.129 mmol) in THF (3 mL) was cooled to 0° C. and slowly treated with 0.5M NaOH (1.29 mL, 0.643 mmol). The reaction mixture was allowed to slowly come to room temperature. Once the reaction was done by TLC, the reaction was acidified with acetic acid and then extracted with EtOAc (20 mL) and H2O (20 mL). The organic layer was dried over anhydrous Na2SO4(s), filtered, and concentrated to give the title compound (0.052 g, 71%)