Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([O:10][CH3:11])=[O:9])=[CH:4][N:3]=1.[C:12]([O:16][C:17]([N:19]1[CH2:25][CH2:24][CH2:23][C@H:20]1[CH2:21]O)=[O:18])([CH3:15])([CH3:14])[CH3:13].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[C:12]([O:16][C:17]([N:19]1[CH2:25][CH2:24][CH2:23][CH:20]1[CH2:21][O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([O:10][CH3:11])=[O:9])=[CH:4][N:3]=1)=[O:18])([CH3:15])([CH3:13])[CH3:14]
Reactant: COC(=O)c1ccc(O)nc1
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1CO
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COC(=O)c1ccc(OCC2CCCN2C(=O)OC(C)(C)C)nc1
Temperature: 70 °C
Reaction time: 6 h
Yield: 44.3 %

Procedure:
To a stirred solution of methyl 2-hydroxypyridine-5-carboxylate (269.8 mg, 1.762 mmol), N-tert-butoxycarbonylprolinol (354.6 mg, 1.762 mmol), and Ph3P (554.6 mg, 2.114 mmol) in THF (10 mL) was slowly added DIAD (0.42 mL, 2.114 mmol) at room temp, and the resulting mixture was stirred for 6 hr at 70° C. The reaction mixture was concentrated and the residue was chromatographed on silica-gel with n-hexane:EtOAc (5:1, v/v) as eluent to give 262.5 mg (44%) methyl 2-[[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy]pyridine-5-carboxylate as an oil. 1H-NMR (400 MHz, CDCl3) δ1.47 (s, 9H), 1.85-1.98 (m, 4H), 3.37 (br s, 2H), 3.92 (s, 3H), 4.12-4.33 (br m, 2H), 4.4 (brs, 1H), 6.75 (m, 1H), 8.15 (m, 1H), 8.79 (m, 1H); MS (FAB) m/z 337 (M++1).
Reaction SMILES: Cl[S:2]([C:5]1[CH:6]=[C:7]([I:15])[C:8]([CH3:14])=[C:9]([CH:13]=1)[C:10]([OH:12])=[O:11])(=[O:4])=[O:3].[NH:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1.N1C=CC=CC=1>O1CCOCC1>[I:15][C:7]1[C:8]([CH3:14])=[C:9]([CH:13]=[C:5]([S:2]([N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)(=[O:4])=[O:3])[CH:6]=1)[C:10]([OH:12])=[O:11]
Reactant: C1CCNC1
Reactant: Cc1c(I)cc(S(=O)(=O)Cl)cc1C(=O)O
Solvent: c1ccncc1
Solvent: C1COCCO1
Product: Cc1c(I)cc(S(=O)(=O)N2CCCC2)cc1C(=O)O
Reaction time: 0.5 h

Procedure:
A round bottom flask was charged with 5-(chlorosulfonyl)-3-iodo-2-methylbenzoic acid (1.00 g, 2.77 mmol), pyrrolidine (0.278 mL, 3.33 mmol), 1,4-dioxane (4 mL) and pyridine (0.20 mL, 2.5 mmol). The mixture was stirred for 30 minutes. The solvent was removed and the residue was purified by flash chromatography to yield the compound as a yellow solid.
Reaction SMILES: [C:1]([C:4]1[C:12]2[S:11][CH2:10][CH:9]([C:13]3[CH:18]=[CH:17][C:16]([CH:19]([CH3:21])[CH3:20])=[CH:15][CH:14]=3)[C:8]=2[C:7]([CH3:22])=[C:6]([NH:23][C:24](=[O:30])[CH2:25][C:26]([CH3:29])([CH3:28])[CH3:27])[C:5]=1[CH3:31])(=[O:3])[CH3:2].C(=O)([O-])[OH:33].[Na+].ClC1C=CC=C(C(OO)=O)C=1.S([O-])(O)(=O)=O.[Na+]>ClCCl>[C:1]([C:4]1[C:12]2[S:11](=[O:33])[CH2:10][CH:9]([C:13]3[CH:18]=[CH:17][C:16]([CH:19]([CH3:20])[CH3:21])=[CH:15][CH:14]=3)[C:8]=2[C:7]([CH3:22])=[C:6]([NH:23][C:24](=[O:30])[CH2:25][C:26]([CH3:29])([CH3:28])[CH3:27])[C:5]=1[CH3:31])(=[O:3])[CH3:2]
Reactant: O=C([O-])O
Reactant: CC(=O)c1c(C)c(NC(=O)CC(C)(C)C)c(C)c2c1SCC2c1ccc(C(C)C)cc1
Agent: O=C(OO)c1cccc(Cl)c1
Agent: O=S(=O)([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CC(=O)c1c(C)c(NC(=O)CC(C)(C)C)c(C)c2c1S(=O)CC2c1ccc(C(C)C)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 12.4 %

Procedure:
To a mixture of N-(7-acetyl-3-(4-isopropylphenyl)-4,6-dimethyl-2,3-dihydro-1-benzothien-5-yl)-3,3-dimethylbutanamide (960 mg, 2.19 mmol) obtained in Example 166 and sodium hydrogen carbonate (276 mg, 3.29 mmol) in dichloromethane (20 mL) was added m-chloroperbenzoic acid (530 mg, 3.07 mmol) at 0° C. and the resulting mixture was stirred at room temperature for two hours. To reaction solution was added an aqueous sodium hydrogensulfate solution, the organic layer separated, and the aqueous layer was extracted with dichloromethane. The combined organic layers were washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate) to obtain 123 mg (yield: 12%) of the title compound as a low polarity isomer. Melting point: 214-216° C. (hexane-ethyl acetate).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:19]([O:20][CH3:21])=[CH:18][C:6]2[CH:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH2:8][NH:9][CH2:10][CH2:11][C:5]=2[CH:4]=1.[CH2:22](Br)[CH2:23][CH2:24][CH3:25].[OH-].[K+]>CO>[CH2:22]([N:9]1[CH2:8][CH:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:6]2[CH:18]=[C:19]([O:20][CH3:21])[C:3]([O:2][CH3:1])=[CH:4][C:5]=2[CH2:11][CH2:10]1)[CH2:23][CH2:24][CH3:25]
Reactant: CCCCBr
Reactant: COc1cc2c(cc1OC)C(c1ccccc1)CNCC2
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: CCCCN1CCc2cc(OC)c(OC)cc2C(c2ccccc2)C1

Procedure:
A mixture of 4.32 g. (0.0154 mole) of 7,8-dimethoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine, 0.02 mole of n-butyl bromide and 0.02 mole of potassium hydroxide is dissolved in 120 ml. of dry methanol and refluxed for 48 hours. The reaction mixture is evaporated to dryness, taken up in ethyl acetate and filtered to remove inorganic salts. The filtrate is washed with water, dried and evaporated to give 3-n-butyl-7,8-dimethoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine as an oil.
Reaction SMILES: C([Li])CCC.[CH3:6][N:7]1[C:11]([CH3:12])=[N:10][N:9]=[N:8]1.[Br:13][C:14]1[CH:25]=[CH:24][C:17]2[C:18](=O)[O:19]C(=O)[NH:21][C:16]=2[CH:15]=1>CCCCCC.O1CCCC1>[NH2:21][C:16]1[CH:15]=[C:14]([Br:13])[CH:25]=[CH:24][C:17]=1[C:18](=[O:19])[CH2:12][C:11]1[N:7]([CH3:6])[N:8]=[N:9][N:10]=1
Reactant: O=c1[nH]c2cc(Br)ccc2c(=O)o1
Reactant: Cc1nnnn1C
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: Cn1nnnc1CC(=O)c1ccc(Br)cc1N
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
A solution of butyl lithium in hexane (2.7M, 104 ml) was added slowly to a stirred solution of 1,5-dimethyltetrazole (27.5 g) in dry tetrahydrofuran (500 ml) at -5° to 0° under nitrogen. After stirring for 1.5 hours, 7-bromo-1H-3,1-benzoxazine-2,4-dione (22.6 g) was added and stirring continued for 18 hours at room temperature and for 3.5 hours at 40° to 50°. The mixture was cooled to room temperature, industrial methylated spirit (15 ml) added and most of the solvents distilled off. The residue was added to water (200 ml) and acidified with 5N hydrochloric acid to pH 1. The resulting solid was collected by filtration and crystallised from ethyl acetate to give the novel compound 1-(2-amino-4-bromophenyl)-2-(1-methyl-1H-tetrazol-5-yl)ethanone, m.p. 159°-160°.
Reaction SMILES: [F:1][C:2]([C:5]1[O:9][C:8]([CH2:10][N:11]2[N:15]=[C:14]([NH2:16])[CH:13]=[N:12]2)=[CH:7][CH:6]=1)([F:4])[CH3:3].[Cl:17][C:18]1[CH:19]=[C:20]([C:24]2[O:28][CH:27]=[N:26][C:25]=2[C:29](O)=[O:30])[CH:21]=[CH:22][CH:23]=1>>[F:4][C:2]([C:5]1[O:9][C:8]([CH2:10][N:11]2[N:15]=[C:14]([NH:16][C:29]([C:25]3[N:26]=[CH:27][O:28][C:24]=3[C:20]3[CH:21]=[CH:22][CH:23]=[C:18]([Cl:17])[CH:19]=3)=[O:30])[CH:13]=[N:12]2)=[CH:7][CH:6]=1)([F:1])[CH3:3]
Reactant: O=C(O)c1ncoc1-c1cccc(Cl)c1
Reactant: CC(F)(F)c1ccc(Cn2ncc(N)n2)o1
Product: CC(F)(F)c1ccc(Cn2ncc(NC(=O)c3ncoc3-c3cccc(Cl)c3)n2)o1

Procedure:
Following general procedure Z2, starting from 2-[5-(1,1-difluoro-ethyl)-furan-2-ylmethyl]-2H-[1,2,3]triazol-4-ylamine and 5-(3-chloro-phenyl)-oxazole-4-carboxylic acid.
Reaction SMILES: Br[CH2:2][CH:3]1[O:19][C:6]2=[C:7]3[C:12](=[C:13]([CH3:15])[CH:14]=[C:5]2[CH:4]1[CH3:20])[NH:11][C:10](=[O:16])[C:9]([CH3:18])([CH3:17])[CH2:8]3.[N-:21]=[N+:22]=[N-:23].[Na+]>CN(C)C=O.O>[N:21]([CH2:2][CH:3]1[O:19][C:6]2=[C:7]3[C:12](=[C:13]([CH3:15])[CH:14]=[C:5]2[CH:4]1[CH3:20])[NH:11][C:10](=[O:16])[C:9]([CH3:18])([CH3:17])[CH2:8]3)=[N+:22]=[N-:23]
Reactant: [N-]=[N+]=[N-]
Reactant: Cc1cc2c(c3c1NC(=O)C(C)(C)C3)OC(CBr)C2C
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1cc2c(c3c1NC(=O)C(C)(C)C3)OC(CN=[N+]=[N-])C2C
Yield: 75.4 %

Procedure:
A solution of 2-bromomethyl-3,5,8,8-tetramethyl-2,3,6,7,8,9-hexahydrofuro[2,3-f]quinoline-7-one (1.8 g, 5.3 mmol) and 90% sodium azide (3.1 g, 42 mmol) in dimethylformamide (30 ml) was stirred at 150° C. for 2 hours. The reaction mixture was poured in water, followed by extracting with ethyl acetate. The extract was washed with water, and dried. The solvent was evaporated, and the residue was recrystallized from ethyl acetate-hexane. 1.2 g of the title compound was obtained as colorless needles (75.5%).
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]([CH3:13])[CH3:12])=[C:4]([NH:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=2)[N:3]=1.[CH3:24][C:25]1[NH:26][CH:27]=[CH:28][N:29]=1>CN1C(=O)CCC1>[CH:11]([N:8]1[CH:7]=[N:6][C:5]2[C:9]1=[N:10][C:2]([N:26]1[CH:27]=[CH:28][N:29]=[C:25]1[CH3:24])=[N:3][C:4]=2[NH:14][CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=1)([CH3:13])[CH3:12]
Reactant: Cc1ncc[nH]1
Reactant: CC(C)n1cnc2c(NCCc3ccc(O)cc3)nc(Cl)nc21
Solvent: CN1CCCC1=O
Product: Cc1nccn1-c1nc(NCCc2ccc(O)cc2)c2ncn(C(C)C)c2n1
Temperature: 240 °C

Procedure:
A microwave reaction tube was charged with 4-(2-(2-chloro-9-isopropyl-9H-purin-6-ylamino)ethyl)phenol (30 mg, 0.091 mmol), 2-methyl-1H-imidazole (59 mg, 0.73 mmol) and 0.5 ml of NMP. The sealed tube was heated under microwave irradiation at 240° C. for 2 hr. The reaction mixture was purified by reverse-phase HPLC(C18 column, eluting with ACN—H2O 0.05% TFA) to afford the title compound as an off-white solid.
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@H:12]([CH2:30][O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33])[CH2:13][CH2:14][C:15]([N:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1)=[O:16])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.I[CH3:40].[H-].[Na+]>CN(C=O)C>[CH2:1]([O:8][C:9]([N:11]([CH3:40])[C@H:12]([CH2:30][O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33])[CH2:13][CH2:14][C:15]([N:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1)=[O:16])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CI
Reactant: CC(C)(C)OC(=O)N1CCN(C(=O)CC[C@@H](CO[Si](C)(C)C(C)(C)C)NC(=O)OCc2ccccc2)CC1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN(C(=O)OCc1ccccc1)[C@@H](CCC(=O)N1CCN(C(=O)OC(C)(C)C)CC1)CO[Si](C)(C)C(C)(C)C
Temperature: 2.5 °C
Reaction time: 0.5 h
Yield: 102.6 %

Procedure:
To a solution of (S)-tert-butyl 4-(4-(benzyloxycarbonylamino)-5-(tert-butyldimethylsilyloxy)pentanoyl)piperazine-1-carboxylate (32.3 g, 58.8 mmol) and iodomethane (7.3 mL, 117.6 mmol) in DMF (450 mL) was added solid sodium hydride (60%, 3.5 g, 88.2 mmol) at 0-5° C. The mixture was stirred at 0-5° C. for 30 min and quenched with saturated NH4Cl solution. The mixture was concentrated to remove most of DMF under high vacuum. The residue was dissolved in EtOAc (700 mL). The organic mixture was washed with water and brine, dried over Na2SO4, filtered, and concentrated to give (S)-tert-butyl 4-(4-((benzyloxycarbonyl)(methyl)amino)-5-(tert-butyldimethylsilyloxy)pentanoyl)piperazine-1-carboxylate (34 g, crude), which was used without further purification. LRMS (M+H) m/z 564.3.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N+:12]([O-])([O-:14])=[O:13].[K+]>OS(O)(=O)=O>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2
Reactant: Brc1cccc2cnccc12
Reactant: O=[N+]([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Product: O=[N+]([O-])c1ccc(Br)c2ccncc12
Temperature: 20 °C

Procedure:
Into a 500 mL 3-necked round bottom flask was placed a solution of 5-bromoisoquinoline (22.24 g, 106.87 mmol) in H2SO4 (120 mL). This was followed by the addition of a solution of KNO3 (15.1 g, 149.36 mmol) in H2SO4 (100 mL), which was added dropwise with stirring, while cooling to a temperature of 20° C. over a time period of 1 hour. The resulting solution was allowed to react, with stirring, for 1 hour while the temperature was maintained at room temperature. The reaction progress was monitored by TLC (ethyl acetate/petroleum ether=1:5). The reaction mixture was then quenched by the adding 600 mL of H2O/ice. Adjustment of the pH to 8-10 was accomplished by the addition of NH3. H2O (30%). A filtration was performed. The filter cake was washed 2 times with 500 mL of H2O. The solid was dried in an oven under reduced pressure. This resulted in 25.59 g (90%) of 5-bromo-8-nitroisoquinoline as a yellow solid.
Reaction SMILES: C1C(=O)N([Br:8])C(=O)C1.C([O:13][C:14]([C:16]1[CH:17]=[CH:18][CH:19]=[C:20]2[C:25]=1[N:24]=[C:23]([NH:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[N:22]=[CH:21]2)=[CH2:15])CCC.O>C1COCC1>[Br:8][CH2:13][C:14]([C:16]1[CH:17]=[CH:18][CH:19]=[C:20]2[C:25]=1[N:24]=[C:23]([NH:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[N:22]=[CH:21]2)=[O:15]
Reactant: O=C1CCC(=O)N1Br
Reactant: C=C(OCCCC)c1cccc2cnc(Nc3ccccc3)nc12
Solvent: C1CCOC1
Solvent: O
Product: O=C(CBr)c1cccc2cnc(Nc3ccccc3)nc12
Temperature: 0 °C
Reaction time: 0.03 h
Yield: 125.1 %

Procedure:
NBS (58.2 mg, 0.327 mmol) was added to a solution 8-(1-butoxyvinyl)-N-phenylquinazolin-2-amine (104.5 mg, 0.327 mmol) in THF (2.4 mL) and water (0.094 mL, 5.23 mmol) at 0° C. and the resulting mixture was stirred at 0° C. for 2 min. The mixture was partitioned between Et2O (50 mL) and water (30 mL). The organic layer was separated, sequentially washed with saturated aq. NaHCO3 (20 mL), water (20 mL), and brine (20 mL), dried over Na2SO4, filtered, and concentrated in vacuo to provide crude 2-bromo-1-(2-(phenylamino)quinazolin-8-yl)ethanone (140 mg) as a yellow-orange oil. NH4OAc (101 mg, 1.309 mmol) and piperidine-2,4-dione (44.4 mg, 0.393 mmol) were added to the resulting oil, and the mixture was taken up in EtOH (2.4 mL) and stirred under argon in a sealed flask at 50° C. for 15.5 h. The reaction was cooled to 25° C. and concentrated in vacuo. The residue was partitioned between DCM (50 mL) and saturated aq. NaHCO3 (30 mL). The aq. layer was extracted with DCM (3×30 mL), and the combined extracts were dried over Na2SO4, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-10% MeOH/DCM) furnished 2-(2-(phenylamino)quinazolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (21.3 mg, 0.060 mmol, 18% yield) as a yellow-orange solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.99 (1H, br. s.), 9.97 (1H, s), 9.35 (1H, s), 8.14 (1H, d, J=7.6 Hz), 7.78 (3H, t, J=7.4 Hz), 7.34-7.45 (4H, m), 7.10 (1H, t, J=7.0 Hz), 7.03-7.07 (1H, m), 3.43 (2H, t, J=6.9 Hz), 2.79 (2H, t, J=6.6 Hz). m/z (ESI, +ve) 356.3 (M+H)+.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:11])[C:6](=[O:12])[CH2:5]2.[CH3:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[N:18][CH:19]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.ClCCl.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>[CH3:11][N:7]1[C:8]2[C:4](=[CH:3][C:2]([C:16]3[CH:17]=[N:18][CH:19]=[C:14]([CH3:13])[CH:15]=3)=[CH:10][CH:9]=2)[CH2:5][C:6]1=[O:12]
Reactant: CN1C(=O)Cc2cc(Br)ccc21
Reactant: Cc1cncc(B(O)O)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: ClCCl
Product: Cc1cncc(-c2ccc3c(c2)CC(=O)N3C)c1
Temperature: 100 °C

Procedure:
To 5-bromo-1-methyl-1,3-dihydro-indol-2-one (CAS#20870-90-0, 80 mg, 0.35 mmol) was added 5-methyl-3-pyridinyl boronic acid (CAS#173999-18-3, 55 mg, 0.39 mmol), in 1,2-dimethoxyethane (2.7 mL) and 2 M aqueous sodium carbonate (0.45 mL, 0.9 mmol). The reaction mixture was degassed and placed under an argon atmosphere, at which time resin bound tetrakis(triphenylphosphine)palladium(0), specifically polystyrene triphenylphosphine palladium (0) [PS—PPh3-Pd(0) (Biotage), 0.09 mmol/g loading, (195 mg, 0.018 mmol)] was added. The reaction vessel was sealed and was heated by microwave irradiation at 100° C. for 1.5 hours. The reaction mixture was cooled to room temperature, diluted with dichloromethane and filtered through glass wool. The filtrate was further diluted with saturated aqueous sodium bicarbonate and the layers were separated. The aqueous layer was extracted two times with dichloromethane, and the organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by silica gel flash chromatography (ethanol-dichloromethane, 0 to 6%) to afford 1-methyl-5-(5-methyl-pyridin-3-yl)-1,3-dihydro-indol-2-one; HRMS: (ESI) m/z 239.1181 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 2.42 (s, 3H), 3.27 (s, 3H), 3.61 (s, 2H), 6.93 (d, J=8.1 Hz, 1H), 7.45-7.58 (m, 2H), 7.67 (s, 1H), 8.42 (s, 1H), 8.63 (s, 1H).
Reaction SMILES: [CH3:1][C:2]1[C:6](/[CH:7]=[CH:8]/[C:9]([O:11][CH3:12])=[O:10])=[C:5]([CH3:13])[NH:4][N:3]=1.[H-].[Na+].[CH2:16](Br)[CH:17]=[CH:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C=O)C>[CH2:16]([N:4]1[C:5]([CH3:13])=[C:6](/[CH:7]=[CH:8]/[C:9]([O:11][CH3:12])=[O:10])[C:2]([CH3:1])=[N:3]1)[CH:17]=[CH:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: COC(=O)/C=C/c1c(C)n[nH]c1C
Reactant: BrCC=Cc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)/C=C/c1c(C)nn(CC=Cc2ccccc2)c1C
Temperature: 0 °C
Reaction time: 1 h
Yield: 67.7 %

Procedure:
(E)-methyl 3-(3,5-dimethyl-1H-pyrazol-4-yl)acrylate (360 mg, 2 mmol) was dissolved in DMF (6 mL). Sodium hydride, (NaH 60% dispersion, 80 mg, 1 equiv) was added in small portions while maintaining the temperature at 0° C. The mixture was then stirred at room temperature for 1 h. The mixture was cooled to 0° C. and cinnamyl bromide (394 mg, 1 equiv) was added. The mixture was then stirred overnight at room temperature. It was quenched with aqueous ammonium chloride, diluted with water, and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography using a gradient of hexane/EtOAc (10:1 to 0:100 v/v). Fractions containing pure product were combined and the solvents were removed under reduced pressure to yield (E)-methyl 3-(1-cinnamyl-3,5-dimethyl-1H-pyrazol-4-yl)acrylate (401 mg, 68%).
Reaction SMILES: [CH2:1]([P:3]([CH2:6][CH2:7][O:8]CCCC)(=[O:5])[OH:4])[CH3:2].[OH-:13].[Na+].C.OO>O.[Pd]>[CH2:1]([P:3]([OH:4])([CH2:6][C:7]([OH:8])=[O:13])=[O:5])[CH3:2]
Reactant: [OH-]
Reactant: CCCCOCCP(=O)(O)CC
Agent: [Pd]
Agent: OO
Agent: [Na+]
Solvent: O
Product: CCP(=O)(O)CC(=O)O
Temperature: 70 °C
Yield: 79 %

Procedure:
19.4 g (0.1 mol) of ethyl-2-butoxyethylphosphinic acid (produced as in Example 6) are dissolved in 150 ml of water and adjusted to pH 9 with 2N NaOH solution. Then, 0.25 g of charcoal with 5% Pd and 1% Bi is added, the suspension is heated to 70° C. and 30% strength hydrogen peroxide solution is passed into the suspension at a flow rate of 1 mol equivalent per hour. All the while, the pH of the suspension is maintained at pH=9 by adding 2N NaOH solution. After the reaction is ended, the reaction solution is filtered to remove the catalyst, which is washed, and made acidic with hydrochloric acid and the water is distilled off in vacuo. The residue is taken up in tetrahydrofuran and extracted. The insoluble salts are filtered off to leave 12.0 g (79% of theory) of 2-(ethylhydroxyphosphinyl)acetic acid as a colorless solid material
Reaction SMILES: Cl[C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][N:3]=1.B(O)(O)[C:10]1[CH:11]=[CH:12][C:13]([CH3:16])=[CH:14][CH:15]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:8][C:7]1[C:2]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)=[N:3][CH:4]=[CH:5][CH:6]=1
Reactant: Clc1cccnc1Cl
Reactant: Cc1ccc(B(O)O)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: Cc1ccc(-c2ncccc2Cl)cc1
Yield: 84 %

Procedure:
{circle around (1)} 100 g (0.676 mol) of 2,3-dichloropyridine, 91.87 g (0.676 mol) of p-tolylboronic acid, and 86 g (0.811 mol) of sodium carbonate were dissolved in 500 mL of 1,2-dimethoxyethane and 500 mL of distilled water, after which 78 g (0.0676 mol) of Pd(PPh3)4 was added. The mixture was heated to reflux for 18 hours so that it was allowed to react. After completion of the reaction, the reaction solution was concentrated under reduced pressure to remove 1,2-dimethoxyethane, and then extracted with ethyl acetate. The extract was treated with magnesium sulfate, filtered, and concentrated under reduced pressure, yielding 3-chloro-2-para-tolylpyridine as represented below in a 84% yield.
Reaction SMILES: CC(C)([O-])C.[K+].[CH3:7][N:8]1[CH:13]([CH2:14][CH3:15])[CH2:12][O:11][CH2:10][C:9]1=[O:16].[N:17](OCC(C)C)=[O:18]>O1CCCC1>[N:17](=[C:10]1[C:9](=[O:16])[N:8]([CH3:7])[CH:13]([CH2:14][CH3:15])[CH2:12][O:11]1)[OH:18]
Reactant: CC(C)CON=O
Reactant: CCC1COCC(=O)N1C
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CCC1COC(=NO)C(=O)N1C
Yield: 92.9 %

Procedure:
A quantity of 33.7 g of potassium t-butoxide, 40.0 g of 4-methyl-5-ethyl-tetrahydro-1,4-oxazin-3-one, and 29.3 g of isobutyl nitrite were caused to react sequentially in 800 ml of anhydrous tetrahydrofuran in a manner similar to that described in Example III. Following a similar workup, 44.7 g of a thick oil were obtained which could not be induced to crystallize. Part (10 grams) was chromatographed on silica gel eluting the product band (3.0 grams) with acetone after unchanged starting material (5.4 grams) had been eluted with isopropyl ether/acetone mixtures. Trituration of the product fraction with ethyl acetate afforded pure oxime product, 2.9 g, mp. 168.5°-170.0°, equivalent to a total yield (in 44.7 g of crude product) of 13.0 grams.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.Cl[CH2:9][C:10]([N:12]1[CH2:17][CH2:16][N:15]([S:18]([C:21]2[CH:30]=[CH:29][C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=2)(=[O:20])=[O:19])[CH2:14][CH2:13]1)=[O:11].C(=O)([O-])[O-].[K+].[K+].O>C(#N)C>[CH:22]1[C:23]2[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:29]=[CH:30][C:21]=1[S:18]([N:15]1[CH2:14][CH2:13][N:12]([C:10](=[O:11])[CH2:9][O:1][C:2]2[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=2)[CH2:17][CH2:16]1)(=[O:20])=[O:19]
Reactant: O=C(CCl)N1CCN(S(=O)(=O)c2ccc3ccccc3c2)CC1
Reactant: Oc1cccnc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Product: O=C(COc1cccnc1)N1CCN(S(=O)(=O)c2ccc3ccccc3c2)CC1
Yield: 11.4 %

Procedure:
3-hydroxy pyridine (97 mg, 1.02 mmol), 2-chloro-1-(4-(naphthalen-2-ylsulfonyl)piperazin-1-yl)ethanone (compound 5, 0.3 g, 0.85 mmol) and anhydrous potassium carbonate (0.352 g, 2.55 mmol) were stirred for over night in dry acetonitrile (20 mL). The mixture was poured into a large volume of water and the solution extracted with ether. Un-reacted phenol was removed with cold 1N NaOH solution. The ether extract was dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The crude material was purified by re-crystallization to yield the title compound (40 mg, 11.46% yield) as an off-white solid. 60% of the un-reacted starting material was also recovered from the reaction.