Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[O:35][C:36]([C:39]3[CH:44]=[CH:43][C:42]([CH2:45][CH:46]([CH3:48])[CH3:47])=[CH:41][CH:40]=3)=[N:37][N:38]=2)=[CH:30][CH:29]=1)(C(C)(C)C)(C)C.C1COCC1>C(OCC)(=O)C>[CH2:45]([C:42]1[CH:41]=[CH:40][C:39]([C:36]2[O:35][C:34]([C:31]3[CH:30]=[CH:29][C:28]([CH2:27][OH:26])=[CH:33][CH:32]=3)=[N:38][N:37]=2)=[CH:44][CH:43]=1)[CH:46]([CH3:48])[CH3:47]
Reactant: CC(C)Cc1ccc(-c2nnc(-c3ccc(CO[Si](C)(C)C(C)(C)C)cc3)o2)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C)Cc1ccc(-c2nnc(-c3ccc(CO)cc3)o2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 88.5 %

Procedure:
Tetrabutylammonium fluoride (1.0 M in THF, 2.0 mL) was added to a solution of 2-[4-({[tert-butyl(dimethyl)silyl]oxy}methyl)phenyl]-5-(4-isobutylphenyl)-1,3,4-oxadiazole (0.50 g, 1.18 mmol) and THF (10 mL) and stirred at room temperature for 16 hours. The reaction mixture was diluted with ethyl acetate (100 mL), washed with water and brine, dried (Na2SO4,), filtered and concentrated in vacuo to give the title compound (0.322 g, 88% yield) as a white solid.
Reaction SMILES: C([O:8][C:9]1[CH:14]=[C:13]([O:15]CC2C=CC=CC=2)[CH:12]=[CH:11][C:10]=1/[CH:23]=[CH:24]/[C:25]([O:27][CH2:28][CH3:29])=[O:26])C1C=CC=CC=1.C(OCC)(=O)C>[OH-].[Pd+2].[OH-].CO>[OH:8][C:9]1[CH:14]=[C:13]([OH:15])[CH:12]=[CH:11][C:10]=1[CH2:23][CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26]
Reactant: CCOC(=O)/C=C/c1ccc(OCc2ccccc2)cc1OCc1ccccc1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CO
Product: CCOC(=O)CCc1ccc(O)cc1O
Reaction time: 2 h
Yield: 96.4 %

Procedure:
To a 500 mL parr shaker flask was charged with ethyl (2E)-3-[2,4-bis(benzyloxy)phenyl]prop-2-enoate (2.3 g, 5.92 mmol), ethyl acetate (10 mL) and methanol (10 mL). To the reaction mixture was added palladium hydroxide (20%) and kept for hydrogenation at 50 psi for 2 h. After completion of the reaction, the reaction mixture was filtered through celite, washed thoroughly with ethyl acetate (25 mL) and concentrated to distill off the solvent. The product was obtained as brown solid (1.2 g, yield: 96.8%).
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[C:11]([N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12]>>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([N:21]2[CH2:20][CH2:19][N:18]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:23][CH2:22]2)=[CH:3][CH:4]=1)([O-:10])=[O:9]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: O=[N+]([O-])c1ccc(F)cc1
Product: CC(C)(C)OC(=O)N1CCN(c2ccc([N+](=O)[O-])cc2)CC1
Yield: 48.8 %

Procedure:
Following Example 188a, 1-fluoro-4-nitrobenzene (2.8 g, 20 mmol) and N-Boc-piperazine (11 g, 60 mmol) were reacted to give 327a as a yellow solid (3 g, 51%). MS: [M+H]+ 308.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1.C1(C)C=CC=CC=1.[SH-].[Na+]>CO.O>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1)[NH2:8]
Reactant: O=[N+]([O-])c1cc(Br)cc([N+](=O)[O-])c1
Agent: [Na+]
Agent: [SH-]
Solvent: Cc1ccccc1
Solvent: CO
Solvent: O
Product: Nc1cc(Br)cc([N+](=O)[O-])c1
Temperature: 80 °C
Reaction time: 3 h
Yield: 99.7 %

Procedure:
1-Bromo-3,5-dinitrobenzene (14.77 g, 59.8 mmol) was dissolved in methanol (150 mL) and toluene (374 mL) and a solution of sodium hydrosulfide (10.06 g, 179 mmol) in water (10 mL) and methanol (150 mL) was added dropwise over a period of 60 minutes. The reaction was stirred at 80° C. for 3 hours. The reaction mixture was cooled to room temperature and then extracted 3 times with ethyl acetate. The organic layers were combined, washed with brine, dried with MgSO4, filtered, and concentrated under reduced pressure. The crude material required no further purification to yield 12.93 g (59.6 mmol, 100%) of 3-bromo-5-nitroaniline.
Reaction SMILES: [CH3:1][CH:2]([CH3:11])[C:3]([C:5]1[CH:6]=[N:7][CH:8]=[CH:9][CH:10]=1)=[O:4].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:32])(=O)=O)=CC=1.[Cl-].[NH4+]>C1COCC1.O>[F:32][C:2]([CH3:11])([CH3:1])[C:3]([C:5]1[CH:6]=[N:7][CH:8]=[CH:9][CH:10]=1)=[O:4]
Reactant: O=S(=O)(c1ccccc1)N(F)S(=O)(=O)c1ccccc1
Reactant: CC(C)C(=O)c1cccnc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Cl-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(F)C(=O)c1cccnc1
Reaction time: 0.5 h
Yield: 90 %

Procedure:
A solution of 2-methyl-1-(pyridin-3-yl)propan-1-one (1.72 g, 11.5 mmol) obtained in Step 2 in THF (20 mL) was slowly added dropwise to lithium bis(trimethylsilyl)amide (1.0 mol/L solution in THF, 13.8 mL, 13.8 mmol) at −78° C. and the mixture was stirred at the same temperature for 30 minutes. Further, N-fluorobenzenesulfonimide (4.36 g, 13.8 mmol) was added and the mixture was stirred for 1.5 hours allowing the temperature to rise slowly to room temperature. A saturated aqueous ammonium chloride solution and water were added to the reaction mixture. Extraction with ethyl acetate, washing with saturated brine and drying over anhydrous sodium sulfate were performed. After filtration, the solvent in the filtrate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1) to give 2-fluoro-2-methyl-1-(pyridin-3-yl)propan-1-one (1.73 g, 89% yield).
Reaction SMILES: [CH3:1][CH:2]1[CH2:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH2:12][CH:13]=O)[CH:9]=2)[C:4](=[O:15])[O:3]1.[CH3:16][CH:17]1[CH2:22][NH:21][CH2:20][CH2:19][NH:18]1.C([BH3-])#N.[Na+]>C(Cl)Cl>[CH3:1][CH:2]1[CH2:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH2:12][CH2:13][N:21]3[CH2:20][CH2:19][NH:18][CH:17]([CH3:16])[CH2:22]3)[CH:9]=2)[C:4](=[O:15])[O:3]1
Reactant: CC1CNCCN1
Reactant: CC1Cc2cc(CC=O)ccc2C(=O)O1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: ClCCl
Product: CC1CN(CCc2ccc3c(c2)CC(C)OC3=O)CCN1
Reaction time: 8 h

Procedure:
Freshly prepared (3-methyl-1-oxo-3,4-dihydro-1H-isochromen-6-yl)acetaldehyde was dissolved in DCM. To the solution was added 2-methyl piperazine (221 mg, 2.2 mmol) followed by sodium cyanoborohydride (165 mg, 2.64 mmol). The reaction mixture was allowed to stir overnight before being quenched with 10 mL of 1N HCl followed by stirring for 30 minutes. The reaction mixture was then treated with 50 mL of saturated sodium bicarbonate solution and extracted with DCM (3×50 mL). The combined organic layers were washed with water and brine, dried with magnesium sulfate, filtered, concentrated and purified via MPLC (30-100% (10% IPA in DCM/DCM) to afford 3-methyl-6-[2-(3-methylpiperazin-1-yl)ethyl]-3,4-dihydro-1H-isochromen-1-one. LC-MS (IE, m/z): 289 [M+1]+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[N:6]([CH2:13][C:14]([F:17])([F:16])[F:15])[C:5]2([C:22]1[CH:27]=[CH:26]C=CC=1)[C:18]([F:21])([F:20])[F:19].ClC1C=C2C(=CC=1)NC(=O)N(CC(F)(F)F)C2(O)C(F)(F)F.C1([Mg]Br)CC1>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[N:6]([CH2:13][C:14]([F:17])([F:16])[F:15])[C:5]2([CH:22]1[CH2:27][CH2:26]1)[C:18]([F:21])([F:20])[F:19]
Reactant: O=C1Nc2ccc(Cl)cc2C(c2ccccc2)(C(F)(F)F)N1CC(F)(F)F
Agent: Br[Mg]C1CC1
Agent: O=C1Nc2ccc(Cl)cc2C(O)(C(F)(F)F)N1CC(F)(F)F
Product: O=C1Nc2ccc(Cl)cc2C(C2CC2)(C(F)(F)F)N1CC(F)(F)F

Procedure:
Utilizing the general procedure outlined for 6-chloro-4-phenyl-3-(2,2,2-trifluoroethyl)-4-(trifluoromethyl)-3,4-dihydroquinazolin-2(1H)-one, 6-chloro-4-hydroxy-3-(2,2,2-trifluoroethyl)-4-(trifluoromethyl)-3,4-dihydroquinazolin-2(1H)-one (217 mg, 0.62 mmol) was reacted with 0.5 M cyclopropyl magnesium bromide (4.9 ml, 2.5 mmol) to afford 6-chloro-4-cyclopropyl-3-(2,2,2-trifluoroethyl)-4-(trifluoromethyl)-3,4-dihydroquinazolin-2(1H)-one as an oil. 1H NMR (CD3OD, 400 MHz) δ 7.89 (d, J=2.0 Hz, 1H), 7.36 (dd, J=2.4 and 8.6 Hz), 1H), 6.91 (dd, J=1.6 Hz and 7.6 Hz, 1H), 4.74 (m, 1H), 4.52 (m, 1H), 1.50 (m, 1H), 1.26 (m, 2H), 1.15 (m, 1H), 1.02 (m, 1H). Exact Mass (Electrospray, M+H) Calc'd, 373.0537; Found, 373.0541.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH2:9][CH3:10])[N:3]=1.S(=O)(=O)(O)O.OS(O)(=O)=O.O=S(=O)=O.[N+:25]([O-])([OH:27])=[O:26]>>[Cl:1][C:2]1[C:7]([N+:25]([O-:27])=[O:26])=[CH:6][CH:5]=[C:4]([O:8][CH2:9][CH3:10])[N:3]=1
Reactant: O=[N+]([O-])O
Reactant: CCOc1cccc(Cl)n1
Agent: O=S(=O)(O)O
Agent: O=S(=O)=O
Product: CCOc1ccc([N+](=O)[O-])c(Cl)n1
Temperature: 0 °C
Reaction time: 5 h
Yield: 93 %

Procedure:
157.6 g (1 mole) of 2-chloro-6-ethoxy-pyridine were slowly added over 45 minutes with stirring to a mixture of 190 ml of concentrated sulfuric acid, 190 ml of 24% oleum and 100 ml of 97% nitric acid while keeping the reaction temperature between 20° and 40° C. with cooling and the mixture was allowed to stand for 5 hours while the temperature returned to room temperature. The mixture was cooled to 0° C. and filtered with a glass frit filter. The solid product was suspended in a mixture of 100 g of potassium carbonate and 250 ml of water and the suspension was stirred for 3 hours at 30° C. and was vacuum filtered. The product was washed with water and dried at 40° C. to obtain 192 g (93% yield) of 2-chloro-3-nitro-6-ethoxy-pyridine with a purity of 98%.
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:30])[CH:10]=[CH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][C:19]([NH:22]C(OC(C)(C)C)=O)([CH3:21])[CH3:20])[CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>ClCCl>[CH2:1]([O:8][C:9](=[O:30])[CH:10]=[CH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][C:19]([NH2:22])([CH3:20])[CH3:21])[CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(Cc1cccc(C=CC(=O)OCc2ccccc2)c1)NC(=O)OC(C)(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC(C)(N)Cc1cccc(C=CC(=O)OCc2ccccc2)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of 3-[3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-phenyl]-acrylic acid benzyl ester (preparation 141), (2.23 g, 5.45 mmol), and trifluoroacetic acid (5 mL) in dichloromethane (10 mL) was stirred for 1 hour at room temperature. The mixture was then concentrated in vacuo and the residue was diluted with sodium hydrogen carbonate solution (10 mL) and extracted with ethyl acetate (3×20 mL). The combined organic solution was dried over magnesium sulfate and concentrated in vacuo to afford the title compound as a yellow oil in quantitative yield.
Reaction SMILES: [NH3:1].C[O:3][C:4]([C:6]1[N:11]=[C:10]([N:12]2[CH2:17][CH2:16][O:15][CH:14]([C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]4[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=4)=[CH:20][CH:19]=3)[CH2:13]2)[CH:9]=[CH:8][CH:7]=1)=O>CO>[F:31][C:28]1[CH:27]=[CH:26][C:25]([O:24][C:21]2[CH:22]=[CH:23][C:18]([CH:14]3[O:15][CH2:16][CH2:17][N:12]([C:10]4[CH:9]=[CH:8][CH:7]=[C:6]([C:4]([NH2:1])=[O:3])[N:11]=4)[CH2:13]3)=[CH:19][CH:20]=2)=[CH:30][CH:29]=1
Reactant: N
Reactant: COC(=O)c1cccc(N2CCOC(c3ccc(Oc4ccc(F)cc4)cc3)C2)n1
Solvent: CO
Product: NC(=O)c1cccc(N2CCOC(c3ccc(Oc4ccc(F)cc4)cc3)C2)n1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of 50 ml of 2M NH3 in methanol was added the crude compound 9 and the resulting solution was stirred for 12 hours at room temperature. The mixture was then concentrated to dryness and the resulting solid was recrystalized in methanol to give 1.1 g of compound 10. 1H NMR (DMSO-D6): δ 8.05 (b, 1H), 7.93 (d, 2H, J=8.8 Hz), 7.62 (d, 1H, J=2.5 Hz), 7.14 (d, 1H, J=2.5 Hz), 7.08 (m, 6H), 5.56 (b, 1H), 4.15 (t, 4H, J=5.1 Hz), 3.47 (t, 4H, J=5.1 Hz). MS: 394.2 (M+1).
Reaction SMILES: C[O:2][C:3]1[C:8]([CH3:9])=[CH:7][C:6]([C:10]2[O:11][C:12]3[C:17]([C:18](=[O:20])[CH:19]=2)=[CH:16][CH:15]=[CH:14][CH:13]=3)=[CH:5][C:4]=1[CH3:21].CC(O)=O.O>I>[OH:2][C:3]1[C:4]([CH3:21])=[CH:5][C:6]([C:10]2[O:11][C:12]3[C:17]([C:18](=[O:20])[CH:19]=2)=[CH:16][CH:15]=[CH:14][CH:13]=3)=[CH:7][C:8]=1[CH3:9]
Reactant: COc1c(C)cc(-c2cc(=O)c3ccccc3o2)cc1C
Agent: I
Solvent: O
Solvent: CC(=O)O
Product: Cc1cc(-c2cc(=O)c3ccccc3o2)cc(C)c1O
Temperature: 110 °C
Reaction time: 2 h
Yield: 85 %

Procedure:
To a solution of 2-hydroxyacetophenone (1.361 g, 10 mmol) in 20 mL anhydrous pyridine was added 3,5-dimethyl-4-methoxybenzoic acid (2.162 g, 12 mmol). The mixture was cooled to 0° C. and phosphorous oxychloride (1 mL) was added. A white precipitate was formed. The reaction mixture was stirred at rt for 2 h under nitrogen atmosphere. Then the reaction mixture was poured into 100 mL cold 2N HCl and extracted with EtOAc (2×200 mL). The combined organic layers were washed with water and brine and dried over anhydrous Na2SO4. The solvent was removed under vacuum to give a colorless liquid (2.89 g, 97%), which was used in the next step without further purification. The compound (2.88 g, 9.65 mmol) was dissolved in 10 mL anhydrous pyridine. Powdered potassium hydroxide (1.62 g, 28.95 mmol) was added and the reaction mixture was stirred at rt overnight under nitrogen. Water (100 mL) was added and the mixture was neutralized to pH 7 with conc. HCl. The yellow solid was filtered off, washed with water and dried under vacuum. Yield: 1.16 g, 40%. To a suspension of the yellow solid (1.14 g, 3.83 mmol) in 8 mL glacial AcOH was added 4 drops of conc. HCl and the reaction mixture was stirred at 110° C. for 2 h. The mixture was cooled to rt and water (50 mL) was added. The solid was isolated by filtration and washed with water and dried under vacuum to give 2-(4-methoxy-3,5-dimethyl phenyl)chromen-4-one (1.05 g, 98%) as a pale green solid. 2-(4-methoxy-3,5-dimethyl phenyl) chromen-4-one was suspended in 20 mL hydroiodic acid and 8 mL glacial AcOH was added. The reaction mixture was stirred at 110° C. for 2 h. The mixture was cooled to rt. Water (100 mL) was added and the solid was isolated by filtration, washed with water and dried under vacuum. The crude compound was washed with 1:1 dichloromethane and methanol (20 mL) to give 0.763 g of 2-(4-hydroxy-3,5-dimethylphenyl)-4H-chromen-4-one (85%) as a pale yellow solid. MS (ES) m/z: 267.06 (M+1); Mp. 255-256° C.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:11]=1[OH:12])[CH:7]=[O:8])[CH3:2].[OH-].[Na+].[CH2:15](Cl)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CN(C)C=O>[CH2:15]([O:12][C:11]1[CH:10]=[CH:9][C:6]([CH:7]=[O:8])=[CH:5][C:4]=1[O:3][CH2:1][CH3:2])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: ClCc1ccccc1
Reactant: CCOc1cc(C=O)ccc1O
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Product: CCOc1cc(C=O)ccc1OCc1ccccc1
Temperature: 60 °C
Reaction time: 2 h

Procedure:
To the solution of 3-ethoxy-4-hydroxy-benzaldehyde (83 g) in N,N-dimethylformamide (400 ml) was gradually added 10 M sodium hydroxide (55 ml) and then benzyl chloride (60 ml) was added at a temperature under 40° C. The mixture was stirred at room temperature for a half an hour and for 2 hours at 60° C. The solution was poured into ice-cold water (2 l) and extracted with diethyl ether. The organic phase was washed with water and 5M sodium hydroxide and then it was dried and evaporated. The product was recrystallized from toluene-heptane.
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][CH2:11][C:10](=[O:14])[CH2:9]1)(OC(C)(C)C)=O.[CH2:15](O)[CH2:16][OH:17].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1>[O:14]1[C:10]2([CH2:11][CH2:12][CH2:13][NH:8][CH2:9]2)[O:17][CH2:16][CH2:15]1
Reactant: CC(C)(C)OC(=O)N1CCCC(=O)C1
Reactant: OCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1
Product: C1CNCC2(C1)OCCO2

Procedure:
To a solution of 1-Boc-3-piperidone (700 mg, 3.51 mmol) in toluene (20 mL) was added ethylene glycol (588 μL, 10.54 mmol) followed by p-toluene sulfonic acid hydrate (1.0 g, 5.27 mmol) and the reaction heated to reflux using Dean-Stark apparatus for 7 h. To the mixture was added NaHCO3 solution, and the organic layer was removed. The aqueous phase was evaporated to dryness and the resulting residue dissolved in THF. Filtration through celite and removal of the solvent in vacuo gave the desired product as light brown oil. δH (CD3OD): 3.99 (2H, s), 3.73-3.57 (2H, m), 3.63 (4H, m), 2.77 (1H, m), 2.73 (1H, m), 1.76 (2H, m).
Reaction SMILES: [C:1]1([CH:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:8]([OH:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:17](Cl)(=O)C(Cl)=O.CO>ClCCl.CN(C=O)C>[C:1]1([CH:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:8]([O:10][CH3:17])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C(O)C(c1ccccc1)c1ccccc1
Reactant: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: CO
Product: COC(=O)C(c1ccccc1)c1ccccc1
Yield: 98.7 %

Procedure:
To a 500 mL three-opening flask were added 2,2-diphenylacetic acid (20 g, 94 mmol) and 200 mL dichloromethane. After stirring, 1 mL DMF was added. To the mixture was slowly added oxalyl chloride (13.16 g, 104 mmol) dropwisely in an ice bath. The reaction was conducted at 25° C. After the completion of reaction, the mixture was evaporated under reduced pressure to remove oxalyl chloride. To the reaction flask were slowly added dichloromethane (100 mL) and anhydrous methanol (3.61 g, 113 mmol) dropwisely under cooling in an ice bath respectively. The reaction was conducted at 25° C. After the completion of reaction, the reaction solution was washed with a saturated aqueous NaCl solution. The organic phase was dried over sodium sulfate, and filtered by suction. The filtrate was evaporated to dryness to produce methyl 2,2-diphenylacetate (21 g) in a yield of 98.7%.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([O:9][CH3:10])=[C:4]([CH3:11])[CH:3]=1.N1C=CC=CC=1.[C:18](Cl)(=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20]>C(Cl)Cl>[C:18]([NH:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([O:9][CH3:10])=[C:4]([CH3:11])[CH:3]=1)(=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20]
Reactant: CC(C)(C)C(=O)Cl
Reactant: COc1c(C)cc(N)cc1C
Solvent: ClCCl
Solvent: c1ccncc1
Product: COc1c(C)cc(NC(=O)C(C)(C)C)cc1C
Temperature: 25 °C
Reaction time: 15 h
Yield: 84.1 %

Procedure:
Into an ice-cold solution of aniline 4 (15.1 g, 100 mmol) dissolved in methylene chloride (100 mL) were added sequentially pyridine (17.5 mL) and pivaloyl chloride (12.3 mL, 100 mmol) dropwise, and the resulting mixture was stirred at room temperature for 15 h. The mixture was diluted with methylene chloride and washed sequentially with 10% aq. hydrochloric acid, saturated aq. sodium bicarbonate and brine. Removal of solvents after drying (MgSO4) gave the pivalamide (19.8 g, 86% yield) as a pale brown solid, mp 126°-128° C. Spectral data: 1H NMR: δ 1.30 (s, 9H), 2.23 (s, 6H), 3.68 (s, 3H), 7.18 (s, 2H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][CH:3]=1.[Mg].O1CCCC1.[F:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]([C:24]2[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=2)=[O:23])=[CH:18][CH:17]=1>C(O)(=O)C.CC1C=CC=CC=1>[F:8][C:5]1[CH:6]=[CH:7][C:2]([C:22]([C:19]2[CH:20]=[CH:21][C:16]([F:15])=[CH:17][CH:18]=2)([C:24]2[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=2)[OH:23])=[CH:3][CH:4]=1
Reactant: Fc1ccc(Br)cc1
Reactant: O=C(c1ccncc1)c1ccc(F)cc1
Agent: [Mg]
Solvent: Cc1ccccc1
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: OC(c1ccncc1)(c1ccc(F)cc1)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 94 %

Procedure:
A Grignard-complex was previously prepared starting from 22.75 parts of 1-bromo-4-fluorobenzene, 3.2 parts of magnesium and 45 parts of anhydrous tetrahydrofuran. The whole was cooled in 2-propane/CO2 to a temperature of -20° to -25° C. A solution of 20.1 parts of (4-fluorophenyl)(4-pyridinyl)methanone in 45 parts of anhydrous methylbenzene was added dropwise, during a 30 minutes-period, at -20° C. Upon completion, the whole was stirred overnight at room temperature. After cooling to 0° C., the reaction mixture was decomposed by the dropwise addition of 50 parts of acetic acid. After stirring for 1 hour at room temperature, the precipitated product was filtered off and set aside. From the filtrate, the organic layer was separated, washed with 50 parts of water, dried, filtered and evaporated. The solid residue and the precipitated product, which was set aside (see above), were washed with water and distilled azeotropically with 180 parts of methylbenzene. The solid distillate was suspended in 80 parts of acetonitrile. The product was filtered off and dried, yielding 28 parts (94%) of α,α-bis(4-fluorophenyl)-4-pyridinemethanol (intermediate 26).
Reaction SMILES: [O:1]=[S:2]1(=[O:19])[CH2:7][CH2:6][N:5]([C:8]2[N:13]=[C:12]3[NH:14][CH:15]=[C:16]([C:17]#[N:18])[C:11]3=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[C:20]([C:24]1[CH:25]=[C:26]2[C:31](=[C:32]([F:34])[CH:33]=1)[C:30](=[O:35])[N:29]([C:36]1[C:44]3[CH2:43][O:42]B(O)[C:40]=3[CH:39]=[CH:38][CH:37]=1)[N:28]=[CH:27]2)([CH3:23])([CH3:22])[CH3:21].N1C=CC=CC=1.[NH4+].[Cl-]>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.ClCCCl>[C:20]([C:24]1[CH:25]=[C:26]2[C:31](=[C:32]([F:34])[CH:33]=1)[C:30](=[O:35])[N:29]([C:36]1[C:44]([CH2:43][OH:42])=[C:40]([N:14]3[C:12]4=[N:13][C:8]([N:5]5[CH2:4][CH2:3][S:2](=[O:1])(=[O:19])[CH2:7][CH2:6]5)=[CH:9][CH:10]=[C:11]4[C:16]([C:17]#[N:18])=[CH:15]3)[CH:39]=[CH:38][CH:37]=1)[N:28]=[CH:27]2)([CH3:23])([CH3:21])[CH3:22]
Reactant: N#Cc1c[nH]c2nc(N3CCS(=O)(=O)CC3)ccc12
Reactant: CC(C)(C)c1cc(F)c2c(=O)n(-c3cccc4c3COB4O)ncc2c1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Agent: [Cl-]
Solvent: ClCCCl
Solvent: c1ccncc1
Product: CC(C)(C)c1cc(F)c2c(=O)n(-c3cccc(-n4cc(C#N)c5ccc(N6CCS(=O)(=O)CC6)nc54)c3CO)ncc2c1
Temperature: 45 °C
Reaction time: 48 h
Yield: 8.3 %

Procedure:
In a 25 mL round-bottomed flask, 6-(1,1-dioxo-1lambda*6*-thiomorpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (122 mg, 442 μmol), 6-tert-butyl-8-fluoro-2-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-4-yl)phthalazin-1(2H)-one (155 mg, 442 μmol, Eq: 1.00) and copper acetate (108 mg) were combined with 1,2-dichloroethane (3.89 ml) to give a blue suspension. Pyridine (69.8 mg, 71.4 μl, 883 μmol, Eq: 2) was added. The reaction mixture was heated to 45° C. and stirred for 2 d. The reaction mixture was poured into 20 mL sat NH4Cl and extracted with EtOAc (3×20 mL). The organic layers were dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 5% to 10% MeOH in DCM), then by HPLC to give 1-[3-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-6-(1,1-dioxo-1lambda*6*-thiomorpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (22 mg, 8%)
Reaction SMILES: [CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[CH:3]=1.[N+:11]([CH2:14][CH3:15])([O-:13])=[O:12].C([O-])(=O)C.[NH4+]>C(O)(=O)C>[CH3:9][O:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([CH:1]=[C:14]([N+:11]([O-:13])=[O:12])[CH3:15])[CH:3]=1
Reactant: COc1cccc(C=O)c1
Reactant: CC[N+](=O)[O-]
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CC(=O)O
Product: COc1cccc(C=C(C)[N+](=O)[O-])c1

Procedure:
A mixture of 71.9 g (0.528 mole) of m-anisaldehyde, 118.9 g (1.584 mole) of nitroethane, 40.7 g (0.528 mole) of ammonium acetate, and 350 ml of glacial acetic acid was heated to reflux for one hour. The mixture was then allowed to cool and partitioned between ether and water. The ether layer was separated and washed sequentially with water, 3N sodium hydroxide, water and brine. The organic phase was dried over anhydrous magnesium sulfate and evaporated in vacuo to give the crude product. After a preliminary distillation at 125° C./0.0001 mm, the product was finally crystallized from absolute ethanol to yield the pure product, a yellow solid, mp 40°-42° C.
Reaction SMILES: [C:1]1([N:7]2[C:11](=[O:12])[CH:10]=[C:9]([CH3:13])[NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[C:25](OC(=O)C)(=[O:27])[CH3:26]>>[C:1]1([N:7]2[C:11](=[O:12])[C:10]([C:25](=[O:27])[CH3:26])=[C:9]([CH3:13])[NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(=O)OC(C)=O
Reactant: Cc1cc(=O)n(-c2ccccc2)[nH]1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Product: CC(=O)c1c(C)[nH]n(-c2ccccc2)c1=O

Procedure:
174 g of 1-phenyl-3-methyl-pyrazol-5-one in 700 ml of acetic anhydride, with the addition of 6 g of p-toluenesulphonic acid, are heated to the boil under reflux for 6 hours. The solvent is then distilled off under a water-pump vacuum, the residue is dissolved hot in 2 l of 5% strength sodium hydroxide solution, the solution is clarified with 8 g of active charcoal, the filtrate is acidified with hydrochloric acid at room temperature and the crystalline precipitate is filtered off, washed with water and dried in vacuo at 40° C. 183 g of 1-phenyl-3-methyl-4-acetyl-pyrazol-5-one are obtained in the form of colourless crystal needles.