Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1([CH2:7][C:8]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:9])[S:6][CH2:5][CH2:4][O:3]1.[OH:17]O>O>[CH3:1][C:2]1([CH2:7][C:8]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:9])[S:6](=[O:17])[CH2:5][CH2:4][O:3]1
Reactant: CC1(CC(=O)Nc2ccccc2)OCCS1
Reactant: OO
Solvent: O
Product: CC1(CC(=O)Nc2ccccc2)OCCS1=O

Procedure:
bringing together the 2-methyl-N-phenyl-1,3-oxathiolane-2-acetamide and hydrogen peroxide under basic conditions, in the presence of a catalytic quantity of a suitable heavy metal compound oxidation catalyst effective to catalyze the oxidation of said 2-methyl-N-phenyl-1,3-oxathiolane-2-acetamide by the said hydrogen peroxide, in a liquid medium comprising water, or water plus at least one nonprotic organic liquid selected from the group consisting of (a) aromatic hydrocarbon solvent having a boiling point not greater than 145° C., (b) chlorinated hydrocarbon solvent having a boiling point not greater than 130° C., and (c) a solvent having a boiling point not greater than 130° C. which is an alkyl ester of an aliphatic carboxylic acid, and subjecting the resulting mixture while agitating to a temperature of from 0°-25° C., whereby 2-methyl-N-phenyl-1,3-oxathiolane-2-acetamide 3-oxide is formed;
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11](=O)[CH2:12][NH2:13])=[CH:6][CH:5]=1.[S-:15][C:16]#[N:17].[K+]>C(O)(=O)C.O>[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]2[N:17]=[C:16]([SH:15])[NH:13][CH:12]=2)=[CH:6][CH:5]=1
Reactant: COc1ccc(CC(=O)CN)cc1
Reactant: N#C[S-]
Agent: Cl
Agent: [K+]
Solvent: CC(=O)O
Solvent: O
Product: COc1ccc(Cc2c[nH]c(S)n2)cc1

Procedure:
A solution of 3-(4-methoxyphenyl)-2-oxo-1-aminopropane, hydrochloride (3.0 g, 14 mmole) and potassium thiocyanate (1.36 g, 14 mmole) in acetic acid (60 ml) was heated under reflux for 15 minutes. The reaction was cooled, diluted with water and the product was filtered and recrystallized from ethyl alcohol and dried to give the product was a solid (1.6 g, 52%).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([S:15][C:16]2[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][CH2:24][CH:25]([NH:36]C(OC(C)(C)C)=O)[CH:26]=[CH:27][P:28](=[O:35])([O:32][CH2:33][CH3:34])[O:29][CH2:30][CH3:31])=[C:18]([Cl:44])[CH:17]=2)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl>CO>[ClH:44].[NH2:36][CH:25]([CH2:24][CH2:23][CH2:22][C:19]1[CH:20]=[CH:21][C:16]([S:15][C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:10]=2)=[CH:17][C:18]=1[Cl:44])[CH:26]=[CH:27][P:28](=[O:35])([O:32][CH2:33][CH3:34])[O:29][CH2:30][CH3:31]
Reactant: CCOP(=O)(C=CC(CCCc1ccc(Sc2cccc(OCc3ccccc3)c2)cc1Cl)NC(=O)OC(C)(C)C)OCC
Agent: Cl
Solvent: CO
Product: CCOP(=O)(C=CC(N)CCCc1ccc(Sc2cccc(OCc3ccccc3)c2)cc1Cl)OCC
Temperature: 25 °C
Reaction time: 6 h
Yield: 184.5 %

Procedure:
The compound of Example 232 (300 mg) was dissolved in methanol (10 mL) containing 10% hydrochloric acid in an ice bath. The mixture was stirred for 6 hours until room temperature and the solvent was concentrated. This gave the desired product as a colorless oil (250 mg).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)[C:11](=[O:23])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(=O)C.[Na+].[Br:29]Br.O>C(O)(=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([CH2:15][C:16]2[CH:17]=[CH:18][C:19]([CH3:22])=[CH:20][CH:21]=2)[C:11](=[O:23])[C:10]=1[Br:29])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1ccc(Cn2ccc(OCc3ccccc3)cc2=O)cc1
Reactant: BrBr
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: Cc1ccc(Cn2ccc(OCc3ccccc3)c(Br)c2=O)cc1
Reaction time: 2 h

Procedure:
The material prepared in Example 1 (2.1 g, 0.007 mol) and sodium acetate (738 mg, 0.009 mol) in glacial acetic acid (15 mL) were cooled to 15° C. Bromine (0.412 mL, 0.008) in glacial acetic acid (5 mL) was added dropwise. Contents were stirred 2 hours, coming to room temperature. Water (200 mL) was added and a light yellow solid was filtered. Mp 150.4-151.2° C. FABHRMS m/z 384.0599 (M+H, C20H19BrNO2 requires 384.0601). 1H NMR (CDCl3/300 MHz) δ: 7.42-7.30 (m, 5H); 7.22-7.08 (m, 5H); 6.02 (d, 1H); 5.20 (s, 2H); 5.12 (s, 2H); 2.32 (s, 3H).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([CH2:12][CH2:13][CH3:14])[C:4](=[O:15])[C:3]=1[C:16]#[N:17].Cl.[C:19]([NH:23][NH2:24])([CH3:22])([CH3:21])[CH3:20]>C(O)C.C(N(CC)CC)C>[NH2:17][C:16]1[N:23]([C:19]([CH3:22])([CH3:21])[CH3:20])[N:24]=[C:2]2[C:11]3[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=3[N:5]([CH2:12][CH2:13][CH3:14])[C:4](=[O:15])[C:3]=12
Reactant: CCCn1c(=O)c(C#N)c(Cl)c2ccccc21
Reactant: CC(C)(C)NN
Agent: Cl
Solvent: CCO
Solvent: CCN(CC)CC
Product: CCCn1c(=O)c2c(N)n(C(C)(C)C)nc2c2ccccc21
Yield: 87.3 %

Procedure:
In a mixture of 60 ml of ethanol and 5 ml of triethylamine, 2.00 g (8.1 mmol) of Compound b and 2.00 g (16 mmol) of t-butylhydrazine hydrochloride were refluxed for 4 hours. The reaction mixture was dried under reduced pressure, and the residue was partitioned between chloroform and water. The chloroform layer was dried under reduced pressure, and the residue was passed through a silica gel column and eluted with a 3:1 (by volume) mixed solvent of hexane and ethyl acetate. The main fraction collected was dried under reduced pressure to obtain 2.11 g (87%) of Compound 7 as a colorless crystal. The product was treated with ethyl acetate saturated with hydrogen chloride to obtain a hydrochloride of Compound 7.
Reaction SMILES: [CH2:1]([NH:3][CH2:4][C:5]1[CH:6]=[N:7][CH:8]=[CH:9][CH:10]=1)[CH3:2].[CH3:11][N:12]=[C:13]=[S:14]>C(OCC)C>[CH3:11][NH:12][C:13]([N:3]([CH2:1][CH3:2])[CH2:4][C:5]1[CH:6]=[N:7][CH:8]=[CH:9][CH:10]=1)=[S:14]
Reactant: CN=C=S
Reactant: CCNCc1cccnc1
Solvent: CCOCC
Product: CCN(Cc1cccnc1)C(=S)NC
Temperature: 25 °C
Reaction time: 1 h
Yield: 100.3 %

Procedure:
In 50 ml of ethyl ether was dissolved 2.4 g of N-ethyl-N-(3-pyridylmethyl)amine followed by addition of 1.3 g of methyl isothiocyanate. The mixture was stirred at room temperature (25° C.) for 1 hour. The resulting precipitate was collected by filtration, washed with a small amount of ethyl ether and dried to give 3.7 g of N-methyl-N'-ethyl-N'-(3-pyridylmethyl)thiourea as white prisms.
Reaction SMILES: C([O:8][C:9](=[O:29])[C:10]1[CH:22]=[C:21]([C:23]2[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=2)[CH:20]=[C:12]([C:13]([N:15]([CH3:19])[CH2:16][CH2:17][CH3:18])=[O:14])[CH:11]=1)C1C=CC=CC=1>[Pd].CO>[CH3:19][N:15]([CH2:16][CH2:17][CH3:18])[C:13](=[O:14])[C:12]1[CH:11]=[C:10]([CH:22]=[C:21]([C:23]2[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=2)[CH:20]=1)[C:9]([OH:29])=[O:8]
Reactant: CCCN(C)C(=O)c1cc(C(=O)OCc2ccccc2)cc(-c2ccncc2)c1
Agent: [Pd]
Solvent: CO
Product: CCCN(C)C(=O)c1cc(C(=O)O)cc(-c2ccncc2)c1

Procedure:
Stir a mixture of N-methyl-N-propyl-5-pyridin-4-yl-isophthalamic acid benzyl ester (1.900 g, 4.891 mmol), 10% palladium on carbon (0.208 g) in MeOH (50 mL) under an atmosphere of hydrogen gas (1 atm) for 0.5 h. Filter through a filtering agent and concentrate to give the title compound (quantitative yield).
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([N:24]2[CH2:28][CH2:27][O:26][C:25]2=[O:29])[CH:5]=[CH:6][C:7]=1[C:8]([N:10]1[CH2:15][CH2:14][N:13]([C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][C:17]=2[CH3:23])[CH2:12][CH2:11]1)=[O:9].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH:38]1(B(O)O)[CH2:40][CH2:39]1.C1(C)C=CC=CC=1>C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.[Cl-].[Cl-].[Pd+2].O>[CH:38]1([C:2]2[CH:3]=[C:4]([N:24]3[CH2:28][CH2:27][O:26][C:25]3=[O:29])[CH:5]=[CH:6][C:7]=2[C:8]([N:10]2[CH2:11][CH2:12][N:13]([C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][C:17]=3[CH3:23])[CH2:14][CH2:15]2)=[O:9])[CH2:40][CH2:39]1
Reactant: OB(O)C1CC1
Reactant: Cc1ccc(N2CCN(C(=O)c3ccc(N4CCOC4=O)cc3Cl)CC2)c(C)c1
Agent: [Pd+2]
Agent: C1CCC(P(C2CCCCC2)C2CCCCC2)CC1
Agent: O=P([O-])([O-])[O-]
Solvent: O
Solvent: Cc1ccccc1
Product: Cc1ccc(N2CCN(C(=O)c3ccc(N4CCOC4=O)cc3C3CC3)CC2)c(C)c1
Yield: 23 %

Procedure:
To a mixture of 3-{3-chloro-4-[4-(2,4-dimethylphenyl)piperazine-1-carbonyl]phenyl}oxazolidin-2-one (347 mg) described in Example 21, bis(tricyclohexylphosphine)palladium (II) dichloride (33 mg), tripotassium phosphate (956 mg) and cyclopropylboronic acid (172 mg) were added toluene (4 mL) and water (200 μL), and the mixture was refluxed for 6 hr. After cooling, water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was washed with saturated brine, and the solvent was evaporated. The residue was purified by column chromatography (chloroform:methanol) to give the title compound (81 mg).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[N:3][C:2]=1[N:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1.Cl[CH2:14][C:15]1[CH:16]=[C:17]([C:21]2[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=2)[CH:18]=[CH:19][CH:20]=1>C1COCC1>[N:1]1[CH:6]=[CH:5][CH:4]=[N:3][C:2]=1[N:7]1[CH2:12][CH2:11][N:10]([CH2:14][C:15]2[CH:16]=[C:17]([C:21]3[CH:26]=[CH:25][C:24]([C:27]([F:28])([F:29])[F:30])=[CH:23][CH:22]=3)[CH:18]=[CH:19][CH:20]=2)[CH2:9][CH2:8]1
Reactant: FC(F)(F)c1ccc(-c2cccc(CCl)c2)cc1
Reactant: c1cnc(N2CCNCC2)nc1
Solvent: C1CCOC1
Product: FC(F)(F)c1ccc(-c2cccc(CN3CCN(c4ncccn4)CC3)c2)cc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A solution of 1.6 g of 1-pyrimidin-2-ylpiperazine in 200 ml of THF is treated with 2.75 g of 3-chloromethyl-4′-trifluoromethylbiphenyl (“H”) [obtainable, for example, by radical chlorination of 3-methyl-4′-trifluoromethylbiphenyl], dissolved in 30 ml of THF, and the mixture is stirred for 4 hours at room temperature. After customary work-up, 1-pyrimidin-2-yl-4-[(4′-trifluoromethyl-3-biphenylyl)methyl]piperazine is obtained.
Reaction SMILES: CO.[Cl:3][C:4]1[C:9]([O:10]C(OC)=O)=[CH:8][C:7]([N:15]2[C:23](=[O:24])[C:18]3=[CH:19][CH2:20][CH2:21][CH2:22][N:17]3[C:16]2=[O:25])=[C:6]([F:26])[CH:5]=1.C(=O)([O-])[O-].[K+].[K+].Cl>C(OCC)C>[Cl:3][C:4]1[C:9]([OH:10])=[CH:8][C:7]([N:15]2[C:23](=[O:24])[C:18]3=[CH:19][CH2:20][CH2:21][CH2:22][N:17]3[C:16]2=[O:25])=[C:6]([F:26])[CH:5]=1
Reactant: COC(=O)Oc1cc(N2C(=O)C3=CCCCN3C2=O)c(F)cc1Cl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOCC
Solvent: CO
Product: O=C1C2=CCCCN2C(=O)N1c1cc(O)c(Cl)cc1F
Yield: 35.6 %

Procedure:
A methanol (40 mL) solution of 2-(4-chloro-2-fluoro-5-methoxycarbonyloxyphenyl)-5,6-dihydroimidazo [1,5-a] pyridine-1,3[2H, 7H]-dione (3.13 g, 8.8 mmol) and potassium carbonate (1.22 g, 8.8 mmol) was stirred at 50°-60° C. for 8 hours. Diethyl ether (20 mL) and 1N hydrochloric acid (30 mL) were added to the resulting mixture, and the organic layer was separated and then the aqueous layer was extracted with diethyl ether (20 mL×2 times). The organic layer combined was washed with a saturated sodium chloride solution (30 mL) and dried over anhydrous magnesium sulfate. After removal of magnesium sulfate by filtration, the filtrate was evaporated to give crude product, which was purified by silica gel column (Wakogel C-200, ethyl acetate/hexane=1/1) to obtain a white solid of 2-(4-chloro-2-fluoro-5-hydroxyphenyl)-5,6-dihydroimidazo [1,5-a] pyridine-1,3[2H, 7H]-dione (0.93 g, yield:5.8%).
Reaction SMILES: [CH2:1]([N:8]1[C:13](=[O:14])[C:12]([C:15]([OH:17])=O)=[C:11]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[C:10]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:35][NH:36][CH3:37]>>[CH2:1]([N:8]1[C:13](=[O:14])[C:12]([C:15](=[O:17])[N:36]([CH3:37])[CH3:35])=[C:11]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[C:10]([C:26]2[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=2)=[N:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CNC
Reactant: COc1ccc(-c2nn(Cc3ccccc3)c(=O)c(C(=O)O)c2-c2ccc(OC)cc2)cc1
Agent: Cl
Product: COc1ccc(-c2nn(Cc3ccccc3)c(=O)c(C(=O)N(C)C)c2-c2ccc(OC)cc2)cc1
Yield: 42.1 %

Procedure:
Using 2-benzyl-5,6-bis(4-methoxyphenyl)-4-carboxy-2H-pyridazin-3-one and dimethylamine hydrochloride as starting materials, the procedures of Example 22 were repeated likewise, whereby the title compound was obtained in a yield of 42.1%.
Reaction SMILES: [N:1]([CH2:4][C:5]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=1)([F:7])[F:6])=[N+]=[N-].[N-]=[N+]=[N-]>C(OCC)(=O)C.[Pd]>[F:7][C:5]([F:6])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=1)[CH2:4][NH2:1]
Reactant: [N-]=[N+]=NCC(F)(F)c1ccccn1
Agent: [Pd]
Agent: [N-]=[N+]=[N-]
Solvent: CCOC(C)=O
Product: NCC(F)(F)c1ccccn1

Procedure:
A stirred solution of 100 mg of 2-(2-azido-1,1-difluoro-ethyl)-pyridine was hydrogenated in 10 mL of ethyl acetate over 100 mg of 10% palladium on carbon using a balloon for 1 h. The catalyst was removed by filtration and the solvents removed at reduced pressure. A total of 1.8 g (9.7 mmol) of the azide was reduced using this procedure to give 2,2-difluoro-2-pyridin-2-yl-ethylamine as a yellow oil: 1H NMR (CDCl3) δ 8.66 (d, 1H, 4.2 Hz), 7.82 (td,1H, 7.7, 1.7 Hz), 7.68 (d, 1H, 8.1 Hz), 7.37–7.40 (m, 1H), 3.44 (t, 2H, 14.3 Hz), 1.41 (br s, 2H).
Reaction SMILES: [C:1]([CH:5]([C:9]([F:11])=[O:10])[C:6]([F:8])=[O:7])([F:4])([F:3])[F:2].[CH2:12](N(CC)CC)C.S(OC)(OC)(=O)=O>CCOCC>[CH3:12][C:5]([C:1]([F:4])([F:3])[F:2])([C:6]([F:8])=[O:7])[C:9]([F:11])=[O:10]
Reactant: CCN(CC)CC
Reactant: O=C(F)C(C(=O)F)C(F)(F)F
Solvent: COS(=O)(=O)OC
Solvent: CCOCC
Product: CC(C(=O)F)(C(=O)F)C(F)(F)F
Reaction time: 3 h
Yield: 48.9 %

Procedure:
A solution of 17.6 g (0.10 mol) of CF3CH(COF)2 in 25 ml of ether was cooled at 0°C and stirred while 9.2 g (0.10 mol) of triethylamine was added dropwise in 15 minutes. Then 25.2 g (0.20 mol) of dimethyl sulfate was added all at once, and the mixture was allowed to stand at 25°C for 3 hours. Distillation gave 9.3 g (49%) of methyltrifluoromethylmalonyl fluoride, bp 62°-65°C. Redistillation gave an analytical sample, bp 64°-65.5°C; ir and nmr spectra were taken on a similarly prepared sample; ir (CCl4): 5.37 (COF) and 7.5-8.5 μ (CF); nmr (CCl4): 1H at 1.92 ppm (broadened singlet, CH3); 19F at 37.8 (quartet, JFF = 10 Hz into quartets, JHF = 1 Hz, 2, (COF) and -71.1 ppm (triplet, JFF = 10 Hz, into quartets, JHF = 0.8 Hz, 3, CF3).
Reaction SMILES: Br[CH2:2][CH:3]1[CH2:6][CH2:5][CH2:4]1.[CH2:7]1[O:11][C:10]2[CH:12]=[C:13]([OH:16])[CH:14]=[CH:15][C:9]=2[O:8]1>>[CH:3]1([CH2:2][O:16][C:13]2[CH:14]=[CH:15][C:9]3[O:8][CH2:7][O:11][C:10]=3[CH:12]=2)[CH2:6][CH2:5][CH2:4]1
Reactant: BrCC1CCC1
Reactant: Oc1ccc2c(c1)OCO2
Product: c1cc2c(cc1OCC1CCC1)OCO2

Procedure:
Starting from commercially available bromomethyl-cyclobutane and sesamol the title compound is obtained as colorless solid.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:12][CH2:11][C:10]([F:14])([F:13])[CH2:9]2)=[CH:4][CH:3]=1.[Li]CCCC.[C:20](=[O:22])=[O:21]>C1COCC1.CCOCC>[F:13][C:10]1([F:14])[CH2:11][CH2:12][C@@H:8]([C:5]2[CH:6]=[CH:7][C:2]([C:20]([OH:22])=[O:21])=[CH:3][CH:4]=2)[CH2:9]1
Reactant: FC1(F)CC[C@@H](c2ccc(Br)cc2)C1
Reactant: O=C=O
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCOCC
Product: O=C(O)c1ccc([C@@H]2CCC(F)(F)C2)cc1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
A solution of 1.0 g (3.8 mmol) of (R)-3-(4-bromophenyl)-1,1-difluorocyclopentane (from Step B) in 15 mL of THF at −78° C. was treated with 1.6 mL (4.0 mmol) of 2.5M BuLi in hexanes. After stirring for 15 min, the reaction mixture was added to a suspension of dry ice in 200 mL of Et2O. The mixture was allowed to warm to rt. The reaction mixture was extracted with 100 mL of 1 N NaOH. After separating phases, the aqueous layer was acidified to pH 1-2 with concentrated HCl. The aqueous phase was extracted with 3×100 mL of CH2Cl2. The combined organic phases were dried and concentrated to give 0.67 g of the title compound: 1H NMR (CD3OD) δ 1.87 (m, 1H), 2.13-2.37 (m, 4H), 2.54 (m, 11H), 3.41 (m, 1H), 7.39 (d, J=8.2, 2H), 7.97 (d, J=8.2, 2H).
Reaction SMILES: CC(C)([O-])C.[Na+].O1CCCC1.Br[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[C:19]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)(=[O:22])[CH2:20][CH3:21]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1([B-](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.O>[C:23]1([C:19](=[O:22])[CH:20]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH3:21])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: Brc1ccccc1
Reactant: CCC(=O)c1ccccc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)[O-]
Solvent: O
Solvent: C1CCOC1
Product: CC(C(=O)c1ccccc1)c1ccccc1
Yield: 98.2 %

Procedure:
A 30-ml four-necked flask was equipped with a stirrer, a thermometer and a reflux condenser. 0.011 g (0.05 mmol) of palladium (II) acetate, 1.442 g (15 mmol) of sodium-tert-butoxide and 10 ml of tetrahydrofuran were weighed in the flask, followed by stirring. Further, 0.026 g (0.05 mmol) of tri-tert-butylphosphonium tetraphenylborate obtained in Example A-1 was weighed in air and added into the flask. The flask was purged with argon, followed by stirring at 25° C. for 30 minutes. 1.570 g (10 mmol) of bromobenzene was added, followed by stirring at 25° C. for 30 minutes. 1.476 g (11 mmol) of propiophenone was added, followed by stirring at 25° C. for 17 hours. After the completion of the reaction, 5 ml of water was added, followed by separation. The organic phase was purified by column chromatography to afford 2.065 g of 1,2-diphenyl-1-propanone (yield: 98 mol % based on bromobenzene). The identification of the product was made by mass spectroscopy, 1H-NMR and 13C-NMR.
Reaction SMILES: [OH:1][N:2]=[C:3]1[CH:8]=[CH:7][C:6](=[C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:10]#[N:11])[CH:5]=[C:4]1[CH3:18].[CH3:19][S:20](Cl)(=[O:22])=[O:21].C(N(CC)CC)C.O>C1COCC1>[CH3:18][C:4]1[C:3](=[N:2][O:1][S:20]([CH3:19])(=[O:22])=[O:21])[CH:8]=[CH:7][C:6](=[C:9]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:10]#[N:11])[CH:5]=1
Reactant: CS(=O)(=O)Cl
Reactant: CC1=CC(=C(C#N)c2ccccc2)C=CC1=NO
Solvent: O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC1=CC(=C(C#N)c2ccccc2)C=CC1=NOS(C)(=O)=O
Temperature: 0 °C
Yield: 52.3 %

Procedure:
16.7 g (70 mmol) of crude (4-Hydroxyimino-3-methyl-cyclohexa-2,5-dienylidene)-phenylacetonitrile are dissolved in 100 ml of THF and cooled in an ice bath. After adding 6.0 ml (77 mmol) of methanesulfonyl chloride, 14.8 ml (106 mmol) of triethylamine are added dropwise to the solution, keeping the temperature below 10° C. The reaction mixture is stirred in the ice bath for 30 min., poured into 250 ml of iced water, and extracted with ethyl acetate. The organic phase is washed with 0.2 N hydrochloric acid, water, and saturated aqueous sodium chloride. The organic phase is dried over MgSO4, the solvent is distilled off, and the residue is purified by recrystallization from toluene. 11.5 g (52%) of (3-Methyl-4-methylsulfonyloxyimino-cyclohexa-2,5-dienylidene)-phenyl-acetonitrile are obtained in the form of bright yellow crystals having a melting point of 136-138° C.(dec.).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH3:9])=[C:4]([OH:11])[CH:3]=1.[Cl-].O[NH3+:14].C([O-])(=O)C.[Na+]>CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]2[C:8]([CH3:9])=[N:14][O:11][C:4]=2[CH:3]=1
Reactant: [NH3+]O
Reactant: CC(=O)c1ccc(F)cc1O
Agent: CC(=O)[O-]
Agent: [Cl-]
Agent: [Na+]
Solvent: CO
Product: Cc1noc2cc(F)ccc12
Temperature: 60 °C
Reaction time: 1 h
Yield: 69.9 %

Procedure:
A mixture of 1-(4-fluoro-2-hydroxyphenyl)ethanone (20 g), hydroxyammonium chloride (18.1 g), sodium acetate (16 g) and methanol (500 mL) was stirred at 60° C. for 1 hr. The reaction mixture was added to ice water, and the obtained crystallized product was collected by filtration and dissolved in tetrahydrofuran (400 mL). N,N′-carbonyldiimidazole (22.5 g) and then a solution of triethylamine (22.3 mL) in tetrahydrofuran (100 mL) were added, and the mixture was stirred at 70° C. for 1 hr. The reaction mixture was diluted with diethyl ether, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound as colorless crystals (13.7 g, 70%).
Reaction SMILES: [OH:1][CH:2]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:3][N:4]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH2:15][C:16]#[CH:17])=[CH:11][CH:12]=2)[C:7]([C:18]2[CH:23]=[CH:22][C:21]([CH:24]([CH3:26])[CH3:25])=[CH:20][CH:19]=2)=[N:6][C:5]1=[O:27].[OH-].[Na+].[C:36](OC(=O)C)(=[O:38])[CH3:37]>>[CH:24]([C:21]1[CH:20]=[CH:19][C:18]([C:7]2[C:8]3[C:13](=[CH:12][CH:11]=[C:10]([O:14][CH2:15][C:16]#[CH:17])[CH:9]=3)[N:4]([CH2:3][CH:2]([O:1][C:36](=[O:38])[CH3:37])[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:5](=[O:27])[N:6]=2)=[CH:23][CH:22]=1)([CH3:26])[CH3:25]
Reactant: C#CCOc1ccc2c(c1)c(-c1ccc(C(C)C)cc1)nc(=O)n2CC(O)c1ccccc1
Reactant: CC(=O)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Product: C#CCOc1ccc2c(c1)c(-c1ccc(C(C)C)cc1)nc(=O)n2CC(OC(C)=O)c1ccccc1

Procedure:
A solution of 100 mg (0.228 mmol) 1-(2-hydroxy-2-phenyl-ethyl)-4-(4-isopropyl-phenyl)-6-prop-2-ynyloxy-1H-quinazolin-2-one in 1 ml acetic anhydride is heated at 100° C. for 18 h. The reaction mixture is poured onto 1 M aqueous NaOH and extracted with ether. The product is purified by preparative reversed phase HPLC.
Reaction SMILES: [F:1][C:2]1[CH:18]=[CH:17][C:5]([CH:6]=[C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:16])[O:8]2)=[CH:4][C:3]=1[N+:19]([O-])=O.[Cl-].[NH4+]>[Fe].O>[NH2:19][C:3]1[CH:4]=[C:5]([CH:17]=[CH:18][C:2]=1[F:1])[CH:6]=[C:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9](=[O:16])[O:8]1
Reactant: O=C1OC(=Cc2ccc(F)c([N+](=O)[O-])c2)c2ccccc21
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Product: Nc1cc(C=C2OC(=O)c3ccccc32)ccc1F
Temperature: 70 °C

Procedure:
A stirred mixture of the above crude 3-(4-fluoro-3nitrobenzylidene)-3H-isobenzofuran-1-one (23.5 g), industrial methylated spirit (400 ml), water (300 ml) and ammonium chloride (8.81 g, 0.165 mol) was heated to 70° C., and iron powder (46.0 g, 0.824 gatom) was added in portions. When the addition was complete, the stirred mixture was heated at 70° C. for a further 2 hours, then it was filtered while hot through Celite. The collected inorganic solids were washed with hot industrial methylated spirit (6×200 ml), then the filtrate and washings were combined and the solvent was removed in vacuo. The residue was triturated with water (300 ml) and the resulting solid was collected by filtration and dried in vacuo for 24 hours to give crude 3-(3-amino-4-fluorobenzylidene)-3H-isobenzofuran-1-one as a yellow solid, m/z (M+H)+. 256, 100% purity, which was used directly in the next stage.
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([N+:10]([O-])=O)[C:3]=1[CH:4]=O.[CH3:13][Si:14]([CH3:21])([CH3:20])[C:15]#[C:16][CH2:17][CH2:18][NH2:19]>C1(C)C=CC=CC=1>[F:1][C:2]1[C:3]2[C:6]([CH:7]=[CH:8][CH:9]=1)=[N:10][N:19]([CH2:18][CH2:17][C:16]#[C:15][Si:14]([CH3:21])([CH3:20])[CH3:13])[CH:4]=2
Reactant: O=Cc1c(F)cccc1[N+](=O)[O-]
Reactant: C[Si](C)(C)C#CCCN
Solvent: Cc1ccccc1
Product: C[Si](C)(C)C#CCCn1cc2c(F)cccc2n1
Yield: 55.7 %

Procedure:
2-Fluoro-6-nitro-benzaldehyde (180 mg, 1.06 mmol) was added to a solution of 4-trimethylsilanyl-but-3-ynylamine (200 mg, 1.40 mmol) in toluene (2 mL) and the reaction mixture was stirred under reflux for 30 min in a Dean-Stark. After evaporation of the solvent, the crude product was dissolved in triethylphosphite (1 mL) and the reaction mixture was stirred at 80° C. for 4 hours. After evaporation, the crude product was purified by flash chromatography (cyclohexane/AcOEt 92.5:7.5) to yield 4-fluoro-2-(4-trimethylsilanyl-but-3-ynyl)-2H-indazole (142 mg, 0.59 mmol, 52%) as a yellow oil.