Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(N(CC)CC)C.[N:8]([C:11]1[CH:16]=[CH:15][N:14]=[CH:13][C:12]=1[CH:17]=O)=[N+:9]=[N-:10].[NH2:19][C:20]1[C:27]([Cl:28])=[CH:26][C:23]([C:24]#[N:25])=[CH:22][C:21]=1[Cl:29]>C(Cl)Cl.[Ti](Cl)(Cl)(Cl)Cl>[N:8]([C:11]1[CH:16]=[CH:15][N:14]=[CH:13][C:12]=1/[CH:17]=[N:19]/[C:20]1[C:21]([Cl:29])=[CH:22][C:23]([C:24]#[N:25])=[CH:26][C:27]=1[Cl:28])=[N+:9]=[N-:10]
Reactant: N#Cc1cc(Cl)c(N)c(Cl)c1
Reactant: [N-]=[N+]=Nc1ccncc1C=O
Agent: Cl[Ti](Cl)(Cl)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: N#Cc1cc(Cl)c(/N=C/c2cnccc2N=[N+]=[N-])c(Cl)c1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
Triethylamine (8.9 mL, 64.2 mmol) was added to a cooled (0° C.) mixture of 4-azidopyridine-3-carbaldehyde (3.2 g, 21.4 mmol) and 4-amino-3,5-dichlorobenzonitrile (4.0 g, 21.4 mmol) in DCM (80 mL) under nitrogen. Titanium tetrachloride (1M, 12.8 mL, 12.8 mmol) was added and then the reaction mixture was stirred for 1 hour at 0° C. After warming to room temperature, the reaction was stirred for an additional 2 h and then concentrated under reduced pressure. The residue was suspended in toluene and filtered though a pad of Celite®. The filtrate was concentrated to dryness under reduced pressure to afford the title compound as an orange solid. This crude material was employed in the next step without further purification or analysis.
Reaction SMILES: C([O:8][C:9]1[CH:25]=[CH:24][CH:23]=[C:22]([OH:26])[C:10]=1[C:11](=[O:21])[CH:12]=[CH:13][C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=1)C1C=CC=CC=1.CN(C)C=O.C(=O)([O-])[O-].[K+].[K+].Br[CH2:39][C:40]([O:42][CH3:43])=[O:41]>CC(C)=O.O>[OH:8][C:9]1[C:10]([C:11](=[O:21])[CH:12]=[CH:13][CH:14]2[CH:15]=[CH:16][C:17]([CH3:20])=[CH:18][CH2:19]2)=[C:22]([O:26][CH2:39][C:40]([O:42][CH3:43])=[O:41])[CH:23]=[CH:24][CH:25]=1
Reactant: COC(=O)CBr
Reactant: Cc1ccc(C=CC(=O)c2c(O)cccc2OCc2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CC(C)=O
Solvent: O
Product: COC(=O)COc1cccc(O)c1C(=O)C=CC1C=CC(C)=CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 2′-benzyloxy-6′-hydroxy-4-methylchalcone (0.69 g) in acetone (10 mL)-N,N-dimethylformamide (10 mL) were added potassium carbonate (0.41 g) and methyl bromoacetate (0.21 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water, and the resulting mixture was extracted with diethyl ether. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was dissolved in methanol (10 mL). To the solution was added 10% palladium-carbon powder (0.29 g), and the mixture was stirred at room temperature under a hydrogen atmosphere for 5 hours. Dichloromethane was added to the mixture, and the insoluble material was removed by filtration. The filtrate was concentrated under reduced pressure to give the title compound (0.58 g).
Reaction SMILES: [Cl:1][C:2]1[N:31]=[CH:30][C:5]2[N:6]=[C:7]([CH3:29])[N:8]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]4)=[CH:13][C:12]=3[O:27]C)[C:9](=[O:10])[C:4]=2[CH:3]=1.B(Br)(Br)Br.O>C(Cl)Cl>[Cl:1][C:2]1[N:31]=[CH:30][C:5]2[N:6]=[C:7]([CH3:29])[N:8]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH2:20][N:21]4[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]4)=[CH:13][C:12]=3[OH:27])[C:9](=[O:10])[C:4]=2[CH:3]=1
Reactant: COc1cc(OCCCN2CCCCC2)ccc1-n1c(C)nc2cnc(Cl)cc2c1=O
Agent: BrB(Br)Br
Solvent: O
Solvent: ClCCl
Product: Cc1nc2cnc(Cl)cc2c(=O)n1-c1ccc(OCCCN2CCCCC2)cc1O
Temperature: 25 °C
Reaction time: 15 h
Yield: 35.7 %

Procedure:
6-chloro-3-[2-methoxy-4-(3-piperidin-1-ylpropoxy)phenyl]-2-methylpyrido[3,4-d]pyrimidin-4(3H)-one synthesized in Example 184 (143 mg, 0.32 mmol) was dissolved in methylene chloride (3 mL), boron tribromide (1M methylene chloride solution, 3.2 mmol) was added on an ice bath, stirred at room temperature for 15 hours, and stirred at 40° C. for 3 hours. Saturated carbonated water was added to stop the reaction, the mixture was extracted with ethyl acetate, and dried with anhydrous sodium sulfate. The product was purified by silica gel column chromatography (chloroform/methanol=20/1), and the target compound (49 mg, 35%) was obtained as a light yellow solid.
Reaction SMILES: [CH3:1][N:2]([C:6]1[CH:25]=[CH:24][C:9]2[N:10]([CH2:17][CH:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[C:11]([C:13]([F:16])([F:15])[F:14])=[N:12][C:8]=2[CH:7]=1)C(=O)C>Cl>[CH3:1][NH:2][C:6]1[CH:25]=[CH:24][C:9]2[N:10]([CH2:17][CH:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[C:11]([C:13]([F:14])([F:15])[F:16])=[N:12][C:8]=2[CH:7]=1
Reactant: CC(=O)N(C)c1ccc2c(c1)nc(C(F)(F)F)n2CC1CCOCC1
Agent: Cl
Product: CNc1ccc2c(c1)nc(C(F)(F)F)n2CC1CCOCC1
Temperature: 95 °C
Yield: 99.9 %

Procedure:
N-Methyl-N-[1-(tetrahydro-2H-pyran-4-ylmethyl)-2-(trifluoromethyl)-1H-benzimidazol-5-yl]acetamide (3.18 g, 8.95 mmol) was dissolved in hydrochloric acid (37%, 60 mL) and then heated overnight at 95° C. After concentration, the residue was treated with 20 mL of 2N NaOH, extracted with EtOAc (4×50 mL). The combined organic phases were washed with brine (20 mL) and dried over Na2SO4. After evaporation, 2.80 g (100%) of a purple white solid was obtained as the title product, which was used directly for Step H. MS (ESI) (M+H)+=314.20.
Reaction SMILES: CN(C)N=[C:4]1[C:13]2[C:8](=[C:9]([O:14][CH3:15])[CH:10]=[CH:11][CH:12]=2)[CH2:7][CH2:6][CH:5]1[CH2:16][CH:17]([O:20]C)OC.P([O-])([O-])([O-])=[O:24].[Cl-].[NH4+].N>C1COCC1.O.O.[Cu](Cl)Cl>[O:20]=[CH:17][CH2:16][CH:5]1[CH2:6][CH2:7][C:8]2[C:13](=[CH:12][CH:11]=[CH:10][C:9]=2[O:14][CH3:15])[C:4]1=[O:24]
Reactant: COc1cccc2c1CCC(CC(OC)OC)C2=NN(C)C
Reactant: O=P([O-])([O-])[O-]
Agent: Cl[Cu]Cl
Agent: N
Agent: [Cl-]
Solvent: O
Solvent: C1CCOC1
Product: COc1cccc2c1CCC(CC=O)C2=O
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 80 %

Procedure:
280 mg of 2-(2,2-dimethoxy-1-ethyl)-5-methoxy-1-tetralone N,N-dimethylhydrazone were dissolved in 12.5 ml of THF and added to 5 ml of phosphate buffer (prepared from 2 ml of 1/15M potassium dihydrogen phosphate and 3 ml of 1/15M disodium hydrogen phosphate) as well as 156 mg of copper (II) chloride dihydrate. After stirring at room temperature for 3.5 hours, the reaction had finished. The mixture was treated with 10 ml of 20% ammonium chloride solution and 0.8 ml of conc ammonia. Then, the mixture was extracted several times with ethyl acetate, dried over sodium sulfate, filtered and evaporated. The residue was chromatographed on silica gel firstly with toluene, then with toluene/ethyl acetate 9:1. 180 mg (80%) of 2-(2-oxoethyl)-5-methoxy-1-tetralone were obtained as a yellowish oil (Rf=0.31, silica gel (toluene/ethyl acetate 9:1)).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9][C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=2)=[CH:5][CH:4]=1.[OH2:18].[OH2:19].O.O.O.O.C(O[O-])(=O)C1C(=CC=CC=1)C([O-])=O.[Mg+2].C(O)C>O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([S:9]([C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=2)(=[O:19])=[O:18])=[CH:7][CH:8]=1
Reactant: O
Reactant: COc1ccc(Sc2ccc(C#N)cc2)cc1
Agent: O=C([O-])c1ccccc1C(=O)O[O-]
Agent: [Mg+2]
Solvent: CCO
Product: COc1ccc(S(=O)(=O)c2ccc(C#N)cc2)cc1
Reaction time: 0.33 h
Yield: 76.7 %

Procedure:
6 g (0.0248 mol) of 4-[(4-methoxyphenyl)thio]benzonitrile and then 18.45 g of magnesium monoperoxyphthalate hexahydrate are added to a mixture of 120 ml of ethanol and 12 ml of water. The reaction medium is kept at 40° C. for 20 minutes. After hydrolysis in iced water, the solution is filtered and the white solid is washed with water. 5.2 g (yield: 77%) of the expected product are thus obtained.
Reaction SMILES: [N+:1]([O-:4])([O-])=[O:2].[K+].OS(O)(=O)=O.[F:11][C:12]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:13]=1[C:14]#[N:15]>>[F:11][C:12]1[CH:19]=[C:18]([F:20])[C:17]([N+:1]([O-:4])=[O:2])=[CH:16][C:13]=1[C:14]#[N:15]
Reactant: O=[N+]([O-])[O-]
Reactant: N#Cc1ccc(F)cc1F
Agent: O=S(=O)(O)O
Agent: [K+]
Product: N#Cc1cc([N+](=O)[O-])c(F)cc1F
Reaction time: 4 h
Yield: 94.8 %

Procedure:
Potassium nitrate (16.4 g, 147.4 mmol) was added to concentrated H2SO4 (85 ml, 1582 mmol) at 0° C., followed by slow addition of 2,4-difluorobenzonitrile (11.0 g, 79.1 mmol). The suspension was stirred at this temperature for an additional 4 hrs and quenched ice/water (800 ml). The resulting solid was collected by filtration and dried to give the title compound (13.8 g, 95%) as a white solid. NMR (400 MHz, CDCl3) 8.48 (m, 1H), 7.24 (m, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH2:23])[CH:11]=[CH:12][C:13]=1[O:14][CH2:15][CH2:16][N:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.[Cl:24][C:25]1[S:29][C:28]([C:30](O)=[O:31])=[CH:27][CH:26]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:23][C:30]([C:28]2[S:29][C:25]([Cl:24])=[CH:26][CH:27]=2)=[O:31])[CH:11]=[CH:12][C:13]=1[O:14][CH2:15][CH2:16][N:17]1[CH2:18][CH2:19][O:20][CH2:21][CH2:22]1
Reactant: Cn1ncc(Cl)c1-c1cc(N)ccc1OCCN1CCOCC1
Reactant: O=C(O)c1ccc(Cl)s1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: Cn1ncc(Cl)c1-c1cc(NC(=O)c2ccc(Cl)s2)ccc1OCCN1CCOCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 15.1 %

Procedure:
To a mixture of 3-(4-chloro-2-methyl-2H-pyrazol-3-yl)-4-(2-morpholin-4-yl-ethoxy)-phenylamine (0.100 g, 0.3 mmol), 5-chlorothiophene-2-carboxylic acid (0.049 g, 0.3 mmol), and HATU (0.114 g, 0.3 mmol) in DMF (4 mL), DIEA (0.157 mL, 0.9 mmol) was added, then the reaction mixture stirred at room temperature overnight. The crude product was purified by prep HPLC. The corresponding fractions were collected and lyophilized to give a TFA-salt of Compound 333 as a brown solid in 15.1% yield. LCMS m/z (%)=481.2 (M+H, 100). 1H NMR (400 MHz, DMSO-d6) δ: 10.41 (s, 1H), 9.95 (bs, 1H), 7.90-7.87 (m, 2H), 7.66 (s, 1H), 7.63 (d, J=2.6 Hz, 1H), 7.31-7.23 (m, 2H), 4.48-4.27 (m, 2H), 3.66 (s, 3H), 3.81-2.87 (m, 10H and water).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:13]([CH3:15])[CH3:14])[C:5]2[O:9][CH2:8][C:7]([CH3:11])([CH3:10])[C:6]=2[CH:12]=1.[CH2:16]([O:18][C:19](=[O:27])[C:20]1[CH:25]=[CH:24][C:23](I)=[CH:22][CH:21]=1)[CH3:17].C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:16]([O:18][C:19](=[O:27])[C:20]1[CH:25]=[CH:24][C:23]([NH:1][C:2]2[CH:3]=[C:4]([CH:13]([CH3:15])[CH3:14])[C:5]3[O:9][CH2:8][C:7]([CH3:10])([CH3:11])[C:6]=3[CH:12]=2)=[CH:22][CH:21]=1)[CH3:17]
Reactant: CCOC(=O)c1ccc(I)cc1
Reactant: CC(C)c1cc(N)cc2c1OCC2(C)C
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Product: CCOC(=O)c1ccc(Nc2cc(C(C)C)c3c(c2)C(C)(C)CO3)cc1
Yield: 60.5 %

Procedure:
Following general procedure E and using 5-amino-3,3-dimethyl-7-isopropyl-2,3-dihydrobenzofuran (Compound 13, 0.085 g, 0.5 mmol), ethyl-4-iodo-benzoate (0.123 g, 0.5 mmol), cesium carbonate (0.228 g, 0.7 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.020 g, 0.021 mmol) and (S)-(-)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.040 g, 0.064 mmol) in 2 mL of anhydrous toluene (reacted in a sealed tube), the title compound (0.107 g, 76%) was obtained. 1H NMR (300 MHz, CDCl3): δ 7.89(d, 2H, J=8.8 Hz), 6.85 (d, 1H, J=2.0 Hz), 6.80 (d, 1H, J=2.0 Hz), 6.78 (d, 2H, J=8.8 Hz), 5.84 (br s, 1H), 4.32 (q, 2H, J=7.2 Hz), 4.25 (s, 2H), 3.08 (heptet, 1H, J=6.9 Hz), 1.36 (t, 3H, J=7.2 Hz), 1.33 (s, 6H), 1.23 (d, 6H, J=6.9 Hz).
Reaction SMILES: Br[Mg][CH:3]1[CH2:6][CH2:5][CH2:4]1.Br[C:8]1[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=1>C1COCC1.[Zn+2].[Br-].[Br-].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH:3]1([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4]1
Reactant: Br[Mg]C1CCC1
Reactant: COC(=O)c1ccc(Br)cc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: [Br-]
Solvent: C1CCOC1
Product: COC(=O)c1ccc(C2CCC2)cc1
Temperature: -40 °C
Reaction time: 1 h

Procedure:
To a stirred mixture of ZnBr2 (83.0 g, 368.53 mmol, 4.00 equiv) in THF (500 mL) under nitrogen at 0° C. was added a solution of bromo(cyclobutyl)magnesium (242 mL, 364 mmol, 1.5 M in THF) dropwise during 20 min. To the resulting mixture were added Pd(dppf)Cl2 (2.00 g, 0.10 equiv) and methyl 4-bromobenzoate (20 g, 93.00 mmol, 1.00 equiv) at −40° C. The resulting mixture was stirred at −40° C. for 1 h under nitrogen, and then carefully quenched with 500 mL of NH4Cl(aq., sat.). The mixture was extracted with 3×500 mL of ethyl acetate. The combined organic layers were washed with 3×500 mL of brine, then dried over anhydrous sodium sulfate, and concentrated under reduced pressure to yield 18.0 g (crude) of the title compound as a light yellow oil.
Reaction SMILES: C([O:3][C:4]([C:6]1[N:7]=[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[O:9][CH:10]=1)=[O:5])C.[OH-].[Na+]>C1COCC1.CO.CCOC(C)=O>[C:11]1([C:8]2[O:9][CH:10]=[C:6]([C:4]([OH:5])=[O:3])[N:7]=2)[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: CCOC(=O)c1coc(-c2ccccc2)n1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: O=C(O)c1coc(-c2ccccc2)n1
Reaction time: 2 h
Yield: 84.1 %

Procedure:
2-Phenyl-oxazole-4-carboxylic acid ethyl ester (500 mg, 2.30 mmol) was dissolved in a mixture of THF (2.3 mL) and MeOH (2.3 mL). To this was added NaOH (10% aqueous, 2.3 mL). The reaction mixture was stirred for 2 h, and was then diluted with EtOAc and washed with 1N HCl The aqueous layer was extracted with EtOAc and the combined organics were dried over Na2SO4, filtered and concentrated to give the product as a white solid (366 mg, 84%).
Reaction SMILES: C(=O)([O-])O.[Na+].[CH2:6]([OH:14])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13].[C:15](OC=C)(=[O:17])[CH3:16].C(OCCCCCCCC)=C>C1(C)C=CC=CC=1>[C:15]([O:14][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])(=[O:17])[CH3:16]
Reactant: CCCCCCCCO
Reactant: C=COC(C)=O
Agent: C=COCCCCCCCC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CCCCCCCCOC(C)=O
Temperature: 100 °C
Reaction time: 2 h

Procedure:
To a mixture of di-μ-chlorobis(1,5-cyclooctadiene)diiridium(I) [Ir(cod)Cl]2 (0.01 mmol) and sodium hydrogencarbonate (1.2 mmol) in toluene (1.0 ml), 1-octanol (130 mg, 1 mmol) and vinyl acetate (2 mmol) were added, followed by stirring at 100° C. in an atmosphere of argon gas for 2 hours. The reaction mixture was analyzed by gas chromatography to find that 1-octyl vinyl ether and octyl acetate were produced in yields of 93% and 2%, respectively, with a conversion from 1-octanol of 99%.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:14]2[NH:15][C:16]3[C:28]4[NH:27][C:26]5[C:21](=[CH:22][CH:23]=[CH:24][C:25]=5[O:29][CH2:30][C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=5)[C:20]=4[C:19]4[C:37](=[O:41])[NH:38][C:39](=[O:40])[C:18]=4[C:17]=3[C:13]=2[CH:12]=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH2:44]([O:51][CH2:52]Cl)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1>CN(C=O)C.O>[CH2:44]([O:51][CH2:52][N:38]1[C:39](=[O:40])[C:18]2[C:17]3[C:13]4[C:14](=[C:9]([O:8][CH2:1][C:2]5[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=5)[CH:10]=[CH:11][CH:12]=4)[NH:15][C:16]=3[C:28]3[NH:27][C:26]4[C:25]([O:29][CH2:30][C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=5)=[CH:24][CH:23]=[CH:22][C:21]=4[C:20]=3[C:19]=2[C:37]1=[O:41])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1
Reactant: ClCOCc1ccccc1
Reactant: O=C1NC(=O)c2c1c1c3cccc(OCc4ccccc4)c3[nH]c1c1[nH]c3c(OCc4ccccc4)cccc3c21
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C1c2c(c3c4cccc(OCc5ccccc5)c4[nH]c3c3[nH]c4c(OCc5ccccc5)cccc4c23)C(=O)N1COCc1ccccc1
Yield: 61.7 %

Procedure:
143.8 mg of 1,11-dibenzyloxy-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione was dissolved in 50 ml of DMF, 128.8 mg of 60% oily sodium hydride (NaH) was added, 36.5 μl of benzyloxymethyl chloride was gradually added under ice cooling over a period of 10 minutes, and the mixture was subjected to reaction at 0° C. for further 1 hour. The reaction solution was diluted with water and extracted with ethyl acetate, the ethyl acetate layer was dried over sodium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (Kiezel gel 60; eluted with chloroform) to give the desired 6-benzyloxymethyl-1,11-dibenzyloxy-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione (yield: 61.7%).
Reaction SMILES: [CH3:1][NH:2][C:3]([NH:5][CH3:6])=[O:4].Cl[Si:8]([CH3:11])([CH3:10])[CH3:9]>C(N(CC)CC)C>[CH3:9][Si:8]([CH3:11])([CH3:10])[N:2]([CH3:1])[C:3]([N:5]([Si:8]([CH3:11])([CH3:10])[CH3:9])[CH3:6])=[O:4]
Reactant: CNC(=O)NC
Reactant: C[Si](C)(C)Cl
Solvent: CCN(CC)CC
Product: CN(C(=O)N(C)[Si](C)(C)C)[Si](C)(C)C
Reaction time: 0.08 h

Procedure:
1,3-dimethylurea (44.0 g, 0.5 mole) and triethylamine (250 mls) were charged to a stirred reaction vessel purged with dry nitrogen. The mixture was stirred for 5 minutes and then chlorotrimethylsilane (167.5 mls, 1.32 moles) was added resulting in the formation of a white precipitate. The resulting reaction mixture was stirred for a further 24 hours at ambient temperature after which it was filtered under a nitrogen atmosphere. The filter cake was washed with dry toluene and the combined organics filtrate was distilled at atmospheric pressure under a nitrogen atmosphere. The residual organics were subjected to fractional distillation at a pressure of 8 mmHg. The fraction distilling at 86° to 88° C. was the required initiator.
Reaction SMILES: O.[CH:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([C:12]([OH:14])=O)[N:3]=1.Cl.[CH3:16][O:17][NH:18][CH3:19].C(N(CC)CC)C.O.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>C(#N)C>[CH3:16][O:17][N:18]([CH3:19])[C:12]([C:4]1[N:3]=[CH:2][C:11]2[C:6]([CH:5]=1)=[CH:7][CH:8]=[CH:9][CH:10]=2)=[O:14]
Reactant: CNOC
Reactant: O=C(O)c1cc2ccccc2cn1
Agent: COc1nc(OC)nc([N+]2(C)CCOCC2)n1
Agent: Cl
Agent: [Cl-]
Solvent: CC#N
Solvent: O
Solvent: CCN(CC)CC
Product: CON(C)C(=O)c1cc2ccccc2cn1
Reaction time: 48 h
Yield: 37.4 %

Procedure:
In 50 mL of acetonitrile was dissolved 0.49 g (2.60 mmol) of isoquinoline-3-carboxylic acid monohydrate. To this 0.28 g (2.87 mmol) of O,N-dimethyl-hydroxylamine hydrochloride, 0.4 mL (2.87 mmol) triethylamine and 0.921 g (3.13 mmol) of 4-(4,6-dimethoxy-[1,3,5]triazin-2-yl)-4-methyl-morpholin-4-ium chloride hydrate were added and stirred for 2 days and then evaporated. A mixture of dichloromethane and water was added to it and the organic layer was evaporated and purified using flash chromatography (0-20% methanol in dichloromethane). Fractions containing pure product were evaporated to yield 210 mg of the free base as a white solid. LC-MSD, m/z for C12H12N2O2 [M+H]+: 217.4, [M+Na]+: 239.4
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]([S:13]([CH3:15])=[O:14])=[CH:9][C:4]=1[C:5]([O:7]C)=[O:6].[OH-].[K+].Cl>ClCCl>[CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]([S:13]([CH3:15])=[O:14])=[CH:9][C:4]=1[C:5]([OH:7])=[O:6]
Reactant: COC(=O)c1cc(S(C)=O)ccc1OC
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: ClCCl
Product: COc1ccc(S(C)=O)cc1C(=O)O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Combine methyl 2-methoxy-5-methylsulfinylbenzoate (2.37 g, 12.0 mmol) and a 1 M aqueous solution of potassium hydroxide (13 mL, 13 mmol). Heat to reflux. After 2 hours, cool to ambient temperature and adjust the pH to about 2 using a 1 M aqueous hydrochloric acid (14.5 mL, 14.5 mmol). Evaporate in vacuo to give a solid. Combine the solid and dichloromethane and stir. Decant the solvent and add more dicliloromethane. Again decant and combine with the first decantate, dry over Na2SO4, filter, and evaporate in vacuo to to give the title compound: mp; 114-116° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1Cl.[C:10]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)(=[O:13])[CH2:11][CH3:12].C(O[Na])(C)(C)C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.COC1C=CC=C(N(C)C2C=CC=CC=2)C=1P(C1CCCCC1)C1CCCCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH:11]([CH3:12])[C:10]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:13]
Reactant: CCC(=O)c1ccccc1
Reactant: COc1ccccc1Cl
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)O[Na]
Solvent: Cc1ccccc1
Product: COc1ccccc1C(C)C(=O)c1ccccc1
Yield: 82.7 %

Procedure:
This reaction is carried out in the same manner as the reaction in example 3. The difference is that, the reactants are o-methoxyphenyl chloride (144.1 mg, 1.0 mmol), propiophenon (161.3 mg, 1.2 mmol), palladium acetate (6.7 mg, 0.030 mmol), 2-Methoxy-6-(N-methyl-N-phenyl-amino)phenyl(dicyclohexyl)phosphine (18.4 mg, 0.045 mmol), t-BuONa (115.5 mg, 1.2 mmol) in 3 mL dry toluene at 110° C. for 16 h. 2-(2′-Methoxyphenyl)-1-phenyl-1-propanone (198.8 mg) was obtained with a yield of 80% as liquid. 1H NMR (300 MHz, CDCl3) δ 8.04-7.98 (m, 2H, ArH), 7.50-7.42 (m, 1H, ArH), 7.41-7.33 (m, 2H, ArH), 7.24-7.13 (m, 2H, ArH), 6.92-6.86 (m, 2H, ArH), 5.13 (q, J=6.9 Hz, 1H, CH), 3.87 (s, 3H, OCH3), 1.51 (d, J=6.9 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 201.2, 155.6, 136.4, 132.4, 130.0, 128.4, 128.2, 127.9, 120.9, 110.7, 55.3, 40.2, 17.5; IR (neat) v (cm−1) 3063, 2974, 2933, 2871, 2837, 1682, 1597, 1584, 1493, 1449, 1371, 1326, 1291, 1245, 1222, 1182, 1113, 1061, 1050, 1028, 1002; MS (70 eV, EI) m/z (%): 241 (M++1, 1.81), 240 (M+, 9.60), 135 (100).
Reaction SMILES: [N:1]1([CH2:6][CH2:7][OH:8])[CH:5]=[CH:4][N:3]=[CH:2]1.[C:9](OC(=O)C)(=[O:11])[CH3:10]>>[C:9]([O:8][CH2:7][CH2:6][N:1]1[CH:5]=[CH:4][N:3]=[CH:2]1)(=[O:11])[CH3:10]
Reactant: OCCn1ccnc1
Reactant: CC(=O)OC(C)=O
Product: CC(=O)OCCn1ccnc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 85.1 %

Procedure:
In a nitrogen atmosphere, a mixture of 112 g of 2-(1H-imidazol-1-yl)ethanol, synthesized in Synthesis Example 1, and 122 g of acetic anhydride was stirred at room temperature for 16 hours. The reaction mixture was subjected to conventional aqueous work-up and then purified by vacuum distillation, obtaining 131 g of 2-(1H-imidazol-1-yl)ethyl acetate (boiling point 102° C./27 Pa, yield 85%).
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:5]=[CH:6][C:7]2[O:11][C:10](=[O:12])[NH:9][C:8]=2[CH:13]=1.[CH3:14][O:15][C:16](=[O:25])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]Br>CN(C=O)C>[CH3:14][O:15][C:16](=[O:25])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][N:9]1[C:8]2[CH:13]=[C:4]([Cl:3])[CH:5]=[CH:6][C:7]=2[O:11][C:10]1=[O:12]
Reactant: O=c1[nH]c2cc(Cl)ccc2o1
Reactant: COC(=O)CCCCCCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)CCCCCCCn1c(=O)oc2ccc(Cl)cc21

Procedure:
The product is produced as described in example 1 from 3 g. of NaH (80% suspension in mineral oil), 17 g. of 5-chloro-benzoxazolin-2-one (produced in usual manners by subjecting 2-amino-4-chloro-phenol-hydrochloride to reaction with phosgene), 200 cc. of DMF, 23.7 g. of 8-bromo-caprylic acid methyl ester and 3 g. of NaJ.