Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH2:8][N:9]2[C:21]3[CH:20]=[CH:19][CH:18]=[C:17]([OH:22])[C:16]=3[C:15]3[C:10]2=[CH:11][CH:12]=[CH:13][C:14]=3[C:23]([O:25]C)=O)[CH:5]=[CH:6][CH:7]=1.Cl.[OH-].[NH4+:29]>C1COCC1.C(OCC)(=O)C>[CH3:1][C:2]1[CH:3]=[C:4]([CH2:8][N:9]2[C:21]3[CH:20]=[CH:19][CH:18]=[C:17]([OH:22])[C:16]=3[C:15]3[C:10]2=[CH:11][CH:12]=[CH:13][C:14]=3[C:23](=[O:25])[NH2:29])[CH:5]=[CH:6][CH:7]=1
Reactant: [NH4+]
Reactant: COC(=O)c1cccc2c1c1c(O)cccc1n2Cc1cccc(C)c1
Agent: Cl
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Cc1cccc(Cn2c3cccc(O)c3c3c(C(N)=O)cccc32)c1
Yield: 40 %

Procedure:
A solution of the 9-[(3-methylphenyl)methyl]-4-hydroxy-5-carbomethoxy carbazole (300 mg, 0.87 mM) in 10 mL THF and 30 mL concentrated aqueous ammonium hydroxide was sonicated for 5 hours at 40-50° C. The mixture was diluted with ethyl acetate and acidified to pH 1 with 5 N HCl. The aqueous layer was extracted three times with ethyl acetate. The combined organic extracts were washed with H2O and saturated brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by column chromatography on silica gel (elution with gradient hexanes/ethyl acetate) to afford 114 mg (40%) of the 9-[(3-methylphenyl)methyl]-4-hydroxy-5-carbamoyl carbazole as an off-white solid. 1H NMR (DMSO-d6) δ 10.5 (s, 1H), 8.8 (br s, 1H), 8.4 (br s, 1H), 7.8 (dd, 1H, J=1 and 8 Hz), 7.4 (m, 2H), 7.3 (t, 1H, J=8 Hz), 7.15-7.0 (m, 3H), 6.85 (d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), 5.95 (d, 1H, J=8 Hz), 5.65 (s, 2H), and 2.25 (s, 3H). IR (KBr, cm−1) 3434, 3203, 1629, 1599, 1579, 1552, 1443, 1330, 1262, 1214, and 776. MS (ES) m/e 329, 331.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][C:5]1([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[F:17])[O:9][CH2:8][CH2:7][O:6]1.[O:18]=[C:19]1[C:23]2([CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[N:22]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:21][NH:20]1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[O:18]=[C:19]1[C:23]2([CH2:24][CH2:25][N:26]([CH2:2][CH2:3][CH2:4][C:5]3([C:10]4[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=4[F:17])[O:9][CH2:8][CH2:7][O:6]3)[CH2:27][CH2:28]2)[N:22]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:21][NH:20]1
Reactant: O=C1NCN(c2ccccc2)C12CCNCC2
Reactant: Fc1ccc(C2(CCCCl)OCCO2)c(F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: O=C1NCN(c2ccccc2)C12CCN(CCCC1(c3ccc(F)cc3F)OCCO1)CC2

Procedure:
A mixture of 4-chloro-1-(2,4-difluorophenyl)-1,1-ethylenedioxybutane (5.3 g), 4-oxo-1-phenyl-1,3,8-triazaspiro[4,5]decane (4.6 g), anhydrous potassium carbonate (0.1 g) and dimethylformamide (58 ml) was heated under refluxing for 2.5 hours. After cooling, the reaction mixture was poured into cold water (400 ml) with vigorous stirring, and the precipitate was collected and washed with water to yield 4-(4-oxo-1-phenyl-1,3,8-triazaspiro[4,5]decan-8-yl)-1-(2,4-difluorophenyl)-1,1-ethylenedioxybutane. M.P. 58° - 62°C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH2:12][CH:13]([CH3:15])[CH3:14])[C:6]([CH2:16][N:17]1C(=O)C3C(=CC=CC=3)C1=O)=[C:5]2[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.O.NN>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH2:12][CH:13]([CH3:15])[CH3:14])[C:6]([CH2:16][NH2:17])=[C:5]2[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: CC(C)Cc1nc2ccc(Cl)cc2c(-c2ccccc2)c1CN1C(=O)c2ccccc2C1=O
Agent: NN
Solvent: O
Solvent: CCO
Product: CC(C)Cc1nc2ccc(Cl)cc2c(-c2ccccc2)c1CN
Yield: 73 %

Procedure:
To a solution of 2-[(6-chloro-2-isobutyl-4-phenylquinolin-3-yl)methyl]-1H-isoindole-1,3(2H)-dione (0.54 g, 1.18 mmol) in ethanol (50 ml), being-heated under reflux, was added hydrazine monohydrate (3 ml, 62 mmol), and the mixture was heated under reflux for 2 hrs. The reaction mixture was partitioned between ethyl acetate (100 ml) and saturated aqueous sodium hydrogen carbonate (50 ml)-water (100 ml). The organic layer was washed with saturated aqueous sodium hydrogen carbonate (50 ml) and then saturated brine (20 ml), and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel column chromatography, and crystallized from n-hexane to give the title compound (0.28 g, yield 73%) as pale-yellow crystals.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([O:14][C:15]([F:18])([F:17])[F:16])[C:11]=1[O:12][CH3:13])[C:6](O)=[O:7])#[N:2].C1(C)C=CC=CC=1.S(Cl)([Cl:28])=O>CN(C)C=O>[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([O:14][C:15]([F:18])([F:17])[F:16])[C:11]=1[O:12][CH3:13])[C:6]([Cl:28])=[O:7])#[N:2]
Reactant: COc1c(C#N)cc(C(=O)O)cc1OC(F)(F)F
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: COc1c(C#N)cc(C(=O)Cl)cc1OC(F)(F)F
Temperature: 60 °C
Reaction time: 6 h

Procedure:
To 3-cyano-4-methoxy-5-trifluoromethoxybenzoic acid (500 mg), toluene (10 mL), N,N-dimethylformamide (3 droplets) and thionyl chloride (0.28 mL) were added, and then the mixture was stirred at 60° C. for 6 hours. The solvent was distilled off under reduced pressure and the obtained residue was azeotroped with toluene and used for the synthesis of (i).
Reaction SMILES: [Cl:1][C:2]1[N:6]([CH3:7])[N:5]=[CH:4][C:3]=1/[CH:8]=[N:9]/[S@@:10]([C:12]([CH3:15])([CH3:14])[CH3:13])=[O:11].[CH3:16][Mg]Br.[Cl-].[NH4+]>ClCCl>[Cl:1][C:2]1[N:6]([CH3:7])[N:5]=[CH:4][C:3]=1[C@@H:8]([NH:9][S@@:10]([C:12]([CH3:15])([CH3:14])[CH3:13])=[O:11])[CH3:16]
Reactant: Cn1ncc(/C=N/[S@](=O)C(C)(C)C)c1Cl
Reactant: C[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: ClCCl
Product: C[C@H](N[S@](=O)C(C)(C)C)c1cnn(C)c1Cl
Temperature: -78 °C
Reaction time: 8 h
Yield: 53.5 %

Procedure:
(R,E)-N-((5-chloro-1-methyl-1H-pyrazol-4-yl)methylene)-2-methylpropane-2-sulfinamide (100 mg, 0.404 mmol) was dissolved in dichloromethane (10 ml) placed under nitrogen and cooled to −78° C. 1.4M methyl magnesium bromide solution (toluene:THF 3:1, 1.04 ml, 1.45 mmol) was added dropwise and reaction stirred overnight while warming to room temperature. Saturated aqueous ammonium chloride solution (20 ml) was added to the reaction and stirred for 5 minutes. The product was extracted with EtOAc (2×15 ml), combined organics were washed with brine (15 ml), dried over Na2SO4, filtered and concentrated and purified by silica gel column chromatography eluted with heptane/ethyl acetate=100/0 to 0/100 to furnish the title product as a clear gum (57 mg, 53% yield). 1H NMR (400 MHz, CD3OD) 1.18-1.19 (9H s) 1.54-1.56 (3H d) 3.81-3.82 (3H s) 4.41-4.47 (1H q) 7.50-7.51 (1H s) MS (ESI) m/z 264 (M+H)+
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8]#[C:9][CH2:10][C:11]#[C:12][CH2:13][CH:14]=[C:15]([CH3:21])[CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].N1C=CC=CC=1.[H][H]>[Pd].O>[Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH:8]=[CH:9][CH2:10][CH:11]=[CH:12][CH2:13][CH:14]=[C:15]([CH3:21])[CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]
Reactant: CCCCCC(C)=CCC#CCC#CCCCCCCCl
Reactant: [H][H]
Agent: [Pd]
Solvent: O
Solvent: c1ccncc1
Product: CCCCCC(C)=CCC=CCC=CCCCCCCCl

Procedure:
A mixture of 11.0 g. of 1-chloro-14-methyl-nonadeca-7,10-diyn-13-ene, 1.5 g. of 5% palladium on barium sulfate, and 80 ml. of pyridine was shaken in a Parr rocker under 40 lb. of hydrogen pressure for about 1.3 hrs., at which time two moles of hydrogen had been absorbed. The reaction mixture was then poured into water and extracted with ether. The extract was washed with water, dilute hydrochloric acid, saturated aqueous sodium chloride, dried over sodium sulfate, and evaporated leaving a residue comprising 1-chloro-14-methyl-7,10,13-nonadecatriene. The residue was distilled in a rocking short-path distillation apparatus, collecting 7.6 g. of a mixture comprising 1-chloro-14-methyl-7,10,13-nonadecatriene at a bath temperature of 180°C. and a pressure of 0.005 mm.
Reaction SMILES: [OH:1][CH2:2][C@@H:3]1[CH2:11][N:6]2[CH2:7][CH2:8][NH:9][CH2:10][C@@H:5]2[CH2:4]1.F[C:13]1[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][CH:14]=1.C(=O)([O-])[O-].[Na+].[Na+]>CS(C)=O.O>[OH:1][CH2:2][C@@H:3]1[CH2:11][N:6]2[CH2:7][CH2:8][N:9]([C:13]3[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][CH:14]=3)[CH2:10][C@@H:5]2[CH2:4]1
Reactant: N#Cc1ccc(F)cc1
Reactant: OC[C@H]1C[C@H]2CNCCN2C1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: N#Cc1ccc(N2CCN3C[C@@H](CO)C[C@H]3C2)cc1
Temperature: 80 °C
Yield: 37.4 %

Procedure:
A mixture of 1.5 g (9.6 mmol) of (7S,8aS)-7-hydroxymethyl-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine (Preparation 13, Step A), 1.75 g (14.4 mmol) of 4-fluorobenzonitrile and 2.04 g (19.2 mmol) of sodium carbonate in 10 mL of DMSO was heated at 80° C. for 16 h. The solution was cooled to room temperature, diluted with water and extracted with 1:1 ethyl acetate:diethyl ether (3×). The combined organic phase was dried (magnesium sulfate), filtered and evaporated. Purification by flash silica gel chromatography with 9:1 chloroform: methanol gave 0.925 g (37%) of the title compound. 13C NMR (CDCl3): δ 31.1, 37.2, 46.7, 51.0, 51.8, 57.6, 62.3, 67.3, 100.1, 114.3, 120.0, 133.5, 153.4. m/z (MH+) 258.
Reaction SMILES: [CH3:1][C:2]([CH3:19])([CH3:18])[C:3]#[C:4][C:5]1[C:10]([F:11])=[CH:9][CH:8]=[CH:7][C:6]=1[NH:12]C(=O)CCC.CC([O-])(C)C.[K+].O>CN(C=O)C>[C:2]([C:3]1[NH:12][C:6]2[C:5]([CH:4]=1)=[C:10]([F:11])[CH:9]=[CH:8][CH:7]=2)([CH3:19])([CH3:18])[CH3:1]
Reactant: CCCC(=O)Nc1cccc(F)c1C#CC(C)(C)C
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)c1cc2c(F)cccc2[nH]1
Temperature: 90 °C
Yield: 151.6 %

Procedure:
To a solution of N-(2-(3,3-dimethylbut-1-ynyl)-3-fluorophenyl)butyramide (6.0 g, 20 mmol) in DMF (100 mL) was added t-BuOK (5.0 g, 50 mmol) at room temperature. The mixture was heated at 90° C. overnight before it was poured into water and extracted with EtOAc (100 mL×3). The organic layers were washed with sat. NaCl and water, dried over anhydrous Na2SO4, and evaporated under vacuum to give 2-tert-butyl-4-fluoro-1H-indole (5.8 g, 97%). 1H NMR (400 MHz, CDCl3) δ 8.17 (br s, 1 H), 7.11 (d, J=7.2 Hz, 1 H), 7.05-6.99 (m, 1 H), 6.76-6.71 (m, 1 H), 6.34 (m, 1 H), 1.41 (s, 9 H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([F:13])[C@H:9]1[C:14]([OH:16])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:17][C:18]1[C:19]([F:26])=[C:20]([CH:23]=[CH:24][CH:25]=1)[CH2:21][NH2:22].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([F:13])[C@H:9]1[C:14](=[O:16])[NH:22][CH2:21][C:20]1[CH:23]=[CH:24][CH:25]=[C:18]([Cl:17])[C:19]=1[F:26])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: NCc1cccc(Cl)c1F
Reactant: CC(C)(C)OC(=O)N1CC[C@@H](F)[C@H]1C(=O)O
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N1CC[C@@H](F)[C@H]1C(=O)NCc1cccc(Cl)c1F
Reaction time: 20 h

Procedure:
To a solution of (2R,3R)-3-fluoro-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (45.0 mg, 0.193 mmol) in CH2Cl2 (5 mL) were added successively 3-chloro-2-fluorobenzylamine (0.024 mL, 0.193 mmol), HBTU (110 mg, 0.289 mmol) and DIPEA (0.067 mL, 0.386 mmol), and stirring was continued at RT for 20 h. The reaction mixture was then diluted with CH2Cl2, and the organics were washed with 0.1N aqueous HCl (2×), aqueous NaHCO3 (2×) and brine (1×), dried (Phase separator) and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (eluent: EtOAc/c-hexane gradient 1:4 to 1:3) to afford the title compound. TLC Rf (EtOAc/c-hexane 1:1)=0.31; MS (LC/MS): 397 [M+Na]+, 319 [MH−tBu]+, 275 [MH−Boc]+; tR (HPLC conditions b): 4.37 min.
Reaction SMILES: O.[CH2:2]([O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[C:16]([CH:18]=O)=O)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:20][CH:21]([NH2:35])[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([O:31][CH3:32])[C:24]=1[O:33][CH3:34].C([O:43]C1C=CC=CC=1C(C=O)=O)C1C=CC=CC=1>CS(C)=O>[CH3:20][CH:21]([N:35]=[C:10]([O:9][CH2:2][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1)[C:15]([C:14]1[CH:13]=[CH:12][CH:11]=[CH:16][CH:18]=1)=[O:43])[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([O:31][CH3:32])[C:24]=1[O:33][CH3:34]
Reactant: COc1ccc(CC(C)N)c(OC)c1OC
Reactant: O=CC(=O)c1ccccc1OCc1ccccc1
Solvent: CS(C)=O
Solvent: O
Product: COc1ccc(CC(C)N=C(OCc2ccccc2)C(=O)c2ccccc2)c(OC)c1OC
Temperature: 20 °C
Reaction time: 2 h

Procedure:
10.3 g of 2-benzyloxyphenylglyoxal hydrate are dissolved in 5 ml of dimethylsulfoxide. 7.6 g of α-methyl-2,3,4-trimethoxyphenethylamine are dissolved in 6 ml of dimethylsulfoxide, and the solution is added to the 2-benzyloxyphenylglyoxal solution under ice-cooling. The mixture is stirred at 20° C. for 2 hours, whereby a solution of α-(α-methyl-2,3,4-trimethoxyphenethylimino)-2-benzyloxyacetophenone in dimethylsulfoxide is obtained.
Reaction SMILES: C(OC([N:11]1[CH2:16][CH2:15][N:14]([CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:13](=[O:25])[CH2:12]1)=O)C1C=CC=CC=1.[H][H]>CO.C(O)(=O)C.[Pd]>[C:21]([O:20][C:18](=[O:19])[CH2:17][N:14]1[CH2:15][CH2:16][NH:11][CH2:12][C:13]1=[O:25])([CH3:24])([CH3:22])[CH3:23]
Reactant: [H][H]
Reactant: CC(C)(C)OC(=O)CN1CCN(C(=O)OCc2ccccc2)CC1=O
Agent: [Pd]
Solvent: CO
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)CN1CCNCC1=O
Yield: 99 %

Procedure:
4-tert-Butoxycarbonylmethyl-3-oxopiperazine-1-carboxylic acid benzyl ester (2.0 g, 5.75 mmol) is dissolved in 20 mL of methanol and 2 mL of acetic acid. Palladium (5%) on carbon (100 mg) is added, and the reaction mixture is stirred in an atmosphere of hydrogen overnight. The mixture is filtered and concentrated. Ethyl acetate is added, and the mixture is neutralized to pH 7 using 1N NaOH. The organic layer is concentrated to give (2-oxo-piperazin-1-yl)acetic acid tert-butyl ester (1.22 g).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][N:3]=1.[Br:9]Br>C(O)(=O)C>[NH2:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([Br:9])=[CH:4][N:3]=1
Reactant: BrBr
Reactant: Cc1ccnc(N)c1
Solvent: CC(=O)O
Product: Cc1cc(N)ncc1Br
Temperature: 17.5 °C

Procedure:
To a solution of 2-amino-4-picoline (20 g, 0.185 mol) in glacial acetic acid (185 mL) was added bromine (12.5 mL, 0.243 mol) dropwise with stirring while maintaining the internal temperature between 15-20° C. by cooling in an ice bath. After the addition was completed, the reaction was stirred for 1 h. The resulting solid was filtered, washed with water, and treated with dilute aqueous sodium hydroxide. The remaining white solid was filtered, washed with water and then hexane. Recrystallization from diethyl ether-cyclohexane afforded the title compound; yield 8.1 g (23%).
Reaction SMILES: I.[S:2]1[C:6]2[CH2:7][C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=3[C:5]=2[N:4]=[C:3]1[NH2:14].[CH3:15][C:16]1[CH:24]=[CH:23][C:19]([C:20](Cl)=[O:21])=[CH:18][CH:17]=1>>[S:2]1[C:6]2[CH2:7][C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=3[C:5]=2[N:4]=[C:3]1[NH:14][C:20](=[O:21])[C:19]1[CH:23]=[CH:24][C:16]([CH3:15])=[CH:17][CH:18]=1
Reactant: Nc1nc2c(s1)Cc1ccccc1-2
Reactant: Cc1ccc(C(=O)Cl)cc1
Agent: I
Product: Cc1ccc(C(=O)Nc2nc3c(s2)Cc2ccccc2-3)cc1
Yield: 25.5 %

Procedure:
Acylation of 8H-Indeno[1,2-d]thiazol-2-ylamine hydroiodide 1a (Prepared in Example 1, Step 1, 100 mg; 0.32 mmol) with 4-methylbenzoyl chloride (0.0.130 mL; 0.96 mmol) in a manner similar to that described in Example 1, Step 3 provided 25 mg of N-(8H-Indeno[1,2-d]thiazol-2-yl)-4-methyl-benzamide 5. EI-HRMS m/e calcd for C16H11N3OS (M+) 293.0623, found 293.0621.
Reaction SMILES: [NH2:1][C:2]1[N:3]=[CH:4][C:5]2[S:10][C:9](=[O:11])[N:8]([C@@H:12]3[O:24][C@H:23]([CH2:25][O:26]C(=O)C)[C@@H:18]([O:19]C(=O)C)[C@H:13]3[O:14]C(=O)C)[C:6]=2[N:7]=1.N1C=CN=C1.[Si:35](Cl)([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36]>CN(C=O)C>[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[S:10][C:9](=[O:11])[N:8]([C@@H:12]3[O:24][C@H:23]([CH2:25][O:26][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])[C@@H:18]([OH:19])[C@H:13]3[OH:14])[C:6]=2[N:7]=1
Reactant: CC(=O)OC[C@H]1O[C@@H](n2c(=O)sc3cnc(N)nc32)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OC[C@H]1O[C@@H](n2c(=O)sc3cnc(N)nc32)[C@H](O)[C@@H]1O
Temperature: 25 °C
Reaction time: 2 h
Yield: 51.8 %

Procedure:
To a solution of 79 (0.68 g, 2.28 mmol) in DMF (10 mL) was added imidazole (0.54 g, 7.93 mmol) and tert-butyldimethylsilyl chloride (0.68 g, 4.56 mmol) sequentially. The reaction mixture was stirred at room temperature for 2 h, at which point it was concentrated and purified by flash column chromatography (silica, MeOH/CHCl3; gradient=5-20%) to afford 0.49 g (52%) 87 as a white solid: 1H (400 MHz, d6-DMSO) δ 8.33 (s, 1H), 6.87 (s, 2H), 5.90 (d, J=4.0 Hz, 1H), 5.33 (d, J=5.6 Hz, 1H), 5.00 (d, J=5.2 Hz, 1H), 4.79 (q, J=5.2 Hz, 1H), 4.16 (q, J=5.2 Hz, 1H), 3.77 (m, 2H), 3.64 (dd, J=12.0, 7.2 Hz, 1H), 0.84 (s, 9H), 0.00 (s, 6H); MS (+)-ES [M+H]+ m/z 415.4.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:17]3[C:16]([NH:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]#[N:26])=[N:15][CH:14]=[N:13][C:12]=3[O:11][C:10]=2[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:5][CH:4]=1.C[Si]([N:37]=[N+:38]=[N-:39])(C)C.C([Sn](=O)CCCC)CCC>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[C:17]3[C:16]([NH:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]4[NH:39][N:38]=[N:37][N:26]=4)=[N:15][CH:14]=[N:13][C:12]=3[O:11][C:10]=2[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)=[CH:7][CH:8]=1
Reactant: C[Si](C)(C)N=[N+]=[N-]
Reactant: COc1ccc(-c2c(-c3ccccc3)oc3ncnc(NCCCCCCC#N)c23)cc1
Agent: CCCC[Sn](=O)CCCC
Solvent: Cc1ccccc1
Product: COc1ccc(-c2c(-c3ccccc3)oc3ncnc(NCCCCCCc4nnn[nH]4)c23)cc1

Procedure:
Stir 0.098 g (0.23 mmol) 7-{[5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]amino}-heptanenitrile, 0.41 g (3.5 mmol) trimethylsilylazide and 86 mg (0.25 mmol) di-n-butyltin oxide in 5 ml toluene overnight at 80° C. After concentrating by evaporation, take up the residue in water, acidify with dilute hydrochloric acid and extract with methylene chloride. Wash the organic phase with sodium chloride solution, dry over magnesium sulphate and concentrate by evaporation. Purify the raw product by RP-HPLC (column: Gromsil 250 mm×30 mm, 10 μm; acetonitrile/water gradient: 0-3 min 5% acetonitrile, 3-34 min 5%→98% acetonitrile, 34-38 min 98% acetonitrile). 61 mg (55% of theor.) of the title compound is obtained as white crystals.
Reaction SMILES: [N+:1]([C:4]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:5]=1[C:6](=[O:19])[C:7]1[CH2:8][CH2:9][CH2:10][CH2:11][C:12]=1[C:13]2=[O:18])([O-])=O.[OH-].[Na+].[H][H]>[Pd]>[NH2:1][C:4]1[C:5]2[C:6](=[O:19])[C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[C:13](=[O:18])[C:14]=2[CH:15]=[CH:16][CH:17]=1
Reactant: [H][H]
Reactant: O=C1C2=C(CCCC2)C(=O)c2c1cccc2[N+](=O)[O-]
Agent: [Pd]
Agent: [Na+]
Agent: [OH-]
Product: Nc1cccc2c1C(=O)c1ccccc1C2=O
Temperature: 25 °C
Yield: 94.1 %

Procedure:
2.6 Grams (0.01 mol) of 5-nitrotetrahydroanthraquinone, 52 grams (0.013 mol) of a 1% aqueous sodium hydroxide solution, and 0.052 grams of a 5% palladium on carbon catalyst were introduced into an electromagnetic agitation-type glass reactor having an inner volume of 200 ml. Then, the atmosphere in the reactor was replaced by hydrogen, followed by hydrogenation while agitating at room temperature. When 0.015 mol of hydrogen was absorbed, the hydrogen in the system was replaced by nitrogen and then by air for oxidizing the resultant over-reduced compound while agitating for 30 minutes. The resultant reaction product was separated together with the catalyst by filtration and was dissolved in N,N-dimethylformamide for separating the catalyst by filtration. To the resultant filtrate was added water for dilution to obtain 2.1 grams of 1-aminoanthraquinone (at a yield of 93.1%). The purity of the 1-aminoanthraquinone was 98%.
Reaction SMILES: I[C:2]1[S:6][C:5]([C:7]2([OH:13])[CH2:12][CH2:11][O:10][CH2:9][CH2:8]2)=[N:4][CH:3]=1.[N+:14]([C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1)([O-:16])=[O:15].[F-].[K+].C(COC)OC>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CO>[N+:14]([C:17]1[CH:22]=[CH:21][C:20]([C:2]2[S:6][C:5]([C:7]3([OH:13])[CH2:12][CH2:11][O:10][CH2:9][CH2:8]3)=[N:4][CH:3]=2)=[CH:19][CH:18]=1)([O-:16])=[O:15]
Reactant: OC1(c2ncc(I)s2)CCOCC1
Reactant: O=[N+]([O-])c1ccc(B(O)O)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [F-]
Agent: [K+]
Solvent: COCCOC
Solvent: CO
Product: O=[N+]([O-])c1ccc(-c2cnc(C3(O)CCOCC3)s2)cc1
Temperature: 90 °C

Procedure:
A solution of Example 1B (1.0 g, 3.2 mmol), 4-nitrophenylboronic acid (0.75 g, 4.5 mmol), KF (0.56 g, 9.6 mmol), and bis(triphenylphosphine)palladium(II) dichloride (0.22 g, 0.32 mmol) in a solvent mixture of dimethoxyethane (5 mL) and methanol (5 mL) was heated to 90° C. for 16 h. The reaction was cooled to room temperature and partitioned between ethyl acetate (10 mL) and H2O (10 mL). The layers were separated, and the aqueous was extracted with additional ethyl acetate (2×10 mL). The combined organics were dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on SiO2 gel, eluting with 50% ethyl acetate in hexane, to give the title compound. MS (ESI) m/z 307 [M+H]+.
Reaction SMILES: [C:1]1([NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH2:7].[CH3:9][O:10][N:11]=[C:12]([C:18](OCC)=[O:19])[C:13](OCC)=[O:14].Cl>C[O-].[Na+]>[CH3:9][O:10][N:11]=[C:12]1[C:18](=[O:19])[NH:8][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=2[NH:7][C:13]1=[O:14]
Reactant: Nc1ccccc1N
Reactant: CCOC(=O)C(=NOC)C(=O)OCC
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Product: CON=c1c(=O)[nH]c2ccccc2[nH]c1=O

Procedure:
A mixture of iN sodium methylate (162 ml), o-phenylenediamine (17.5 g, 162 mmol) and diethyl 2-(methoxyimino)malonate (32.91 g, 162 mmol) is heated to reflux for 5 hr. After cooling, the mixture is acidified with 2N HCl (162 ml) and pale yellowish crystals (14.3 g, 41%) are filtered off.
Reaction SMILES: C(CC[C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:13]([CH3:43])([CH3:42])[C@H:14]3[C@:27]([CH3:30])([CH2:28][CH:29]=2)[C@@H:26]2[C@:17]([CH3:41])([C@@:18]4([CH3:40])[C@H:23]([CH2:24][CH2:25]2)[C@H:22]2[C@H:31]([C:34]([CH3:36])=[CH2:35])[CH2:32][CH2:33][C@:21]2([C:37]([OH:39])=[O:38])[CH2:20][CH2:19]4)[CH2:16][CH2:15]3)=[CH:8][CH:7]=1)(O)=O.B(C1C=CC([NH:53][C:54](=[O:60])[CH2:55][CH2:56][C:57]([OH:59])=[O:58])=CC=1)(O)O.B(O)O>>[C:57]([CH2:56][CH2:55][C:54]([NH:53][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:13]([CH3:42])([CH3:43])[C@H:14]3[C@:27]([CH3:30])([CH2:28][CH:29]=2)[C@@H:26]2[C@:17]([CH3:41])([C@@:18]4([CH3:40])[C@H:23]([CH2:24][CH2:25]2)[C@H:22]2[C@H:31]([C:34]([CH3:36])=[CH2:35])[CH2:32][CH2:33][C@:21]2([C:37]([OH:39])=[O:38])[CH2:20][CH2:19]4)[CH2:16][CH2:15]3)=[CH:8][CH:7]=1)=[O:60])([OH:59])=[O:58]
Reactant: C=C(C)[C@@H]1CC[C@]2(C(=O)O)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(CCC(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Reactant: O=C(O)CCC(=O)Nc1ccc(B(O)O)cc1
Agent: OBO
Product: C=C(C)[C@@H]1CC[C@]2(C(=O)O)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(NC(=O)CCC(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12

Procedure:
The title compound was prepared following the methods described above for (1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-9-(4-(2-carboxyethyl)phenyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysene-3a-carboxylic acid (example 4a) using 4-(4-boronophenylamino)-4-oxobutanoic acid as the reactant boronic acid. The product was isolated as a white solid (2.98 mg, 9%). LCMS: m/e 628.63 (M−H)−, 3.71 min (method 2). 1H NMR (599 MHz, DMSO-D6_CDCl3) δ ppm 0.91 (s, 3H), 0.93 (s, 3H), 0.98 (s, 3H), 0.99 (s, 3H), 1.02 (s, 3H), 1.03-1.71 (m, 17H), 1.71 (s, 3H), 1.84-1.93 (m, 2H), 2.09 (dd, J=17.87, 5.57 Hz, 1H), 2.20 (d, J=12.30 Hz, 1H), 2.29-2.39 (m, 1H), 2.59-2.62 (m, 2H), 2.97-3.10 (m, 1H), 3.30-3.33 (m, 2H), 4.61 (br. s, 1H), 4.74 (s, 1H), 5.24 (d, J=5.27 Hz, 1H), 7.03 (d, J=8.79 Hz, 2H), 7.51 (d, J=8.20 Hz, 2H).