Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[C:11]([C:12]([O:14]C)=[O:13])=[C:10]([C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)[C:9]2[CH2:8][N:7]([C:23]([O:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[O:24])[CH2:6][CH2:5][C:4]=2[N:3]=1.[Cl-].[Li+]>CS(C)=O.O>[CH2:26]([O:25][C:23]([N:7]1[CH2:6][CH2:5][C:4]2[N:3]=[C:2]([CH3:1])[C:11]([C:12]([OH:14])=[O:13])=[C:10]([C:16]3[CH:17]=[CH:18][C:19]([CH3:22])=[CH:20][CH:21]=3)[C:9]=2[CH2:8]1)=[O:24])[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
Reactant: COC(=O)c1c(C)nc2c(c1-c1ccc(C)cc1)CN(C(=O)OCc1ccccc1)CC2
Agent: [Cl-]
Agent: [Li+]
Solvent: CS(C)=O
Solvent: O
Product: Cc1ccc(-c2c3c(nc(C)c2C(=O)O)CCN(C(=O)OCc2ccccc2)C3)cc1
Temperature: 130 °C
Reaction time: 2 h
Yield: 15.9 %

Procedure:
A mixture of 6-benzyl 3-methyl 2-methyl-4-(p-tolyl)-7,8-dihydro-1,6-naphthyridine-3,6(5H)-dicarboxylate (intermediate 10) (0.482 g, 1.12 mmol) and lithium chloride (0.475 g, 11.19 mmol) in 2,6-lutadine (10 mL) and DMSO (10.00 mL) was stirred at 130° C. for 2 h. The mixture was cooled to room temperature, diluted with water and extracted with EtOAc to remove unreacted starting material and impurities. The aqueous phase was made acidic with 1N HCl and extracted with EtOAc (2×'s) then CH2Cl2. The organic extracts were combined, dried (Na2SO4), filtered and concentrated to provide 6-((benzyloxy)carbonyl)-2-methyl-4-(p-tolyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxylic acid (74.2 mg, 15% yield) as an amber oil. 1H NMR (400 MHz, CDCl3) δ ppm 7.33 (br. s., 4H), 7.24 (d, J=7.83 Hz, 3H), 7.13 (d, J=7.58 Hz, 2H), 5.11 (s, 2H), 4.36 (s, 2H), 3.78 (t, J=5.62 Hz, 2H), 3.30 (br. s., 2H), 2.80 (br. s., 3H), 2.38 (s, 3H). LCMS (M+H) calcd for C25H25N2O4: 417.18. found: 417.4.
Reaction SMILES: S(Cl)([Cl:3])=O.[NH2:5][C:6]1[C:19]2[C:18](=[O:20])[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11](=[O:21])[C:10]=2[C:9]([NH2:22])=[CH:8][CH:7]=1>>[Cl:3][C:8]1[CH:7]=[C:6]([NH2:5])[C:19]2[C:18](=[O:20])[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11](=[O:21])[C:10]=2[C:9]=1[NH2:22]
Reactant: O=S(Cl)Cl
Reactant: Nc1ccc(N)c2c1C(=O)c1ccccc1C2=O
Product: Nc1cc(Cl)c(N)c2c1C(=O)c1ccccc1C2=O
Yield: 50 %

Procedure:
A mixture of thionyl chloride (320 g) and 1,4-diamino anthraquinone (20 g) is refluxed for 24 hours. The mixture is then cooled and poured onto crushed ice. The precipitate is filtered, dried and purified by recrystallization from carbon tetrachloride. The yield is 50 percent 2-chloro-1,4-diamino anthraquinone with a melting point of 207° C. to 210° C.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][C:12]([N:14]2[CH2:18][CH:17]([CH2:19][C:20]([CH3:23])([CH3:22])[CH3:21])[C:16]3([C:31]4[C:26](=[CH:27][C:28]([Cl:32])=[CH:29][CH:30]=4)[NH:25][C:24]3=[O:33])[CH:15]2[C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([Cl:40])[C:35]=2[F:41])=[O:13])=[CH:7][CH:6]=1)=[O:4].[Li+].[OH-].CO>O1CCCC1.O>[C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][C:12]([N:14]2[CH2:18][CH:17]([CH2:19][C:20]([CH3:23])([CH3:22])[CH3:21])[C:16]3([C:31]4[C:26](=[CH:27][C:28]([Cl:32])=[CH:29][CH:30]=4)[NH:25][C:24]3=[O:33])[CH:15]2[C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([Cl:40])[C:35]=2[F:41])=[O:13])=[CH:7][CH:6]=1)([OH:4])=[O:2]
Reactant: COC(=O)c1ccc(OC(=O)N2CC(CC(C)(C)C)C3(C(=O)Nc4cc(Cl)ccc43)C2c2cccc(Cl)c2F)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)(C)CC1CN(C(=O)Oc2ccc(C(=O)O)cc2)C(c2cccc(Cl)c2F)C12C(=O)Nc1cc(Cl)ccc12

Procedure:
In a manner similar to the method described in Example 13, rac-(2′S,3′S,4′S)-6-chloro-2′-(3-chloro-2-fluoro-phenyl)-4′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-1′-carboxylic acid 4-methoxycarbonyl-phenyl ester (10 mg, 0.02 mmol) was heated with aqueous LiOH (4 mg, 0.2 mmol) in tetrahydrofuran (3 mL), water (3 mL), and methanol (1 mL) at room temperature for 18 h to give rac-(2′S,3′S,4′S)-6-chloro-2′-(3-chloro-2-fluoro-phenyl)-4′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-1′-carboxylic acid 4-carboxy-phenyl ester as a white solid (Yield, 8 mg, 82%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[CH:19][C:20]([CH2:24][N:25]4[CH2:28][CH:27]([C:29]([O:31]C)=[O:30])[CH2:26]4)=[N:21][C:22]=3[CH3:23])[N:13]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][CH:9]([CH3:11])[CH3:10].[OH-].[Na+]>>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[CH:19][C:20]([CH2:24][N:25]4[CH2:26][CH:27]([C:29]([OH:31])=[O:30])[CH2:28]4)=[N:21][C:22]=3[CH3:23])[N:13]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][CH:9]([CH3:10])[CH3:11]
Reactant: COC(=O)C1CN(Cc2ccc(-c3noc(-c4ccc(CC(C)C)c(Cl)c4)n3)c(C)n2)C1
Agent: [Na+]
Agent: [OH-]
Product: Cc1nc(CN2CC(C(=O)O)C2)ccc1-c1noc(-c2ccc(CC(C)C)c(Cl)c2)n1
Yield: 71.8 %

Procedure:
The title compound (76 mg) was synthesized in a yield of 72% as a white crystalline solid by conducting the reaction similar to that mentioned in Example 3 (3e) using methyl 1-({5-[5-(3-chloro-4-isobutylphenyl)-1,2,4-oxadiazol-3-yl]-6-methylpyridin-2-yl}methyl)azetidine-3-carboxylate (0.11 g, 0.24 mmol) that was obtained in Example 24 (24j) and a 1 N aqueous solution of sodium hydroxide (0.72 mL, 0.72 mmol).
Reaction SMILES: C([N:9]1[CH2:18][CH2:17][C:16]2[N:15]=[C:14]([CH3:19])[NH:13][C:12]=2[C:11]2[CH:20]=[CH:21][CH:22]=[CH:23][C:10]1=2)(=O)C1C=CC=CC=1>Cl.O1CCOCC1>[CH3:19][C:14]1[NH:13][C:12]2[C:11]3[CH:20]=[CH:21][CH:22]=[CH:23][C:10]=3[NH:9][CH2:18][CH2:17][C:16]=2[N:15]=1
Reactant: Cc1nc2c([nH]1)-c1ccccc1N(C(=O)c1ccccc1)CC2
Agent: Cl
Solvent: C1COCCO1
Product: Cc1nc2c([nH]1)-c1ccccc1NCC2
Temperature: 25 °C
Yield: 65.3 %

Procedure:
6-Benzoyl-2-methyl-1,4,5,6-tetrahydro-1,3,6-triaza-benzo[e]azulene from Example E5.8 (160 mg, 0.53 mmol) was dissolved in a 6M HCl/dioxan solution (50 ml) and heated at reflux for 18 h. The reaction mixture was cooled to room temperature and reduced in vacuo. The residue was partitioned between EtOAc and saturated NaHCO3 (aq) and the layers were separated. The organic layer was washed with brine, dried, filtered and reduced in vacuo to yield the title compound (69 mg, 66%).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:26])[CH2:4][C@H:5]1[C:9]2[CH:10]=[CH:11][C:12]([O:14][C@H:15]3[C:23]4[C:18](=[C:19]([OH:25])[CH:20]=[CH:21][C:22]=4[F:24])[CH2:17][CH2:16]3)=[CH:13][C:8]=2[O:7][CH2:6]1.[N:27]1[C:36]2[C:31](=[CH:32][C:33](B(O)O)=[CH:34][CH:35]=2)[CH:30]=[CH:29][CH:28]=1>>[CH3:1][O:2][C:3](=[O:26])[CH2:4][C@H:5]1[C:9]2[CH:10]=[CH:11][C:12]([O:14][C@H:15]3[C:23]4[C:18](=[C:19]([O:25][C:33]5[CH:32]=[C:31]6[C:36](=[CH:35][CH:34]=5)[N:27]=[CH:28][CH:29]=[CH:30]6)[CH:20]=[CH:21][C:22]=4[F:24])[CH2:17][CH2:16]3)=[CH:13][C:8]=2[O:7][CH2:6]1
Reactant: COC(=O)C[C@@H]1COc2cc(O[C@@H]3CCc4c(O)ccc(F)c43)ccc21
Reactant: OB(O)c1ccc2ncccc2c1
Product: COC(=O)C[C@@H]1COc2cc(O[C@@H]3CCc4c(Oc5ccc6ncccc6c5)ccc(F)c43)ccc21

Procedure:
The title compound is prepared from {(S)-6-[(R)-7-fluoro-4-hydroxy-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester and quinoline-6-boronic acid following a procedure analogous to that described for Intermediate 6. LC (method 4): tR=0.64 min; Mass spectrum (ESI+): m/z=486 [M+H]+.
Reaction SMILES: [Br:1][C:2]1[N:7]2[N:8]=[C:9]([CH2:11][CH3:12])[CH:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1.F[B-](F)(F)F.[O:18]=[N+:19]=[O:20].C(OCC)(=O)C>C(#N)C>[Br:1][C:2]1[N:7]2[N:8]=[C:9]([CH2:11][CH3:12])[C:10]([N+:19]([O-:20])=[O:18])=[C:6]2[CH:5]=[CH:4][CH:3]=1
Reactant: CCc1cc2cccc(Br)n2n1
Reactant: O=[N+]=O
Agent: F[B-](F)(F)F
Solvent: CC#N
Solvent: CCOC(C)=O
Product: CCc1nn2c(Br)cccc2c1[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 50.8 %

Procedure:
After dissolving 7-bromo-2-ethylpyrazolo[1,5-a]pyridine (1.1 g) in acetonitrile (20 mL), nitronium tetrafluoroborate (1.3 g) was added while stirring on ice, and stirring was continued for 30 minutes. The reaction mixture was added to ice water, extraction was performed with ethyl acetate and the extract was washed with water and brine. After drying over anhydrous magnesium sulfate and filtration, the solvent was concentrated under reduced pressure, the residue was purified by silica gel column chromatography, and the title compound (670 mg) was obtained from the n-hexane:ethyl acetate (10:1) fraction as yellow crystals.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:14])[CH2:4][C:5]1[C:10](I)=[CH:9][C:8]([Cl:12])=[CH:7][C:6]=1[Cl:13].[CH3:15][N:16]1C(=O)CCC1>[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3](=[O:14])[CH2:4][C:5]1[C:10]([C:15]#[N:16])=[CH:9][C:8]([Cl:12])=[CH:7][C:6]=1[Cl:13]
Reactant: CN1CCCC1=O
Reactant: COC(=O)Cc1c(Cl)cc(Cl)cc1I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C-]#N
Agent: [Zn+2]
Product: COC(=O)Cc1c(Cl)cc(Cl)cc1C#N
Temperature: 110 °C

Procedure:
A mixture of 2,4-dichloro-6-iodophenylacetic acid methyl ester (0.95 mmol), Zn(CN)2 (0.95 mmol) and tetrakis(triphenylphosphine)palladium (0.05 mmol) in 1.5 mL anhydrous NMP was degassed and heated under argon in a closed vial to 110° C. for 2.5 h. The reaction mixture was cooled to RT, quenched with 10% aq Na2CO3 solution and extracted with EtOAc (3×). The combined organic layers were dried over MgSO4 and concentrated in vacuo. Purification by CC using Hept/EtOAc (9/1) gives the desired product as yellow oil.
Reaction SMILES: [F:1][C:2]([F:16])([F:15])[O:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12](=[S:14])[NH2:13])=[CH:6][CH:5]=1.[Cl:17][CH2:18][C:19]([CH2:21]Cl)=O>C(O)C>[Cl:17][CH2:18][C:19]1[N:13]=[C:12]([CH:11]=[CH:10][C:7]2[CH:6]=[CH:5][C:4]([O:3][C:2]([F:15])([F:1])[F:16])=[CH:9][CH:8]=2)[S:14][CH:21]=1
Reactant: NC(=S)C=Cc1ccc(OC(F)(F)F)cc1
Reactant: O=C(CCl)CCl
Solvent: CCO
Product: FC(F)(F)Oc1ccc(C=Cc2nc(CCl)cs2)cc1
Yield: 15.5 %

Procedure:
12.7 g (48.3 mmol) 3-(4-Trifluoromethoxy-phenyl)-acrylthioamide, 18.4 g (145 mmol) 1,3-dichloroacetone and 120 ml ethanol were refluxed for 4 h. After evaporation the residue was purified by chromatography on silica gel (ethyl acetate/isohexane 1:10) to yield 2.40 g 4-chloromethyl-2-[2-(4-trifluoromethoxy-phenyl)-vinyl]-thiazole as yellow solid.
Reaction SMILES: Cl[CH2:2]CC[Si](C)(Cl)Cl.ClCCC[Si](Cl)(Cl)Cl.[Cl:17][CH2:18][CH2:19][CH2:20][Si:21]([CH3:26])([CH:24]=[CH2:25])[CH:22]=[CH2:23]>>[Cl:17][CH2:18][CH2:19][CH2:20][Si:21]([CH:26]=[CH2:2])([CH:24]=[CH2:25])[CH:22]=[CH2:23]
Reactant: C[Si](Cl)(Cl)CCCCl
Reactant: C=C[Si](C)(C=C)CCCCl
Agent: ClCCC[Si](Cl)(Cl)Cl
Product: C=C[Si](C=C)(C=C)CCCCl

Procedure:
In Step 1, a halogenated silane, such as 3-chloropropyldimethylchlorosilane, is reacted with a Grinard reagent, such as vinyl magnesium chloride, to form 3-chloropropyldimethylvinylsilane. When 3-chloropropylmethyldichlorosilane or 3-chloropropyltrichlorosilane is used as the halogenated silane instead of 3-chloropropyldimethylchlorosilane, 3-chloropropylmethyldivinylsilane or 3-chloropropyltrivinylsilane is obtained, respectively. The reaction is generally carried out by dropwise adding the halogenated silane to a solution of vinyl magnesium chloride in THF. The reaction temperature may be in a range of from 20 to 75 degrees C. The reaction is exothermic. Therefore, if the temperature rises too high, the reaction mixture may be cooled. After the completion of the addition, the reaction mixture is stirred for further 30 minutes to 10 hours. Then, the salt is dissolved in diluted hydrochloric acid and the organic phase is recovered and purified to obtain an intermediate product.
Reaction SMILES: [C:1]([N:4]1[CH2:9][CH2:8][CH:7]([C:10]([N:12]2[CH2:17][CH2:16][C@@H:15]([NH:18][CH3:19])[C@H:14]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=3)[CH2:13]2)=[O:11])[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[C:28]1([C:34]2[CH:38]=[C:37]([C:39]([OH:41])=O)[O:36][N:35]=2)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>>[C:1]([N:4]1[CH2:5][CH2:6][CH:7]([C:10]([N:12]2[CH2:17][CH2:16][C@@H:15]([N:18]([CH3:19])[C:39]([C:37]3[O:36][N:35]=[C:34]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)[CH:38]=3)=[O:41])[C@H:14]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=3)[CH2:13]2)=[O:11])[CH2:8][CH2:9]1)(=[O:3])[CH3:2]
Reactant: O=C(O)c1cc(-c2ccccc2)no1
Reactant: CN[C@@H]1CCN(C(=O)C2CCN(C(C)=O)CC2)C[C@H]1c1ccc(Cl)c(Cl)c1
Product: CC(=O)N1CCC(C(=O)N2CC[C@@H](N(C)C(=O)c3cc(-c4ccccc4)no3)[C@H](c3ccc(Cl)c(Cl)c3)C2)CC1

Procedure:
Using the compound obtained in Example 78 and 3-phenylisoxazole-5-carboxylic acid, and by the reaction and purification in the same manner as in Example 3, the title compound was obtained.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].C1(CN)CCCCC1.[O:17]=[C:18]1[C:26]2([CH2:30][O:29][C:28]3[CH:31]=[C:32]4[C:36](=[CH:37][C:27]2=3)[CH2:35][CH2:34][O:33]4)[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[N:19]1[CH2:38][C:39]1[CH:47]=[CH:46][C:42]([C:43](O)=[O:44])=[CH:41][CH:40]=1.O=C1C2(COC3C=C4C(=CC2=3)CCO4)C2C(=CC=CC=2)N1CC1C=C(C=CC=1)C(O)=O>>[F:1][C:2]1[CH:3]=[C:4]([NH:5][C:43](=[O:44])[C:42]2[CH:46]=[CH:47][C:39]([CH2:38][N:19]3[C:20]4[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:26]4([CH2:30][O:29][C:28]5[CH:31]=[C:32]6[C:36](=[CH:37][C:27]4=5)[CH2:35][CH2:34][O:33]6)[C:18]3=[O:17])=[CH:40][CH:41]=2)[CH:6]=[CH:7][CH:8]=1
Reactant: Nc1cccc(F)c1
Reactant: O=C(O)c1ccc(CN2C(=O)C3(COc4cc5c(cc43)CCO5)c3ccccc32)cc1
Agent: NCC1CCCCC1
Agent: O=C(O)c1cccc(CN2C(=O)C3(COc4cc5c(cc43)CCO5)c3ccccc32)c1
Product: O=C(Nc1cccc(F)c1)c1ccc(CN2C(=O)C3(COc4cc5c(cc43)CCO5)c3ccccc32)cc1

Procedure:
Following the procedure as described in EXAMPLE 12 and making non-critical variations using 3-fluoroaniline to replace cyclohexanemethylamine, and 4-[(2′-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-1′(2′H)-yl)methyl]benzoic acid to replace 3-[(2′-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-1′(2′H)-yl)methyl]benzoic acid, N-(3-fluorophenyl)-4-[(2′-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-1′(2′H)-yl)methyl]benzamide was obtained (50%) as a colorless solid: mp>250° C.; 1H NMR (300 MHz, CDCl3) δ8.03 (s, 1H), 7.89-7.82 (m, 2H), 7.63-7.56 (m, 1H), 7.48-7.41 (m, 2H), 7.34-7.15 (m, 4H), 7.09-7.01 (m, 1H), 6.89-6.80 (m, 1H), 6.78-6.72 (m, 1H), 6.47 (s, 1H), 6.42 (s, 1H), 5.01 (ABq, 2H), 4.82 (ABq, 2H), 4.57-4.48 (m, 2H), 3.01-2.92 (m, 2H); 13C NMR (75 MHz, CDCl3) δ178.3, 163.6 (d, JC-F=248.0 Hz), 161.4, 141.7, 139.7, 139.5 (d, JC-F=10.8 Hz), 134.3, 132.4, 130.0 (d, JC-F=9.4 Hz), 128.8, 127.9, 127.6, 124.1, 123.8, 120.0, 119.7, 118.7, 115.4 (d, JC-F=2.9 Hz), 111.2 (d, JC-F=21.3 Hz), 109.2, 107.6 (d, JC-F=26.4 Hz), 93.3, 80.5, 72.4, 57.8, 43.8, 28.9; MS (ES+) m/z 507.2 (M+1).
Reaction SMILES: [Si:1]([O:8][C@H:9]1[CH2:35][CH2:34][C@@:33]2([CH3:36])[C@@H:11]([CH2:12][CH2:13][C@@H:14]3[C@@H:32]2[C@@H:31]([OH:37])[C@@H:30]([O:38][C:39](=[O:41])[CH3:40])[C@@:29]2([CH3:42])[C@H:15]3[CH2:16][C@@H:17]3[O:22][C@@:21]4([O:28][CH2:27][C@H:25]([CH3:26])[CH2:24][CH2:23]4)[C@@H:19]([CH3:20])[C@@H:18]32)[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:43][Si:44](OS(C(F)(F)F)(=O)=O)([CH3:46])[CH3:45].N1C(C)=CC=CC=1C>>[Si:1]([O:8][C@H:9]1[CH2:35][CH2:34][C@@:33]2([CH3:36])[C@@H:11]([CH2:12][CH2:13][C@@H:14]3[C@@H:32]2[C@@H:31]([O:37][Si:44]([CH3:46])([CH3:45])[CH3:43])[C@@H:30]([O:38][C:39](=[O:41])[CH3:40])[C@@:29]2([CH3:42])[C@H:15]3[CH2:16][C@@H:17]3[O:22][C@@:21]4([O:28][CH2:27][C@H:25]([CH3:26])[CH2:24][CH2:23]4)[C@@H:19]([CH3:20])[C@@H:18]32)[CH2:10]1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]
Reactant: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Reactant: CC(=O)O[C@@H]1[C@H](O)[C@H]2[C@@H](CC[C@H]3C[C@@H](O[Si](C)(C)C(C)(C)C)CC[C@@]32C)[C@@H]2C[C@@H]3O[C@]4(CC[C@@H](C)CO4)[C@@H](C)[C@@H]3[C@@]12C
Solvent: Cc1cccc(C)n1
Product: CC(=O)O[C@@H]1[C@H](O[Si](C)(C)C)[C@H]2[C@@H](CC[C@H]3C[C@@H](O[Si](C)(C)C(C)(C)C)CC[C@@]32C)[C@@H]2C[C@@H]3O[C@]4(CC[C@@H](C)CO4)[C@@H](C)[C@@H]3[C@@]12C

Procedure:
(3β,5α,11β,12β,25R)-3-(t-butyldimethylsilyloxy)-12-acetoxyspirostan-11-ol was silylated with trimethylsilyltrifiate and 2,6-lutidine in methylene chlodde according to the procedure described in Tetrahadron Letters, 1981, 22, 3455.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]2[C:9]3[C:14]([C:15]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[C:16]4[C:21]=2[CH:20]=[CH:19][CH:18]=[CH:17]4)=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH:5]=[CH:6][CH:7]=1.[CH:28]1[C:36]2[C:35]3[CH:37]=[CH:38][CH:39]=[CH:40][C:34]=3[O:33][C:32]=2[C:31]([C:41]2[CH:42]=[CH:43][C:44]3[NH:45][C:46]4[C:51]([C:52]=3[CH:53]=2)=[CH:50][CH:49]=[CH:48][CH:47]=4)=[CH:30][CH:29]=1.CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>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].CCCCCC.C1(C)C=CC=CC=1>[CH:28]1[C:36]2[C:35]3[CH:37]=[CH:38][CH:39]=[CH:40][C:34]=3[O:33][C:32]=2[C:31]([C:41]2[CH:42]=[CH:43][C:44]3[N:45]([C:6]4[CH:7]=[CH:2][CH:3]=[C:4]([C:8]5[C:21]6[C:16]([C:15]([C:22]7[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=7)=[C:14]7[C:9]=5[CH:10]=[CH:11][CH:12]=[CH:13]7)=[CH:17][CH:18]=[CH:19][CH:20]=6)[CH:5]=4)[C:46]4[C:51]([C:52]=3[CH:53]=2)=[CH:50][CH:49]=[CH:48][CH:47]=4)=[CH:30][CH:29]=1
Reactant: Brc1cccc(-c2c3ccccc3c(-c3ccccc3)c3ccccc23)c1
Reactant: c1ccc2c(c1)[nH]c1ccc(-c3cccc4c3oc3ccccc34)cc12
Agent: [Pd]
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Agent: CC(C)(C)[O-]
Solvent: Cc1ccccc1
Solvent: CCCCCC
Product: c1ccc(-c2c3ccccc3c(-c3cccc(-n4c5ccccc5c5cc(-c6cccc7c6oc6ccccc67)ccc54)c3)c3ccccc23)cc1
Yield: 90.7 %

Procedure:
In a 100-mL three-neck flask were put 1.2 g (3.0 mmol) of 9-(3-bromophenyl)-10-phenylanthracene, 1.0 g (3.0 mmol) of 3-(dibenzofuran-4-yl)-9H-carbazole, and 0.87 g (9.1 mmol) of sodium tert-butoxide. After the air in the flask was replaced with nitrogen, to this mixture were added 20 mL of toluene and 0.2 mL of tri(tert-butyl)phosphine (a 10 wt % hexane solution). This mixture was degassed by being stirred while the pressure was reduced. After the degassing, 87 mg (0.15 mmol) of bis(dibenzylideneacetone)palladium(0) was added to this mixture. This mixture was stirred at 110° C. for 6 hours under a nitrogen stream. After the stirring, the obtained mixture was suction-filtered through Celite (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 531-16855), alumina, and Florisil (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 540-00135). The filtrate was concentrated to give a yellow solid. The obtained solid was recrystallized from toluene to give 1.8 g of a white solid which was the object of the synthesis in 88% yield. The synthesis scheme of Step 2 is illustrated in (b-10).
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([P:20]([C:40]2[CH:45]=[C:44]([C:46]([CH3:49])([CH3:48])[CH3:47])[C:43]([O:50][Si](C)(C)C)=[C:42]([C:55]([CH3:58])([CH3:57])[CH3:56])[CH:41]=2)[C:21]2[CH:26]=[C:25]([C:27]([CH3:30])([CH3:29])[CH3:28])[C:24]([O:31][Si](C)(C)C)=[C:23]([C:36]([CH3:39])([CH3:38])[CH3:37])[CH:22]=2)[CH:8]=[C:9]([C:16]([CH3:19])([CH3:18])[CH3:17])[C:10]=1[O:11][Si](C)(C)C)([CH3:4])([CH3:3])[CH3:2].O>CO>[C:27]([C:25]1[CH:26]=[C:21]([P:20]([C:7]2[CH:8]=[C:9]([C:16]([CH3:19])([CH3:18])[CH3:17])[C:10]([OH:11])=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[CH:6]=2)[C:40]2[CH:45]=[C:44]([C:46]([CH3:47])([CH3:48])[CH3:49])[C:43]([OH:50])=[C:42]([C:55]([CH3:58])([CH3:57])[CH3:56])[CH:41]=2)[CH:22]=[C:23]([C:36]([CH3:39])([CH3:37])[CH3:38])[C:24]=1[OH:31])([CH3:28])([CH3:29])[CH3:30]
Reactant: CC(C)(C)c1cc(P(c2cc(C(C)(C)C)c(O[Si](C)(C)C)c(C(C)(C)C)c2)c2cc(C(C)(C)C)c(O[Si](C)(C)C)c(C(C)(C)C)c2)cc(C(C)(C)C)c1O[Si](C)(C)C
Solvent: O
Solvent: CO
Product: CC(C)(C)c1cc(P(c2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)c2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)cc(C(C)(C)C)c1O

Procedure:
A solution of 5.0 g (5.8 mmol) of tris(3,5-di-tert-butyl-4-trimethylsilyloxyphenyl)phosphine and 4.0 ml of water in 100 ml of methanol is heated at reflux temperature for 48 hours. The solvent is removed in vacuo from the reaction mixture and the residue is recrystallized from nitromethane. The mass spectrum shows a molecular ion at m/z=646.
Reaction SMILES: [OH:1][C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:4][CH:3]=1.[CH2:15](O)[CH:16]=[CH:17][CH3:18].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1C=CC=CC=1>[C:9]([O:8][C:6]([C:5]1[CH:13]=[CH:14][C:2]([O:1][CH2:15]/[CH:16]=[CH:17]/[CH3:18])=[CH:3][CH:4]=1)=[O:7])([CH3:10])([CH3:11])[CH3:12]
Reactant: CC(C)(C)OC(=O)c1ccc(O)cc1
Reactant: CC=CCO
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: c1ccccc1
Product: C/C=C/COc1ccc(C(=O)OC(C)(C)C)cc1
Reaction time: 3 h
Yield: 0.1 %

Procedure:
A solution of 1,1-dimethylethyl 4-hydroxybenzoate (3.68 g, 18.9 mol) and 2-buten-1-ol (1.37 g, 18.9 mol) in dry benzene (100 ml) at 22° C. was treated with triphenylphosphine (5.48 g, 20.9 mmol) followed by a solution of diisopropyl azodicarboxylate (4.22 g, 20.9 mmol) in dry benzene (10 ml) added dropwise over 7 minutes. After 3 hours at 22° C., the solvent was concentrated under reduced pressure and the residue was chromatographed on silica gel. Elution with a mixture of toluene and ethyl acetate (99:1) gave 3.70 g (79%) of the title material as a clear oil: bp 85-90° C./0.1 torr (bulb to bulb, air bath temperature).
Reaction SMILES: [NH2:1][C:2]1[C:3]([OH:16])=[C:4]([C:8]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[O:9])[CH:5]=[CH:6][CH:7]=1.[CH3:17][O:18][C:19]1[C:20](=O)[C:21](=[O:25])[C:22]=1[O:23]C>CO>[OH:16][C:3]1[C:4]([C:8]([N:10]2[CH2:11][CH2:12][O:13][CH2:14][CH2:15]2)=[O:9])=[CH:5][CH:6]=[CH:7][C:2]=1[NH:1][C:20]1[C:21](=[O:25])[C:22](=[O:23])[C:19]=1[O:18][CH3:17]
Reactant: Nc1cccc(C(=O)N2CCOCC2)c1O
Reactant: COc1c(OC)c(=O)c1=O
Solvent: CO
Product: COc1c(Nc2cccc(C(=O)N3CCOCC3)c2O)c(=O)c1=O
Yield: 54.2 %

Procedure:
A solution of 1.00 g (4.5 mmol) of (3-amino-2-hydroxyphenyl)morpholin-4-ylmethanone and 2.56 g (18.0 mmol) of 3,4-dimethoxycyclobut-3-ene-1,2-dione in 100 ml of methanol was heated at 50° C. for five and a half hours. The reaction medium was concentrated. The residue was taken up in ethyl acetate and was washed twice with a 1 M aqueous sodium dihydrogen phosphate solution. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated. The solvent was evaporated off and the residue was chromatographed on silica gel (200 g prepacked column, eluent dichloromethane/methanol from 0 to 5% of methanol). 0.81 g of a yellow solid was obtained (dirty fraction). This solid was taken up in methanol with stirring, filtered and rinsed with methanol. 0.50 g of product was obtained in the form of a pale yellow solid. Yield=33%.