Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[C:11]([C:13]([OH:16])([CH3:15])[CH3:14])[N:10]=[C:9]2[C:17]2[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=2[F:24])=[CH:4][CH:3]=1.[CH3:25][S:26]([C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1)(=[O:28])=[O:27].C(=O)([O-])[O-].[K+].[K+].COCCOC>[Pd].O>[F:24][C:18]1[CH:19]=[CH:20][CH:21]=[C:22]([F:23])[C:17]=1[C:9]1[N:8]([C:5]2[CH:6]=[CH:7][C:2]([C:33]3[CH:32]=[CH:31][CH:30]=[C:29]([S:26]([CH3:25])(=[O:28])=[O:27])[CH:34]=3)=[CH:3][CH:4]=2)[CH:12]=[C:11]([C:13]([OH:16])([CH3:15])[CH3:14])[N:10]=1
Reactant: CS(=O)(=O)c1cccc(B(O)O)c1
Reactant: CC(C)(O)c1cn(-c2ccc(Br)cc2)c(-c2c(F)cccc2F)n1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: COCCOC
Product: CC(C)(O)c1cn(-c2ccc(-c3cccc(S(C)(=O)=O)c3)cc2)c(-c2c(F)cccc2F)n1
Temperature: 80 °C
Yield: 76.7 %

Procedure:
2-[1-(4-Bromo-phenyl)-2-(2,6-difluoro-phenyl)-1H-imidazol-4-yl]-propan-2-ol (250 mg, 0.64 mmol), (3-methylsulfonylphenyl)boronic acid (254 mg, 1.27 mmol), and potassium carbonate (398 mg, 2.88 mmol) were placed into a flask. 6 mL, of mixture of DME (1,2-dimethoxyethane) and water (9:1, V/V) was added. The flask was flushed with argon for 15 min, and then Pd catalyst (Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct, 52 mg, 0.064 mmol) was added. The mixture was heated to 80° C. overnight. After cooling to room temperature, all solvent was removed. The crude product was purified by column chromatography on silica gel (45→99% EtOAc/Hexane) to give an off-white solid (230 mg, 77% yield). 1H-NMR (400 MHz, CDCl3): δ 1.70 (s, 6H), 2.71 (s, 1H), 3.09 (s, 3H), 6.92-6.88 (m, 2H), 7.21 (s, 1H), 7.39-7.28 (m, 3H), 7.59-7.57 (m, 2H), 7.66 (t, 1H, J=7.8), 7.86-7.83 (M, 1H), 7.95-7.92 (m, 1H), 8.12 (t, 1H, J=1.7). MS (ES): 491.4 [M+Na]+
Reaction SMILES: C([O:3][C:4]([C:6]12[CH2:24][CH:23]1[CH:22]=[CH:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][N:15]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1)[C:14](=[O:34])[N:13]1[CH:9]([CH2:10][CH:11]([O:35][CH2:36][O:37][CH2:38][CH3:39])[CH2:12]1)[C:8](=[O:40])[NH:7]2)=[O:5])C.C1COCC1.CO.[Li+].[OH-]>ClCCl.CO>[CH2:38]([O:37][CH2:36][O:35][CH:11]1[CH2:10][CH:9]2[N:13]([C:14](=[O:34])[N:15]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH:21]=[CH:22][CH:23]3[C:6]([C:4]([OH:5])=[O:3])([NH:7][C:8]2=[O:40])[CH2:24]3)[CH2:12]1)[CH3:39]
Reactant: CCOCOC1CC2C(=O)NC3(C(=O)OCC)CC3C=CCCCCCN(Cc3ccc(OC)cc3)C(=O)N2C1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: ClCCl
Solvent: CO
Product: CCOCOC1CC2C(=O)NC3(C(=O)O)CC3C=CCCCCCN(Cc3ccc(OC)cc3)C(=O)N2C1
Yield: 101.9 %

Procedure:
A solution of the ester 135 (0.775 g, 1.39 mmol) in 1:1:1 THF-Methanol-aq. 1M LiOH (36 ml) was stirred at rt for 3.5 h after which TLC (95:5 and 9:1 dichloromethane-methanol) and LC-MS indicated complete conversion into the carboxylic acid. The reaction mixture was then concentrated into approximately ⅓ of the volume, then diluted with water (10 ml) and acidified to approx. pH 4 using aq. 10% citric acid (60 ml) upon which a precipitate formed. The mixture was washed with ethyl acetate (3×25 ml) and the combined organic layers were washed with brine (2×50 ml), then dried (Na2SO4), filtered and concentrated. The residue was concentrated from toluene (3×10 ml) which gave the crude title compound as an off-white foam (0.75 g, quantitative). LR-MS: Calcd for C28H40N3O7: 530. Found: 530 [M−H].
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH2:10][OH:11])[CH:5]=[C:6]([CH2:8][OH:9])[CH:7]=1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[Na+].Br[CH2:21][CH2:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([C:30](=[O:32])[CH3:31])=[CH:26][CH:25]=1>CC(N(C)C)=O>[OH:9][CH2:8][C:6]1[CH:7]=[C:2]([CH:3]=[C:4]([CH2:10][OH:11])[CH:5]=1)[O:1][CH2:21][CH2:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([C:30](=[O:32])[CH3:31])=[CH:26][CH:25]=1
Reactant: CC(=O)c1ccc(OCCBr)cc1
Reactant: OCc1cc(O)cc(CO)c1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Product: CC(=O)c1ccc(OCCOc2cc(CO)cc(CO)c2)cc1
Reaction time: 8 h
Yield: 85.5 %

Procedure:
To a stirred solution of (5-hydroxy-1,3-phenylene)dimethanol (3.0, 20.0 mmol), sodium carbonate (2.5 g, 29.0 mmol) and sodium iodide (0.45 g, 2.9 mmol) in 60 ml of DMA was added 1-(4-(2-bromoethoxy)phenyl)ethanone (5.0, 20.57 mmol). The mixture was stirred overnight, evaporated and purified on SiO2 chromatography eluted with EtAc/Hexane (4:1 to 5:1) to afford 5.41 g (86%) of the title compound. 1H NMR (CD3OD) 7.99 (ddd, 2H, J=2.8, 4.8, 9.8 Hz), 7.07 (ddd, 2H, J=2.8, 4.7, 9.8 Hz), 6.94 (s, 1H), 6.89 (s, 2H), 4.58 (s, 4H), 4.42 (dd, 2H, J=2.2, 6.1 Hz), 4.37 (m, 2H), 2.55 (s, 3H); 13C NMR 199.55, 164.66, 160.59, 144.72, 132.03, 131.74, 119.16, 115.64, 113.11, 68.36, 67.87, 65.20, 26.53; MS m/z+339.2 (M+Na).
Reaction SMILES: [NH2:1][C:2]1[O:3][C:4]([C:7]([C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)=O)=[CH:5][N:6]=1.O.[CH3:17][NH2:18]>C(O)(C)(C)C>[F:15][C:12]1[CH:13]=[CH:14][C:9]([C:7]2[C:4]([OH:3])=[CH:5][N:6]=[C:2]([NH:18][CH3:17])[N:1]=2)=[CH:10][CH:11]=1
Reactant: CN
Reactant: Nc1ncc(C(=O)c2ccc(F)cc2)o1
Solvent: CC(C)(C)O
Solvent: O
Product: CNc1ncc(O)c(-c2ccc(F)cc2)n1
Temperature: 50 °C
Reaction time: 2 h
Yield: 66 %

Procedure:
(2-Amino-1,3-oxazol-5-yl)(4-fluorophenyl)methanone (US2005032859, 1 g, 4.85 mmol) and 40% methyl amine water in excess (50 mL) were combined in tert-butanol (50 mL). The mixture was stirred at 50° C. under nitrogen for 2 hours. The mixture was concentrated in vacuo. The residue was filtered through a pad of silica gel using neat ethyl acetate as eluant. The solution was concentrated in vacuo to afford 0.73 g (66%) of 4-(4-fluorophenyl)-2-(methylamino)pyrimidin-5-ol as a crystalline brown solid. MS m/z 220 [M]+
Reaction SMILES: [F:1][CH:2]([F:29])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:11][CH:12]=[C:13]([CH2:15][CH2:16][C:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[O:25][CH2:26][CH3:27])=[O:18])[N:14]=2)=[CH:6][C:5]=1[OH:28].[CH2:30]1[CH2:40]CN2C(=NCCC2)[CH2:32][CH2:31]1.BrCCC=C.O>C(O)C.C(OCC)(=O)C>[CH2:32]([O:28][C:5]1[CH:6]=[C:7]([C:10]2[O:11][CH:12]=[C:13]([CH2:15][CH2:16][C:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[O:25][CH2:26][CH3:27])=[O:18])[N:14]=2)[CH:8]=[CH:9][C:4]=1[O:3][CH:2]([F:1])[F:29])[CH2:31][CH:30]=[CH2:40]
Reactant: C1CCC2=NCCCN2CC1
Reactant: CCOc1ccccc1C(=O)CCc1coc(-c2ccc(OC(F)F)c(O)c2)n1
Agent: C=CCCBr
Solvent: O
Solvent: CCO
Solvent: CCOC(C)=O
Product: C=CCCOc1cc(-c2nc(CCC(=O)c3ccccc3OCC)co2)ccc1OC(F)F
Reaction time: 8 h

Procedure:
A 0.12 g quantity of the compound obtained in Example 229 and 0.14 ml of DBU were dissolved in 3 ml of ethanol, 0.12 g of 4-bromo-1-butene was then added to the obtained solution, and heating and refluxing were conducted overnight. After cooling, water was added to the obtained reaction mixture, and ethyl acetate extract was performed. The organic layer was washed twice with water, concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=3:1). The obtained crystals were recrystallized from ethanol, thereby yielding 80 mg of white powdery 3-[2-(3-but-3-enyloxy-4-difluoromethoxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propan-1-one.
Reaction SMILES: [I:1][C:2]1[S:6][C:5]([NH:7][C:8](=O)[C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)=[N:4][C:3]=1[C:20]([F:23])([F:22])[F:21].P(Cl)(Cl)(Cl)(Cl)[Cl:25].P(Cl)(Cl)(Cl)=O>>[I:1][C:2]1[S:6][C:5]([N:7]=[C:8]([Cl:25])[C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)=[N:4][C:3]=1[C:20]([F:23])([F:22])[F:21]
Reactant: ClP(Cl)(Cl)(Cl)Cl
Reactant: O=C(Nc1nc(C(F)(F)F)c(I)s1)c1cccc(C(F)(F)F)c1
Solvent: O=P(Cl)(Cl)Cl
Product: FC(F)(F)c1cccc(C(Cl)=Nc2nc(C(F)(F)F)c(I)s2)c1

Procedure:
N-(5-Iodo-4-trifluoromethylthiazol-2-yl)-3-trifluoromethylbenzamide (9.3 g was mixed with phosphorous pentachloride (4.2 g) and phosphorous oxychloride (25 ml) and the mixture was refluxed for 7 hr. The excess phosphorous oxychloride was removed under reduced pressure and the residue was mixed with cold water then extracted with chloroform. The extract was dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure then the residue was recrystallized from chloroform-n-hexane to give N-(5-iodo-4-trifluoromethylthiazol-2-yl)-3-trifluoromethylbenzimidoyl chloride as yellow needles (8.5 g), m. p. 136-137° C.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][NH:8][C:9](=[O:26])[CH2:10][C@@:11]1([C:20]2[S:21][C:22]([Br:25])=[CH:23][CH:24]=2)[S:17](=[O:19])(=[O:18])[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.[N:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[C:33](O)=[O:34].Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][NH:8][C:9](=[O:26])[CH2:10][C@@:11]1([C:20]2[S:21][C:22]([Br:25])=[CH:23][CH:24]=2)[S:17](=[O:19])(=[O:18])[CH2:16][CH2:15][N:14]([C:33]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][N:27]=2)=[O:34])[CH2:13][CH2:12]1
Reactant: O=C(C[C@]1(c2ccc(Br)s2)CCNCCS1(=O)=O)NOC1CCCCO1
Reactant: O=C(O)c1ccccn1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: O=C(C[C@]1(c2ccc(Br)s2)CCN(C(=O)c2ccccn2)CCS1(=O)=O)NOC1CCCCO1
Temperature: 0 °C
Reaction time: 2 h
Yield: 91.2 %

Procedure:
A mixture of N-(2-tetrahydropyranyloxy)-2-[(S)-7-(5-bromo-2-thienyl)-1,1-dioxoperhydro-1,4-thiazepin-7-yl]acetamide (2.40 g), 2-pyridinecarboxylic acid (695 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.48 g) and 1-hydroxybenzotriazole (1.04 g) in anhydrous dimethylformamide (24 ml) was stirred at 0° C. for 2 hours. The mixture was partitioned between ethyl acetate and water. The organic layer was separated, washed with saturated sodium bicarbonate solution, water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of chloroform and methanol (50:1) to give N-(2-tetrahydropyranyloxy)-2-[(S)-7-(5-bromo-2-thienyl)-4-(2-pyridinecarbonyl)-1,1-dioxoperhydro-1,4-thiazepin-7-yl]acetamide as a colorless amorphous powder (2.68 g).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][NH:5][C:4](=[O:8])[CH:3]=1.[CH2:9]([O:11][C:12]1[CH:20]=[CH:19][C:15]([C:16](Cl)=[O:17])=[CH:14][CH:13]=1)[CH3:10]>>[CH2:9]([O:11][C:12]1[CH:20]=[CH:19][C:15]([C:16]([O:8][C:4]2[CH:3]=[C:2]([O:1][C:16](=[O:17])[C:15]3[CH:14]=[CH:13][C:12]([O:11][CH2:9][CH3:10])=[CH:20][CH:19]=3)[CH:7]=[CH:6][N:5]=2)=[O:17])=[CH:14][CH:13]=1)[CH3:10]
Reactant: CCOc1ccc(C(=O)Cl)cc1
Reactant: O=c1cc(O)cc[nH]1
Product: CCOc1ccc(C(=O)Oc2ccnc(OC(=O)c3ccc(OCC)cc3)c2)cc1
Yield: 6 %

Procedure:
The general procedure of Example 16 was followed using 1.00 g of 4-hydroxy-2-pyridone and 3.32 g of 4-ethoxybenzoyl chloride to produce 220 mg of the title compound in a yield of 6%.
Reaction SMILES: [C:1]([C@@H:9]1[CH2:13][CH:12]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:17][CH:16]=2)[N:11](/[CH:27]=[CH:28]/[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:10]1=[O:35])(=O)C1C=CC=CC=1.C=O.N1CCOCC1>CO>[C:18]1([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:17]=[CH:16][C:15]([CH2:14][C@H:12]2[N:11](/[CH:27]=[CH:28]/[C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[C:10](=[O:35])[C:9](=[CH2:1])[CH2:13]2)=[CH:20][CH:19]=1
Reactant: O=C(c1ccccc1)[C@@H]1CC(Cc2ccc(-c3ccccc3)cc2)N(/C=C/c2ccccc2)C1=O
Agent: C=O
Solvent: CO
Solvent: C1COCCN1
Product: C=C1C[C@@H](Cc2ccc(-c3ccccc3)cc2)N(/C=C/c2ccccc2)C1=O
Temperature: 25 °C

Procedure:
Biphenyl-4-ylmethyl-2-oxo-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester (4a, R1=t-butoxycarbonyl, R4=hydroxyl) (3.95 g, 10.0 mmol) is dissolved in 10 mL of methanol, add paraformaldehyde (0.60 g, 20.0 mmol) and morpholine (1.05 g, 12.0 mmol), the mixture is heated to refluxed for 2 h under nitrogen atmosphere, cool to room temperature, evaporate the solvent under vacuum, the residue is dissolved in 50 mL of ethyl acetate, ish with 1% HCl(aq), 10% sodium hydrogen carbonate(aq) and brine, dry over anhydrous sodium sulfate and concentrate under vacuum to obtain (R)-5-Biphenyl-4-ylmethyl-3-methylene-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (1a, R1=t-butoxycarbonyl). 1HNMR (400 MHz, CDCl3): 1.62 (s, 9H, (CH3) 3), 2.56 (m, 1H, 3-CHH), 2.60 (m, 1H, 3CHH), 2.70 (d, 1H, 5-CHH), 3.26 (d, 1H, 5-CHH), 4.43 (m, 1H, 4-CH), 5.45 (d, 1H, C═CHH), 6.17 (d, 1H, C═CHH), 7.20˜7.60 (9H, m, aromatic); m/z (+ESI) 381 ([MNa]+, 7%), 364 ([MH]+, 12), 308(100), 264 (10).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:27]=[CH:26][C:6]([CH2:7][N:8]2[C:12]3[N:13]=[CH:14][CH:15]=[C:16]([NH:17][CH2:18][CH2:19][N:20]4[CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)[C:11]=3[CH:10]=[N:9]2)=[CH:5][CH:4]=1.[H-].[Na+].F[C:31]1[CH:36]=[CH:35][C:34]([N+:37]([O-:39])=[O:38])=[CH:33][C:32]=1[F:40]>CN(C=O)C.CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:12]3[N:13]=[CH:14][CH:15]=[C:16]([N:17]([C:31]4[CH:36]=[CH:35][C:34]([N+:37]([O-:39])=[O:38])=[CH:33][C:32]=4[F:40])[CH2:18][CH2:19][N:20]4[CH2:21][CH2:22][O:23][CH2:24][CH2:25]4)[C:11]=3[CH:10]=[N:9]2)=[CH:26][CH:27]=1
Reactant: COc1ccc(Cn2ncc3c(NCCN4CCOCC4)ccnc32)cc1
Reactant: O=[N+]([O-])c1ccc(F)c(F)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COc1ccc(Cn2ncc3c(N(CCN4CCOCC4)c4ccc([N+](=O)[O-])cc4F)ccnc32)cc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 81.2 %

Procedure:
1-(4-Methoxybenzyl)-N-(2-morpholinoethyl)-1H-pyrazolo[3,4-b]pyridin-4-amine (0.025 g, 0.06804 mmol) was charged to a pressure tube in DMF (1 mL). NaH (0.004082 g, 0.1021 mmol) was added, and the reaction was allowed to stir at room temperature for 15 minutes. 1,2-difluoro-4-nitrobenzene (0.009389 ml, 0.08505 mmol) was added, and the reaction was stirred at room temperature for 3 hours. The reaction mixture was diluted with EtOAc (25 mL) and washed with water (15 mL). The organics were then dried with brine, dried over Na2SO4, filtered and concentrated. Purification via flash Si 5 g eluting with 1-5% MeOH/DCM to afford 28 mg (80%) of product as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.32 (d, 1H), 8.14 (m, 2H), 7.61 (t, 1H), 7.30 (m, 2H), 6.82 (d, 3H), 6.43 (d, 1H), 5.54 (s, 2H), 4.05 (t, 2H), 3.75 (s, 3H), 3.59 (t, 4H), 2.76 (t, 2H), 2.44 (m, 4H); 19F NMR (376 MHz, CDCl3) −113.92 (s, 1F); LRMS (apci pos): 307.1 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[OH:8].C([O-])([O-])=O.[K+].[K+].I[CH2:16][CH3:17]>CC(C)=O>[CH2:16]([O:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[Br:1])[CH3:17]
Reactant: CCI
Reactant: Oc1ccccc1Br
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOc1ccccc1Br
Temperature: 25 °C
Yield: 87 %

Procedure:
To a solution of 2-bromophenol (1.3 ml, 0.012 mol) in 50 ml acetone was added K2CO3 (4.1 g, 0.03 mol) and iodoethane (1.0 ml, 0.013 mol). The reaction mixture was heated to reflux for 8 h, cooled to ambient temperature and filtered. The solvent was removed under reduced pressure and the residue was taken up in EtOAc. The organic phase was washed with 1N NaOH×2, water and brine. Drying over Na2SO4 afforded 2.1 g (88%) of 2-ethoxybromobenzene.
Reaction SMILES: [CH3:1][CH:2]1[CH2:6][N:5]([C:7]2[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=2)[NH:4][C:3]1=[O:14].[Si:15](Cl)([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16].C(N(CC)CC)C.N12CCCN=C1CCCCC2>C1(C)C=CC=CC=1.CN(C1C=CN=CC=1)C>[CH3:1][CH:2]1[CH2:6][N:5]([C:7]2[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=2)[N:4]=[C:3]1[O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16]
Reactant: Cc1ccc(N2CC(C)C(=O)N2)cc1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Solvent: C1CCC2=NCCCN2CC1
Product: Cc1ccc(N2CC(C)C(O[Si](C)(C)C(C)(C)C)=N2)cc1
Temperature: 25 °C
Yield: 98 %

Procedure:
To a stirred solution under nitrogen of 4-methyl-1-p-tolyl-3-pyrazolidinone (19.0 g, 0.10 mole) and t-butyldimethylsilyl chloride (16.6 g, 0.11 mole) in 200 ml toluene, was added sequentially triethylamine (10.6 g, 0.11 mole), 1,8-diazabicyclo- [5.4.0]-undec-7-ene (0.1 g), and 4-(N,N-dimethylamino) pyridine (0.1 g). The mixture was refluxed for 16 hours, cooled to room temperature and filtered. The salts were washed with ether and the solvents of the combined filtrate were removed under reduced pressure. The resulting residue was treated with 200 ml adhydrous ether, filtered to remove salts, and dried over anhydrous magnesium sulfate. Removal of the solvent yielded 29.8 g (98% yield).
Reaction SMILES: [C:1]1([C:7]2[NH:8][C:9]3[C:14]([CH:15]=2)=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.Cl.[NH:18]1[CH2:23][CH2:22][C:21](=O)[CH2:20][CH2:19]1.P(=O)(O)(O)O.CCOC(C)=O>CC(O)=O>[NH:18]1[CH2:19][CH:20]=[C:21]([C:15]2[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[NH:8][C:7]=2[C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:22][CH2:23]1
Reactant: O=C1CCNCC1
Reactant: c1ccc(-c2cc3ccccc3[nH]2)cc1
Agent: Cl
Agent: O=P(O)(O)O
Solvent: CCOC(C)=O
Solvent: O
Solvent: CC(=O)O
Product: C1=C(c2c(-c3ccccc3)[nH]c3ccccc23)CCNC1
Temperature: 25 °C
Reaction time: 6 h
Yield: 72.9 %

Procedure:
2-Phenylindole (25 g, 130 mmol) was stirred at 80° C. in AcOH (200 ml), and 4-piperidone hydrochloride hydrate (50 g, 376 mmol) and 1M phosphoric acid (100 ml) added. After a further 6 h, the mixture was poured into ice/ammonia, and extracted with EtOAc (3×200 ml). The combined organic layers were washed with water and brine, dried, and evaporated in vacuo to give a pale yellow solid. This was suspended in boiling EtOAc (200 ml), cooled to room temperature overnight, and the solid collected, washed with EtOAc and dried to give the title compound (26 g, 73%) as a pale yellow solid; δH (360 MHz, d6-DMSO) 2.00-2.10 (2H, m, NCH2CH2), 2.89 (2H, t, J 5, NCH2CH2), 3.40-3.45 (2H, m, NCH2CH), 5.78 (1H, br s, NCH2CH), 7.00 (1H, t, J 7, indole-H), 7.08 (1H, t, J 7, indole-H), 7.20-7.50 (5H, m, ArH), 7.69 (2H, d, J 7, ArH), 11.3 (1H, br s, indole NH); m/z (ES+) 275 (M++H).
Reaction SMILES: [H-].[Na+].[C:3](#[N:7])[CH2:4][C:5]#[N:6].I[C:9]1[CH:14]=[C:13]([CH3:15])[C:12]([C:16]2[C:21]([CH3:22])=[CH:20][N:19]=[CH:18][C:17]=2[CH3:23])=[C:11]([CH3:24])[CH:10]=1.Cl>COCCOC>[CH3:22][C:21]1[CH:20]=[N:19][CH:18]=[C:17]([CH3:23])[C:16]=1[C:12]1[C:11]([CH3:24])=[CH:10][C:9]([CH:4]([C:3]#[N:7])[C:5]#[N:6])=[CH:14][C:13]=1[CH3:15]
Reactant: N#CCC#N
Reactant: Cc1cncc(C)c1-c1c(C)cc(I)cc1C
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: COCCOC
Product: Cc1cncc(C)c1-c1c(C)cc(C(C#N)C#N)cc1C
Temperature: 25 °C
Reaction time: 1 h
Yield: 95.3 %

Procedure:
To an ice-cooled suspension of NaH (0.12 g, 5.0 mmol) in anhydrous 1,2-dimethoxyethane (8 mL) was added dropwise via syringe a solution of malononitrile (0.165 g, 2.50 mmol) in anhydrous 1,2-dimethoxyethane (2 mL) under N2. The mixture was stirred for 1 h at room temperature under N2. Next, 11 (0.674 g, 2.00 mmol) and tetrakis(triphenyphosphine)palladium(0) (0.232 g, 0.200 mmol) were added to the resulting pink suspension under an N2 flow. The reaction mixture was next stirred at 85° C. under N2 for 5 h. The solvent was then removed under reduced pressure. The resulting solid was washed with benzene (20 mL), dissolved in water, and filtered to give a dark-yellow aqueous solution. This solution was neutralized with 5% HCl to pH=7, and the resulting yellow precipitate was collected by filtration to give an orange solid. The crude product was purified by flash chromatography on silica gel eluting with 1:1 hexane:ethyl acetate, to give 0.525 g (95.5%) of the title compound as red solid: mp 58-60° C.; 1H NMR (400 MHz, CDCl3): δ 8.412 (s, 2H), 7.286 (s, 2H), 5.100 (s, 1H), 1.946 (s, 6H), 1.895 (s, 6H); 13C NMR (100 MHz, CDCl3): δ 149.066, 146.564, 139.513, 137.283, 130.441, 126.692, 125.518, 112.024, 28.059, 19.988, 16.704; Anal. Calcd. for C18H17N3.H2O: C, 73.69; H, 6.53; N, 14.32. Found; C, 73.36; H, 6.35; N, 14.07.
Reaction SMILES: [C:1]([C:4]1[C:9](=[O:10])[C:8]2[CH:11]=[C:12]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:13]([NH:15][S:16]([CH3:19])(=[O:18])=[O:17])=[CH:14][C:7]=2[O:6][CH:5]=1)(O)=[O:2].[NH2:27][C:28]1[NH:32][N:31]=[N:30][N:29]=1.C1(N=C=NC2CCCCC2)CCCCC1>>[CH3:19][S:16]([NH:15][C:13]1[C:12]([O:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:11][C:8]2[C:9](=[O:10])[C:4]([C:1]([NH:27][C:28]3[NH:32][N:31]=[N:30][N:29]=3)=[O:2])=[CH:5][O:6][C:7]=2[CH:14]=1)(=[O:18])=[O:17]
Reactant: Nc1nnn[nH]1
Reactant: CS(=O)(=O)Nc1cc2occ(C(=O)O)c(=O)c2cc1Oc1ccccc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Product: CS(=O)(=O)Nc1cc2occ(C(=O)Nc3nnn[nH]3)c(=O)c2cc1Oc1ccccc1

Procedure:
3-Carboxy-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one was reacted with 5-aminotetrazole in the presence of dicyclohexylcarbodiimide to obtain 7-methylsulfonylamino-6-phenoxy-3-(1,2,3,4-tetrazol-5-yl-aminocarbonyl)-4H-1-benzopyran-4-one.
Reaction SMILES: O.C[O:3][C:4]1[C:9]([O:10][CH3:11])=[C:8]([O:12][CH3:13])[C:7]([O:14]C)=[C:6]([CH3:16])[C:5]=1[CH:17]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][OH:24]>C(#N)C>[CH3:13][O:12][C:8]1[C:7](=[O:14])[C:6]([CH3:16])=[C:5]([CH:17]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][OH:24])[C:4](=[O:3])[C:9]=1[O:10][CH3:11]
Reactant: COc1c(C)c(C(CCCCCCO)c2ccccc2)c(OC)c(OC)c1OC
Solvent: CC#N
Solvent: O
Product: COC1=C(OC)C(=O)C(C(CCCCCCO)c2ccccc2)=C(C)C1=O
Reaction time: 0.33 h
Yield: 83.8 %

Procedure:
A solvent mixture of acetonitrile (12 ml) and water (6 ml) was added to 2.01 g (5.0 mmole) of 7-(2,3,4,5-tetramethoxy-6-methylphenyl)-7-phenylheptanol and 2.51 g (5×3 mmole) of 2,6-pyridinecarboxylic acid, and a cooled solution of 8.22 g (5×3 mmole) of ceric ammonium nitrate in 50% aqueous acetonitrile (16 ml) was added dropwise to the mixture over the 20 minutes period under ice-cooling. After stirring was continued for another 20 minutes under ice-cooling, the insoluble matter was filtered out, and the acetonitrile was distilled off under reduced pressure. Isopropyl ether was added to the residue to carry out extraction. The isopropyl ether layer was separated out, washed with aqeuous sodium chloride solution, dried (magnesium sulfate) and evaporated. The residue was chromatographed on a silica gel column to elute with isopropyl ether/ethyl acetate to give 1.56 g (84%) of 7-(5,6-dimethoxy-3-methyl-1,4-benzoquinon -2-yl)-7-phenylheptanol. Its typical physical properties and nuclear magnetic resonance spectrum data are shown in Table 1. By following the procedure of this Example, the Compound No. 57 was prepared.
Reaction SMILES: [CH2:1]([N:3]([CH2:6]/[CH:7]=[C:8](\[CH3:14])/[CH:9]([O:12][CH3:13])[O:10][CH3:11])[CH2:4][CH3:5])[CH3:2]>O1CCCC1>[CH2:1]([N:3](/[CH:6]=[CH:7]/[C@H:8]([CH3:14])[CH:9]([O:12][CH3:13])[O:10][CH3:11])[CH2:4][CH3:5])[CH3:2]
Reactant: CCN(CC)C/C=C(\C)C(OC)OC
Solvent: C1CCOC1
Product: CCN(/C=C/[C@H](C)C(OC)OC)CC
Temperature: 90 °C

Procedure:
A pyrex bomb tube was charged with 2.02 g (10 mmol) of (E)-N,N-diethyl-4,4-dimethoxy-3-methyl-2-butenylamine, 10 ml of tetrahydrofuran and 83.2 mg (0.10 mmol) of [η4 -bicyclo[2.2.1]hepta-2,5-diene][(S)-(6,6'-dimethyl-2,2'-biphenylylene)-bis(diphenylphosphine)] rhodium (I) tetrafluoroborate. After degasifying the mixture, the tube was sealed and heated at 90° C. for 56 hours in a bomb tube oven. The red-brown solution was evaporated and the residue was distilled in a bulb-tube at about 70°/0.2 mmHg. There was obtained (1E,3S)-N,N-diethyl-4,4-dimethoxy-3-methyl-1-butenylamine; purity according to gas chromatography 70%; [α]D20 =-12.9° (c=4.05% in hexane). The corresponding (S)-4,4-dimethoxy-3-methylbutanal has a rotation [α]D20 =-23.3° (c=4.66% in hexane); purity according to gas chromatography 96%.