Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[Mg]Br.[N:13]12[CH2:20][CH2:19][C:16]([C:21]([O:23]CC)=O)([CH2:17][CH2:18]1)[CH2:15][CH2:14]2>C1COCC1>[N:13]12[CH2:14][CH2:15][C:16]([C:21]([C:3]3[CH:2]=[CH:1][C:10]4[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=4)[CH:4]=3)([C:2]3[CH:3]=[CH:4][C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[CH:1]=3)[OH:23])([CH2:17][CH2:18]1)[CH2:19][CH2:20]2
Reactant: Br[Mg]c1ccc2ccccc2c1
Reactant: CCOC(=O)C12CCN(CC1)CC2
Solvent: C1CCOC1
Product: OC(c1ccc2ccccc2c1)(c1ccc2ccccc2c1)C12CCN(CC1)CC2
Temperature: 25 °C
Yield: 77.3 %

Procedure:
A solution of (2-naphthalenyl)magnesiumbromide (0.5 M in THF, 6.5 mL, 3.25 mmol) was chilled down to 0° C. under Ar. Ethyl 1-azabicyclo[2.2.2]octane-4-carboxylate (0.1597 g, 0.871 mmol) in THF (4 mL) was slowly added to the reaction mixture at 0° C. over 20 min. The reaction was allowed to warm up to room temperature and then heated at 60° C. for 16 h. The reaction was chilled in an ice bath, quenched with saturated NH4Cl, and concentrated under vacuum. The resulting residue was treated with H2O and extracted with EtOAc. The combined organic layers were dried with MgSO4, filtered, and concentrated under vacuum to yield the desired product (0.265 g, 77.3%). EI-MS m/z 394 (M+H+) Rt (1.90 min).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH2:9][S:10]([C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17](=[O:22])/[C:16]/2=[CH:23]\[C:24]1[NH:25][C:26]([CH3:32])=[CH:27][C:28]=1[C:29](O)=[O:30])(=[O:12])=[O:11].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH2:55][CH2:56][CH:57]([OH:65])[CH2:58][N:59]1[CH2:64][CH2:63][O:62][CH2:61][CH2:60]1>CN(C=O)C>[OH:65][CH:57]([CH2:58][N:59]1[CH2:64][CH2:63][O:62][CH2:61][CH2:60]1)[CH2:56][NH:55][C:29]([C:28]1[CH:27]=[C:26]([CH3:32])[NH:25][C:24]=1/[CH:23]=[C:16]1\[C:17](=[O:22])[NH:18][C:19]2[C:15]\1=[CH:14][C:13]([S:10]([CH2:9][C:3]1[C:4]([Cl:8])=[CH:5][CH:6]=[CH:7][C:2]=1[Cl:1])(=[O:11])=[O:12])=[CH:21][CH:20]=2)=[O:30]
Reactant: Cc1cc(C(=O)O)c(/C=C2\C(=O)Nc3ccc(S(=O)(=O)Cc4c(Cl)cccc4Cl)cc32)[nH]1
Reactant: NCC(O)CN1CCOCC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: Cc1cc(C(=O)NCC(O)CN2CCOCC2)c(/C=C2\C(=O)Nc3ccc(S(=O)(=O)Cc4c(Cl)cccc4Cl)cc32)[nH]1
Temperature: 25 °C

Procedure:
To a mixture of 2-[5-(2,6-dichloro-phenylmethanesulfonyl)-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-5-methyl-1H-pyrrole-3-carboxylic acid (100 mg, 0.2 mmol), HOBt (33 mg, 1.2 eq.), EDAC.HCl (47 mg, 1.2 eq.) and 1-amino-3-morpholin-4-yl-propan-2-ol (34 mg, 1.1 eq.) in DMF (2 mL) was added TEA (0.071 mL, 2.5 eq.). After stirring at rt for 2 weeks, the reaction was concentrated, diluted with DCM. Solid sodium bicarbonate was added to the mixture followed by stirring for 15 mins. The orange suspension was then loaded on to a silica gel to give the titled compound as an orange solid.
Reaction SMILES: [OH:1][C:2]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:3]=1[NH2:4].[CH2:12]([N:19]=[C:20]=[O:21])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>>[OH:1][C:2]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:3]=1[NH:4][C:20]([NH:19][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:21]
Reactant: O=C=NCc1ccccc1
Reactant: Nc1ccc([N+](=O)[O-])cc1O
Product: O=C(NCc1ccccc1)Nc1ccc([N+](=O)[O-])cc1O
Yield: 63 %

Procedure:
N-(2-Hydroxy-4-nitrophenyl)-N′-(benzyl)urea was prepared from 2-hydroxy 4-nitro aniline (308 mg, 2.0 mmol) and benzyl isocyanate (2 mmol) according to the procedure in General Method A. The product was purified by dilution with methylene chloride and precipitation with hexanes. Filtering afforded the title compound (362 mg, 52%). EI-MS m/z 288 (M+H)+
Reaction SMILES: [F:1][C:2]([F:44])([F:43])[C:3]1[CH:4]=[C:5]([CH:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[CH:35]=[C:34]([CH:36]([CH3:38])[CH3:37])[C:33]([F:39])=[CH:32][C:31]=3[O:40]C)[CH:14]2[CH3:42])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.B(Br)(Br)Br>C(Cl)Cl>[F:44][C:2]([F:1])([F:43])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:28])([F:29])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[CH:35]=[C:34]([CH:36]([CH3:38])[CH3:37])[C:33]([F:39])=[CH:32][C:31]=3[OH:40])[C@H:14]2[CH3:42])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1
Reactant: COc1cc(F)c(C(C)C)cc1-c1ccc(C(F)(F)F)cc1CN1C(=O)OC(c2cc(C(F)(F)F)cc(C(F)(F)F)c2)C1C
Agent: BrB(Br)Br
Solvent: ClCCl
Product: CC(C)c1cc(-c2ccc(C(F)(F)F)cc2CN2C(=O)O[C@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)[C@@H]2C)c(O)cc1F
Reaction time: 1 h
Yield: 73.8 %

Procedure:
A solution of 4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-3-((4′-fluoro-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl)methyl)-4-methyl-1,3-oxazolidin-2-one (54) [prepared by methods described in WO2007/005572] (1.4 g) in DCM (5 mL) was treated with BBr3 (0.9 mL) at 15-16° C. and the reaction mixture stirred for 1 hr. The mixture was quenched with ice and diluted with EtOAc (150 mL). The mixture was washed with water, sat'd NaHCO3 solution, and brine, dried (Na2SO4), filtered and the solvent concentrated under reduced pressure. The crude product was purified by chromatography on silica gel to give 1.01 g (60%) of 55. 1H NMR (CDCl3) δ: 7.85 (s, 1H), 7.75-7.62 (m, 4H), 7.42 (m, 1H), 6.96 (dd, 1H), 7.69 (dd, 1H), 5.64 (d, 0.5H), 5.39 (d, 0.5H), 4.92-4.80 (m, 1H), 4.18 (d, 0.5H), 3.99 (d, 0.5H), 3.85 (m, 0.5H), 3.75 (m, 0.5H), 3.19 (m, 1H), 1.17-1.25 (m, 6H), 0.57 (d, 1.5H), 0.45 (d, 1.5H).
Reaction SMILES: [F:1][C:2]([F:14])([F:13])[C:3]1[C:4]([S:9]([OH:12])(=[O:11])=[O:10])=[N:5][CH:6]=[CH:7][CH:8]=1.[F:15]F>C(#N)C>[F:15][N+:5]1[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:13])([F:1])[F:14])[C:4]=1[S:9]([O-:12])(=[O:11])=[O:10]
Reactant: FF
Reactant: O=S(=O)(O)c1ncccc1C(F)(F)F
Solvent: CC#N
Product: O=S(=O)([O-])c1c(C(F)(F)F)ccc[n+]1F

Procedure:
To a mixture of 3-(trifluoromethyl)pyridine-2-sulfonic acid (115 mg, 0.5 mmol) and acetonitrile (20 ml) in a flask on a cooling bath kept at -10° C., a mixed gas of 10% fluorine/90% nitrogen was introduced at a flow rate of 15 ml/min. The total amount of the fluorine gas was 1.5 mmol. Thereafter, the nitrogen gas alone was introduced for 30 minutes. After the reaction mixture was concentrated, ethyl acetate was added to the residue. The precipitated crystal was recovered by filtration to obtain N-fluoro-3-(trifluoromethyl)pyridinium-2-sulfonate (84.6 mg, 0.345 mmol). Yield, 69%. Melting point, 180°-196° C. (with decomposition).
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[NH:6]1[CH:10]=[N:9][CH:8]=[N:7]1.C(N(CC)CC)C.[F:18][C:19]1[C:20](=O)[NH:21][C:22](=[O:29])[N:23]([CH2:25][CH:26]([CH3:28])[CH3:27])[CH:24]=1.O>CC#N>[F:18][C:19]1[C:20]([N:6]2[CH:10]=[N:9][CH:8]=[N:7]2)=[N:21][C:22](=[O:29])[N:23]([CH2:25][CH:26]([CH3:27])[CH3:28])[CH:24]=1
Reactant: CC(C)Cn1cc(F)c(=O)[nH]c1=O
Reactant: c1nc[nH]n1
Solvent: O
Solvent: CC#N
Solvent: O=P(Cl)(Cl)Cl
Product: CC(C)Cn1cc(F)c(-n2cncn2)nc1=O
Reaction time: 1 h
Yield: 72.8 %

Procedure:
Phosphoryl trichloride (3.3 g, 21 mmol) was added to a solution of 1,2,4-triazole (6.7 g, 97 mmol) in CH3CN (53 mL) under nitrogen at room temperature. The mixture was cooled to 0° C., whereupon triethylamine (Et3N, 9.5 g, 92 mmol) was added dropwise followed by the addition of a solution of 5-fluoro-1-isobutylpyrimidine-2,4(1H,3H)-dione (2.0 g, 11 mmol) in CH3CN (30 mL). After stiffing for 1 h at room temperature, Et3N (3.6 g, 36 mmol) and then water (5 mL, 280 mmol) were added, and the reaction mixture was stirred for an additional 10 min. The crude reaction mixture was then concentrated in vacuo. Recrystallization from EtOAc/petroleum ether provided 5-fluoro-1-isobutyl-4-(1H-1,2,4-triazol-1-yl)pyrimidin-2(1H)-one (1.9 g, 74%) as an off white crystalline solid: mp 150-153° C.; 1H NMR (400 MHz, CDCl3) δ 9.26 (s, 1H), 8.23 (s, 1H), 7.84 (d, J=5.7 Hz, 1H), 3.79 (d, J=7.4 Hz, 2H), 2.28 (dt, J=13.7, 6.9 Hz, 1H), 1.02 (d, J=6.7 Hz, 6H); ESIMS m/z 238 ([M+H]+).
Reaction SMILES: Cl.[N:2]1([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=3)[N:9]=2)[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.Br[CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[C:30]1([CH2:29][CH2:28][N:5]2[CH2:6][CH2:7][N:2]([C:8]3[C:16]4[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=4)[N:10]([C:17]4[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:24])[F:25])=[CH:19][CH:18]=4)[N:9]=3)[CH2:3][CH2:4]2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1
Reactant: BrCCc1ccccc1
Reactant: FC(F)(F)c1ccc(-n2nc(N3CCNCC3)c3ccccc32)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: FC(F)(F)c1ccc(-n2nc(N3CCN(CCc4ccccc4)CC3)c3ccccc32)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 91.3 %

Procedure:
A stirred mixture of 4.0 g of 3-(1-piperazinyl)-1-[4-(trifluoromethyl)phenyl]-1H-indazole hydrochloride, 2.4 g of (2-bromoethyl)benzene, 1.8 g of potassium carbonate and 60 ml of dimethylformamide was heated, under nitrogen, at 70°-75° for 8 hours, and then stirred at ambient temperature for 8 hours. The reaction mixture was poured into water, and the aqueous mixture extracted with ethyl acetate. The extract was washed with water, dried over anhydrous magnesium sulfate and concentrated to an oil. The oil was chromatographed on a Water's Model High Pressure Liquid Chromatograph utilizing silica columns and eluting with hexane/ethyl acetate (30%). Concentration of the appropriate fractions gave 4.3 g of 3-[4-(2-phenylethyl)-1-piperazinyl]-1-[4-(trifluoromethyl)phenyl]-1H-indazole. The free base was dissolved in diethyl ether and treated with hydrogen chloride to precipitate the corresponding hydrochloride salt. Recrystallization from ethanol/diethyl ether gave 3.1 g of 3-[4-(2-phenylethyl)-1-piperazinyl]-1-[ 4-(trifluoromethyl) phenyl]-1H-indazole hydrochloride, mp 255°-257°.
Reaction SMILES: Cl[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][C:17]=3[F:24])=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[N:9]2)=[CH:4][CH:3]=1.[CH:25]([B-](F)(F)F)=[CH2:26].[K+].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:25]([C:2]1[CH:11]=[C:10]2[C:5]([C:6]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][C:17]=3[F:24])=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[N:9]2)=[CH:4][CH:3]=1)=[CH2:26]
Reactant: COC(=O)c1cc(-c2ccc(OC)cc2F)c2ccc(Cl)cc2n1
Reactant: C=C[B-](F)(F)F
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: C=Cc1ccc2c(-c3ccc(OC)cc3F)cc(C(=O)OC)nc2c1
Temperature: 85 °C
Reaction time: 1 h
Yield: 71.2 %

Procedure:
Methyl 7-chloro-4-(2-fluoro-4-methoxyphenyl)quinoline-2-carboxylate (1.8 g, 5.21 mmol) was dissolved in dioxane (23.43 ml), degassed 10 minutes with N2. Added potassium vinyltrifluoroborate (1.395 g, 10.41 mmol), palladium(II) acetate (0.088 g, 0.390 mmol), 2-bicyclohexylphosphino-2′,6′-dimethoxybiphenyl (0.321 g, 0.781 mmol) and cesium carbonate (5.09 g, 15.62 mmol) followed by degassed water (2.60 ml). Degassed with N2 for another 10 minutes and then the mixture was stirred at 85° C. for 1 hour. Reaction was complete. The reaction mixture was cooled to ambient temperature and then diluted with EtOAc. Partitioned EtOAc with water, washed EtOAc extract with brine, dried using anhy. MgSO4 and then concentrated. The residue was purified by column chromatography on silica gel, eluting with hexanes to EtOAc to afford methyl 7-ethenyl-4-(2-fluoro-4-methoxyphenyl)quinoline-2-carboxylate (1.25 g, 3.71 mmol, 71.2% yield) as a yellow solid.
Reaction SMILES: [NH2:1][C:2]1[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[C:16](OC(C)=C)(=[O:18])[CH3:17]>C(OCC)(=O)C>[C:16]([N:8]1[CH2:7][CH2:6][C:5]2[C:10](=[C:11]([C:12]([F:15])([F:13])[F:14])[C:2]([NH2:1])=[CH:3][CH:4]=2)[CH2:9]1)(=[O:18])[CH3:17]
Reactant: Nc1ccc2c(c1C(F)(F)F)CNCC2
Reactant: C=C(C)OC(C)=O
Solvent: CCOC(C)=O
Product: CC(=O)N1CCc2ccc(N)c(C(F)(F)F)c2C1

Procedure:
7-Amino-8-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline (8.7 g., 0.04 m.) is treated with isopropenyl acetate (8.0 g., 0.08 m.) in refluxing ethyl acetate to give N-acetyl-7-amino-8-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([C:18]2[C:26]([OH:27])=[C:25]([CH3:28])[C:24]([CH3:29])=[C:23]3[C:19]=2[CH2:20][CH2:21][CH2:22]3)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([O:16][CH3:17])=[O:15])=[CH:4][CH:3]=1.[Cr](Cl)([O-])(=O)=[O:31].[NH+]1C=CC=CC=1>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([C:18]2[C:26]([OH:27])=[C:25]([CH3:28])[C:24]([CH3:29])=[C:23]3[C:19]=2[CH2:20][CH2:21][C:22]3=[O:31])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([O:16][CH3:17])=[O:15])=[CH:4][CH:3]=1
Reactant: COC(=O)CCCCC[C@H](c1ccc(F)cc1)c1c(O)c(C)c(C)c2c1CCC2
Reactant: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: Cc1ccccc1
Product: COC(=O)CCCCC[C@H](c1ccc(F)cc1)c1c(O)c(C)c(C)c2c1CCC2=O
Reaction time: 23 h
Yield: 65.7 %

Procedure:
To a solution of methyl (R)-7-(4-fluorophenyl)-7-(5-hydroxy-6,7-dimethylindan-4-yl)heptanoate (16.0 g, 40.2 mmol) in toluene (640 ml) was added a mixture of pyridinium chlorochromate (43.3 g, 0.20 ml) and Celite (52 g) at 0° C. under argon atmosphere, followed by stirring for 23 hours at the same temperature. Insolubles were filtered and washed with toluene. The filtrate and washes were combined and concentrated. The residue was subjected to a silica gel column chromatography to give methyl (R)-7-(4-fluorophenyl)-7-(5-hydroxy-6,7-dimethyl-l-oxoindan-4-yl)heptanoate (10.9 g). The compound obtained is the same as Compound No. 15. Likewise, Compound 29 was prepared. Physico-chemical properties and spectral data are shown in [Table 6].
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[O:13][CH:14]=[C:15]([C:17]([OH:19])=O)[N:16]=2)=[CH:8][CH:7]=1.[NH:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>ClCCl>[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]2[O:13][CH:14]=[C:15]([C:17]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[O:19])[N:16]=2)=[CH:10][CH:11]=1
Reactant: O=C(O)c1coc(-c2ccc(OCCCCl)cc2)n1
Reactant: C1COCCN1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(c1coc(-c2ccc(OCCCCl)cc2)n1)N1CCOCC1
Temperature: 25 °C
Reaction time: 24 h
Yield: 98 %

Procedure:
A solution of 2-[4-(3-chloropropoxy)phenyl]-1,3-oxazole-4-carboxylic acid i34 (0.5 g, 1.57 mmol, 1 eq), morpholine (0.15 g, 1.73 mmol, 1.1 eq) and triethylamine (0.44 ml, 3.14 mmol, 2 eq) in dichloromethane (20 ml) is cooled to 0° C. N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.33 g, 1.73 mmol, 1.1 eq) and 1-hydroxybenzotriazole (0.04 g, 0.31 mmol, 0.2 eq) are added to the solution and the mixture is stirred 24 h at room temperature. The mixture is then washed with water and a saturated solution of aqueous ammonium chloride. The organic layer is dried over magnesium sulfate, filtered and concentrated under vacuum to give 0.54 g of 4-({2-[4-(3-chloropropoxy)phenyl]-1,3-oxazol-4-yl}carbonyl)morpholine i35.
Reaction SMILES: OC(C1[O:5][C:6](=[O:20])[C:7]2[C:12](C=1C1C=CC=CC=1)=[CH:11][CH:10]=[CH:9][CH:8]=2)C.Br[C:22]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)C(=O)O[C:23]=1[CH:33]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH3:34].C1(B(O)O)C=CC=CC=1>>[O:20]=[C:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:22]([C:31]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[C:23]([CH:33]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH3:34])[O:5]1
Reactant: CC(O)c1oc(=O)c2ccccc2c1-c1ccccc1
Reactant: CC(NC(=O)OC(C)(C)C)c1oc(=O)c2ccccc2c1Br
Agent: OB(O)c1ccccc1
Product: CC(NC(=O)OC(C)(C)C)c1oc(=O)c2ccccc2c1-c1ccccc1
Yield: 22.6 %

Procedure:
The title compound was made in a way similar to that of intermediate B1 from tert-butyl 1-(4-bromo-1-oxo-1H-isochromen-3-yl)ethylcarbamate (Intermediate A3, 500 mg, 1.358 mmol), phenylboronic acid (215 mg, 1.765 mmol), to give the title compound (112 mg, 22.6%) as a yellowish oil.
Reaction SMILES: [C:1](Cl)(Cl)=[S:2].C(=O)(O)[O-].[Na+].[Cl:10][C:11]1[CH:12]=[C:13]([CH:17]([C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=2)[CH2:18][NH2:19])[CH:14]=[CH:15][CH:16]=1>C(Cl)Cl>[Cl:10][C:11]1[CH:12]=[C:13]([CH:17]([C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=2)[CH2:18][N:19]=[C:1]=[S:2])[CH:14]=[CH:15][CH:16]=1
Reactant: NCC(c1ccc([N+](=O)[O-])cc1)c1cccc(Cl)c1
Reactant: S=C(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: O=[N+]([O-])c1ccc(C(CN=C=S)c2cccc(Cl)c2)cc1

Procedure:
A solution of 1.192 mmol of thiophosgene in 5 ml of methylene chloride was added to an aqueous solution of 2.71 mmol of sodium bicarbonate. Then, over the course of 15 minutes, a mixture of 1.084 mmol of 2-(3-chlorophenyl)-2-(4-nitrophenyl)ethylamine was added dropwise to this mixture. After removal of the organic phase and extraction of the aqueous phase once again with dichloromethane, the combined organic phases were washed with water and the solvent was removed by distillation under reduced pressure in a Rotavapor. The reddish oily 2-(3-chlorophenyl)-2-(4-nitrophenyl)ethyl isothiocyanate was stored in a closed vessel with exclusion of moisture in a refrigerator until processed further.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([S:9][CH2:10][CH:11]2[CH2:13][CH2:12]2)[N:4]=1.C([O:16][C:17](=[O:28])[CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[C:22]([Cl:27])[CH:21]=1)C>>[Cl:27][C:22]1[CH:21]=[C:20]([CH2:19][CH2:18][C:17]([OH:28])=[O:16])[CH:25]=[CH:24][C:23]=1[O:26][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([S:9][CH2:10][CH:11]2[CH2:13][CH2:12]2)[N:4]=1
Reactant: CCOC(=O)CCc1ccc(O)c(Cl)c1
Reactant: ClCc1cccc(SCC2CC2)n1
Product: O=C(O)CCc1ccc(OCc2cccc(SCC3CC3)n2)c(Cl)c1
Yield: 63.5 %

Procedure:
2-Chloromethyl-6-cyclopropylmethylsulfanyl-pyridine (43 mg, 0.20 mmol) obtained in Step D of Preparation Example 20 and 3-(3-chloro-4-hydroxy-phenyl)-propionic acid ethyl ester (51 mg, 0.22 mmol) obtained in Step C of Preparation Example 42 were used to react sequentially in the same manner as in Steps A and B of Example 1 to obtain the title compound (48 mg, 72%).
Reaction SMILES: [CH2:1]([OH:23])[C@H:2]1[O:7][C@H:6](O[C@]2(CO)O[C@H](CO)[C@@H](O)[C@@H]2O)[C@H:5]([OH:20])[C@@H:4]([OH:21])[C@@H:3]1[OH:22].[CH2:24]([OH:46])[C@H:25]1[O:30][C@H:29]([O:31][C@H:32]2[C@H:37]([OH:38])[C@@H:36]([OH:39])[C@H:35]([OH:40])[O:34][C@@H:33]2[CH2:41][OH:42])[C@H:28]([OH:43])[C@@H:27]([OH:44])[C@@H:26]1[OH:45]>>[CH2:1]([OH:23])[C@H:2]1[O:7][C@H:6]([O:46][CH2:24][C@H:25]2[O:30][C@H:29]([O:31][C@@H:32]([C@H:37]([OH:38])[C@@H:36]([OH:39])[CH:35]=[O:40])[C@H:33]([OH:34])[CH2:41][OH:42])[C@H:28]([OH:43])[C@@H:27]([OH:44])[C@@H:26]2[OH:45])[C@H:5]([OH:20])[C@@H:4]([OH:21])[C@@H:3]1[OH:22]
Reactant: OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O
Reactant: OC[C@H]1O[C@@](CO)(O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@@H](O)[C@@H]1O
Product: O=C[C@H](O)[C@@H](O)[C@H](O[C@H]1O[C@H](CO[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@@H](O)[C@H](O)[C@H]1O)[C@H](O)CO

Procedure:
A mixture containing 3 parts by weight of sucrose and 7 parts by weight of "SUNMALT-S®", a maltose powder commercialized by Hayashibara Co., Ltd., Okayama, Japan, was prepared into a 30% aqueous solution. In accordance with the method in Experiment 1-2, the resultant aqueous solution was subjected to the action of dextransucrase to obtain a panose-rich saccharide solution.
Reaction SMILES: [O:1]=[C:2]1[O:6][C@H:5]([C:7]([OH:9])=[O:8])[CH2:4][CH2:3]1.[CH:10]1[C:11]2[C:26](=[O:27])[C:25]([C:28]([OH:30])=[O:29])=[CH:24][N:23]([CH:31]3[CH2:33][CH2:32]3)[C:12]=2[CH:13]=[C:14]([N:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)[C:15]=1[F:16].O>CC(C)=O>[CH:10]1[C:11]2[C:26](=[O:27])[C:25]([C:28]([OH:30])=[O:29])=[CH:24][N:23]([CH:31]3[CH2:32][CH2:33]3)[C:12]=2[CH:13]=[C:14]([N:17]2[CH2:18][CH2:19][NH:20][CH2:21][CH2:22]2)[C:15]=1[F:16].[O:1]=[C:2]1[O:6][C@H:5]([C:7]([O-:9])=[O:8])[CH2:4][CH2:3]1
Reactant: O=C1CC[C@@H](C(=O)O)O1
Agent: O=C(O)c1cn(C2CC2)c2cc(N3CCNCC3)c(F)cc2c1=O
Solvent: CC(C)=O
Solvent: O
Product: O=C1CC[C@@H](C(=O)[O-])O1
Reaction time: 0.5 h

Procedure:
0.781 G (0.006 mole) of (S)-5-oxotetrahydrofuran-2-carboxylic acid and 1.99 g (0.006 mole) of Ciprofloxacin were added to 10 mL of distilled water. The resulting mixture was stirred for 30 minutes to dissolve it completely. After adding 20 mL of anhydrous acetone, the resulting solution was further stirred for 30 minutes under ice-cooling and allowed to stand to precipitate solids. The precipitated solids were filtered under reduced pressure through a filter paper (Whatman Filter Paper No. 1), washed three times with each 30 mL of anhydrous acetone,-and dried under vacuum to give 2.27 g of the titled compound as white solids. M.P. 214°-219° C. (decomposition) [α]D25 =-3.33 (H2O)
Reaction SMILES: C[N:2](C)[CH:3]=[N:4][C:5]([C:7]1[N:16]=[C:15]2[N:9]([CH2:10][CH2:11][O:12][C:13]3[CH:20]=[C:19]([Cl:21])[N:18]=[CH:17][C:14]=32)[CH:8]=1)=O.Cl.[F:24][C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=1[NH:32]N>C(O)(=O)C>[Cl:21][C:19]1[N:18]=[CH:17][C:14]2[C:15]3[N:9]([CH2:10][CH2:11][O:12][C:13]=2[CH:20]=1)[CH:8]=[C:7]([C:5]1[N:32]([C:26]2[CH:27]=[CH:28][C:29]([F:31])=[CH:30][C:25]=2[F:24])[N:2]=[CH:3][N:4]=1)[N:16]=3
Reactant: CN(C)C=NC(=O)c1cn2c(n1)-c1cnc(Cl)cc1OCC2
Reactant: NNc1ccc(F)cc1F
Agent: Cl
Solvent: CC(=O)O
Product: Fc1ccc(-n2ncnc2-c2cn3c(n2)-c2cnc(Cl)cc2OCC3)c(F)c1
Temperature: 95 °C
Reaction time: 2.5 h
Yield: 77.8 %

Procedure:
8-Chloro-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulene-2-carboxylic acid 1-dimethylamino-methylideneamide (0.00907 mol) was dissolved in Acetic acid (36 mL). 2,4-Difluorophenylhydrazine hydrochloride (1.965 g, 0.01088 mol) was added and the reaction was stirred at 95° C. for 2.5 hours. The AcOH was removed in vacuo. The crude was triturated in iPrOH to afford 2.828 g (78% yield over 2 steps) of 8-Chloro-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulene as a light brown powder clean by 1H NMR. MS(ESI+) 401.1
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([CH3:17])=[C:5]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[NH:6]2.[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C=O)C>[CH2:18]([N:6]1[C:7]2[C:3](=[C:2]([Br:1])[CH:10]=[CH:9][CH:8]=2)[C:4]([CH3:17])=[C:5]1[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: Cc1c(-c2ccccc2)[nH]c2cccc(Br)c12
Reactant: BrCc1ccccc1
Solvent: CN(C)C=O
Product: Cc1c(-c2ccccc2)n(Cc2ccccc2)c2cccc(Br)c12

Procedure:
The desired product was prepared using a procedure similar to step 2 of example 3. Thus, 4-bromo-3-methyl-2-phenyl-1H-indole (1.467 g, 5.126 mmol) was reacted with k-t-butoxide (0.604 g, 5.383 mmol) and benzyl bromide (0.924 g, 5.383 mmol) in DMF (15 ml) to give the product (1.286 g, 3.651 mmol, 71%) as a colorless oil. 1H DMSO-d6) δ 2.40 (s, 3H), 5.27 (s, 2H), 6.79-6.81 (m, 2H), 6.98 (t, J=7.6 Hz, 1H), 7.15-7.21 (m, 3H), 7.23 (dd, J=0.8, 7.5 Hz, 1H), 7.36-7.38 (m, 3H), 7.43-7.53 (m, 3H); [ESI(+)], m/z 376/378 (M+H)+.