Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][S:2][CH2:3][CH2:4][C:5]1[N:6]([CH2:10][CH2:11][CH2:12][CH2:13][C:14]2[CH:38]=[CH:37][C:17]([O:18][CH2:19][C:20]3[N:21]=[C:22](/[CH:25]=[CH:26]/[C:27]4[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=4)[O:23][CH:24]=3)=[CH:16][CH:15]=2)[CH:7]=[CH:8][N:9]=1.ClC1C=CC=C(C(OO)=[O:47])C=1>>[CH3:1][S:2]([CH2:3][CH2:4][C:5]1[N:6]([CH2:10][CH2:11][CH2:12][CH2:13][C:14]2[CH:38]=[CH:37][C:17]([O:18][CH2:19][C:20]3[N:21]=[C:22](/[CH:25]=[CH:26]/[C:27]4[CH:32]=[CH:31][C:30]([C:33]([F:35])([F:34])[F:36])=[CH:29][CH:28]=4)[O:23][CH:24]=3)=[CH:16][CH:15]=2)[CH:7]=[CH:8][N:9]=1)=[O:47]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CSCCc1nccn1CCCCc1ccc(OCc2coc(/C=C/c3ccc(C(F)(F)F)cc3)n2)cc1
Product: CS(=O)CCc1nccn1CCCCc1ccc(OCc2coc(/C=C/c3ccc(C(F)(F)F)cc3)n2)cc1
Yield: 73.8 %

Procedure:
Using 4-[[4-[4-[2-[2-(methylsulfanyl)ethyl]-1H-imidazol-1-yl]butyl]phenoxy]methyl]-2-[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]-1,3-oxazole (250 mg) and 70% m-chloroperbenzoic acid (114 mg), the same reaction as Example 11-(ii) was carried out to yield the titled compound (190 mg) as a colorless amorphous form.
Reaction SMILES: S1(CCCC1)(=O)=O.[F:8][C:9]([F:20])([F:19])[C:10]1[CH:11]=[C:12]([CH:16]=[CH:17][CH:18]=1)[C:13](Cl)=[O:14].[H][H].Cl>[Pd].[O-]S([O-])(=O)=O.[Ba+2]>[F:8][C:9]([F:19])([F:20])[C:10]1[CH:11]=[C:12]([CH:16]=[CH:17][CH:18]=1)[CH:13]=[O:14]
Reactant: O=C(Cl)c1cccc(C(F)(F)F)c1
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Agent: O=S(=O)([O-])[O-]
Solvent: O=S1(=O)CCCC1
Product: O=Cc1cccc(C(F)(F)F)c1
Yield: 84 %

Procedure:
In a three-necked flask equipped with a stirrer, a gas inlet tube and a reflux condenser, 250 g of sulpholane (thiolane-S-dioxide), 5 g of Pd-BaSO4 (Pd content: 5% by weight) and 100 g (0.48 mol) of 3-trifluoromethylbenzoyl chloride from Example 1 are heated at 140° C. while hydrogen is being passed through. The elimination of hydrogen chloride which commenced immediately was complete in 3 hours. The 3-trifluoromethylbenzaldehyde formed was distilled off without the catalyst having been filtered off. Boiling point 69°-70° C./20 mbars, nD20 1.4648, 70 g; Yield: 84% of theory.
Reaction SMILES: [CH2:1]([Mg]Br)[CH3:2].C#C.[CH3:7][O:8][CH:9]1[C:18]2[CH:17]=[CH:16][C:15](=[O:19])[CH2:14][C:13]=2[CH:12]([O:20][CH3:21])[CH2:11][CH2:10]1>O1CCCC1>[CH3:7][O:8][C:9]1[C:18]2[CH2:17][CH2:16][C:15]([C:1]#[CH:2])([OH:19])[CH2:14][C:13]=2[C:12]([O:20][CH3:21])=[CH:11][CH:10]=1
Reactant: COC1CCC(OC)C2=C1C=CC(=O)C2
Reactant: CC[Mg]Br
Agent: C#C
Solvent: C1CCOC1
Product: C#CC1(O)CCc2c(OC)ccc(OC)c2C1

Procedure:
Acetylene, purified by passing it first through a dry ice acetone trap, then through concentrated sulfuric acid, was bubbled rapidly through freshly distilled tetrahydrofuran (20 ml) under nitrogen for one hour. Ethylmagnesium bromide (50 ml, 3.15 M in ether, 15.8 mmole) was added slowly. The temperature was maintained between 28°-33° C. by cooling with a water bath. After the complete addition of ethylmagnesium bromide, the passage of the acetylene gas was continued and 1,4-dimethoxy-6-tetralone (XIII) (1.03 g, 5 mmole) in dry tetrahydrofuran (5,0 ml) was added with stirring. After addition, the passage of the acetylene was continued for an extra one hour and the reaction mixture was left stirring at room temperature overnight. The reaction mixture was quenched with saturated oxalic acid and extracted with chloroform. The chloroform extract was washed well with water, dried over anhydrous magnesium sulfate, and evaporated to dryness. The oil residue was triturated with ether to give 1,4-dimethoxy-6-ethynyl-6-hydroxy-5,8-dihydro-(7H)naphthalene (XIV) as a white solid, m.p. 103°-105° C. (ethanol).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]([C:22](=[O:31])[C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)[CH:14]([CH3:32])[CH2:13]2)[C:9](=[O:11])[CH3:10])=[CH:4][CH:3]=1.CO[CH:35]1[CH2:39][CH2:38][CH:37](OC)O1.OS(O)(=O)=O.NC1C=CC=CC=1.C([O-])(O)=O.[Na+]>CO.C1COCC1>[CH3:30][O:29][C:26]1[CH:25]=[CH:24][C:23]([C:22]([N:15]2[C:16]3[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=3)[C@H:12]([N:8]([C:5]3[CH:6]=[CH:7][C:2]([N:1]4[CH:35]=[CH:39][CH:38]=[CH:37]4)=[CH:3][CH:4]=3)[C:9](=[O:11])[CH3:10])[CH2:13][C@@H:14]2[CH3:32])=[O:31])=[CH:28][CH:27]=1
Reactant: COC1CCC(OC)O1
Reactant: COc1ccc(C(=O)N2c3ccccc3C(N(C(C)=O)c3ccc(N)cc3)CC2C)cc1
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Solvent: Nc1ccccc1
Product: COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(-n4cccc4)cc3)C[C@@H]2C)cc1

Procedure:
N-(4-amino-phenyl)-N-[1-(4-methoxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide (22 mg, 0.05 mmol) was dissolved in MeOH:THF (1 mL each) and cooled to 10° C. 2,5-dimethoxy-tetrahydrofuran (1.25 equiv.) was dissolved in THF and catalytic H2SO4, and added drop wise to the aniline mixture. The mixture was poured into sat. NaHCO3 and extracted with ethyl acetate. The organic layer was dried, filtered and concentrated, and the crude residue was purified by preparative HPLC to afford the title compound as an off-white solid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[NH:18][C:19]([C:21]1([C:24](=[O:33])[NH:25][C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[CH2:23][CH2:22]1)=[O:20])[O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8](C(N)=O)[CH:7]=1.O.FC(F)(F)C(OI(C1C=CC=CC=1)OC(=O)C(F)(F)F)=O.[N:56]1C=CC=CC=1>CN(C)C=O>[NH2:56][C:8]1[CH:7]=[C:6]([O:5][C:4]2[CH:15]=[CH:16][C:17]([NH:18][C:19]([C:21]3([C:24]([NH:25][C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=4)=[O:33])[CH2:22][CH2:23]3)=[O:20])=[C:2]([F:1])[CH:3]=2)[CH:11]=[CH:10][N:9]=1
Reactant: NC(=O)c1cc(Oc2ccc(NC(=O)C3(C(=O)Nc4ccc(F)cc4)CC3)c(F)c2)ccn1
Reactant: c1ccncc1
Agent: O=C(OI(OC(=O)C(F)(F)F)c1ccccc1)C(F)(F)F
Solvent: O
Solvent: CN(C)C=O
Product: Nc1cc(Oc2ccc(NC(=O)C3(C(=O)Nc4ccc(F)cc4)CC3)c(F)c2)ccn1
Reaction time: 8 h
Yield: 66 %

Procedure:
4-(3-Fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridine-2-carboxamide (101 mg) was dissolved in N,N-dimethylformamide (1.0 ml) under a nitrogen atmosphere, and water (0.01 ml), [bis(trifluoroacetoxy)iodo]benzene (109 mg) and pyridine (0.0541 ml) were added at room temperature in this order, followed by stirring overnight. Water (0.01 ml), [bis(trifluoroacetoxy)iodo]benzene (109 mg) and pyridine (0.0541 ml) were added at room temperature in this order, followed by further stirring for 24 hr. The reaction mixture was partitioned between ethyl acetate and a 1N aqueous solution of sodium hydroxide. The organic layer was separated, washed with brine, and dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate). Fractions containing the target compound were concentrated under reduced pressure, and the residue was dried under reduced pressure to provide the titled compound as white foam (62.2 mg, 66%).
Reaction SMILES: Br[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([N+:11]([O-:13])=[O:12])[CH:9]=2)[N:4](S(C2C=CC(C)=CC=2)(=O)=O)[N:3]=1.[C:24]([Si:28]([CH3:34])([CH3:33])[O:29][CH2:30][C:31]#[CH:32])([CH3:27])([CH3:26])[CH3:25].C1COCC1>[Cu]I.C(N(CC)CC)C>[Si:28]([O:29][CH2:30][C:31]#[C:32][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([N+:11]([O-:13])=[O:12])[CH:9]=2)[NH:4][N:3]=1)([C:24]([CH3:25])([CH3:26])[CH3:27])([CH3:33])[CH3:34]
Reactant: C#CCO[Si](C)(C)C(C)(C)C
Reactant: Cc1ccc(S(=O)(=O)n2nc(Br)c3cc([N+](=O)[O-])cnc32)cc1
Agent: [Cu]I
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)(C)[Si](C)(C)OCC#Cc1n[nH]c2ncc([N+](=O)[O-])cc12
Temperature: 25 °C
Yield: 17.1 %

Procedure:
Triethylamine (4 mL) was added to a solution of 3-bromo-5-nitro-1-tosyl-1H-pyrazolo[3,4-b]pyridine (0.825 g, 3.40 mmol), tert-butyldimethyl(prop-2-ynyloxy)silane (0.89 g, 5.09 mmol) in THF (20 mL) PdCl2(PPh3)2 (0.119 g, 0.170 mmol) was added to the mixture, and the mixture was stirred at room temperature for 5 minutes before CuI (0.065 g, 0.34 mmol) was added. The reaction mixture was heated to reflux under argon for 40 hours. The reaction mixture was cooled to room temperature and concentrated. The crude product was purified by column chromatography, eluting with hexanes/ethyl acetate (4:1) to give 3-(3-(tert-butyldimethylsilyloxy)prop-1-ynyl)-5-nitro-1H-pyrazolo[3,4-b]pyridine (0.193 g, 17%) as a solid.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][C:5]1[C:10]([CH2:11]O)=[CH:9][N:8]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)[N:6]=1.S(Cl)([Cl:25])=O>ClCCl.CCOCC>[Cl:25][CH2:11][C:10]1[C:5]([CH2:4][CH2:3][O:2][CH3:1])=[N:6][C:7]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)=[N:8][CH:9]=1
Reactant: O=S(Cl)Cl
Reactant: COCCc1nc(-c2ccc(C(F)(F)F)cc2)ncc1CO
Solvent: CCOCC
Solvent: ClCCl
Product: COCCc1nc(-c2ccc(C(F)(F)F)cc2)ncc1CCl
Yield: 100 %

Procedure:
A solution of 3.23 g (10.34 mmol) [4-(2-methoxy-ethyl)-2-(4-trifluoromethyl-phenyl)-pyrimidin-5-yl]-methanol and 0.788 ml (10.86 mmol) thionylchloride in 30 ml dichloromethane was stirred for 1 h at RT. The reaction mixture was taken up in ether and washed with sodium bicarbonate solution and water. The ether phase was concentrated under reduced pressure to give 3.42 g of pure 5-chloromethyl-4-(2-methoxy-ethyl)-2-(4-trifluoromethyl-phenyl)-pyrimidine.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]([CH3:12])[CH3:11])[C:5]=1[N:13]=[C:14]=[S:15])([CH3:3])[CH3:2].[CH2:16]([NH:18][CH2:19][C:20](O)=[O:21])[CH3:17].C(N(CC)CC)C>C(Cl)(Cl)Cl>[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]([CH3:11])[CH3:12])[C:5]=1[N:13]1[C:20](=[O:21])[CH2:19][N:18]([CH2:16][CH3:17])[C:14]1=[S:15])([CH3:2])[CH3:3]
Reactant: CC(C)c1cccc(C(C)C)c1N=C=S
Reactant: CCNCC(=O)O
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: CCN1CC(=O)N(c2c(C(C)C)cccc2C(C)C)C1=S
Yield: 27 %

Procedure:
The title compound was prepared by the procedure described in Example 16 using 21.9 g of 2,6-diisopropylphenyl-isothiocyanate, 18.4 g of N-ethyl glycine, 20.2 g of triethyl amine, and 300 mL of chloroform. Purification was achieved through crystallization from ethanol. The title compound (8.2 g) was obtained as light yellow solid, m.p. 159°-161° C. Anal. Calcd. for. C17H24N2O S: C, 67.07; H, 7.94; N, 9.20. Found: C, 66.92; H, 8.03; N, 9.13. Mass spectrum (PBEI, M.+) m/z 304.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[N:7]=[C:6]([C:8]2[N:9]=[CH:10][N:11]3[C:17]4[CH:18]=[CH:19][CH:20]=[C:21]([Cl:22])[C:16]=4[C:15](=[O:23])[N:14]4[CH2:24][CH2:25][C@H:13]4[C:12]=23)[O:5][N:4]=1.C(N(C(C)C)C(C)C)C.Br[CH2:36][C:37]1[C:38]([CH2:43]Br)=[CH:39][CH:40]=[CH:41][CH:42]=1>C(Cl)Cl>[Cl:22][C:21]1[C:16]2[C:15](=[O:23])[N:14]3[CH2:24][CH2:25][C@H:13]3[C:12]3[N:11]([CH:10]=[N:9][C:8]=3[C:6]3[O:5][N:4]=[C:3]([CH2:2][N:1]4[CH2:43][C:38]5[C:37](=[CH:42][CH:41]=[CH:40][CH:39]=5)[CH2:36]4)[N:7]=3)[C:17]=2[CH:18]=[CH:19][CH:20]=1
Reactant: NCc1noc(-c2ncn3c2[C@@H]2CCN2C(=O)c2c(Cl)cccc2-3)n1
Reactant: BrCc1ccccc1CBr
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=C1c2c(Cl)cccc2-n2cnc(-c3nc(CN4Cc5ccccc5C4)no3)c2[C@@H]2CCN12
Yield: 62.3 %

Procedure:
5 g (14 mmol) of (S)-1-(3-aminomethyl-1,2,4-oxadiazol-5-yl)-8-chloro-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one, 50 ml of methylene chloride, 12 ml (70 mmol) of N-ethyldiisopropylamine and 3.7 g (14 mmol) of α,α'-dibromo-o-xylene were stirred at room temperature for 72 hours. The reaction solution was washed three times with water, dried over magnesium sulfate and evaporated. The residue was chromatographed on 70 g of silica gel while eluting with methylene chloride/ethyl acetate 7/3. There were obtained 4.0 g (62%) of (S)-8-chloro-12,12a-dihydro-1-(3-isoindolin-2-ylmethyl-1,2,4-oxadiazol-5-yl)-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one, which was converted into the hydrochloride of m.p. 170°-175°.
Reaction SMILES: C(O[C@@H:5]1[CH2:9][N:8]([CH:10]2[CH2:15][CH2:14]O[CH2:12][CH2:11]2)[CH2:7][C@H:6]1[NH:16][C:17](=[O:32])[CH2:18][NH:19][C:20](=[O:31])[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=1)C=C.[S:33]1CCC(=O)CC1.O1CCC(=O)CC1>>[O:32]=[C:17]([NH:16][CH:6]1[CH2:5][CH2:9][N:8]([CH:10]2[CH2:15][CH2:14][S:33][CH2:12][CH2:11]2)[CH2:7]1)[CH2:18][NH:19][C:20](=[O:31])[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=1
Reactant: O=C1CCSCC1
Reactant: C=CCO[C@@H]1CN(C2CCOCC2)C[C@H]1NC(=O)CNC(=O)c1cccc(C(F)(F)F)c1
Agent: O=C1CCOCC1
Product: O=C(CNC(=O)c1cccc(C(F)(F)F)c1)NC1CCN(C2CCSCC2)C1

Procedure:
The title compound was synthesized in similar fashion to rel-N-(2-{[(3R,4R)-4-(allyloxy)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-yl]amino}-2-oxoethyl)-3-(trifluoromethyl)benzamide, tetrahydro-4H-thiopyran-4-one was substituted for tetrahydro-4H-pyran-4-one and was isolated as a white solid. 1H-NMR (DMSO) δ: 1.48-1.60 (m, 2H), 1.90-2.50 (m, 8H), 2.60-2.70 (m, 2H), 2.79-2.96 (m, 2×), 3.70-4.05 (m, 6H), 5.05-5.25 (m, 2H), 5.75-5.95 (m, 1H), 7.70 (t, J=8.2 Hz, 1H), 7.93 (d, J=8.2 Hz, 1H), 8.18 (m, 2H), 9.00 (m, 1H). MS m/z: 472 (M+1).
Reaction SMILES: [NH2:1][C:2]1[C:6]([Br:7])=[CH:5][NH:4][N:3]=1.CO[CH:10](OC)[CH2:11][CH:12](OC)OC.O>C(O)(=O)C>[Br:7][C:6]1[CH:5]=[N:4][N:3]2[CH:12]=[CH:11][CH:10]=[N:1][C:2]=12
Reactant: COC(CC(OC)OC)OC
Reactant: Nc1n[nH]cc1Br
Solvent: O
Solvent: CC(=O)O
Product: Brc1cnn2cccnc12
Temperature: 25 °C
Yield: 39 %

Procedure:
A solution of 3-amino-4-bromopyrazole (2.0 g, 12 mmol) and 1,1,3,3-tetramethoxypropane (4.1 mL, 25 mmol) in acetic acid (5 mL) was heated at reflux for 4 h. Water (2 mL) was added and the mixture heated at reflux for a further 0.5 h, allowed to cool to ambient temperature and concentrated in vacuo. The residue was triturated in methanol. The solid thus obtained was washed with cold methanol, ethyl acetate, and hexanes to provide 3-bromopyrazolo[1,5-a]pyrimidine as a brownish solid in 39% yield (0.953 g): 1H NMR (300 MHz, DMSO-d6) δ9.13 (d, J=6.5 Hz, 1H), 8.61 (s, 1H), 8.35 (s, 1H), 7.19-7.02 (m, 1H); MS (ES+) m/z 197.9 (M+1), 199.9 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]2([O:19][CH3:20])[C@H:13]([OH:14])[C@@H:12]([OH:15])[C@H:11]([OH:16])[C@@H:10]([CH2:17][OH:18])[O:9]2)=[CH:4][C:3]=1[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][O:31][CH:32]2[CH2:34][CH2:33]2)=[CH:24][CH:23]=1.[CH3:35][C:36]([Si:39](Cl)([CH3:41])[CH3:40])([CH3:38])[CH3:37]>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[Si:39]([O:18][CH2:17][C@H:10]1[O:9][C@:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][O:31][CH:32]4[CH2:34][CH2:33]4)=[CH:24][CH:23]=3)[CH:4]=2)([O:19][CH3:20])[C@H:13]([OH:14])[C@@H:12]([OH:15])[C@@H:11]1[OH:16])([C:36]([CH3:38])([CH3:37])[CH3:35])([CH3:41])[CH3:40]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: CO[C@@]1(c2ccc(Cl)c(Cc3ccc(OCCOC4CC4)cc3)c2)O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Product: CO[C@@]1(c2ccc(Cl)c(Cc3ccc(OCCOC4CC4)cc3)c2)O[C@H](CO[Si](C)(C)C(C)(C)C)[C@@H](O)[C@H](O)[C@H]1O
Reaction time: 16 h

Procedure:
(2S,3R,4S,5S,6R)-2-[4-chloro-3-[[4-[2-(cyclopropoxy)ethoxy]phenyl]methyl]phenyl]-6-(hydroxymethyl)-2-methoxy-tetrahydropyran-3,4,5-triol 1a (Prepared according to the method in WO2010022313) (3.0 g, 6.06 mmol) was dissolved in 20 mL pyridine, followed by addition of 4-dimethylamino pyridine (148 mg, 1.21 mmol) and TBSCl (1.1 g, 7.27 mmol) in turn. The reaction mixture was stirred for 16 hours, then concentrated under reduced pressure. The residue was dissolved in 100 mL ethyl acetate and 100 mL water and partitioned. The aqueous phase was extracted with ethyl acetate (100 mL), and the organic layer was washed with water (50 mL), combined, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography with elution system A to obtain the title compound (2S,3R,4S,5S,6R)-6-[(tert-butyl(dimethyl)silyl)oxymethyl]-2-[4-chloro-3-[[4-[2-(cyclopropoxy)ethoxy]phenyl]methyl]phenyl]-2-methoxy-tetrahydropyran-3,4,5-triol 1b (3.0 g, yellow solid), yield: 81.1%. 1H NMR (400 MHz, CD3OD): δ 7.50 (dd, 1H), 7.38 (m, 2H), 7.08 (d, 2H), 6.82 (d, 2H), 4.04 (m, 5H), 3.88 (m, 1H), 3.82 (m, 2H), 3.75 (m, 1H), 3.59 (m, 1H), 3.40 (m, 2H), 3.07 (m, 1H), 3.06 (s, 3H), 0.90 (s, 9H), 0.53 (m, 4H), 0.10 (s, 3H), 0.07 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N:8]2[CH:12]=[C:11]([Si](C)(C)C)[N:10]=[N:9]2)[N:3]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N:8]2[CH:12]=[CH:11][N:10]=[N:9]2)[N:3]=1
Reactant: C[Si](C)(C)c1cn(-c2cccc(Cl)n2)nn1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: O
Product: Clc1cccc(-n2ccnn2)n1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 2-chloro-6-[4-(trimethylsilyl)-1H-1,2,3-triazol-1-yl]pyridine (675 mg, 2.67 mmol) in THF (10 mL) was added TBAF (1.0 M in THF, 8.01 mL, 8.01 mmol). The reaction was stirred at room temperature for 2 h. It was subsequently diluted with water and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (MgSO4), filtered, and evaporated. The crude residue was purified by flash chromatography (10-60% EtOAc/hexanes) to afford the title compound as a colorless solid.
Reaction SMILES: CO.[OH-].[Na+].[CH:5]1[CH2:10][CH2:9][CH:8]([C:11]2[N:12]([C:22]3[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=3)[CH:13]=[C:14]([C:19](=[O:21])[CH:20]=2)[C:15]([O:17]C)=[O:16])[CH2:7][CH:6]=1>C(O)(=O)C>[CH:5]1[CH2:10][CH2:9][CH:8]([C:11]2[N:12]([C:22]3[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=3)[CH:13]=[C:14]([C:19](=[O:21])[CH:20]=2)[C:15]([OH:17])=[O:16])[CH2:7][CH:6]=1
Reactant: COC(=O)c1cn(-c2ccc(O)cc2)c(C2CC=CCC2)cc1=O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CO
Product: O=C(O)c1cn(-c2ccc(O)cc2)c(C2CC=CCC2)cc1=O
Yield: 73.2 %

Procedure:
In a mixture consisting of 5 ml of methanol and 5 ml of a 1N aqueous sodium hydroxide solution was dissolved 0.5 g of methyl 6-(cyclohexen-4-yl)-1-(4-hydroxyphenyl)-4-oxo-1,4-dihydronicotinate, and they wre reacted at room temperature for 30 minutes. After completion of the reaction, the reaction mixture was adjusted to a pH of 5.5 with acetic acid, and the precipitated crystals were collected by filtration, washed with 30 ml of water, and dried to obtain 0.35 g of 6-(cyclohexen-4-yl)-1-(4-hydroxyphenyl)-4-oxo-1,4-dihydronicotinic acid having a melting point of 250° C. or more.
Reaction SMILES: [CH3:1][C:2]([CH3:22])=[CH:3][CH2:4][CH2:5]/[C:6](/[CH3:21])=[CH:7]/[CH2:8][CH2:9]/[C:10](/[CH3:20])=[CH:11]/[CH2:12][S:13][CH2:14][C@H:15]([NH2:19])[C:16]([OH:18])=[O:17].C([O-])([O-])=O.[K+].[K+].[C:29]1(=[O:35])[O:34][C:32](=[O:33])[CH2:31][CH2:30]1.Cl>C1COCC1>[C:16]([C@@H:15]([NH:19][C:29](=[O:35])[CH2:30][CH2:31][C:32]([OH:34])=[O:33])[CH2:14][S:13][CH2:12]/[CH:11]=[C:10](\[CH3:20])/[CH2:9][CH2:8]/[CH:7]=[C:6](\[CH3:21])/[CH2:5][CH2:4][CH:3]=[C:2]([CH3:22])[CH3:1])([OH:18])=[O:17]
Reactant: O=C1CCC(=O)O1
Reactant: CC(C)=CCC/C(C)=C/CC/C(C)=C/CSC[C@H](N)C(=O)O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CC(C)=CCC/C(C)=C/CC/C(C)=C/CSC[C@H](NC(=O)CCC(=O)O)C(=O)O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of S-trans, trans-farnesyl-L-cysteine (500 mg, 1.54 mmol) in THF, a first portion of K2CO3 (2 mmol) was added and the resultant solution was cooled to 5° C. with vigorous stirring. To this stirred solution was added succinic anhydride (308 mg, 3.1 mmol) dropwise while maintaining the pH at 9.0-10.0 with another portion of K2CO3 (4 mmol). The mixture was stirred at room temperature for 2 h, HPLC analysis showed completion of the reaction. The pH of the reaction mixture then adjusted to 2.0 by the addition of 2 N HCl solution. The acidic solution was extracted three times with 10 mL of ethyl acetate. The combined organic extract was washed with water, brine and dried over Na2SO4, the solvent was removed on rotary evaporator to afford crude Compound B, which was further purified by preparative HPLC (535 mg, 82%) to yield Compound B. 1H-NMR (500 MHz, CDCl3): δ 1.59 (s, 6H), 1.66 (s, 6H), 2.05 (m, 8H), 2.60 (m, 2H), 2.48 (m, 2H), 2.86 (dd, 1H), 2.94 (dd, 1H), 3.10 (dd, 1H), 3.12 (dd, 1H), 4.68 (dd, 1H), 5.06 (m, 2H), 5.20 (t, 1H). 13C-NMR (125 MHz, CDCl3): δ 16.0, 16.1, 17.7, 25.7, 26.5, 26.7, 29.4, 29.8, 30.5, 32.6, 39.6, 39.7, 52.2, 119.3, 123.8, 124.3, 131.3, 135.4, 140.3, 173.4, 174.2, 176.8; ES-MS: mass calcd for Chemical Formula: C22H35NO5S 425.6. Found (M+Na) m/z 448.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9](Cl)=[N:10][OH:11].[C:13]([C:15]1[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[CH:17][CH:16]=1)#[CH:14]>O1CCCC1.C(N(CC)CC)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[CH:14]=[C:13]([C:15]2[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[CH:17][CH:16]=2)[O:11][N:10]=1
Reactant: C#Cc1ccc(C#N)cc1
Reactant: ON=C(Cl)c1c(Cl)cccc1Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: N#Cc1ccc(-c2cc(-c3c(Cl)cccc3Cl)no2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
2,6-Dichloro-N-hydroxybenzenecarboximidoyl chloride (2.67 g, 11.9 mmol) and 4-ethynylbenzonitrile (1.50 g, 11.9 mmol) were dissolved in anhydrous tetrahydrofuran (150 mL) and triethylamine (2.15 mL). The mixture was stirred at room temperature for 1 h then heated at reflux for 6 h to generate the 2,6-dichlorophenyl nitrile oxide intermediate, which reacted by a 1,3-dipolar cycloaddition reaction with 4-ethynylbenzonitrile. The solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate and washed successively with water and brine. The ethyl acetate solution was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting solid was purified by column chromatography on silica gel, eluting with 7:3 hexanes-ethyl acetate. The appropriate fractions were combined to give 3-(2,6-dichlorophenyl)-5-(4-cyanophenyl) isoxazole as a white solid, 0.58 g.
Reaction SMILES: [C:1]1([C:7]2[C:8]([C:16]3[CH:23]=[CH:22][C:19]([CH:20]=[O:21])=[CH:18][CH:17]=3)=[N:9][C:10]3[N:11]([N:13]=[CH:14][N:15]=3)[CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:24][C:25]([F:33])([F:32])C1N=C(N)NN=1>>[C:1]1([C:7]2[C:8]([C:16]3[CH:17]=[CH:18][C:19]([CH:20]=[O:21])=[CH:22][CH:23]=3)=[N:9][C:10]3[N:11]([N:13]=[C:14]([C:25]([F:33])([F:32])[F:24])[N:15]=3)[CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Nc1nc(C(F)(F)F)n[nH]1
Reactant: O=Cc1ccc(-c2nc3ncnn3cc2-c2ccccc2)cc1
Product: O=Cc1ccc(-c2nc3nc(C(F)(F)F)nn3cc2-c2ccccc2)cc1

Procedure:
This compound was prepared in a manner according to 4-(6-phenyl[1,2,4]triazolo[1,5-a]pyrimidin-5-yl)benzaldehyde by using 5-trifluoromethyl-2H-[1,2,4]triazol-3-ylamine in the first step.