Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1(=[O:11])[NH:5][C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[Br:45][C:46]1[CH:47]=[N:48][C:49]2[C:54]([CH:55]=1)=[CH:53][C:52]([CH2:56]O)=[CH:51][CH:50]=2>C1COCC1.CCOC(C)=O>[Br:45][C:46]1[CH:47]=[N:48][C:49]2[C:54]([CH:55]=1)=[CH:53][C:52]([CH2:56][N:5]1[C:1](=[O:11])[C:2]3[C:3](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:4]1=[O:6])=[CH:51][CH:50]=2
Reactant: O=C1NC(=O)c2ccccc21
Reactant: OCc1ccc2ncc(Br)cc2c1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: O=C1c2ccccc2C(=O)N1Cc1ccc2ncc(Br)cc2c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of phthalimide (281 mg, 1.9 mmol), triphenyl phosphine (500 mg, 1.9 mmol) in 10 mL of THF was added DIAD (386 mg, 1.9 mmol) dropwise at 0° C. and the mixture was stirred at this temperature for 10 min. (3-Bromo-quinolin-6-yl)-methanol (413 mg, 1.7 mmol) was added to the above solution in one portion and the resulting solution was stirred at rt for 30 min, then heated at 40° C. for 5 h. After cooling, the reaction mixture was taken up with EtOAc, washed with water, extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with EtOAc/hexane gradient to afford the title compound. 1H-NMR (400 MHz, CDCl3) δ ppm 8.89 (d, 1H), 8.31 (d, 1H), 8.06 (d, 1H), 7.90-7.86 (m, 3H), 7.82-7.73 (m, 3H), 5.04 (s, 2H). LCMS (method A): [MH]+=368/370, tR=5.54 min.
Reaction SMILES: [CH:1]([C:4]1([C:13]([O:15]C(C)(C)C)=[O:14])[CH2:8][CH2:7][C:6](OC)([O:9]C)[CH2:5]1)([CH3:3])[CH3:2].O>Cl.O1CCOCC1>[CH:1]([C:4]1([C:13]([OH:15])=[O:14])[CH2:8][CH2:7][C:6](=[O:9])[CH2:5]1)([CH3:3])[CH3:2]
Reactant: COC1(OC)CCC(C(=O)OC(C)(C)C)(C(C)C)C1
Agent: Cl
Solvent: C1COCCO1
Solvent: O
Product: CC(C)C1(C(=O)O)CCC(=O)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 104.8 %

Procedure:
tert-Butyl 1-isopropyl-3,3-dimethoxycyclopentanecarboxylate (8.32 g, 30.5 mmol) was dissolved in 4 N anhydrous HCl in dioxane (50 mL) and water (10 mL) was added. The reaction mixture was stirred at room temperature overnight, then was concentrated. The residue was dissolved in DCM, dried over anhydrous MgSO4, filtered, and concentrated to give 5.44 g of 1-isopropyl-3-oxocyclopentanecarboxylic acid (used without purification). 1H NMR (500 MHz, CDCl3) δ 2.70 (d, J=18.1 Hz, 1H), 2.44-2.39 (m, 1H), 2.30-2.15 (m, 2H), 2.14 (dd, J=18.1, 1.0 Hz, 1H), 2.06 (p, J=6.9 Hz, 1H), 1.98 (m, 1H), 0.98 (dd, J=11.4, 6.9 Hz, 6H).
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1[CH:13]=[CH:12][C:11](I)=[CH:10][C:9]=1[N+:15]([O-:17])=[O:16])([CH3:4])([CH3:3])[CH3:2].[C:19]1(B(O)O)[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][CH:20]=1>>[C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:27]2[C:28]3[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:24]=[CH:25][CH:26]=2)=[CH:10][C:9]=1[N+:15]([O-:17])=[O:16])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)Nc1ccc(I)cc1[N+](=O)[O-]
Reactant: OB(O)c1cccc2ccccc12
Product: CC(C)(C)OC(=O)Nc1ccc(-c2cccc3ccccc23)cc1[N+](=O)[O-]

Procedure:
Prepared from (4-iodo-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example A1) and 1-naphthylboronic acid according to the general procedure B. Obtained as a yellow foam (1.0 g).
Reaction SMILES: N1C=CC=CC=1.[Si:7]([N:14]1[CH:17]([CH2:18][CH2:19][OH:20])[CH2:16][C:15]1=[O:21])([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8]>C(Cl)Cl.[O-2].[O-2].[O-2].[Cr+6]>[Si:7]([N:14]1[CH:17]([CH2:18][CH:19]=[O:20])[CH2:16][C:15]1=[O:21])([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8]
Reactant: CC(C)(C)[Si](C)(C)N1C(=O)CC1CCO
Agent: [Cr+6]
Agent: [O-2]
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)N1C(=O)CC1CC=O
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 73.5 %

Procedure:
Anhydrous chromium trioxide (CrO3) (1.94 g, 19.4 mmol) is added to a solution of anhydrous pyridine (3.07 g, 38.8 mmole) in anhydrous methylene chloride (CH2Cl2) (50 ml). The resulting mixture is stirred at room temperature for 15 mins. A solution of N-(t-butyldimethylsilyl)-4-(2-hydroxyethyl)-azetidin-2-one (0.74 g, 3.23 mmol) in anhydrous CH2Cl2 (5 ml) is added all at once. After stirring at room temperature for 5 mins, the mixture is decanted and the dark, gummy residue is washed with more CH2Cl2. The combined CH2Cl2 supernatant is evaporated i.v. The residue is taken up in diethyl ether and filtered to remove chromium salts. The ethereal filtrate is washed with 5% NaHCO3, 5% HCl, 5% NaHCO3 and brine, dried with MgSO4, filtered, and evaporated i.v. to yield N-(t-butyldimethylsilyl)-4-(2-oxoethyl)-azetidin-2-one (0.54 g) as an off-white solid: ir (CHCl3) 5.77, 5.80, 7.36, 7.60, 7.99, 8.50 and 11.95 cm-1 ; nmr (CDCl3) δ0.23 (s,3), 0.27 (s,3), 0.98 (s,9), 2.63 (ddd,1), 2.65 (dd,1), 3.07 (ddd,1), 3.37 (dd), 3.97 (m,1), and 9.78 (t,1); mass spectrum m/e 170 and 128.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:5]=[C:4]([N:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[C:22]([O:23][CH3:24])[C:17]=3[N:16]=[C:15]2[CH:25]([F:27])[F:26])[N:3]=1.[NH:28]1[CH2:31][CH:30]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[CH2:29]1>>[F:26][CH:25]([F:27])[C:15]1[N:14]([C:4]2[N:5]=[C:6]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)[N:7]=[C:2]([N:28]3[CH2:31][CH:30]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:37])([CH3:36])[CH3:38])[CH2:29]3)[N:3]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[C:22]([O:23][CH3:24])[C:17]=2[N:16]=1
Reactant: CC(C)(C)OC(=O)NC1CNC1
Reactant: COc1cccc2c1nc(C(F)F)n2-c1nc(Cl)nc(N2CCOCC2)n1
Product: COc1cccc2c1nc(C(F)F)n2-c1nc(N2CCOCC2)nc(N2CC(NC(=O)OC(C)(C)C)C2)n1
Yield: 90 %

Procedure:
Reaction of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole and tert-butyl 3-azetidinylcarbamate gave tert-butyl 1-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-3-azetidinylcarbamate in 90% yield: mp (CH2Cl2/hexanes) 217-220° C.; 1H NMR (DMSO-d6) δ 7.98 (d, J=8.0 Hz, 1H), 7.73 (t, JHF=53.0 Hz, 1H), 8.24 (t, J=8.2 Hz, 1H), 6.95 (d, J=7.8 Hz, 1H), 4.42 and 4.36-4.32 (2m, 3H), 4.01-3.98 (m, 2H), 3.79-3.77 (m, 4H), 3.68 (m, 4H), 1.40 (s, 9H). Anal. Calcd. for C24H30F2N8O4: C, 54.1; H, 5.7; N, 21.0. Found: C, 54.4; H, 5.8; N, 21.2%.
Reaction SMILES: [C:1]([NH:5][CH2:6][CH:7]([OH:21])[CH2:8][O:9][C:10]1[CH:19]=[C:18]2[C:13]([CH:14]=[N:15][NH:16][C:17]2=S)=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].O.[NH2:23][NH2:24]>>[C:1]([NH:5][CH2:6][CH:7]([OH:21])[CH2:8][O:9][C:10]1[CH:19]=[C:18]2[C:13]([CH:14]=[N:15][N:16]=[C:17]2[NH:23][NH2:24])=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)NCC(O)COc1ccc2cn[nH]c(=S)c2c1
Reactant: NN
Solvent: O
Product: CC(C)(C)NCC(O)COc1ccc2cnnc(NN)c2c1

Procedure:
7-(3-t-Butylamino-2-hydroxypropoxy)-1(2H)-phthalazinthione was reacted with hydrazine hydrate in a similar manner to that described in Example 1(viii) to give 7-(3-t-butylamino-2-hydroxypropoxy)-1-hydrazinophthalazine.
Reaction SMILES: C[O:2][C:3]1[C:12]2[S:11][CH2:10][C:9](=O)[CH2:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.[CH3:14][NH:15][CH3:16].[ClH:17]>C1(C)C=CC=CC=1>[ClH:17].[OH:2][C:3]1[C:12]2[S:11][CH2:10][CH:9]([N:15]([CH3:16])[CH3:14])[CH2:8][C:7]=2[CH:6]=[CH:5][CH:4]=1
Reactant: COc1cccc2c1SCC(=O)C2
Reactant: CNC
Agent: Cl
Solvent: Cc1ccccc1
Product: CN(C)C1CSc2c(O)cccc2C1
Reaction time: 0.5 h

Procedure:
To a solution of 5 g of 8-methoxy-3,4-dihydro-2H-[1]-benzothiopyran-3-one (J. Chem. Soc. 1948, 1610), and 4 g of anhydrous dimethylamine in 50 ml of toluene is stirred with 4 A molecular sieves for 2 hours. The reaction mixture is filtered and the solvent removed in vacuo. This residue is added to a solution of 3.2g of sodium cyanoborohydride in 10 ml of acetic acid and 50 ml of ethanol. After 30 minutes at room temperature, the reaction mixture is poured onto 3N hydrochloric acid, and washed with ether. After basification of the aqueous layer followed by ether extraction, the organic layer is dried over magnesium sulfate and the solvent removed in vacuo. The residue is added to a solution of lithium diphenylphosphide prepared from 4.9 g diphenylphosphine, 19 ml of 1.3M butyl lithium in hexane and 70 ml of dry tetrahydrofuran, and the mixture is refluxed for 1 hour. The reaction mixture is poured onto 2N hydrochloric acid and washed with ether. After neutralization of the aqueous layer with sodium bicarbonate, the product is extracted with ether and the solvent is removed in vacuo after drying over magnesium sulfate. The residue is dissolved in ethanol; after acidification with 5.4N ethanolic hydrogen chloride and cooling, 8-hydroxy-3,4-dihydro-N,N-dimethyl-2H-[1]-benzothiopyran-3-amine hydrochloride, melting point 172°-173°, is obtained.
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][N:3]=1.[CH3:10][Mg]Br>C1COCC1>[F:1][C:2]1[N:3]=[CH:4][C:5]([CH:6]([OH:7])[CH3:10])=[CH:8][CH:9]=1
Reactant: C[Mg]Br
Reactant: O=Cc1ccc(F)nc1
Solvent: C1CCOC1
Product: CC(O)c1ccc(F)nc1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 83.1 %

Procedure:
A solution of 6-fluoronicotinaldehyde (1.12 g, 8.95 mmol, Frontier Scientific, Cat#: F1911, Batch#: RP09-2154) in THF (11.0 mL) was treated dropwise with methylmagnesium bromide (1.4 M solution in PhMe/THF (75:25), 7.03 mL, 9.85 mmol, Aldrich) and allowed to stir at RT for 20 min. The reaction mixture was quenched by the addition of a saturated solution of NH4Cl (aq.) and allowed to stir for 10 min. The reaction mixture was extracted with EtOAc (2×60 mL), dried over MgSO4, filtered and concentrated. Purification on the ISCO (12 g column, 25-70% EtOAc in hexanes) gave the title compound (1.05 g, 83% yield) as a pale yellow viscous oil. 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J=2.0Hz, 1H); 7.85 (td, J=8.1, 2.5 Hz, 1H); 6.93 (dd, J=8.4, 2.9 Hz, 1H); 4.98 (qd, J=6.5, 3.9 Hz, 1H); 1.53 (d, J=6.5 Hz, 3H). m/z (ESI, +ve) 142.1 (M+H)+.
Reaction SMILES: [CH2:1]([O:8][CH2:9][N:10]1[C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:13]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:12]=[CH:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[F:32][C:33]([F:37])([F:36])[S:34]Cl.C(=O)(O)[O-].[Na+]>C1COCC1.CCOCC.CCCCCC.O>[CH2:1]([O:8][CH2:9][N:10]1[C:14]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)=[C:13]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:12]=[C:11]1[S:34][C:33]([F:37])([F:36])[F:32])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: c1ccc(COCn2cnc(-c3ccccc3)c2-c2ccccc2)cc1
Reactant: FC(F)(F)SCl
Agent: O=C([O-])O
Agent: [Li]CCCC
Agent: [Na+]
Solvent: CCCCCC
Solvent: CCOCC
Solvent: O
Product: FC(F)(F)Sc1nc(-c2ccccc2)c(-c2ccccc2)n1COCc1ccccc1
Reaction time: 0.25 h

Procedure:
In glassware dried with a heat gun and under nitrogen, to a mixture of 1.7 g (5 mmole) of 1-benzyloxymethyl-4,5-diphenylimidazole in 25 ml THF and 25 ml ether at -78° was added dropwise a solution of 3.75 ml of 1.6 M n-butyl lithium solution in hexane in 25 ml ether. The reaction mixture was stirred at -78° ca. 15 minutes then 0.8 g (6 mmole) of trifluoromethanesulfenyl chloride (TOXIC) was added as a gas. The mixture was stirred at -78° for 2 hours, then RT overnight. The mixture was added to 200 ml water and neutralized with sodium bicarbonate. The mixture was extracted with ether and the ether extracts were dried and concentrated. The residue was chromatographed on 200 g SilicAR CC-7, eluting with toluene to give, after recrystallization from hexane, 0.5 g (23%) of product, mp 97°-8°.
Reaction SMILES: [N+:1]([C:4]1[NH:5][CH:6]=[C:7]([CH2:9][C:10]([F:16])([F:15])[C:11](OC)=[O:12])[N:8]=1)([O-:3])=[O:2].[NH3:17]>CO>[N+:1]([C:4]1[NH:5][CH:6]=[C:7]([CH2:9][C:10]([F:16])([F:15])[C:11]([NH2:17])=[O:12])[N:8]=1)([O-:3])=[O:2]
Reactant: N
Reactant: COC(=O)C(F)(F)Cc1c[nH]c([N+](=O)[O-])n1
Solvent: CO
Product: NC(=O)C(F)(F)Cc1c[nH]c([N+](=O)[O-])n1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To methyl 3-(2'-nitroimidazolyl)-2,2-difluoropropionate (5.00 g, 21.3 mmol), 10% ammonia solution (80 ml) in methanol was added and stirred for 3 hours at a room temperature. Then, the reaction mixture was concentrated. Methanol (100 ml) was added to the concentrate and throughly stirred. Insoluble fraction was filtered off. The filtrate was concentrated, subjected to silica gel column chromatography and recrystallized from ethanol to obtain 3-(2'-nitroimidazolyl)-2,2-difluoropropionic acid amide (2.57 mg). m.p. 149.5°-151.5° C.
Reaction SMILES: [Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8]([O:10]CC)=[O:9].[Li+].[OH-].Cl>CCO.O>[Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8]([OH:10])=[O:9]
Reactant: CCOC(=O)CCCCCCBr
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=C(O)CCCCCCBr
Temperature: 25 °C
Reaction time: 8 h
Yield: 96.5 %

Procedure:
to a solution of ethyl 7-bromoheptanoate (2.0 g, 8.43 mmol, 1 eq) in EtOH (15 mL) and H2O (10 mL) was added LiOH (2.0 g, 83.3 mmol, 10 eq). The mixture was stirred overnight at room temperature. The mixture was neutralized with 2N aqueous HCl with cooling in an ice-water bath, and the mixture was extracted with EtOAc. The EtOAc layer was separated, washed with water and brine, and dried over Na2SO4. Filtration and concentration in vacuo gave 1.7 g (96%) of the 7-Bromoheptanoic acid as a white solid.
Reaction SMILES: [CH3:1][C:2]1([CH3:19])[CH2:7][CH2:6][N:5]([C:8]2[CH:18]=[CH:17][C:11]([C:12]([O:14]CC)=[O:13])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.O[Li].O.CO>C1COCC1.O>[CH3:1][C:2]1([CH3:19])[CH2:7][CH2:6][N:5]([C:8]2[CH:18]=[CH:17][C:11]([C:12]([OH:14])=[O:13])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1
Reactant: CCOC(=O)c1ccc(N2CCC(C)(C)CC2)cc1
Agent: [Li]O
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: CC1(C)CCN(c2ccc(C(=O)O)cc2)CC1
Temperature: 25 °C

Procedure:
A solution of Example 119B (260 mg, 1.0 mmol) and LiOH.H2O (158 mg, 4.0 mmol) in THF (19 mL), water (5 mL), and methanol (5 mL) was heated to 75° C. for 18 hours, cooled to room temperature, concentrated, and adjusted to pH 3-4 with 1N HCl. The precipitate was collected by filtration, washed with water, and dried under vacuum to provide the desired product. MS(DCI(+)) m/e 234 (M+H)+.
Reaction SMILES: F[C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([O:18][CH3:19])[CH:16]=3)[C:11](=[O:20])[N:10]([CH3:21])[C:9]=2[CH3:22])[CH:5]=[CH:6][CH:7]=1.[F:23]C1C=CC(C=O)=CC=1>>[F:23][C:7]1[CH:6]=[CH:5][C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([O:18][CH3:19])[CH:16]=3)[C:11](=[O:20])[N:10]([CH3:21])[C:9]=2[CH3:22])=[CH:3][CH:2]=1
Reactant: COc1ccc2c(=O)n(C)c(C)c(-c3cccc(F)c3)c2c1
Reactant: O=Cc1ccc(F)cc1
Product: COc1ccc2c(=O)n(C)c(C)c(-c3ccc(F)cc3)c2c1

Procedure:
Following the procedure for 4-(3-fluorophenyl)-6-methoxy-2,3-dimethylisoquinolin-1(2H)-one, using (in Step A) 4-fluorobenzaldehyde in place of 3-fluorobenzaldehyde, the title compound was synthesized.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]([O:10][CH3:11])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:18][C:19]([CH3:21])=O.C(Br)C#C>C1(C)C=CC=CC=1>[CH2:21]([O:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]([O:10][CH3:11])[CH:3]=1)[C:19]#[CH:18]
Reactant: CC(C)=O
Reactant: COc1ccc(O)cc1OC
Agent: C#CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: C#CCOc1ccc(OC)c(OC)c1

Procedure:
Following the same procedure as in Example 1, 13.8 g (0.1 mole) of 1-hydroxy-3,4-dimethoxybenzene, 13.8 g (0.1 mole) of anhydrous potassium carbonate in ml 50 of acetone and 14.9 g (0.1 mole) of a solution of propargyl bromide in toluene (80% w/w) were reacted. After work up and evaporation of the mixture u.v. (25° C./21 mbar) a residue was obtained that was purified on silica gel column (eluant n-hexane:ethyl acetate 5:1 v/v). A thick oil that after some time solidified with low melting point (28-30° C.) (b.p.: 109-110° C./ 3 mbar) was obtained whose NMR and MS analyses corresponded to those of the aforementioned compound.
Reaction SMILES: [C:1]([NH:4][C:5]([CH:16]=[CH:17][CH2:18][CH2:19][CH3:20])([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:3])[CH3:2].C[N+]1([O-])CC[O:25]CC1.S([O-])([O-])=O.[Na+].[Na+]>CC(C)=O.O.[Os](=O)(=O)(=O)=O>[C:1]([NH:4][C:5]([CH2:16][CH2:17][CH2:18][CH2:19][CH:20]=[O:25])([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:3])[CH3:2]
Reactant: CCCC=CC(NC(C)=O)(C(=O)OCC)C(=O)OCC
Reactant: C[N+]1([O-])CCOCC1
Agent: O=[Os](=O)(=O)=O
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: O
Product: CCOC(=O)C(CCCCC=O)(NC(C)=O)C(=O)OCC
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Diethyl 2-acetamido-2-pentenylmalonate (4.0 g) was dissolved in 210 ml of acetone and 3.3 g of N-methylmorpholine-N-oxide and 36 ml of a 1% aqueous osmium tetraoxide solution were added thereto. The mixture was stirred at room temperature for 2 hours. A solution of 700 mg of sodium sulfite in 20 ml of water was added thereto and the mixture was stirred for 15 minutes. The reaction mixture was concentrated and subjected to silica gel column chromatography using chloroform/methanol (10:1) as an eluent and a fraction having an Rf value: 0.3 (chloroform:methanol=10:1) was concentrated. The residue was dissolved in 630 ml of 1,4-dioxane and 70 ml of a 0.2M aqueous meta-sodium periodate solution was added thereto. The mixture was stirred at room temperature for 2 hours. The reaction mixture was filtrated, concentrated, extracted with ethyl acetate and washed with water. The hexane layer was dried and concentrated to give 4.17 g of colorless, oily diethyl 2-acetamido-2-(4-formylbutyl)malonate.
Reaction SMILES: [K+].[Br-].[OH:3][C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=[N:6][C:5]=1[C:14]1[N:15]=[CH:16][C:17]2[C:22]([C:23]=1[OH:24])=[CH:21][CH:20]=[CH:19][CH:18]=2>C(Cl)(Cl)Cl>[OH:3][C:4]1[C:5]([C:14]2[C:23]([OH:24])=[CH:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]=2)=[N:6][C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[CH:9][CH:8]=2
Reactant: Oc1c(-c2ncc3ccccc3c2O)ncc2ccccc12
Agent: [Br-]
Agent: [K+]
Solvent: ClC(Cl)Cl
Product: Oc1cc2ccccc2nc1-c1nc2ccccc2cc1O

Procedure:
Yield 0.17 g 94.4%)--melting point>360° C.--RF (silica gel/i-propanol)=0.82.--IR (KBr): 3420 cm-1 (m), 3067-2550 (m, OH), 1574 (m), 1508 (m), 1503 (m), 1466 (m), 1425 (w), 1400 (w), 1376 (m), 1332 (s), 1281 (w), 1249 (w), 1217 (s), 1161 (w), 1141 (s), 755 (s).--UV/VIS (chloroform): λmax (ε)=399 nm (9202), 328 nm (7975).--1H-NMR ((D6)DMSO/TMS): δ:6.96-7.58 (m, 6H, 5-H, 5'-H, 6-H, 6'-H, 7-H, 7'-H), 7.98 (d, J8,7 =J8',7' 8.0 Hz, 2H, 8-H, 8'-H), 8.87 (s, 2H, 4-H, 4'-H).--MS (70 eV): m/z (%)=298 (18) M+ +1, 288 (100) M+, 287 (16), 271 (7) M+ -OH, 260 (7), 259 (17), 232 (5), 231 (9), 204 (7), 176 (s), 88 (4).
Reaction SMILES: [CH3:1][C:2]1[CH:12]=[CH:11][C:5]2[CH:6]=[C:7]([C:9]#[N:10])[O:8][C:4]=2[CH:3]=1.C1C(=O)N([Br:20])C(=O)C1>C(Cl)(Cl)(Cl)Cl>[Br:20][CH2:1][C:2]1[CH:12]=[CH:11][C:5]2[CH:6]=[C:7]([C:9]#[N:10])[O:8][C:4]=2[CH:3]=1
Reactant: Cc1ccc2cc(C#N)oc2c1
Reactant: O=C1CCC(=O)N1Br
Solvent: ClC(Cl)(Cl)Cl
Product: N#Cc1cc2ccc(CBr)cc2o1
Temperature: 25 °C

Procedure:
6-methylbenzofuran-2-carbonitrile (12 g, 76 mmol), NBS (13.59 g, 76 mmol), and AlBN (1.25 g, 7.64 mmol) were dissolved in carbon tetrachloride (191 ml). The mixture was heated to reflux overnight. After 18 h the reaction was cooled to RT and concentrated under reduced pressure. The product was then crashed out using MeOH and the slurry was placed in the fridge overnight. The slurry was filtered and the collected PPT was washed with MeOH. The collected PPT was pure 6-(bromomethyl)benzofuran-2-carbonitrile (13.864 g). 1H NMR (400 MHz, DMSO-d6) δ 4.87 (s, 2H), 7.52 (dd, J=8.2, 1.4 Hz, 1H), 7.83 (d, J=8.2 Hz, 1H), 7.87 (d, J=1.5 Hz, 1H), 8.11 (d, J=1.0 Hz, 1H).
Reaction SMILES: CS(O[CH2:6][C@@H:7]1[O:11][C:10](=[O:12])[N:9]([C:13]2[CH:22]=[C:21]3[C:16]([CH:17]=[C:18]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[C:30]([F:33])([F:32])[F:31])[NH:19][C:20]3=[O:23])=[CH:15][CH:14]=2)[CH2:8]1)(=O)=O.[NH:34]1[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1>C(#N)C>[O:12]=[C:10]1[N:9]([C:13]2[CH:22]=[C:21]3[C:16]([CH:17]=[C:18]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[C:30]([F:31])([F:33])[F:32])[NH:19][C:20]3=[O:23])=[CH:15][CH:14]=2)[CH2:8][C@H:7]([CH2:6][N:34]2[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]2)[O:11]1
Reactant: C1CCNCC1
Reactant: CS(=O)(=O)OC[C@H]1CN(c2ccc3cc(-c4ccccc4C(F)(F)F)[nH]c(=O)c3c2)C(=O)O1
Solvent: CC#N
Product: O=C1O[C@@H](CN2CCCCC2)CN1c1ccc2cc(-c3ccccc3C(F)(F)F)[nH]c(=O)c2c1
Yield: 73 %

Procedure:
The methanesulfonic acid (R)-2-oxo-3-[1-oxo-3-(2-trifluoromethylphenyl)-1,2-dihydroisoquinolin-7-yl]oxazolidin-5-ylmethyl(20 mg, 0.0415 mmol) obtained in step A was dissolved in acetonitrile (0.1 ml). Thereafter, piperidine (8.2 μl) was added to the solution, and the obtained mixture was stirred under heating to reflux for 12 hours. Thereafter, the reaction solution was concentrated, and the obtained residue was then purified by silica gel column chromatography (methylene chloride:methanol=30:1), so as to obtain 7-((S)-2-oxo-5-piperidin-1-ylmethyloxazolidin-3-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one (14.3 mg, 73%) in the form of a colorless amorphous substance.
Reaction SMILES: [N+:1]([C:4]1[C:17]([CH3:18])=[CH:16][C:7]([C:8]([NH:10][CH2:11][C:12]([OH:15])([CH3:14])[CH3:13])=[O:9])=[CH:6][C:5]=1[CH3:19])([O-])=O>CO.[Pd]>[NH2:1][C:4]1[C:5]([CH3:19])=[CH:6][C:7]([C:8]([NH:10][CH2:11][C:12]([OH:15])([CH3:13])[CH3:14])=[O:9])=[CH:16][C:17]=1[CH3:18]
Reactant: Cc1cc(C(=O)NCC(C)(C)O)cc(C)c1[N+](=O)[O-]
Agent: [Pd]
Solvent: CO
Product: Cc1cc(C(=O)NCC(C)(C)O)cc(C)c1N
Yield: 84.4 %

Procedure:
4-Nitro-N-(2-hydroxy-2-methyl-propyl)-3,5-dimethyl-benzamide (1.2 g, 4.51 mmol) is suspended in methanol (10 mL) and hydrogenated at 3 bar for 3 hours using 10% palladium on activated carbon (120 mg) as the catalyst. The mixture is filtered through celite and the solvent removed under vacuum to give the title compound (Yield 900 mg).