Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N1C=CC=CC=1.[CH:7]1([CH2:15][CH2:16][OH:17])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1.C(OCC)C>ClCCl>[CH:7]1([CH2:15][CH:16]=[O:17])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1
Reactant: OCCC1CCCCCCC1
Solvent: CCOCC
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=CCC1CCCCCCC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 1,1,1-tris(acetoxy)-1,1-dihydro-1,2-benziodoxol-3(1H)-one (490 mg) in dichloromethane (3 mL) was added pyridine (0.25 mL). To the solution was added a solution of 2-cyclooctylethanol (120 mg) in dichlormethane (3 mL) under ice cooling. The reaction solution was stirred at room temperature for 3 hours. To the solution was added diethyl ether, and it was washed in turn with aqueous sodium thiosulfate, 1N hydrochloric acid, saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium chloride. The solution was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the title compound. This product was subjected to the subsequent step without further purification.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=1[CH:11]=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+]>CO>[CH2:1]([O:8][C:9]1[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=1[CH2:11][OH:12])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=Cc1ccccc1OCc1ccccc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: OCc1ccccc1OCc1ccccc1
Reaction time: 1 h
Yield: 104 %

Procedure:
To a solution of 2-benzyloxybenzaldehyde (2.0 g) in methanol (20 mL), NaBH4 (356 mg, 9.42 mmol) was added under ice cooling and stirred for 1 hour. After addition of additional NaBH4 (49 mg), the reaction mixture was stirred at room temperature for 1.5 hours. The reaction mixture was concentrated and water was added to the resulting residue, followed by extracting the mixture with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to give 2-benzyloxybenzyl alcohol (2.1 g) as a colorless oil.
Reaction SMILES: CS([O:5][CH2:6][C:7]1[CH:12]=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[CH2:14])[N:10]=[C:9]([Cl:18])[N:8]=1)(=O)=O.[F:19][CH2:20][CH:21](O)[CH2:22][F:23].[OH-].[Na+]>C1C=CC=CC=1.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:18][C:9]1[N:8]=[C:7]([CH2:6][O:5][CH:21]([CH2:22][F:23])[CH2:20][F:19])[CH:12]=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[CH2:14])[N:10]=1
Reactant: C=C(OCC)c1cc(COS(C)(=O)=O)nc(Cl)n1
Reactant: OC(CF)CF
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=S(=O)([O-])O
Agent: [Na+]
Solvent: c1ccccc1
Product: C=C(OCC)c1cc(COC(CF)CF)nc(Cl)n1
Temperature: 25 °C
Yield: 10.8 %

Procedure:
To a solution of (2-chloro-6-(1-ethoxyvinyl)pyrimidin-4-yl)methyl methanesulfonate (0.50 g, 1.71 mmol) in benzene (10 mL), was added 1,3-difluoro-2-propanol (0.246 g, 2.56 mmol). Sodium hydroxide (5M (aq), 0.512 mL, 2.56 mmol) and tetrabutylammonium hydrogen sulfate (0.058 g, 0.17 mmol) were added. The mixture was stirred vigorously at rt over night. The mixture was filtered through a short silica plug with magnesium sulfate. The filter plug was eluted with EtOAc and the solvents were evaporated. The residue was purified by preparative HPLC to give the title compound as a solid (0.054 g, 11%).
Reaction SMILES: C[O:2][C:3]([C:5]1[O:6][C:7]([CH3:19])=[C:8]([CH2:10][O:11][C:12]2[CH:17]=[CH:16][C:15](I)=[CH:14][CH:13]=2)[CH:9]=1)=[O:4].[F:20][C:21]([F:32])([F:31])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1B(O)O>>[CH3:19][C:7]1[O:6][C:5]([C:3]([OH:2])=[O:4])=[CH:9][C:8]=1[CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2[C:21]([F:32])([F:31])[F:20])=[CH:14][CH:13]=1
Reactant: COC(=O)c1cc(COc2ccc(I)cc2)c(C)o1
Reactant: OB(O)c1ccccc1C(F)(F)F
Product: Cc1oc(C(=O)O)cc1COc1ccc(-c2ccccc2C(F)(F)F)cc1

Procedure:
Compound (102) was prepared from compound (20) and (2-trifluoromethyl-phenyl)-boronic acid by adapting the procedure of Example 5(b). LC/MS System B; Rt=1.93 mins, m/z (ES−)=375 (M−H for C20H15F3O4).
Reaction SMILES: [CH2:1]([N:3]1[CH2:9][CH2:8][CH2:7][N:6]([C:10]2[CH:20]=[CH:19][C:13]([C:14]([O:16]CC)=O)=[CH:12][CH:11]=2)[CH2:5][CH2:4]1)[CH3:2].[CH3:21][O:22][C:23]1[CH:24]=[C:25]([CH2:31][CH2:32][C:33]2[CH:34]=[C:35]([NH2:38])[NH:36][N:37]=2)[CH:26]=[C:27]([O:29][CH3:30])[CH:28]=1.C[Al](C)C.C(Cl)Cl.CCOCC>C1(C)C=CC=CC=1>[CH3:30][O:29][C:27]1[CH:26]=[C:25]([CH2:31][CH2:32][C:33]2[CH:34]=[C:35]([NH:38][C:14](=[O:16])[C:13]3[CH:12]=[CH:11][C:10]([N:6]4[CH2:7][CH2:8][CH2:9][N:3]([CH2:1][CH3:2])[CH2:4][CH2:5]4)=[CH:20][CH:19]=3)[NH:36][N:37]=2)[CH:24]=[C:23]([O:22][CH3:21])[CH:28]=1
Reactant: COc1cc(CCc2cc(N)[nH]n2)cc(OC)c1
Reactant: CCOC(=O)c1ccc(N2CCCN(CC)CC2)cc1
Agent: C[Al](C)C
Solvent: CCOCC
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: CCN1CCCN(c2ccc(C(=O)Nc3cc(CCc4cc(OC)cc(OC)c4)n[nH]3)cc2)CC1
Yield: 25.6 %

Procedure:
N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]-4-(4-ethyl-1,4-diazepan-1 was prepared using the same procedure as for Example 159, but starting from ethyl 4-(4-ethyl-1,4-diazepan-1-yl)benzoate (0.502 g, 1.4 mmol), 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (0.346 g, 1.40 mmol) and A 2M solution of trimethylaluminium (1.750 mL, 3.50 mmol) in toluene. The crude product was purified by preparative HPLC, using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford a gum which solidified on trituration with DCM/Ether to afford the title compound (0.171 g, 25.6%) as a white solid.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][S:5]([C:8]1[CH:17]=[CH:16][C:11]([C:12]([O:14]C)=[O:13])=[CH:10][CH:9]=1)(=[O:7])=[O:6].CC(C)([O-])C.[K+]>CC(O)(C)C.O>[CH:4]1([S:5]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([OH:14])=[O:13])=[CH:10][CH:9]=2)(=[O:7])=[O:6])[CH2:2][CH2:3]1
Reactant: COC(=O)c1ccc(S(=O)(=O)CCCCl)cc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CC(C)(C)O
Solvent: O
Product: O=C(O)c1ccc(S(=O)(=O)C2CC2)cc1
Temperature: 80 °C
Reaction time: 0.42 h
Yield: 79 %

Procedure:
To a solution of methyl 4-(3-chloropropylsulfonyl)benzoate (1.89 g, 6.83 mmol) in 2-methylpropan-2-ol (20 mL) was added potassium tert-butoxide (1.53 g, 13.7 mmol) and the slurry heated at 80° C. for 10 min. Additional 2-methylpropan-2-ol (20 mL) was added to facilitate stirring and the heating continued for 25 min. The reaction mixture was diluted with water (100 mL) and washed with ethyl acetate (3×100 mL). The aqueous layer was acidified with 1N HCl and extracted with ethyl acetate (3×100 mL). The combined organics were dried over Na2SO4, filtered and the solvent removed in vacuo to provide 4-cyclopropylsulfonylbenzoic acid (1.22 g, 79%) as a beige solid. ESI-MS m/z calc. 226.0. found 227.3 (M+1)+; Retention time: 0.86 minutes (3 min run).
Reaction SMILES: Br[CH:2]([C:8]1[CH:18]=[CH:17][CH:16]=[CH:15][C:9]=1[C:10]([O:12]CC)=O)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[CH2:19]([NH2:21])[CH3:20]>O1CCCC1>[CH2:19]([N:21]1[C:10](=[O:12])[C:9]2[C:8](=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:2]1[C:3]([O:5][CH2:6][CH3:7])=[O:4])[CH3:20]
Reactant: CCOC(=O)c1ccccc1C(Br)C(=O)OCC
Reactant: CCN
Solvent: C1CCOC1
Product: CCOC(=O)C1c2ccccc2C(=O)N1CC
Temperature: 20 °C
Reaction time: 48 h

Procedure:
A solution of ethyl 2-[1-bromo-2-(ethyloxy)-2-oxoethyl]benzoate (2.11 g, 6.7 mmol) in anhydrous tetrahydrofuran (200 ml) was treated with a 2M solution of ethylamine in tetrahydrofuran (8 ml, 16 mmol) and stirred at 20° C. for 48 hrs. The tetrahydrofuran was removed by evaporation and then the residue was taken up in ethyl acetate (150 ml) and water (150 ml). The aqueous phase was separated and extracted with more ethyl acetate (100 ml) and then the combined organic fractions was washed with saturated aqueous sodium chloride solution (150 ml) and then dried over magnesium sulphate and evaporated to give a yellow oil. The oil was purified by automated flash silica-gel column chromatography (using a Biotage SP4), eluting with 10-50% gradient of ethyl acetate in hexane, to give ethyl 2-ethyl-3-oxo-2,3-dihydro-1H-isoindole-1-carboxylate (1.4 g) as a colourless oil which solidified on standing and was used in the next step without further purification.
Reaction SMILES: C(Cl)Cl.[C:4]([C:7]12[CH2:16][CH:11]3[CH2:12][CH:13]([CH2:15][CH:9]([N:10]3[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:8]1)[CH2:14]2)(=O)[NH2:5].C(N(CC)CC)C.FC(F)(F)C(OC(=O)C(F)(F)F)=O>CCOC(C)=O>[C:4]([C:7]12[CH2:16][CH:11]3[CH2:12][CH:13]([CH2:15][CH:9]([N:10]3[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:8]1)[CH2:14]2)#[N:5]
Reactant: CC(C)(C)OC(=O)N1C2CC3CC1CC(C(N)=O)(C3)C2
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1C2CC3CC1CC(C#N)(C3)C2
Reaction time: 6 h
Yield: 70 %

Procedure:
A 50 mL RB flask fitted with magnetic stirrer was charged with 5 mL of DCM and tert-butyl 5-carbamoyl-2-azatricyclo[3.3.1.13,7]decane-2-carboxylate, Intermediate-11 (0.8 g, 2.8 mmol). Under N2 atm, triethyl amine (1.15 g, 11.4 mmol) and trifluoroacetic anhydride (2.4 g, 11.4 mmol) was added and stirred for 6 hr. After completion of the reaction (reaction was monitored by TLC), reaction mixture was quenched with KHSO4 solution and extracted with DCM (50 ml×3). The organic layer was washed with saturated sodium bi carbonate solution followed by brine solution. Finally the reaction mixture was dried over anhydrous sodium sulfate and concentrated to give crude Intermediate-13, which was subjected to column chromatogram (10% EtOAc in PE) as a off-white solid (0.5 g, yield=70%).
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.Cl[CH2:13][C:14]1[N:18]=[CH:17][O:16][N:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[O:16]1[CH:17]=[N:18][C:14]([CH2:13][N:5]2[C:1](=[O:11])[C:2]3=[CH:10][CH:9]=[CH:8][CH:7]=[C:3]3[C:4]2=[O:6])=[N:15]1
Reactant: ClCc1ncon1
Reactant: O=C1NC(=O)c2ccccc21
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C1c2ccccc2C(=O)N1Cc1ncon1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 83.5 %

Procedure:
Phthalimide (892 mg, 6.01 mmol) was dissolved in DMF (10 mL) followed by addition of 3-(chloromethyl)-1,2,4-oxadiazole (713 mg, 6.01 mmol), cesium carbonate (2.95 g, 9.02 mmol) and tetrabutylammonium iodide (3.35 g, 8.02 mmol), and then the mixture was stirred at room temperature for 2.5 hours. Water was added to the reaction mixture, and the resulting precipitate was collected by filtration and dried under reduced pressure to give N-(1,2,4-oxadiazol-3-ylmethyl)phthalimide (1.15 g; yield 83%).
Reaction SMILES: [N+:1]([O-:4])([OH:3])=[O:2].C(OC(=O)C)(=O)C.[N+:12]([O-:15])([OH:14])=[O:13].O[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1.C1C=CC=CC=1>CCCCCC>[N+:1]([O-:4])([OH:3])=[O:2].[O:13]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1)[N+:12]([O-:15])=[O:14]
Reactant: OCc1ccccn1
Solvent: CC(=O)OC(C)=O
Solvent: c1ccccc1
Solvent: CCCCCC
Product: O=[N+]([O-])OCc1ccccn1
Reaction time: 8 h

Procedure:
Fuming nitric acid (4.1 ml) was added dropwise to acetic anhydride (13.5 ml) with stirring at 5° to 10° C. After the mixture was stirred for 30 minutes at 5° C., 2-hydroxymethylpyridine nitrate (3.3 g) was added in some portions thereto. The resulting mixture was stirred for 3 hours at 0° to 5° C. A mixture of benzene (15 ml) and n-hexane (30 ml) was added thereto. The mixture formed two layers. The upper layer was separated and discarded while the remaining lower layer was again treated with a mixture of benzene (10 ml) and n-hexane (10 ml). After the separation of the layers, the lower layer was again separated, mixed with benzene (10 ml) and made homogeneous with isopropyl alcohol (10 ml). The resulting mixture was allowed to stand overnight in a refrigerator to give crystals. The crystals were collected by filtration and washed with diethyl ether to give white crystals of 2-nitroxymethylpyridine nitrate (2.4 g), mp. 75° to 77° C.
Reaction SMILES: [Cl:1][C:2]1[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:3]=1[CH2:4][N:5]1[CH2:9][C@H:8]([C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[C@@H:7]([CH2:15][N:16]2[CH2:21][CH2:20][CH:19]([CH2:22][O:23][CH2:24][CH2:25][CH2:26][NH2:27])[CH2:18][CH2:17]2)[CH2:6]1.[C:33](OC(=O)C)(=[O:35])[CH3:34].N1C=CC=CC=1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:1][C:2]1[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:3]=1[CH2:4][N:5]1[CH2:9][C@H:8]([C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[C@@H:7]([CH2:15][N:16]2[CH2:21][CH2:20][CH:19]([CH2:22][O:23][CH2:24][CH2:25][CH2:26][NH:27][C:33](=[O:35])[CH3:34])[CH2:18][CH2:17]2)[CH2:6]1
Reactant: NCCCOCC1CCN(C[C@H]2CN(Cc3ccc(Cl)cc3Cl)C[C@@H]2c2ccsc2)CC1
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(=O)NCCCOCC1CCN(C[C@H]2CN(Cc3ccc(Cl)cc3Cl)C[C@@H]2c2ccsc2)CC1

Procedure:
A solution of 0.03 g (0.06 mmol) of 1-(2,4-dichlorobenzyl)-3-(S)-(4-(3-aminopropyloxymethyl)piperidinylmethyl)-4-(S)-(3-thienyl)pyrrolidine, 0.02 mL (0.12 mmol) of acetic anhydride, 0.025 mL (0.3 mmol) of pyridine and a catalytic amount of DMAP in 0.5 mL of CH2Cl2 was stirred at rt for 18 h. The reaction mixture was concentrated and the residue was purified by chromatography (silica, CH2Cl2:methanol, 9:1) to give the title compound. Mass Spectrum (ESI) m/e=538 (M+1 35Cl, 35Cl), 540 (M+1 35Cl, 37Cl), and 542 (M+1 37Cl, 37Cl).
Reaction SMILES: [F:1][C:2]1[C:15]([F:16])=[CH:14][C:5]([C:6]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[O:7])=[C:4]([N+:17]([O-:19])=[O:18])[CH:3]=1.[CH2:20]([O:22][CH:23]([O-])[O-])[CH3:21]>C(O)(=O)C>[F:1][C:2]1[C:15]([F:16])=[CH:14][C:5]([C:6]([C:8](=[CH:23][O:22][CH2:20][CH3:21])[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[O:7])=[C:4]([N+:17]([O-:19])=[O:18])[CH:3]=1
Reactant: CCOC([O-])[O-]
Reactant: CCOC(=O)CC(=O)c1cc(F)c(F)cc1[N+](=O)[O-]
Solvent: CC(=O)O
Product: CCOC=C(C(=O)OCC)C(=O)c1cc(F)c(F)cc1[N+](=O)[O-]

Procedure:
To 3 ml of acetic acid anhydrous were added 3 g (0.01 mol) of ethyl 4,5-difluoro-2-nitrobenzoylacetate and 2.44 g (0.016 mol) of ethylorthoformate.
Reaction SMILES: [C:1]([C:4]1[CH:13]=[C:12]2[C:7]([C:8](=[O:31])[N:9]([CH2:15][CH2:16][CH2:17][CH2:18][N:19]3[CH2:24][CH:23]=[C:22]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH2:21][CH2:20]3)[C:10](=[O:14])[NH:11]2)=[CH:6][CH:5]=1)(=[O:3])N.[OH-:32].[Na+].Cl>C(O)C>[C:1]([C:4]1[CH:13]=[C:12]2[C:7]([C:8](=[O:31])[N:9]([CH2:15][CH2:16][CH2:17][CH2:18][N:19]3[CH2:24][CH:23]=[C:22]([C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH2:21][CH2:20]3)[C:10](=[O:14])[NH:11]2)=[CH:6][CH:5]=1)([OH:32])=[O:3]
Reactant: NC(=O)c1ccc2c(=O)n(CCCCN3CC=C(c4ccccc4)CC3)c(=O)[nH]c2c1
Reactant: [OH-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: O=C(O)c1ccc2c(=O)n(CCCCN3CC=C(c4ccccc4)CC3)c(=O)[nH]c2c1

Procedure:
A mixture of 7-carbamoyl-3-[4-(4-phenyl-1,2,3,6-tetrahydropyridin-1-yl)butyl]-1,2,3,4-tetrahydroquinazoline-2,4-dione (0.15 g), 1N sodium hydroxide solution (5 ml) and ethanol (5 ml) was stirred under reflux for 10 hours. After cooling, 1N hydrochloric acid (6 ml) was added and the precipitated crystals were collected to give 7-carboxy-3-[4-(4-phenyl-1,2,3,6-tetrahydropyridin-1-yl)butyl]-1,2,3,4-tetrahydroquinazoline-2,4-dione (0.15 g).
Reaction SMILES: [C:1]([C:3]1[CH:10]=[CH:9][C:6]([NH:7][CH3:8])=[CH:5][CH:4]=1)#[N:2].[C:11]1([N:17]([CH2:32][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[C:18]([C:20]2[CH:21]=[CH:22][C:23]3[S:27][C:26]([CH2:28]OC)=[N:25][C:24]=3[CH:31]=2)=[O:19])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>ClCCl.C(O)C>[C:11]1([N:17]([CH2:32][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[C:18]([C:20]2[CH:21]=[CH:22][C:23]3[S:27][C:26]([CH2:28][N:7]([C:6]4[CH:9]=[CH:10][C:3]([C:1]#[N:2])=[CH:4][CH:5]=4)[CH3:8])=[N:25][C:24]=3[CH:31]=2)=[O:19])[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: CCOC(=O)CCN(C(=O)c1ccc2sc(COC)nc2c1)c1ccccc1
Reactant: CNc1ccc(C#N)cc1
Solvent: ClCCl
Solvent: CCO
Product: CCOC(=O)CCN(C(=O)c1ccc2sc(CN(C)c3ccc(C#N)cc3)nc2c1)c1ccccc1
Yield: 57 %

Procedure:
Prepared analogously to Example 9e from 4-cyano-N-methyl-aniline and 2-methoxymethyl-benzothiazole-5-carboxylic acid-N-phenyl-N-(2-ethoxycarbonylethyl)-amide. Yield: 57% of theory, Rf value: 0.46 (silica gel; dichloromethane/ethanol=19:1).
Reaction SMILES: [C:1]1([C:7]#[C:8][C:9]2[CH:10]=[C:11]([C@@H:15]3[C@@H:19]([C:20]4[NH:24][N:23]=[N:22][N:21]=4)[O:18][C:17](=[O:25])[NH:16]3)[CH:12]=[CH:13][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:26](=O)([O-])[O-].[K+].[K+].IC>O1CCCC1>[CH3:26][N:22]1[N:23]=[N:24][C:20]([C@H:19]2[O:18][C:17](=[O:25])[NH:16][C@@H:15]2[C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([C:8]#[C:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH:10]=2)=[N:21]1
Reactant: O=C1N[C@H](c2cccc(C#Cc3ccccc3)c2)[C@@H](c2nnn[nH]2)O1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: C1CCOC1
Product: Cn1nnc([C@H]2OC(=O)N[C@@H]2c2cccc(C#Cc3ccccc3)c2)n1
Reaction time: 6 h
Yield: 11785.7 %

Procedure:
To a solution of (4R,5S)-4-(3-(phenylethynyl)phenyl)-5-(1H-tetrazol-5-yl)oxazolidin-2-one (18.6 mg, 0.056 mmol) in tetrahydrofuran (5 mL) was added potassium carbonate (38.8 mg, 0.281 mmol) and iodomethane (0.035 mL, 0.561 mmol) and the reaction mixture was held at 50° C. for 6 hours. The reaction mixture was concentrated and purified by Preparative HPLC Method 16 providing (4R,5S)-5-(2-methyl-2H-tetrazol-5-yl)-4-(3-(phenylethynyl)phenyl)oxazolidin-2-one (2.4 mg, 6.60 mmol, 11.76% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 4.43 (s, 3H) 5.27 (s, 1H) 5.75 (s, 1H) 7.39-7.46 (m, 4H) 7.49 (t, J=7.63 Hz, 1H) 7.55-7.62 (m, 3H) 8.69 (s, 1H). Mass spec.: 344.11 (M−H)−.
Reaction SMILES: [F:1][C:2]1[CH:15]=[C:14]2[C:5]([S:6](=[O:21])(=[O:20])[C:7]3[CH:8]=[C:9]([C:17](O)=[O:18])[CH:10]=[CH:11][C:12]=3[C:13]2=[O:16])=[CH:4][CH:3]=1.S(Cl)(Cl)=O.C[N:27](C)C=O>>[F:1][C:2]1[CH:15]=[C:14]2[C:5]([S:6](=[O:21])(=[O:20])[C:7]3[CH:8]=[C:9]([C:17]([NH2:27])=[O:18])[CH:10]=[CH:11][C:12]=3[C:13]2=[O:16])=[CH:4][CH:3]=1
Reactant: CN(C)C=O
Reactant: O=C(O)c1ccc2c(c1)S(=O)(=O)c1ccc(F)cc1C2=O
Solvent: O=S(Cl)Cl
Product: NC(=O)c1ccc2c(c1)S(=O)(=O)c1ccc(F)cc1C2=O

Procedure:
A mixture of 7-fluoro-9-oxo-3-thioxanthene carboxylic acid 10,10-dioxide (see example 6), 34.0 g (0.11 mol), and thionyl chloride, 130.9 g (1.10 mol), was heated at reflux for 2.0 hr. Dimethyl formamide, 1 ml, was added to the mixture, giving a solution which was heated at reflux overnight. The reaction was cooled, and a yellow crystalline solid, 27.85 g, was collected and washed with ether. A portion of the acid chloride, 5.0 g, was placed in concentrated NH4OH, 50 mL, and heated on a steam bath for 0.5 hr. The solid was filtered and washed with H2O and acetone to give 3.82 g of the amide. A small amount of the amide was recrystallized from DMF:MeOH/75:25 to provide 0.3 g of a light yellow crystalline 7-fluoro-9-oxothioxanthene-3-carboxamide 10,10-dioxide, m.p. 307°-310° C. TLC (CHCl3 /MeOH/9/1) Rf =0.45.
Reaction SMILES: [CH:1]1[CH:2]=[C:3]2[C:8]3=[C:9]([C:11]([NH:13][C:14](=[O:15])[C:7]3=[CH:6][CH:5]=[CH:4]2)=[O:12])[CH:10]=1.CN(C)C=O.[OH-].[K+].[Br:23][CH2:24][CH2:25][CH2:26][CH2:27]Br>CO>[Br:23][CH2:24][CH2:25][CH2:26][CH2:27][N:13]1[C:14](=[O:15])[C:7]2[CH:6]=[CH:5][CH:4]=[C:3]3[C:8]=2[C:9](=[CH:10][CH:1]=[CH:2]3)[C:11]1=[O:12]
Reactant: BrCCCCBr
Reactant: O=C1NC(=O)c2cccc3cccc1c23
Agent: [K+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: CO
Product: O=C1c2cccc3cccc(c23)C(=O)N1CCCCBr
Reaction time: 1 h

Procedure:
100 g. (0.5 mole) of 1,8-naphthalimide is suspended in 2100 ml. of dimethylformamide and the mixture is heated to 90° to form a complete solution. A solution of 36.3 g. (0.55 mole) of potassium hydroxide (85%) in 100 ml. of methanol is added resulting in the immediate formation of a yellow precipitate. The resulting mixture is stirred for one hour at 90° and cooled to 25°. 245 g. (1.0 mole) of 1,4-dibromobutane is added and the mixture is again heated to 90° and stirred for an additional hour. A precipitate remains in the mixture but is more granular than the initial material. The reaction mixture is cooled and the precipitate filtered off. The solvent is removed under vacuum and the residue is diluted with 500 ml. of hexane immediately precipitating crude 2-(4-bromobutyl)-1H-benz[de]isoquinoline-1,3(2H)-dione. The precipitate is filtered off, washed with fresh hexane and dried for 2 hours at 50° (0.1 mm.) to yield 2-(4-bromobutyl)-1H-benz[de]isoquinoline-1,3(2H)-dione. An analytically pure sample is prepared by dissolving the above product in hot 95% ethanol and recrystallizing by allowing the solution to cool to 25°. The resulting precipitate is dried for two hours at 50° (0.1 mm.) to yield pure 2-(4-bromobutyl)-1H-benz[de]isoquinoline-1,3(2 H)-dione, m.p. 113°-115°.
Reaction SMILES: [C:1]([C:3]1[N:4]=[C:5]([CH2:13][O:14][C@H:15]2[CH2:19][CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16]2)[C:6]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2)#[N:2].[NH:27]([C:29](OCC)=[O:30])[NH2:28].C1CCN2C(=NCCC2)CC1>CN1C(=O)CCC1>[NH:17]1[CH2:18][CH2:19][C@H:15]([O:14][CH2:13][C:5]2[C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[CH:12]=[C:3]([C:1]3[NH:2][C:29](=[O:30])[NH:27][N:28]=3)[N:4]=2)[CH2:16]1
Reactant: CC(C)(C)OC(=O)N1CC[C@H](OCc2nc(C#N)cc3ccccc23)C1
Reactant: CCOC(=O)NN
Solvent: C1CCC2=NCCCN2CC1
Solvent: CN1CCCC1=O
Product: O=c1[nH]nc(-c2cc3ccccc3c(CO[C@H]3CCNC3)n2)[nH]1
Temperature: 170 °C
Yield: 15.6 %

Procedure:
A mixture of (S)-tert-butyl 3-((3-cyanoisoquinolin-1-yl)methoxy)pyrrolidine-1-carboxylate (54.6 mg, 0.154 mmol) in NMP (0.4 mL), ethyl hydrazinecarboxylate (80 mg, 0.772 mmol) and DBU (0.012 mL, 0.077 mmol) was heated at 170° C. overnight and then filtered. The product in the filtrate was purified by mass-triggered HPLC eluting with a gradient of 35-60% ACN in water (acid mode). The product-containing fractions were concentrated in vacuo, treated with neat TFA (1 mL) for 5 minutes, and again concentrated in vacuo. The concentrate was dispersed in ACN/water (1:1) and lyophilized to give the title compound (7.5 mg, 16%). ESI-MS m/z [M+H]+ 312.6.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:13][C:12](=[O:14])[CH2:11][C:10](=[O:15])[CH2:9]1.[CH3:16][O:17][CH2:18][C:19](O)=[O:20].C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C1C=CN=CC=1.CN(C)C=O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:13][C:12](=[O:14])[C:11](=[C:19]([OH:20])[CH2:18][O:17][CH3:16])[C:10](=[O:15])[CH2:9]1
Reactant: O=C1CC(=O)CC(c2ccccc2Cl)C1
Reactant: COCC(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: CN(C)C=O
Product: COCC(O)=C1C(=O)CC(c2ccccc2Cl)CC1=O
Temperature: 25 °C
Reaction time: 72 h
Yield: 65 %

Procedure:
To a solution of 5-(2-chlorophenyl)cyclohexane-1,3-dione (1.0 g), 4-dimethylaminopyridine (0.82 g) and methoxyacetic acid (0.73 g) in dimethylformamide (40 ml) was added dicyclohexylcarbodiimide (1.0 g), and the mixture was stirred at room temperature for 3 days. Under reduced pressure, the solvent was evaporated, and to the residue was added ethyl acetate. Insoluble materials were filtered off, and the organic layer was extracted with 1N sodium hydroxide solution. To the aqueous layer was added 1N hydrochloric acid to make the solution acidic, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated to give 5-(2-chlorophenyl)-2-(1-hydroxy-2-methoxyethylidene)cyclohexane-1,3-dione (0.86 g) as oil.