Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[C:3]([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)=[N:4][CH:5]=[N:6][CH:7]=1.[CH3:15][N:16](C=O)C>Cl.O.C(OCC)(=O)C>[C:15]([C:2]1[C:3]([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)=[N:4][CH:5]=[N:6][CH:7]=1)#[N:16]
Reactant: CN(C)C=O
Reactant: Cc1ccc(-c2ncncc2Br)cc1
Agent: Cl
Solvent: O
Solvent: CCOC(C)=O
Product: Cc1ccc(-c2ncncc2C#N)cc1
Temperature: 50 °C

Procedure:
A mixture of 5-bromo-4-(p-tolyl)pyrimidine (10 g, 40.2 mmol) and cuprous cyanide (4.4 g, 44.2 mmol) in DMF (20 ml) was heated under reflux for 3 hours. To the reaction mixture was added a solution of ferric chloride. 6 hydrate (13 g, 48.2 mmol) in a mixture of hydrochloric acid (7 ml) and water (55 ml) and the mixture was heated at 50° C. for 10 minutes. After the reaction solution was taken up in ethyl acetate and water, the mixture was extracted with ethyl acetate. The extract was washed with water and concentrated to dryness. The residue was purified by column chromatography on silica gel to give a crystalline product. Recrystallization from isopropyl ether-hexane afforded colorless needles (5 g, 64%), m.p. 127°-128° C.
Reaction SMILES: [O:1]=[C:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[C@H:6]2[CH2:13][CH2:14][N:15](C(OC(C)(C)C)=O)[CH2:16][C@H:5]2[CH2:4][NH:3]1.Cl.CO>C(OCC)C>[CH2:13]1[C@H:6]2[C@H:5]([CH2:4][NH:3][C:2](=[O:1])[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=32)[CH2:16][NH:15][CH2:14]1
Reactant: CC(C)(C)OC(=O)N1CC[C@@H]2c3ccccc3C(=O)NC[C@@H]2C1
Agent: Cl
Solvent: CCOCC
Solvent: CO
Product: O=C1NC[C@@H]2CNCC[C@@H]2c2ccccc21
Reaction time: 8 h

Procedure:
To a suspension of Example 180G in 400 mL of diethyl ether was added 80 mL of HCl/methanol (5N) at 25° C. The mixture was stirred overnight. The solid formed was collected and dried to obtain the title compound as the hydrochloride salt.
Reaction SMILES: [CH:1]([Mg]Cl)([CH3:3])[CH3:2].[Br:6][C:7]1[CH:14]=[CH:13][C:10]([CH:11]=[O:12])=[CH:9][CH:8]=1>O1CCCC1>[Br:6][C:7]1[CH:14]=[CH:13][C:10]([CH:11]([OH:12])[CH:1]([CH3:3])[CH3:2])=[CH:9][CH:8]=1
Reactant: O=Cc1ccc(Br)cc1
Reactant: CC(C)[Mg]Cl
Solvent: C1CCOC1
Product: CC(C)C(O)c1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 24 %

Procedure:
A solution of isopropylmagnesium chloride (17.0 L, 1M in tetrahydrofuran) was added dropwise to the solution of 4-bromobenzaldehyde (2.1 g, 11.4 mol) in tetrahydrofuran (30 mL) at −10° C. Then the mixture was stirred at 25° C. for 4 hours. The resultant reaction was quenched with saturated ammonium chloride aqueous (20 mL). The organic phase was separated, dried over sodium sulfate, filtered and concentrated to give a residue. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=2:1) to give 1-(4-bromophenyl)-2-methylpropan-1-ol (620 mg, 24%). 1H NMR (300 MHz, CDCl3): δ 7.98-7.85 (m, 2H), 7.48-7.35 (m, 2H), 5.17 (s, 1H), 4.49 (d, J=6.6 Hz, 1H), 2.35-2.30 (m, 1H), 1.01 (d, J=6.6 Hz, 6H).
Reaction SMILES: [OH-].[Na+].[CH2:3]1[C:11]2[C:6](=[CH:7][C:8]([CH:12]=O)=[CH:9][CH:10]=2)[CH2:5][CH2:4]1.[CH3:14][C:15]([CH3:17])=[O:16]>O>[CH2:3]1[C:11]2[C:6](=[CH:7][C:8]([CH:12]=[CH:14][C:15](=[O:16])[CH3:17])=[CH:9][CH:10]=2)[CH2:5][CH2:4]1
Reactant: O=Cc1ccc2c(c1)CCC2
Reactant: CC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC(=O)C=Cc1ccc2c(c1)CCC2
Yield: 81 %

Procedure:
An aqueous solution of 10% sodium hydroxide (50-70 ml) was added dropwise over a period of 5 minutes to a suspension of indane-5-carboxaldehyde (18.50 g; 127 mmole) in acetone (50 ml) and water (50 ml). The mixture was stirred at a temperature of 65° C. for a period of 11/2 hours and then extracted with dichloromethane (200 ml). The organic extract was washed several times with water, dried over anhydrous sodium sulphate, and the solvent was removed under reduced pressure using a rotary evaporator to give 1-(5-indanyl)but-1-en-3-one (19.25 g; 81%) as a viscous oil.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:24])[C:5]1[C:17]([F:18])=[C:16]([NH:19][S:20]([CH3:23])(=[O:22])=[O:21])[CH:15]=[C:7]([C:8]([N:10]([CH3:14])[CH2:11][CH2:12][CH3:13])=[O:9])[CH:6]=1)[CH3:2].[C:25](=O)([O-])[O-].[K+].[K+].IC>CN(C=O)C.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:1]([O:3][C:4](=[O:24])[C:5]1[C:17]([F:18])=[C:16]([N:19]([S:20]([CH3:23])(=[O:21])=[O:22])[CH3:25])[CH:15]=[C:7]([C:8]([N:10]([CH3:14])[CH2:11][CH2:12][CH3:13])=[O:9])[CH:6]=1)[CH3:2]
Reactant: O=C([O-])[O-]
Reactant: CCCN(C)C(=O)c1cc(NS(C)(=O)=O)c(F)c(C(=O)OCC)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: CCCN(C)C(=O)c1cc(C(=O)OCC)c(F)c(N(C)S(C)(=O)=O)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 92.6 %

Procedure:
Dissolve 6-fluoro-5-methanesulfonylamino-N-methyl-N-propyl-isophthalamic acid ethyl ester (0.160 g, 0.444 mmol) in DMF (1.0 mL). Add potassium carbonate (44.4 mg, 0.32 mmol), iodomethane (41.5 μL, 0.67 mmol) and tetrabutylammonium bromide (14.3 mg, 0.04 mmol) to the solution. Stir the resulting slurry at room temperature for 16 h. Quench with saturated aqueous sodium sulfate solution (10 mL) and extract with ethyl acetate (3×30 mL). Combine the organic layers and dry (magnesium sulfate). Azeotrope the residue with xylenes to remove residual DMF. Purify (silica gel chromatography, eluting with 40:60 ethyl acetate:dichloromethane) to give the title compound as a solid (111 mg, 67%).
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]([Br:24])(Br)(Br)Br.[CH3:25][O:26][C:27]([C:29]1[N:30]=[N:31][N:32]([C:42]2[CH:47]=[C:46]([CH:48]([CH3:50])[CH3:49])[C:45]([O:51][CH2:52][C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=3)=[CH:44][C:43]=2[O:59][CH2:60][C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)[C:33]=1[C:34]1[CH:39]=[CH:38][C:37](CO)=[CH:36][CH:35]=1)=[O:28]>C(Cl)Cl>[CH3:25][O:26][C:27]([C:29]1[N:30]=[N:31][N:32]([C:42]2[CH:47]=[C:46]([CH:48]([CH3:50])[CH3:49])[C:45]([O:51][CH2:52][C:53]3[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=3)=[CH:44][C:43]=2[O:59][CH2:60][C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)[C:33]=1[C:34]1[CH:35]=[CH:36][C:37]([CH2:20][Br:24])=[CH:38][CH:39]=1)=[O:28]
Reactant: BrC(Br)(Br)Br
Reactant: COC(=O)c1nnn(-c2cc(C(C)C)c(OCc3ccccc3)cc2OCc2ccccc2)c1-c1ccc(CO)cc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: COC(=O)c1nnn(-c2cc(C(C)C)c(OCc3ccccc3)cc2OCc2ccccc2)c1-c1ccc(CBr)cc1
Reaction time: 1 h
Yield: 87 %

Procedure:
Triphenylphosphine (1.45 g, 5.54 mmol) and carbon tetrabromide (1.84 g, 5.54 mmol) were added to a solution of 1-(2,4-bis-benzyloxy-5-isopropyl-phenyl)-5-(4-hydroxymethyl-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid methyl ester (2.4 g, 4.26 mmol) in dry DCM (48 ml) at 0° C. The mixture was stirred at this temperature for one hour, then the solvent was removed under reduced pressure and the residue was purified by column chromatography (PE/AcOEt: 70:30). The title compound was obtained as an oil (2.32 g, 87%).
Reaction SMILES: [Br:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:10](Cl)(=[O:14])[CH:11]([CH3:13])[CH3:12].[Cl-].[Al+3].[Cl-].[Cl-].Cl>ClC1C=CC=CC=1Cl>[Br:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([C:10](=[O:14])[CH:11]([CH3:13])[CH3:12])=[CH:6][CH:5]=1
Reactant: CC(C)C(=O)Cl
Reactant: BrCCc1ccccc1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: Clc1ccccc1Cl
Product: CC(C)C(=O)c1ccc(CCBr)cc1
Temperature: 0 °C
Reaction time: 8 h
Yield: 108.9 %

Procedure:
2-Bromoethylbenzene (10.0 g, 0.0540 mol) is mixed with 6.6 g (0.062 mol) of isobutyryl chloride and 100 ml of 1,2-dichlorobenzene. The mixture is cooled internally to 0° C., and 9.4 g (0.070 mol) of aluminum chloride is added portion wise over 3 hours while keeping the reaction mixture at 0-5° C. The reaction mixture is stirred overnight, then poured into a mixture of ice and concentrated hydrochloric acid. After stirring for 30 minutes, the organic layer is washed with dilute hydrochloric acid, sodium bicarbonate solution, and water, then dried over sodium sulfate and concentrated to give 15.0 g of crude 1-[4-(2-bromoethyl)phenyl]-2-methylpropan-1-one.
Reaction SMILES: [CH3:1][N:2]1[C:6]2[CH:7]=[C:8](Br)[CH:9]=[CH:10][C:5]=2[NH:4][C:3]1=[O:12].[Cl:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1>>[Cl:13][C:14]1[CH:19]=[C:18]([C:8]2[CH:9]=[CH:10][C:5]3[NH:4][C:3](=[O:12])[N:2]([CH3:1])[C:6]=3[CH:7]=2)[CH:17]=[CH:16][CH:15]=1
Reactant: OB(O)c1cccc(Cl)c1
Reactant: Cn1c(=O)[nH]c2ccc(Br)cc21
Product: Cn1c(=O)[nH]c2ccc(-c3cccc(Cl)c3)cc21

Procedure:
Prepared from 1-methyl-6-bromo-1,3-dihydro-benzoimidazol-2-one and 3-chloro-phenyl boronic acid in the same fashion as that of Example 5. mp 219-220° C.; 1H-NMR (DMSO-d6) δ11.0 (s, 1H), 7.75 (bs, 1H), 7.65 (dd, 1H, J=7.5, 1.76 Hz), 7.49-7.44 (m, 2H), 7.39-7.32 (m, 2H), 7.06 (d, 1H, J=7.94 Hz), 3.35 (s, 3H); MS (ES) m/z 259([M+H]+, 100%); Anal. Calc. For C14H11ClN2O: C, 65; H, 4.29; N, 10.83. Found: C, 64.44; H, 4.36; N, 10.6.
Reaction SMILES: [F:1][C:2]1[C:3](F)=[C:4]2[O:9][CH2:8][C@H:7]([CH3:10])[N:6]3[CH:11]=[C:12]([C:17]([OH:19])=[O:18])[C:13](=[O:16])[C:14]([CH:15]=1)=[C:5]23.Cl.[CH3:22][C:23]1[N:24]=[N:25][N:26]([CH:28]2[CH2:32][CH2:31][NH:30][CH2:29]2)[CH:27]=1.C1CCN2C(=NCCC2)CC1>C(#N)C>[F:1][C:2]1[C:3]([N:30]2[CH2:31][CH2:32][CH:28]([N:26]3[CH:27]=[C:23]([CH3:22])[N:24]=[N:25]3)[CH2:29]2)=[C:4]2[O:9][CH2:8][C@H:7]([CH3:10])[N:6]3[CH:11]=[C:12]([C:17]([OH:19])=[O:18])[C:13](=[O:16])[C:14]([CH:15]=1)=[C:5]23
Reactant: Cc1cn(C2CCNC2)nn1
Reactant: C[C@H]1COc2c(F)c(F)cc3c(=O)c(C(=O)O)cn1c23
Agent: Cl
Solvent: C1CCC2=NCCCN2CC1
Solvent: CC#N
Product: Cc1cn(C2CCN(c3c(F)cc4c(=O)c(C(=O)O)cn5c4c3OC[C@@H]5C)C2)nn1

Procedure:
A solution of 70.25 mg (0.25 mmol) of (-)-9,10-difluoro-3(S)-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid and 141 mg (0.75 mmol) of 3-(4-methyl-1,2,3-triazol-1-yl)pyrrolidine hydrochloride in 3 ml of acetonitrile in the presence of 152.24 mg (1 mmol) of DBU was refluxed for 3 days under nitrogen atmosphere. The suspension was then evaporated and water was added to the residue and solid collected and washed with methanol to yield after drying 50 mg of the desired product, m.p. 241°-242° C. 1H NMR (TFA) δ: 9.16 (s, 1H), 8.37 (s, 1H), 7.99 (d, 13.3Hz, 1H), 5.75-5.6 (m, 1H), 5.15-4.1 (m, 7H), 3-2.6 (m, 2H), 2.67 (s , 3H), 1.8 (d, 6.8Hz, 3H). Anal. calcd. for C20H20FN5O4 . 1/2 H2O: C, 56.87; H, 5.01; N, 16.58. Found: C, 57.30; H, 4.77; N, 16.75.
Reaction SMILES: [C:1]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:15][C:16]([S@@:19]([NH2:21])=[O:20])([CH3:18])[CH3:17]>O1CCOCC1.[Cl-].[Na+].O>[C:2]1([C:1]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:21][S@:19]([C:16]([CH3:18])([CH3:17])[CH3:15])=[O:20])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(c1ccccc1)c1ccccc1
Reactant: CC(C)(C)[S@@](N)=O
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: CC(C)(C)[S@](=O)N=C(c1ccccc1)c1ccccc1
Temperature: 105 °C
Reaction time: 0.17 h

Procedure:
In a flame dried flask under N2, benzophenone (0.514 g, 2.82 mmol) was dissolved in anhydrous dioxane (5 mL). Ti(IV) ethoxide (1.479 mL, 7.05 mmol) was added followed by (S)-(−)-2-methyl-2-propanesulfinamide (0.376 g, 3.10 mmol). The rxn was heated to 105° C. After 4.5 hr the reaction was cooled to RT and brine (15 mL) was added. A precipitate formed and the reaction was rapidly stirred for 10 min. The suspension was filtered through celite and the filter cake was washed with brine and ethyl acetate. The layers of the filtrate were separated. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo to afford a yellow oil. The oil was purified by flash column chromatography (90:10 hexanes/ethyl acetate). The fractions were combined and concentrated in vacuo to afford (S)-N-(diphenylmethylene)-2-methylpropane-2-sulfinamide as a light yellow oil. 1H NMR (CDCl3) δ 7.51-7.43 (broad m, 10H), 1.30 (s, 9H). [M+H]+=286.1.
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([C:16]3[S:17][CH:18]=[CH:19][CH:20]=3)=[C:12]([F:21])[CH:11]=2)=[CH:6][CH:5]=1)[CH2:2][CH3:3].[Li]CCCC.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:37])(=O)=O)=CC=1.O>C1COCC1>[F:37][C:18]1[S:17][C:16]([C:13]2[CH:14]=[CH:15][C:10]([C:7]3[CH:6]=[CH:5][C:4]([CH2:1][CH2:2][CH3:3])=[CH:9][CH:8]=3)=[CH:11][C:12]=2[F:21])=[CH:20][CH:19]=1
Reactant: CCCc1ccc(-c2ccc(-c3cccs3)c(F)c2)cc1
Reactant: O=S(=O)(c1ccccc1)N(F)S(=O)(=O)c1ccccc1
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Product: CCCc1ccc(-c2ccc(-c3ccc(F)s3)c(F)c2)cc1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
4.0 g (13.5 mmol) of 2-(4′-propyl-3-fluorobiphenyl-4-yl)thiophene (“PGT-3-H”) are initially introduced at −20° C. in THF, and 9.3 ml (14.8 mmol) of n-BuLi (15% solution in hexane) are added dropwise. The mixture is warmed to 0° C. and stirred at this temperature for 30 min. The batch is cooled to −78° C., and a solution of 5.11 g (16.2 mmol) of N-fluorobenzenesulfonimide (NFSI) in THF is metered in. After 30 min at −78° C., the batch is warmed to room temperature. Water is added, and the mixture is extracted a number of times with MTBE. The combined organic phases are washed with water and sat. sodium chloride solution and dried using sodium sulfate. The solution is evaporated to dryness, and the residue is purified by chromatography (SiO2, n-pentane). The further purification is carried out by recrystallisation from ethanol and n-heptane, giving 2-fluoro-5-(3-fluoro-4′-propylbiphenyl-4-yl)thiophene (“PGT-3-F”) as a colourless solid having an m.p. of 64° C.
Reaction SMILES: [C:1](Cl)(Cl)=[O:2].[CH2:5]([N:12]1[CH2:17][CH2:16][CH:15]([NH:18][CH2:19][CH2:20][NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:14][CH2:13]1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>C1(C)C=CC=CC=1.[OH-].[K+]>[CH2:5]([N:12]1[CH2:13][CH2:14][CH:15]([N:18]2[CH2:19][CH2:20][N:21]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:1]2=[O:2])[CH2:16][CH2:17]1)[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1
Reactant: c1ccc(CN2CCC(NCCNc3ccccc3)CC2)cc1
Reactant: O=C(Cl)Cl
Agent: [K+]
Agent: [OH-]
Solvent: Cc1ccccc1
Product: O=C1N(c2ccccc2)CCN1C1CCN(Cc2ccccc2)CC1
Yield: 66.4 %

Procedure:
With stirring, 15 g of phosgene are introduced at 5° to 10° C. in the course of 1 hour into a suspension of 10 g of 1-benzyl-4-(2-phenylamino-1-ethylamino)-piperidine in 100 ml of toluene and 48.5 ml of 3 N potassium hydroxide solution. After stirring for 2 hours at 5° to 10° C., the reaction mixture is made alkaline with 43 ml of 6 N potassium hydroxide solution and brought to room temperature. After it has been stirred for a further 15 hours at room temperature, the reaction mixture is filtered with suction and the residue is recrystallised from isopropanol-methanol to yield 7.2 g of 1-(1-benzyl-4-piperidinyl)-3-phenyl-2-imidazolidinone.
Reaction SMILES: C1C=C(Cl)C=C(C(OO)=[O:9])C=1.[CH2:12]([N:14]1[C:20]2[N:21]=[CH:22][C:23]([CH2:25][CH2:26][O:27][C:28]3[C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[N:31]=[CH:30][CH:29]=3)=[CH:24][C:19]=2[C:18](=[O:38])[N:17]([CH3:39])[C:16]2[CH:40]=[CH:41][C:42]([C:44]([F:47])([F:46])[F:45])=[N:43][C:15]1=2)[CH3:13]>C(Cl)Cl>[CH2:12]([N:14]1[C:20]2[N:21]=[CH:22][C:23]([CH2:25][CH2:26][O:27][C:28]3[C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[N+:31]([O-:9])=[CH:30][CH:29]=3)=[CH:24][C:19]=2[C:18](=[O:38])[N:17]([CH3:39])[C:16]2[CH:40]=[CH:41][C:42]([C:44]([F:46])([F:45])[F:47])=[N:43][C:15]1=2)[CH3:13]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCN1c2ncc(CCOc3ccnc4ccccc34)cc2C(=O)N(C)c2ccc(C(F)(F)F)nc21
Solvent: ClCCl
Product: CCN1c2ncc(CCOc3cc[n+]([O-])c4ccccc34)cc2C(=O)N(C)c2ccc(C(F)(F)F)nc21
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 54 %

Procedure:
Solid mCPBA (80-85%, m-chloroperbenzoic acid) (16 mg, 0.08 mmol) was added to a solution of 5,11-dihydro-11-ethyl-5-methyl-8-{2-(4-quinolinyloxy)ethyl}-2-(trifluoromethyl)-6H-dipyrido[3,2-b:2′,3′-e][1,4]diazepin-6-one (22 mg, 0.04 mmol) in CH2Cl2 (0.5 mL) at room temperature. The mixture was stirred at room temperature for 2.5 h then diluted with CH2Cl2. The resulting solution was successively washed with aqueous 10% Na2S2O3, aqueous saturated NaHCO3 and brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (MeOH:CHCl3, 5% to 10%) to give the title compound (11 mg, 52% yield) as a white solid: MS (ESI) m/z 511 (MH)+.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]1[CH2:11][CH:10]([CH2:12][O:13][C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-])=O)=[CH:16][CH:15]=2)[O:9][C:8]1=[O:23].[H][H]>O1CCOCC1.CN(C)C=O.[C].[Pd]>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]1[CH2:11][CH:10]([CH2:12][O:13][C:14]2[CH:15]=[CH:16][C:17]([NH2:20])=[CH:18][CH:19]=2)[O:9][C:8]1=[O:23]
Reactant: [H][H]
Reactant: O=C1OC(COc2ccc([N+](=O)[O-])cc2)CN1c1ccccn1
Agent: [Pd]
Solvent: C1COCCO1
Solvent: CN(C)C=O
Product: Nc1ccc(OCC2CN(c3ccccn3)C(=O)O2)cc1
Yield: 81.2 %

Procedure:
A 0.47 g quantity of 10% palladium carbon was added to a solution of 4.64 g of 4-[3-(2-pyridyl)-2-oxooxazolidin-5-yl]methoxynitrobenzene in 50 ml of 1,4-dioxane and 150 ml of N,N-dimethylformamide. The mixture was stirred at room temperature for 2.5 hours in a stream of hydrogen under 5 atmospheric pressure. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. Methanol was added to the obtained residue to collect the crystals by filtration. Thus, 3.41 g of the title compound was obtained (yield 81%).
Reaction SMILES: NC1C=C2C(CCC(C)(C)N2)=CC=1.[CH2:14]([C:16]1([CH2:29][CH3:30])[CH2:25][CH2:24][C:23]2[C:18](=[CH:19][C:20]([N+:26]([O-])=O)=[CH:21][CH:22]=2)[NH:17]1)[CH3:15]>CCOC(C)=O.CCO.[Pd]>[NH2:26][C:20]1[CH:19]=[C:18]2[C:23]([CH2:24][CH2:25][C:16]([CH2:29][CH3:30])([CH2:14][CH3:15])[NH:17]2)=[CH:22][CH:21]=1
Reactant: CCC1(CC)CCc2ccc([N+](=O)[O-])cc2N1
Agent: [Pd]
Agent: CC1(C)CCc2ccc(N)cc2N1
Solvent: CCO
Solvent: CCOC(C)=O
Product: CCC1(CC)CCc2ccc(N)cc2N1
Yield: 93.8 %

Procedure:
This compound was prepared in a manner similar to that described for 7-amino-1,2,3,4-tetrahydro-2,2-dimethylquinoline (structure 19 of Scheme III, where R1 =R2 =Me) from for 2,2-diethyl-1,2,3,4-tetrahydro-7-nitroquinoline (0.311 g, 1.33 mmol) and 10% Pd/C (31 mg, 10% by weight) in EtOAc (4.0 mL) and EtOH (4.0 mL) to afford 255 mg (94%) of 7-amino-2,2-diethyl-1,2,3,4-tetrahydroquinoline. Data for 7-amino-2,2-diethyl-1,2,3,4-tetrahydroquinoline: Rf 0.26 (4:1 hexanes:ethyl acetate); 1H NMR (400 MHz, CDCl3) 6.77 (d, J=7.9H, 1H), 6.12 (dd, J=7.9, 1.9, 1H), 6.05 (d, J=2.0, 1H), 4.68 (broad s, 3H), 2.62 (t, J=6.7, 2H), 1.67 (t, J=6.7, 2H), 1.38-1.55 (m, 4H), 0.85 (t, J=7.4, 6H).
Reaction SMILES: [Cl:1][C:2]([C:7]([CH3:10])([CH3:9])[CH3:8])=[CH:3][C:4]([OH:6])=[O:5].S(Cl)(Cl)=O.O.[CH3:16]O>>[Cl:1][C:2]([C:7]([CH3:10])([CH3:9])[CH3:8])=[CH:3][C:4]([O:6][CH3:16])=[O:5]
Reactant: CC(C)(C)C(Cl)=CC(=O)O
Reactant: CO
Solvent: O=S(Cl)Cl
Solvent: O
Product: COC(=O)C=C(Cl)C(C)(C)C
Yield: 87 %

Procedure:
To a solution of 3-chloro-4,4-dimethylpent-2-enoic acid (0.8 g, 4.92 mmol) in methanol (20 mL) was added thionyl chloride (0.714 mL, 9.846 mmol) drop wise under stirring at ice cold temperature. The reaction mixture was refluxed for 2 h and attained to rt. The mixture was poured into ice cooled water and stirred for 15 min. The solution was extracted with chloroform (3×100 mL) and the combined organic layer was washed with water, brine, dried over sodium sulfate and filtered. Solvent was evaporated and the residue was chromatographed over silica gel column using hexane-ethyl acetate (95:5) as eluents to give the product as a pale green color oil (750 mg, 87%). 1H NMR (400 MHz, CDCl3): δ 6.08 (1H, s), 3.75 (3H, s), 1.24 (9H, s).
Reaction SMILES: [CH3:1][O:2][C:3]1[N:7]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[C:21]3[NH:25][N:24]=[N:23][N:22]=3)=[CH:11][CH:10]=2)[C:6]2[C:26]([C:30]([O:32]C)=[O:31])=[CH:27][CH:28]=[CH:29][C:5]=2[N:4]=1.[OH-].[Na+]>CO>[CH3:1][O:2][C:3]1[N:7]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[C:21]3[NH:25][N:24]=[N:23][N:22]=3)=[CH:13][CH:14]=2)[C:6]2[C:26]([C:30]([OH:32])=[O:31])=[CH:27][CH:28]=[CH:29][C:5]=2[N:4]=1
Reactant: COC(=O)c1cccc2nc(OC)n(Cc3ccc(-c4ccccc4-c4nnn[nH]4)cc3)c12
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: COc1nc2cccc(C(=O)O)c2n1Cc1ccc(-c2ccccc2-c2nnn[nH]2)cc1
Yield: 79.8 %

Procedure:
To a solution of methyl 2-methoxy-1-[[2′-(1 H-tetrazol-5-yl)-biphenyl-4-yl]methyl]benzimidazole-7-carboxylate (0.22 g) in methanol (10 ml) was added 1N-NaOH (1.5 ml). The mixture was heated for 6 Hours under reflux. The reaction mixture was concentrated to dryness and to the residue was added water. The mixture was adjusted to pH 3-4 with 1N-HCl to give crystals. Recrystallization from methanol-chloroform gave colorless needles (0.17 g, 77%), m.p. 208-209° C.
Reaction SMILES: Cl[C:2]1[C:3]2[N:4]([C:12]([CH2:15][CH3:16])=[N:13][N:14]=2)[C:5]2[C:10]([N:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.Cl[C:18]1[C:19]2[N:20](C=NN=2)[C:21]2C(N=1)=CC=C[CH:22]=2.C(NCC)C.C(NCCC)CC>>[CH2:19]([N:20]([CH2:21][CH3:22])[C:2]1[C:3]2[N:4]([C:12]([CH2:15][CH3:16])=[N:13][N:14]=2)[C:5]2[C:10]([N:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH3:18]
Reactant: CCc1nnc2c(Cl)nc3ccccc3n12
Reactant: Clc1nc2ccccc2n2cnnc12
Solvent: CCCNCCC
Solvent: CCNCC
Product: CCc1nnc2c(N(CC)CC)nc3ccccc3n12
Yield: 69 %

Procedure:
This compound was prepared by the method of Example 11, utilizing 4-chloro-1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline (the product of Example 4) as starting material in place of 4-chloro-[1,2,4]triazolo[4,3-a]quinoxaline (the product of Example 2) and diethylamine as reagent in place of di-n-propylamine. The crude product was recrystallized from cyclohexane to afford 3.54 g. (69% yield) of pure 4-diethylamino-1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline as a white solid (m.p. 98°-100° C.).
Reaction SMILES: [O:1]([CH2:8][C:9]([NH:11][CH:12]1[CH2:15][N:14]([C:16](=[C:33]([CH3:36])[CH2:34]Br)[C:17]([O:19][CH:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[C:13]1=[O:37])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:38](OCC)(=[O:40])C.O(CC(NC1CN(C(OC)(C(C)=C)C(OC(C2C=CC=CC=2)C2C=CC=CC=2)=O)C1=O)=O)C1C=CC=CC=1>CO.Cl([O-])(=O)(=O)=O.[Ag+]>[O:1]([CH2:8][C:9]([NH:11][CH:12]1[CH2:15][N:14]([C:16](=[C:33]([CH3:36])[CH2:34][O:40][CH3:38])[C:17]([O:19][CH:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[C:13]1=[O:37])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(CBr)=C(C(=O)OC(c1ccccc1)c1ccccc1)N1CC(NC(=O)COc2ccccc2)C1=O
Reactant: CCOC(C)=O
Agent: [Ag+]
Agent: C=C(C)C(OC)(C(=O)OC(c1ccccc1)c1ccccc1)N1CC(NC(=O)COc2ccccc2)C1=O
Agent: [O-][Cl+3]([O-])([O-])[O-]
Solvent: CO
Product: COCC(C)=C(C(=O)OC(c1ccccc1)c1ccccc1)N1CC(NC(=O)COc2ccccc2)C1=O
Reaction time: 1 h

Procedure:
To a solution of 281 mg (0.5 mmol) of benzhydryl 2-(3-phenoxyacetamido-2-oxoazetidin-1-yl)-3-methyl-4-bromo-2-butenoate in 10 ml of methanol at 0° was added 207 mg (1 mmol) of silver perchlorate. The reaction mixture was stirred for 1 hour. A large amount of ethyl acetate was added. The resulting solution was washed thoroughly with brine, dried, and evaporated in vacuo to dryness to provide a mixture of the title product and benzhydryl 2-(3-phenoxyacetamido-2-oxoazetidin-1-yl)-2-methoxy-3-methyl-3-butenoate. The products were separated by preparative thin layer chromatography (silica gel plates developed with 1:1/hexane:ethylacetate). A purified sample of 46 mg of the title product was isolated: nmr (CDCl3) δ 2.20 (s, 3, CH3), 3.25 (s, 3, OCH3), 4.37 (s, 2, CH2OCH3), 3.73 (t, 1) and 3.50 (q, 1) [C4 --H], 4.97 (m, 1, C3 --H), 4.47 (s, 2, side chain CH2) and 7.2 (b, ArH).