Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][N:9]=[CH:10][C:11]1([C:18]([OH:20])=[O:19])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C1C=CC(N=NC2C=CC(S(O)(=O)=O)=CC=2)=CC=1)C.Cl.C([BH3-])#N.[Na+]>CO>[CH2:1]([O:8][NH:9][CH2:10][C:11]1([C:18]([OH:20])=[O:19])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)C1(C=NOCc2ccccc2)CCCCCC1
Agent: CN(C)c1ccc(N=Nc2ccc(S(=O)(=O)O)cc2)cc1
Agent: Cl
Agent: [BH3-]C#N
Solvent: CO
Product: O=C(O)C1(CNOCc2ccccc2)CCCCCC1
Temperature: 0 °C

Procedure:
A solution of 1-(benzyloxyimino-methyl)-cycloheptanecarboxylic acid (4.44 g, 16.1 mmol) in methanol (200 mL) at 0° C. under an argon atmosphere was added a trace amount of methyl orange. A solution of saturated methanolic HCl was added until a persistent red color was observed. Sodium cyanoborohydride (1.3 g, 20.9 mmol) was added portionwise alternately with methanolic HCl to maintain the red color. The reaction mixture was maintained at 0° C. for an additional 2 h and the volatiles were removed in vacuo to yield the title compound that was used without further purification. MH+278.
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[C:12]2[O:11][C:10](=[O:13])[NH:9][C:8]=2[CH:7]=[CH:6][CH:5]=1.Br[CH2:15][C:16]([NH2:18])=[O:17]>CN(C=O)C>[F:3][C:4]1[C:12]2[O:11][C:10](=[O:13])[N:9]([CH2:15][C:16]([NH2:18])=[O:17])[C:8]=2[CH:7]=[CH:6][CH:5]=1
Reactant: O=c1[nH]c2cccc(F)c2o1
Reactant: NC(=O)CBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: NC(=O)Cn1c(=O)oc2c(F)cccc21
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
In a three neck flask, fitted with a magnetic stirrer, under inert atmosphere, NaH (in oil, 60 w/w, 1.8 g, 45.15 mmol) is carefully added by portion into a solution of 7-fluoro-1,3-benzoxazol-2(3H)-one 2 (5.76 g, 37.62 mmol) in dried DMF (80 ml) at 0° C. After 0.25 h, 2-bromo-acetamide (6.22 g, 45.15 mmol) is added. The reaction mixture is stirred for 1 h at room temperature, quenched with water, concentrated in vacuo and the residue is recrystallized in EtOH/H2O (80/20 (v/v)) to afford 2-(7-fluoro-2-oxo-1,3-benzoxazol-3(2H)-yl)acetamide.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[CH3:9][C:10]([C:12]1[CH:17]=[CH:16][C:15](F)=[CH:14][C:13]=1[Cl:19])=[O:11].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:19][C:13]1[CH:14]=[C:15]([O:8][C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[CH:16]=[CH:17][C:12]=1[C:10](=[O:11])[CH3:9]
Reactant: CC(=O)c1ccc(F)cc1Cl
Reactant: Oc1ccc(Cl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(=O)c1ccc(Oc2ccc(Cl)cc2)cc1Cl
Temperature: 25 °C

Procedure:
A mixture of 4-chlorophenol (186 g), 2-chloro-4-fluoroacetophenone (250 g) and potassium carbonate (238 g) in DMF (960 mL) was heated to reflux for 48 h. After cooling to room temperature, the reaction mixture was partitioned between MTBE and water and the aqueous phase was extracted twice with MTBE. The combined organic phases were consecutively washed with 10% LiCl solution, dil. NaOH solution and water and dried. The solvent was evaporated under reduced pressure and the crude material was crystallized from diisopropyl ether.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13](Br)=[CH:12][CH:11]=2)=[C:6]([F:17])[C:5]=1[F:18])[CH3:2].C([Li])CCC.[B:24](OC)([O:27]C)[O:25]C.Cl>C(OCC)(=O)C.C1COCC1.CCCCCC>[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([B:24]([OH:27])[OH:25])=[CH:12][CH:11]=2)=[C:6]([F:17])[C:5]=1[F:18])[CH3:2]
Reactant: CCOc1ccc(-c2ccc(Br)cc2)c(F)c1F
Reactant: COB(OC)OC
Agent: Cl
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CCOc1ccc(-c2ccc(B(O)O)cc2)c(F)c1F
Temperature: 0 °C
Reaction time: 2 h
Yield: 131.8 %

Procedure:
The compound (3) (10.0 g) and THF (100 ml) were put in a reaction vessel under a nitrogen atmosphere, and cooled to −74° C. n-Butyllithium (1.57 M in a n-hexane solution; 22.4 ml) was added dropwise thereto in the temperature range of −74° C. to −70° C., and the mixture obtained was stirred for another 2 hours. Subsequently, trimethyl borate (4.0 g) in a THF (50 ml) solution was added dropwise thereto in the temperature range of −74° C. to −65° C., and the mixture was stirred for another 8 hours while allowing the temperature to come to 25° C. Then, the reaction mixture was poured into a vessel containing 1N-hydrochloric acid (100 ml) and ice-water (500 ml), and mixed. Ethyl acetate (300 ml) was added thereto and the mixture was allowed to be separated into organic and aqueous phases, and then an extractive operation was carried out. The organic phase obtained was fractionated, washed sequentially with a saturated aqueous solution of sodium hydrogencarbonate and brine, and then dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, giving 11.7 g of 4-ethoxy-2,3-difluoro-1,1′-biphenyl-4′-boronic acid (6). The yield based on the compound (3) was 81.1%.
Reaction SMILES: [H-].[Na+].[C:3]([NH:10][CH2:11][CH2:12][CH2:13][OH:14])([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].F[C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=1>O1CCCC1.[Cl-].[NH4+]>[C:6]([O:5][C:3](=[O:4])[NH:10][CH2:11][CH2:12][CH2:13][O:14][C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=1)([CH3:7])([CH3:8])[CH3:9]
Reactant: CC(C)(C)OC(=O)NCCCO
Reactant: O=[N+]([O-])c1ccc(F)cc1
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NCCCOc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 76.4 %

Procedure:
To a suspension of sodium hydride (2.48 g, 98.1 mmol) (Aldrich, 95%) in tetrahydrofuran (150 mL) was added a solution of 3-(Boc-amino)-1-propanol (8.1 g, 46.8 mmol) (Aldrich) in tetrahydrofuran (25 mL) at −10° C. After stirred for 15 minutes, the reaction was allowed to warm to room temperature and stirred for a further 30 minute. To this mixture was added a solution of 1-fluoro-4-nitro-benzene (6.92 g, 49.07 mmol) (Aldrich) and the reaction was stirred at room temperature for 2 hours. The resulting mixture was poured in cool aqueous ammonium chloride solution (100 mL). The aqueous layer was extracted with ethyl acetate (3×40 mL) and the combined organic extracts were washed with brine (3×30 mL), dried (Na2SO4) and evaporated in vacuo. The residue was purified on silica gel with 85:15 hexane/ethyl acetate to provide [3-(4-nitrophenoxy)propyl]carbamic acid tert-butyl ester (10.6 g, 73% yield) as light yellow solid. MS (ES) MH+=297.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:32]=[CH:33][C:34]=1[F:35])[CH2:5][N:6]1[C:11](=[O:12])[C:10]2[C:13]([O:22][CH3:23])=[C:14]3[C:19](=[O:20])[N:18]([CH3:21])[CH2:17][CH2:16][N:15]3[C:9]=2[C:8]([CH:24]([C:30]#[N:31])[CH2:25][C:26](OC)=[O:27])=[N:7]1>[Ni]>[Cl:1][C:2]1[CH:3]=[C:4]([CH:32]=[CH:33][C:34]=1[F:35])[CH2:5][N:6]1[C:11](=[O:12])[C:10]2[C:13]([O:22][CH3:23])=[C:14]3[C:19](=[O:20])[N:18]([CH3:21])[CH2:17][CH2:16][N:15]3[C:9]=2[C:8]([CH:24]2[CH2:25][C:26](=[O:27])[NH:31][CH2:30]2)=[N:7]1
Reactant: COC(=O)CC(C#N)c1nn(Cc2ccc(F)c(Cl)c2)c(=O)c2c(OC)c3n(c12)CCN(C)C3=O
Agent: [Ni]
Product: COc1c2n(c3c(C4CNC(=O)C4)nn(Cc4ccc(F)c(Cl)c4)c(=O)c13)CCN(C)C2=O
Reaction time: 48 h

Procedure:
A mixture of methyl 3-[2-(3-chloro-4-fluorobenzyl)-10-methoxy-8-methyl-1,9-dioxo-1,2,6,7,8,9-hexahydropyrazino[1′,2′:1,5]pyrrolo[2,3-d]pyridazin-4-yl]-3-cyanopropanoate (0.12 g, 0.24 mmol) and Raney nickel (200 mg; washed successively with deionized water until neutral to pH paper and three times with absolute ethanol) in absolute ethanol (35 mL) was subjected to an atmosphere of hydrogen gas at 50 psi in a Parr hydrogenation vessel at room temperature for 48 hours. The product mixture was filtered through a pad of Celite. The filtrate was concentrated under vacuum. The residue was subjected to reverse phase preparative HPLC purification. Collection and lyophilization of appropriate fractions provide the title compound. ES MS M+1=474
Reaction SMILES: N(C(OC(C)C)=O)=NC(OC(C)C)=O.O[CH:16]([C:27](=[CH2:35])[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:17][CH2:18][CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[C:36]([OH:44])(=[O:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.CCOCC>[C:36]([O:44][CH2:35]/[C:27](/[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=[CH:16]\[CH2:17][CH2:18][CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=[O:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1
Reactant: O=C(O)c1ccccc1
Reactant: C=C(C(=O)OC(C)(C)C)C(O)CCCCc1ccccc1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: CCOCC
Product: CC(C)(C)OC(=O)/C(=C/CCCCc1ccccc1)COC(=O)c1ccccc1
Temperature: 0 °C
Yield: 81.4 %

Procedure:
Diisopropyl azodicarboxylate (5 mL, 25 mmol) is added dropwise over 5 minutes to a solution of t-butyl 2-(1-hydroxy-5-phenylpentyl)acrylate (5.59 g, 19.3 mmol), benzoic acid (3 g, 25 mmol) and triphenyl phosphine (6.5 g, 25 mmol) in THF (100 mL) at -55° C. The reaction is maintained between -55 and -50° C. for 45 minutes and then the reaction is allowed to warm to 0° C. The solution is diluted with ether (300 mL) and washed with 1 N NaOH (2×40 mL) and brine (70 mL). The resulting solution is dried (MgSO4) and concentrated in vacuo. The crude reaction product is partially dissolved in 20% ether/petroleum ether and applied to a silica gel column as a slurry. The column is eluted using gradient elution (silica, 10 to 20% ether in petroleum ether) to obtain (E)-2-t-Butoxycarbonyl-7-phenylhept-2-enyl benzoate (6.2 g, 82%): 1H NMR (300 MHz, CDCl3) δ 8.01 (d, J=7.0 Hz, 2H), 7.53-7.49 (m, 1 H), 7.41 (t, J=7.5 Hz, 2H), 7.28-7.23 (m, 2H), 7.20-7.10 (m, 3H), 6.99 (t, J=7.8 Hz, 1H), 5.05 (s, 2H), 2.61 (t, J=7.5 Hz, 2H), 2.36 (q, J=7.5 Hz, 2H), 1.72-1.46 (m, 4H), 1.47 (s, 9H); MS (FAB) m/e 395 (M+H)+.
Reaction SMILES: [CH3:1][C:2]([NH2:6])([CH2:4][CH3:5])[CH3:3].[Br:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[S:14](Cl)(=[O:16])=[O:15]>ClCCl>[Br:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[S:14]([NH:6][C:2]([CH3:3])([CH3:1])[CH2:4][CH3:5])(=[O:16])=[O:15]
Reactant: O=S(=O)(Cl)c1ccccc1Br
Reactant: CCC(C)(C)N
Solvent: ClCCl
Product: CCC(C)(C)NS(=O)(=O)c1ccccc1Br
Reaction time: 15 h
Yield: 87.7 %

Procedure:
To a solution of 2-methyl-2-butanamine (11.4 mL, 97.8 mmol) in dichloromethane (100 mL) was added, dropwise over a 10 min period, a solution of 2-bromobenzenesulfonyl chloride (10.0 g, 39.1 mmol) in dichloromethane (ca. 50 mL). After stirring for 15 h the reaction was concentrated in vacuo. The residue was crystallized from methyl t-butyl ether to provide 10.5 g (87%) of 2-bromo-N-(1,1-dimethylpropyl)benzenesulfonamide in two crops: LCMS (neg. ion spectrum) m/z 304/306.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[C:12]2[N:11]=[C:10]3[N:13]([C:17]4[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=4[C:24]([F:27])([F:26])[F:25])[CH2:14][CH2:15][CH2:16][N:9]3[C:8]=2[C:7]([CH:28]([OH:31])[CH2:29][CH3:30])=[CH:6][CH:5]=1.[CH3:32]I>CN(C)C=O.O>[Cl:3][C:4]1[C:12]2[N:11]=[C:10]3[N:13]([C:17]4[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=4[C:24]([F:25])([F:27])[F:26])[CH2:14][CH2:15][CH2:16][N:9]3[C:8]=2[C:7]([CH:28]([O:31][CH3:32])[CH2:29][CH3:30])=[CH:6][CH:5]=1
Reactant: CI
Reactant: CCC(O)c1ccc(Cl)c2nc3n(c12)CCCN3c1ccc(Cl)cc1C(F)(F)F
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCC(OC)c1ccc(Cl)c2nc3n(c12)CCCN3c1ccc(Cl)cc1C(F)(F)F
Reaction time: 0.08 h
Yield: 78.3 %

Procedure:
Sodium hydride (60% in oil, 40.0 mg, 1.00 mmol) was added to a stirred solution of 1-{9-chloro-1-[4-chloro-2-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl}propan-1-ol (370 mg, 0.833 mmol) in N,N-dimethylformamide (3.0 mL) at room temperature. After stirring 5 min, methyl iodide (177 mg, 1.25 mmol) was added to the mixture, and the mixture was stirred at, room temperature for 4 hr. The mixture was diluted with water, and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 10-40% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was recrystallized from ethyl acetate/diisopropyl ether to give the title compound as a colorless crystal (299 mg, 0.652 mmol, 78%).
Reaction SMILES: Cl.[CH3:2][N:3]([CH3:33])[C:4]([C:6]1[N:27]([CH:28]2[CH2:32][CH2:31][CH2:30][CH2:29]2)[C:9]2[N:10]=[C:11]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([N:21]4[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]4)=[CH:17][N:16]=3)[N:12]=[CH:13][C:8]=2[CH:7]=1)=[O:5].C(=O)([O-])[O-].[K+].[K+].Br[CH2:41][CH2:42][F:43]>C(#N)C.CN(C=O)C>[CH3:2][N:3]([CH3:33])[C:4]([C:6]1[N:27]([CH:28]2[CH2:32][CH2:31][CH2:30][CH2:29]2)[C:9]2[N:10]=[C:11]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([N:21]4[CH2:22][CH2:23][N:24]([CH2:41][CH2:42][F:43])[CH2:25][CH2:26]4)=[CH:17][N:16]=3)[N:12]=[CH:13][C:8]=2[CH:7]=1)=[O:5]
Reactant: CN(C)C(=O)c1cc2cnc(Nc3ccc(N4CCNCC4)cn3)nc2n1C1CCCC1
Reactant: FCCBr
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: CN(C)C=O
Product: CN(C)C(=O)c1cc2cnc(Nc3ccc(N4CCN(CCF)CC4)cn3)nc2n1C1CCCC1
Temperature: 80 °C
Yield: 55 %

Procedure:
To a solution of 7-cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide hydrochloride (150 mg, 0.318 mmol) and potassium carbonate (132 mg, 0.955 mmol) in acetonitrile (3 mL) and DMF (2 mL) is added 1-bromo-2-fluoroethane (0.035 mL, 0.478 mmol) and the reaction mixture is heated to 80° C. for 24 h in a sealed reaction vial. Upon cooling, the reaction mixture is partitioned between dichloromethane and water. The organic layer is separated and the aqueous layer extracted further with dichloromethane. The combined organics are ished with brine, dried (MgSO4), filtered and concentrated. The crude product is purified using silica gel chromatography (0 to 10% methanol/dichloromethane) to give 7-cyclopentyl-2-{5-[4-(2-fluoro-ethyl)-piperazin-1-yl]-pyridin-2-ylamino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (84 mg, 55%) as an off white solid.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[C:12]2[C:7]([CH2:8][CH2:9][CH2:10][C:11]2=O)=[CH:6][CH:5]=1)([O-])=O.O.Cl.[H][H]>C(O)C.[Pd]>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]2[CH2:8][CH2:9][CH2:10][CH2:11][C:12]=2[CH:13]=1
Reactant: O=C1CCCc2ccc([N+](=O)[O-])cc21
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Solvent: CCO
Solvent: O
Product: Nc1ccc2c(c1)CCCC2
Yield: 86687.8 %

Procedure:
7-Nitrotetralone (20.0 g, 0.105 mmol) was dissolved in 400 ml of ethanol, and 40 ml of water, 10 ml of concentrated HCl, and 4.0 g of 10% palladium on carbon were added. The reaction mixture was reacted with hydrogen at 30-40 psi for 16 hours. Following hydrogenation, the reaction mixture was filtered and the solvents were evaporated, yielding white crystals. The crystals were washed with acetone, dissolved in cold 10% NaOH, and extracted with EtOAc (3 x). The combined organic layers were washed with water, dried over Na2SO4, filtered and evaporated, to give 2-amino-5,6,7,8-tetrahydronaphthalene (13.4 g, 87.1% yield) as a brown oil.
Reaction SMILES: CO.[CH3:3][O:4][C:5](=[O:24])[C@@H:6]([NH:14][C:15]([C@@H:17]1[C@@H:19]([CH2:20][CH2:21][CH2:22][CH3:23])[O:18]1)=[O:16])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[N-:25]=[N+:26]=[N-:27].[Na+].S([O-])([O-])(=O)=O.[Mg+2]>>[CH3:3][O:4][C:5](=[O:24])[C@@H:6]([NH:14][C:15](=[O:16])[C@@H:17]([OH:18])[C@@H:19]([N:25]=[N+:26]=[N-:27])[CH2:20][CH2:21][CH2:22][CH3:23])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: CCCC[C@H]1O[C@@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)OC
Reactant: [N-]=[N+]=[N-]
Agent: O=S(=O)([O-])[O-]
Agent: [Mg+2]
Agent: [Na+]
Solvent: CO
Product: CCCC[C@H](N=[N+]=[N-])[C@H](O)C(=O)N[C@@H](Cc1ccccc1)C(=O)OC
Yield: 69 %

Procedure:
A suspension of 30 ml of methanol containing 558 mg (1.84 mmol) of (2S-trans)-N-[(2S)-1-methoxy-1-oxo-3-phenyl-2-propyl]-3-butyloxiranecarboxamide, 239 mg (3.68 mmol) of sodium azide and 228 mg (1.89 mmol) of anhydrous magnesium sulfate was refluxed for 5 hours. After the temperature of the reaction mixture was returned to room temperature, under reduced pressure, the reaction mixture was concentrated and ethyl acetate was added to the concentrate, and then, the resulting mixture was washed successively with water, and then a saturated NaCl solution. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography to obtain 442 mg (Yield: 69%) of the title compound.
Reaction SMILES: [CH:1]1([C:7](=[O:11])/[CH:8]=[CH:9]/Cl)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[I-:12].[Na+]>CC(C)=O>[CH:1]1([C:7](=[O:11])/[CH:8]=[CH:9]/[I:12])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C(/C=C/Cl)C1CCCCC1
Reactant: [I-]
Agent: [Na+]
Solvent: CC(C)=O
Product: O=C(/C=C/I)C1CCCCC1
Yield: 101.7 %

Procedure:
A solution of 153 g of (25C) and 500 g of sodium iodide in 700 ml of dry acetone (distilled from anhydrous potassium carbonate) was refluxed under argon for 18 hours. The solvent was then removed by evaporation in vacuo. The residue was mixed with water and extracted three times with ether. The combined extract was dried over anhydrous magnesium sulfate and then evaporated in vacuo to yield 238 g of the desired product which had the following spectral properties: nmr (CDCl3) δ 0.9-2.8 (11H, m), 7.30 (1H, d, J=15 Hz) and 7.92 ppm (1H, d, J=15 Hz).
Reaction SMILES: C([Li])CCC.[C:6]1([C:12]2[S:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[C:17]1([CH:23]([CH3:26])[CH:24]=[O:25])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.Cl>CCCCCC.O1CCCC1>[C:17]1([CH:23]([CH3:26])[CH:24]([C:14]2[S:13][C:12]([C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=3)=[CH:16][CH:15]=2)[OH:25])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: c1ccc(-c2cccs2)cc1
Reactant: CC(C=O)c1ccccc1
Agent: Cl
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CC(c1ccccc1)C(O)c1ccc(-c2ccccc2)s1
Temperature: -78 °C
Reaction time: 1.5 h
Yield: 96.2 %

Procedure:
Under a nitrogen atmosphere 13.7 mL of a 2.6M solution of n-butyllithium in n-hexane was added to a cold (-78° C.) stirred solution of 5.2 grams (0.0325 mole) of 2-phenylthiophene in 61 mL of tetrahydrofuran. This mixture was stirred at -78° C. for 1.5 hours. To this cold mixture was added 2-phenylpropionaldehyde (4.6 gram, 0.0336 mole), and the mixture was stirred for 15 minutes. The mixture was allowed to warm to room temperature and stir for two days. The mixture was cooled to 0° C., and approximately 45 mL of 1.2 N hydrochloric acid was added. The organic phase was separated from the aqueous phase and the aqueous phase, was extracted with chloroform. The chloroform extract was combined with the organic phase and washed with an aqueous, ammonium chloride solution. The washed organic phase was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure leaving a residue. This residue was purified by column chromatography on silica gel, eluting with ethyl acetate:n-hexane (10:90), to yield 9.2 g of 2-phenyl-1-(5-phenylthien-2-yl)-1-propanol as an oil.
Reaction SMILES: [N+:1]([CH:4]=[C:5](SC)[NH:6][CH2:7][CH2:8][S:9][CH2:10][C:11]1[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][N:12]=1)([O-:3])=[O:2].[CH2:20]([NH2:23])[C:21]#[CH:22]>C(#N)C>[N+:1]([CH:4]=[C:5]([NH:23][CH2:20][C:21]#[CH:22])[NH:6][CH2:7][CH2:8][S:9][CH2:10][C:11]1[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][N:12]=1)([O-:3])=[O:2]
Reactant: CSC(=C[N+](=O)[O-])NCCSCc1ncccc1Cl
Reactant: C#CCN
Solvent: CC#N
Product: C#CCNC(=C[N+](=O)[O-])NCCSCc1ncccc1Cl
Reaction time: 16 h

Procedure:
A solution of 1-nitro-2-methylthio-2-{2-[(3-chloro-2-pyridyl)methylthio]ethylamino}ethylene (0.61 g; 1.91 mmoles) [prepared according to the procedure described in U.S. Pat. No. 4,024,260] and propargylamine (1.72 g; 31.2 mmoles) in acetonitrile (15 ml) was stirred and heated to reflux temperature under a positive pressure of nitrogen for 7 hours then allowed to stand at ambient temperature for 16 hours. The reaction mixture was filtered and 346 mg of product collected. Recrystallization from methanol with activated carbon treatment gave the title compound; mp 171°-171.5°.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH:18]=[CH:17][CH:16]=[CH:15]2)=[CH:10][C:9]=1[NH2:19])(C)(C)C.[CH3:21][O:22][C:23]([C:25]1[N:26]=[C:27]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([C:36]3OC(C)(C)O[C:40](=[O:42])[CH:41]=3)[CH:31]=2)[O:28][CH:29]=1)=[O:24].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:21][O:22][C:23]([C:25]1[N:26]=[C:27]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([C:36]3[CH2:41][C:40](=[O:42])[NH:19][C:9]4[CH:10]=[C:11]([N:14]5[CH:18]=[CH:17][CH:16]=[CH:15]5)[CH:12]=[CH:13][C:8]=4[N:7]=3)[CH:31]=2)[O:28][CH:29]=1)=[O:24]
Reactant: COC(=O)c1coc(-c2cccc(C3=CC(=O)OC(C)(C)O3)c2)n1
Reactant: CC(C)(C)OC(=O)Nc1ccc(-n2cccc2)cc1N
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)c1coc(-c2cccc(C3=Nc4ccc(-n5cccc5)cc4NC(=O)C3)c2)n1

Procedure:
The title compound was prepared from (2-amino-4-pyrrol-1-yl-phenyl)-carbamic acid tert.-butyl ester (Example J2) (680 mg) and 2-[3-(2,2-dimethyl-6-oxo-6H-[1,3]dioxin-4-yl)-phenyl]-oxazole-4-carboxylic acid methyl ester (Example L7) (820 mg) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (770 mg).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]([NH:13][NH2:14])=[O:12])=[CH:6][CH:5]=1)([O-:3])=[O:2].Cl.[C:16](=N)(N)[CH3:17].C([O-])(=O)C.[Na+]>O>[CH3:16][C:17]1[N:10]([C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=2)[C:11](=[O:12])[NH:13][N:14]=1
Reactant: CC(=N)N
Reactant: NNC(=O)Nc1ccc([N+](=O)[O-])cc1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Product: Cc1n[nH]c(=O)n1-c1ccc([N+](=O)[O-])cc1
Temperature: 140 °C
Yield: 34 %

Procedure:
A mixture of 4 parts of N-(4-nitrophenyl)hydrazinecarboxamide, 5 parts of ethanimidamide hydrochloride and 5 parts of sodium acetate is stirred and heated for 4 hours at 140° C. The reaction mixture is cooled, water is added and the whole is stirred till the product is crystallized. It is filtered off and recrystallized from 2-propanol, yielding 1.5 parts (34%) of 2,4-dihydro-5-methyl-4-(4-nitrophenyl)-3H-1,2,4-triazol-3-one; mp. 226.1° C.
Reaction SMILES: C([O:3][C:4]([C:6]1[N:7]=[CH:8][N:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[NH:12][C:11](=[O:19])[C:10]=12)=[O:5])C.Cl>[OH-].[Na+]>[O:19]=[C:11]1[NH:12][C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:9]2[CH:8]=[N:7][C:6]([C:4]([OH:5])=[O:3])=[C:10]12
Reactant: CCOC(=O)c1ncn2c1c(=O)[nH]c1ccccc12
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: O=C(O)c1ncn2c1c(=O)[nH]c1ccccc12
Temperature: 25 °C
Yield: 96.2 %

Procedure:
4-Oxo-4,5-dihydroimidazo[1,5-a]quinoxaline 3-carboxylic acid ethyl ester (3.5 g) was dissolved in 100 ml of 0.5 N sodium hydroxide solution. The solution was heated on steam bath for one hour, cooled to room temperature, then acidified by concentrated hydrochloric acid (5 ml). The product precipitated out as a white solid (3.0 g, 95% yield), m.p. >300° C.