Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2](=[CH:6][C:7]1[CH:12]=[CH:11][C:10]([N+:13]([O-])=O)=[CH:9][CH:8]=1)[C:3]([OH:5])=[O:4].[CH3:16]O>CCOC(C)=O.CCOCC.CC(O)=O>[CH3:16][O:5][C:3](=[O:4])/[C:2](/[CH3:1])=[CH:6]/[C:7]1[CH:12]=[CH:11][C:10]([NH2:13])=[CH:9][CH:8]=1
Reactant: CC(=Cc1ccc([N+](=O)[O-])cc1)C(=O)O
Reactant: CO
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Solvent: CCOCC
Product: COC(=O)/C(C)=C/c1ccc(N)cc1
Temperature: 25 °C

Procedure:
α-Methyl-4-nitrocinnamic acid (53 mg, 0.25 mmol) was dissolved in EtOAc and MeOH and a solution of CH2N2 in Et2O was added until a persistent yellow color was observed. A couple of drops of AcOH were added to destroy the excess CH2N2. The mixture was diluted with EtOAc and the organic layer was washed with H2O, aqueous NaOH (1N) and brine, dried over anhydrous MgSO4 and concentrated to dryness. The residue was re-dissolved in EtOH (2 mL), SnCl22H2O (289 mg, 1.28 mmol) was added and the reaction mixture was heated to reflux for 1 h. The mixture was cooled to RT, diluted with EtOAc and quenched by the addition of aqueous, saturated NaHCO3. The organic layer was separated, washed with brine, dried over anhydrous MgSO4 and concentrated to dryness to give the title compound (40 mg) as a yellow solid.
Reaction SMILES: [H-].[Na+].[N+:3]([C:6]1[CH:11]=[CH:10][N:9]=[C:8]2[NH:12][CH:13]=[CH:14][C:7]=12)([O-:5])=[O:4].[CH3:15]I>CC(N(C)C)=O>[CH3:15][N:12]1[C:8]2=[N:9][CH:10]=[CH:11][C:6]([N+:3]([O-:5])=[O:4])=[C:7]2[CH:14]=[CH:13]1
Reactant: CI
Reactant: O=[N+]([O-])c1ccnc2[nH]ccc12
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Product: Cn1ccc2c([N+](=O)[O-])ccnc21
Reaction time: 0.5 h

Procedure:
170 mg (4.29 mmol) of sodium hydride are added to a solution of 500 mg (3.06 mmol) of 4-nitro-1H-pyrrolo[2,3-b]pyridine (Antonini, Ippolito; Claudi, Francesco; Cristalli, Gloria; Franchetti, Palmarisa; Grifantini, Mario; Martelli, Sante; J. Med. Chem. 1982, 25, 1258-1261.) in 10 ml of absolute DMA, and the suspension is stirred for 30 min. A solution of 230 μl (3.68 mmol) of methyl iodide in 2 ml of absolute DMA is then slowly added dropwise, and the mixture is again stirred for 60 min. After concentration under reduced pressure, the residue is purified by column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 10:1).
Reaction SMILES: C([N:4]1[CH:8]=[C:7]([C:9]2[C:13]3[C:14]([O:18][CH:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[N:15][CH:16]=[CH:17][C:12]=3[N:11]([C:25]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[N:10]=2)[CH:6]=[C:5]1[C:44]([O:46]C)=[O:45])(C)C.[Li+].[OH-].Cl.[CH2:51]1[CH2:55]OC[CH2:52]1>>[CH:51]([C:5]1([C:44]([OH:46])=[O:45])[CH2:6][C:7]([C:9]2[C:13]3[C:14]([O:18][CH:19]4[CH2:20][CH2:21][O:22][CH2:23][CH2:24]4)=[N:15][CH:16]=[CH:17][C:12]=3[N:11]([C:25]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)([C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=3)[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[N:10]=2)=[CH:8][NH:4]1)([CH3:55])[CH3:52]
Reactant: COC(=O)c1cc(-c2nn(C(c3ccccc3)(c3ccccc3)c3ccccc3)c3ccnc(OC4CCOCC4)c23)cn1C(C)C
Reactant: C1CCOC1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Product: CC(C)C1(C(=O)O)CC(c2nn(C(c3ccccc3)(c3ccccc3)c3ccccc3)c3ccnc(OC4CCOCC4)c23)=CN1
Temperature: 25 °C
Yield: 97 %

Procedure:
Methyl 1-isopropyl-4-(4-(tetrahydro-2H-pyran-4-yloxy)-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-yl)-1 H-pyrrole-2-carboxylate (200 mg, 0.32 mmol) was dissolved in THF (8 mL). A 1 N LiOH solution (8 mL) was introduced and resulting mixture was refluxed for 12 hours. After cooling to room temperature, the mixture was neutralized to pH 7 with 5 N HCl. THF was removed at reduced pressure. The residue was partitioned between ethyl acetate (30 mL) and water (30 mL). The organic phase was washed with brine and dried over anhydrous Na2SO4 and concentrated to give the crude desired product as a yellow solid (190 mg, 97%). LC-MS (Method F): m/z=613.4 [M+H]+; 6.19 min. 1H-NMR (500 MHz, CDCl3): δ 7.74 (s, 1H), 7.53 (d, J=6.0, 1H), 7.30-7.37 (m, 9H), 7.23 (s, 1H), 7.16 (d, J=7.5, 6H), 5.79 (d, J=6.0, 1H), 5.41-5.48 (m, 2H), 3.91 (d, J=11.5, 2H), 3.49 (t, J=11.0, 2H), 2.15 (d, J=12.0, 2H), 1.72-1.79 (m, 2H), 1.42 (d, J=7.0, 6H).
Reaction SMILES: C([O:3][C:4]([C:6]1([NH:15][CH2:16][C:17]2[C:25]3[O:24][CH2:23][CH2:22][C:21]=3[CH:20]=[CH:19][CH:18]=2)[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7]1)=[O:5])C.O1CCOCC1.CO>O>[O:24]1[C:25]2[C:17]([CH2:16][NH:15][C:6]3([C:4]([OH:5])=[O:3])[CH2:14][C:13]4[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=4)[CH2:7]3)=[CH:18][CH:19]=[CH:20][C:21]=2[CH2:22][CH2:23]1
Reactant: CCOC(=O)C1(NCc2cccc3c2OCC3)Cc2ccccc2C1
Solvent: C1COCCO1
Solvent: CO
Solvent: O
Product: O=C(O)C1(NCc2cccc3c2OCC3)Cc2ccccc2C1
Reaction time: 16 h
Yield: 96.6 %

Procedure:
A 100 mL round bottom flask containing 2-[(2,3-Dihydro-benzofuran-7-ylmethyl)-amino]-indan-2-carboxylic acid ethyl ester (367, 350 mg, 1.037 mmol) is charged with 1,4-dioxane (3 mL) and MeOH (3 mL). A stirring bar is added and stirring is initiated. After dissolution, water (1.5 mL) is added followed by the LiOH monohydrate (110 mg, 2.52 mmol). After 16 h, tlc analysis (silica, 50% EtOAc/Heptanes) indicates that the starting material is completely consumed. Amberlyst highly acidic exchange resin (0.5 g) is added to the reaction vial. The reaction is capped and allowed to stir at ambient temperature. After 6 h, the contents of the flask are filtered through a pad of Celite. The solvent is removed from the filtrate. The residue is reconstituted with iPrOH/toluene (20+20 mL) and the solvent is removed. This process is repeated 1 time. Pumping to constant weight provided white solid (0.31 g, 99%).
Reaction SMILES: [N+](C1C=C(C=CC=1)C(C(C)CC#N)=O)([O-])=O.Cl.[N+:18]([C:21]1[CH:22]=[C:23]([CH:32]=[CH:33][CH:34]=1)[C:24]([CH:26]([CH3:31])[CH2:27][C:28](O)=[O:29])=O)([O-:20])=[O:19].O.[NH2:36][NH2:37]>C(O)C>[CH3:31][CH:26]1[C:24]([C:23]2[CH:32]=[CH:33][CH:34]=[C:21]([N+:18]([O-:20])=[O:19])[CH:22]=2)=[N:37][NH:36][C:28](=[O:29])[CH2:27]1
Reactant: CC(CC(=O)O)C(=O)c1cccc([N+](=O)[O-])c1
Reactant: NN
Agent: CC(CC#N)C(=O)c1cccc([N+](=O)[O-])c1
Agent: Cl
Solvent: CCO
Solvent: O
Product: CC1CC(=O)NN=C1c1cccc([N+](=O)[O-])c1

Procedure:
A 28 g. portion of 3-(m-nitrobenzoyl)butyronitrile [prepared as described in J. Org. Chem., Vol. 38, No. 23, 4044-4048 (1973)] is added to one liter of 6N hydrochloric acid and is stirred at reflux for one hour using a magnetic stirrer and a heating mantle. The reaction mixture is cooled and extracted with methylene chloride. The organic layer is separated and extracted with saturated sodium bicarbonate. The bicarbonate layer is added dropwise to a stirred cold hydrochloric acid solution and the resulting solid is kept cold in ice then is filtered and air dried to afford 27.24 g. of 3-m-nitrobenzoyl butyric acid as a white solid. The entire amount of the preceding compound is mixed with 12.8 ml. of 99% hydrazine hydrate in 140 ml. of ethyl alcohol and is stirred at reflux for 3 hours. A solid begins to appear after about half an hour. The reaction mixture is cooled in an ice bath and the resulting solid is filtered and air dried to afford the compound 4,5-dihydro-5 -methyl-6-(m-nitrophenyl)-3(2H)-pyridazinone as white to light yellow crystals.
Reaction SMILES: [CH3:1][N:2]([C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-])=O)=[C:14]([N:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[CH:13]=1)[C:3]([N:5]1[CH2:10][CH2:9][N:8]([CH3:11])[CH2:7][CH2:6]1)=[O:4]>CO.[Pd]>[NH2:18][C:15]1[CH:16]=[CH:17][C:12]([N:2]([CH3:1])[C:3]([N:5]2[CH2:6][CH2:7][N:8]([CH3:11])[CH2:9][CH2:10]2)=[O:4])=[CH:13][C:14]=1[N:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1
Reactant: CN1CCN(C(=O)N(C)c2ccc([N+](=O)[O-])c(N3CCCCC3)c2)CC1
Agent: [Pd]
Solvent: CO
Product: CN1CCN(C(=O)N(C)c2ccc(N)c(N3CCCCC3)c2)CC1

Procedure:
Using a procedure similar to Example 23, step (a), 4-methyl-piperazine-1-carboxylic acid methyl-(4-nitro-3-piperidin-1-yl-phenyl)-amide (110 mg, 0.3 mmol, as prepared in the previous step) was stirred in MeOH in the presence of 5% Pd—C (65 mg) to afford crude 4-methyl-piperazine-1-carboxylic acid (4-amino-3-piperidin-1-yl-phenyl)-methyl-amide as an oil, which in a manner similar to Example 4, step (c) was coupled to 5-cyano-furan-2-carbonyl chloride (64.6 μL, 412 mmol) in the presence of DIEA (115 μL, 0.6 mmol) using a procedure similar to Example 2 to afford 54.4 mg (40%) of the title compound as a bright yellow solid. 1H-NMR (CDCl3, 400 MHz): δ 9.62 (s, 1H), 8.41 (d, 1H, J=8.5 Hz), 7.29 (d, 1H, J=3.8 Hz), 7.24 (d, 1H, J=3.8 Hz), 6.95-6.92 (m, 2H), 3.24-3.26 (M, 4H), 3.22 (s, 3H), 2.84-2.82 (m, 4H), 2.21-2.26 (m, 7H), 1.84-1.79 (m, 4H), 1.66 (m, 2H); Mass spectrum (ESI, m/z): Calcd. for C24H30N6O3, 451.2 (M+H), found 451.1.
Reaction SMILES: [C:1]([O:6][CH3:7])(=[O:5])[C:2]([CH3:4])=O.[C:8]([O:16][CH2:17][CH3:18])(=[O:15])[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11].CCOCC>C(OC(=O)C)(=O)C.[Cl-].[Cl-].[Zn+2]>[CH2:17]([O:16][C:8](=[O:15])[C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[C:2]([C:1]([O:6][CH3:7])=[O:5])[CH3:4])[CH3:18]
Reactant: CCOC(=O)CC(=O)OCC
Reactant: COC(=O)C(C)=O
Agent: [Cl-]
Agent: [Zn+2]
Solvent: CC(=O)OC(C)=O
Solvent: CCOCC
Product: CCOC(=O)C(C(=O)OCC)=C(C)C(=O)OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 77.3 %

Procedure:
A mixture of ZnCl2 (42 g, 308 mmol) in acetic anhydride (100 mL) was stirred at r.t. for 2 h. The resulting solution was decanted, and to this solution was added methyl pyruvate (15.5 mL, 171 mmol) and diethyl malonate (26 mL, 171 mmol). The resulting mixture was heated at 100° C. for 1 h, then left standing at r.t. for 16 h. Ether (250 mL) was added and the mixture was washed with ice water and saturated NaHCO3. The organic layer was dried over MgSO4 and concentrated to give a dark brown oil, which was distilled under reduced pressure to give 32.3 g of the title compound as a yellow oil. 1H NMR (CDCl3, 200 MHz): δ=4.15-4.40 (m, 4H), 3.78 (s, 3H), 2.20 (s, 3H), 1.20-1.40 (m, 6H).
Reaction SMILES: II.[Mg].[C:4]([O:7][C:8]1[C:13]([CH:14](Br)[CH2:15][CH2:16]Br)=[CH:12][CH:11]=[CH:10][C:9]=1[Cl:19])(=[O:6])[CH3:5].Cl>C1COCC1>[C:4]([O:7][C:8]1[C:13]([CH:14]2[CH2:16][CH2:15]2)=[CH:12][CH:11]=[CH:10][C:9]=1[Cl:19])(=[O:6])[CH3:5]
Reactant: CC(=O)Oc1c(Cl)cccc1C(Br)CCBr
Agent: Cl
Agent: II
Agent: [Mg]
Solvent: C1CCOC1
Product: CC(=O)Oc1c(Cl)cccc1C1CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 100.5 %

Procedure:
Iodine (catalytic amount) was added to a mixture of magnesium (1.97 g, 81 mmol) and anhydrous THF (30 ml) under a nitrogen atmosphere, and the mixture was stirred at room temperature for 30 minutes. Subsequently, a solution of 2-chloro-6-(1,3-dibromopropyl)phenyl acetate (28.5 g, 77 mmol) in anhydrous THF (90 ml) was added to the mixture at 80° C. over 45 minutes. After the mixture was stirred at 80° C. for 1 hour, the mixture was further stirred at room temperature for 2 hours. The reaction mixture was ice-cooled and 1M hydrochloric acid (80 ml) was added thereto. The mixture was extracted with ethyl acetate (2×100 ml). The organic layer was combined and successively washed with water and a saturated aqueous NaCl solution, followed by drying with anhydrous sodium sulfate. After the solid was removed by filtration, the filtrate was concentrated to obtain 16.3 g of 2-chloro-6-cyclopropylphenyl acetate as a brown oil.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH:6]=O.[CH3:8][C:9]([S:12]([NH2:14])=[O:13])([CH3:11])[CH3:10]>C1COCC1.C(OCC)(=O)C.[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[O:1]1[CH:5]=[CH:4][N:3]=[C:2]1/[CH:6]=[N:14]/[S:12]([C:9]([CH3:11])([CH3:10])[CH3:8])=[O:13]
Reactant: CC(C)(C)S(N)=O
Reactant: O=Cc1ncco1
Agent: [Ti+4]
Agent: CC[O-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(C)S(=O)/N=C/c1ncco1
Temperature: 25 °C
Reaction time: 8 h
Yield: 67.7 %

Procedure:
In a round-bottomed flask, oxazole-2-carbaldehyde (300 mg, 3.09 mmol) was dissolved in THF (7 ml) and 2-methylpropane-2-sulfinamide (450 mg, 3.71 mmol) and titanium(IV) ethoxide (1.3 ml, 6.18 mmol) were added. The reaction mixture was stirred at room temperature overnight then slowly quenched by dropwise addition of brine (2 ml) which resulted in the formation of a thick yellow precipitate. The reaction mixture was diluted with ethyl acetate and stirred vigorously at room temperature for 10 min. The suspension was filtered over Celite and rinsed with ethyl acetate. The filtrate was concentrated and the residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-30% EtOAc) to afford 419 mg (68%) of 2-methyl-propane-2-sulfinic acid 1-oxazol-2-yl-meth-(E)-ylideneamide as a light yellow solid.
Reaction SMILES: Cl[CH2:2][CH2:3][C:4]1[C:9](=[O:10])[N:8]2[CH:11]=[CH:12][CH:13]=[CH:14][C:7]2=[N:6][C:5]=1[CH3:15].Cl.[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([CH:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)=[O:25])=[CH:20][CH:19]=1.C(=O)([O-])[O-].[Na+].[Na+]>CC(C)CC(=O)C>[F:17][C:18]1[CH:19]=[CH:20][C:21]([C:24]([CH:26]2[CH2:31][CH2:30][N:29]([CH2:2][CH2:3][C:4]3[C:9](=[O:10])[N:8]4[CH:11]=[CH:12][CH:13]=[CH:14][C:7]4=[N:6][C:5]=3[CH3:15])[CH2:28][CH2:27]2)=[O:25])=[CH:22][CH:23]=1
Reactant: O=C(c1ccc(F)cc1)C1CCNCC1
Reactant: Cc1nc2ccccn2c(=O)c1CCCl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(=O)CC(C)C
Product: Cc1nc2ccccn2c(=O)c1CCN1CCC(C(=O)c2ccc(F)cc2)CC1

Procedure:
A mixture of 5 parts of 3-(2-chloroethyl)-2-methyl-4H-pyrido-[1,2-a]pyrimidin-4-one, 4.9 parts of (4-fluorophenyl)(4-piperidinyl)-methanone hydrochloride, 5 parts of sodium carbonate and 160 parts of 4-methyl-2-pentanone is stirred and refluxed for 24 hours. The reaction mixture is cooled, washed with water and the layers are separated. The organic phase is dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (92:8 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from a mixture of ethanol and 1,1'-oxybisethane, yielding 3 parts of 3-[2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl]-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one; mp. 139° C.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl:7][C:8]1[C:22]([Cl:23])=[CH:21][C:11]2[C:12]3[CH2:13][CH2:14][C:15](=O)[NH:16][C:17]=3[CH2:18][CH2:19][C:10]=2[CH:9]=1.[OH-].[Na+]>O1CCCC1>[Cl:7][C:8]1[C:22]([Cl:23])=[CH:21][C:11]2[C:12]3[CH2:13][CH2:14][CH2:15][NH:16][C:17]=3[CH2:18][CH2:19][C:10]=2[CH:9]=1
Reactant: O=C1CCC2=C(CCc3cc(Cl)c(Cl)cc32)N1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: Clc1cc2c(cc1Cl)C1=C(CC2)NCCC1

Procedure:
1.57 g (0.042 mol) of lithium aluminum hydride are suspended in 60 ml of tetrahydrofuran under argon, 5.56 g (0.021 mol) of 8,9-dichloro-1,4,5,6-tetrahydrobenzo[f]-quinolin-3(2H)-one are slowly added thereto and the mixture is boiled under reflux for 2.5 hours. The mixture is then cooled to 0°, 5.2 ml of 18 percent sodium hydroxide solution are added dropwise thereto and the precipitate formed is removed by filtration. On evaporation of the filtrate, there is obtained 8,9-dichloro -1,2,3,4,5,6-hexahydrobenzo[f]quinoline as a yellow oil which is processed directly.
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][CH:4]=1.[CH2:13]([Mg]Br)[CH3:14].B(F)(F)F>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C(OCC)C>[F:1][C:2]([F:11])([F:12])[C:3]1[CH:10]=[CH:9][C:6]([C:7]2([NH2:8])[CH2:14][CH2:13]2)=[CH:5][CH:4]=1
Reactant: N#Cc1ccc(C(F)(F)F)cc1
Reactant: CC[Mg]Br
Agent: [Ti+4]
Agent: CC(C)[O-]
Agent: FB(F)F
Solvent: CCOCC
Product: NC1(c2ccc(C(F)(F)F)cc2)CC1
Yield: 180 %

Procedure:
The title compound was prepared according to the procedure described in Intermediate-12 by using of 4-(trifluoromethyl)benzonitrile (1.0 g, 0.58 mmol), diethyl ether (20 mL), titanium isopropoxide (2.0 g, 0.70 mmol), ethyl magnesium bromide (4.30 mL, 12.86 mmol) and boron trifluoride solution (1.5 mL) to afford 0.210 g of desired product. 1HNMR (CDCl3): δ 1.05 (s, 2H), 1.60 (s, 2H), 1.78 (s, 2H), 7.36 (d, J=7.8 Hz, 2H), 7.55 (d, J=8.1 Hz, 2H).
Reaction SMILES: [I:1]C1N(C2C=C3C(=C(C)C=2)NC(=O)C=C3)C(C)=NC=1.[CH3:20][C:21]1[N:22]([C:26]2[CH:27]=[C:28]3[C:33](=[C:34]([CH3:36])[CH:35]=2)[NH:32][C:31](=[O:37])[CH:30]=[CH:29]3)[CH:23]=[CH:24][N:25]=1>>[I:1][C:24]1[N:25]=[C:21]([CH3:20])[N:22]([C:26]2[CH:27]=[C:28]3[C:33](=[C:34]([CH3:36])[CH:35]=2)[NH:32][C:31](=[O:37])[CH:30]=[CH:29]3)[CH:23]=1
Reactant: Cc1cc(-n2c(I)cnc2C)cc2ccc(=O)[nH]c12
Reactant: Cc1cc(-n2ccnc2C)cc2ccc(=O)[nH]c12
Product: Cc1cc(-n2cc(I)nc2C)cc2ccc(=O)[nH]c12

Procedure:
n-Butyllithium (16.42 cm3 of a 1.55M solution in n-hexane) was added dropwise to a stirred solution of 6-(4,5-di-iodo-2-methylimidazol-1-yl)-8-methyl-2-(1H)-quinolone (5.0 g) in tetrahydrofuran (100 cm3) at -30° under nitrogen. After 30 minutes saturated aqueous ammonium chloride solution (20 cm3) was added, and the mixture was warmed to room temperature. The mixture was then basified with saturated sodium carbonate solution to pH 10 (approximately) and extracted with methanol:ethyl acetate (1:19 by volume, 100 cm3) and then methanol:dichloromethane (1:19 by volume, 2×200 cm3). The combined and dried (MgSO4) organic extracts were evaporated in vacuo to give a residue which was chromatographed on silica (Merck "MK 60.9385" [Trade Mark]). Elution with methanol:dichloromethane, 1:19 by volume, followed by combination and evaporation of the appropriate fractions gave a solid which was recrystallised from methanol/ethyl acetate to afford the title compound, (0.87 g), which was shown spectroscopically to be identical to the product of Preparation 4. Also eluted were fractions which when combined and evaporated afforded a solid, (2.28 g), which was shown to be a mixture of the title compound, 6-(5-iodo-2-methylimidazol-1-yl)-8-methyl-2-(1H)-quinolone, and 6-(2-methylimidazol-1-yl)-8-methyl-2-(1H)-quinolone.
Reaction SMILES: [O:1]=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9](CO)[OH:10])[OH:8])[OH:6])[OH:4].O=C[C@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O>>[O:1]=[CH:2][C@H:3]([C@@H:5]([C@@H:7]([CH2:9][OH:10])[OH:8])[OH:6])[OH:4]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Agent: O=C[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Product: O=C[C@@H](O)[C@H](O)[C@H](O)CO

Procedure:
In another aspect of the second embodiment, D-arabinonic acid reactant 90 may be prepared by decarboxylation 80 of a D-glucose starting material 60 by one or more reactions. Referring to FIG. 2, the starting material can be converted to an arabinonic reactant 90 or a ribonic acid reactant 40 by one or more reaction steps. Preferably, a suitable C-6 sugar starting material is decarboxylated at the C-1 position. Optionally, a starting material comprising D-(+)-allose or D-(+)-altrose can undergo a decarboxylation reaction 35 to produce an intermediate comprising D-(−)-ribose (aldehyde) that can subsequently undergo an oxidation reaction 37 to produce the desired reactant 40 comprising D-ribonic acid. Similarly, a starting material comprising D-(+)-glucose or D-(+)-mannose can undergo a decarboxylation reaction 85 to produce an intermediate comprising D-(−)-arabinose (aldehyde) that can subsequently undergo an oxidation reaction 87 to produce the desired reactant 90 comprising D-arabinonic acid. U.S. Pat. No. 4,515,667 describes a process for the photochemical decarboxylation of an alpha-hydroxy carboxylic acid to the corresponding alcohol which process comprises irradiating a mixture of a solution of an alpha-hydroxy carboxylic acid and a metal titanate.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][N:15]2[CH2:20][CH2:19][NH:18][CH2:17][C:16]2=[O:21])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C.[Br:34][C:35]1[CH:36]=[C:37]([S:41](Cl)(=[O:43])=[O:42])[CH:38]=[CH:39][CH:40]=1>O>[Br:34][C:35]1[CH:36]=[C:37]([S:41]([N:18]2[CH2:19][CH2:20][N:15]([CH2:14][CH:11]3[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]3)[C:16](=[O:21])[CH2:17]2)(=[O:43])=[O:42])[CH:38]=[CH:39][CH:40]=1
Reactant: O=S(=O)(Cl)c1cccc(Br)c1
Reactant: CC(C)(C)OC(=O)N1CCC(CN2CCNCC2=O)CC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1CCC(CN2CCN(S(=O)(=O)c3cccc(Br)c3)CC2=O)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 50.9 %

Procedure:
To a mixture of 1-[1-(tert-butoxycarbonyl)-4-piperidylmethyl]-2-piperazinone (1.19 g), sodium carbonate (848 mg), ethyl acetate (40 ml) and water (20 ml) was added 3-bromobenzenesulfonyl chloride (1.02 g), and the mixture was stirred at room temperature for 1 hour. The organic layer was separated, washed with saturated brine, dried and concentrated, and the residue was purified with silica gel column chromatography (hexane:ethyl acetate=1:2) to give colorless crystals of the title compound (1.05 g).
Reaction SMILES: [C:1]([C:4]1[CH:30]=[CH:29][C:7]([O:8][CH2:9][CH2:10][CH2:11][S:12][CH2:13][CH:14]2[CH2:18][O:17][C:16]([CH2:24][CH2:25][C:26]([OH:28])=[O:27])([CH2:19][CH2:20][C:21]([OH:23])=[O:22])[S:15]2)=[C:6]([CH2:31][CH2:32][CH3:33])[C:5]=1[OH:34])(=[O:3])[CH3:2].ClC1C(C(OO)=[O:43])=CC=CC=1>C(Cl)Cl>[C:1]([C:4]1[CH:30]=[CH:29][C:7]([O:8][CH2:9][CH2:10][CH2:11][S:12]([CH2:13][CH:14]2[CH2:18][O:17][C:16]([CH2:19][CH2:20][C:21]([OH:23])=[O:22])([CH2:24][CH2:25][C:26]([OH:28])=[O:27])[S:15]2)=[O:43])=[C:6]([CH2:31][CH2:32][CH3:33])[C:5]=1[OH:34])(=[O:3])[CH3:2]
Reactant: O=C(OO)c1ccccc1Cl
Reactant: CCCc1c(OCCCSCC2COC(CCC(=O)O)(CCC(=O)O)S2)ccc(C(C)=O)c1O
Solvent: ClCCl
Product: CCCc1c(OCCCS(=O)CC2COC(CCC(=O)O)(CCC(=O)O)S2)ccc(C(C)=O)c1O
Yield: 44 %

Procedure:
The title compound was prepared according to the procedure of Example 46 using the sulfide obtained in Example 3 (0.15 g, 0.0003 mol) and m chloroperbenzoic acid (0.062 g, 0.0003 mol) in methylene chloride (3 ml). The crude product was chromatographed on silica gel using ethyl acetate containing 0.5% acetic acid to give 0.070 g (45%) of the desired product as an oil.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].C([O-])([O-])=O.[K+].[K+].[Cl:23][C:24]1[N:29]=[C:28](Cl)[C:27]([Cl:31])=[CH:26][N:25]=1.O>C1COCC1>[Cl:23][C:24]1[N:29]=[C:28]([NH:1][C:2]2[CH:10]=[CH:9][C:8]([N:11]3[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]3)=[CH:7][C:3]=2[C:4]([NH2:6])=[O:5])[C:27]([Cl:31])=[CH:26][N:25]=1
Reactant: Clc1ncc(Cl)c(Cl)n1
Reactant: NC(=O)c1cc(N2CCCCC2)ccc1N
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: NC(=O)c1cc(N2CCCCC2)ccc1Nc1nc(Cl)ncc1Cl
Reaction time: 72 h
Yield: 58.8 %

Procedure:
To a solution of 2-amino-5-piperidin-1-yl-benzamide (1.05 g, 4.6 mmol, Heterocyclic Comm. 2001, 7, 473-480) in THF (10 mL) was added K2CO3 (0.76 g, 5.5 mmol) and 2,4,5-trichloropyrimidine (0.84 g, 4.6 mmol). After stirring for 72 h, addition of water (5 mL) gave a precipitate that was removed by filtration and washed with water (5×3 mL) and ether (3×2 mL) to afford 2-(2,5-dichloro-pyrimidin-4-ylamino)-5-piperidin-1-yl-benzamide as a yellow solid (0.99 g) that was used without further purification in the subsequent step.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]([C:11]1[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=1)=[O:10].[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([S:25](Cl)(=[O:27])=[O:26])=[CH:21][CH:20]=1>>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][S:25]([C:22]2[CH:21]=[CH:20][C:19]([O:18][CH3:17])=[CH:24][CH:23]=2)(=[O:27])=[O:26])=[C:3]([C:9]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=2)=[O:10])[CH:4]=1
Reactant: Nc1ccc(Cl)cc1C(=O)c1ccncc1
Reactant: COc1ccc(S(=O)(=O)Cl)cc1
Product: COc1ccc(S(=O)(=O)Nc2ccc(Cl)cc2C(=O)c2ccncc2)cc1

Procedure:
The title compound was prepared according to the general procedure for the synthesis of N-Aryl-benzenesulfonamides previously described using 116 mg of (2-Amino-5-chloro-phenyl)-pyridin-4-yl-methanone and 101 mg of 4-methoxy-benzenesulfonyl chloride. 1H-NMR (400 MHz, CDCl3): δ 3.74 (s, 3H), 6.77 (d, 2H, J=8.8 Hz), 7.21 (m, 2H), 7.27 (d, 1H, J=2 Hz), 7.52 (dd, 1H, J=8.8 Hz, 2.8 Hz), 7.63 (m, 2H), 7.76 (d, 1H, J=8.8 Hz), 8.76 (d, 2H, J=5.6 Hz), 9.88 (s, 1H). MS: m/z 403.9 (M++1).