Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(=O)([O-])[O-].[Ba+2].[C:6]([OH:14])(=[O:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH3:15][CH2:16][CH2:17][CH2:18][CH:19]1[C:54](=[O:55])[O:53][CH:52]([CH:56]([CH:58]([OH:66])[CH2:59][CH2:60][CH2:61][NH:62][C:63]([NH2:65])=[NH:64])[CH3:57])[CH:51]([CH3:67])[CH:50]=[C:49]([CH3:68])[CH2:48][CH2:47][CH2:46][CH2:45][CH:44]([OH:69])[CH2:43][CH:42]([OH:70])[CH2:41][CH:40]([OH:71])[CH2:39][CH:38]([OH:72])[CH2:37][CH:36]([OH:73])[CH:35]([O:74][C@H:75]2[O:79][C@H:78]([CH2:80][OH:81])[C@@H:77]([OH:82])[C@@H:76]2[OH:83])[CH:34]=[C:33]([CH3:84])[CH:32]([OH:85])[CH2:31][CH2:30][CH2:29][CH:28]([OH:86])[CH2:27][CH2:26][CH2:25][CH:24]([OH:87])[CH2:23][CH2:22][CH:21]([CH3:88])[CH:20]1[OH:89].S([O-])([O-])(=O)=O>CO>[CH3:15][CH2:16][CH2:17][CH2:18][CH:19]1[C:54](=[O:55])[O:53][CH:52]([CH:56]([CH:58]([OH:66])[CH2:59][CH2:60][CH2:61][NH:62][C:63]([NH2:65])=[NH:64])[CH3:57])[CH:51]([CH3:67])[CH:50]=[C:49]([CH3:68])[CH2:48][CH2:47][CH2:46][CH2:45][CH:44]([OH:69])[CH2:43][CH:42]([OH:70])[CH2:41][CH:40]([OH:71])[CH2:39][CH:38]([OH:72])[CH2:37][CH:36]([OH:73])[CH:35]([O:74][C@H:75]2[O:79][C@H:78]([CH2:80][OH:81])[C@@H:77]([OH:82])[C@@H:76]2[OH:83])[CH:34]=[C:33]([CH3:84])[CH:32]([OH:85])[CH2:31][CH2:30][CH2:29][CH:28]([OH:86])[CH2:27][CH2:26][CH2:25][CH:24]([OH:87])[CH2:23][CH2:22][CH:21]([CH3:88])[CH:20]1[OH:89].[C:6]([O-:14])(=[O:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: O=C(O)c1ccccc1
Agent: CCCCC1C(=O)OC(C(C)C(O)CCCNC(=N)N)C(C)/C=C(\C)CCCCC(O)CC(O)CC(O)CC(O)CC(O)C(O[C@H]2O[C@H](CO)[C@@H](O)[C@@H]2O)/C=C(\C)C(O)CCCC(O)CCCC(O)CCC(C)C1O
Agent: CCCCC1C(=O)OC(C(C)C(O)CCCNC(=N)N)C(C)C=C(C)CCCCC(O)CC(O)CC(O)CC(O)CC(O)C(O[C@H]2O[C@H](CO)[C@@H](O)[C@@H]2O)C=C(C)C(O)CCCC(O)CCCC(O)CCC(C)C1O
Agent: O=C([O-])[O-]
Solvent: CO
Product: O=C([O-])c1ccccc1
Reaction time: 0.33 h

Procedure:
0.087 g (0.444 millimole) of barium carbonate are suspended in 15 ml of methanol whereupon 0.11 g (0.91 millimole) of benzoic acid is added. The suspension thus obtained is heated to boiling until a clear solution is obtained. The clear and colorless solution is added to a suspension of 1.0 g (0.887 millimoles) of primycin sulfate and 80 ml of methanol and the reaction mixture is heated to boiling for 20 minutes under stirring. The hot solution is filtered through Celite and the filtrate is evaporated to dryness in vacuo. The residue is treated with ether, filtered and the solid is washed on the filter with 15 ml of a 2:1 mixture of acetone and water. Thus 0.98 g of primycin benzoate is obtained in the form of a white powder, yield 90.6%. Mp.: 170°-171° C., /α/D25 =+36.9°.
Reaction SMILES: C([Li])CCC.[CH:6]#[C:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[CH:13]([CH:15]1[CH2:19][CH2:18][CH:17]([O:20][CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][O:22]2)[CH:16]1[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][C:33]([OH:35])=[O:34])=[O:14]>CCCCCC.C1(C)C=CC=CC=1.CCOCC>[OH:14][CH:13]([CH:15]1[CH2:19][CH2:18][CH:17]([O:20][CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][O:22]2)[CH:16]1[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][C:33]([OH:35])=[O:34])[C:6]#[C:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: O=CC1CCC(OC2CCCCO2)C1CCCCCCC(=O)O
Reactant: C#CCCCCC
Agent: [Li]CCCC
Solvent: Cc1ccccc1
Solvent: CCOCC
Solvent: CCCCCC
Product: CCCCCC#CC(O)C1CCC(OC2CCCCO2)C1CCCCCCC(=O)O
Temperature: -70 °C
Reaction time: 0.17 h

Procedure:
Under a nitrogen atmosphere at -40° C, a solution of 70.4 ml of n-butyl lithium in hexane (2.3 molar) is added dropwise to a solution of 1-heptyne (14.78 g, 2.2 equivalents) in 50 ml of toluene. The mixture is stirred at the same temperature for 10 minutes. The solution is transferred carefully to an addition funnel and added at to a solution of 2-formyl-5 -(tetrahydropyran-2-yloxy)-cyclopentaneheptanoic acid (22.82 g, 1 equivalent), described in Example 1, in 50 ml of toluene cooled to -70° C. The reaction is stirred at the same temperature for 2 hr. The mixture then is diluted with ether and washed with water. The aqueous layer is acidified with acetic acid and extracted with ether. The ether extract is washed with water, dried and concentrated to give the title compound, nmr (CDCl3) δ0.89 (+, 3H), 3.90 (broad, 1H), 4.33 (m, 1H).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]3[N:16]=[CH:15][C:14]([CH2:17][CH2:18][N:19]4[CH2:23][CH2:22][CH2:21][C:20]4=[O:24])=[CH:13][CH:12]=3)[S:10][C:3]=12.[F:25][C:26]1[CH:31]=[C:30]([N+:32]([O-:34])=[O:33])[CH:29]=[CH:28][C:27]=1[OH:35].C(=O)([O-])[O-].[K+].[K+]>C1(OC2C=CC=CC=2)C=CC=CC=1>[F:25][C:26]1[CH:31]=[C:30]([N+:32]([O-:34])=[O:33])[CH:29]=[CH:28][C:27]=1[O:35][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]3[N:16]=[CH:15][C:14]([CH2:17][CH2:18][N:19]4[CH2:23][CH2:22][CH2:21][C:20]4=[O:24])=[CH:13][CH:12]=3)[S:10][C:3]=12
Reactant: O=[N+]([O-])c1ccc(O)c(F)c1
Reactant: O=C1CCCN1CCc1ccc(-c2cc3nccc(Cl)c3s2)nc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: c1ccc(Oc2ccccc2)cc1
Product: O=C1CCCN1CCc1ccc(-c2cc3nccc(Oc4ccc([N+](=O)[O-])cc4F)c3s2)nc1
Temperature: 200 °C
Yield: 46.7 %

Procedure:
To chlorothienopyridine 292 (1.2 g, 3.4 mmol) in diphenyl ether (20 mL) was added 2-fluoro-4-nitrophenol (1.58 g, 10.1 mmol) and potassium carbonate (2.32 g, 16.8 mmol) and the resultant mixture was heated to 200° C. for 10 h. Extra 2-fluoro-4-nitrophenol (1.58 g, 10.1 mmol) and potassium carbonate (2.32 g, 16.8 mmol) were added and the mixture was heated at 200° C. for a further 6 h. The mixture was cooled to RT, partitioned between ethyl acetate and 1M aqueous NaOH then filtered through celite. The organic phase was collected, washed with water and brine, dried (anhydrous MgSO4), filtered and concentrated. The residue was purified by silica gel chromatography (10% methanol/ethyl acetate) to afford title compound 293 (0.76 g, 47% yield), contaminated with ˜10% starting material 292, as a yellow solid. MS (M+H): 479.5
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.[CH3:9][O:10][C:11]1[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[CH:15][C:12]=1[CH2:13][NH2:14].C(N(CC)CC)C.O>C(O)C>[CH3:9][O:10][C:11]1[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[CH:15][C:12]=1[CH2:13][NH:14][C:2]1[N:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1
Reactant: Fc1cnc(Cl)nc1
Reactant: COc1ccc(CN)c(OC)c1
Solvent: CCO
Solvent: O
Solvent: CCN(CC)CC
Product: COc1ccc(CNc2ncc(F)cn2)c(OC)c1
Temperature: 50 °C
Yield: 51.6 %

Procedure:
2-Chloro-5-fluoropyrimidine (4.05 g, 30.6 mmol), 2,4-dimethoxybenzylamine (5.0 mL, 31 mmol) and triethylamine (3.72 g, 36.7 mmol) were stirred in ethanol (200 mL) and heated at 50° C. for 48 hours. The cooled reaction mixture was poured into water and extracted with ethyl ether (×2). The combined organic phase was dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexanes to ethyl acetate gradient elution) then triturated with ethyl ether:hexanes. The solid was collected by filtration and dried in vacuo to afford the title compound as a white solid (4.16 g).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH2:11])=[NH:10])=[CH:4][CH:3]=1.[O-][CH2:13][CH3:14].[Na+]>C(O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]2[N:11]=[C:8]([C:14]3[CH:13]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=3)[CH:5]=[CH:6][N:10]=2)=[CH:6][CH:7]=1
Reactant: CC[O-]
Reactant: N=C(N)Cc1ccc(Br)cc1
Agent: [Na+]
Solvent: CCO
Product: Brc1ccc(Cc2nccc(-c3ccc(Br)cc3)n2)cc1
Yield: 154.7 %

Procedure:
To a stirred mixture of 4-bromophenylacetamidine (11.25 g, 0.04 mole) and 1-dimethylamino-3-dimethylimonio-1-(4-bromophenyl)-1-propane perchlorate (15.25 g, 0.04 mole) in 100 mL of dry ethanol is added 0.04 mole sodium ethoxide (prepared from 0.92 g Na and 65 mL ethanol). After stirring for 30 min at room temperature a further equivalent of sodium ethoxide is added, and the mixture is heated under reflux for 2 hr. The solvent is removed under reduced pressure, and the yellow-brown residue triturated with 150 mL water. The solid is filtered, washed with water, dried in air and recrystallized from ether:hexane (1:3) to give 12.5 g (77%) of a pale yellow crystalline solid, mp 93°-94° C.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([CH:13]1[CH2:15][CH2:14]1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.Cl.[C:39]([CH:41]1[CH2:44][NH:43][CH2:42]1)#[N:40].C(N(CC)C(C)C)(C)C.Cl>ClCCl.O>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([CH:13]1[CH2:15][CH2:14]1)[C:10]([N:43]1[CH2:44][CH:41]([C:39]#[N:40])[CH2:42]1)=[O:12])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)N[C@@H](C(=O)O)C1CC1
Reactant: N#CC1CNC1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[B-](F)(F)F
Solvent: ClCCl
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N[C@@H](C(=O)N1CC(C#N)C1)C1CC1
Temperature: 25 °C
Reaction time: 5 h
Yield: 83.5 %

Procedure:
(R)-2-(tert-butoxycarbonylamino)-2-cyclopropylacetic acid (2.25 g, 10.5 mmol) and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (3.69 g, 11.5 mmol) were dissolved in dichloromethane (105 mL). 3-Cyanoazetidine hydrochloride (1.36 g, 11.5 mmol) and then N,N-diisopropylethylamine (4.5 mL, 26.1 mmol) were added and the mixture was stirred at room temperature for 5 h. Water, dilute HCl and more dichloromethane were added, the layers were separated and the aqueous layer was extracted once more with dichloromethane. The combined organic layers were washed with sodium chloride solution, dried over sodium sulfate and concentrated. The residue was purified by silica gel chromatography (methanol/dichloromethane) to give 2.45 g (83%) of [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-carbamic acid tert-butyl ester.
Reaction SMILES: C(N(CC)CC)C.[CH3:8][C:9]1[CH:14]=[C:13]([CH3:15])[N:12]=[C:11]([N:16]2[CH2:21][CH2:20][N:19]([C:22]3[CH:27]=[CH:26][C:25]([N+:28]([O-:30])=[O:29])=[CH:24][C:23]=3[OH:31])[CH2:18][CH2:17]2)[CH:10]=1.[C:32](Cl)(=[O:34])[CH3:33].O>ClCCl>[CH3:8][C:9]1[CH:14]=[C:13]([CH3:15])[N:12]=[C:11]([N:16]2[CH2:17][CH2:18][N:19]([C:22]3[CH:27]=[CH:26][C:25]([N+:28]([O-:30])=[O:29])=[CH:24][C:23]=3[O:31][C:32](=[O:34])[CH3:33])[CH2:20][CH2:21]2)[CH:10]=1
Reactant: CC(=O)Cl
Reactant: Cc1cc(C)nc(N2CCN(c3ccc([N+](=O)[O-])cc3O)CC2)c1
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)Oc1cc([N+](=O)[O-])ccc1N1CCN(c2cc(C)cc(C)n2)CC1
Temperature: 25 °C
Yield: 64.8 %

Procedure:
Triethylamine (1.0 mL, 7.17 mmol) was added to a solution of 2-[4-(4,6-dimethyl-pyridin-2-yl)-piperazin-1-yl]-5-nitro-phenol (500 mg, 1.52 mmol) in dry dichloromethane (20 mL) followed by the dropwise addition of acetyl chloride (0.2 mL, 2.80 mmol). After stirring for 15 min water was added and the mixture warmed to room temperature. The organic phase was separated and the aqueous phase was extracted with dichloromethane (2×30 mL). The combined organic phases were successively washed with water (2×30 mL) then brine (2×30 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was triturated with 5% dichloromethane in petroleum ether (2×20 mL) to afford acetic acid 2-[4-(4,6-dimethyl-pyridin-2-yl)-piperazin-1-yl]-5-nitro-phenyl ester (365 mg, 65%) as a pale brownish-yellow solid.
Reaction SMILES: [CH2:1]1[C:6]2[O:7][C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=3[C:5]=2[CH2:4][CH2:3][N:2]1C(OC)=O>Cl>[CH2:1]1[C:6]2[O:7][C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=3[C:5]=2[CH2:4][CH2:3][NH:2]1
Reactant: COC(=O)N1CCc2c(oc3ccccc23)C1
Agent: Cl
Product: c1ccc2c3c(oc2c1)CNCC3
Temperature: 0 °C
Yield: 88.9 %

Procedure:
A mixture of methyl 3,4-dihydro[1]benzofuro[2,3-c]pyridine-2(1H)-carboxylate (0.150 g, 0.6493 mmol) and concentrated HCl (10 ml) was refluxed for 18 h. The reaction mixture was cooled to 0° C., quenched with saturated aqueous NaHCO3 (100 mL), and extracted with ethyl acetate (2×50 mL), the organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to furnish 1,2,3,4-tetrahydro[1]benzofuro[2,3-c]pyridine (0.1 g, 46%). 1H NMR (200 MHz, CDCl3): δ 3.15 (m, 4H), 4.40 (m, 2H), 7.35 (m, 2H), 7.51 (m, 2H). MS: 160 (M+).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]=[N:10][N:11]([CH3:27])[C:12]=1[C:13]1[N:14]=[CH:15][N:16]([C:18]2[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[CH:20][N:19]=2)[CH:17]=1.C1N=C[N:30](C(N2C=NC=C2)=O)C=1.[OH-].[NH4+]>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]=[N:10][N:11]([CH3:27])[C:12]=1[C:13]1[N:14]=[CH:15][N:16]([C:18]2[CH:26]=[CH:25][C:21]([C:22]([NH2:30])=[O:23])=[CH:20][N:19]=2)[CH:17]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: Cn1nnc(-c2ccccc2Cl)c1-c1cn(-c2ccc(C(=O)O)cn2)cn1
Agent: [NH4+]
Agent: [OH-]
Solvent: CN(C)C=O
Product: Cn1nnc(-c2ccccc2Cl)c1-c1cn(-c2ccc(C(N)=O)cn2)cn1
Temperature: 60 °C
Reaction time: 1 h
Yield: 73.3 %

Procedure:
To a solution of 6-(4-(4-(2-chlorophenyl)-1-methyl-1H-1,2,3-triazol-5-yl)-1H-imidazol-1-yl)nicotinic acid (74 mg, 0.194 mmol) in DMF (3 mL) was added CDI (38 mg, 0.233 mmol) and the resulting mixture stirred at 60° C. for 1 h. After cooling to room temperature ammonium hydroxide (305 μL, 1.94 mmol) was added and reaction mixture was stirred for 1 h and then evaporated. Purification by chromatography (reverse phase HPLC) afforded the title compound (54 mg, 73%) as a white foam. MS: m/e=380.1 [M+H]+.
Reaction SMILES: Cl[C:2]1[C:11]2[C:10](=[O:12])[N:9]([CH3:13])[C:8](=[O:14])[N:7]([CH3:15])[C:6]=2[N:5]=[CH:4][CH:3]=1.[N-:16]=[N+:17]=[N-:18].[Na+]>CN(C=O)C>[N:16]([C:2]1[C:11]2[C:10](=[O:12])[N:9]([CH3:13])[C:8](=[O:14])[N:7]([CH3:15])[C:6]=2[N:5]=[CH:4][CH:3]=1)=[N+:17]=[N-:18]
Reactant: Cn1c(=O)c2c(Cl)ccnc2n(C)c1=O
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cn1c(=O)c2c(N=[N+]=[N-])ccnc2n(C)c1=O
Temperature: 25 °C
Reaction time: 6 h
Yield: 83.5 %

Procedure:
1.35 g of Compound 1 was dissolved in 10 ml of DMF and 0.52 g of 90% sodium azide was added thereto. The solution was stirred for 6 hr at room temperature and the solvent was distilled off under reduced pressure. After adding water, the resulting crystals were separated by filtration to give 1.16 g of 5-azido-1,3-dimethylpyrido[2,3-d]pyrimidine-2,4-dione (Compound 3)
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.Cl[CH2:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10][CH:9]=1.O>C(Cl)Cl>[C:8]1([CH2:7][N:1]2[CH:5]=[CH:4][N:3]=[CH:2]2)[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10][CH:9]=1
Reactant: ClCc1cccc2ccccc12
Reactant: c1c[nH]cn1
Solvent: O
Solvent: ClCCl
Product: c1ccc2c(Cn3ccnc3)cccc2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 65.2 %

Procedure:
A mixture of imidazole (15.4 g) and 1-chloromethyl-naphthalene (14.9 ml, 0.1 mol) in 200 ml of methylene chloride was stirred at room temperature overnight. The mixture was stirred with 200 ml of water, the layers were separated, the organic layer was washed with water (2×200 ml), the resulting solids were removed by filtration and then the organic layer was stirred with 30 ml of conc. HCl and 200 ml of water. The methylene chloride layer was discarded, and the aqueous layer was extracted with 100 ml of ether. The above aqueous layer was basified with 3N NaOH solution, extracted with methylene chloride, and the organic layer was dried over magnesium sulfate. The above organic solution was concentrated in vacuo to afford 13.58 g of 1-(1-naphthylmethyl)imidazole.
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[S:3]([O:6]S(C(F)(F)F)(=O)=O)(=[O:5])=[O:4].N1C=CC=CC=1.O[CH2:23][C:24]([CH3:46])([CH3:45])[O:25][C:26]1[C:27]([CH2:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[C:28]2[C:33](=[CH:34][CH:35]=1)[C:32](=[O:36])[CH2:31][CH2:30][CH2:29]2>ClCCl>[F:1][C:2]([F:15])([F:14])[S:3]([O:6][CH2:45][C:24]([CH3:46])([O:25][C:26]1[CH:35]=[CH:34][C:33]2[C:32](=[O:36])[CH2:31][CH2:30][CH2:29][C:28]=2[C:27]=1[CH2:37][CH2:38][C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1)[CH3:23])(=[O:5])=[O:4]
Reactant: CC(C)(CO)Oc1ccc2c(c1CCc1ccccc1)CCCC2=O
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(C)(COS(=O)(=O)C(F)(F)F)Oc1ccc2c(c1CCc1ccccc1)CCCC2=O
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 90 %

Procedure:
Trifluoromethanesulfonic anhydride (0.12 mL, 0.74 mmol) was added to a solution of pyridine (0.14 mL, 1.77 mmol) in dichloromethane (0.5 mL). The resulting mixture was added over 15 min to an ice-cooled solution of 6-(2-hydroxy-1,1-dimethylethoxy)-5-(2-phenylethyl)-3,4-dihydro-1(2H)-naphthalenone (100 mg, 0.30 mmol) in dichloromethane (0.5 mL). The resulting mixture was stirred for 15 min and was then quenched by the addition of water (2 mL). The mixture was diluted with 1 M aqueous hydrochloric acid (10 mL) and extracted with ethyl acetate (3×5 mL). The combined extracts were washed with 1 M aqueous hydrochloric acid (10 mL), saturated aqueous copper sulfate (3×5 mL), and was then dried (brine, Na2SO4) and concentrated. The residue was purified by dry-flash column chromatography (SiO2, 5-40% ethyl acetate-hexane) to give 2-methyl-2-{[5-oxo-1-(2-phenylethyl)-5,6,7,8-tetrahydro-2-naphthalenyl]oxy}propyl trifluoromethanesulfonate as a colorless oil, 125 mg, 90% yield. NMR spectrum was consistent with structure. MS EI: M+• 470.1376 (M+• 470.1375).
Reaction SMILES: [C:1]([OH:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH:9]=[CH:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].COC(=O)CCCCCCCC=CCCCCCCCC.C1([Se]Br)C=CC=CC=1.[N:50]([O-:52])=[O:51].[Na+].C(N1C2N=CNC=2C(=O)N(C)C1=O)C(C)C.B(F)(F)F>Cl[Hg]Cl.CC#N.O1CCCC1>[CH3:18][CH2:17][CH2:16][CH2:15][CH2:14]/[CH:13]=[CH:12]\[CH2:11]/[C:10](/[N+:50]([O-:52])=[O:51])=[CH:9]\[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][C:1]([OH:20])=[O:19]
Reactant: O=N[O-]
Reactant: CCCCCCCCC=CCCCCCCCC(=O)O
Agent: Br[Se]c1ccccc1
Agent: CC(C)Cn1c(=O)n(C)c(=O)c2[nH]cnc21
Agent: Cl[Hg]Cl
Solvent: CCCCCCCCC=CCCCCCCCC(=O)OC
Solvent: CC#N
Solvent: C1CCOC1
Product: CCCCC/C=C\C/C(=C\CCCCCCCC(=O)O)[N+](=O)[O-]

Procedure:
Materials. 9-Octadecenoic acid (oleic acid) and its respective methyl ester, methyl-9-octadecenoate was purchased from Nu-Check Prep (Elysian, Minn.). LNO2 and [13C]LNO2 were synthesized as previously described (9,12); OA-NO2 and [13C]OA-NO2 were synthesized as described in below. Phenylselenium bromide, HgCl2, NaNO2, anhydrous tetrahydrofuran (THF), CH3CN, CDCl3, insulin, dexaniethasone and 3-isobutyl-1-methylxantliine were obtained from Sigma/Aldrich (St Louis, Mo.). Silica gel G and HF thin layer chromatography plates (250 and 2000 μm) were from Analtech (Newark, Del.). Methanolic BF3, horseradish peroxidase-linked goat anti-rabbit IgG and Coomasie Blue were from Pierce (Rockford, Ill.). Synthetic solvents were of HPLC grade or better from Fisher Scientific (Fairlawn, N.J.). Solvents used for extractions and mass spectrometric analyses were from Burdick and Jackson (Muskegon, Mich.). [13C]Oleic acid and [13C]linoleic acid were purchased from Cambridge Isotope Laboratories, Inc. (Andover, Mass.). Anti-PPARγ and anti-β-actin antibodies were from Santa Cruz (Santa Cruz, Calif.); anti-aP2 antibody was from Chemicon International Inc. (Temecula, Calif.).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[OH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16].[Br:25][CH2:26][CH2:27][CH2:28]Br>C(#N)C>[Br:25][CH2:26][CH2:27][CH2:28][O:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][C:15]([O:17][CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[O:16]
Reactant: BrCCCBr
Reactant: O=C(Cc1ccccc1O)OCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: O=C(Cc1ccccc1OCCCBr)OCc1ccccc1

Procedure:
A solution of 100 g of 2-hydroxyphenylacetic acid, 75 cm3 of benzyl alcohol and 0.5 g of paratoluenesulphonic acid in 1400 cm3 of toluene is refluxed for 2 hours while removing the water formed. After cooling, treating with 3 g of animal black and filtering, the reaction mixture is concentrated to 150 cm3 and 300 cm3 of isopropyl oxide are added. The crystals obtained by cooling to 0° C. are drained, washed and dried to give 82.5 g of benzyl 2-hydroxyphenylacetate. 174 g of potassium carbonate are added to a solution of 153 g of this ester in a mixture of 500 cm3 of 1,3-dibromopropane and 2500 cm3 of acetonitrile, and the mixture is refluxed for 17 hours. The reaction mixture is cooled, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue is taken up in 500 cm3 of ethyl acetate and the organic phase is washed with 400 cm3 of water twice and twice with 250 cm3 of a saturated solution of sodium chloride and then dried and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (particle size 0.2-0.063 mm, diameter 9 cm, height 55 cm), eluting with a cyclohexane and ethyl acetate mixture (95/5 by volume) and collecting fractions of 500 cm3. Fractions 12 to 18 are pooled and concentrated to dryness under reduced pressure (2.7 kPa) to give 90 g of benzyl 2-(3-bromopropoxy)phenyl-acetate in the form of a yellow oil. A solution of 40 g of this product in 500 cm3 of acetonitrile is heated in an autoclave with 27 g of sodium iodide and 90 g of dimethylamine for 16 hours at 80° C. The reaction mixture is cooled, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue is purified by acid-base treatment to give 29.3 g of benzyl 2-(3-dimethylaminopropoxy)phenylacetate in the form of a yellow oil. Hydrogenation of this ester, at atmospheric pressure at 40° C. in ethyl acetate in the presence of palladium hydroxide followed by crystallization from ethyl acetate, yield 17.5 g of 2-(3-dimethylaminopropoxy)phenylacetic acid in the form of white crystals; melting point 98° C.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[NH:8][C:7]2=[O:14])([O-:3])=[O:2].Br[CH2:16][C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[N:8]([CH2:16][C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18])[C:7]2=[O:14])([O-:3])=[O:2]
Reactant: O=C1NC(=O)c2cc([N+](=O)[O-])ccc21
Reactant: O=C(CBr)OCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C(CN1C(=O)c2ccc([N+](=O)[O-])cc2C1=O)OCc1ccccc1
Yield: 78 %

Procedure:
A solution of 5-nitroisoindoline-1,3-dione (1.00 g, 5.20 mmol), benzyl 2-bromoacetate (1.225 ml, 7.81 mmol) and K2CO3 (1.079 g, 7.81 mmol) in DMF (10 ml) was heated at 90° C. for 2 hours. The insoluble inorganic salts were filtered off, and the filtrate was diluted with ethyl acetate and washed with 1N HCl and with brine. The organic layer was dried over Na2SO4 and the solvent was removed under vacuum. The residue was purified by crystallization from MeOH to afford benzyl 2-(5-nitro-1,3-dioxoisoindolin-2-yl)acetate (1.39 g, 4.08 mmol, 78% yield, MS/ESI+ not detectable [MH]+).
Reaction SMILES: C1(O)C=CC=CC=1.[C:8]1([CH2:14][CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.CCC.[Br:27]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>>[C:8]1([CH:14]([Br:27])[CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: c1ccc(CCCOc2ccccc2)cc1
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: Oc1ccccc1
Solvent: CCC
Product: BrC(CCOc1ccccc1)c1ccccc1

Procedure:
Following the above procedure but using phenol in place of m-methoxyphenol, there was prepared 1-phenyl-3-phenoxypropane distilling at 146°-9° C. at 6 torr. This propane derivative was brominated α to the phenyl group with N-bromosuccinimide and benzoyl peroxide to yield 1-phenyl-3-phenoxypropylbromide which compound was in turn reacted with dimethylamine in a sealed reaction vessel to yield N,N-dimethyl 1-phenyl-3-phenoxypropylamine boiling in the range 116°-118° C. at 0.3 torr. The hydrochloride salt was prepared by the above procedure to yield N,N-dimethyl 1-phenyl-3-phenoxy-propylamine hydrochloride melting at 165°-167° C. after recrystallization from an ethyl acetate/acetone solvent mixture.