Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([OH:8])([OH:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:9]1(O)CCCCC1.COC1CCCCC1O.C1(O)C=CC=CC=1.C1(OC)C(=CC=CC=1)O>CO>[CH3:9][O:7][C:1]1([OH:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: OC1(O)CCCCC1
Reactant: OC1CCCCC1
Agent: COC1CCCCC1O
Agent: COc1ccccc1O
Solvent: CO
Solvent: Oc1ccccc1
Product: COC1(O)CCCCC1

Procedure:
Ruthenium Catalyzed Hydrogenations. For guaiacol hydrogenation in the presence of ruthenium catalyst the products were similar to those identified earlier in our laboratory. At 150° C., 54% of the guaiacol had already been converted by the time the reactor reached temperature, time zero in FIG. 1. The primary product was that resulting from saturation of the phenolic ring, 2-methoxycyclohexanol (40% yield @ 1 h). Cyclohexanediol was the secondary product (8%), although cyclohexanol was also significant (4%). The methanol byproduct was found (1%). There was little phenol formed at this temperature. At 200° C. the initial conversion of guaiacol during heatup was 62%. As shown in FIG. 2 the methoxycyclohexanols were still the main product (38% yield @ 4 h), but cyclohexanediol became less important (3%) while more cyclohexanol was formed (8%). More methanol was present (2%), as was more phenol. At 250° C., 60% of the guaiacol was converted by the time the reactor reached temperature. As shown in FIG. 3 cyclohexanol almost surpassed methoxycyclohexanols as the main product. Methoxycyclohexanol yield peaked at 17% in the 1 to 2 h range before reacting on to secondary products. The maximum cyclohexanol yield was 13%. Cyclohexanediol was only a minor product (1%). More phenol was evident and cyclohexane became a significant product (2%); however, the hexane recovery is likely limited by its low solubility in the water. More cyclohexane may have been actually produced and remained in the reactor as a separate light phase, which could not be sampled by our method. Over the period of the test, the amount of aqueous phase products is reduced. A large methane gas product was produced in this test, as has been reported for processing at these conditions of temperature and catalyst wherein phenol was extensively gasified at as low as 250° C.xi. At 300° C., phenol is the primary product that was recoverable. Cyclohexanol and methoxycyclohexanol are early products which are reduced to low levels within the first hour at temperature. All three isomers of methyl-phenol (cresols) are significant byproducts, as is benzene. Cyclohexane is present in the water product only at low concentration, but is likely present as a significant product in a separate phase. Because of the large amount of methane gas formation, this test was hydrogen limited with the reactor pressure surpassing the pressure set point after 1 h of operation and this factor is expected to have skewed the mechanism away from the high-use hydrogenation pathways, such as saturation of the aromatic ring. xi Elliott, D. C.; Hart, T. R.; Neuenschwander, G. G. “Chemical Processing in High-Pressure Aqueous Environments. 8. Improved Catalysts for Hydrothermal Gasification.” Ind. Eng. Chem. Res. 45(11) 3776-81, 2006.
Reaction SMILES: C([O-])([O-])=O.[K+].[K+].[CH2:7]([NH2:9])[CH3:8].Cl[C:11]1[C:16]([N+:17]([O-:19])=[O:18])=[CH:15][N:14]=[C:13]([C:20]([F:23])([F:22])[F:21])[CH:12]=1>C1COCC1.C(#N)C>[CH2:7]([NH:9][C:11]1[C:16]([N+:17]([O-:19])=[O:18])=[CH:15][N:14]=[C:13]([C:20]([F:23])([F:21])[F:22])[CH:12]=1)[CH3:8]
Reactant: O=[N+]([O-])c1cnc(C(F)(F)F)cc1Cl
Reactant: CCN
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: C1CCOC1
Product: CCNc1cc(C(F)(F)F)ncc1[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 2 h

Procedure:
K2CO3 (4.15 g, 30.01 mmol), and 2.0 M solution of EtNH2 (15 mL, 30.01 mmol) in THF are added o a solution of 4-chloro-5-nitro-2-trifluoromethyl-pyridine (3.4 g, 15.0 mmol) in acetonitrile (30 mL) under cold conditions. The reaction is complete after stirring at 0° C. for 2 h. Usual work up affords ethyl-(5-nitro-2-trifluoromethyl-pyridin-4-yl)-amine as an yellow-orange viscous oil. 1H NMR (300 MHz, CDCl3): δ 9.24 (s, 1H), 7.09 (s, 1H), 3.45 (t, J=7.2 Hz, 2H), 1.42 (t, J=7.2 Hz, 3H).
Reaction SMILES: [N:1]1([C:6]([CH:8]2[CH2:16][C:15]3[C:10](=[CH:11][C:12]([O:19][CH3:20])=[C:13]([O:17][CH3:18])[CH:14]=3)[C:9]2=[O:21])=[S:7])[CH:5]=[CH:4]N=C1.N[C:23]1[CH:24]=[C:25]([CH:28]=CC=1)[CH2:26][OH:27]>C1COCC1>[OH:27][CH2:26][C:25]1[CH:28]=[C:5]([NH:1][C:6]([CH:8]2[CH2:16][C:15]3[C:10](=[CH:11][C:12]([O:19][CH3:20])=[C:13]([O:17][CH3:18])[CH:14]=3)[C:9]2=[O:21])=[S:7])[CH:4]=[CH:23][CH:24]=1
Reactant: Nc1cccc(CO)c1
Reactant: COc1cc2c(cc1OC)C(=O)C(C(=S)n1ccnc1)C2
Solvent: C1CCOC1
Product: COc1cc2c(cc1OC)C(=O)C(C(=S)Nc1cccc(CO)c1)C2

Procedure:
2-(Imidazole-1-carbothioyl)-5,6-dimethoxy-indan-1-one, Intermediate B, (1.0 g, 3.3 mmol) was mixed with 3-aminobenzyl alcohol (0.40 g, 3.3 mmol), and 30 mL THF in a flask. 5,6-Dimethoxy-1-oxo-indan-2-carbothioic acid (3-hydroxymethyl-phenyl)-amide was obtained after stirring the reaction mixture for 4 hours at room temperature. HPLC/MS m/z 358 (M+H)+. The intermediate was not isolated, the mixture was mixed with hydrazine (0.13 mL, 4 mmol), and acetic acid (2–3 drops). The reaction was heated at 78° C. for 12 hours. The reaction solution was then diluted with ethyl acetate, washed with water, and dried over Na2SO4. The solvent was removed and the title compound was purified by HPLC with a C-18 reversed phase column and CH3CN—H2O-TFA as gradient solvents. The title compound, [3-(6,7-Dimethoxy-2,4-dihydro-indeno[1,2-c]pyrazol-3-ylamino)-phenyl]-methanol, Compound 36, was obtained as a solid TFA salt. MS m/z 338 (M+H)+; HPLC:100% (uv 214 mu);
Reaction SMILES: [CH3:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH:3]1[C:15]1[N:19]2[C:20]3[CH:26]=[CH:25][N:24](S(C4C=CC(C)=CC=4)(=O)=O)[C:21]=3[N:22]=[CH:23][C:18]2=[CH:17][N:16]=1.[OH-].[Na+].CC(O)=O>O1CCOCC1>[C:15]1([CH:3]2[CH:2]([CH3:1])[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:14])[CH3:13])=[O:9])[CH2:4]2)[N:19]2[C:20]3[CH:26]=[CH:25][NH:24][C:21]=3[N:22]=[CH:23][C:18]2=[CH:17][N:16]=1
Reactant: Cc1ccc(S(=O)(=O)n2ccc3c2ncc2cnc(C4CN(C(=O)OC(C)(C)C)CCC4C)n23)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: CC(=O)O
Product: CC1CCN(C(=O)OC(C)(C)C)CC1c1ncc2cnc3[nH]ccc3n12
Temperature: 60 °C
Yield: 92.8 %

Procedure:
To a solution of tert-butyl 4-methyl-3-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)piperidine-1-carboxylate (19.0 g, 37.3 mmol) in 1,4-dioxane (100 mL) was added aqueous NaOH (1N, 74.6 mL, 74.6 mmol). The reaction was heated at about 60° C. for about 30 min and allowed to cool to ambient temperature followed by the addition of 10% aqueous AcOH (250 mL). The mixture was extracted with with EtOAc (2×250 mL) and the combined organic layers were washed with brine (200 mL), dried over anhydrous Na2SO4, and filtered. The filtrate was concentrated under reduced pressure and purified by silica gel chromatography (330 g) eluting with a gradient of 10-70% EtOAc in heptane to provide tert-butyl 3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-methylpiperidine-1-carboxylate (12.3 g, 93%) as a white foam: LC/MS (Table 2, Method a) Rt=1.96 min; MS m/z: 356 (M+H)+.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]1([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][CH2:29]O)=[CH:22][CH:21]=1.C(Br)(Br)(Br)[Br:38]>C(Cl)Cl>[Br:38][CH2:29][CH2:28][CH2:27][O:26][C:23]1[CH:24]=[CH:25][C:20]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[CH:21][CH:22]=1
Reactant: BrC(Br)(Br)Br
Reactant: OCCCOc1ccc(-c2ccccc2)cc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: BrCCCOc1ccc(-c2ccccc2)cc1
Temperature: 25 °C

Procedure:
Triphenylphosphine (1.61 g, 6.14 mmol) was added to a solution of 3-(biphenyl-4-yloxy)-propan-1-ol (Example 291, Step 6) (1.00 g, 4.38 mmol) and carbon tetrabromide (1.81 g, 5.47 mmol) in CH2Cl2 (20 mL) at 0° C. The mixture was warmed to room temperature and stirred for about an hour and then extracted with ethyl acetate (50 mL). The organic layer was washed with H2O (3×50 mL) and brine (3×25 mL), and then dried (MgSO4), filtered and concentrated. The crude product was purified by silica gel column chromatography (silica gel, hexanes/ethyl acetate, 9:1) to produce 4-(3-bromo-propoxy)-biphenyl. 1H-NMR (200.15 MHz, CDCl3): d 7.57–7.29 (m, 7H), 6.98 (dd, 2H, J=6.72, 1.88), 4.45 (t, 2H, J=5.92), 3.62 (t, 2H, J=6.44), 2.34 (qn, 2H, J=5.92).
Reaction SMILES: [CH3:1][C:2]([C:12]1[C:20]2[O:19][CH2:18][CH2:17][C:16]=2[CH:15]=[CH:14][CH:13]=1)([CH3:11])[CH2:3][C:4]1([C:7]([F:10])([F:9])[F:8])[CH2:6][O:5]1.[N:21]1[CH:26]=[CH:25][C:24]([N:27]2[C:35]3[CH:34]=[CH:33][CH:32]=[C:31]([NH2:36])[C:30]=3[CH:29]=[N:28]2)=[CH:23][CH:22]=1>CS(C)=O.CO>[O:19]1[C:20]2[C:12]([C:2]([CH3:11])([CH3:1])[CH2:3][C:4]([CH2:6][NH:36][C:31]3[CH:32]=[CH:33][CH:34]=[C:35]4[C:30]=3[CH:29]=[N:28][N:27]4[C:24]3[CH:25]=[CH:26][N:21]=[CH:22][CH:23]=3)([OH:5])[C:7]([F:10])([F:8])[F:9])=[CH:13][CH:14]=[CH:15][C:16]=2[CH2:17][CH2:18]1
Reactant: Nc1cccc2c1cnn2-c1ccncc1
Reactant: CC(C)(CC1(C(F)(F)F)CO1)c1cccc2c1OCC2
Solvent: CS(C)=O
Solvent: CO
Product: CC(C)(CC(O)(CNc1cccc2c1cnn2-c1ccncc1)C(F)(F)F)c1cccc2c1OCC2
Temperature: 150 °C
Yield: 8.5 %

Procedure:
A mixture of racemic 7-{1,1-dimethyl-2-[2-(trifluoromethyl)-2-oxiranyl]ethyl}-2,3-dihydro-1-benzofuran (which may be prepared according to WO 04/063163, 27 mg, 0.095 mmol) and 1-(4-pyridinyl)-1H-indazol-4-amine (Intermediate 5) (20 mg, 0.095 mmol) was heated by microwave (200 W) at 150° C. for 20 minutes. The crude product was cooled, dissolved in DMSO/MeOH and purified by mass-directed autopreparation. The appropriate fractions were evaporated to give the title compound (4 mg).
Reaction SMILES: [CH3:1][C:2](C)([O-:4])[CH3:3].[K+].[C:7]1([CH2:13][C:14]#[N:15])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.Cl[C:17]1[CH:22]=[C:21]([O:23][CH2:24][C:25]#[C:26][CH3:27])[N:20]=[CH:19][N:18]=1.[Cl-].[NH4+]>O1CCCC1>[C:14]([CH:13]([C:17]1[CH:22]=[C:21]([O:23][CH2:24][C:25]#[C:26][CH3:27])[N:20]=[CH:19][N:18]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)#[N:15].[C:2]([C:3]1[CH:22]=[C:21]([O:23][CH2:24][C:25]#[C:26][CH3:27])[N:20]=[CH:19][N:18]=1)(=[O:4])[C:1]1[CH:11]=[CH:12][CH:7]=[CH:13][CH:14]=1
Reactant: N#CCc1ccccc1
Reactant: CC(C)(C)[O-]
Reactant: CC#CCOc1cc(Cl)ncn1
Agent: [Cl-]
Agent: [K+]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CC#CCOc1cc(C(=O)c2ccccc2)ncn1
Product: CC#CCOc1cc(C(C#N)c2ccccc2)ncn1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
In 5 ml of tetrahydrofuran was suspended 0.46 g of potassium t-butoxide, to which 0.39 g of phenylacetonitrile and 0.5 g of 4-chloro-6-(2-butynyloxy)pyrimidine were added, followed by stirring at room temperature for 8 hours. The reaction mixture was then poured into a saturated aqueous ammonium chloride solution and extracted three times with chloroform. The chloroform layers were combined and washed with a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate and then concentrated. The residue was subjected to silica gel column chromatography to give 0.16 g of 4-(α-cyanobenzyl)-6-(2-butynyloxy)pyrimidine (the present compound (74)) and 0.19 g of 4-benzoyl-6-(2-butynyloxy)pyrimidine (the present compound (75)).
Reaction SMILES: Br[CH2:2][CH2:3][N:4]([S:28]([CH3:31])(=[O:30])=[O:29])[C:5]1[C:6]([CH:25]2[CH2:27][CH2:26]2)=[CH:7][C:8]2[C:12]([CH:13]=1)=[N:11][N:10]([C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)[C:9]=2[C:21]([NH:23][CH3:24])=[O:22].Cl.[NH:33]1[CH2:36][CH:35]([OH:37])[CH2:34]1.C(=O)([O-])[O-].[K+].[K+]>CC#N>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([N:10]2[C:9]([C:21]([NH:23][CH3:24])=[O:22])=[C:8]3[C:12]([CH:13]=[C:5]([N:4]([CH2:3][CH2:2][N:33]4[CH2:36][CH:35]([OH:37])[CH2:34]4)[S:28]([CH3:31])(=[O:30])=[O:29])[C:6]([CH:25]4[CH2:27][CH2:26]4)=[CH:7]3)=[N:11]2)=[CH:15][CH:16]=1
Reactant: OC1CNC1
Reactant: CNC(=O)c1c2cc(C3CC3)c(N(CCBr)S(C)(=O)=O)cc2nn1-c1ccc(Cl)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CNC(=O)c1c2cc(C3CC3)c(N(CCN3CC(O)C3)S(C)(=O)=O)cc2nn1-c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To a stirred solution of 6-[2-bromoethyl(methylsulfonyl)amino]-2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-indazole-3-carboxamide (5 mg, 0.01 mmol) in MeCN (500 uL) was added azetidin-3-ol hydrochloride (6.6 mg, 0.06 mmol) followed by potassium carbonate (6 mg). The resultant suspension was heated at 65 deg C. in a sealed vial and after 3 days, cooled to RT then filtered through a cotton wool plug. The residue was washed with MeCN (2 mL) and the volatiles removed in vacuo. The residual colourless oil was purified by preparative HPLC/MS (MeCN/0.1% formic acid in water (v/v)-gradient elution) to give Compound (22) as a white amorphous solid (4.5 mg, 91%). 1H NMR (400 MHz, CD3CN) δ 7.90 (s, 1H), 7.63-7.53 (m, 4H), 7.42 (s, 1H), 7.03 (br s, 1H), 4.67-4.40 (m, 2H), 4.17 (br s, 2H), 3.96 (br s, 2H), 3.80 (br s, 1H), 3.38 (br s, J=41.2 Hz, 2H), 3.16 (s, 3H), 2.91 (d, J=4.8 Hz, 3H), 2.34-2.33 (m, 1H), 1.18-1.01 (m, 3H), 0.68-0.58 (m, 1H). ESI-MS m/z calculated for [M+H]+: 518.16. found: 518.10.
Reaction SMILES: [CH:1]([C:4]1[C:5](=[O:20])[NH:6][C:7](=[O:19])[NH:8][C:9]=1[S:10][C:11]1[CH:16]=[C:15]([CH3:17])[CH:14]=[C:13]([CH3:18])[CH:12]=1)([CH3:3])[CH3:2].Cl[CH2:22][C:23]1[CH:36]=[CH:35][C:34]2[C:33](=[O:37])[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:26](=[O:38])[C:25]=2[CH:24]=1>>[CH:24]1[C:25]2[C:26](=[O:38])[C:27]3[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:33](=[O:37])[C:34]=2[CH:35]=[CH:36][C:23]=1[CH2:22][N:8]1[C:9]([S:10][C:11]2[CH:12]=[C:13]([CH3:18])[CH:14]=[C:15]([CH3:17])[CH:16]=2)=[C:4]([CH:1]([CH3:3])[CH3:2])[C:5](=[O:20])[NH:6][C:7]1=[O:19]
Reactant: O=C1c2ccccc2C(=O)c2cc(CCl)ccc21
Reactant: Cc1cc(C)cc(Sc2[nH]c(=O)[nH]c(=O)c2C(C)C)c1
Product: Cc1cc(C)cc(Sc2c(C(C)C)c(=O)[nH]c(=O)n2Cc2ccc3c(c2)C(=O)c2ccccc2C3=O)c1
Yield: 32.2 %

Procedure:
5-Isopropyl-6-(3,5-dimethylphenyl)thio-2,4-pyrimidinedione and 2-chloromethyl anthraquinone were reacted by the same way with the example 1 to obtain the titled compound (165 mg, yield: 32.2%).
Reaction SMILES: [OH:1][C:2]([CH3:23])([CH3:22])/[CH:3]=[CH:4]/[CH:5]=[CH:6]/[CH2:7][C@H:8]([C:10]1[C@:11]2([CH3:21])[C@@H:16]([CH2:17][CH2:18][CH:19]=1)[C:15](=[O:20])[CH2:14][CH2:13][CH2:12]2)[CH3:9].[Si:24](C1NC=CN=1)([CH3:27])([CH3:26])[CH3:25]>C(Cl)Cl>[CH3:9][C@@H:8]([C:10]1[C@:11]2([CH3:21])[C@@H:16]([CH2:17][CH2:18][CH:19]=1)[C:15](=[O:20])[CH2:14][CH2:13][CH2:12]2)[CH2:7]/[CH:6]=[CH:5]/[CH:4]=[CH:3]/[C:2]([CH3:22])([O:1][Si:24]([CH3:27])([CH3:26])[CH3:25])[CH3:23]
Reactant: C[Si](C)(C)c1ncc[nH]1
Reactant: C[C@H](C/C=C/C=C/C(C)(C)O)C1=CCC[C@H]2C(=O)CCC[C@]12C
Solvent: ClCCl
Product: C[C@H](C/C=C/C=C/C(C)(C)O[Si](C)(C)C)C1=CCC[C@H]2C(=O)CCC[C@]12C

Procedure:
420 mg of (4aS,8aR)-5-((3E,5E)-(R)-7-hydroxy-1,7-dimethyl-octa-3,5-dienyl)-4a-methyl-3,4,4a,7,8,8a-hexahydro-2H-naphthalen-1-one were reacted at RT with 0.389 ml of TMS-imidazole (2 equivalents) in 1.3 ml of CH2Cl2. After 20 hours the mixture was poured onto crushed ice, extracted with ether, washed with brine, dried over magnesium sulfate and evaporated to dryness. Flash chromatography (SiO2, hexane/AcOEt=95/5) yielded 463 mg of (4aS,8aR)-5-[(3E,5E)-(R)-(1,7-dimethyl-7-trimethylsilanyloxy-octa-3,5-dienyl)]-4a-methyl-3,4,4a,7,8,8a-hexahydro-2H-naphthalen-1-one as colourless oil.
Reaction SMILES: [H-].[Na+].[CH3:3][CH:4]([OH:20])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:9][CH:8]=1.[H][H].Cl[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=1>CN(C)C=O.O>[CH3:3][CH:4]([O:20][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:9][CH:8]=1
Reactant: CC(O)COc1ccc(Oc2ccccc2)cc1
Reactant: Clc1ccccn1
Reactant: [H][H]
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(COc1ccc(Oc2ccccc2)cc1)Oc1ccccn1
Temperature: 25 °C
Yield: 79 %

Procedure:
To a suspension of sodium hydride (200 mg, 5.0 mmol; 60% in oil) in dimethylformamide (5 ml), a solution of 1-methyl-2-(4-phenoxyphenoxy)ethanol (1.22 g, 5.0 mmol) in dimethylformamide (3 ml) was dropwise added with stirring, and the mixture was kept at an inner temperature of 50° to 60° C. until the generation of hydrogen gas ceased. 2-Chloropyridine (684 mg, 6.0 mmol) was dropwise added thereto, followed by stirring at 100° to 110° C. for 5 hours. The reaction mixture was cooled to room temperature, poured into water (100 ml) and extracted with toluene (40 ml) three times. The toluene layer was dried over anhydrous magnesium sulfate, and the solvent was removed by evaporation. The residue was purified by silica gel column chromatography to give 2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine (1.27 g) as pale yellow liquid. nD20.5 1.5823. Upon being allowed to stand for a few days, the liquid solidified to give crystals. M.P., 49.7° C.
Reaction SMILES: [Cl:1][CH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=1.[C:13]1([P:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[Cl-].[PH4+]>C(#N)C>[Cl-:1].[C:3]1([CH2:2][P+:19]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: ClCc1cccc2ccccc12
Agent: [Cl-]
Agent: [PH4+]
Solvent: CC#N
Product: c1ccc([P+](Cc2cccc3ccccc23)(c2ccccc2)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
340 g (1.93 mol) of 1-chloromethylnaphthalene (Aldrich) are dissolved together with 505.7 g (1.93 mol) of triphenylphosphine in 2 l of acetonitrile. The mixture is subsequently boiled at reflux with stirring for 5 hours. The phosphonium chloride begins to precipitate out after about 2 hours. The mixture is left to cool at room temperature and the crystals are filtered off with suction.
Reaction SMILES: I[C:2]1[O:3][C:4]([C:7]2[N:12]=[C:11]([NH:13][C:14]3[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][N:15]=3)[CH:10]=[CH:9][CH:8]=2)=[CH:5][N:6]=1.[C:21]1(B(O)O)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:20][C:18]1[CH:17]=[CH:16][N:15]=[C:14]([NH:13][C:11]2[CH:10]=[CH:9][CH:8]=[C:7]([C:4]3[O:3][C:2]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[N:6][CH:5]=3)[N:12]=2)[CH:19]=1
Reactant: Cc1ccnc(Nc2cccc(-c3cnc(I)o3)n2)c1
Reactant: OB(O)c1ccccc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: Cc1ccnc(Nc2cccc(-c3cnc(-c4ccccc4)o3)n2)c1
Temperature: 90 °C
Reaction time: 18 h
Yield: 75.5 %

Procedure:
A solution of [6-(2-iodo-oxazol-5-yl)-pyridin-2-yl]-(4-methyl-pyridin-2-yl)-amine (46 mg, 0.121 mmol), phenylboronic acid (30 mg, 0.246 mmol), K2CO3 (37 mg, 0.268 mmol) and Pd(PPh3)4 (14 mg, 0.012 mmol) in a mixture of THF (4 ml) and water (2 ml) was stirred at 90° C. for 18 h. The cooled reaction mixture was treated with water and extracted with EtOAc. The combined organics were dried over MgSO4, filtered and evaporated under reduced pressure before purification by column chromatography on SiO2 eluting with 30% EtOAc in cyclohexane to afford the title compound as a pale orange solid (30 mg, 75%). 1H NMR (DMSO-d6, 300 MHz): δ=9.79 (s, 1H), 8.12 (m, 2H), 8.02 (s, 1H), 7.93 (s, 1H), 7.86 (s, 1H), 7.78 (m, 2H), 7.58 (m, 2H), 7.40 (t, J=7.0 Hz, 1H), 7.33 (t, J=7.0 Hz, 1H), 6.78 (d, J=5.0 Hz, 1H), 2.37 (s, 3H). (ESI+) m/z 329 (M+H)+. Retention time=2.84 mins (method 1).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:25])[C:4]1[CH:9]=[CH:8][C:7]([NH2:10])=[C:6]([CH2:11][S:12]([C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH:18]=[CH:17][CH:16]=2)(=[O:14])=[O:13])[CH:5]=1.Cl.[N:27]([O-])=O.[Na+].C(=O)(O)[O-].[Na+]>C1COCC1.O>[CH3:1][O:2][C:3]([C:4]1[CH:5]=[C:6]2[C:7](=[CH:8][CH:9]=1)[NH:10][N:27]=[C:11]2[S:12]([C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[CH:17][CH:16]=1)(=[O:13])=[O:14])=[O:25]
Reactant: O=N[O-]
Reactant: COC(=O)c1ccc(N)c(CS(=O)(=O)c2cccc3ccccc23)c1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: COC(=O)c1ccc2[nH]nc(S(=O)(=O)c3cccc4ccccc34)c2c1
Temperature: 3 °C

Procedure:
A mixture of 4-amino-3-(naphthalene-1-sulfonylmethyl)benzoic acid methyl ester (0.9 g, 2.5 mmoles) in THF (5 mL), and 4M HCl (10 mL) was stirred in a round bottom flask, under nitrogen, at 3° C. A solution of sodium nitrite (0.18 g, 2.62 mmoles) in H2O (1 mL) was added dropwise. The reaction mixture was poured into a cold solution of saturated sodium bicarbonate (100 mL) and extracted with EtOAc. Compound was dried over Na2SO4, and concentrated under vacuum to afford the title compound as an off white solid (0.82 g, 2.25 mmoles).
Reaction SMILES: [CH3:1][C@H:2]1[CH2:33][C:32]([CH3:34])=[CH:31][C@@H:30]([CH2:35][CH:36]=[CH2:37])[C:28](=[O:29])[CH2:27][C@H:26]([OH:38])[C@@H:25]([CH3:39])[C@@H:24](/[C:40](/[CH3:51])=[CH:41]/[C@H:42]2[CH2:47][C@@H:46]([O:48][CH3:49])[C@H:45]([OH:50])[CH2:44][CH2:43]2)[O:23][C:21](=[O:22])[C@H:20]2[N:15]([CH2:16][CH2:17][CH2:18][CH2:19]2)[C:13](=[O:14])[C:11](=[O:12])[C@:9]2([OH:52])[O:10][C@@H:5]([C@@H:6]([O:54][CH3:55])[CH2:7][C@H:8]2[CH3:53])[C@@H:4]([O:56][CH3:57])[CH2:3]1.N1C=CC=CC=1.[C:64](OC(=O)C)(=[O:66])[CH3:65]>ClCCl>[C:64]([O:50][CH:45]1[CH2:44][CH2:43][CH:42]([CH:41]=[C:40]([CH:24]2[CH:25]([CH3:39])[CH:26]([OH:38])[CH2:27][C:28](=[O:29])[CH:30]([CH2:35][CH:36]=[CH2:37])[CH:31]=[C:32]([CH3:34])[CH2:33][CH:2]([CH3:1])[CH2:3][CH:4]([O:56][CH3:57])[CH:5]3[O:10][C:9]([OH:52])([CH:8]([CH3:53])[CH2:7][CH:6]3[O:54][CH3:55])[C:11](=[O:12])[C:13](=[O:14])[N:15]3[CH:20]([CH2:19][CH2:18][CH2:17][CH2:16]3)[C:21](=[O:22])[O:23]2)[CH3:51])[CH2:47][CH:46]1[O:48][CH3:49])(=[O:66])[CH3:65]
Reactant: CC(=O)OC(C)=O
Reactant: C=CC[C@@H]1C=C(C)C[C@H](C)C[C@H](OC)[C@H]2O[C@@](O)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@H](/C(C)=C/[C@@H]3CC[C@@H](O)[C@H](OC)C3)[C@H](C)[C@@H](O)CC1=O)[C@H](C)C[C@@H]2OC
Agent: C=CC[C@@H]1/C=C(\C)C[C@H](C)C[C@H](OC)[C@H]2O[C@@](O)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@H](/C(C)=C/[C@@H]3CC[C@@H](O)[C@H](OC)C3)[C@H](C)[C@@H](O)CC1=O)[C@H](C)C[C@@H]2OC
Solvent: ClCCl
Solvent: c1ccncc1
Product: C=CCC1C=C(C)CC(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(OC(C)=O)C(OC)C3)C(C)C(O)CC1=O)C(C)CC2OC
Reaction time: 5 h

Procedure:
To a solution of the FR-900506 substance (10.4 mg) in dichloromethane (0.2 ml) were added pyridine (0.1 ml) and acetic anhydride (0.05 ml) at room temperature, and the mixture was stirred for 5 hours. The solvent was removed from the reaction mixture under reduced pressure. The residue was subjected to silica gel thin layer chromatography (developing solvent: diethyl ether and dichloromethane, 1:2 v/v) to give 12-[2-(4-acetoxy-3-methoxycyclohexyl)-1-methylvinyl]-17-allyl-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone (6.0 mg).