Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][N:11]2[N:14]=[C:15]([N:17]([CH2:19][CH2:20][F:21])[CH3:18])[N:16]=[C:10]2[CH:9]=1)(C)(C)C.[ClH:23].O1CCOCC1>>[ClH:23].[F:21][CH2:20][CH2:19][N:17]([CH3:18])[C:15]1[N:16]=[C:10]2[CH:9]=[C:8]([NH2:7])[CH:13]=[CH:12][N:11]2[N:14]=1
Reactant: CN(CCF)c1nc2cc(NC(=O)OC(C)(C)C)ccn2n1
Agent: Cl
Solvent: C1COCCO1
Product: CN(CCF)c1nc2cc(N)ccn2n1
Temperature: 25 °C
Reaction time: 16 h
Yield: 96.3 %

Procedure:
A mixture of {2-[(2-fluoro-ethyl)-methyl-amino]-[1,2,4]triazolo[1,5-a]pyridin-7-yl}-carbamic acid tert-butyl ester (1.7 g, 5.5 mmol) and hydrochloric acid in dioxane (4N, 39.2 ml, 156.7 mmol) was stirred at 25° C. for 16 h. Volatiles were removed in vacuo to afford N2-(2-Fluoro-ethyl)-N2-methyl-[1,2,4]triazolo[1,5-a]pyridine-2,7-diamine hydrochloride as a light yellow solid (1.3 g, 96.3%). MS: m/z=210.2 (M+H+).
Reaction SMILES: C(O[CH:4]([OH:9])[C:5]([F:8])([F:7])[F:6])C.C(=O)([O-])[O-].[K+].[K+].Cl.[N+:17]([CH2:20][CH2:21][CH3:22])([O-:19])=[O:18]>>[F:8][C:5]([F:6])([F:7])[CH:4]([OH:9])[CH:20]([N+:17]([O-:19])=[O:18])[CH2:21][CH3:22]
Reactant: CCC[N+](=O)[O-]
Reactant: CCOC(O)C(F)(F)F
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CCC(C(O)C(F)(F)F)[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 48 h

Procedure:
A mixture of 1-nitropropane (10 mL), trifluoroacetaldehyde ethyl hemiacetal (20.2 mL), and potassium carbonate (15.4 g) was stirred at 25° C. for 48 h. The solution was made acidic by addition of 1N hydrochloric acid and the product extracted into dichloromethane. The solution was dried (MgSO4) and the solvent evaporated to give an oil, which was distilled (60° C., 133 Pa) to provide 1,1,1-trifluoro-3-nitro-2-pentanol (15 g) as a mixture of diastereoisomers; MS: m/z=188(M+1).
Reaction SMILES: Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:4][CH2:3]1.C([O-])([O-])=O.[K+].[K+].Br[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1>CN(C=O)C.O>[N:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[N:2]1[CH2:7][CH2:6][CH:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:4][CH2:3]1
Reactant: Brc1ccccn1
Reactant: CCOC(=O)CC1CCNCC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)CC1CCN(c2ccccn2)CC1
Temperature: 130 °C
Reaction time: 16 h
Yield: 25.1 %

Procedure:
To a stirred solution of ethyl 2-(piperidin-4-yl)acetate, hydrochloride (2.0 g, 9.63 mmol) in DMF (40 mL) was added K2CO3 (3.99 g, 28.9 mmol) followed by 2-bromopyridine (1.521 g, 9.63 mmol) and stirred at 130° C. for 16 h. Reaction mixture was diluted with water (200 mL) and extracted with ethyl acetate (2×100 mL). The combined organic layer was washed with water (2×100 mL), brine (100 mL) and dried over Na2SO4 filtered and concentrated under reduced pressure. The residues was purified by column chromatography using 100-200 silica gel by eluting with 20% ethyl acetate in petroleum ether to afford ethyl 2-(1-(pyridin-2-yl)piperidin-4-yl)acetate (600 mg, 19.86% yield) as color less liquid. LCMS (ES) m/e 249.20 (M+H)+.
Reaction SMILES: [CH2:1]1[O:11][C:4]2([CH2:9][CH2:8][C:7](=[O:10])[CH2:6][CH2:5]2)[O:3][CH2:2]1.[H-].[Na+].[CH:14](OCC)=[O:15]>C(O)C.O1CCCC1>[OH:15][CH:14]=[C:8]1[C:7](=[O:10])[CH2:6][CH2:5][C:4]2([O:3][CH2:2][CH2:1][O:11]2)[CH2:9]1
Reactant: O=C1CCC2(CC1)OCCO2
Reactant: CCOC=O
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCO
Product: O=C1CCC2(CC1=CO)OCCO2

Procedure:
1,4-Cyclohexanedione monoethylene ketal (5.00 g) was added to a mixture of sodium hydride (1.40 g of a 60% suspension in mineral oil), 10 ml of ethyl formate, 1 drop of ethanol and 200 ml of tetrahydrofuran. The reaction mixture was heated at reflux for 2.5 hours, cooled and partitioned between water and ethyl ether. The ethereal layer was extracted several times with 0.5N sodium hydroxide and the combined aqueous portions were washed once with ether. The aqueous solution was acidified slowly to a pH of 4 with 5N hydrochloric acid and the slurry was exhaustively extracted with dichloromethane. The combined extracts were dried over magnesium sulfate and concentrated in vacuo to provide a dark oil. The oil was distilled bulb-to-bulb (120° C./lmm) to afford 7-(hydroxymethylene)-1,4-dioxaspiro-[4.5]decan-8-one as a colorless oil.
Reaction SMILES: [Br:1][C:2]1[O:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.[NH2:9][N:10]1[CH2:15][CH2:14][NH:13][C:12](=[O:16])[C:11]1=[O:17]>C(O)(=O)C>[Br:1][C:2]1[O:8][C:5]([CH:6]=[N:9][N:10]2[CH2:15][CH2:14][NH:13][C:12](=[O:16])[C:11]2=[O:17])=[CH:4][CH:3]=1
Reactant: NN1CCNC(=O)C1=O
Reactant: O=Cc1ccc(Br)o1
Solvent: CC(=O)O
Product: O=C1NCCN(N=Cc2ccc(Br)o2)C1=O
Reaction time: 0.5 h
Yield: 38.5 %

Procedure:
1.9 pts. by wt. of 5-bromofurfural, 1.3 pts. by wt. of 1-amino-2,3-dioxo-piperazine and 7 pts. by vol. of glacial acetic acid were warmed to 90° for 10 minutes and then left for 30 minutes at RT. The precipitate is filtered off, washed with 3 pts. by vol. of glacial acetic acid and recrystallised from dimethylformamide, with the addition of animal charcoal. 1.1 pts. by wt. (38.5%) of 1-(5-bromofurfurylideneamino)-2,3-dioxo-piperazine are obtained as yellowish crystals of decomp. pt. 220°.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][CH2:10][OH:11])=[CH:4][CH:3]=1.C1(C=CC(O)=CC=1)O>C(O)=O>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[CH:9][CH:10]=[O:11])=[CH:4][CH:3]=1
Reactant: Cc1ccc(C#CCO)cc1
Agent: Oc1ccc(O)cc1
Solvent: O=CO
Product: Cc1ccc(C=CC=O)cc1
Yield: 80 %

Procedure:
A mixture of 250 g of 75% strength aqueous formic acid, 50 g of p-methylphenylethynylcarbinol and 0.5 g of hydroquinone is refluxed for 1 hour and then worked up as described in Example 1 to give 40 g (corresponding to 80% of theory) of p-methylcinnamaldehyde having a boiling point of 90°-95° C./0.1 mbar.
Reaction SMILES: [NH2:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8]CC)=[O:7])=[CH:4][CH:3]=1.[CH2:13]([S:17](Cl)(=[O:19])=[O:18])[CH2:14][CH2:15][CH3:16]>N1C=CC=CC=1>[CH2:13]([S:17]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([OH:8])=[O:7])=[CH:11][CH:12]=1)(=[O:19])=[O:18])[CH2:14][CH2:15][CH3:16]
Reactant: CCOC(=O)c1ccc(N)cc1
Reactant: CCCCS(=O)(=O)Cl
Solvent: c1ccncc1
Product: CCCCS(=O)(=O)Nc1ccc(C(=O)O)cc1

Procedure:
In a manner similar to Preparation 9 react ethyl 4-aminobenzoate with 1-butanesulfonyl chloride and pyridine to obtain the title compound.
Reaction SMILES: Br[C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][NH:6]2.[NH2:11][CH:12]([C:14]1[CH:15]=[C:16]([Cl:30])[C:17]([CH3:29])=[C:18]([C:27]#[N:28])[C:19]=1[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=1)[CH3:13].C(N(CC)C(C)C)(C)C>C(O)(C)C>[Cl:30][C:16]1[C:17]([CH3:29])=[C:18]([C:27]#[N:28])[C:19]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=2)=[C:14]([CH:12]([NH:11][C:2]2[N:10]=[CH:9][N:8]=[C:7]3[C:3]=2[N:4]=[CH:5][NH:6]3)[CH3:13])[CH:15]=1
Reactant: Brc1ncnc2[nH]cnc12
Reactant: Cc1c(Cl)cc(C(C)N)c(-c2cccc(F)c2)c1C#N
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(C)O
Product: Cc1c(Cl)cc(C(C)Nc2ncnc3[nH]cnc23)c(-c2cccc(F)c2)c1C#N
Temperature: 90 °C

Procedure:
A mixture of 6-bromo-9H-purine (41 mg, 0.21 mmol), 6-(1-aminoethyl)-4-chloro-3′-fluoro-3-methylbiphenyl-2-carbonitrile (50 mg, 0.2 mmol), and N,N-diisopropylethylamine (0.060 mL, 0.35 mmol) in isopropyl alcohol (0.7 mL) was heated at 90° C. under nitrogen overnight. The mixture was evaporated and the resulting mixture was purified on RP-HPLC (XBridge C18 Column, eluting with a gradient of acetonitrile in water with 0.2% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product. LCMS calculated for C21H17ClFN6 (M+H)+: m/z=407.1. found: 407.1.
Reaction SMILES: [CH:1]([C:3]([CH:5]=[CH2:6])=[O:4])=[CH2:2].[NH2:7][C@H:8]1[CH2:39][CH2:38][C:11]2[N:12]=[C:13]([NH:15][C:16](=[O:37])[C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([CH2:23][N:24]4[CH:28]=[C:27]([C:29]5[CH:34]=[CH:33][C:32]([C:35]#[N:36])=[CH:31][CH:30]=5)[CH:26]=[N:25]4)[CH:18]=3)[S:14][C:10]=2[CH2:9]1>C(Cl)Cl.CO>[C:35]([C:32]1[CH:31]=[CH:30][C:29]([C:27]2[CH:26]=[N:25][N:24]([CH2:23][C:19]3[CH:18]=[C:17]([CH:22]=[CH:21][CH:20]=3)[C:16]([NH:15][C:13]3[S:14][C:10]4[CH2:9][C@@H:8]([N:7]5[CH2:6][CH2:5][C:3](=[O:4])[CH2:1][CH2:2]5)[CH2:39][CH2:38][C:11]=4[N:12]=3)=[O:37])[CH:28]=2)=[CH:34][CH:33]=1)#[N:36]
Reactant: C=CC(=O)C=C
Reactant: N#Cc1ccc(-c2cnn(Cc3cccc(C(=O)Nc4nc5c(s4)C[C@@H](N)CC5)c3)c2)cc1
Solvent: ClCCl
Solvent: CO
Product: N#Cc1ccc(-c2cnn(Cc3cccc(C(=O)Nc4nc5c(s4)C[C@@H](N4CCC(=O)CC4)CC5)c3)c2)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 28.9 %

Procedure:
Add a solution of divinyl ketone (0.08 g 1.03 mmol) in 1 mL of CH2Cl2 to a solution of N—((S)-6-amino-4,5,6,7-tetrahydro-benzothiazol-2-yl)-3-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-benzamide (0.47 g, 1.03 mmol) in 10 mL of CH2Cl2 and 10 mL of MeOH. Stir the solution for 3 h at room temperature and concentrate the mixture. Purify the residue via column chromatography eluting with 1-10% CH2Cl2/MeOH to give 0.16 g, 30% yield of 3-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-N—[(S)-6-(4-oxo-piperidin-1-yl)-4,5,6,7-tetrahydro-benzothiazol-2-yl]-benzamide. Both 1 cms and NMR show that the product exists as a mixture of ketone and hydrate. MS, ES+ 555.70 (M+H2O+H), rt 1.21 min.
Reaction SMILES: [NH2:1][CH:2]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:3]([O:5][CH2:6][CH3:7])=[O:4].Cl.[O-:20][C:21]#[N:22].[K+]>C(O)C.O>[NH:1]([CH:2]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:21]([NH2:22])=[O:20]
Reactant: N#C[O-]
Reactant: CCOC(=O)CCCCCCC(N)C(=O)OCC
Agent: Cl
Agent: [K+]
Solvent: O
Solvent: CCO
Product: CCOC(=O)CCCCCCC(NC(N)=O)C(=O)OCC
Temperature: 25 °C
Reaction time: 7 h

Procedure:
A stirred solution of diethyl 2-aminononanedioate (10 g) in ethanol (77 ml) was cooled in ice-water and treated with 2N hydrochloric acid (38.6 ml) followed by a solution of potassium cyanate (6.255 g) in water (20 ml). The cooling bath was removed and the suspension was stirred for 7 hours at room temperature then set aside overnight. The ethanol was evaporated in vacuo and the residue was shaken with water and chloroform; the chloroform phase was separated, washed with water and dried (MgSO4), and the chloroform was evaporated to give an oil which was heated on the steam bath for 6 hours. The resulting oil crystallised on standing at room temperature. The crystals were stirred with ether and collected, affording pure diethyl 2-ureidononanedioate, m.p. 79°-80° C.
Reaction SMILES: [CH:1]([NH:4][CH2:5][CH2:6][NH:7][C:8](=[O:16])[CH2:9][N:10]1[CH2:14][CH2:13][CH2:12][C:11]1=[O:15])([CH3:3])[CH3:2].[CH3:17][Si:18]([CH2:21]Cl)([CH3:20])[CH3:19]>C(N(CC)CC)C>[CH:1]([N:4]([CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[CH2:5][CH2:6][NH:7][C:8](=[O:16])[CH2:9][N:10]1[CH2:14][CH2:13][CH2:12][C:11]1=[O:15])([CH3:3])[CH3:2]
Reactant: CC(C)NCCNC(=O)CN1CCCC1=O
Reactant: C[Si](C)(C)CCl
Solvent: CCN(CC)CC
Product: CC(C)N(CCNC(=O)CN1CCCC1=O)C[Si](C)(C)C
Temperature: 150 °C
Reaction time: 24 h
Yield: 50.7 %

Procedure:
A mixture of 5.00 g (22.0 mmol) of N-[2-(isopropylamino)ethyl]-2-oxo-pyrrolidineacetamide, 8.10 g (66.0 mmol) of trimethylsilylmethyl chloride, 30 ml of triethylamine and 50 ml of N,N-dimethylformaide was stirred at 150° C. for 24 hours in a shield tube. After cooled, the reaction mixture was concentrated in vacuo and chromatographed the residue on alumina column to afford 3.5 g (Yield: 51.3%) of the desired compound as colorless oil.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH3:12])[C:3]=1[C:4]([OH:6])=O.C(N(C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:46]([O:53][C:54]1[CH:59]=[C:58]([NH:60][C:61]2[N:66]=[C:65]([N:67]3[CH2:72][C@@H:71]([NH:73][C:74]([O:76][C:77]([CH3:80])([CH3:79])[CH3:78])=[O:75])[CH2:70][C@@H:69]([NH:81][C:82]([O:84][C:85]([CH3:88])([CH3:87])[CH3:86])=[O:83])[CH2:68]3)[N:64]=[C:63]([N:89]3[CH2:94][C@@H:93]([NH:95][C:96]([O:98][C:99]([CH3:102])([CH3:101])[CH3:100])=[O:97])[CH2:92][C@@H:91]([NH:103][C:104]([O:106][C:107]([CH3:110])([CH3:109])[CH3:108])=[O:105])[CH2:90]3)[N:62]=2)[CH:57]=[CH:56][C:55]=1[NH2:111])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>CN(C=O)C>[CH2:46]([O:53][C:54]1[CH:59]=[C:58]([NH:60][C:61]2[N:66]=[C:65]([N:67]3[CH2:72][C@@H:71]([NH:73][C:74]([O:76][C:77]([CH3:78])([CH3:79])[CH3:80])=[O:75])[CH2:70][C@@H:69]([NH:81][C:82]([O:84][C:85]([CH3:88])([CH3:87])[CH3:86])=[O:83])[CH2:68]3)[N:64]=[C:63]([N:89]3[CH2:90][C@@H:91]([NH:103][C:104]([O:106][C:107]([CH3:110])([CH3:109])[CH3:108])=[O:105])[CH2:92][C@@H:93]([NH:95][C:96]([O:98][C:99]([CH3:102])([CH3:101])[CH3:100])=[O:97])[CH2:94]3)[N:62]=2)[CH:57]=[CH:56][C:55]=1[NH:111][C:4](=[O:6])[C:3]1[C:7]([O:11][CH3:12])=[CH:8][CH:9]=[CH:10][C:2]=1[OH:1])[C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1
Reactant: CC(C)(C)OC(=O)N[C@@H]1C[C@H](NC(=O)OC(C)(C)C)CN(c2nc(Nc3ccc(N)c(OCc4ccccc4)c3)nc(N3C[C@H](NC(=O)OC(C)(C)C)C[C@H](NC(=O)OC(C)(C)C)C3)n2)C1
Reactant: COc1cccc(O)c1C(=O)O
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COc1cccc(O)c1C(=O)Nc1ccc(Nc2nc(N3C[C@H](NC(=O)OC(C)(C)C)C[C@H](NC(=O)OC(C)(C)C)C3)nc(N3C[C@H](NC(=O)OC(C)(C)C)C[C@H](NC(=O)OC(C)(C)C)C3)n2)cc1OCc1ccccc1
Temperature: 80 °C
Reaction time: 0.42 h
Yield: 34.5 %

Procedure:
2-Hydroxy-6-methoxy-benzoic acid (87) (0.067 g=0.4 mmol), iPr2EtN (0.6 mmol) and HBTU (0.44 mmol) were dissolved in DMF (2 mL) and shaken in a sealed vial for 25 min. 2-Benzyloxy-N4-(4,6-bis-((3R,5S)-3,5-bis-(tert-butoxycarbonylamino)-piperidin-1-yl)-[1,3,5]triazin-2-yl)-benzene-1,4-diamine (83) (0.184 g, 0.2 mmol) was added and the mixture was heated to 80° C. for 3 h. LC-MS indicated complete coupling at this point. Upon concentrating, the crude product was dissolved in CHCl3 (4 mL), washed with aqueous sat. NaHCO3 (2×2 mL), water (2×2 mL) and concentrated to dryness. Purification by ISCO (15–100% EtOAc/hexanes) gave the desired product (88) (0.073 g, 0.069 mmol, 34.5% yield). LC-MS (ESI): (exact mass: 1069.56) m/e═1070.9 [M+1]+ (100%).
Reaction SMILES: S(Cl)([Cl:3])=O.O[CH2:6][C:7]1[C:15]2[O:14][C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:12][C:11]=2[CH:10]=[CH:9][CH:8]=1.N1C=CC=CC=1>C(Cl)Cl>[Cl:3][CH2:6][C:7]1[C:15]2[O:14][C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:12][C:11]=2[CH:10]=[CH:9][CH:8]=1
Reactant: O=S(Cl)Cl
Reactant: OCc1cccc2cc(-c3ccccc3)oc12
Solvent: ClCCl
Solvent: c1ccncc1
Product: ClCc1cccc2cc(-c3ccccc3)oc12
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 83 %

Procedure:
Thionyl chloride (0.65 ml) is added to a mixture of 7-hydroxymethyl-2-phenylbenzofuran (1.0 g), pyridine (0.38 ml) and methylene chloride (8 ml) under ice-cooling, and the mixture is stirred at room temperature for 30 minutes. The mixture is concentrated under reduced pressure to remove solvent, and the residue is dissolved in ethyl acetate. The solution is washed with water, dried and concentrated under reduced pressure to remove solvent. The residue is recrystallized from n-hexane, whereby 7-chloromethyl-2-phenylbenzofuran (0.9 g) is obtained. Yield: 83%.
Reaction SMILES: [CH3:1][C:2]1([CH3:31])[CH2:7][C:6](=[O:8])[C:5](=[C:9]([NH:11][C@@H:12]2[C@@H:25]([OH:26])[C@H:24]([OH:27])[C@@H:23]([CH2:28][OH:29])[O:22][C@@H:13]2[O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH3:10])[C:4](=[O:30])[CH2:3]1.[C:32]1([C:38](Br)([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>CN(C=O)C.N1C=CC=CC=1>[CH3:1][C:2]1([CH3:31])[CH2:7][C:6](=[O:8])[C:5](=[C:9]([NH:11][C@@H:12]2[C@@H:25]([OH:26])[C@H:24]([OH:27])[C@@H:23]([CH2:28][O:29][C:38]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)([C:45]3[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=3)[C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=3)[O:22][C@@H:13]2[O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH3:10])[C:4](=[O:30])[CH2:3]1
Reactant: CC(N[C@H]1[C@@H](OCc2ccccc2)O[C@H](CO)[C@@H](O)[C@@H]1O)=C1C(=O)CC(C)(C)CC1=O
Reactant: BrC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Solvent: c1ccncc1
Product: CC(N[C@H]1[C@@H](OCc2ccccc2)O[C@H](COC(c2ccccc2)(c2ccccc2)c2ccccc2)[C@@H](O)[C@@H]1O)=C1C(=O)CC(C)(C)CC1=O
Temperature: 100 °C
Reaction time: 15 h
Yield: 66.9 %

Procedure:
A mixture of Benzyl 2-Deoxy-2-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethylamino]-α-D-glucopyranoside (100 mg, 0.23 mmol), triphenylmethylbromide (149 mg, 0.46 mmol) in DMF/pyridine 1:1 (2 ml) was stirred at 100° C. for 15 h. The reaction mixture was evaporated, the residue was taken up in CHCl3 (10 ml), washed with water (3 ml), dried over MgSO4 and concentrated. The residue was purified by chromatography using CHCl3/MeOH 10:1 as the mobile phase to give Benzyl 2-Deoxy-2-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethylamino]-6-O-triphenylmethyl-α-D-glucopyranoside (14) (104 mg, 64%).
Reaction SMILES: [CH2:1]([C:3]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][NH:5][N:4]=1)[CH3:2].[CH3:12][O:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1.N1C=CC=CC=1>CN(C)C(=O)C.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH2:1]([C:3]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][N:5]([C:18]2[CH:17]=[CH:16][CH:15]=[C:14]([O:13][CH3:12])[CH:19]=2)[N:4]=1)[CH3:2]
Reactant: COc1cccc(B(O)O)c1
Reactant: CCc1n[nH]cc1C(=O)OC
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: c1ccncc1
Solvent: CC(=O)N(C)C
Product: CCc1nn(-c2cccc(OC)c2)cc1C(=O)OC
Temperature: 25 °C
Reaction time: 8 h
Yield: 54.5 %

Procedure:
Methyl 3-ethyl-1H-pyrazole-4-carboxylate (2.5 g) synthesized in Example 39(1) was dissolved in N,N-dimethylacetamide (50 mL), 3-methoxyphenylboronic acid (5.0 g), copper acetate (6.0 g) and pyridine (5.3 mL) were added, and the mixture was stirred at room temperature overnight. The reaction mixture was filtered through celite, 1N hydrochloric acid (50 mL) was added to the filtrate, and the mixture was extracted with diethyl ether. The extract was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2, volume ratio) to give the title object compound (2.3 g, 54%) as a pale-yellow oil.
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([CH3:12])=[N:7]2.[CH3:13][C:14]1[CH:15]=[CH:16][C:17]([S:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[C:18]([NH2:20])[CH:19]=1>CCO>[CH3:12][C:6]1[N:7]=[C:8]2[C:3]([C:2]([NH:20][C:18]3[CH:19]=[C:14]([CH3:13])[CH:15]=[CH:16][C:17]=3[S:21][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)=[CH:11][CH:10]=[N:9]2)=[CH:4][CH:5]=1
Reactant: Cc1ccc(Sc2ccccc2)c(N)c1
Reactant: Cc1ccc2c(Cl)ccnc2n1
Solvent: CCO
Product: Cc1ccc(Sc2ccccc2)c(Nc2ccnc3nc(C)ccc23)c1

Procedure:
A stirred solution of the product from Example 1d (65 mg, 0.36 mmol) and the product from Example 1f (77 mg, 0.36 mmol) in 3 mL of EtOH was heated at 80° C. for 7 h. Concentrated under vacuum. Recrystallized from THF with a few drops of MeOH. Filtration gave the title compound as the hydrochloride salt as a white solid (62 mg, 43%) 1H NMR (300 MHz, CDCl3) δ ppm: 1.62 (brs, 1H) 2.43 (s, 3H) 2.52 (s, 3H) 6.02 (d, J=7.0 Hz, 1H) 7.05-7.35 (m, 8H) 7.70 (brs, 1H) 8.00 (d, J=7.0 Hz, 1H) 8.85 (d, J=8.5 Hz, 1H) 10.80 (brs, 1H); MS (ESI+) m/z 358 (M−Cl)+; (ESI−) m/z 356 (M−HCl)−.
Reaction SMILES: [C:1]1([O:8][CH3:9])[C:2](=[CH:4][CH:5]=[CH:6][CH:7]=1)[OH:3]>[Ru]>[CH3:9][O:8][CH:1]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:2]1[OH:3]
Reactant: COc1ccccc1O
Agent: [Ru]
Product: COC1CCCCC1O
Yield: 40 %

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: [CH3:1][CH2:2][CH2:3][CH2:4][C:5]([C@H:8]([OH:27])/[CH:9]=[CH:10]/[C@@H:11]1[C@@H:16]([CH2:17]/[CH:18]=[CH:19]\[CH2:20][CH2:21][CH2:22][C:23]([OH:25])=[O:24])[C:14](=[O:15])[CH2:13][C@H:12]1[OH:26])([CH3:7])[CH3:6].[CH:28](Cl)(Cl)Cl.C(Cl)(Cl)Cl>>[CH3:1][CH2:2][CH2:3][CH2:4][C:5]([C@@H:8]([OH:27])/[CH:9]=[CH:10]/[C@@H:11]1[C@@H:16]([CH2:17]/[CH:18]=[CH:19]\[CH2:20][CH2:21][CH2:22][C:23]([O:25][CH3:28])=[O:24])[C:14](=[O:15])[CH2:13][C@H:12]1[OH:26])([CH3:7])[CH3:6]
Reactant: CCCCC(C)(C)[C@H](O)/C=C/[C@H]1[C@H](O)CC(=O)[C@@H]1C/C=C\CCCC(=O)O
Reactant: ClC(Cl)Cl
Product: CCCCC(C)(C)[C@@H](O)/C=C/[C@H]1[C@H](O)CC(=O)[C@@H]1C/C=C\CCCC(=O)OC
Reaction time: 6 h

Procedure:
2 mg 3H labelled 16,16-dimethyl PGE2, methyl ester Ono 802 ex May and Baker is dissolved in 0.67 g ethanol C2H5OH, 0.67 g chloroform CHCl3 is added. A slice of the polymer 1 mm×11 mm×22 mm weighing 0.2678 g is added to the Ono solution in a polythene bag which is then sealed. After 6 hours swelling the bag is cut open and the swollen gel is weighed. Uptake 0.97 g solution i.e. 1.45 mg Ono. The sample is then dried and the in vitro release of Ono into phosphate buffer pH 7.4 at 37° is measured as in Ex. 12. The half life of Ono in this sample is 6.3 hours. The results for 3 different thicknesses of polymer sample are given to the Table.