Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[C:2]1C=CC(O)=CC=1.C(=O)([O-])[O-].[K+].[K+].[I:15][C:16]1[CH:32]=[CH:31][C:19]([O:20][CH:21]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH3:22])=[CH:18][CH:17]=1>CN(C=O)C>[I:15][C:16]1[CH:32]=[CH:31][C:19]([O:20][CH:21]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:2])[CH3:22])=[CH:18][CH:17]=1
Reactant: CCCCCCCCC(C)Oc1ccc(I)cc1
Reactant: Oc1ccc(I)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCCCCCCCC(C)Oc1ccc(I)cc1
Temperature: 84 °C
Reaction time: 13 h
Yield: 31 %

Procedure:
The above product (31.3 g, 136.7 mmol) was reacted with 4-iodophenol (30.1 g, 136.8 mmol), and potassium carbonate (18.9 g, 136.7 mmol) in DMF (270 ml) at 80° C. as for 2-(4-iodophenoxy)decane. After stirring for 13 hrs, the reaction was analyzed by 1H NMR indicating that the reaction was about 66% complete. The temperature of the oil was increased 84° C. After an additional 34 hrs, 1H NMR spectral analysis indicated that the reaction was complete. The reaction was processed as for 2-(4-iodophenoxy)-decane except at 2 times the volume to give a light yellow oil. This product was further purified by flash column chromatography (silica, hexanes) to give 2-(4-iodophenoxy)-undecane (16.1 g, 31%) as a clear oil.
Reaction SMILES: [NH3:1].Cl[C:3]1[C:8]([CH3:9])=[N:7][N:6]2[C:10]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=3)=[N:11][N:12]=[C:5]2[N:4]=1>CO>[NH2:1][C:3]1[C:8]([CH3:9])=[N:7][N:6]2[C:10]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=3)=[N:11][N:12]=[C:5]2[N:4]=1
Reactant: N
Reactant: Cc1nn2c(Cc3ccc(O)cc3)nnc2nc1Cl
Solvent: CO
Product: Cc1nn2c(Cc3ccc(O)cc3)nnc2nc1N
Temperature: 70 °C

Procedure:
NH3 gas was bubbled through a solution of 4-(7-chloro-6-methyl-[1,2,4]triazolo[4,3-b][1,2,4]triazin-3-ylmethyl)-phenol (70 mg, 0.25 mmol) in methanol (5 mL) at 0° C. The saturated solution was stirred at 70° C. until the starting material disappeared. After evaporation of solvent, the residue was purified on a silica gel column eluting with 10% methanol in dichloromethane to provide 4-(7-amino-6-methyl-[1,2,4]triazolo[4,3-b][1,2,4]triazin-3-ylmethyl)-phenol (35 mg). 1H-NMR (400 MHz, DMSO-d6) δ 9.22 (s, 1H), 7.05 (d, 2H), 6.65 (d, 2H), 4.12 (s, 2H), 2.35 (s, 3H). MS (m/z) 257 [M+1].
Reaction SMILES: [Mg].[CH:2](I)([CH3:4])[CH3:3].[N:6]1[CH:11]=[CH:10][CH:9]=[C:8]2[CH2:12][C:13]3[CH:19]=[C:18]([CH:20]=[O:21])[CH:17]=[CH:16][C:14]=3[O:15][C:7]=12.[Cl-].[NH4+]>CCOCC>[N:6]1[CH:11]=[CH:10][CH:9]=[C:8]2[CH2:12][C:13]3[CH:19]=[C:18]([CH:20]([OH:21])[CH:2]([CH3:4])[CH3:3])[CH:17]=[CH:16][C:14]=3[O:15][C:7]=12
Reactant: O=Cc1ccc2c(c1)Cc1cccnc1O2
Reactant: CC(C)I
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: CCOCC
Product: CC(C)C(O)c1ccc2c(c1)Cc1cccnc1O2

Procedure:
A Grignard reagent is prepared from 2.14 g of magnesium and 13.1 g of isopropyl iodide in 50 ml of ether in a conventional manner. 12.5 g of 5H-[1]benzopyrano[2,3-b]pyridine-7-carbaldehyde is added to the Grignard reagent, and the mixture is stirred under reflux for 2 hours. After cooling, a saturated ammonium chloride solution is added to the reaction mixture, and the ether layer is separated. The ether is distilled off to give crude 1-(5H-[1]benzopyrano [2,3-b]pyridin-7-yl)-2-methyl-1-propanol.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]([CH:14]1[CH2:16][CH2:15]1)=[O:13])=[C:5]2Cl.[NH2:18][C:19]1[CH:20]=[N:21][C:22]([N:25]2[CH2:29][CH2:28][CH:27]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:26]2)=[N:23][CH:24]=1>>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]([CH:14]1[CH2:16][CH2:15]1)=[O:13])=[C:5]2[NH:18][C:19]1[CH:24]=[N:23][C:22]([N:25]2[CH2:29][CH2:28][CH:27]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])[CH2:26]2)=[N:21][CH:20]=1
Reactant: CC(C)(C)OC(=O)NC1CCN(c2ncc(N)cn2)C1
Reactant: O=C(c1cnc2ccc(Br)cc2c1Cl)C1CC1
Product: CC(C)(C)OC(=O)NC1CCN(c2ncc(Nc3c(C(=O)C4CC4)cnc4ccc(Br)cc34)cn2)C1
Yield: 60.7 %

Procedure:
Following General procedure C, (6-bromo-4-chloroquinolin-3-yl)(cyclopropyl)methanone (311 mg, 1 mmol) was reacted with tert-butyl 1-(5-aminopyrimidin-2-yl)pyrrolidin-3-ylcarbamate (418 mg, 1.5 mmol) to afford the desired product (336 mg, 61%) as a yellow solid: ESI MS m/z 553 [C26H29BrN6O3+H]+.
Reaction SMILES: [CH:1]1[C:6]([N+:7]([O-:9])=[O:8])=[CH:5][CH:4]=[C:3]([O:10][C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[CH:2]=1.C([O-])(=O)C>>[CH:5]1[C:6]([N+:7]([O-:9])=[O:8])=[CH:1][CH:2]=[C:3]([OH:10])[CH:4]=1
Reactant: O=[N+]([O-])c1ccc(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)cc1
Agent: CC(=O)[O-]
Product: O=[N+]([O-])c1ccc(O)cc1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
Enzyme assay. β-Glucosidase was routinely assayed using a reaction mixture (1 ml) containing 4 mM p-nitrophenyl β-D-glucoside (pNPβG), 50 mM acetate buffer, pH 5.0 and appropriately diluted enzyme solution. After incubation at 50° C. for 30 min, the reaction was stopped by adding ice-cold 0.5M Na2CO3 (1 ml) and the color developed as a result of p-nitrophenol (pNP) liberation was measured at 405 nm. One unit (U) of β-glucosidase corresponds to the release of 1 μmol pNP. min-1 in the reaction mixture under these assay conditions.
Reaction SMILES: [C:1]([C:4]1[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=1[C:6]([OH:8])=O)(=O)[CH3:2].[C:13]1([C:19]2[CH2:20][CH2:21][N:22]([CH2:25][CH2:26][CH2:27][NH2:28])[CH2:23][CH:24]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.Cl.C1(C2CCN(CCCN)CC=2)C=CC=CC=1.C([BH3-])#N.[Na+].[C:50]([OH:55])(=[O:54])[C:51]([OH:53])=[O:52]>C(#N)C.C(C(C)=O)C>[C:50]([OH:55])(=[O:54])[C:51]([OH:53])=[O:52].[CH3:2][CH:1]1[C:4]2[C:5](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:6](=[O:8])[N:28]1[CH2:27][CH2:26][CH2:25][N:22]1[CH2:21][CH:20]=[C:19]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:24][CH2:23]1
Reactant: CC(=O)c1ccccc1C(=O)O
Reactant: NCCCN1CC=C(c2ccccc2)CC1
Agent: Cl
Agent: O=C(O)C(=O)O
Agent: [BH3-]C#N
Solvent: CC#N
Solvent: CCC(C)=O
Product: CC1c2ccccc2C(=O)N1CCCN1CC=C(c2ccccc2)CC1
Reaction time: 4 h

Procedure:
2.5 g of 2-acetylbenzoic acid is added to a solution of 3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)-1-aminopropane (7.8 g) in acetonitrile (90 cc) at a temperature close to 20° C. in the course of 10 minutes. Agitation is continued for 4 hours then 7.6 g of 3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)-1-aminopropane hydrochloride is added in the course of 30 minutes. Then 1.2 g of sodium cyanoborohydride is added to the suspension obtained, in the course of 5 minutes. Agitation is continued for 16 hours. The suspension is filtered and the precipitate washed with acetonitrile (20 cc). The organic extracts are combined, diluted with methylene chloride (200 cc) then washed with distilled water (120 cc), dried over anhydrous magnesium sulphate, treated with animal charcoal, filtered and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C. The residue obtained is poured onto alumina (750 g) contained in a column of 6 cm diameter. Elution is carried out with ethyl acetate (1000 cc) and the corresponding eluates are eliminated. Then elution is carried out with a mixture of ethyl acetate and methanol (98-2 by volume) (1000 cc) and the corresponding eluates are evaporated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 50° C. The residue obtained is dissolved in methyl ethyl ketone (20 cc). A solution of oxalic acid (0.3 g) in methyl ethyl ketone (10 cc) is added and agitation continued for 1 hour at a temperature close to 20° C. The precipitate formed is separated by filtration and recrystallized from boiling acetonitrile (80 cc). 0.9.g of 3-methyl-2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate are thus obtained, melting at 147° C.
Reaction SMILES: [CH:1]1([CH2:4][N:5]2[CH2:25][CH2:24][C@:12]34[C:13]5[C:14]6[O:23][C@H:11]3[C:10](=[O:26])[CH2:9][CH2:8][C@@:7]4([OH:27])[C@H:6]2[CH2:19][C:18]=5[CH:17]=[CH:16][C:15]=6[C:20]([NH2:22])=[O:21])[CH2:3][CH2:2]1.[Cl-].[NH4+]>C(O)C.[Zn]>[CH:1]1([CH2:4][N:5]2[CH2:25][CH2:24][C@@:12]34[C:13]5[C:14]([OH:23])=[C:15]([C:20]([NH2:22])=[O:21])[CH:16]=[CH:17][C:18]=5[CH2:19][C@@H:6]2[C@:7]3([OH:27])[CH2:8][CH2:9][C:10](=[O:26])[CH2:11]4)[CH2:3][CH2:2]1
Reactant: NC(=O)c1ccc2c3c1O[C@H]1C(=O)CC[C@@]4(O)[C@@H](C2)N(CC2CC2)CC[C@]314
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: CCO
Product: NC(=O)c1ccc2c(c1O)[C@]13CCN(CC4CC4)[C@H](C2)[C@]1(O)CCC(=O)C3
Temperature: 90 °C
Yield: 48 %

Procedure:
A mixture of (5a)-17-(cyclopropylmethyl)-14-hydroxy-6-oxo-4,5-epoxymorphinan-3-carboxamide [P3] (3.0 g, 8.15 mmol), Zinc powder (2.67 g, 40.76 mmol), and ammonium chloride (3.05 g, 57.1 mmol) in ethanol (500 mL) was heated at 90° C. for 1 hour. The reaction mixture was allowed to return to room temperature then filtered. The residual solid was washed with excess methanol (500 mL) followed by 7% ammonium hydroxide (100 mL). The combined filtrates were concentrated under reduced pressure and the residue partitioned between dichloromethane and 7% ammonium hydroxide solution. The aqueous phase was washed with further DCM and the combined organic layers dried (MgSO4). Filtration and removal of the solvent under reduced pressure giving 17-(cyclopropylmethyl)-4,14-dihydroxy-6-oxomorphinan-3-carboxamide [P4] (1.45 g, 48% yield); LC/MS (r.t. 10.7 minutes [5 to 95% B]), 371 (M+H)+.
Reaction SMILES: [N+]([O-])([O-])=O.[La+3:5].[N+]([O-])([O-])=O.[N+]([O-])([O-])=O.[La].[O-2].[La+3].[O-2].[O-2].[La+3].[C:20](=[O:23])([O-:22])[OH:21].[NH4+]>[N+]([O-])(O)=O.[N+]([O-])([O-])=O>[C:20](=[O:21])([O-:23])[O-:22].[La+3:5].[C:20](=[O:21])([O-:23])[O-:22].[C:20](=[O:21])([O-:23])[O-:22].[La+3:5]
Reactant: O=C([O-])O
Agent: O=[N+]([O-])[O-]
Agent: [La+3]
Agent: [La]
Solvent: O=[N+]([O-])O
Product: O=C([O-])[O-]

Procedure:
An aqueous solution of lanthanum nitrate in a concentration of 0.2 mole/liter as lanthanum and having a pH of 3 was prepared by dissolving lanthanum oxide in nitric acid and i liter of this nitrate solution was admixed under agitation at room temperature with I liter of an aqueous solution containing 79 g (1 mole) of ammonium hydrogen carbonate to give an aqueous slurry of lanthanum carbonate. The amount of the ammonium hydrogen carbonate added to the nitrate solution was in excess of 67% over the stoichiometrically equivalent amount to the lanthanum nitrate.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([CH3:10])=[C:5]([CH3:9])[C:6]=1[C:7]#[N:8].[C:11]([N:19]=[C:20]=[S:21])(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>O1CCOCC1>[C:7]([C:6]1[C:5]([CH3:9])=[C:4]([CH3:10])[S:3][C:2]=1[NH:1][C:20]([NH:19][C:11](=[O:18])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)=[S:21])#[N:8]
Reactant: Cc1sc(N)c(C#N)c1C
Reactant: O=C(N=C=S)c1ccccc1
Solvent: C1COCCO1
Product: Cc1sc(NC(=S)NC(=O)c2ccccc2)c(C#N)c1C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 2-amino-4,5-dimethylthiophene-3-carbonitrile (1.52 g, 10.0 mmol) in 1.4-dioxane (20 mL) was added benzoylisothiocyanate (1.63 g, 10.0 mmol). The reaction mixture was then stirred at room temperature under nitrogen overnight. The precipitation was collected by filtration, washed with EtOAc/Hexanes (1:4), and dried under vacuum overnight to give N-(3-Cyano-4,5-dimethylthiophen-2-ylcarbamothioyl)benzamide as a white solid. 1H NMR (400 MHz, CDCl3) δ 2.23 (s, 3H), 2.31 (s, 3H), 7.58-7.54 (m, 2H), 7.68-7.66 (m, 1H), 7.94 (d, J=7.2 Hz, 2H), 9.13 (bs, 1H). MS 316 (MH+).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][O:9][CH2:10][C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:14][N:15]1CCOCC1.ClC(OCC(C)C)=O.CN.C(O)C>C1COCC1>[CH3:14][NH:15][C:11](=[O:13])[CH2:10][O:9][NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2]
Reactant: CN1CCOCC1
Reactant: CC(C)(C)OC(=O)NOCC(=O)O
Agent: CC(C)COC(=O)Cl
Agent: CN
Solvent: C1CCOC1
Solvent: CCO
Product: CNC(=O)CONC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 72.7 %

Procedure:
A solution of 2-(tert-butoxycarbonylaminooxy)acetic acid (87a, 1 g, 5.23 mmol) in anhydrous THF was chilled in an ice bath and N-methylmorpholine (863 μL, 7.85 mmol) and isobutyl chloroformate (746 μL, 5.75 mmol) were added sequentially. The mixture was stirred under an N2 atmosphere for 20 min. A 33 wt % solution of methanamine in ethanol (1.3 mL, 10.46 mmol) was added to the reaction which was subsequently allowed to warm to room temperature with stirring overnight. The THF was removed in vacuo and the residue was partitioned between ethyl acetate and water. The organic phase was washed with H2O×2 and dried over anhydrous Na2SO4. The ethyl acetate was removed in vacuo to yield tert-butyl 2-(methylamino)-2-oxoethoxycarbamate (87b, 775 mg, 3.80 mmol).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15](=[O:17])[CH3:16])=[CH:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[OH:8].C1(C)C=CC(S(O[CH:28]([CH3:35])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])(=O)=O)=CC=1.[OH-].[K+]>C(O)C>[Br:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15](=[O:17])[CH3:16])=[CH:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:28]([CH3:35])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]
Reactant: CCCCCCC(C)OS(=O)(=O)c1ccc(C)cc1
Reactant: CC(=O)c1ccc(-c2ccc(O)c(Br)c2)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: CCCCCCC(C)Oc1ccc(-c2ccc(C(C)=O)cc2)cc1Br

Procedure:
The above 3'-bromo-4'-hydroxy-4-acetylbiphenyl (200 g) was treated with 1.2 times equivalents of R 1-methylheptyl p-toluenesulfonate and potassium hydroxide in 97% ethanol (1 l) for 6 hours under reflux. The reaction mixture was worked up in a usual way to obtain crude oily 3'-bromo-4'-(1-methylheptyloxy)-4-acetylbiphenyl (163 g).
Reaction SMILES: [CH2:1]([C:3]1[C:7](I)=[CH:6][N:5]([C@H:9]2[CH2:14][CH2:13][C@H:12]([OH:15])[CH2:11][CH2:10]2)[N:4]=1)[CH3:2].C1COCC1.C([Mg]Cl)(C)C.CO[B:28]1[O:32][C:31]([CH3:34])([CH3:33])[C:30]([CH3:36])([CH3:35])[O:29]1.[NH4+].[Cl-]>>[CH2:1]([C:3]1[C:7]([B:28]2[O:32][C:31]([CH3:34])([CH3:33])[C:30]([CH3:36])([CH3:35])[O:29]2)=[CH:6][N:5]([C@H:9]2[CH2:14][CH2:13][C@H:12]([OH:15])[CH2:11][CH2:10]2)[N:4]=1)[CH3:2]
Reactant: COB1OC(C)(C)C(C)(C)O1
Reactant: CCc1nn([C@H]2CC[C@H](O)CC2)cc1I
Agent: CC(C)[Mg]Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CCc1nn([C@H]2CC[C@H](O)CC2)cc1B1OC(C)(C)C(C)(C)O1
Reaction time: 1 h

Procedure:
To a solution of trans-4-(3-ethyl-4-iodo-1H-pyrazol-1-yl)cyclohexanol (150.0 mg, 0.4685 mmol) in THF (10 mL, 100 mmol) at rt was added 2 M isopropylmagnesium chloride in THF (0.70 mL, 1.4 mmol), and the mixture was stirred for 1 h. The reaction was quenched with 2-methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.31 mL, 1.9 mmol), and allowed to stir at rt for 1 h. Sat. NH4Cl was added, and the organic solvent was removed in vacuo. The material was extracted with DCM and water. The organic layer was concentrated in vacuo to afford the title compound as a white solid. The material was used in the next step without further purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[O:11][CH2:12][C:13]1[N:14]=[C:15]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:16][C:17]=1[CH3:18])[CH2:6][OH:7].Cl[C:26]1[C:31]([C:32]#[N:33])=[CH:30][CH:29]=[CH:28][N:27]=1.CN(C)C=O.[H-].[Na+]>O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[O:11][CH2:12][C:13]1[N:14]=[C:15]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:16][C:17]=1[CH3:18])[CH2:6][O:7][C:26]1[N:27]=[CH:28][CH:29]=[CH:30][C:31]=1[C:32]#[N:33]
Reactant: N#Cc1cccnc1Cl
Reactant: COc1cc(CO)ccc1OCc1nc(-c2ccccc2)oc1C
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1cc(COc2ncccc2C#N)ccc1OCc1nc(-c2ccccc2)oc1C
Temperature: 25 °C
Reaction time: 15 h
Yield: 90 %

Procedure:
To a mixture of 3-methoxy-4-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]benzyl alcohol (4.00 g), 2-chloro-3-cyanopyridine (1.62 g) and N,N-dimethylformamide (40 mL) was added sodium hydride (60%, oil, 515 mg) under ice-cooling. The reaction mixture was stirred at room temperature for 15 hrs. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The obtained crystals were recrystallized from ethyl acetate-hexane to give 2-[3-methoxy-4-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]benzyloxy]nicotinonitrile as pale-yellow crystals (4.50 g, 90%). melting point: 117-118° C.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.CCCCCC.[C:19]([O:22][CH2:23][CH3:24])(=[O:21])[CH3:20].[CH3:25][N:26]([CH3:40])[C:27](=[O:39])[O:28][C:29]1[CH:34]=[CH:33][C:32]([CH:35]=[O:36])=[C:31]([CH:37]=[CH2:38])[CH:30]=1.[Cl-].[NH4+]>O1CCCC1>[CH3:25][N:26]([CH3:40])[C:27]([O:28][C:29]1[CH:34]=[CH:33][C:32]([CH:35]([OH:36])[CH2:20][C:19]([O:22][CH2:23][CH3:24])=[O:21])=[C:31]([CH:37]=[CH2:38])[CH:30]=1)=[O:39]
Reactant: CCOC(C)=O
Reactant: C=Cc1cc(OC(=O)N(C)C)ccc1C=O
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCCCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: C=Cc1cc(OC(=O)N(C)C)ccc1C(O)CC(=O)OCC
Yield: 99.8 %

Procedure:
To a solution of diisopropylamine (1.26 g, 12.5 mmol) in tetrahydrofuran (30 ml) was added 1.6M solution of n-butyllithium in hexane (7.20 ml, 11.5 mmol) at −20° C. with stirring, and the resulting mixture was stirred for 20 minutes at −20° C. under a nitrogen atmosphere. Subsequently, ethyl acetate (1.07 ml, 11.0 mmol) was added at −78° C., and the resulting mixture was stirred for 20 minutes at −78° C. under a nitrogen atmosphere. Subsequently, to the reaction mixture was added a solution of 4-formyl-3-vinyl-phenyl dimethylcarbamate (2.11 g, 9.62 mmol) obtained in step (c) of Example 192 in tetrahydrofuran at −78° C., and the resulting mixture was stirred for 30 minutes at −78° C. under a nitrogen atmosphere. After stirring, to the reaction mixture was added saturated aqueous ammonium chloride solution (40 ml), and the resulting mixture was extracted with ethyl acetate (40 ml×2). The organic layer was washed successively with water (40 ml×1) and saturated aqueous sodium chloride solution (40 ml×1), dried over anhydrous sodium sulfate, filtered, and evaporated in vacuo to afford the crude product. The crude product was purified by chromatography on a silica gel column using a mixed solvent of hexane and ethyl acetate (1:1-1:2) as the eluent to afford the title compound (2.95 g, yield: 99%) as a colorless oil.
Reaction SMILES: FC(F)(F)C(O)=O.C(OC([NH:15][C:16]1([C:20]2[CH:25]=[CH:24][C:23]([C:26]3[C:35](=[O:36])[C:34]4[C:29](=[C:30]([C:37]([OH:39])=[O:38])[CH:31]=[CH:32][CH:33]=4)[O:28][C:27]=3[C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)=[CH:22][CH:21]=2)[CH2:19][CH2:18][CH2:17]1)=O)(C)(C)C>C(Cl)Cl.C1(C)C=CC=CC=1>[NH2:15][C:16]1([C:20]2[CH:21]=[CH:22][C:23]([C:26]3[C:35](=[O:36])[C:34]4[C:29](=[C:30]([C:37]([OH:39])=[O:38])[CH:31]=[CH:32][CH:33]=4)[O:28][C:27]=3[C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)=[CH:24][CH:25]=2)[CH2:17][CH2:18][CH2:19]1
Reactant: CC(C)(C)OC(=O)NC1(c2ccc(-c3c(-c4ccccc4)oc4c(C(=O)O)cccc4c3=O)cc2)CCC1
Solvent: O=C(O)C(F)(F)F
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: NC1(c2ccc(-c3c(-c4ccccc4)oc4c(C(=O)O)cccc4c3=O)cc2)CCC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 69.4 %

Procedure:
trifluoro-acetic acid: 3-[4-(1-tert-Butoxycarbonylamino-cyclobutyl)-phenyl]-4-oxo-2-phenyl-4H-chromene-8-carboxylic acid (18 mg, 0.035 mmol) was treated with a solution of 25% TFA in DCM (4 mL) and stirred at RT for 1 h. The reaction mixture was diluted with toluene and concentrated in vacuo. The resultant residue was triturated with diethyl ether and DCM, and concentrated in vacuo to give the title compound as a light tan solid (10 mg, 54%). 1H NMR (400 MHz, DMSO-d6): δ 13.44 (bs, 1H), 8.44 (s, 3H), 8.28-8.23 (m, 2H), 7.57 (t, J=7.7 Hz, 1H), 7.48-7.36 (m, 5H), 7.33-7.27 (m, 4H), 2.64-2.53 (m, 2H), 2.51-2.42 (m, 2H), 2.18-2.05 (m, 1H), 1.85-1.73 (m, 1H). LCMS (Method E): RT=2.89 min, [M+H]+=412.
Reaction SMILES: O=[N+]([O-])[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[Ce+4].[NH4+].[NH4+].C(#N)C.[C:31]([C:34]1([CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][C:58]([OH:60])=[O:59])[CH2:42][C:41]2[C:36](=[C:37]([O:49]C)[C:38]([O:47][CH3:48])=[C:39]([O:45][CH3:46])[C:40]=2[O:43]C)[CH2:35]1)([OH:33])=[O:32]>O>[C:31]([C:34]1([CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][C:58]([OH:60])=[O:59])[CH2:42][C:41]2[C:40](=[O:43])[C:39]([O:45][CH3:46])=[C:38]([O:47][CH3:48])[C:37](=[O:49])[C:36]=2[CH2:35]1)([OH:33])=[O:32]
Reactant: COc1c2c(c(OC)c(OC)c1OC)CC(CCCCCCCC(=O)O)(C(=O)O)C2
Agent: O=[N+]([O-])[O-]
Agent: [Ce+4]
Agent: [NH4+]
Solvent: O
Solvent: CC#N
Product: COC1=C(OC)C(=O)C2=C(CC(CCCCCCCC(=O)O)(C(=O)O)C2)C1=O
Reaction time: 0.25 h
Yield: 38.8 %

Procedure:
A water (1 ml) solution of CAN (287 mg, 0.523 mmols) was dropwise added to an acetonitrile (2 ml) solution of 8-(2-carboxy-4,5,6,7-tetramethoxyindan-2-yl)octanoic acid (88.6 mg, 0.209 mmols) with cooling with ice and then stirring was continued for 15 minutes. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution and then dried. The solvent was evaporated in vacuo, and the resulting crude product was purified by silica gel column chromatography (hexane:ethyl acetate=1:1 to ethyl acetate only) followed by recrystallization from hexane-ethyl acetate to obtain the entitled compound (32 mg) as crystals.
Reaction SMILES: [N:1](/[C:4](=[CH:9]\[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:12]([N+:24]([O-:26])=[O:25])[CH:11]=1)/[C:5]([O:7][CH3:8])=[O:6])=[N+]=[N-]>C1(C)C(C)=CC=CC=1>[CH2:17]([O:16][C:13]1[CH:14]=[C:15]2[C:10]([CH:9]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[NH:1]2)=[CH:11][C:12]=1[N+:24]([O-:26])=[O:25])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: COC(=O)/C(=C/c1ccc(OCc2ccccc2)c([N+](=O)[O-])c1)N=[N+]=[N-]
Solvent: Cc1ccccc1C
Product: COC(=O)c1cc2cc([N+](=O)[O-])c(OCc3ccccc3)cc2[nH]1
Temperature: 25 °C
Yield: 14.8 %

Procedure:
To a stirred solution of 200 ml of boiling xylene 4.93 g ((13.9 mmol) of methyl (Z)-2-azido-3-(4-benzyloxy-3-nitrophenyl)acrylate is added in small portions. After completion of the addition the reaction mixture is refluxed until the gas formation is over (about 0.5 h), then cooled to room temperature, the precipitated product is filtered off and washed with n-hexane to yield 0.67 g (15%) of the title compound. Mp.: 184-187° C. (xylene).
Reaction SMILES: [Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[N:6][N:5]=[C:4]2[NH:14][N:15]=[C:16]([CH3:17])[C:3]=12.O[CH2:19][C:20]([N:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1)=[O:21]>>[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[N:6][N:5]=[C:4]2[N:14]([CH2:19][C:20]([N:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)=[O:21])[N:15]=[C:16]([CH3:17])[C:3]=12
Reactant: O=C(CO)N1CCCC1
Reactant: Cc1n[nH]c2nnc(-c3ccccc3)c(Cl)c12
Product: Cc1nn(CC(=O)N2CCCC2)c2nnc(-c3ccccc3)c(Cl)c12

Procedure:
Compound Iw was synthesized from 4-chloro-3-methyl-5-phenyl-1H-pyrazolo[3,4-c]pyridazine and 2-hydroxy-1-(pyrrolidin-1-yl)ethanone following the general procedure for the Mitsunobu reaction described above.
Reaction SMILES: [C:1]1([N:7]2[C:11](=[O:12])[CH:10]=[CH:9][C:8]2=[O:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:14][NH:15][C:16]([NH:18][CH3:19])=[O:17].C1(C)C(O)=CC=CC=1>>[CH3:14][N:15]1[C:9](=[CH:10][C:11]([NH:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[O:12])[C:8](=[O:13])[N:18]([CH3:19])[C:16]1=[O:17]
Reactant: O=C1C=CC(=O)N1c1ccccc1
Reactant: CNC(=O)NC
Agent: Cc1ccccc1O
Product: CN1C(=O)C(=CC(=O)Nc2ccccc2)N(C)C1=O

Procedure:
A solution of 17.3 parts of N-phenyl maleic imide and 8.8 parts of N,N'-dimethyl urea in 100 parts of cresol is stirred for three hours at 190° C. The solvent is distilled off in vacuo and the residue fractionated. The oily liquid which distills at a boiling point of 220° C./0.1 Torr solidifies after a while and may be recrystallised from n-propanol (Mp. 114°-115° C.). IR and NMR-spectra confirm the assumed compound.