Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:7]=[CH:8][CH:9]=1)(=[O:3])[CH3:2].[BH4-].[Na+].[Cl-].[NH4+]>CO.O1CCCC1>[OH:3][CH:1]([C:4]1[CH:5]=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:7]=[CH:8][CH:9]=1)[CH3:2]
Reactant: CC(=O)c1cccc(-c2ccccc2)c1
Agent: [BH4-]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CO
Solvent: C1CCOC1
Product: CC(O)c1cccc(-c2ccccc2)c1
Reaction time: 1 h
Yield: 99.4 %

Procedure:
To a solution of 9.82 g (50 mmol) of 3-acetylbiphenyl in 80 ml of dry methanol and 80 ml of dry tetrahydrofuran was added 3.36 g (80 mmol) of sodium borohydride portionwise with ice-cooling, and the mixture was stirred for 1 hour. To the reaction solution was added 600 ml of an about 5% aqueous solution of ammonium chloride and the mixture was extracted with tert-butyl methyl ether. The organic layer was dried and concentrated to obtain 9.86 g (49.7 mmol) of 3-(1-hydroxyethyl)biphenyl as an oil.
Reaction SMILES: [CH2:1]([O:7][C:8]1[CH:15]=[CH:14][C:11]([CH:12]=[O:13])=[CH:10][CH:9]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].C([O:18][C:19](=[O:30])[C:20](CO)([CH2:26]O)[C:21](OCC)=[O:22])C.C1(C)C=CC(S(O)(=O)=O)=CC=1.[OH-].[K+]>C1C=CC=CC=1.C(O)C.CCCCCC>[CH2:1]([O:7][C:8]1[CH:15]=[CH:14][C:11]([CH:12]2[O:22][CH2:21][CH:20]([C:19]([OH:30])=[O:18])[CH2:26][O:13]2)=[CH:10][CH:9]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCOC(=O)C(CO)(CO)C(=O)OCC
Reactant: CCCCCCOc1ccc(C=O)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CCCCCC
Solvent: CCO
Solvent: c1ccccc1
Product: CCCCCCOc1ccc(C2OCC(C(=O)O)CO2)cc1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
20.6 g (0.1 mol) 4-n-hexoxybenzaldehyde and 24.2 g (0.11 mol) bis-hydroxymethyl-malonic acid-diethyl ester are heated in 150 ml benzene in a corresponding amount of 0.2 g p-toluenesulfonic acid, while stirring for 8 hours. After cooling, the benzene is carefully washed with 2% NaHCO3 solution, then with water, and then distilled under vacuum (rotating evaporator), with the residue being recrystallized from alcohol (2-(4-n-hexoxyphenyl)-1,3-dioxane-5,5-dicarboxylic acid-diethyl ester I). The yield at I is 31 g (76% of theoretical). I melts at 30° C. (from n-hexane). 31 g (0.074 mol) I and 18 g (0.32 mol) KOH in 150 ml 95% ethanol is heated for one hour at reflux in the continued preparation. Ethanol is then distilled from the reaction residue, water added to the residue, and the aqueous phase concentrated to 30-50 ml. After addition of 100 ml ether, it is cooled to 0° C. and concentrated HCl is added while stirring (up to pH 1). Subsequently, the ether fraction is immediately separated, washed with water, dried with Na2SO4, and the solvent removed in the rotating evaporator. The residue (16.5 g, 62% of theoretical) of 2(4-n-hexoxyphenyl)-1,3-dioxane-5,5-dicarboxylic acid (decomposition above 135° C.) is decarboxylized with a water jet vacuum pump at 120° to 170° C. Having completed the brisk CO2 development, the residue of benzene or cyclohexane is recrystallized. The yield of 5 n is 63% of theoretical. The melting point of 5 n is 176° to 178° C. Additional examples are listed in Table 5.
Reaction SMILES: [CH3:1][NH:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([C:14]1[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=1)[CH:9]=[CH:8]2)=[O:4].[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([N:28]=[C:29]=[O:30])=[CH:24][C:23]=1[C:31]([F:34])([F:33])[F:32]>>[CH3:1][NH:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:29]([NH:28][C:25]3[CH:26]=[CH:27][C:22]([Cl:21])=[C:23]([C:31]([F:33])([F:32])[F:34])[CH:24]=3)=[O:30])=[CH:16][CH:15]=1)[CH:9]=[CH:8]2)=[O:4]
Reactant: O=C=Nc1ccc(Cl)c(C(F)(F)F)c1
Reactant: CNC(=O)c1ccc2c(ccn2-c2ccc(N)cc2)c1
Product: CNC(=O)c1ccc2c(ccn2-c2ccc(NC(=O)Nc3ccc(Cl)c(C(F)(F)F)c3)cc2)c1

Procedure:
The title compound can be synthesized from 1-(4-aminophenyl)-1H-indole-5-carboxylic acid methylamide and 4-chloro-3-(trifluoromethyl)phenyl isocyanate in the same manner as in Step C in Example 1.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[CH:4][NH:5][CH:6]=1.[H-].[Na+].[CH3:9][Si:10]([CH2:13][CH2:14][O:15][CH2:16]Cl)([CH3:12])[CH3:11]>O1CCCC1>[CH3:1][C:2]1[N:3]=[CH:4][N:5]([CH2:16][O:15][CH2:14][CH2:13][Si:10]([CH3:12])([CH3:11])[CH3:9])[CH:6]=1
Reactant: Cc1c[nH]cn1
Reactant: C[Si](C)(C)CCOCCl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1cn(COCC[Si](C)(C)C)cn1
Temperature: 25 °C
Reaction time: 1 h
Yield: 34.8 %

Procedure:
Into a 1-L three neck round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 4-methyl-1H-imidazole (10 g, 121.8 mmol) in tetrahydrofuran (200 mL). This was followed by the addition of sodium hydride (7.32 g, 182.7 mmol, 60%) in several batches at 0° C. and stirred for 1 h at room temperature. To this was added SEM-Cl (30.5 g, 199.7 mmol) at 0° C. The mixture was stirred for 1 h at room temperature, then carefully quenched with 50 mL of brine. The aqueous phase was extracted with 1×800 mL of ethyl acetate. The organic layer was washed with 1×300 mL of brine, 2×300 mL of sodium bicarbonate (sat.), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:1) ethyl acetate as eluent to furnish 9 g (35%) of the title compound as a yellow oil.
Reaction SMILES: Cl.[F:2][C:3]1[C:8]([F:9])=[C:7]([F:10])[CH:6]=[CH:5][C:4]=1[NH:11][NH2:12].C(O[CH:16]=[C:17]([C:23]([CH3:25])=O)[C:18]([O:20]CC)=[O:19])C.[OH-].[Na+]>C(O)C>[F:2][C:3]1[C:8]([F:9])=[C:7]([F:10])[CH:6]=[CH:5][C:4]=1[N:11]1[C:23]([CH3:25])=[C:17]([C:18]([OH:20])=[O:19])[CH:16]=[N:12]1
Reactant: CCOC=C(C(C)=O)C(=O)OCC
Reactant: NNc1ccc(F)c(F)c1F
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: Cc1c(C(=O)O)cnn1-c1ccc(F)c(F)c1F
Yield: 68 %

Procedure:
To a mixed solvent of 1N hydrochloric acid aqueous solution (120 ml) and ethanol (120 ml), were added 2,3,4-trifluorophenylhydrazine (9.3 g) and ethyl 2-(ethoxymethylene)acetoacetate (10.7 g) prepared according to a method described in J. Chem. Soc. Perkin trans. I, 1875 (1988), and the mixture was stirred at reflux temperature for three hours. Next, sodium hydroxide (2.8 g) was added and the mixture was further stirred for an hour. Ethanol was evaporated in vacuo, the organic layer was separated with toluene, hydrochloric acid was added to the aqueous layer and the precipitated solid was collected by filtration to give the titled compound (10 g).
Reaction SMILES: [CH3:1][C:2]1([CH3:10])[NH:6][C:5](=[O:7])[C:4]([CH3:9])([CH3:8])[NH:3]1.[OH-].[Na+].[Cl:13]Cl.[K+].[Br-]>>[Cl:13][N:3]1[C:4]([CH3:9])([CH3:8])[C:5](=[O:7])[NH:6][C:2]1([CH3:10])[CH3:1]
Reactant: CC1(C)NC(=O)C(C)(C)N1
Reactant: ClCl
Agent: [Br-]
Agent: [K+]
Agent: [Na+]
Product: CC1(C)NC(=O)C(C)(C)N1Cl

Procedure:
14.2 Grams (0.1 mole) of 2,2,5,5-tetramethylimidazolidin-4-one prepared as in example 2 was dissolved in 100 milliliters of 1 Normal sodium hydroxide solution (0.1 mole) in a 250 milliliter flask. The flask containing the mixture was placed in an ice bath and maintained at or below 10° C. with stirring while chlorine gas was bubbled in until the pH reached 7.0. The product 1-chloro-2,2,5,5-tetramethylimidazolidin-4-one which precipitated as a white solid was recovered by suction filtration and was purified by recrystallization from an ether/hexane mixture. The product yield was 17.7 grams or 95% of that theoretically expected. The product had a melting point range of 157.0°-157.5° C. Analysis of the product by proton NMR and IR spectroscopy yielded the following results: 1H NMR (CDCl3) δ=1.32 (S,6H), δ=1.46 (S,6H), δ=7.57 (Broad,1H); IR (KBr) 1670, 1720, 3160 cm-1.
Reaction SMILES: [H-].[Na+].[CH3:3][C:4]1[C:13]([CH3:14])=[C:12](O)[C:11]2[C:6](=[C:7]([F:20])[CH:8]=[C:9]([C:16]([CH3:19])([CH3:18])[CH3:17])[CH:10]=2)[N:5]=1.[CH3:21][O:22][CH2:23][C:24](Cl)=[O:25]>O1CCCC1>[CH3:3][C:4]1[C:13]([CH3:14])=[C:12]([C:24](=[O:25])[CH2:23][O:22][CH3:21])[C:11]2[C:6](=[C:7]([F:20])[CH:8]=[C:9]([C:16]([CH3:19])([CH3:18])[CH3:17])[CH:10]=2)[N:5]=1
Reactant: COCC(=O)Cl
Reactant: Cc1nc2c(F)cc(C(C)(C)C)cc2c(O)c1C
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COCC(=O)c1c(C)c(C)nc2c(F)cc(C(C)(C)C)cc12
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
In tetrahydrofuran (10 ml) was suspended 60% sodium hydride (165 mg). The compound 1 (680 mg) was added to the suspension under ice cooling, and the mixture was stirred for 30 min. Further, methoxyacetyl chloride (200 μl) was added thereto, and the mixture was stirred for 3 hr. The reaction solution thus obtained was poured into ice water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was then removed under the reduced pressure. The crude product was purified by chromatography on silica gel (Wako Gel C-200, elution solvent: n-hexane-ethyl acetate (3:1)) to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-methoxyacetylquinoline (compound 10, 390 mg). 1H-NMR data on this compound in deutro-chloroform were as shown below.
Reaction SMILES: [Cl:1][C:2]1[CH:16]=[C:15]([F:17])[C:14]([N:18]2[C:23](=[O:24])[CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[N:20]([CH3:29])[C:19]2=[O:30])=[CH:13][C:3]=1[O:4][CH:5]([CH2:10][CH2:11]Br)[C:6]([O:8][CH3:9])=[O:7].CC(C)([O-])C.[K+]>C1COCC1>[Cl:1][C:2]1[CH:16]=[C:15]([F:17])[C:14]([N:18]2[C:23](=[O:24])[CH:22]=[C:21]([C:25]([F:28])([F:26])[F:27])[N:20]([CH3:29])[C:19]2=[O:30])=[CH:13][C:3]=1[O:4][C:5]1([C:6]([O:8][CH3:9])=[O:7])[CH2:10][CH2:11]1
Reactant: COC(=O)C(CCBr)Oc1cc(-n2c(=O)cc(C(F)(F)F)n(C)c2=O)c(F)cc1Cl
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: COC(=O)C1(Oc2cc(-n3c(=O)cc(C(F)(F)F)n(C)c3=O)c(F)cc2Cl)CC1
Reaction time: 2 h
Yield: 70 %

Procedure:
Into 10 ml of THF was dissolved 0.44 g of the obtained methyl 2-[2-chloro-4-fluoro-5-{3-methyl-2,6-dioxo-4-(tri-fluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl}phenoxy]-4-bromobutanoate and 0.10 g of potassium t-butoxide was added to the solution at −15° C. Cooling bath was removed and the solution was stirred until the solution became room temperature taking 2 hours. The reaction solution was poured into aqueous diluted hydrochloric acid and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent:hexane/ethyl acetate=4/1) to give 0.26 g of methyl 1-[2-chloro-4-fluoro-5-{3-methyl-2,6-dioxo-4-(trifluoro-methyl)-1,2,3,6-tetrahydropyrimidin-1-yl}phenoxy]cyclo-propanecarboxylate (Compound 1-2).
Reaction SMILES: [CH3:1]I.[F:3][C:4]1[CH:5]=[C:6]([C:10]2[S:14][C:13]([CH3:15])=[N:12][C:11]=2[C:16]([N:18]2[CH2:23][CH:22]([OH:24])[CH2:21][CH2:20][CH:19]2[C:25]([O:27][CH3:28])=[O:26])=[O:17])[CH:7]=[CH:8][CH:9]=1>CC#N.C(Cl)Cl>[F:3][C:4]1[CH:5]=[C:6]([C:10]2[S:14][C:13]([CH3:15])=[N:12][C:11]=2[C:16]([N:18]2[CH2:23][CH:22]([O:24][CH3:1])[CH2:21][CH2:20][CH:19]2[C:25]([O:27][CH3:28])=[O:26])=[O:17])[CH:7]=[CH:8][CH:9]=1
Reactant: CI
Reactant: COC(=O)C1CCC(O)CN1C(=O)c1nc(C)sc1-c1cccc(F)c1
Solvent: CC#N
Solvent: ClCCl
Product: COC(=O)C1CCC(OC)CN1C(=O)c1nc(C)sc1-c1cccc(F)c1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
MeI (6.8 mmol, 0.43 mL) was added to a mixture of methyl 1-(5-(3-fluorophenyl)-2-methylthiazole-4-carbonyl)-5-hydroxypiperidine-2-carboxylate (0.68 mmol, 0.26 g) and Ag2O (3.4 mmol, 0.8 g) in CH3CN (3 mL) at rt. The resulting mixture was stirred at rt for two days. The reaction mixture was diluted with DCM and filtered through a pad of diatomaceous earth. The filtrate was concentrated in vacuo to give desired product methyl 1-(5-(3-fluorophenyl)-2-methylthiazole-4-carbonyl)-5-methoxypiperidine-2-carboxylate which was used for next step without further purification (Y: 96%).
Reaction SMILES: CCCC[N+](CCCC)(CCCC)CCCC.[F-].[CH3:19][N:20]1[CH:24]=[C:23]([C:25]2[CH:26]=[CH:27][C:28]3[N:29]([C:31]([CH:34]([C:36]4[CH:52]=[CH:51][C:39]5[N:40](COCC[Si](C)(C)C)[CH:41]=[N:42][C:38]=5[CH:37]=4)[OH:35])=[CH:32][N:33]=3)[N:30]=2)[CH:22]=[N:21]1>C1COCC1>[NH:40]1[C:39]2[CH:51]=[CH:52][C:36]([CH:34]([C:31]3[N:29]4[N:30]=[C:25]([C:23]5[CH:22]=[N:21][N:20]([CH3:19])[CH:24]=5)[CH:26]=[CH:27][C:28]4=[N:33][CH:32]=3)[OH:35])=[CH:37][C:38]=2[N:42]=[CH:41]1
Reactant: Cn1cc(-c2ccc3ncc(C(O)c4ccc5c(c4)ncn5COCC[Si](C)(C)C)n3n2)cn1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: Cn1cc(-c2ccc3ncc(C(O)c4ccc5[nH]cnc5c4)n3n2)cn1

Procedure:
TBAF (1 M, 200 uL) was added to (rac)-[6-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-yl]-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-5-yl]-methanol (Stage 162.2, 42 mg, 0.088 mmol) dissolved in THF (3 ml). The reaction mixture was heated at reflux for 1 h. After evaporation of the solvent, the residue was taken into EtOAc and washed with saturated aqueous sodium carbonate. The aqueous phase was again extracted with EtOAc (3×) and combined organic layers were dried on Na2SO4. After evaporation of the solvent, the title compound was obtained as an oil (tR 0.01 min (conditions 2), MH+=346).
Reaction SMILES: [CH3:1][CH:2]([CH2:8][CH2:9][CH3:10])/[CH:3]=[CH:4]/[C:5](O)=[O:6].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:44][O:45][C:46]1[CH:55]=[C:54]([N:56]2[CH2:61][CH2:60][NH:59][CH2:58][CH2:57]2)[C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[N:47]=1>CN(C=O)C>[CH3:44][O:45][C:46]1[CH:55]=[C:54]([N:56]2[CH2:61][CH2:60][N:59]([C:5](=[O:6])/[CH:4]=[CH:3]/[CH:2]([CH3:1])[CH2:8][CH2:9][CH3:10])[CH2:58][CH2:57]2)[C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[N:47]=1
Reactant: COc1cc(N2CCNCC2)c2ccccc2n1
Reactant: CCCC(C)/C=C/C(=O)O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CCCC(C)/C=C/C(=O)N1CCN(c2cc(OC)nc3ccccc23)CC1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 40 %

Procedure:
(E)-4-Methyl-hept-2-enoic acid (21.3 mg, 0.15 mmol) was dissolved in DMF (350 μl), diisopropylethylamine was added (26 μl, 0.15 mmol) followed by HATU (57 mg, 0.15 mmol dissolved in 0.25 ml DMF). The mixture was stirred at room temperature for 15 minutes, then 2-methoxy-4-piperazin-1-yl-quinoline (36.4 mg, 0.15 mmol, dissolved in 1 ml DMF) was added and stirring was continued overnight. The mixture was evaporated under reduced pressure, the residue was dissolved in dichloromethane and the resulting solution was washed with 5% sodium bicarbonate solution, water, evaporated to dryness under reduced pressure. The residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile) to yield 21.1 mg (0.06 mmol, 39.8%) of a solid.
Reaction SMILES: [CH3:1][C:2]([N:7]1[CH:11]=[C:10]([C:12]2[CH:35]=[CH:34][C:15]3[C:16]4[N:17]=[C:18]([C:24]5[N:25]([CH2:29][C:30]([F:33])([F:32])[F:31])[N:26]=[CH:27][N:28]=5)[S:19][C:20]=4[CH2:21][CH2:22][O:23][C:14]=3[CH:13]=2)[CH:9]=[N:8]1)([CH3:6])[C:3](O)=[O:4].O1CCCC1.[AlH4-].[Li+]>>[CH3:6][C:2]([N:7]1[CH:11]=[C:10]([C:12]2[CH:35]=[CH:34][C:15]3[C:16]4[N:17]=[C:18]([C:24]5[N:25]([CH2:29][C:30]([F:31])([F:33])[F:32])[N:26]=[CH:27][N:28]=5)[S:19][C:20]=4[CH2:21][CH2:22][O:23][C:14]=3[CH:13]=2)[CH:9]=[N:8]1)([CH3:1])[CH2:3][OH:4]
Reactant: CC(C)(C(=O)O)n1cc(-c2ccc3c(c2)OCCc2sc(-c4ncnn4CC(F)(F)F)nc2-3)cn1
Agent: [AlH4-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(C)(CO)n1cc(-c2ccc3c(c2)OCCc2sc(-c4ncnn4CC(F)(F)F)nc2-3)cn1
Temperature: 25 °C
Reaction time: 2 h
Yield: 14.6 %

Procedure:
2-Methyl-2-(4-{2-[2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl}-pyrazol-1-yl)-propionic acid (0.250 g, 0.000496 mol) in dry tetrahydrofuran (1.0 mL, 0.012 mol) cooled to 0° C. Lithium tetrahydroaluminate (1M solution in THF, 1.0 mL, 0.0010 mol), was added dropwise at 0° C. and the mixture was allowed to warm to room temperature and stirred for 2 h. The reaction was quenched with saturated Na2SO4 until no more hydrogen evolution was observed. MgSO4 was added and the solution was filtered and rinsed with copious amounts of methylene chloride. The solvent was removed in vacuo and the crude material was purified by reverse-phase HPLC to give 332 (35.4 mg) as a colorless solid. MS(ESI+) 491.1.
Reaction SMILES: [CH2:1]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:23]=[CH:22][C:21]([O:24][CH2:25][CH:26]([OH:31])[C:27]([F:30])([F:29])[F:28])=[CH:20][N:19]=3)=[CH:14][CH:13]=2)=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH2:4][CH3:5].[C:32](O)(=[O:37])[CH2:33][CH2:34][CH2:35][CH3:36].C1CCC(N=C=NC2CCCCC2)CC1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH2:1]([C:6]1[CH:7]=[CH:8][C:9]([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[N:23]=[CH:22][C:21]([O:24][CH2:25][CH:26]([O:31][C:32](=[O:37])[CH2:33][CH2:34][CH2:35][CH3:36])[C:27]([F:30])([F:28])[F:29])=[CH:20][N:19]=3)=[CH:16][CH:17]=2)=[CH:10][CH:11]=1)[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: CCCCCc1ccc(-c2ccc(-c3ncc(OCC(O)C(F)(F)F)cn3)cc2)cc1
Reactant: CCCCC(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CCCCCc1ccc(-c2ccc(-c3ncc(OCC(OC(=O)CCCC)C(F)(F)F)cn3)cc2)cc1
Yield: 94.1 %

Procedure:
A mixed solution of 2-(4'-pentylbiphenyl-4-yl)-5-(2-hydroxy-3,3,3-trifluoropropoxy)-pyrimidine (80 mg), pentanoic acid (20 mg), DCC (50 mg), DMAP (10 mg) and methylene chloride (10 ml) was stirred at room temperature, followed by filtering off deposited solids, concentrating the mother liquid, purifying the residue by means of silica gel column chromatography and recrystalizing from ethanol to obtain the objective 2-(4'-pentylbiphenyl-4-yl)-5-(2-pentanoyloxy-3,3,3-trifluoropropoxy)-pyrimidine (90 mg). Cr 33° C. mesophase 84° C. iso
Reaction SMILES: [ClH:1].C([N:9]1[CH2:15][CH2:14][CH2:13][C:12]([CH2:17][OH:18])([OH:16])[CH2:11][CH2:10]1)C1C=CC=CC=1.[H][H]>[C].[Pd].CCO>[ClH:1].[OH:18][CH2:17][C:12]1([OH:16])[CH2:13][CH2:14][CH2:15][NH:9][CH2:10][CH2:11]1
Reactant: [H][H]
Reactant: OCC1(O)CCCN(Cc2ccccc2)CC1
Agent: [Pd]
Agent: Cl
Solvent: CCO
Product: OCC1(O)CCCNCC1

Procedure:
A solution of tert-butanol of N-methylmorpholine-N-oxide and osmium tetroxide was added to a mixture of 1-benzyl-4-methyleneazepane hydrochloride and THF-water and stirred at room temperature for 24 hours. Then the reaction solution was processed with 4M hydrochloric acid (HCl)-ethyl acetate (EtOAc) solution to give 1-benzyl-4-(hydroxymethyl)azepane-4-ol hydrochloride. 10% palladium carbon was added to a solution of EtOH of the obtained 1-benzyl-4-(hydroxymethyl)azepane-4-ol hydrochloride and stirred for six hours at room temperature under the hydrogen atmosphere to give 4-(hydroxymethyl)azepane-4-ol hydrochloride.
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([Cl:11])[N:3]=1.[CH:12](O)([CH3:14])[CH3:13].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:12]([CH3:14])[CH3:13])=[C:4]([Cl:11])[N:3]=1
Reactant: CC(C)O
Reactant: Clc1nc(Cl)c2[nH]cnc2n1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)n1cnc2c(Cl)nc(Cl)nc21
Temperature: 25 °C
Reaction time: 24 h
Yield: 77 %

Procedure:
2,6-Dichloropurine (2 mmol), isopropanol (8 mmol) and triphenylphosphine (4 mmol) were taken up in 40 ml anhydrous tetrahydrofuran and diisoproplyazidodicarboxylate (4 mmol) was added drop wise at room temperature over a period of 30 min. The reaction mixture was then stirred at room temperature for a further 24 h. The reaction was periodically monitored by TLC or LC-MS. The reaction mixture was poured in to a beaker containing ice-cold water. Extraction of the aqueous layer, using 3×100 ml portions of ethyl acetate, afforded the crude product. This was purified by chromatography on a silica gel column (10-80% ethyl acetate in petroleum ether, gradient elution), to give 2,6-dichloro-9-isopropyl-9H-purine in a yield of 77%.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH2:3][CH2:2]1.O[CH:11]([NH:15][C:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:17])[C:12]([OH:14])=[O:13].O>OS(O)(=O)=O.C(O)(=O)C>[C:16]([NH:15][CH:11]([C:8]1[CH:7]=[CH:6][C:5]2[O:1][CH2:2][CH2:3][C:4]=2[CH:9]=1)[C:12]([OH:14])=[O:13])(=[O:17])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: O=C(NC(O)C(=O)O)c1ccccc1
Reactant: c1ccc2c(c1)CCO2
Agent: O=S(=O)(O)O
Solvent: CC(=O)O
Solvent: O
Product: O=C(NC(C(=O)O)c1ccc2c(c1)CCO2)c1ccccc1
Reaction time: 0.5 h
Yield: 94 %

Procedure:
2,3-Dihydrobenzofuran (4.8 g, 40 mmole) is stirred with 9.0 g (40 mmole) of α-hydroxyhippuric acid in 200 ml of 10% H2SO4 -acetic acid mixture. The reaction is run at room temperature for 0.5 hour. After the half-hour, the reaction mixture is poured into 500 ml of water. The aqueous solution is extracted with ethyl acetate (4 × 100 ml). The ethyl acetate extracts are dried over magnesium sulfate and then evaporated to give α-benzamido(2,3-dihydro-5-benzofuranyl)acetic acid. Recrystallization of the crude benzamido compound from hexane-methylene chloride gives 11.56 g (94% yield).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:11])[CH3:10].Br[C:13]([CH3:20])([CH3:19])[C:14]([O:16][CH2:17][CH3:18])=[O:15]>>[OH:1][C:2]1[CH:7]=[C:6]([O:8][C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])([CH3:20])[CH3:19])[CH:5]=[CH:4][C:3]=1[C:9](=[O:11])[CH3:10]
Reactant: CCOC(=O)C(C)(C)Br
Reactant: CC(=O)c1ccc(O)cc1O
Product: CCOC(=O)C(C)(C)Oc1ccc(C(C)=O)c(O)c1

Procedure:
This compound was synthesized from 2′,4′-dihydroxyacetophenone and ethyl bromoisobutyrate (1 eq) according to general method 4 described earlier.
Reaction SMILES: [N+]([O-])([O-])=O.[U+2:5](=[O:7])=[O:6].[N+]([O-])([O-])=O.[CH:12]([OH:14])=[O:13]>>[CH:12]([O-:14])=[O:13].[U+2:5](=[O:7])=[O:6].[CH:12]([O-:14])=[O:13]
Reactant: O=CO
Agent: O=[N+]([O-])[O-]
Agent: O=[U+2]=O
Product: O=C[O-]

Procedure:
In accordance with the present invention, U3O8 having a controlled particle size distribution is directly prepared from an aqueous solution of uranyl nitrate by adding formic acid to effect a denitration and form an unsaturated solution of uranyl formate. Additional stoichiometric excess of formic acid is added to the unsaturated uranyl formate to precipitate uranyl formate monohydrate. The resulting crystalline uranyl formate monohydrate is then calcined to produce U3O8 having a controlled particle size distribution. It has been found that U3O8 powder prepared by this technique has the following desirable physical characteristics: (1) no large particles, (2) crystalline particle morphology, and (3) narrow particle size distribution that is compatible with aluminum powder. The foregoing properties are achieved without grinding or sieving operations.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]=[C:6]2[C:13]1[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:16]2=[N:17][CH:18]=[C:19]([CH2:21][NH2:22])[N:20]=[C:15]2[CH:14]=1.N1C=CC=CC=1.[CH3:38][C:39](OC(C)=O)=[O:40].CC(O)=O>C1COCC1.CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]=[C:6]2[C:13]1[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:30])([CH3:29])[CH3:31])[C:16]2=[N:17][CH:18]=[C:19]([CH2:21][NH:22][C:39](=[O:40])[CH3:38])[N:20]=[C:15]2[CH:14]=1
Reactant: COc1ccc2c(c1)c(-c1cc3nc(CN)cnc3n1COCC[Si](C)(C)C)cn2C
Reactant: CC(=O)OC(C)=O
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: COc1ccc2c(c1)c(-c1cc3nc(CNC(C)=O)cnc3n1COCC[Si](C)(C)C)cn2C
Yield: 102 %

Procedure:
(6-(5-Methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)methanamine (0.185 g, 0.423 mmol, Preparation #I.1) in THF (5 mL) was treated with pyridine (0.044 mL, 0.55 mmol) and Ac2O (0.044 mL, 0.46 mmol). After about 5 min the mixture was treated with AcOH (0.024 mL, 0.42 mmol), diluted with EtOAc (20 mL) and then washed with water (15 mL) and brine (10 mL). The organic layer was dried over anhydrous MgSO4, filtered and evaporated under reduced pressure to give N-((6-(5-Methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)methyl)acetamide (0.207 g, 102%, crude): LC/MS (Table 2, Method a) Rt=2.63 min; MS m/z 480 (M+H)+.