Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[CH:5]=[CH:4][C:3]([C:6]2[S:10][C:9]([NH:11]C=O)=[N:8][C:7]=2[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:2]1>CO.C1COCC1.Cl>[O:1]1[CH:5]=[CH:4][C:3]([C:6]2[S:10][C:9]([NH2:11])=[N:8][C:7]=2[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:2]1
Reactant: O=CNc1nc(-c2ccccc2)c(-c2ccoc2)s1
Agent: Cl
Solvent: C1CCOC1
Solvent: CO
Product: Nc1nc(-c2ccccc2)c(-c2ccoc2)s1

Procedure:
N-(5-Furan-3-yl-4-phenyl-thiazol-2-yl)-formamide (5.7 g, 21 mmol) was dissolved in a mixture of methanol (210 mL) and THF (90 mL), and conc. squeous hydrochloric acid (8.7 mL) was added dropwise at room temperature. The reaction mixture was stirred over night and the solvent was removed by evaporation. The residue was extracted with ethyl acetate, and washed with NaHCO3 (aq.; sat.) and water and dried over sodium sulfate. The solvent was removed and the crude product was purified on neutral Al2O3 using 30-35% ethyl acetate in hexane as eluent. Yield: 2.5 g, 49%.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:8][CH2:9][CH2:10][CH2:11][CH:12]([O:18][CH2:19]Cl)[CH2:13][CH2:14][CH2:15][CH2:16][CH3:17].O>CCOCC>[Cl:8][CH2:9][CH2:10][CH2:11][CH:12]([O:18][CH2:19][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH2:13][CH2:14][CH2:15][CH2:16][CH3:17]
Reactant: Brc1ccccc1
Reactant: CCCCCC(CCCCl)OCCl
Solvent: CCOCC
Solvent: O
Product: CCCCCC(CCCCl)OCc1ccccc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 85.7 %

Procedure:
A solution of bromobenzene (13.18 g., 0.084 mole) in ether (50 ml.) is added to a suspension of Mg (2.04 g., 0.084 mole) in ether (50 ml.) dropwise so as to maintain a gentle reflux. After complete addition of the bromobenzene, the mixture is heated on a steam bath for an additional hour. The reaction mixture is then cooled to 5°-10° C. by means of an ice-water bath, and 1-chloro-4-chloromethoxynonane (19.05 g., 0.084 mole) is added dropwise over 15 minutes. The resulting suspension is stirred for 18 hours at room temperature. The reaction mixture is diluted with ether (100 ml.), cooled to 0°-5° C., and cold water (75 ml.) is added with vigorous stirring while the temperature is kept below 5° C. Let stir at 0°-5° C. for about 15 minutes. The aqueous phase is separated from the ether phase (A), and the aqueous layer is extracted with ether (150 ml., B). Organic solution A is combined with B, washed with H2O (100 ml.), 5% K2CO3 (100 ml.), again with H2O (100 ml.), finally with saturated NaCl solution, and is dried over anhydrous Na2SO4. Removal of the solvent in vacuo yields 1-chloro-4-benzyloxynonane (19.28 g., 0.072 mole, 85.7% yield).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16](=O)[C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([N+:24]([O-:26])=[O:25])[CH:18]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:37])=CC=1>O1CCOCC1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16](=[S:37])[C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([N+:24]([O-:26])=[O:25])[CH:18]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Nc1ccc(OCc2ccccc2)cc1)c1ccc(Cl)c([N+](=O)[O-])c1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: C1COCCO1
Product: O=[N+]([O-])c1cc(C(=S)Nc2ccc(OCc3ccccc3)cc2)ccc1Cl
Yield: 77 %

Procedure:
N-(4-Benzyloxy-phenyl)-4-chloro-3-nitro-benzamide (19.15 g, 50 mmol), Lawesson reagent (11 g, 27 mmol, commercially available) and dioxane (150 ml) were stirred together and heated under reflux for 4 h. When no more starting amide was present, as showed by TLC, the reaction mixture was cooled and the solvent removed under reduced pressure. The crude product was dissolved in minimum boiling toluene to recrystallise. The purified product was filtered and washed with cold toluene and cold hexane to give the thioamide, in 77% yield.
Reaction SMILES: C([O:4][C@@H:5]1[C@H:9]([O:10]C(=O)C)[C@@H:8]([CH3:14])[O:7][C@H:6]1[N:15]1[CH:32]=[C:31]([C:33]#[C:34][Si](C)(C)C)[C:19]([NH:20][C:21]([O:23][CH2:24][C:25]([CH3:30])([CH3:29])[CH2:26][O:27][CH3:28])=[O:22])=[N:18][C:16]1=[O:17])(=O)C.C([O-])([O-])=O.[K+].[K+]>CO>[C:33]([C:31]1[C:19]([NH:20][C:21]([O:23][CH2:24][C:25]([CH3:29])([CH3:30])[CH2:26][O:27][CH3:28])=[O:22])=[N:18][C:16](=[O:17])[N:15]([CH:32]=1)[C@@H:6]1[O:7][C@H:8]([CH3:14])[C@@H:9]([OH:10])[C@H:5]1[OH:4])#[CH:34]
Reactant: COCC(C)(C)COC(=O)Nc1nc(=O)n([C@@H]2O[C@H](C)[C@@H](OC(C)=O)[C@H]2OC(C)=O)cc1C#C[Si](C)(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: C#Cc1cn([C@@H]2O[C@H](C)[C@@H](O)[C@H]2O)c(=O)nc1NC(=O)OCC(C)(C)COC
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 60.4 %

Procedure:
2',3'-di-O-acetyl-5'-deoxy-N4 -[(3-methoxy-2,2- dimethylpropoxy)carbonyl]-5-[2-(trimethylsilyl)ethynyl]-cytidine (100 mg, 0.18 mmol) was dissolved in methanol (4 ml), followed by addition of K2CO3 (38 mg,0.27 mmol). After stirring for 30 min at room temperature, the reaction mixture was evaporated under reduced pressure. Purification of the residue by preparative thin layer chlomatography on silica gel (using dichloromethane:methanol=20:1 as a developing solvent) gave 5'-deoxy-5- ethynyl-N4 -[(3-methoxy-2,2-dimethylpropoxy)carbonyl]cytidine (43 mg, 60%).
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:17]([O:19]C)=[O:18])=[N:4][C:5]([C:9]2[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=2[F:16])=[C:6]([F:8])[CH:7]=1.O.[OH-].[Li+].C1COCC1.Cl>O>[NH2:1][C:2]1[C:3]([C:17]([OH:19])=[O:18])=[N:4][C:5]([C:9]2[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=2[F:16])=[C:6]([F:8])[CH:7]=1
Reactant: COC(=O)c1nc(-c2c(F)cccc2F)c(F)cc1N
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: Nc1cc(F)c(-c2c(F)cccc2F)nc1C(=O)O
Temperature: 50 °C
Yield: 85.7 %

Procedure:
To a mixture of methyl 3-amino-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxylate (84.0 mg, 0.298 mmol) and lithium hydroxide, monohydrate (40.2 mg, 0.958 mmol), THF (2.0 mL) was added followed by water (1.0 mL). The mixture was heated at 50° C. for 3 h. The reaction was then cooled to 0° C. for, and 1 M HCl was added slowly until the pH reached 2. The reaction mixture was then diluted with water (20 mL), extracted with EtOAc (3×20 mL), and the combined organic extract was washed with brine (30 mL), dried over Na2SO4, and concentrated under reduced pressure to give the sub-title compound as a white solid (68.5 mg, 86%). LCMS calc. for C12H8F3N2O2 (M+H)+: m/z=269.0. found 269.0.
Reaction SMILES: [O:1]=[C:2]1[CH2:10][C:9]2[C:4](=[C:5]([CH2:11][CH2:12][C:13]([OH:15])=O)[CH:6]=[CH:7][CH:8]=2)[NH:3]1>C(OC(=O)C)(=O)C>[CH2:10]1[C:9]2=[C:4]3[C:5](=[CH:6][CH:7]=[CH:8]2)[CH2:11][CH2:12][C:13](=[O:15])[N:3]3[C:2]1=[O:1]
Reactant: O=C(O)CCc1cccc2c1NC(=O)C2
Solvent: CC(=O)OC(C)=O
Product: O=C1CCc2cccc3c2N1C(=O)C3
Reaction time: 1 h

Procedure:
A solution of 2,3-dihydro-2-oxo-1H-indole-7-propanoic acid (2.0 g, 0.0098 mole) in acetic anhydride (8 ml) is heated to 90° C. with stirring for one hour. Excess acetic anhydride is removed at reduced pressure. The red crystalline material is purified by flash chromatography over silica (elution with 23:2 dichloromethane:diethyl ether). Final purification by fractional sublimation yields 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2,4(1H)-dione, mp 194°-197° C.
Reaction SMILES: CC([O-])(C)C.[K+].[CH2:7]([O:9][C:10](=[O:14])[CH2:11][N+:12]#[C-:13])[CH3:8].[N:15]([C:18]1[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=1)=[C:16]=[S:17]>O1CCCC1>[CH2:7]([O:9][C:10]([C:11]1[N:12]=[CH:13][S:17][C:16]=1[NH:15][C:18]1[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=1)=[O:14])[CH3:8]
Reactant: S=C=Nc1cccnc1
Reactant: [C-]#[N+]CC(=O)OCC
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CCOC(=O)c1ncsc1Nc1cccnc1
Temperature: -40 °C
Yield: 44 %

Procedure:
A three-necked flask equipped with a mechanical stirrer, a dropping funnel and an argon inlet was charged with anhydrous tetrahydrofurane (THF) (25.00 ml). Solid potassium tert-butylate (5.46 g, 44.20 mmol) was added and the slurry was stirred until dissolution was complete. The mixture was cooled to −40° C. by means of a dry ice/acetone bath. A solution of isocyano-acetic acid ethyl ester (5.00 g, 44.20 mmol) and 3-isothiocyanato-pyridine (6.02 g, 44.20 mmol) in anhydrous THF (50.00 ml) was added dropwise via the dropping funnel at such a rate that the temperature did not exceed −35° C. and the mixture remained homogeneously stirred (a thick precipitate forms). After addition was complete, the mixture was stirred for further 1 hour letting the temperature free to rise. The reaction was quenched by addition of glacial acetic acid (2.50 ml). The mixture was diluted with THF and ethyl acetate and filtered through celite. The filtrate was evaporated to a dark yellow solid residue, which was purified by flash chromatography (heptane/ethyl acetate) to yield 5-(pyridin-3-ylamino)-thiazole-4-carboxylic acid ethyl ester (4.85 g, 44%) as a light yellow solid, MS (ISP): m/e=250.2 (M+H+).
Reaction SMILES: [CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:23])[CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[O:33]1COCO[CH2:34]1>C(Cl)Cl.[Ti](Cl)(Cl)(Cl)Cl>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:23])[C@@H:15]([CH2:34][OH:33])[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C1OCOCO1
Reactant: O=C(CCc1ccccc1)N1C(=O)OC[C@@H]1Cc1ccccc1
Agent: Cl[Ti](Cl)(Cl)Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: O=C1OC[C@H](Cc2ccccc2)N1C(=O)[C@@H](CO)Cc1ccccc1
Reaction time: 0.33 h

Procedure:
1 M of titanium tetrachloride in DCM (43 mL) was added to a solution of intermediate (7b) (12.7 g, 41 mmol) in DCM (150 mL) at 0° C. under nitrogen. After 20 minutes, DIPEA (7.9 mL, 45.2 mmol) was added dropwise at 0° C. After 80 minutes, 1,3,5-trioxane (4.1 g, 45.2 mmol) in DCM (30 mL) was added, followed by a second equivalent of 1 M titanium tetrachloride in DCM after 10 minutes. After 2.5 hours at 0° C., the mixture was quenched with saturated aqueous NH4Cl (150 mL). The product was extracted with water (100 mL) and DCM (3×200 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo to yield intermediate (7c), which was used in the next step without further purification.
Reaction SMILES: [CH2:1]([O:3][C:4]([CH2:6]P(=O)(OCC)OCC)=[O:5])[CH3:2].[H-].[Na+].[C:17]1([CH3:30])[CH:22]=[CH:21][C:20]([C:23](=O)[C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:19][CH:18]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[C:17]1([CH3:30])[CH:18]=[CH:19][C:20](/[C:23](=[CH:6]/[C:4]([O:3][CH2:1][CH3:2])=[O:5])/[C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:21][CH:22]=1
Reactant: CCOC(=O)CP(=O)(OCC)OCC
Reactant: CCOC(=O)C(=O)c1ccc(C)cc1
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)/C=C(\C(=O)OCC)c1ccc(C)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 92.5 %

Procedure:
A solution of diethyl ethoxycarbonylmethylphosphonate (3.3 g) in anhydrous tetrahydrofuran (20 ml) is added dropwise to a suspension of sodium hydride (60%, oily) (676 mg) in anhydrous tetrahydrofuran (30 ml) under a nitrogen atmosphere and ice cooling, and further a solution of ethyl 4-tolylglyoxylate (2.96 g) in anhydrous tetrahydrofuran (22 ml) is added dropwise thereto. The mixture is stirred at room temperature for 30 minutes, a 10% aqueous citric acid solution is added to the reaction mixture, and the whole is extracted with ether. The organic layer is washed with water and saturated brine successively, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography to give 3.57 g (88%) of diethyl 2-(4-tolyl)maleate.
Reaction SMILES: [O:1]=[C:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][C:6]([C:12]#N)=[CH:7][CH:8]=2)[NH:3]1.[OH2:14]>C(O)=O.[Ni]>[O:1]=[C:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][C:6]([CH:12]=[O:14])=[CH:7][CH:8]=2)[NH:3]1
Reactant: N#Cc1ccc2c(c1)NC(=O)CC2
Reactant: O
Agent: [Ni]
Solvent: O=CO
Product: O=Cc1ccc2c(c1)NC(=O)CC2
Temperature: 100 °C

Procedure:
Step R1-3: To a suspension of 2-oxo-1,2,3,4-tetrahydroquinoline-7-carbonitrile (160 g) in HCO2H (1.6 L) was added Raney Nickel Catalyst (slurry in water, 160 g) at room temperature over 30 minutes. The mixture was heated at 100° C. for 2 hours. After cooling to room temperature, the reaction mixture was filtrated through a pad of Celite and washed with HCO2H. The filtrate was concentrated to obtain a solid. The solid was stirred with water (1.3 L) and filtrated to obtain 2-oxo-1,2,3,4-tetrahydroquinoline-7-carbaldehyde as a pale brown solid (156 g).
Reaction SMILES: [CH2:1]([C:8]1[N:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([NH2:24])[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[Cl:25])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:26][C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][C:34]=1[Cl:35])[CH:30]=O>>[CH2:1]([C:8]1[N:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([NH:24][CH2:30][C:29]3[CH:32]=[CH:33][C:34]([Cl:35])=[C:27]([Cl:26])[CH:28]=3)[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[Cl:25])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Nc1cccc(-c2c(Cc3ccccc3)nnc3c(Cl)cccc23)c1
Reactant: O=Cc1ccc(Cl)c(Cl)c1
Product: Clc1ccc(CNc2cccc(-c3c(Cc4ccccc4)nnc4c(Cl)cccc34)c2)cc1Cl

Procedure:
The title compound was prepared from [3-(3-benzyl-8-chlorocinnolin-4-yl)phenyl]amine and 3,4-dichlorobenzaldehyde according to the procedure of Step 5 Example 6. MS (ES) m/z 504.6.
Reaction SMILES: [CH:1]1[C:14]2[NH:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[S:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.I[CH2:16][CH3:17].[OH-].[K+]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[CH2:16]([N:13]1[C:14]2[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=2[S:6][C:7]2[C:12]1=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH3:17]
Reactant: CCI
Reactant: c1ccc2c(c1)Nc1ccccc1S2
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=S(=O)([O-])O
Agent: [K+]
Solvent: Cc1ccccc1
Product: CCN1c2ccccc2Sc2ccccc21

Procedure:
A mixture of 10 g (0.05 mol) of phenothiazine (from Fluka), 11.7 g (0.075 mol) of iodoethane (from Aldrich), 4.2 g (0.075 mol) of potassium hydroxide, and 0.25 g of tetra-n-butylammonium hydrogen sulfate (from Aldrich) in 200 ml of dry toluene was refluxed for 24 hrs. The cooled reaction mixture was filtered and the solvent was evaporated. The product was recrystallized from methanol. The yield of 10-ethylphenothiazine was 10.2 g (90%). The product had a melting point of 103–104° C. (recrystallized from methanol). A 1H NMR spectrum yielded the following results (100 MHz, CDCl3, δ, ppm): 1.40 (t, J=7.0 Hz, 3H, CH3); 3.90 (q, J=7.0 Hz, 2H, CH2); 6.78–7.32 (m, 8H, Ar).
Reaction SMILES: C([O:4][C:5]([CH3:7])=[CH2:6])(=O)C.C[O-].C([Sn+](CCCC)CCCC)CCC.[Cl:23][C:24]1[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:25]=1[CH:31]=[CH:32][CH:33]=[O:34].C(O)(=O)CC(O)=O>CCOCC>[Cl:23][C:24]1[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:25]=1[CH:31]=[CH:32][CH:33]([OH:34])[CH2:6][C:5](=[O:4])[CH3:7]
Reactant: C=C(C)OC(C)=O
Reactant: O=CC=Cc1ccc(Cl)cc1Cl
Agent: CCCC[Sn+](CCCC)CCCC
Agent: C[O-]
Agent: O=C(O)CC(=O)O
Solvent: CCOCC
Product: CC(=O)CC(O)C=Cc1ccc(Cl)cc1Cl
Temperature: -20 °C
Reaction time: 1 h
Yield: 81 %

Procedure:
2-Acetoxypropene (3.3 ml, 30 mmole) and tri-n-butyltin methoxide (5.7 g, 24 mmole) were combined and stirred at 60°-70° C. under N2 for 1 hour then placed under vacuum for an additional 30 minutes. 3-(2,4-Dichlorophenyl)propenal (4 g, 20 mmole) was added and the reaction mixture was stirred at 70° C. under N2 for 4 hours. The clear reaction mixture was then cooled, treated with malonic acid (1 g, 10 mmole) in ether (20 ml) and refluxed for 30 minutes. After cooling to -20° C., the reaction mixture was filtered and the precipitate was washed with ether (4×10 ml). The ethereal solutions were combined, evaporated and the residual oil was chromatographed on a 60 mm column with 15 cm of silica gel (230-400 mesh). Elution with chloroform-methanol (99:1, v:v; 2.0 L) provided the title compound as a thick yellow oil (4.2 g, 81%); pmr CDCl3) 2.2 (3H, s), 2.73 (2H, d), 4.73 (H, m), 6.10 (H, dd).
Reaction SMILES: C([O:3][C:4]([C:6]1[S:10][C:9]([NH:11][C:12](=[O:28])[CH:13]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[CH2:14][CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)=[N:8][CH:7]=1)=[O:5])C.[OH-].[Na+]>C(O)C>[CH:15]1([CH2:14][CH:13]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[C:12]([NH:11][C:9]2[S:10][C:6]([C:4]([OH:5])=[O:3])=[CH:7][N:8]=2)=[O:28])[CH2:19][CH2:18][CH2:17][CH2:16]1
Reactant: CCOC(=O)c1cnc(NC(=O)C(CC2CCCC2)c2ccc(Cl)c(Cl)c2)s1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)c1cnc(NC(=O)C(CC2CCCC2)c2ccc(Cl)c(Cl)c2)s1
Temperature: 25 °C
Yield: 22.4 %

Procedure:
A solution of 2-[3-cyclopentyl-2-(3,4-dichlorophenyl)-propionylamino]-thiazole-5-carboxylic acid ethyl ester (prepared as in Example 1(B)(g), 1.0 g, 2.27 mmol) in absolute ethanol (10 mL) was treated with a 1N aqueous sodium hydroxide solution (4.77 mL, 4.77 mmol). The reaction mixture was heated under reflux for 15 h. The reaction mixture was allowed to cool to 25° C. and then concentrated in vacuo to remove absolute ethanol. The resulting yellow residue was acidified to pH=2 with concentrated hydrochloric acid and extracted with ethyl acetate (2×75 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. Recrystallization from ethyl acetate afforded 2-[3-cyclopentyl-2-(3,4-dichlorophenyl)-propionylamino]-thiazole-5-carboxylic acid (210 mg, 22%) as a white solid: mp 269-270° C.; FAB-HRMS m/e calcd for C18H18Cl2N2O3S (M+H)+ 413.0493, found 413.0483.
Reaction SMILES: [CH3:1][C@:2]12[C:8]([CH3:10])([CH3:9])[C@H:5]([CH2:6][CH2:7]1)[CH:4]=[C:3]2[C:11]1[CH:20]=[CH:19][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][CH:12]=1>C(OCC)(=O)C.C(O)C.[Pd]>[CH3:1][C@:2]12[C:8]([CH3:9])([CH3:10])[C@H:5]([CH2:6][CH2:7]1)[CH2:4][CH:3]2[C:11]1[CH:12]=[CH:13][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:19][CH:20]=1
Reactant: COC(=O)c1ccc(C2=C[C@H]3CC[C@]2(C)C3(C)C)cc1
Agent: [Pd]
Solvent: CCO
Solvent: CCOC(C)=O
Product: COC(=O)c1ccc(C2C[C@H]3CC[C@]2(C)C3(C)C)cc1

Procedure:
A mixture of Example 372B (100 mg) and 10% Pd/C (20 mg) in ethyl acetate (5 mL) and ethanol (5 mL) at room temperature was stirred under H2 for 18 hours, filtered, and concentrated to provide the desired product. MS (DCI(+)) m/e 245 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[C:3](=[S:17])[NH:4][C:5]([C:8]2([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH2:10][CH2:9]2)=[CH:6][CH:7]=1.[I:18][C:19]1[CH:27]=[CH:26][C:22]([C:23](Cl)=O)=[CH:21][CH:20]=1.NC1C(=S)NC=CC=1>>[I:18][C:19]1[CH:27]=[CH:26][C:22]([C:23]2[S:17][C:3]3[C:2]([N:1]=2)=[CH:7][CH:6]=[C:5]([C:8]2([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=4)[CH2:10][CH2:9]2)[N:4]=3)=[CH:21][CH:20]=1
Reactant: O=C(Cl)c1ccc(I)cc1
Reactant: Nc1ccc(C2(c3ccccc3)CC2)[nH]c1=S
Agent: Nc1ccc[nH]c1=S
Product: Ic1ccc(-c2nc3ccc(C4(c5ccccc5)CC4)nc3s2)cc1

Procedure:
Reaction of 3-amino-6-(1-phenylcyclopropyl)pyridine-2(1H)-thione (503.8 mg, 2.079 mmol) and 4-iodobenzoyl chloride (554 mg, 2.079 mmol) according to Reference V and the general procedure for the condensation of 3-aminopyridine-2-thione with aryl acid chlorides gave 2-(4-iodophenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine as a white solid. MS (ESI) m/z: Calculated: 454.0; Observed: 454.9 (M++1).
Reaction SMILES: [O:1]1[C@H:3]2[CH2:4][C@H:5]3[C@:18]([CH3:20])([CH2:19][C@@H:2]12)[C@@H:17]1[C@H:8]([C@H:9]2[C@@:13]([CH2:15][CH2:16]1)([CH3:14])[C@@H:12]([OH:21])[C@@H:11]([N:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1)[CH2:10]2)[CH2:7][CH2:6]3.[OH:27][CH:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1>>[OH:27][CH:28]1[CH2:33][CH2:32][N:31]([C@H:2]2[CH2:19][C@@:18]3([CH3:20])[C@@H:5]([CH2:6][CH2:7][C@@H:8]4[C@@H:17]3[CH2:16][CH2:15][C@@:13]3([CH3:14])[C@H:9]4[CH2:10][C@H:11]([N:22]4[CH2:23][CH2:24][CH2:25][CH2:26]4)[C@@H:12]3[OH:21])[CH2:4][C@@H:3]2[OH:1])[CH2:30][CH2:29]1
Reactant: OC1CCNCC1
Reactant: C[C@]12C[C@H]3O[C@H]3C[C@@H]1CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](O)[C@@H](N3CCCC3)C[C@@H]12
Product: C[C@]12C[C@H](N3CCC(O)CC3)[C@@H](O)C[C@@H]1CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](O)[C@@H](N3CCCC3)C[C@@H]12
Yield: 76.5 %

Procedure:
2α,3α-Epoxy-16β-(1-pyrrolidinyl)-5α-androstane-17β-ol is reacted with 4-hydroxypiperidine as described in Example 3 to obtain the title product in a yield of 76.5%, m.p.: 188°-190° C.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH2:7][NH2:8])([O-:3])=[O:2].Cl[C:13]1[C:14]2[CH:26]=[C:25]([CH3:27])[S:24][C:15]=2[N:16]=[C:17]([C:19]2[O:23][N:22]=[CH:21][CH:20]=2)[N:18]=1>>[O:23]1[C:19]([C:17]2[N:18]=[C:13]([NH:8][CH2:7][C:6]3[CH:9]=[CH:10][CH:11]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[C:14]3[CH:26]=[C:25]([CH3:27])[S:24][C:15]=3[N:16]=2)=[CH:20][CH:21]=[N:22]1
Reactant: NCc1cccc([N+](=O)[O-])c1
Reactant: Cc1cc2c(Cl)nc(-c3ccno3)nc2s1
Product: Cc1cc2c(NCc3cccc([N+](=O)[O-])c3)nc(-c3ccno3)nc2s1

Procedure:
With the procedure of Example 1, the reaction of 3-nitrobenzylamine with 4-chloro-2-(isoxazol-5-yl)-6-methyl-thieno-[2,3-d]-pyrimidine yields 2-(isoxazol-5-yl)-4-(3-nitrobenzylamino)-6-methyl-thieno-[2,3-d]-pyrimidine.
Reaction SMILES: [SH:1][C:2]1[CH:3]=[C:4]([B:8]([OH:10])[OH:9])[CH:5]=[CH:6][CH:7]=1.Br[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][C:20]([OH:22])=[O:21])=[CH:15][CH:14]=1>>[C:20]([CH2:19][C:16]1[CH:17]=[CH:18][C:13]([CH2:12][S:1][C:2]2[CH:3]=[C:4]([B:8]([OH:10])[OH:9])[CH:5]=[CH:6][CH:7]=2)=[CH:14][CH:15]=1)([OH:22])=[O:21]
Reactant: OB(O)c1cccc(S)c1
Reactant: O=C(O)Cc1ccc(CBr)cc1
Product: O=C(O)Cc1ccc(CSc2cccc(B(O)O)c2)cc1

Procedure:
3-(4-Carboxymethyl-benzylsulfanyl)-phenylboronic acid was prepared from 3-mercaptophenylboronic acid and 4-bromomethylphenyl acetic acid according to the procedure of Example 12;
Reaction SMILES: [OH2:1].[N+]([O-])([O-])=O.[La+3:6].[N+]([O-])([O-])=O.[N+]([O-])([O-])=O.[N+]([O-])([O-])=O.[Sr+2:19].[N+]([O-])([O-])=O.[OH2:24].[N+]([O-])([O-])=O.[Al+3:29].[N+]([O-])([O-])=O.[N+]([O-])([O-])=O.[OH2:38].[N+]([O-])([O-])=O.[Cr+3:43].[N+]([O-])([O-])=O.[N+]([O-])([O-])=O>>[Cr:43]([O-:38])([O-:24])=[O:1].[Al+3:29].[Sr+2:19].[La+3:6].[Cr:43]([O-:38])([O-:24])=[O:1].[Cr:43]([O-:38])([O-:24])=[O:1].[Cr:43]([O-:38])([O-:24])=[O:1]
Reactant: O
Reactant: [Cr+3]
Agent: O=[N+]([O-])[O-]
Agent: [Al+3]
Agent: [La+3]
Product: O=[Cr]([O-])[O-]

Procedure:
Using the same procedure as described in Example 1, lanthanum nitrate hydrate, strontium nitrate, aluminum nitrate hydrate, and chromium nitrate hydrate were combined to produce lanthanum strontium aluminum chromite La1-ySryCr1-xAlxO3, where y=0.0 to 0.3 and x=0.0 to 0.3. This refractory ceramic exhibits good electrical conductivity.
Reaction SMILES: [CH2:1]([C:5]1[N:6]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[CH:16][CH:15]=2)[C:7]([Cl:12])=[C:8]([CH2:10][OH:11])[N:9]=1)[CH2:2][CH2:3][CH3:4]>C(Cl)Cl.O=[Mn]=O>[CH2:1]([C:5]1[N:6]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]([O:28][C:29]([CH3:30])([CH3:32])[CH3:31])=[O:27])=[CH:16][CH:15]=2)[C:7]([Cl:12])=[C:8]([CH:10]=[O:11])[N:9]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc(CO)c(Cl)n1Cc1ccc(-c2ccccc2C(=O)OC(C)(C)C)cc1
Agent: O=[Mn]=O
Solvent: ClCCl
Product: CCCCc1nc(C=O)c(Cl)n1Cc1ccc(-c2ccccc2C(=O)OC(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 0.1 %

Procedure:
A mixture of 2-butyl-1-[(2'-t-butoxycarbonylbiphen-4-yl)methyl]-5-chloro-1H-imidazole-4-methanol (European Patent Applications 253,310) (145 mg, 319 mmol), MnO2 (550 mg, 6.4 mmol), 3A powdered sieves (500 mg) in CH2Cl2 (10 mL) was stirred at room temperature for 3 hours. The mixture was filtered and evaporated to give 142 mg of the title compound as a glass. 1H NMR (300 MHz, CD3OD)δ 9.82 (s, 1H), 7.70 (dd, 1H, J=7 and 1.5 Hz), 7.50 (td, 1H, J=7 and 1.5 Hz), 7.40 (td, 1H, J=7 and 1.5 Hz), 7.31-7.26 (m, 3H), 7.15 (apparent d, 2H, J=3 Hz), 5.38 (s, 2H), 2.73 (t, 2H, J= 7.5 Hz), 1.72-1.62 (m, 2H), 1.45-1.30 (m, 2H) 1.21 (s, 9H), 0.90 (t, 3H, J=7 Hz).