Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:8]=2)[CH:3]=1.CCCCCC.C([Li])CCC.C([O:32][B:33](OC(C)C)[O:34]C(C)C)(C)C.Cl>C1(C)C=CC=CC=1.C(OCC)C.C1COCC1>[C:12]1([C:7]2[CH:8]=[C:9]3[C:4](=[CH:5][CH:6]=2)[CH:3]=[C:2]([B:33]([OH:34])[OH:32])[CH:11]=[CH:10]3)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Reactant: Brc1ccc2cc(-c3ccccc3)ccc2c1
Agent: Cl
Agent: [Li]CCCC
Solvent: Cc1ccccc1
Solvent: CCCCCC
Solvent: C1CCOC1
Product: OB(O)c1ccc2cc(-c3ccccc3)ccc2c1
Temperature: 60 °C
Yield: 66.2 %

Procedure:
Under an argon gas atmosphere, a mixture of 100.0 g (353.1 mmol) of 2-bromo-6-phenylnaphthalene, 1.2 L of dehydrated THF and 1.2 L of dehydrated diethyl ether was cooled down to minus 20 degree C. Then, 280 ml (437 mmol) of hexane solution of 1.56M n-butyllithium was dropped into the mixture while the mixture was being stirred. The reaction mixture was further stirred at minus 20 degrees for 1 hour. The reaction mixture was cooled down to minus 60 degrees C., and 199.3 g (1.06 mol) of triisopropylborate was dropped into the mixture. The reaction mixture was warmed up and then stirred at room temperature for 16 hours. The reaction mixture was added with aqueous solution of hydrochloric acid and stirred at room temperature for 1 hour. After the reaction, the reaction mixture was added with toluene, and aqueous phase thereof was eliminated. Then, organic phase thereof was washed with water and dried with magnesium sulfate, and the solvent was distilled away under reduced pressure. By recrystallizing the obtained solid with hexane, 58.0 g of 6-phenylnaphthalene-2-boronic acid was obtained at an yield of 55%.
Reaction SMILES: [NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.[H-].[Na+].[F:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[C@@:16]1([C@@H:19]([OH:21])[CH3:20])[CH2:18][O:17]1>CN(C=O)C>[F:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[C@:16]([OH:17])([C@H:19]([OH:21])[CH3:20])[CH2:18][N:1]1[CH:5]=[N:4][CH:3]=[N:2]1
Reactant: C[C@H](O)[C@]1(c2cc(F)ccc2F)CO1
Reactant: c1nc[nH]n1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C[C@@H](O)[C@](O)(Cn1cncn1)c1cc(F)ccc1F
Temperature: 70 °C
Yield: 74.3 %

Procedure:
1,2,4-Triazole (7 mg; 0.1 mmol) is dissolved in DMF (0.5 ml). Sodium hydride (4.4 mg; 60% suspension in paraffin; 0.1 mmol) is added and the reaction mixture is heated to 70° C. for one hour. The reaction mixture is cooled to room temperature and 1(S)-[2(S)-(2,5-Difluoro-phenyl)-oxiranyl]-ethanol (5 mg; 0.025 mmol from example 8) dissolved in DMF (0.5 ml) is added slowly. The reaction mixture is then heated to 70° C. for three hours. The solvent is evaporated. The residue is taken-up in ethyl acetate (5 ml) and water (3 ml). The phases are separated. The aqueous layer is extracted 3 times with ethyl acetate (3 times 5 ml). The combined organic phases are washed twice with water (2 times 5 ml). The organic phase is dried over sodium sulfate. The solids are filtered off and the solvent is removed under reduced pressure. 5 mg of (2R,3R)-2-(2,5-Difluoro-phenyl)-1-[1,2,4]-triazol-1-yl-butane-2,3-diol are obtained as a light yellow oil.
Reaction SMILES: C1(C)C=CC=CC=1.Cl.[NH:9]=[C:10]1[CH:15]=[CH:14][N:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:12]=[CH:11]1.[C:22](Cl)(=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[OH-].[Na+]>O>[C:22]([N:9]=[C:10]1[CH:15]=[CH:14][N:13]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:12]=[CH:11]1)(=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: N=c1ccn(-c2ccccc2)nc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Solvent: O
Product: O=C(N=c1ccn(-c2ccccc2)nc1)c1ccccc1
Yield: 71.6 %

Procedure:
80 ml of toluene were added to a solution of 10.0 g (48.2 millimoles) of 1,4-dihydro-4-imino-1-phenylpyridazine hydrochloride in 80 ml of water. First 6.8 g (48.4 millimoles) of benzoyl chloride and then, in the course of 15 minutes, 4.0 g (100 millimoles) of NaOH in 20 ml of water were added to the two-phase system at room temperature, whilst stirring, the mixture was stirred for a further hour at room temperature and the product was then filtered off under suction. The solid obtained was washed with water, dried and recrystallized from ethanol. 9.5 g (72% of theory) of 4-benzoylimino-1,4-dihydro-1-phenylpyridazine were isolated as yellow crystals of melting point 175°-176° C.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[OH:10])[CH:5]=[O:6].[CH2:11](Br)[CH2:12]Br.[OH-].[Na+]>[Cu].C(O)C>[CH2:11]1[CH2:12][O:10][C:9]2[CH:8]=[CH:7][C:4]([CH:5]=[O:6])=[CH:3][C:2]=2[O:1]1
Reactant: O=Cc1ccc(O)c(O)c1
Reactant: BrCCBr
Agent: [Cu]
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=Cc1ccc2c(c1)OCCO2

Procedure:
(i)(a) A mixture of 3,4-dihydroxybenzaldehyde (10.0 g), ethylene dibromide (13.61 g), copper powder (trace), sodium hydroxide (5.80 g) and ethanol (500 ml) was heated at reflux for 2 days. Subsequently, the solvent was evaporated and the residue was dissolved in dichloromethane. The organic phase was shaken with a little water and then dried over anhydrous magnesium sulphate. The solvent was evaporated and the residue was purified by column chromatography over silica gel (eluant dichloromethane) giving 3,4-ethylenedioxybenzaldehyde as an oil. The product was characterized by proton nuclear magnetic resonance spectroscopy. Pmr spectrum (CDCl3 ; δ in ppm): 4.35 (4H, s); 6.98 (1H, d); 7.40 (2H, m); 9.70 (1H, s).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:10][C:11]([O:13]CC)=O)=[CH:4][C:3]=1[O:22][CH3:23].CCCCCC>C1C=CC(C2C=CC=CC=2)=CC=1.C1C=CC(OC2C=CC=CC=2)=CC=1>[Br:1][C:2]1[CH:7]=[C:6]2[C:5](=[CH:4][C:3]=1[O:22][CH3:23])[NH:8][C:9]([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)=[CH:10][C:11]2=[O:13]
Reactant: CCOC(=O)C=C(Nc1ccc(Br)c(OC)c1)c1ccccc1
Solvent: c1ccc(Oc2ccccc2)cc1
Solvent: c1ccc(-c2ccccc2)cc1
Solvent: CCCCCC
Product: COc1cc2[nH]c(-c3ccccc3)cc(=O)c2cc1Br
Temperature: 25 °C
Yield: 88.5 %

Procedure:
DOWTHERM A (450 mL) was heated to reflux (˜300 C). A mixture of the product from step 2 (49 g, 130 mmol) in DOWTHERM A (50 mL) was added to the heated DOWTHERM A solution portionwise. The mixture was stirred at reflux for 30 min after the addition was complete. The mixture was cooled RT, and hexane (400 mL) was added. The mixture was stirred for 30 min and filtered, and the solids were washed with hexane to give the title compound (38 g, 88% yield). LRMS (M+H)+ Calcd.: 330.0; found 330.2.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.Br[CH2:10][CH:11]=[CH2:12].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:12]([O:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[CH:11]=[CH2:10]
Reactant: Oc1ccc(F)cc1
Reactant: C=CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: C=CCOc1ccc(F)cc1
Temperature: 60 °C
Reaction time: 3.5 h
Yield: 61.4 %

Procedure:
Into a 1 L round-bottomed flask containing 500 ml of acetonitrile was added 4-fluorophenol (30.0 g, 267.6 mmol), 3-bromoprop-1-ene (41.7 g, 344.7 mmol, 1.3 eq), and potassium carbonate (55 g, 398 mmol, 1.5 eq). The mixture was stirred for 3.5 hours at 60° C. (oil bath). The solids were filtered off and the filtrate was concentrated under vacuum leaving 25.0 grams of the crude product as a yellow oil; 61%.
Reaction SMILES: [CH3:1][C@@H:2]1[CH2:24][C:23]2[C:25](=[O:26])[C:18](=[CH:19][C:20]([C:22]=2OC)=[O:21])[NH:17][C:15](=[O:16])[C:14]([CH3:29])=[CH:13][CH:12]=[CH:11][C@H:10]([O:30][CH3:31])[C@@H:9]([O:32][C:33]([NH2:35])=[O:34])[C:8]([CH3:36])=[CH:7][C@H:6]([CH3:37])[C@@H:5]([OH:38])[C@@H:4]([O:39][CH3:40])[CH2:3]1.[CH3:41][N:42]([CH3:46])[CH2:43][CH2:44][NH2:45]>C(Cl)Cl>[CH3:1][C@@H:2]1[CH2:24][C:23]2[C:25](=[O:26])[C:18](=[CH:19][C:20]([C:22]=2[NH:45][CH2:44][CH2:43][N:42]([CH3:46])[CH3:41])=[O:21])[NH:17][C:15](=[O:16])[C:14]([CH3:29])=[CH:13][CH:12]=[CH:11][C@H:10]([O:30][CH3:31])[C@@H:9]([O:32][C:33]([NH2:35])=[O:34])[C:8]([CH3:36])=[CH:7][C@H:6]([CH3:37])[C@@H:5]([OH:38])[C@@H:4]([O:39][CH3:40])[CH2:3]1
Reactant: COC1=C2C[C@@H](C)C[C@H](OC)[C@H](O)[C@@H](C)C=C(C)[C@H](OC(N)=O)[C@@H](OC)C=CC=C(C)C(=O)NC(=CC1=O)C2=O
Reactant: CN(C)CCN
Agent: COC1=C2C[C@@H](C)C[C@H](OC)[C@H](O)[C@@H](C)/C=C(\C)[C@H](OC(N)=O)[C@@H](OC)/C=C\C=C(/C)C(=O)NC(=CC1=O)C2=O
Agent: CO[C@H]1/C=C\C=C(/C)C(=O)NC2=CC(=O)C(NCCN(C)C)=C(C[C@@H](C)C[C@H](OC)[C@H](O)[C@@H](C)/C=C(\C)[C@@H]1OC(N)=O)C2=O
Solvent: ClCCl
Product: CO[C@H]1C=CC=C(C)C(=O)NC2=CC(=O)C(NCCN(C)C)=C(C[C@@H](C)C[C@H](OC)[C@H](O)[C@@H](C)C=C(C)[C@@H]1OC(N)=O)C2=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of geldanamycin (1.5 g, 2.68 mmol) (NCI, Lot No. 3059-25-1) and N,N-dimethylethylenediamine (1.5 mL, 13.7 mmol) (Aldrich, Lot No. 04216AL) in dry methylene chloride (30 mL) (Burdick & Jackson, Lot No. BH516) was stirred at room temperature for 1 hour and subsequently poured into ice water (50 mL). After the organic layer and the aqueous layer became visually separated, the aqueous layer was extracted with methylene chloride (2×10 mL). The combined methylene chloride solution was washed with water (2×10 mL), dried with MgSO4 (J.T. Baker, Lot No. E01098) and evaporated in an aspirator. The remaining residue was purified by silica gel chromatography (30 g) (EM Science, Lot No. 325TA509634) eluting with 10% methanol (Chempure, Lot No. M178KMDH) in methylene chloride. The fractions containing product were combined and concentrated in an aspirator. The residue was then dissolved in hot methylene chloride (3 mL), cooled to room temperature and diluted with hexane (60 mL) (Chempure, Lot No. M148KMRC). This mixture was then stirred at room temperature for 30 minutes. A purple powder formed and was collected by filtration, washed with hexane (2×10 mL) and dried at 55° C./0.1 mmHg for 6 hours to give pure target compound. Approximately 1.59 g of 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (96%) was isolated and used in Example 1.
Reaction SMILES: C(NC)C.[CH2:5]([C:7]1[N:15]=[C:14]([NH:16][CH3:17])[N:13]=[C:12]2[C:8]=1[NH:9][CH:10]=[N:11]2)[CH3:6].C1C(=O)NC(=O)N([C@@H:26]2[O:30][C@H:29]([CH2:31][OH:32])[C@@H:28]([OH:33])[C@@H:27]2[OH:34])C=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[N-]=[N+]=[N-].[K+].[C@@H]1(N2C=CC(=O)NC2=O)O[C@H](CO)[C@@H](O)[C@H]1O>C(#N)C.C(O)CC>[CH2:5]([C:7]1[N:15]=[C:14]([NH:16][CH3:17])[N:13]=[C:12]2[C:8]=1[NH:9][CH:10]=[N:11]2)[CH3:6].[C@@H:26]1([N:11]2[CH:10]=[N:9][C:8]3[C:12]2=[N:13][C:14]([NH:16][CH3:17])=[N:15][C:7]=3[CH2:5][CH3:6])[O:30][C@H:29]([CH2:31][OH:32])[C@@H:28]([OH:33])[C@@H:27]1[OH:34]
Reactant: O=c1ccn([C@@H]2O[C@H](CO)[C@@H](O)[C@@H]2O)c(=O)[nH]1
Agent: CCNC
Agent: CCc1nc(NC)nc2nc[nH]c12
Agent: O=P([O-])([O-])[O-]
Solvent: CC#N
Solvent: CCCO
Product: CCc1nc(NC)nc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O
Temperature: 37 °C
Yield: 157 %

Procedure:
6-Ethyl(methyl)aminopurine was prepared by nucleophilic displacement of the chlorine group on 6-chloropurine (Sigma Chemicals, St. Louis, Mo.) by ethyl-(methyl)amine in acetonitrile. 6-Ethyl(methyl)aminopurine (2.8 mmoles, 0.5 g) and uracil arabinoside (5.6 mmoles, 1.38g) were suspended in 575 ml of a 10 mM potassium phosphate, 0.04% potassium azide solution, pH of 7.4, containing 10% n-propanol (v/v). Purified uridine phosphorylase (6000 I.U.) and purine nucleoside phosphorylase (8400 I.U.) (Krenitsky, T. A. et al., Biochemistry, 20, 3615 (1981) and U.S. Pat. No. 4,381,344) were added and the solution stirred at 37° C. Nineteen days later the reaction was filtered and the filtrate chromatographed on a 2.5×13 cm column containing Dowex-1-hydroxide resin. The resin was eluted with 90% methanol/water (v/v). Fractions containing the product were combined and the solvent removed under vacuum. The residue was dissolved in 30% n-propanol/water (v/v) and chromatographed on BioRad P-2 column (7.5×90 cm). Product containing fraction were combined and after lyophilization yielded 0.680 g of 9-β-D-arabinofuranosyl-6-ethyl(methyl)amino-9 H-Purine. NMR and mass spectrometry were consistent with the structure.
Reaction SMILES: [Br:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=1.[F:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[OH:20].C(=O)([O-])[O-].[Cs+].[Cs+].O>CN1C(=O)CCC1>[Br:1][C:2]1[C:3]([O:20][C:14]2[CH:15]=[CH:16][C:17]([F:19])=[CH:18][C:13]=2[F:12])=[N:4][CH:5]=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=1
Reactant: O=[N+]([O-])c1cnc(Cl)c(Br)c1
Reactant: Oc1ccc(F)cc1F
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN1CCCC1=O
Product: O=[N+]([O-])c1cnc(Oc2ccc(F)cc2F)c(Br)c1
Temperature: 60 °C
Yield: 60.4 %

Procedure:
A solution of 3-bromo-2-chloro-5-nitropyridine (2.4 g, 10 mmol) and 2,4-difluorophenol (1 mL, 11 mmol) in NMP (20 ml) was treated with cesium carbonate (3.9 g, 12 mmol). The resulting mixture was heated to 60° C. for 12 h. The mixture was treated with water (100 ml) and extracted with EtOAc (3×50 ml); the combined organic extracts were washed with saturated bicarbonate solution (aq), dried over sodium sulfate, filtered and concentrated in vacuo to afford a yellow solid. The solid was purified by silica gel column chromatography (gradient of 5 to 30% EtOAc in hexanes) to afford the free base of the title compound (2 g, 59%) as a yellow solid. LCMS (M+H)+=332.
Reaction SMILES: [C:1]([CH2:4][O:5][C:6]1[CH:19]=[CH:18][C:9]([CH2:10][CH:11]2[S:15][C:14](=[O:16])[NH:13][C:12]2=[O:17])=[CH:8][CH:7]=1)(O)=O.[CH3:20][NH:21][C:22](=[O:30])[C:23]1[C:24](=[CH:26][CH:27]=[CH:28][CH:29]=1)[NH2:25].C1(C)C(C)=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[CH3:20][N:21]1[C:22](=[O:30])[C:23]2[C:24](=[CH:26][CH:27]=[CH:28][CH:29]=2)[N:25]=[C:1]1[CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:10][CH:11]2[S:15][C:14](=[O:16])[NH:13][C:12]2=[O:17])=[CH:18][CH:19]=1
Reactant: CNC(=O)c1ccccc1N
Reactant: O=C(O)COc1ccc(CC2SC(=O)NC2=O)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1C
Solvent: CO
Product: Cn1c(COc2ccc(CC3SC(=O)NC3=O)cc2)nc2ccccc2c1=O
Temperature: 175 °C

Procedure:
A suspension of 5-[4-[(carboxy)methoxy]benzyl]thiazolidine-2,4-dione obtained by following a procedure described in any of Examples 25-28 (100 g., 0.36 M), N-methyl anthranilamide (58.7 g, 0.39 M), xylene (100 ml) and p-toluenesulfonic acid (200 mg) was taken in a round bottom flask fitted with a mechanical stirrer, oil bath and Dean-Stark condenser. The reaction mixture was heated to reflux (Internal temperature 150-155° C., oil bath temperature 170-180° C.) for a period of 12-15 h while monitoring the reaction by TLC. After completion of the reaction, reaction mass was cooled to 80° C. and methanol (700 ml) was added slowly through a dropping funnel. The reaction mass was allowed to attain room temperature while stirring and the solid thus obtained was filtered and washed with methanol (150 ml) and dried at 100-120° C. for 1 h to afford 5-[4-[[3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]methoxy]benzyl]thiazolidine-2,4-dione as a white solid (95 g, Y=68%, P=98%).
Reaction SMILES: Cl.[NH2:2]O.[C:4]([CH2:10][C:11]#[N:12])(=[O:9])[C:5]([CH3:8])([CH3:7])[CH3:6]>>[NH2:12][C:11]1[CH:10]=[C:4]([C:5]([CH3:8])([CH3:7])[CH3:6])[O:9][N:2]=1
Reactant: NO
Reactant: CC(C)(C)C(=O)CC#N
Agent: Cl
Product: CC(C)(C)c1cc(N)no1

Procedure:
In adding the hydroxylamine hydrochloride to the reaction mixture, it appears that a quick addition is preferable. Best results appear to be obtained by adding an aqueous solution of the hydroxylamine hydrochloride to the basic solution of the pivalyl acetonitrile, and then, within the first 15 to 30 minutes, adjusting the pH to within the range of from about 5.0 to about 8.0, preferably from about 6.0 to about 7.0, with the pH range of choice being pH about 6.2 to about 6.5. This careful control of the pH of the reaction mixture is important in order to obtain the maximum yield of the 3-amino-5-(t-butyl)isoxazole since the reaction is very sensitive to the pH. A pH lower than about 5.0 results in the formation of an isoxazolone compound as the principal product. Higher pH values, that is, above about pH 8.0, result in unacceptably large amounts of the 5-amino-3-(t-butyl)isoxazole, compared to the amount of the desired 3-amino-5-(t-butyl)isoxazole. Even at pH 7.0, the ratio of the desired 3-amino compound to the 5-amino compound is less desirable.
Reaction SMILES: CCOC(/N=N/C(OCC)=O)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:32][C:33]1[CH:34]=[C:35]([OH:40])[CH:36]=[CH:37][C:38]=1[F:39].C(OC([N:48]1[CH2:53][CH2:52][CH:51](O)[CH2:50][CH2:49]1)=O)(C)(C)C.Cl>C1COCC1.O1CCOCC1>[Cl:32][C:33]1[CH:34]=[C:35]([CH:36]=[CH:37][C:38]=1[F:39])[O:40][CH:51]1[CH2:52][CH2:53][NH:48][CH2:49][CH2:50]1
Reactant: CC(C)(C)OC(=O)N1CCC(O)CC1
Reactant: Oc1ccc(F)c(Cl)c1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: C1COCCO1
Product: Fc1ccc(OC2CCNCC2)cc1Cl
Reaction time: 8 h
Yield: 105.2 %

Procedure:
DEAD (0.43 ml) was added to a solution of triphenylphosphine (0.72 g), 3-chloro-4-fluorophenol (0.403 g) and 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (0.5 g) in THF at RT. The resulting mixture was stirred overnight, HCl in dioxan (2 ml of 4M) was added and the mixture stirred at RT overnight. The mixture was then evaporated to dryness and triethylamine (5 ml) was added. The mixture was evaporated and the residue was dissolved in methanol (10 ml), placed onto a SCX cartridge (Varian, 10 g, SCX cartridge available from International Sorbent Technology Isolute® Flash SCX-2) and eluted: first with methanol then with 10% NH3 in methanol. The basic fractions were combined and evaporated to give the product as an oil (0.6 g).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][N:8]=[CH:7]2)([O-:3])=[O:2].C(=O)([O-])[O-].[K+].[K+].[CH2:19](Br)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C(#N)C>[CH2:19]([N:9]1[C:10]2[C:6](=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:12][CH:11]=2)[CH:7]=[N:8]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: BrCc1ccccc1
Reactant: O=[N+]([O-])c1ccc2[nH]ncc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: O=[N+]([O-])c1ccc2c(cnn2Cc2ccccc2)c1
Temperature: 70 °C
Reaction time: 8 h
Yield: 45.1 %

Procedure:
To a solution of 5-nitroindazole (10.0 g, 61.3 mmol) in acetonitrile (100 mL) was added potassium carbonate (16.9 g, 122.6 mmol) and benzyl bromide (13.6 g, 79.7 mmol). The resulting yellow reaction mixture was heated with stirring at 70° C. overnight. Upon cooling down, the solid was filtered off and washed with methylene chloride. The filtrate was concentrated to dryness and the resulting residue was purified by flash chromatography eluting with 17–25% ethyl acetate in hexanes (v/v) yielding 7.0 g (44%) of the corresponding 1-Benzyl-5-nitro-1H-indazole as a yellow solid.
Reaction SMILES: [C:1]([OH:10])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4].[CH3:11][O:12][C:13]1[CH:14]=[C:15]2[CH2:24][CH:23]([CH2:25][CH:26]3[CH2:31][CH2:30][N:29]([CH2:32][C:33]4[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=4)[CH2:28][CH2:27]3)[C:21](=[O:22])[C:16]2=[CH:17][C:18]=1[O:19][CH3:20]>C(OCC)(=O)C>[CH3:11][O:12][C:13]1[CH:14]=[C:15]2[CH2:24][CH:23]([CH2:25][CH:26]3[CH2:27][CH2:28][N:29]([CH2:32][C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[CH2:30][CH2:31]3)[C:21](=[O:22])[C:16]2=[CH:17][C:18]=1[O:19][CH3:20].[C:1]([O-:10])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4]
Reactant: O=C(O)c1ccccc1O
Agent: COc1cc2c(cc1OC)C(=O)C(CC1CCN(Cc3ccccc3)CC1)C2
Solvent: CCOC(C)=O
Product: O=C([O-])c1ccccc1O
Temperature: 25 °C

Procedure:
Salicylic acid (1.38 g, dissolved in 35 ml of absolute ethanol) is slowly added to a solution of Donepezil (3.79 g) in ethyl acetate (70 ml) with stirring at room temperature. The solid precipitated is filtered and dried at 55° C. under vacuum to give the title compound. Melting point: 176.5° C.
Reaction SMILES: C(=O)([O-])[O-].[Sr+2:5].[C:6]([OH:15])(=[O:14])[C:7]1[C:8](=[CH:10][CH:11]=[CH:12][CH:13]=1)[OH:9]>O>[C:6]([O-:15])(=[O:14])[C:7]1[C:8](=[CH:10][CH:11]=[CH:12][CH:13]=1)[OH:9].[Sr+2:5].[C:6]([O-:15])(=[O:14])[C:7]1[C:8](=[CH:10][CH:11]=[CH:12][CH:13]=1)[OH:9]
Reactant: O=C(O)c1ccccc1O
Agent: O=C([O-])[O-]
Agent: [Sr+2]
Solvent: O
Product: O=C([O-])c1ccccc1O
Reaction time: 4 h

Procedure:
A suspension of strontium carbonate (1.0 g, 6.77 mmol) and salicylic acid (1.87 g, 13.5 mmol) in water (25 ml) was stirred for 4 hours. The solution became pale yellow and almost clear. The solution was filtered at room temperature and the filtrate was evaporated to dryness and dried in vacuo at ambient temperature. The title compound was isolated as a pale red powder. Yield 2.1 g (86%). Melting point above 300° C.
Reaction SMILES: [C:1]([OH:6])(=[O:5])[CH:2]([CH3:4])[OH:3].[C:7]([OH:16])(=[O:15])[C:8]1[C:9](=[CH:11][CH:12]=[CH:13][CH:14]=1)[OH:10].[OH-].[CH2:18]([P+:22]([CH2:31][CH2:32][CH2:33][CH3:34])([CH2:27][CH2:28][CH2:29][CH3:30])[CH2:23][CH2:24][CH2:25][CH3:26])[CH2:19][CH2:20][CH3:21]>CC(C)=O>[C:7]([O-:16])(=[O:15])[C:8]1[C:9](=[CH:11][CH:12]=[CH:13][CH:14]=1)[OH:10].[CH2:31]([P+:22]([CH2:18][CH2:19][CH2:20][CH3:21])([CH2:23][CH2:24][CH2:25][CH3:26])[CH2:27][CH2:28][CH2:29][CH3:30])[CH2:32][CH2:33][CH3:34].[C:1]([OH:6])(=[O:5])[CH:2]([CH3:4])[OH:3]
Reactant: O=C(O)c1ccccc1O
Agent: CC(O)C(=O)O
Agent: CCCC[P+](CCCC)(CCCC)CCCC
Agent: [OH-]
Solvent: CC(C)=O
Product: O=C([O-])c1ccccc1O
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
Lactic acid (0.4504 g, 5 mmol), salicylic acid (0.6909 g, 5 mmol) and tetrabutylphosphonium hydroxide (˜40% sol. in H2O) (3.414 g, 5 mmol) were dissolved in 20 ml of acetone and stirred for 15 min at room temperature. The solvent was evaporated and the remaining viscous liquid was dried at 0.01 mbar with stirring for 24 hrs. The desired compound is isolated as a colourless liquid; 1H-NMR (300 MHz, d6-DMSO) δ(ppm)=7.63 (dd, J1=7.6 Hz, J2=1.9 Hz), 7.11 (m, 1H), 6.58 (m, 3H), 4.03 (q, J=6.9 Hz, 1H), 2.17 (m, 8H), 1.42 (m, 16 H), 1.23 (d, 7.0 Hz, 3H), 0.90 (t, J=7.3 Hz, 12 H). 31P-NMR (121.5 MHz, d6-DMSO) δ(ppm)=35.0. 13C-NMR (75 MHz, d6-DMSO) δ(ppm)=176.3, 171.1, 163.0, 131.2, 129.9, 120.5, 117.8, 115.767.3, 23.4 (d, J=15.8 Hz), 22.6 (d, J=4.3 Hz), 20.5, 17.3 (d, J=47.7 Hz), 13.3 (s).
Reaction SMILES: C(=O)([O-])[O-].[OH-].[Na+:6].[C:7]([OH:16])(=[O:15])[C:8]1[C:9](=[CH:11][CH:12]=[CH:13][CH:14]=1)[OH:10]>O>[C:7]([O-:16])(=[O:15])[C:8]1[C:9](=[CH:11][CH:12]=[CH:13][CH:14]=1)[OH:10].[Na+:6]
Reactant: O=C(O)c1ccccc1O
Agent: O=C([O-])[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C([O-])c1ccccc1O

Procedure:
The alkali metal salt of the aromatic carboxylic acid used for the production of the developing sheet of the invention is prepared by reacting an aromatic carboxylic acid with an alkali metal hydroxide or carbonate. An example of this procedure is as follows: 30 g of sodium hydroxide is dissolved in 300 ml of water, to which 100 g of salicycilic acid is then added with agitation. The agitation is continued for a while to dissolve the salicylic acid completely and then the solution is evaporated to dryness to obtain 110 g of sodium salicylate.