Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].F[C:4]1[CH:9]=[CH:8][C:7]([S:10]([C:13]2[C:14]([NH:20][C:21]3[C:26]([CH3:27])=[CH:25][C:24]([CH3:28])=[CH:23][C:22]=3[CH3:29])=[N:15][C:16]([CH3:19])=[N:17][CH:18]=2)(=[O:12])=[O:11])=[CH:6][CH:5]=1.[NH:30]1[CH:34]=[CH:33][N:32]=[CH:31]1.[NH4+].[Cl-]>O1CCOCC1>[N:30]1([C:4]2[CH:9]=[CH:8][C:7]([S:10]([C:13]3[C:14]([NH:20][C:21]4[C:26]([CH3:27])=[CH:25][C:24]([CH3:28])=[CH:23][C:22]=4[CH3:29])=[N:15][C:16]([CH3:19])=[N:17][CH:18]=3)(=[O:12])=[O:11])=[CH:6][CH:5]=2)[CH:34]=[CH:33][N:32]=[CH:31]1
Reactant: c1c[nH]cn1
Reactant: Cc1cc(C)c(Nc2nc(C)ncc2S(=O)(=O)c2ccc(F)cc2)c(C)c1
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: C1COCCO1
Product: Cc1cc(C)c(Nc2nc(C)ncc2S(=O)(=O)c2ccc(-n3ccnc3)cc2)c(C)c1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 49.7 %

Procedure:
Sodium hydride (60% in oil, 32 mg, 0.78 mmol) was added to a solution of [5-(4-fluoro-benzenesulfonyl)-2-methylpyrimidin-4-yl]-(2,4,6-trimethylphenyl)-amine (100 mg, 0.26 mmol) and imidazole (53 mg, 0.78 mmol) in 1,4-dioxane (4 mL). The mixture was stirred at room temperature for 10 min and then heated at reflux under N2 for 24 h. The mixture was cooled to room temperature, and saturated aqueous NH4Cl was added. The mixture was extracted three times with CH2Cl2, and the combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel (EtOAc) to provide the target compound (56 mg, 50%) as a white solid: mp 230–232° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.82 (s, 1H), 8.48 (br s, 1H), 8.44 (s, 1H), 8.34 (d, J=8.7 Hz, 2H), 7.95 (d, J=8.7 Hz, 2H), 7.90 (s, 1H), 7.15 (s, 1H), 6.89 (s, 2H), 2.25 (s, 3H), 2.24 (s, 3H), 1.86 (s, 6H); APCI MS m/z 434 [(M+H)+, calcd for C23H24N5O2S, 434.1].
Reaction SMILES: [H-].[Na+].[F:3][C:4]([F:22])([F:21])[C:5]1[CH:6]=[C:7]([CH:15]2[O:19][C:18](=[O:20])[NH:17][CH2:16]2)[CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1.Br[CH2:24][C:25]1[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][C:26]=1[I:35]>C1COCC1>[F:22][C:4]([F:3])([F:21])[C:5]1[CH:6]=[C:7]([CH:15]2[O:19][C:18](=[O:20])[N:17]([CH2:24][C:25]3[CH:30]=[C:29]([C:31]([F:32])([F:34])[F:33])[CH:28]=[CH:27][C:26]=3[I:35])[CH2:16]2)[CH:8]=[C:9]([C:11]([F:12])([F:13])[F:14])[CH:10]=1
Reactant: FC(F)(F)c1ccc(I)c(CBr)c1
Reactant: O=C1NCC(c2cc(C(F)(F)F)cc(C(F)(F)F)c2)O1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=C1OC(c2cc(C(F)(F)F)cc(C(F)(F)F)c2)CN1Cc1cc(C(F)(F)F)ccc1I
Reaction time: 0.33 h

Procedure:
A stirred suspension of sodium hydride (60% in oil, 167 mg, 4.18 mmol) in THF (5 mL) was treated at 0° C. with 5-[3,5-bis(trifluoromethyl)phenyl]-1,3-oxazolidin-2-one (500 mg, 1.67 mmol) dissolved in THF (1 mL), under an atmosphere of N2. The reaction was stirred for 20 min and a solution of 2-(bromomethyl)-1-iodo-4-(trifluoromethyl)benzene (610 mg, 1.67 mmol) in THF (1 mL) was added dropwise. The reaction was stirred at room temperature for 18 h. The reaction was quenched with H2O (1 mL) and partitioned between EtOAc (80 mL) and H2O (25 mL). The aqueous phase was re-extracted with EtOAc (2×20 mL) and the combined organic extracts were washed with brine (30 mL), dried (MgSO4) and concentrated in vacuo to give the crude product. This was purified by flash silica-gel chromatography (0-30% EtOAc in hexanes gradient) to afford 5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]1,3-oxazolidin-2-one. Rf=0.55 (515% EtOAc/hexanes). LCMS 584 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 8.05 (d, J=8.2 Hz, 1H), 7.95 (br s, 1H), 7.85 (br s, 2H), 7.51 (br s, 1H), 7.32 (m, 1H), 5.72 (t, J=8.0 Hz, 1H), 4.74 (d, J=15.5 Hz, 1H), 4.64 (d, J=15.3 Hz), 4.14 (t, J=7.1 Hz, 1H), 3.47 (dd, J=7.1, 1.6 Hz).
Reaction SMILES: [CH2:1]([NH2:4])[CH2:2][NH2:3].[N+:5]([O-:8])([O-:7])=[O:6].[NH4+]>>[N+:5]([O-:8])([OH:7])=[O:6].[N+:5]([O-:8])([OH:7])=[O:6].[CH2:1]([NH2:4])[CH2:2][NH2:3]
Reactant: O=[N+]([O-])[O-]
Agent: [NH4+]
Solvent: NCCN
Product: O=[N+]([O-])O

Procedure:
The reaction of ethylenediamine and ammonium nitrate is a quantitative acid-base reaction to form a salt, ethylenediamine dinitrate, and a weak base, ammonia, according to the following chemical equation: ##STR1## The basic reaction proceeds fairly rapidly but the product and byproduct may remain in a slurry state for several days prior to solidification. The product is explosive in the slurry state and may be used as is or poured into place for use as an explosive. The solidification of the product ethylenediamine dinitrate can be hastened by the removal of the byproduct ammonia. This can be accomplished by heating or otherwise removing the ammonia or by reacting the ammonia with an additional substance to form a solid.
Reaction SMILES: [Na].[CH3:2][C:3]1[CH:8]=[C:7]([CH3:9])[CH:6]=[CH:5][C:4]=1[CH2:10][C:11]#[N:12].[C:13](OCC)(=[O:15])[CH3:14]>>[C:11]([CH:10]([C:4]1[CH:5]=[CH:6][C:7]([CH3:9])=[CH:8][C:3]=1[CH3:2])[C:13](=[O:15])[CH3:14])#[N:12]
Reactant: CCOC(C)=O
Reactant: Cc1ccc(CC#N)c(C)c1
Agent: [Na]
Product: CC(=O)C(C#N)c1ccc(C)cc1C
Temperature: 25 °C
Reaction time: 16 h
Yield: 74 %

Procedure:
Sodium pellets (9.8 g, 0.43 mol) were added portionwise to a solution of 2,4-dimethylphenylacetonitrile (48 g, 0.33 mol) in ethyl acetate (150 mL) at ambient temperature. The reaction mixture was heated to reflux temperature and stirred for 16 hours. The resulting suspension was cooled to room temperature and filtered. The collected precipitate was washed with copious amounts of ether and then air-dried. The solid was dissolved in water and a 1N HCl solution was added until the pH=5-6. The mixture was extracted with ethyl acetate (3×200 mL); the combined organic layers were dried over MgSO4 and filtered. Solvent was removed in vacuo to afford a white solid (45.7 g, 74% yield): NMR (CDCl3, 300 MHz) :; CI-MS: 188 (M+H).
Reaction SMILES: [C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[CH:13]=[C:12](Cl)[C:11]([C:15]([F:18])([F:17])[F:16])=[CH:10][C:9]=1[N+:19]([O-:21])=[O:20])([CH3:4])([CH3:3])[CH3:2].[NH:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>CS(C)=O>[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[CH:13]=[C:12]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[C:11]([C:15]([F:18])([F:17])[F:16])=[CH:10][C:9]=1[N+:19]([O-:21])=[O:20])([CH3:4])([CH3:3])[CH3:2]
Reactant: C1COCCN1
Reactant: CC(C)(C)OC(=O)Nc1cc(Cl)c(C(F)(F)F)cc1[N+](=O)[O-]
Solvent: CS(C)=O
Product: CC(C)(C)OC(=O)Nc1cc(N2CCOCC2)c(C(F)(F)F)cc1[N+](=O)[O-]

Procedure:
The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example A1) (1.62 g, 5 mmol), morpholine (2.18 mL, 25 mmol) in DMSO (10 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.83 g, 94%).
Reaction SMILES: [C:1]([OH:5])(=[O:4])[CH2:2][OH:3].[Cl-].[La+3:7].[Cl-].[Cl-]>>[C:1]([O-:5])(=[O:4])[CH2:2][OH:3].[La+3:7].[C:1]([O-:5])(=[O:4])[CH2:2][OH:3].[C:1]([O-:5])(=[O:4])[CH2:2][OH:3]
Reactant: O=C(O)CO
Agent: [Cl-]
Agent: [La+3]
Product: O=C([O-])CO

Procedure:
In another example, chemically equivalent amounts of neutralised glycolic acid and lanthanum chloride were mixed at 50° C. to form lanthanum glycolate crystals with a narrow particle size range averaging about 20 microns. The glycolic acid (70% wt/wt water) was neutralised with sodium hydroxide at a rate to ensure that the resultant temperature was between 50° and 60° and that boiling did not occur during neutralisation. Lanthanum chloride solution of about 48% wt/wt water was then added slowly to the hot neutralised glycolic acid solution while stirring. The rate of addition in this case was kept between 100 ml and 200 ml per minute while the temperature was maintained at about 50° C. The resultant precipitate was separated from the liquor, dried and confirmed by analysis to be substantially lanthanum glycolate.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[N:4]=[C:5]([C:21]([OH:23])=O)[C:6](=[O:20])[N:7]2[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1.C(Cl)(=O)C(Cl)=O.[C:30]1(=[O:37])[CH2:35][CH2:34][CH2:33][C:32](=[O:36])[CH2:31]1.C(N(CC)CC)C.CC(C)(O)C#N>C(Cl)(Cl)Cl.CN(C)C=O>[Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[N:4]=[C:5]([C:21]([C:31]1[C:32](=[O:36])[CH2:33][CH2:34][CH2:35][C:30]=1[OH:37])=[O:23])[C:6](=[O:20])[N:7]2[C:12]1[CH:13]=[CH:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=1
Reactant: O=C1CCCC(=O)C1
Reactant: COc1ccc(-n2c(=O)c(C(=O)O)nc3c(Cl)cccc32)cc1
Agent: CC(C)(O)C#N
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Solvent: CN(C)C=O
Product: COc1ccc(-n2c(=O)c(C(=O)C3=C(O)CCCC3=O)nc3c(Cl)cccc32)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 70.6 %

Procedure:
6.7 g (20 mmol) of 5-chloro-1-(4-methoxyphenyl)-2-oxo-1,2-dihydroquinoxaline-3-carboxylic acid was dissolved in chloroform (300 mL), and to this solution, N,N-dimethylformamide (0.5 mL) and 5.2 g (41 mmol) of oxalyl chloride were added sequentially. The mixture was stirred for one hour at room temperature. After confirming the completion of the reaction, the solvent was distilled off under reduced pressure. The residue thus obtained was dissolved in chloroform (70 mL), and this solution was added dropwise at 0° C. over 5 minutes to a solution prepared by dissolving 2.5 g (22 mmol) of 1,3-cyclohexanedione and 2.5 g (25 mmol) of triethylamine in chloroform (70 mL). The reaction solution was returned to room temperature and stirred for 3 hours, and then 0.86 g (10 mmol) of acetone cyanohydrin and 2.5 g (25 mmol) of triethylamine were added thereto. The mixture was stirred for 12 hours at room temperature. The reaction solution was washed with 10% hydrochloric acid and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue thus obtained was washed with ethyl acetate, to obtain 6.0 g (yield: 70%) of 5-chloro-3-(2-hydroxy-6-oxo-1-cyclohexenecarbonyl)-1-(4-methoxyphenyl)quinoxalin-2(1H)-one as a pale orange-colored powder.
Reaction SMILES: C(N(CC)CC)C.[OH:8][CH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.[N+:15]([C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Cl)=[CH:20][CH:19]=1)([O-:17])=[O:16]>ClCCl>[N+:15]([C:18]1[CH:25]=[CH:24][C:21]([CH2:22][C:9]2([OH:8])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:20][CH:19]=1)([O-:17])=[O:16]
Reactant: O=[N+]([O-])c1ccc(CCl)cc1
Reactant: OC1CCNCC1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=[N+]([O-])c1ccc(CC2(O)CCNCC2)cc1
Reaction time: 12 h

Procedure:
137 mL (0.983 mol) of triethylamine is added to a solution of 41.5 g (0.410 mol) of 4-hydroxypiperidine in 500 mL of dichloromethane. Then 56.28 g (0.328 mol) of 4-nitrobenzylchloride is slowly added. The reaction mixture is boiled for 12 hours. The solid formed is suction filtered, the filtrate is washed twice with water and dried over magnesium sulfate. The solvent is evaporated down. Yield: 66.45 g (86% of theory); C12H16N2O3 (M=236.27); calc.: molecular ion peak (M+H)+: 237; found: molecular ion peak (M+H)+: 237.
Reaction SMILES: [CH3:1][C:2]1[C:6]([C:7]2[C:8]([O:28][CH3:29])=[CH:9][C:10]3[C:11]4[N:19]([CH2:20][CH:21]5[CH2:26][CH2:25][O:24][CH2:23][CH2:22]5)[C:18](=O)[NH:17][C:12]=4[CH:13]=[N:14][C:15]=3[CH:16]=2)=[C:5]([CH3:30])[O:4][N:3]=1.O=P(Cl)(Cl)Cl.P(Cl)(Cl)(Cl)(Cl)Cl.[NH:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1>CN1C(=O)CCC1.C(Cl)Cl>[CH3:1][C:2]1[C:6]([C:7]2[C:8]([O:28][CH3:29])=[CH:9][C:10]3[C:11]4[N:19]([CH2:20][CH:21]5[CH2:22][CH2:23][O:24][CH2:25][CH2:26]5)[C:18]([N:42]5[CH2:47][CH2:46][O:45][CH2:44][CH2:43]5)=[N:17][C:12]=4[CH:13]=[N:14][C:15]=3[CH:16]=2)=[C:5]([CH3:30])[O:4][N:3]=1
Reactant: C1COCCN1
Reactant: COc1cc2c(cc1-c1c(C)noc1C)ncc1[nH]c(=O)n(CC3CCOCC3)c12
Agent: ClP(Cl)(Cl)(Cl)Cl
Solvent: O=P(Cl)(Cl)Cl
Solvent: ClCCl
Solvent: CN1CCCC1=O
Product: COc1cc2c(cc1-c1c(C)noc1C)ncc1nc(N3CCOCC3)n(CC3CCOCC3)c12
Temperature: 120 °C
Yield: 1.8 %

Procedure:
7-(3,5-Dimethyl-4-isoxazolyl)-8-(methyloxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one (220 mg, 0.539 mmol) (for a preparation see intermediate 14) was dissolved in POCl3 (2 ml, 21.46 mmol), PCl5 (0.2 g, 0.960 mmol) was added and the mixture was heated at 120° C. for 24 h. The reaction mixture was evaporated in vacuo to give a beige solid. The solid was dissolved in NMP (0.5 ml) and morpholine (0.3 ml, 3.44 mmol) was added, then the solution was heated in the microwave at 150° C. for 1 h. The solution was loaded onto a 20 g SCX-2 cartridge and washed with methanol (30 ml), then eluted with 2M methanolic ammonia (30 ml) and the eluant evaporated in vacuo to give a beige gum. This was dissolved in DCM (3 ml) and loaded onto a 25 g silica column, then eluted with 2M methanolic ammonia/DCM (0-10%, 25 column volumes) and product containing fractions were evaporated in vacuo to give 7-(3,5-dimethyl-4-isoxazolyl)-8-(methyloxy)-2-(4-morpholinyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinoline (4.7 mg, 9.84 μmol, 1.827% yield) as a beige solid. LCMS (formate) Rt 0.70 min, MH+ 478
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:32])=[C:6]([CH:31]=1)[O:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:19]=[CH:18][C:17]([C:20]3[N:21]=[N:22][N:23]([CH2:25][C:26]([O:28]CC)=[O:27])[N:24]=3)=[CH:16][N:15]=2)[CH2:10][CH2:9]1.[OH-].[Na+]>C1COCC1.CO>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:32])=[C:6]([CH:31]=1)[O:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:15]=[CH:16][C:17]([C:20]3[N:21]=[N:22][N:23]([CH2:25][C:26]([OH:28])=[O:27])[N:24]=3)=[CH:18][N:19]=2)[CH2:10][CH2:9]1
Reactant: CCOC(=O)Cn1nnc(-c2cnc(N3CCC(Oc4cc(Br)ccc4Cl)CC3)nc2)n1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: O=C(O)Cn1nnc(-c2cnc(N3CCC(Oc4cc(Br)ccc4Cl)CC3)nc2)n1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To a solution of the ethyl (5-{2-[4-(5-bromo-2-chlorophenoxy)piperidin-1-yl]pyrimidin-5-yl}-2H-tetrazol-2-yl)acetate (50 mg, 0.096 mmol) in THF (319 μL) and MeOH (159 μL) was added 2 N NaOH (96 μL, 0.191 mmol) and the was mixture stirred at RT for 10 min. The THF and MeOH were evaporated and the aqueous layer was washed with Et2O (2×2 mL). The aqueous layer was acidified to pH 1 with 2 N HCl and stirred for 5 min. The mixture was filtered and washed with water followed by 1:1 Et2O/hexanes. The solid was dried under high vacuum to afford the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[NH:6][CH2:5]2.[C:12]([O:16][C:17](=O)[O:18]C(C)(C)C)([CH3:15])([CH3:14])[CH3:13].CO>O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[N:6]([C:17]([O:16][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:18])[CH2:5]2
Reactant: O=C1NCc2cc(Br)ccc21
Reactant: CC(C)(C)OC(=O)OC(C)(C)C
Solvent: C1CCOC1
Solvent: CO
Product: CC(C)(C)OC(=O)N1Cc2cc(Br)ccc2C1=O
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 49.7 %

Procedure:
Under nitrogen atmosphere, 70 mg of 5-bromo-1-oxo-isoindoline was dissolved in 2 ml of tetrahydrofuran, cooled down to 0° C., and then 4 mg of N,N-dimethylaminopyridine and 144 mg of di-tert-butylcarbonate were added. The mixture was stirred at room temperature for 30 min. Methanol was added to the reaction solution, and the solvents were distilled outunder reduced pressure. Water was added to the residues, extracted with ethyl acetate. Ethyl acetate layer was washed with saturated saline solution, and dried with anhydrous sodium sulfate. After distilling out the solvents under reduced pressure, the residues were separated and purified by silicagel column chromatography (ethyl acetate/hexane=1/2), to obtain 51.2 mg of the above compound as a white solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[O:10][C:11]3[C:17]([F:18])=[C:16]([CH2:19][C:20]([O:22]C)=[O:21])[CH:15]=[CH:14][C:12]=3[N:13]=2)=[C:4]([CH3:24])[CH:3]=1.[OH-].[Na+]>C1COCC1.CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[O:10][C:11]3[C:17]([F:18])=[C:16]([CH2:19][C:20]([OH:22])=[O:21])[CH:15]=[CH:14][C:12]=3[N:13]=2)=[C:4]([CH3:24])[CH:3]=1
Reactant: COC(=O)Cc1ccc2nc(Nc3ccc(F)cc3C)oc2c1F
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: Cc1cc(F)ccc1Nc1nc2ccc(CC(=O)O)c(F)c2o1
Temperature: 25 °C
Reaction time: 12 h
Yield: 109.2 %

Procedure:
In THF/methanol (2:1, v/v, 120 ml) was dissolved methyl (2-(4-fluoro-2-methylphenylamino)-7-fluoro-6-benzoxazolyl)acetate (1.32 g, 3.97 mmol). To the resulting solution was added 1N NaOH (40 ml). After stirring at room temperature for 12 hours, the reaction mixture was distilled under reduced pressure to remove the solvent. The residue was acidified with 1N HCl. The crystals thus precipitated were collected by filtration under reduced pressure, washed with water and dried under reduced pressure to give (2-(4-fluoro-2-methylphenylamino)-7-fluoro-6-benzoxazolyl)acetic acid (1.38 g, 100%) as a colorless solid.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][C:10]([C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)=[C:11]([C:13]([NH:15][C:16]3[S:17][CH:18]=[CH:19][N:20]=3)=[O:14])[N:12]=2)=[CH:4][CH:3]=1.[CH3:29][N:30]([CH3:35])[CH2:31][CH2:32][CH2:33]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>>[CH3:29][N:30]([CH3:35])[CH2:31][CH2:32][CH2:33][O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][C:10]([C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)=[C:11]([C:13]([NH:15][C:16]3[S:17][CH:18]=[CH:19][N:20]=3)=[O:14])[N:12]=2)=[CH:4][CH:3]=1
Reactant: COc1ccc(-c2[nH]c(-c3ccc(O)cc3)nc2C(=O)Nc2nccs2)cc1
Reactant: CN(C)CCCO
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: COc1ccc(-c2[nH]c(-c3ccc(OCCCN(C)C)cc3)nc2C(=O)Nc2nccs2)cc1

Procedure:
2-(4-Hydroxyphenyl)-5-(4-methoxyphenyl)-N-(2-thiazolyl)-imidazole-4-carboxamide, 3-dimethylaminopropanol, triphenyl-phosphine and diethyl azodicarboxylate are reacted and treated in the same manner as in Example 24 to give 2-(4-(3-dimethylamino-propyloxy)phenyl)-5-(4-methoxyphenyl)-N-(2-thiazolyl)imidazole-4-carboxamide.
Reaction SMILES: [C:1]([C:3]1([OH:27])[CH2:8][CH2:7][N:6]([C:9]2[CH:14]=[CH:13][C:12]([N:15]3[CH2:19][C@H:18]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:17][C:16]3=[O:25])=[CH:11][C:10]=2[F:26])[CH2:5][CH2:4]1)#[N:2].S(=O)(=O)(O)[OH:29]>>[NH2:2][C:1]([C:3]1([OH:27])[CH2:4][CH2:5][N:6]([C:9]2[CH:14]=[CH:13][C:12]([N:15]3[CH2:19][C@H:18]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:17][C:16]3=[O:25])=[CH:11][C:10]=2[F:26])[CH2:7][CH2:8]1)=[O:29]
Reactant: O=S(=O)(O)O
Reactant: CC(=O)NC[C@H]1CN(c2ccc(N3CCC(O)(C#N)CC3)c(F)c2)C(=O)O1
Product: CC(=O)NC[C@H]1CN(c2ccc(N3CCC(O)(C(N)=O)CC3)c(F)c2)C(=O)O1
Yield: 62 %

Procedure:
The compound was obtained by reacting (S)—N-{3-[4-(4-cyano-4-hydroxypiperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (12 mmol) with 95% aqueous sulfuric acid at a temperature 25° C. for 14 hours and purifying the compound by silica gel column chromatography in 62% yield. M.P. 238-40° C. and MS (M+1)=395 (MH+, 100%) for M.F.=C18H23FN4O5.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C@@H:9]([CH2:13][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH3:15])[CH2:10][CH:11]=O)[CH:5]=[CH:6][C:7]=1[Cl:8].Cl.[NH:24]1[CH2:29][CH2:28][C:27]2([C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH:31]=[CH:30]2)[CH2:26][CH2:25]1.[BH3-]C#N.[Na+]>CO.C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:9]([CH2:13][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH3:15])[CH2:10][CH2:11][N:24]2[CH2:29][CH2:28][C:27]3([C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[CH:31]=[CH:30]3)[CH2:26][CH2:25]2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: CN(C[C@@H](CC=O)c1ccc(Cl)c(Cl)c1)C(=O)OC(C)(C)C
Reactant: C1=CC2(CCNCC2)c2ccccc21
Agent: Cl
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: CN(C[C@@H](CCN1CCC2(C=Cc3ccccc32)CC1)c1ccc(Cl)c(Cl)c1)C(=O)OC(C)(C)C
Yield: 78.6 %

Procedure:
To a solution of 3.46 g (10 mmol) of 3-(S)-(3,4-dichlorophenyl)-4-(t-butoxycarbonyl-methylamino)butanal (Example 1) in 20 mL of methanol were added 3.11 g (14 mmol) of spiro(1H-indene-1,4'-piperidine) hydrochloride and 3 g of powdered 4 Å molecular sieves. After 15 min a solution of 2.52 g (40 mmol) of NaCNBH3 in 30 mL of THF was dropwise added. Some gas evolution was observed. After stirring the reaction overnight, the mixture was filtered through a pad of celite, the reaction flask and the pad were rinsed with methanol. The filtrate was concentrated to approximately 10 ml and the residue was partitioned between saturated NaHCO3 and Et2O:EtOAC. The organic layer was washed with water, brine and dried over NA2SO4. The filtrate was concentrated and the residue was chromatographed on a flash column using a gradient of 49:49:2 to 98:0:2 EtOAc: Hexane: triethylamine to furnish 4.05 g (79%) of the title compound as a foam.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10](=[N:12]O)[CH3:11])=[CH:2]1.C(O)(=O)C.[H][H]>C(O)C.[C].[Pd]>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]([NH2:12])[CH3:11])=[CH:2]1
Reactant: CC(=NO)c1c[nH]c2ccccc12
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Solvent: CC(=O)O
Product: CC(N)c1c[nH]c2ccccc12
Yield: 74.5 %

Procedure:
10% palladium-carbon (water content: 50%, 12.2 mg) was added to a solution of 1-(1H-indol-3-yl)ethanone oxime (0.20 g) obtained as above and acetic acid (0.7 mL) in ethanol (7 mL) at room temperature. The reaction mixture was stirred in a hydrogen stream at room temperature for 10 hours, and then filtered on a celite. The filtrate was concentrated under reduced pressure. The residue was extracted with chloroform. The organic layer was washed sequentially with a 1 N aqueous solution of sodium hydroxide and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Carrier: Chromatorex™ NH, elution solvent:chloroform-methanol system) to obtain 0.137 g of the title compound.
Reaction SMILES: C([O:5][C:6](=[O:30])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][O:16][C:17]2[C:18]([NH:23][C:24]3[S:25][CH:26]=[C:27]([CH3:29])[N:28]=3)=[N:19][CH:20]=[CH:21][CH:22]=2)[CH:10]=1)(C)(C)C.[F:31][C:32]([F:37])([F:36])[C:33]([OH:35])=[O:34]>C(Cl)Cl>[F:31][C:32]([F:37])([F:36])[C:33]([OH:35])=[O:34].[CH3:29][C:27]1[N:28]=[C:24]([NH:23][C:18]2[C:17]([O:16][CH2:15][C:11]3[CH:10]=[C:9]([CH:14]=[CH:13][CH:12]=3)[O:8][CH2:7][C:6]([OH:30])=[O:5])=[CH:22][CH:21]=[CH:20][N:19]=2)[S:25][CH:26]=1
Reactant: Cc1csc(Nc2ncccc2OCc2cccc(OCC(=O)OC(C)(C)C)c2)n1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1csc(Nc2ncccc2OCc2cccc(OCC(=O)O)c2)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 80.4 %

Procedure:
tert-Butyl-2-(3-((2-(4-methylthiazol-2-ylamino)pyridin-3-yloxy)methyl)phenoxy)acetate (680 mg, 1.59 mmol) and CH2Cl2 (5 mL) were combined in a 50 mL round-bottomed flask. Trifluoroacetic acid (5 mL) was added and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated and the resultant solid was triturated with 40% methanol in CH2Cl2 to provide 2-(3-((2-(4-methylthiazol-2-ylamino)pyridin-3-yloxy)methyl)phenoxy)acetic acid trifluoroacetate salt (621 mg, 80.4% yield) as a white solid. 1H NMR (d6-DMSO) δ 7.92 (dd, 1H), 7.49 (dd, 1 h), 7.32 (t, 1H), 7.16 (m, 2H), 7.00 (dd, 1 h), 6.88 (dd, 1H), 6.72 (q, 1H), 5.26 (s, 2H), 4.69 (s, 2h), 2.29 (d, 3H). Mass spectrum (apci) m/z=372 (M+H-TFA).