Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH-].[Na+].[CH3:3][C:4]1[C:5]([Se:18][C:19]2[CH:29]=[CH:28][C:22]([C:23]([O:25]CC)=[O:24])=[CH:21][CH:20]=2)=[CH:6][C:7]2[C:8]([CH3:17])([CH3:16])[CH2:9][CH2:10][C:11]([CH3:15])([CH3:14])[C:12]=2[CH:13]=1.CO.Cl>C1COCC1.C(OCC)C.O.O>[CH3:3][C:4]1[C:5]([Se:18][C:19]2[CH:20]=[CH:21][C:22]([C:23]([OH:25])=[O:24])=[CH:28][CH:29]=2)=[CH:6][C:7]2[C:8]([CH3:17])([CH3:16])[CH2:9][CH2:10][C:11]([CH3:14])([CH3:15])[C:12]=2[CH:13]=1
Reactant: CCOC(=O)c1ccc([Se]c2cc3c(cc2C)C(C)(C)CCC3(C)C)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: Cc1cc2c(cc1[Se]c1ccc(C(=O)O)cc1)C(C)(C)CCC2(C)C

Procedure:
Sodium hydroxide (450 mg, 11.25 mmol) is added to a solution of ethyl 4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthylselanyl)benzoate (450 mg, 1.04 mmol) in a mixture of 10 ml of THF, 1 ml of methanol and 1 ml of water. The reaction medium is refluxed for 12 h. It is then poured into an ethyl ether/water mixture, acidified to pH 1 with concentrated hydrochloric acid solution and extracted with ethyl ether. After separation of the phases by settling, the organic phase is washed twice with water, dried over anhydrous magnesium sulphate and concentrated on a rotary evaporator under vacuum at 40° C.
Reaction SMILES: [BH4-].[Na+].C[O:4][C:5](=[O:32])[C@H:6]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:29]=[CH:28][S:27][C:26]=2[CH:30]=[O:31])=[CH:21][CH:20]=1)[NH:7][C:8](=[O:17])[C:9]1[C:14]([Cl:15])=[CH:13][CH:12]=[CH:11][C:10]=1[Cl:16]>>[Cl:16][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]([Cl:15])[C:9]=1[C:8]([NH:7][C@H:6]([C:5]([OH:32])=[O:4])[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:29]=[CH:28][S:27][C:26]=2[CH2:30][OH:31])=[CH:21][CH:20]=1)=[O:17]
Reactant: COC(=O)[C@H](Cc1ccc(-c2ccsc2C=O)cc1)NC(=O)c1c(Cl)cccc1Cl
Agent: [BH4-]
Agent: [Na+]
Product: O=C(N[C@@H](Cc1ccc(-c2ccsc2CO)cc1)C(=O)O)c1c(Cl)cccc1Cl

Procedure:
The title compound was prepared by NaBH4 reduction of N-(2,6-Dichlorobenzoyl)-4-(2-formyl-3-thienyl)-L-phenylalanine methyl ester followed by hydrolysis as described in Example 50. ESMS m/z 472 (M+-Na), 448 (M−H)−.
Reaction SMILES: C([NH:8][C:9]1[CH:14]=[C:13]([C:15]2[N:19]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([CH3:26])[CH:21]=3)[N:18]=[C:17]([CH3:27])[CH:16]=2)[CH:12]=[CH:11][N:10]=1)C1C=CC=CC=1>C(O)(=O)C.[OH-].[Pd+2].[OH-]>[NH2:8][C:9]1[CH:14]=[C:13]([C:15]2[N:19]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([CH3:26])[CH:21]=3)[N:18]=[C:17]([CH3:27])[CH:16]=2)[CH:12]=[CH:11][N:10]=1
Reactant: Cc1cccc(-n2nc(C)cc2-c2ccnc(NCc3ccccc3)c2)c1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CC(=O)O
Product: Cc1cccc(-n2nc(C)cc2-c2ccnc(N)c2)c1
Reaction time: 9 h
Yield: 56.1 %

Procedure:
A mixture of 2-benzylamino-4-[1-(3-methylphenyl)-3-methyl-1H-pyrazol-5-yl]pyridine (Example 19; 1.03 g, 0.0029 mol) and palladium hydroxide (0.2 g)in acetic acid was hydrogenated under 60 psi at 40° C. for 9 hours. The mixture was cooled and filtered through a pad of Celite™. The filtrate was concentrated and purified by chromatography on silica gel (ethyl acetate/hexane, 1:1) to give 0.43 g of product as a white solid: mp: 124-125° C.; Anal. Calc'd. for C16H16N4: C, 72.70; H, 6.10; N, 21.20. Found: C, 72.41; H, 6.31; N, 20.63.
Reaction SMILES: [CH2:1]([C:8]1[S:12][C:11]([NH2:13])=[N:10][C:9]=1[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:22][O:23][C:24]1[CH:25]=[C:26]([CH2:32][CH2:33][C:34](Cl)=[O:35])[CH:27]=[CH:28][C:29]=1[O:30][CH3:31]>>[CH2:1]([C:8]1[S:12][C:11]([NH:13][C:34](=[O:35])[CH2:33][CH2:32][C:26]2[CH:27]=[CH:28][C:29]([O:30][CH3:31])=[C:24]([O:23][CH3:22])[CH:25]=2)=[N:10][C:9]=1[C:14]1[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc(CCC(=O)Cl)cc1OC
Reactant: COc1ccc(-c2nc(N)sc2Cc2ccccc2)cc1
Product: COc1ccc(-c2nc(NC(=O)CCc3ccc(OC)c(OC)c3)sc2Cc2ccccc2)cc1
Yield: 65 %

Procedure:
A procedure similar to that in Example 4 was used. 5-benzyl-4-(4-methoxy-phenyl)-thiazol-2-ylamine prepared in Example 1 and 3-(3,4-dimethoxy-phenyl)-propionyl chloride prepared in the step 1 were used as starting materials, allowed to react at 35-40° C. for 10 hours, followed by post-treatment to obtain a crude product, which was purified by a silica gel column chromatography eluted with petroleum ether and ethyl acetate (4:1) to obtain a product as a white solid in a yield of 65.0%, mp: 142-143└. 1H-NMR (CDCl3, 400 MHz) δ: 2.12 (2H, t, J=7.72 Hz), 2.74 (2H, t, J=7.72 Hz), 3.80 (6H, s, 2×OCH3), 3.83 (3H, s, OCH3), 4.18 (2H, s, CH2), 6.51 (1H, dd, J=8.16, 1.96 Hz, ArH), 6.56 (1H, d, J=1.96 Hz, ArH), 6.69 (1H, d, J=8.16 Hz, ArH), 6.83 (2H, d, J=8.68 Hz, ArH), 7.21˜7.33 (5H, m, ArH), 7.42 (2H, d, J=8.68 Hz, ArH), 11.05 (1H, br, CONH); EI-MS m/e (%): 488.1 (M+, 66), 296.0 (100); HREI-MS Calcd. for C28H28N2O4S: 488.1770. found: 488.1764. Anal. Calcd. for C28H28N2O4S: C, 68.83; H, 5.78; N, 5.73. found: C, 68.69; H, 5.67; N, 6.09.
Reaction SMILES: C(Cl)(Cl)Cl.[OH:5][CH2:6][CH2:7][N:8]([CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)[C:9]([CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[NH:21][C:20](=[O:25])[CH:19]=[CH:18]2)=[O:10].C(N(CC)CC)C.[C:39](Cl)(=[O:46])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>C(Cl)(Cl)Cl.CO>[C:39]([O:5][CH2:6][CH2:7][N:8]([CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)[C:9]([CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[NH:21][C:20](=[O:25])[CH:19]=[CH:18]2)=[O:10])(=[O:46])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1
Reactant: O=C(CCCOc1ccc2[nH]c(=O)ccc2c1)N(CCO)C1CCCCC1
Reactant: O=C(Cl)c1ccccc1
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Solvent: CO
Product: O=C(OCCN(C(=O)CCCOc1ccc2[nH]c(=O)ccc2c1)C1CCCCC1)c1ccccc1

Procedure:
Into 100 ml of chloroform were added 3.7 g of 6-{3-[N-(2-hydroxyethyl)-N-cyclohexylaminocarbonyl]propoxy}carbostyril and 1.8 ml of triethylamine and the outside of the reaction vessel containing said mixture was ice-cooled. Then 1.4 ml of benzoyl chloride was added dropwise to the mixture under stirring condition. After the addition operation the reaction mixture was further stirred at room temperature for 1 hour. Then the reaction mixture was washed with 5% NaHCO3 aqueous solution, diluted hydrochloric acid and water in this order, then dried with anhydrous sodium sulfate. The drying agent was removed by filtration and the mother liquor is concentrated. The residue thus obtained is treated by a silica-gel column chromatography [the solvent used was a mixture of chloroform:methanol 30:1 (v/v)] and the elute was recrystallized from chloroform-petroleum ether to obtain 3.0 g of 6-{3-[N-(2-benzoyloxyethyl)-N-cyclohexylaminocarbonyl]propoxy}carbostyril as in the form of colorless needle-like crystals. Melting point: 94°-96° C.
Reaction SMILES: [C@@H:1]1([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1.[CH3:18][C:19]([Si:22](Cl)([CH3:24])[CH3:23])([CH3:21])[CH3:20]>C(Cl)Cl>[Si:22]([O:7][CH2:6][C@H:5]1[O:8][C@@H:1]([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[CH2:2][C@@H:3]1[OH:4])([C:19]([CH3:21])([CH3:20])[CH3:18])([CH3:24])[CH3:23]
Reactant: Cc1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O
Reactant: CC(C)(C)[Si](C)(C)Cl
Solvent: ClCCl
Product: Cc1cn([C@H]2C[C@H](O)[C@@H](CO[Si](C)(C)C(C)(C)C)O2)c(=O)[nH]c1=O

Procedure:
A solution of thymidine dT (2.85 g, 11.76 mmol), imidiazole (2.44 g, 35.80 mmol) and TBSCl (1.77 g, 11.76 mmol) in anhydrous CH2Cl2 (20 mL) was stirred at room temperature overnight under a N2 atmosphere. The reaction mixture was then concentrated in vacuo to a viscous oil, followed by the addition of ethyl ether (60 mL) and water (60 mL). The organic layer was separated and washed twice with water (20 mL each), and the combined aqueous layer was extracted with ethyl ether (20 mL). The combined organic layer was dried over Na2SO4, concentrated in vacuo and purified by silica gel column chromatography to give 5′-O-tert-butyldimethylsilyl-thymidine dT.01 (3.44 g, 82%) as a white solid.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]2[N:8]([CH2:20][CH2:21][C:22]([O:25][CH3:26])([CH3:24])[CH3:23])[N:9]=[C:10]([NH:11][C:12]3[C:17]([Cl:18])=[CH:16][CH:15]=[CH:14][C:13]=3[Cl:19])[C:5]2=[CH:4][N:3]=1.C1COCC1.[CH3:32][NH:33]C.[C:35]([OH:41])([C:37]([F:40])([F:39])[F:38])=[O:36]>O1CCOCC1>[C:35]([OH:41])([C:37]([F:40])([F:39])[F:38])=[O:36].[Cl:18][C:17]1[CH:16]=[CH:15][CH:14]=[C:13]([Cl:19])[C:12]=1[NH:11][C:10]1[C:5]2[C:6](=[N:7][C:2]([NH:33][CH3:32])=[N:3][CH:4]=2)[N:8]([CH2:20][CH2:21][C:22]([O:25][CH3:26])([CH3:23])[CH3:24])[N:9]=1
Reactant: COC(C)(C)CCn1nc(Nc2c(Cl)cccc2Cl)c2cnc(Cl)nc21
Reactant: CNC
Solvent: C1COCCO1
Solvent: O=C(O)C(F)(F)F
Solvent: C1CCOC1
Product: CNc1ncc2c(Nc3c(Cl)cccc3Cl)nn(CCC(C)(C)OC)c2n1
Temperature: 100 °C
Reaction time: 23 h

Procedure:
A sealed tube containing 55 mg (0.13 mmol) of 6-chloro-N-(2,6-dichlorophenyl)-1-(3-methoxy-3-methylbutyl)-1H-pyrazolo[3,4-d]pyrimidin-3-amine (prepared as described in Example 1, Step B), 650 μl (2.0 M, 1.3 mmol) of a THF solution of dimethylamine and 120 μl (1.6 mmol) of TFA in 3 mL 1,4-dioxane was heated at 100° C. for 21 h. After this time, 650 μl (2.0 M, 1.3 mmol) of a THF solution of dimethylamine and 120 μl (1.6 mmol) of TFA were added, and heating was continued at 100° C. for an additional 23 h. The orange solution was concentrated, and the residue was purified by HPLC (Capcell Pak C18 5 μm, gradient of 80% A:20% B to 30% A:70% B over 45 min; A=0.5% TFA in water, B=0.5% TFA in acetonitrile) to give the title compound. 1H-NMR (CDCl3) δ 1.25 (s, 6H), 2.01-2.08 (m, 2H), 3.05 (s, 3H), 3.22 (s, 3H), 4.19-4.26 (m, 2H), 6.60 (s, 1H), 7.24 (t, J=8.4 Hz, 1H), 7.46 (d, J=8.1 Hz, 2H), 7.77 (s, 1H), 9.49 (s, 1H). Mass Spectrum (ESI) m/e=409.1.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]3[NH:17][C:16](=[O:18])[NH:15][C:11]3=[N:12][C:13]=2[CH3:14])=[CH:4][CH:3]=1.[CH:19](O)=O>>[CH3:19][NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]3[NH:17][C:16](=[O:18])[NH:15][C:11]3=[N:12][C:13]=2[CH3:14])=[CH:4][CH:3]=1
Reactant: O=CO
Reactant: Cc1nc2[nH]c(=O)[nH]c2cc1-c1ccc(N)cc1
Product: CNc1ccc(-c2cc3[nH]c(=O)[nH]c3nc2C)cc1

Procedure:
It is contemplated that 6-(4-aminophenyl)-1,3-dihydro-5-methyl-2H-imidazo[4,5-b]pyridin-2-one can be alkylated by reacting it with formic acid followed by reduction of the intermediate formylamino derivative to obtain 6-[4-(methylamino)phenyl]-1,3-dihydro-5-methyl-2H-imidazo[4,5-b]pyridin-2-one [I; Ar =4-CH3NHC6H4, R1 and R3H, R5 =CH3 ]; or by reacting it with formaldehyde under reducing conditions to obtain 6-[4-(dimethylamino)pheny]-1,3-dihydro-5-methyl-2H-imidazo[4,5-b]pyridin-2-one [I; Ar =4-(CH3)2NC6H4, R1 and R3 =H, R5 =CH3 ].
Reaction SMILES: S(=O)(=O)(O)O.[OH:6][C:7]1[C:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:14][CH:13]=[CH:12][C:8]=1[C:9]([OH:11])=[O:10].[CH3:22]O>>[OH:6][C:7]1[C:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:14][CH:13]=[CH:12][C:8]=1[C:9]([O:11][CH3:22])=[O:10]
Reactant: O=C(O)c1cccc(-c2ccccc2)c1O
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)c1cccc(-c2ccccc2)c1O
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Methanol (50 ml) was treated with concentrated sulphuric acid (4.9 g, 2.66 ml) cautiously. 2-Hydroxy-3-phenylbenzoic acid (10.7 g, 50 mmol) was added and the reaction mixture stirred at ambient temperature for 18 hours. The mixture was then heated at reflux for 4 hours, cooled to ambient temperature and evaporated. The residue was partitioned between ethyl acetate/and water, the organic layer washed twice with water, dried (MgSO4) and evaporated to give methyl 2-hydroxy-3-phenylbenzoate.
Reaction SMILES: [F:1][C:2]([F:38])([F:37])[C:3]1[CH:4]=[C:5]([CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1)[CH2:6][N:7]([CH2:20][CH2:21][NH:22]C(OC(C)(C)C)=O)[C:8]([C:10]1[C:11](Cl)=[N:12][C:13]([S:17][CH3:18])=[N:14][C:15]=1[Cl:16])=[O:9]>C(OCC)(=O)C.Cl>[F:38][C:2]([F:1])([F:37])[C:3]1[CH:4]=[C:5]([CH:30]=[C:31]([C:33]([F:36])([F:34])[F:35])[CH:32]=1)[CH2:6][N:7]1[C:8](=[O:9])[C:10]2[C:15]([Cl:16])=[N:14][C:13]([S:17][CH3:18])=[N:12][C:11]=2[NH:22][CH2:21][CH2:20]1
Reactant: CSc1nc(Cl)c(C(=O)N(CCNC(=O)OC(C)(C)C)Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)c(Cl)n1
Agent: Cl
Solvent: CCOC(C)=O
Product: CSc1nc(Cl)c2c(n1)NCCN(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)C2=O
Reaction time: 1 h
Yield: 68 %

Procedure:
3 mol/L hydrogen chloride-ethyl acetate (30 mL) was added to N-[3,5-bis(trifluoromethyl)benzyl]-N-[2-(t-butoxycarbonylamino)ethyl]-4,6-dichloro-2-(methylthio)pyrimidine-5-carboxylic acid amide (Compound of Reference Example 5; 11.8 g) while the solution was chilled on an ice bath. The reaction mixture was stirred for 1 hour and then additional 1 hour at room temperature. The solvent was removed and the resulting residue was dissolved in N,N-dimethylformamide (20 mL). To this solution, potassium carbonate (5.37 g) was added and the mixture was stirred at 100° C. for 1 hour. The reaction mixture was diluted with ethyl acetate, was sequentially washed with water and a saturated aqueous solution of sodium chloride, and was then dried over anhydrous sodium sulfate. Following removal of the solvent, the residue was purified on a silica gel column chromatography (ethyl acetate:hexane=2:1) to obtain 6-[3,5-bis(trifluoromethyl)benzyl]-4-chloro-2-(methylthio)-5-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-e][1,4]diazepin (6.22 g, 68%).
Reaction SMILES: [C:1]1(=[O:10])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1>C1C=CC=CC=1.CCOCC>[CH:1]1([OH:10])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1
Reactant: O=C1CCc2ccccc21
Solvent: CCOCC
Solvent: c1ccccc1
Product: OC1CCc2ccccc21
Temperature: 35 °C
Reaction time: 1 h
Yield: 74.4 %

Procedure:
20 g Indanone (obtained according to Example VIII) is added to a solution of 1.5 molequivalent NaAlH2 (OC2H4OCH3)2 in a mixture of benzene and ether in the course of which the temperature raises to 35° C. Then the reaction mixture is stirred during one hour, poured out into ice and extracted with ether. The solution in ether is washed with NaCl solution, dried and evaporated. The residue is distilled under diminished pressure yielding 15.1 g indanol. B.p. 115° C./1 mm Hg. The indanol is dissolved in 100 ml cyclohexane and during 30 min. gaseous HCl is introduced followed by N2 to remove the excess of HCl. The reaction mixture is evaporated and the residue is distilled under diminished pressure yielding 12.9 g indanyl chloride. B.p. 95° C./1 mm Hg.
Reaction SMILES: C([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([NH:13][C:14]3[N:19]=[C:18]([NH:20][C:21]4[CH:22]=[N:23][C:24]5[C:29]([CH:30]=4)=[CH:28][CH:27]=[CH:26][CH:25]=5)[CH:17]=[CH:16][N:15]=3)[CH:11]=2)[C:6]([CH3:32])([CH3:31])[CH2:5]1)(=O)C.CCOC(C)=O.C([O-])(O)=O.[Na+]>CCO.Cl>[CH3:31][C:6]1([CH3:32])[C:7]2[C:12](=[CH:11][C:10]([NH:13][C:14]3[N:19]=[C:18]([NH:20][C:21]4[CH:22]=[N:23][C:24]5[C:29]([CH:30]=4)=[CH:28][CH:27]=[CH:26][CH:25]=5)[CH:17]=[CH:16][N:15]=3)=[CH:9][CH:8]=2)[NH:4][CH2:5]1
Reactant: CC(=O)N1CC(C)(C)c2ccc(Nc3nccc(Nc4cnc5ccccc5c4)n3)cc21
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CCO
Product: CC1(C)CNc2cc(Nc3nccc(Nc4cnc5ccccc5c4)n3)ccc21

Procedure:
A mixture of N2-(1-acetyl-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-N4-(3-quinolinyl)-2,4-pyrimidinediamine (Example 110, 170 mg, 0.266 mmol) was dissolved in EtOH (6 mL) and 10 drops conc. HCl were added. The mixture was heated to reflux in a sealed tube for 72 h. The crude mixture was poured into EtOAc (125 mL) and sat NaHCO3 (20 mL). The organics were dried over anhydrous MgSO4 and concentrated under reduced pressure. The crude product was purified via medium pressure liquid chromatography using linear gradient starting from 0:100 MeOH/CH2Cl2 ending with 10:90 MeOH/CH2Cl2 as the solvent system to yield the desired product as a tan solid. M+H—383; Calc'd for C23H22N6—382.
Reaction SMILES: [C:1]([O:5][C:6]([C@@H:8]1[CH2:12][C@@H:11](O)[CH2:10][N:9]1[S:14]([C:17]1[CH:26]=[CH:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=1)(=[O:16])=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(OC([C@@H]1C[C@H](OS(C)(=O)=O)CN1S(C1C=CC2C(=CC=CC=2)C=1)(=O)=O)=O)(C)(C)C.[C:57]([O-:60])(=[S:59])[CH3:58].[K+]>>[C:1]([O:5][C:6]([C@@H:8]1[CH2:12][C@@H:11]([S:59][C:57](=[O:60])[CH3:58])[CH2:10][N:9]1[S:14]([C:17]1[CH:26]=[CH:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=1)(=[O:15])=[O:16])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC([O-])=S
Reactant: CC(C)(C)OC(=O)[C@@H]1C[C@@H](O)CN1S(=O)(=O)c1ccc2ccccc2c1
Agent: CC(C)(C)OC(=O)[C@@H]1C[C@H](OS(C)(=O)=O)CN1S(=O)(=O)c1ccc2ccccc2c1
Agent: [K+]
Product: CC(=O)S[C@@H]1C[C@@H](C(=O)OC(C)(C)C)N(S(=O)(=O)c2ccc3ccccc3c2)C1

Procedure:
(2S,4R)-4-Hydroxy-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid tert-butyl ester via (2S,4S)-4-Methanesulfonyloxy-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid tert-butyl ester which was treated with potassium thioacetate at 100° C. to give (2S,4R)-4-Acetylsulfanyl- 1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid tert-butyl ester as light yellow solid, MS: 359 (M-HSCOCH3).
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]1[C:8](=[O:9])[C:7]2=[CH:10][CH:11]=[CH:12][CH:13]=[C:6]2[C:5]1=[O:14].C(N(CC)CC)C.[Br:22][C:23]([CH3:28])([CH3:27])[C:24](Br)=[O:25].O>C1COCC1>[C:8]1(=[O:9])[N:4]([CH2:3][CH2:2][O:1][C:24](=[O:25])[C:23]([Br:22])([CH3:28])[CH3:27])[C:5](=[O:14])[C:6]2=[CH:13][CH:12]=[CH:11][CH:10]=[C:7]12
Reactant: CC(C)(Br)C(=O)Br
Reactant: O=C1c2ccccc2C(=O)N1CCO
Solvent: O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(C)(Br)C(=O)OCCN1C(=O)c2ccccc2C1=O
Reaction time: 0.75 h
Yield: 75.8 %

Procedure:
N-(2-hydroxyethyl)phthalimide (19.12 g, 0.1 mol) was dissolved in anhydrous THF (250 mL) with triethylamine (28.1 mL, 0.2 mol) under nitrogen in a 500 mL round bottom flask equipped with a magnetic stirrer and dropping funnel. The flask was cooled to 0° C. with an ice/salt bath before the dropwise addition of 2-bromo-2-methylpropionyl bromide (13.9 mL, 0.11 mol). The mixture was stirred for 45 minutes and allowed to reach room temperature before the mixture was poured into an excess of cold water and the product extracted with diethyl ether (3×100 mL). The organic layer was subsequently washed with a saturated aqueous solution of sodium carbonate (3×100 mL), acidified water (pH 4.6, 3×100 mL) and again with saturated aqueous solution of sodium carbonate (3×100 mL). The organic layer was dried over anhydrous magnesium sulphate and filtered. The product was isolated via reduction under reduced pressure to obtain a white solid (25.79 g, 75.8% yield). 1H NMR (CDCl3) δ (ppm) 1.81 (s, 6H, C(CH3)2Br), 3.95 (t, 2H, J=5.3 Hz, CH2—N), 4.35 (t, 2H, J=5.4 Hz, CH2—O), 7.67 (m, 2H, Haro), 7.78 (m, 2H, Haro). 13C NMR (CDCl3) δ (ppm) 31.00 (2C, C(CH3)2Br), 37.12 (1C, CH2—N), 55.92 (1C, C(CH3)2Br), 63.42 (1C, CH2—O), 123.78 (2C, Caro), 132.35 (1C, CIVaro), 133.54 (2C, Caro), 168.40 (2C, Ccycl═O), 171.87 (1C, C═O). IR (solid, ATR cell) ν (cm−1) 2975, 1774 (Ccycl═O), 1705 (C═O), 1417, 1392, 1321, 1276, 1158, 1105, 1063, 985, 763, 716, 632. Melting point 63-65° C.
Reaction SMILES: Cl([O-])(=O)(=O)=O.[Na+].[OH:7][C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[CH:10][CH:9]=1.[OH-].[Na+].[I-:19].[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+].Cl>CO>[I:19][C:9]1[CH:10]=[C:11]([CH:15]=[CH:16][C:8]=1[OH:7])[C:12]([OH:14])=[O:13]
Reactant: [I-]
Reactant: O=C(O)c1ccc(O)cc1
Agent: Cl
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: CO
Product: O=C(O)c1ccc(O)c(I)c1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
3.6% sodium perchlorate solution is added dropwise to a mixture of 4-hydroxybenzoic acid (12.75 g, 0.92 mol), sodium hydroxide (3.7 g, 0.92 mol) and sodium iodide (13.85 g, 0.92 mol) in methanol (350 ml) at 0° C. The mixture is left stirring for two hours at 0° C. 100 ml of 10% sodium thiosulphate solution are added. After stirring, the mixture is acidified with hydrochloric acid to pH 1. It is extracted with 600 ml of ethyl ether. The organic phase is washed twice with 400 ml of water, dried over magnesium sulphate and concentrated on a rotary evaporator under vacuum at 40° C.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([S:8][C:9]2[CH:10]=[C:11]([NH:15][C:16](=[O:19])[CH:17]=[CH2:18])[CH:12]=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[O:20]1[CH2:25][CH2:24][N:23]([C:26]2[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][CH:27]=2)[CH2:22][CH2:21]1>>[O:20]1[CH2:21][CH2:22][N:23]([C:26]2[CH:27]=[CH:28][C:29]([NH:30][C:2]3[N:7]=[C:6]([S:8][C:9]4[CH:10]=[C:11]([NH:15][C:16](=[O:19])[CH:17]=[CH2:18])[CH:12]=[CH:13][CH:14]=4)[CH:5]=[CH:4][N:3]=3)=[CH:31][CH:32]=2)[CH2:24][CH2:25]1
Reactant: Nc1ccc(N2CCOCC2)cc1
Reactant: C=CC(=O)Nc1cccc(Sc2ccnc(Cl)n2)c1
Product: C=CC(=O)Nc1cccc(Sc2ccnc(Nc3ccc(N4CCOCC4)cc3)n2)c1
Yield: 42.2 %

Procedure:
In a procedure analogous to Example 8, reaction of N-(3-(2-chloropyrimidin-4-ylthio)phenyl)acrylamide (1.10 g, 3.77 mmol) and 4-morpholinoaniline (806 mg, 4.52 mmol) furnished the product (690 mg, 43%).
Reaction SMILES: Br[CH2:2][CH:3]1[CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=2)[CH2:4]1.[N-:21]=[N+:22]=[N-:23].[Na+]>CN(C=O)C>[N:21]([CH2:2][CH:3]1[CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=2)[CH2:4]1)=[N+:22]=[N-:23]
Reactant: [N-]=[N+]=[N-]
Reactant: Clc1ccc(C2CC(CBr)Cc3ccccc32)cc1Cl
Agent: [Na+]
Solvent: CN(C)C=O
Product: [N-]=[N+]=NCC1Cc2ccccc2C(c2ccc(Cl)c(Cl)c2)C1

Procedure:
Referring to Scheme 2, acylation of the alpha-tetralone 4-(3,4-dichlorophenyl)-3,4-dihydro-2H-naphthalen-1-one (Compound 1) with diethylcarbonate was followed by reduction with triethylsilane to give 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid ethyl ester (Compound 10). Reduction and conversion to 3-bromomethyl-1-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalene (Compound 12) is followed by alkylation with sodium azide in DMF to give 3-azidomethyl-1-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalene (Compound 13). Chiral separation of Compound 13 is followed by hydrogenation to give a compound of the invention, C-[4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-2-yl]-methylamine (Compound 14). Alternatively, reduction and conversion to 3-bromomethyl-1-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalene (Compound 12) is followed by alkylation with substituted amines to give 1-phenyl-3-aminoalkyl-1,2,3,4-tetrahydronaphthalenes (Compound 15).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:14][OH:15])[CH:5]=[N:6][C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11]>CCOC(C)=O.[O-2].[Mn+4].[O-2]>[Cl:1][C:2]1[C:7]([O:8][CH2:9][C:10]([F:12])([F:13])[F:11])=[N:6][CH:5]=[C:4]([CH:3]=1)[CH:14]=[O:15]
Reactant: OCc1cnc(OCC(F)(F)F)c(Cl)c1
Agent: [Mn+4]
Agent: [O-2]
Solvent: CCOC(C)=O
Product: O=Cc1cnc(OCC(F)(F)F)c(Cl)c1
Temperature: 120 °C
Yield: 85.2 %

Procedure:
To a solution of (5-chloro-6-(2,2,2-trifluoroethoxyl)pyridin-3-yl)methanol (4.00 g, 16.56 mmol) in EtOAc (15 mL) was added manganese(IV) oxide (16.93 g, 166 mmol). The reaction was heated with microwave at 120° C. for 30 minutes. The mixture was then filtered through a pad of celite, and rinsed with EtOAc. The filtrated was concentrated to give crude product (3.38 g).