Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][CH3:9].[C:10]([C:14]1[CH:20]=[C:19]([OH:21])[CH:18]=[C:17]([C:22]([CH3:25])([CH3:24])[CH3:23])[C:15]=1[OH:16])([CH3:13])([CH3:12])[CH3:11]>>[C:10]([C:14]1[C:15](=[O:16])[C:17]([C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:18][C:19]([OH:21])([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[O:8][CH3:9])[CH:20]=1)([CH3:13])([CH3:12])[CH3:11]
Reactant: COc1ccccc1Br
Reactant: CC(C)(C)c1cc(O)cc(C(C)(C)C)c1O
Product: COc1ccccc1C1(O)C=C(C(C)(C)C)C(=O)C(C(C)(C)C)=C1

Procedure:
Using the method described in Example 1, 2-bromo-methoxybenzene is reacted with 2,6-di(t-butyl)hydroquinone to provide 2,6-di(t-butyl)-4-hydroxy-4-(2'-methoxyphenyl)-2,5-cyclohexadienone. This product is dissolved in ethanol and reduced with hydrogen gas on a Parr apparatus using palladium on charcoal as the catalyst. The white solid product is recrystallized from benzene to provide 2,6-di(t-butyl)-4-(2'-methoxyphenyl)phenol, m.p. 98.5°-100° C.
Reaction SMILES: CN([CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:15][CH3:16])[C:12]=2[Cl:14])[NH:7][CH:6]=1)C.[C-:17]#[N:18].[K+].CI>>[C:17]([CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:15][CH3:16])[C:12]=2[Cl:14])[NH:7][CH:6]=1)#[N:18]
Reactant: [C-]#N
Reactant: COc1ccc2[nH]cc(CN(C)C)c2c1Cl
Agent: [K+]
Solvent: CI
Product: COc1ccc2[nH]cc(CC#N)c2c1Cl
Yield: 91.2 %

Procedure:
Reaction of 3-dimethylaminomethyl-4-chloro-5-methoxy-indole (2.00 g, 8.40 mmol) with potassium cyanide (2.08 g, 32.0 mmol) and methyl iodide (4.72 g, 33.0 mmol) and subsequent workup as described in 1 (d) gave 3-cyanomethyl-4-chloro-5-methoxyindole (1.69 g), m.p. 138°-9° C.
Reaction SMILES: [C:1]([O:5][C:6](=[O:28])[CH2:7][C@H:8]([C:18]1[O:22][N:21]=[C:20]([C:23](OCC)=[O:24])[N:19]=1)[CH2:9][CH2:10][CH2:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)([CH3:4])([CH3:3])[CH3:2].[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1>C(O)C>[CH:12]1([CH2:11][CH2:10][CH2:9][C@@H:8]([C:18]2[O:22][N:21]=[C:20]([C:23]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[O:24])[N:19]=2)[CH2:7][C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:28])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]1
Reactant: C1COCCN1
Reactant: CCOC(=O)c1noc([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)n1
Solvent: CCO
Product: CC(C)(C)OC(=O)C[C@@H](CCCC1CCCCC1)c1nc(C(=O)N2CCOCC2)no1
Temperature: 25 °C
Reaction time: 17 h
Yield: 81.3 %

Procedure:
A solution of ethyl 5-{(1R)-1-[2-(tert-butoxy)-2-oxoethyl]-4-cyclohexylbutyl}-1,2,4-oxadiazole-3-carboxylate (Preparation 3) (300 mg, 0.76 mmol) in ethanol (4 ml) was cooled to 0° C. then treated with morpholine (0.066 ml, 7.60 mmol). The resulting mixture was warmed to room temperature and stirred under a nitrogen atmosphere for 17 hours. Further morpholine (0.53 ml, 6.08 mmol) was added and the mixture heated to 60° C. for 8 hours. The mixture was cooled and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with dichloromethane:ethyl acetate (80:20) to afford title compound as a yellow oil (269 mg)
Reaction SMILES: C([O:3][C:4](=[O:41])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:27]=[C:26]([C:28](=[O:32])[N:29]([CH3:31])[CH3:30])[CH:25]=[C:24](Br)[CH:23]=2)[C:10]=1[CH2:34][CH2:35][C:36]([O:38]CC)=[O:37])C.[Cl:42][C:43]1[CH:44]=[C:45](B(O)O)[CH:46]=[CH:47][CH:48]=1>>[C:36]([CH2:35][CH2:34][C:10]1[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:23]=[C:24]([C:45]3[CH:46]=[CH:47][CH:48]=[C:43]([Cl:42])[CH:44]=3)[CH:25]=[C:26]([C:28](=[O:32])[N:29]([CH3:30])[CH3:31])[CH:27]=2)=[CH:12][CH:13]=[CH:14][C:9]=1[O:8][CH2:7][CH2:6][CH2:5][C:4]([OH:41])=[O:3])([OH:38])=[O:37]
Reactant: CCOC(=O)CCCOc1cccc(CCCCCCOc2cc(Br)cc(C(=O)N(C)C)c2)c1CCC(=O)OCC
Reactant: OB(O)c1cccc(Cl)c1
Product: CN(C)C(=O)c1cc(OCCCCCCc2cccc(OCCCC(=O)O)c2CCC(=O)O)cc(-c2cccc(Cl)c2)c1

Procedure:
The title compound was prepared according to the general procedure described in Steps 3 and 4 of Method F starting from 4-[3-[6-(3-bromo-5-dimethylcarbamoyl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester and 3-chlorophenylboronic acid. LC/MS indicated a purity of 100% as measured by UV 214 nM.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:12][CH2:11][C@@H:10]([OH:13])[CH2:9]2)=[CH:4][CH:3]=1.[Si:14](Cl)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]>CN(C=O)C>[Si:14]([O:13][C@@H:10]1[CH2:11][CH2:12][N:8]([C:5]2[N:6]=[N:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[CH2:9]1)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: O[C@@H]1CCN(c2ccc(Cl)nn2)C1
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)O[C@@H]1CCN(c2ccc(Cl)nn2)C1
Temperature: 25 °C
Reaction time: 6 h
Yield: 84.9 %

Procedure:
To a solution of compound 27 (815 mg, 4.08 mmol) in DMF (15 mL) were added t-butyldimethylsilyl chloride (738 mg, 4.9 mmol) amd imidazole (556 mg, 8.16 mmol). The thus obtained solution was stirred at room temperature for 6 h. The reaction mixture was concentrated and the residue was purified by chromatography on silica gel eluting with 15% to 50% to give the compound 28 as a white solid (1.087 g, 85%). LCMS-ESI (POS), M/Z, M+1: Found 314.1, Calculated 314.1.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([C:12]([F:15])([F:14])[F:13])[N:3]=1.[S:16]([O-:19])([OH:18])=[O:17].[Na+:20].C(O)C>O>[F:9][C:8]([F:11])([F:10])[C:6]1[CH:5]=[C:4]([C:12]([F:15])([F:14])[F:13])[N:3]=[C:2]([S:16]([O-:19])(=[O:18])=[O:17])[CH:7]=1.[Na+:20]
Reactant: FC(F)(F)c1cc(Cl)nc(C(F)(F)F)c1
Reactant: O=S([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: O=S(=O)([O-])c1cc(C(F)(F)F)cc(C(F)(F)F)n1
Yield: 66.5 %

Procedure:
A mixture of 2-chloro-4,6-bis(trifluoromethyl)pyridine (2.50 g, 10 mmol), sodium hydrogen sulfite (4.2 g, 40 mmol), ethanol (40 ml) and water (40 ml) was heated under reflux for 96.5 hours. The reaction mixture was evaporated to dryness under reduced pressure. To the residue, conc. hydrochloric acid was added and the mixture was again evaporated to dryness. The residued was extracted with methanol, and a methanol phase was filtered. The filtrate was evaporated to dryness under reduced pressure to obtain sodium 4,6-bis(trifluoromethyl)pyridine-2-sulfonate (2.11 g). Yield, 66%.
Reaction SMILES: CS(O[CH2:6][C:7]1[CH:16]=[CH:15][C:14]2[C@H:13]([NH:17]C(OC(C)(C)C)=O)[CH2:12][CH2:11][CH2:10][C:9]=2[CH:8]=1)(=O)=O.[F:25][CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.Cl.C([O-])([O-])=O.[K+].[K+]>C1COCC1>[F:25][CH:26]1[CH2:31][CH2:30][N:29]([CH2:6][C:7]2[CH:8]=[C:9]3[C:14](=[CH:15][CH:16]=2)[C@H:13]([NH2:17])[CH2:12][CH2:11][CH2:10]3)[CH2:28][CH2:27]1
Reactant: FC1CCNCC1
Reactant: CC(C)(C)OC(=O)N[C@@H]1CCCc2cc(COS(C)(=O)=O)ccc21
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: N[C@@H]1CCCc2cc(CN3CCC(F)CC3)ccc21

Procedure:
A mixture of (R)-(5-(tert-butoxycarbonylamino)-5,6,7,8-tetrahydronaphthalen-2-yl)methyl methanesulfonate (2.0 g, 5.633 mmol, 1.0 eq.), 4-fluoropiperidine.HCl (0.78 g, 5.633 mmol, 1.0 eq.) and K2CO3 (2.33 g, 16.9 mmol, 3.0 eq.) in THF (25 ml) was heated at reflux for 16 h. After completion of the reaction (monitored by TLC), the solvent was evaporated under reduced pressure and the residue was dissolved in ethyl acetate (150 ml), washed with water (100 ml) and brine (100 ml), and dried over Na2SO4. The solvent was evaporated under reduced pressure to give the crude product which was purified by column chromatography (silica gel; 40% ethyl acetate/hexanes) to yield the title compound as a light yellow solid. Yield: 60% (1.22 g, 3.37 mmol) 2. TFA (1 ml) was added to a solution of (R)-tert-butyl 6-((4-fluoropiperidin-1-yl)methyl)-1,2,3,4-tetrahydronaphthalen-1-ylcarbamate (325 mg, 0.898 mmol, 1.0 eq.) in DCM (4 ml) at 0° C. and the resulting reaction mixture was stirred at 25° C. for 4 h. The solvent was evaporated under reduced pressure and the residue was azeotroped with toluene to yield the desired product which was employed in the next step.
Reaction SMILES: O[C:2]1[C:14]2[C:13]3[CH:12]=[CH:11][C:10]([C:15]([F:18])([F:17])[F:16])=[CH:9][C:8]=3[NH:7][C:6]=2[C:5]([C:19]#[N:20])=[CH:4][N:3]=1.O=P(Cl)(Cl)[Cl:23].C([O-])(O)=O.[Na+]>CCOC(C)=O>[Cl:23][C:2]1[C:14]2[C:13]3[CH:12]=[CH:11][C:10]([C:15]([F:18])([F:17])[F:16])=[CH:9][C:8]=3[NH:7][C:6]=2[C:5]([C:19]#[N:20])=[CH:4][N:3]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: N#Cc1cnc(O)c2c1[nH]c1cc(C(F)(F)F)ccc12
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Product: N#Cc1cnc(Cl)c2c1[nH]c1cc(C(F)(F)F)ccc12
Temperature: 175 °C

Procedure:
A mixture of 1-hydroxy-7-(trifluoromethyl)-5H-pyrido[4,3-b]indole-4-carbonitrile in an excess of POCl3 was heated in a microwave apparatus at 175° C. for a period of 13 min. The reaction mixture was poured slowly into cold EtOAc and saturated NaHCO3. The organic phase was separated, dried over Na2SO4, filtered and evaporated to give the title compound.
Reaction SMILES: [C:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(N(C(C)C)CC)(C)C.[F:23][C:24]([F:35])([F:34])[C:25]1[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=1[C:27](Cl)=[O:28]>ClCCl>[C:4]([O:3][C:1]([N:8]1[CH2:9][CH2:10][N:11]([C:27](=[O:28])[C:26]2[CH:30]=[CH:31][CH:32]=[CH:33][C:25]=2[C:24]([F:23])([F:34])[F:35])[CH2:12][CH2:13]1)=[O:2])([CH3:7])([CH3:6])[CH3:5]
Reactant: O=C(Cl)c1ccccc1C(F)(F)F
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N1CCN(C(=O)c2ccccc2C(F)(F)F)CC1
Temperature: 25 °C
Reaction time: 0.02 h
Yield: 95 %

Procedure:
To a stirred solution of 1-Boc-piperazine (1.96 g, 10.5 mmol) and diisopropylethylamine (2.714 g, 21 mmol, 3.63 mL) in dichloromethane (50 mL) was added 2-trifluoromethylbenzoyl chloride (2.086 g, 10.0 mmol) dropwise. The resulting mixture was stirred at room temperature for 1 minutes and then quenched with water (25 mL). The organic phase was separated and washed with H2O, brine, dried over MgSO4 and then concentrated in vacuo to afford product 4-(2-trifluoromethylbenzoyl)-piperazine-1-carboxylic acid tert-butyl ester as pale yellow solid. Yield 95%, 3.575 g.
Reaction SMILES: [CH2:1]([NH:13][C:14](=[O:18])[C@H:15]([CH3:17])[NH2:16])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[OH-].[Na+].[CH:21](=O)[C:22]1[C:23](=[CH:25][CH:26]=[CH:27][CH:28]=1)[OH:24].[BH4-].[Na+]>CO>[CH2:1]([NH:13][C:14](=[O:18])[C@H:15]([CH3:17])[NH:16][CH2:21][C:22]1[CH:28]=[CH:27][CH:26]=[CH:25][C:23]=1[OH:24])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: O=Cc1ccccc1O
Reactant: CCCCCCCCCCCCNC(=O)[C@H](C)N
Agent: [BH4-]
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCCCCCCCCCCCNC(=O)[C@H](C)NCc1ccccc1O
Reaction time: 1 h

Procedure:
L-alanine laurylamide (2.5 g) and 1 g of sodium hydroxide were dissolved in 20 ml of methanol, and 1.0 ml of salicylaldehyde and 0.1 g of sodium borohydride were added thereto in this order. After the mixture was stirred for 1 hour, 1.0 ml of salicylaldehyde and 0.1 g of sodium borohydride were added thereto again in this order. The mixture was stirred overnight at room temperature, and the insoluble matter was then separated through filtration. The filtrate was adjusted to a pH of 7 with hydrochloric acid, and concentrated under reduced pressure. The resulting oil was dissolved in diethyl ether, washed with water, and then dried over with magnesium sulfate. After the drying agent was separated through filtration, the filtrate was concentrated under reduced pressure to give 3 g of N-(2-hydroxybenzyl)-L-alanine laurylamide.
Reaction SMILES: [CH:1]1([S:4]([NH:7][C:8]([C:10]2([NH:15][C:16]([CH:18]3[CH2:22][CH:21]([O:23][C:24]4[CH:29]=[CH:28][N:27]=[C:26](Cl)[N:25]=4)[CH2:20][CH:19]3[C:31]([N:33]([CH2:35][CH2:36][CH2:37][CH2:38][CH:39]=[CH2:40])[CH3:34])=[O:32])=[O:17])[CH2:12][CH:11]2C=C)=[O:9])(=[O:6])=[O:5])[CH2:3][CH2:2]1.[NH:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1>C1COCC1.ClCCCl>[CH3:34][N:33]1[C:31](=[O:32])[CH:19]2[CH:18]([CH2:22][CH:21]([O:23][C:24]3[CH:29]=[CH:28][N:27]=[C:26]([N:41]4[CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)[N:25]=3)[CH2:20]2)[C:16](=[O:17])[NH:15][C:10]2([C:8]([NH:7][S:4]([CH:1]3[CH2:3][CH2:2]3)(=[O:6])=[O:5])=[O:9])[CH:11]([CH2:12]2)[CH:40]=[CH:39][CH2:38][CH2:37][CH2:36][CH2:35]1
Reactant: C1COCCN1
Reactant: C=CCCCCN(C)C(=O)C1CC(Oc2ccnc(Cl)n2)CC1C(=O)NC1(C(=O)NS(=O)(=O)C2CC2)CC1C=C
Solvent: C1CCOC1
Solvent: ClCCCl
Product: CN1CCCCC=CC2CC2(C(=O)NS(=O)(=O)C2CC2)NC(=O)C2CC(Oc3ccnc(N4CCOCC4)n3)CC2C1=O
Temperature: 150 °C

Procedure:
Compound 10f (31 mg, 0.052 mmol) and morpholine (0.1 ml) in THF was left at ambient temperature for 20 hrs, volatiles were stripped of and the residue was dissolved in DCE (15 ml) to which Hoyeda-Grubbs II catalyst (7 mg) was added. The mixture was heated in a microwave oven at 150° C. for 10 min under an atmosphere of nitrogen, then concentrated to dryness and purified by column chromatography on silica gel eluted with DCM-MeOH 2% followed by prep. HPLC-MS-UV to give pure title compound, (4.7 mg), (M+H)+616.2.
Reaction SMILES: C([N-]C(C)C)(C)C.[Li+].[F:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[N:11]=1.Cl[C:18]([O:20][CH3:21])=[O:19].O>O1CCCC1>[F:9][C:10]1[C:15]([C:18]([O:20][CH3:21])=[O:19])=[CH:14][CH:13]=[C:12]([F:16])[N:11]=1
Reactant: Fc1cccc(F)n1
Reactant: COC(=O)Cl
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: COC(=O)c1ccc(F)nc1F
Reaction time: 3 h
Yield: 43.2 %

Procedure:
To a stirred solution of 91 ml (0.182 mol) of 2.0 molar lithium diisopropylamide (in hexanes) in 200 mL dry tetrahydrofuran cooled to -70° under nitrogen was added dropwise a solution of 20.0 g of 2,6-difluoropyridine (0.174 mol) in 75 mL dry tetrahydrofuran such that the temperature was maintained below -60°. The solution was stirred at -70° fo 3 hours and was then added via a cannula to a solution 21.7 g (0.230 mol) of methyl chloroformate in 100 mL dry tetrahydrofuran cooled to -70° under nitrogen. After stirring another hour at -70°, the mixture was poured into water and extracted with ether. The combined organic layers were washed with brine, dried over magnesium sulfate, and evaporated to a semisolid which was purified by flash chromatography to afford 13.0 g (43%) orange oil: NMR (CDCl3, 200 MHz) 3.95 (3H, s), 6.9 (1H, m), 8.5 (1H, m); IR (neat) 1745, 1730, 1610, 1415, 1290 cm-1.
Reaction SMILES: [N-:1]=[N+]=[N-].[Na+].O.S(=O)(=O)(O)O.[F:11][C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[C:18](=[O:22])[CH2:17][CH2:16][CH2:15]2>C(Cl)(Cl)Cl>[F:11][C:12]1[CH:21]=[CH:20][C:19]2[NH:1][C:18](=[O:22])[CH2:17][CH2:16][CH2:15][C:14]=2[CH:13]=1
Reactant: O=C1CCCc2cc(F)ccc21
Reactant: [N-]=[N+]=[N-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Solvent: ClC(Cl)Cl
Product: O=C1CCCc2cc(F)ccc2N1
Temperature: 0 °C
Reaction time: 2 h
Yield: 11.6 %

Procedure:
Sodium azide 1.1 g (16.92 mmol) was added to a mixture of 6.0 mL of chloroform and 1.1 mL of water at 0° C. Concentrated sulfuric acid (0.44 mL) was added dropwise and the mixture stirred at 0° C. for two hours then filtered. The chloroform layer containing hydrazoic acid was added to a solution of 1.3 g (7.92 mmol) of 6-fluoro-1-tetralone (prepared by the method of Allinger and Jones, J. Org. Chem., 27, 70-76 (1962)) in 4.8 mL of chloroform. Additional sulfuric acid (2.16 mL) was added dropwise with stirring while maintaining the temperature below 40° C. The mixture was stirred at 40° C. for two hours then at room temperature for 16 hours. The mixture was transferred to a separatory funnel and the layers were separated. The aqueous layer was added to ice; the resulting precipitate was extracted with methylene chloride (5×). The combined extracts were washed with brine, dried over magnesium sulfate and filtered through a silica plug. Solvents were removed under vacuum to afford 162 mg (0.92 mmol,11%) of the product. 1H NMR (300 MHz, CDCl3): 2.21 (m,2H), 2.32 (t,7 Hz,2H), 2.77 (t,7 Hz,2H), 6.93 (m,3H), 7.8 (br s,1H). FAB-MS: calculated for C10H10FNO 179; found 180 (M+H,100%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:9][C:10]2([C:23]([O:25][CH3:26])=[O:24])[CH2:15][CH2:14][N:13](CC3C=CC=CC=3)[CH2:12][CH2:11]2)[CH:6]=[CH:7][CH:8]=1.[H][H]>[Pd].C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:9][C:10]2([C:23]([O:25][CH3:26])=[O:24])[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[CH:6]=[CH:7][CH:8]=1
Reactant: COC(=O)C1(Nc2cccc(OC)c2)CCN(Cc2ccccc2)CC1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: COC(=O)C1(Nc2cccc(OC)c2)CCNCC1

Procedure:
A mixture of 60 parts of methyl 4-[N-(3-methoxyphenyl)amino]-1-(phenylmethyl)-4-piperidinecarboxylate and 400 parts of ethanol is hydrogenated at normal pressure and at room temperature with 10 parts of palladium-on-charcoal catalyst 10%. After the calculated amount of hydrogen is taken up, the catalyst is filtered off and the filtrate is evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and 10% of methanol, previously saturated with gaseous ammonia, as eluent. The pure fractions are collected and the eluent is evaporated, yielding methyl 4-[N-(3-methoxyphenyl)amino]-4-piperidinecarboxylate as an oily residue.
Reaction SMILES: [CH2:1]([C:3]1[C:4]([C:12]2[O:13][CH:14]=[CH:15][CH:16]=2)=[N:5][C:6]([NH2:11])=[N:7][C:8]=1[S:9][CH3:10])[CH3:2].C1(C2[O:25]N2S(C2C=CC=CC=2)(=O)=O)C=CC=CC=1>ClCCl>[CH2:1]([C:3]1[C:4]([C:12]2[O:13][CH:14]=[CH:15][CH:16]=2)=[N:5][C:6]([NH2:11])=[N:7][C:8]=1[S:9]([CH3:10])=[O:25])[CH3:2]
Reactant: O=S(=O)(c1ccccc1)N1OC1c1ccccc1
Reactant: CCc1c(SC)nc(N)nc1-c1ccco1
Solvent: ClCCl
Product: CCc1c(-c2ccco2)nc(N)nc1S(C)=O
Reaction time: 16 h
Yield: 45.4 %

Procedure:
To a stirred suspension of 350 mg (1.49 mmol) 5-ethyl-4-furan-2-yl-6-methylsulfanyl-pyrimidin-2-ylamine in 15 ml dichloromethane was added 780 mg (3.00 mmol) 3-phenyl-2-(phenylsulfonyl)oxaziridine and stirring continued for 16 hours at room temperature. The reaction mixture was then partitioned between dichloromethane and water and the phases separated. The organic phase was dried over sodium sulfate and concentrated in vacuo. Chromatography (ethyl acetate then methanol/ethyl acetate 1/5) afforded 170 mg (46%) 5-ethyl-4-furan-2-yl-6-methanesulfinyl-pyrimidin-2-ylamine as a yellow crystalline solid. ES-MS m/e (%): 252 (M+H+, 100).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([NH:14][C:15](=[O:27])[O:16][CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([Br:25])=[CH:21][C:20]=2[CH3:26])[CH:6]=[CH:7][C:8]=1[S:9]([CH2:12][CH3:13])(=[O:11])=[O:10])#[N:2].Br[C:29]1C=C(C)C(CCO)=C(C)C=1.C(C1C=C(NC(=O)OC2C=CC=CC=2)C=CC=1S(CC)(=O)=O)#N>>[C:1]([C:3]1[CH:4]=[C:5]([NH:14][C:15](=[O:27])[O:16][CH2:17][CH2:18][C:19]2[C:24]([CH3:29])=[CH:23][C:22]([Br:25])=[CH:21][C:20]=2[CH3:26])[CH:6]=[CH:7][C:8]=1[S:9]([CH2:12][CH3:13])(=[O:10])=[O:11])#[N:2]
Reactant: Cc1cc(Br)cc(C)c1CCO
Reactant: CCS(=O)(=O)c1ccc(NC(=O)OCCc2ccc(Br)cc2C)cc1C#N
Agent: CCS(=O)(=O)c1ccc(NC(=O)Oc2ccccc2)cc1C#N
Product: CCS(=O)(=O)c1ccc(NC(=O)OCCc2c(C)cc(Br)cc2C)cc1C#N
Yield: 59 %

Procedure:
Using a procedure analogous to that used to prepare 31A, 32B (400 mg, 1.75 mmol) was reacted with 25A (579 mg, 1.75 mmol) to give 32C (480 mg, 59%) as a white solid. MS (ESI) m/z 465.1/467.1 (M+H)+.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([N+:9]([O-:11])=[O:10])[CH:4]=1.[CH2:12]([S-:15])[CH2:13][CH3:14].[Na+].O>CN(C=O)C>[N+:9]([C:5]1[CH:4]=[C:3]([CH:8]=[CH:7][CH:6]=1)[CH2:2][S:15][CH2:12][CH2:13][CH3:14])([O-:11])=[O:10]
Reactant: CCC[S-]
Reactant: O=[N+]([O-])c1cccc(CCl)c1
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCSCc1cccc([N+](=O)[O-])c1
Temperature: 60 °C
Reaction time: 8 h
Yield: 91.2 %

Procedure:
A solution of 1-(chloromethyl)-3-nitrobenzene (10.0 g, 58.1 mmol) in DMF (30 mL) was stirred at room temperature, then sodium propane-1-thiolate (5.7 g, 58.1 mmol) was added, followed by stirring at 60° C. overnight. After water was added, the aqueous layer was extracted with ethyl acetate 3 times. The combined organic phase was washed with brine, dried over sodium sulfate and concentrated to give (3-nitrobenzyl)(propyl)sulfane (11.2 g, yield 91%).
Reaction SMILES: Br[C@H:2]1[CH2:6][O:5][C@@H:4]([CH2:7][S:8]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)(=[O:10])=[O:9])[CH2:3]1.[C:18]([O-:21])(=[S:20])[CH3:19].[K+]>C(#N)C>[F:17][C:14]1[CH:15]=[CH:16][C:11]([S:8]([CH2:7][C@@H:4]2[O:5][CH2:6][C@@H:2]([S:20][C:18](=[O:21])[CH3:19])[CH2:3]2)(=[O:10])=[O:9])=[CH:12][CH:13]=1
Reactant: CC([O-])=S
Reactant: O=S(=O)(C[C@H]1C[C@@H](Br)CO1)c1ccc(F)cc1
Agent: [K+]
Solvent: CC#N
Product: CC(=O)S[C@@H]1CO[C@@H](CS(=O)(=O)c2ccc(F)cc2)C1
Yield: 55.8 %

Procedure:
The title compound is prepared by the procedure of Example 5 using 0.969 g of product from Example 30, 0.360 g of potassium thioacetate, and 9 ml of acetonitrile to give 0.533 g of the desired product.
Reaction SMILES: C([O:8][C:9]1[CH:10]=[C:11]([C@@H:15]([NH:24][C:25]([C@@H:27]2[CH2:32][CH2:31][CH2:30][N:29]([C:33](=[O:49])[CH2:34][CH2:35][CH:36]3[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH2:37]3)[CH2:28]2)=[O:26])[CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH:12]=[N:13][CH:14]=1)C1C=CC=CC=1>C(OCC)(=O)C.CO.[Pd]>[C:20]([O:19][C:17](=[O:18])[CH2:16][C@H:15]([NH:24][C:25]([C@@H:27]1[CH2:32][CH2:31][CH2:30][N:29]([C:33](=[O:49])[CH2:34][CH2:35][CH:36]2[CH2:37][CH2:38][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:40][CH2:41]2)[CH2:28]1)=[O:26])[C:11]1[CH:12]=[N:13][CH:14]=[C:9]([OH:8])[CH:10]=1)([CH3:21])([CH3:23])[CH3:22]
Reactant: CC(C)(C)OC(=O)C[C@H](NC(=O)[C@@H]1CCCN(C(=O)CCC2CCN(C(=O)OC(C)(C)C)CC2)C1)c1cncc(OCc2ccccc2)c1
Agent: [Pd]
Solvent: CO
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)C[C@H](NC(=O)[C@@H]1CCCN(C(=O)CCC2CCN(C(=O)OC(C)(C)C)CC2)C1)c1cncc(O)c1
Yield: 93.5 %

Procedure:
Tert-butyl 4-{3-[(3R)-3-({(1S)-1-[5-(benzyloxy)pyridin-3-yl]-3-tert-butoxy-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (1.69 g, 2.49 mmol) in ethyl acetate (73 mL) and methanol (12 mL) was stirred for 20 hours at room temperature under a hydrogen atmosphere in the presence of palladium on charcoal (10%, 170 mg). The suspension was filtrated through celite, which were washed thoroughly with methanol. The solution was concentrated under reduced pressure and the residue was purified by chromatography on silica gel (methanol in ethyl acetate 0 to 15%) to yield 1.37 g of Tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-hydroxypyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH3:8].[C:9]1([NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>>[C:3]1([CH3:8])[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[N:15]([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: c1ccc(Nc2ccccc2)cc1
Reactant: Cc1ccccc1Br
Product: Cc1ccccc1N(c1ccccc1)c1ccccc1
Yield: 99.5 %

Procedure:
According to the general procedure A, 2-bromotoluene (188 mg, 1.10 mmol) reacted with diphenylamine (169 mg, 1.00 mmol) to give the title compound (258 mg, 99%) as a white solid at room temperature for 4 h. Reaction of 2-chlorotoluene (70 mg, 0.55 mmol) with diphenylamine (85 mg, 0.50 mmol) proceeded at 80° C. for 21 h to give the title compound (134 mg, 99%). 1H-NMR (400 MHz, CDCl3): δ 7.14-7.27 (m, 8H), 7.01-6.92 (m, 6H), 2.06 (s, 3H). 13C{1H}-NMR (100 MHz, CDCl3): δ 147.46, 145.37, 136.49, 131.67, 129.61, 128.99, 127.33, 125.95, 121.50, 121.33, 18.56. GC/MS(EI): m/z 259 (M+).