Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[C:3]([Cl:15])=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=1.CC1(C)C(C)(C)OB([C:24]2[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=2)O1.ClCCl.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1COCC1.CCOC(C)=O.O>[Cl:15][C:3]1[C:2]([C:24]2[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=2)=[C:7]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)[CH:6]=[CH:5][N:4]=1
Reactant: CC1(C)OB(c2ccncc2)OC1(C)C
Reactant: Clc1ccc(-c2ccnc(Cl)c2Br)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Solvent: ClCCl
Product: Clc1ccc(-c2ccnc(Cl)c2-c2ccncc2)cc1
Temperature: 100 °C
Yield: 62.9 %

Procedure:
In a pressure tube, to a stirring solution of 3-bromo-2-chloro-4-(4-chlorophenyl)pyridine (1.3 g, 4.49 mmol) in THF (60 mL) at room temperature under argon was added 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (2.3 g, 11.21 mmol), 1,1′-bis(diphenylphosphino)ferrocene palladium (II) chloride complex with dichloromethane (350 mg, 0.43 mmol), and powdered K3PO4 (1.9 g, 8.96 mmol). The resulting suspension was stirred and heated at 100° C. under argon for 12 h. After the reaction mixture was cooled to room temperature, water (40 mL) and EtOAc (50 mL) were added. The layers were separated. The organic layer was dried (MgSO4), filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography (silica gel column eluting with 20% ethyl acetate-hexanes) to isolate 850 mg of the title compound as a white solid. HPLC/MS: retention time=2.157 min, [M+H]+=301.
Reaction SMILES: [CH3:1][Mg]Br.[CH3:4][C:5]([C:8]1[O:9][C:10]2[C:11](=[CH:15][C:16]3[CH2:17][CH2:18][CH2:19][N:20]4[C:25]=3[C:24]=2[CH2:23][CH2:22][CH2:21]4)[C:12](=O)[CH:13]=1)([CH3:7])[CH3:6].[F:26][B-:27]([F:30])([F:29])[F:28].[H+]>CCOCC.O1CCCC1.O>[F:26][B-:27]([F:30])([F:29])[F:28].[CH3:4][C:5]([CH:8]1[CH:13]=[C:12]([CH3:1])[C:11]2=[CH:15][C:16]3[CH2:17][CH2:18][CH2:19][N:20]4[C:25]=3[C:24]([CH3+:23][CH2:22][CH2:21]4)=[C:10]2[O:9]1)([CH3:7])[CH3:6]
Reactant: CC(C)(C)c1cc(=O)c2cc3c4c(c2o1)CCCN4CCC3
Reactant: C[Mg]Br
Agent: F[B-](F)(F)F
Agent: [H+]
Solvent: O
Solvent: C1CCOC1
Solvent: CCOCC
Product: CC1=CC(C(C)(C)C)Oc2c1cc1c3c2[CH3+]CCN3CCC1
Temperature: 0 °C
Reaction time: 17 h
Yield: 44 %

Procedure:
Methyl magnesium bromide (5.0 mL of a 3.0M solution in ether, 15 mmol) was added dropwise at 0° C. to a solution of 11-[1,1-dimethylethyl]-9-oxo-2,3,6,7-tetrahydro-1H,5H-[1]benzopyrano[6,7,8-ij]quinolizine (2.68 g, 9.03 mmol, prepared in Example 34 above) in dry tetrahydrofuran (10 mL) and the solution was allowed to stand at room temperature for about 17 hours. The reaction mixture was then cooled again to 0° C. and more methyl magnesium bromide (1 mL of a 3M solution in ether, 3 mmol) was added dropwise. The reaction mixture was allowed to attain room temperature and stirred for a further 8 hours, after which time the reaction mixture was poured into tetrafluoroboric acid (44 mL of a 4.4% solution in water) and the resultant mixture was extracted with dichloromethane. The organic phase was separated and dried over sodium sulfate. Removal of solvent, followed by trituration of the residue with ethyl acetate and filtration, gave 11-[1,1-dimethylethyl]-9-methyl-2,3,6,7-tetrahydro-1H,5H-[1]benzopyrano[6,7,8-ij]quinolizinium tetrafluoroborate (1.49 g, 44% yield) as a red solid which melted at 168°-170° C. The structure of this compound was confirmed by mass spectroscopy and by 1H and 13C NMR spectroscopy.
Reaction SMILES: C[O-].[Na+].[I-:4].[Na+].CC(C)(C([O-])=O)C([O-])=O.[Na+].[Na+].[C:17]1([CH2:23][CH2:24][CH2:25][CH2:26]Cl)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>COCCOC.CC(C)=O>[C:17]1([CH2:23][CH2:24][CH2:25][CH2:26][I:4])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: ClCCCCc1ccccc1
Reactant: [I-]
Agent: CC(C)(C(=O)[O-])C(=O)[O-]
Agent: C[O-]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: COCCOC
Product: ICCCCc1ccccc1
Temperature: 70 °C
Reaction time: 0.25 h
Yield: 59.3 %

Procedure:
R=Me Dimethyl malonate (5.7 mL, 50.0 mmol) was added in one portion to a solution of sodium methoxide (6.6 g, 50.0 mmol) in DME (45 mL) at rt and stirred for 15 min. In a separate reaction vessel, 4(4'-chlorophenyl)-a-bromoacetophenone (14.0 g, 45.0 mmol) was dissolved in DME (136 mL) along with sodium iodide (6.7 g, 45.0 mmol). The NaI solution was allowed to stir for 15 min at rt. The sodium dimethylmalonate solution was transferred via cannula dropwise into the 4(4'-chlorophenyl)-a-bromoacetophenone solution; stirring continued 1 hr at rt. The solvent was removed in vacuo and the resulting oil dissolved in 1:1 methylene chloride:diethyl ether (700 mL). The organic phase was washed with water (250 mL), and saturated sodium chloride solution (250 mL). The organic layer was dried (MgSO4), filtered, and concentrated in vacuo. The resulting oil was recrystallized using 4:1 chloroform:methanol with hexane to precipitate the methyl 2-carbomethoxy-4[4'-(4"-chloro phenyl)phenyl]-4-oxobutanoate (10.43 g, 64%). 1H NMR (DMSO) d 8.06 (d, J=8.1 Hz, 2H), 7.66 (d, J=8.5 Hz, 2H), 7.56 (d, J=8.5 Hz, 2H), 7.45 (d, J=8.1 Hz, 2H), 3.95 (t, J=7.0 Hz, 1H), 3.70 (s, J=7.0 Hz, 6H), 3.66 (s, 2H). ##STR178## Step 2 (A)--Preparation of 4-phenyl-1-iodobutane. Sodium iodide (8.9 g, 59.2 mol) and 4-phenyl-1-chlorobutane (5.0 g, 29.6 mol) were added to acetone (29.6 mL) at rt. The mixture was heated to 70° C. for 12 h. The resulting solution was gravity filtered to remove salts. The solvent was removed under reduced pressure and excess salts were dissolved in water (100 mL). Hexane (100 mL) was added to the aqueous mixture. The phases were separated and the organic phase was washed with saturated sodium bisulfite solution (3×50 mL), treated with decolorizing carbon, and gravity filtered. The organic layer was then dried (MgSO4), filtered, and concentrated in vacuo to afford 4-phenyl-1-iodobutane (6.94 g, 90%).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[N:11]([CH2:32][CH:33]([CH3:35])[CH3:34])[C:12](=[O:31])[C:13]2[C:18]([C:19]=1[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[F:26])=[CH:17][C:16]([C:27]([O:29]C)=[O:28])=[CH:15][CH:14]=2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].O.Cl>O1CCCC1.CO>[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[N:11]([CH2:32][CH:33]([CH3:35])[CH3:34])[C:12](=[O:31])[C:13]2[C:18]([C:19]=1[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[F:26])=[CH:17][C:16]([C:27]([OH:29])=[O:28])=[CH:15][CH:14]=2)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: COC(=O)c1ccc2c(=O)n(CC(C)C)c(CNC(=O)OC(C)(C)C)c(-c3ccccc3F)c2c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: CC(C)Cn1c(CNC(=O)OC(C)(C)C)c(-c2ccccc2F)c2cc(C(=O)O)ccc2c1=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 94.4 %

Procedure:
To a solution of methyl 3-[[(tert-butoxycarbonyl)amino]methyl]-4-(2-fluorophenyl)-2-isobutyl-1-oxo-1,2-dihydro-6-isoquinolinecarboxylate (1.93 g, 4 mmol) in tetrahydrofuran (10 mL) and methanol (10 mL) was added 1N sodium hydroxide (8 mL). The obtained mixture was stirred at room temperature for 1 h. The reaction mixture was poured into water, acidified with 1N hydrochloric acid and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained crystals were recrystallized from ethyl acetate-isopropyl ether to give 3-[[(tert-butoxycarbonyl)amino]methyl]-4-(2-fluorophenyl)-2-isobutyl-1-oxo-1,2-dihydro-6-isoquinolinecarboxylic acid (1.77 g, 94.7%) as crystals.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[S:16][N:15]=[CH:14][N:13]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH:17]1[CH2:21][CH2:20][C@@H:19]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:18]1.C1(C2C=CC=CC=2)C=CC=CC=1P(C(C)(C)C)C(C)(C)C.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[C:25]([O:24][C:23](=[O:29])[NH:22][C@@H:19]1[CH2:20][CH2:21][N:17]([C:2]2[CH:7]=[CH:6][C:5]([S:8](=[O:10])(=[O:9])[NH:11][C:12]3[S:16][N:15]=[CH:14][N:13]=3)=[CH:4][CH:3]=2)[CH2:18]1)([CH3:28])([CH3:26])[CH3:27]
Reactant: CC(C)(C)OC(=O)N[C@@H]1CCNC1
Reactant: O=S(=O)(Nc1ncns1)c1ccc(Br)cc1
Agent: [Pd]
Agent: CC(C)(C)P(c1ccccc1-c1ccccc1)C(C)(C)C
Agent: CC(C)(C)[O-]
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N[C@@H]1CCN(c2ccc(S(=O)(=O)Nc3ncns3)cc2)C1
Yield: 20.9 %

Procedure:
Prepared using general procedure 74. The reaction was set up with 4-bromo-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (750 mg, 2.34 mmol), (R)-tert-butyl pyrrolidin-3-ylcarbamate (436 mg, 2.34 mmol), Pd2(dba)3 (64 mg, 0.07 mmol), biphenyl-2-yldi-tert-butylphosphine (84 mg, 0.28 mmol), sodium tert-butoxide (630 mg, 6.6 mmol), and toluene (6.0 mL). Purification via silica gel chromatography using 10% MeOH in CH2Cl2 gave the desired pyrrolidine as an orange solid (213 mg, 0.49 mmol, 21% yield). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=326.3; tR=1.39 min:
Reaction SMILES: [NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:3]1=[O:14].[CH:15](=O)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[O-]S([O-])(=O)=O.[Mg+2]>C(Cl)Cl>[CH:15](=[N:1][C@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:3]1=[O:14])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: O=Cc1ccccc1
Reactant: CCOC(=O)CN1CCC[C@H](N)C1=O
Agent: O=S(=O)([O-])[O-]
Agent: [Mg+2]
Solvent: ClCCl
Product: CCOC(=O)CN1CCC[C@H](N=Cc2ccccc2)C1=O
Reaction time: 21 h
Yield: 89 %

Procedure:
To a solution of 22 (4.7586 g, 0.0200 mol) and benzaldehyde (2.1224 g, 0.0200 mol, 2.03 mL) in 50 mL CH2Cl2 at 0° under N2 was added anhydrous MgSO4 (5.0 g) and Et33N (4.05 g, 0.040 mol, 5.58 mL). The mixture was stirred from 0° to ambient temperature over 21 hrs, filtered under N2, and the solvent was evaporated. The residue was dissolved in 300 mL of diethyl ether, extracted with 50 mL portions of water (3×), brine, dried over MgSO4, filtered under N2 and evaporated to afford 5.13 g (89% yield) of product 23 as a light yellow viscous oil. The material was hydrolytically labile and was stored at 0° under a N2 atmosphere.
Reaction SMILES: Cl[CH2:2][C:3]1[N:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]2=[N:5][C:4]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[N+:18]([O-])=O.[CH2:21]([N:23](CC)[CH2:24]C)C.CNC.C1COCC1>C(Cl)Cl>[CH3:21][N:23]([CH2:2][C:3]1[N:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]2=[N:5][C:4]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[NH2:18])[CH3:24]
Reactant: O=[N+]([O-])c1ccccc1-c1nc2ccccn2c1CCl
Reactant: CCN(CC)CC
Agent: CNC
Solvent: ClCCl
Solvent: C1CCOC1
Product: CN(C)Cc1c(-c2ccccc2N)nc2ccccn12
Temperature: 0 °C
Reaction time: 8 h
Yield: 61.6 %

Procedure:
To 3-Chloromethyl-2-(2-nitro-phenyl)-imidazo[1,2-a]pyridine (324 mg, 1.0 mmol) suspended in CH2Cl2 (20 ml) cooled to 0° C. was added dropwise triethylamine (303 mg, 3 eq), followed by 2 M dimethylamine in THF (8 mmol, 4 ml) in two portions over a 5 hour period. The reaction mixture was concentrated to dryness, dissolved in CH2Cl2 (20 ml) washed with water, brine, dried over Na2SO4, concentrated and purified by chromatography using a 9:1 mixture of CH2Cl2 /MeOH. The fractions were concentrated, dissolved in THF (15 ml), and stirred over H2 balloon with 10% Pd/C (10 mg) overnight. The reaction mixture was filtered through Celite and concentrated to obtain the product as a yellow solid (164 mg). (MS, M++H=267.1)
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.C1(C)C=CC=CC=1.[Cl:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[NH:25][CH:24]=[CH:23]2>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.O>[Cl:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[N:25]([S:7]([C:4]1[CH:5]=[CH:6][C:1]([CH3:11])=[CH:2][CH:3]=1)(=[O:9])=[O:8])[CH:24]=[CH:23]2
Reactant: Clc1ccc2[nH]ccc2c1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=S(=O)([O-])O
Solvent: Cc1ccccc1
Solvent: O
Product: Cc1ccc(S(=O)(=O)n2ccc3cc(Cl)ccc32)cc1
Temperature: 25 °C
Reaction time: 11 h
Yield: 103.7 %

Procedure:
p-Toluenesulfonyl chloride (2 g) and tetrabutyl ammonium hydrogen sulfate (250 mg) were added to a toluene (20 ml) solution containing 5-chloroindole (1.52 g), followed by stirring at room temperature for 11 hours. Water was added to the reaction solution, followed by extraction with ethyl acetate. The resultant was washed with water (×3) and saturated saline and dried over anhydrous sodium sulfate. Subsequently, the solvent was distilled away under reduced pressure, the obtained residue was purified by silica gel chromatography (n-hexane:ethyl acetate=0:1 to 1:1), and a colorless solid of 5-chloro-1-tosyl-1H-indole (3.18 g) was thus obtained.
Reaction SMILES: [N:1]1([C:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[S:9][N:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[Cl:16][CH2:17][CH:18]=[CH:19][CH2:20]Cl.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>C1(C)C=CC=CC=1>[Cl:16][CH2:17][CH:18]=[CH:19][CH2:20][N:4]1[CH2:5][CH2:6][N:1]([C:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[S:9][N:8]=2)[CH2:2][CH2:3]1
Reactant: c1ccc2c(N3CCNCC3)nsc2c1
Reactant: ClCC=CCCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: ClCC=CCN1CCN(c2nsc3ccccc23)CC1
Reaction time: 2 h

Procedure:
A mixture of 3-(1-piperazinyl)-1,2-benzisothiazole (1 g; 4.56 mmol), 1,4-dichloro-2-butene (2.9 g; 22.8 mmol), anhydrous potassium carbonate (0.79 g; 5.7 mmol) and dry dimethylformamide (10 ml) was stirred at a bath temperature of 90° to 100° C. for 2 hours. After completion of the reaction, toluene (100 ml) was added to the mixture, which was washed three times with water (50 ml). The toluene layer was washed with a saturated sodium chloride solution and dried over magnesium sulfate. The crude oil thus obtained was purified by silica gel chromatography to give the objective compound. IR νmaxNujol (cm-1): 1590, 1560, 1490, 1450, 1420.
Reaction SMILES: [Br:1][C:2]1[C:9]([OH:10])=[C:8]([O:11][CH3:12])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[C:13]([O-])([O-])=O.[K+].[K+].COS(OC)(=O)=O>CN(C=O)C>[Br:1][C:2]1[C:9]([O:10][CH3:13])=[C:8]([O:11][CH3:12])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5]
Reactant: O=C([O-])[O-]
Reactant: COc1ccc(C=O)c(Br)c1O
Agent: [K+]
Solvent: COS(=O)(=O)OC
Solvent: CN(C)C=O
Product: COc1ccc(C=O)c(Br)c1OC
Temperature: -10 °C
Reaction time: 8 h
Yield: 91 %

Procedure:
A stirred suspension of 2-bromo-3-hydroxy-4-methoxybenzaldehyde (commercially available, 24 g, 104 mmol) and K2CO3 (29.4 g, 213 mmol) in DMF (125 ml) was cooled to −10° C. Dimethylsulfate (9.6 ml, 102 mmol) was added, the reaction was warmed to room temperature and stirred overnight. The resulting solution was quenched with water (375 ml) and the resulting suspension stirred overnight. The resulting suspension was filtered and the solid dried in vacuo at 50° C. to give 23.1 g of the subtitle product (91%).
Reaction SMILES: [OH:1][C:2]1[CH:19]=[CH:18][C:17]2[C@@H:16]3[C@H:7]([C@H:8]4[C@@:12]([CH2:14][CH2:15]3)([CH3:13])[C:11](=[O:20])[CH2:10][CH2:9]4)[CH2:6][CH2:5][C:4]=2[C:3]=1[CH3:21].[C:22]12(O)[CH2:31][CH:26]3[CH2:27][CH:28]([CH2:30][CH:24]([CH2:25]3)[CH2:23]1)[CH2:29]2.B(F)(F)F.CCOCC>CCCCC>[C:22]12([C:19]3[C:2]([OH:1])=[C:3]([CH3:21])[C:4]4[CH2:5][CH2:6][C@@H:7]5[C@@H:16]([C:17]=4[CH:18]=3)[CH2:15][CH2:14][C@@:12]3([CH3:13])[C@H:8]5[CH2:9][CH2:10][C:11]3=[O:20])[CH2:31][CH:26]3[CH2:27][CH:28]([CH2:30][CH:24]([CH2:25]3)[CH2:23]1)[CH2:29]2
Reactant: OC12CC3CC(CC(C3)C1)C2
Reactant: Cc1c(O)ccc2c1CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Agent: FB(F)F
Solvent: CCOCC
Solvent: CCCCC
Product: Cc1c(O)c(C23CC4CC(CC(C4)C2)C3)cc2c1CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Yield: 65.2 %

Procedure:
To a suspension of the known 3-hydroxy-4-methylestra-1,3,5(10)-trien-17-one (ref. Kaneko et al., 1964; Chemical Abstracts Registry Number [68969-90-4], 30 mg, 0.11 mmol) and 30 mg (0.197 mmol) of 1-adamantanol in 1 mL of anhydrous pentane was added 0.02 mL of boron trifluoride diethyl etherate while cooling with an ice bath and stirring. After stirring at 0° C. for 15 min. the reaction was stirred at room temperature for 45 min. Ice was added and the white solid that formed was filtered, washed with water and dried over P2O5. The crude product was purified by chromatography (silica gel eluted with 7% ethyl acetate in hexanes) to give 30 mg of pure product (68% yield). After recrystallization from methylene chloride-hexanes the product had: m.p. 262-263° C.; 1H NMR(CDCl3) δ0.90 (s, 3H, CH3), 2.13 (s, 3H, CH3), 2.7 (m, 2H, CH2), 7.11 (s, 1H, Ar—H); 13C NMR (CDCl3) δ11.02, 13.70, 21.44, 26.22, 26.67, 27.54, 28.95 (3∴C), 31.56, 35.84, 36.60, 36.98 (3×C), 37.63, 40.82 (3×C), 44.60, 47.91, 50.34, 121.41, 121.51, 131.45, 133.32, 150.79, 221.49. (Anal. calc'd. for C29H39O2: C, 83.21; H, 9.15. Found: C, 83.45; H, 8.94.)
Reaction SMILES: [CH2:1]([N:3]([CH2:12][CH3:13])[C:4](=O)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[CH3:2].C(Cl)(=O)C(Cl)=O.[Li][AlH][SeH:22]>C(OCC)C>[CH2:1]([N:3]([CH2:12][CH3:13])[C:4](=[Se:22])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[CH3:2]
Reactant: CCN(CC)C(=O)c1ccccc1
Reactant: [Li][AlH][SeH]
Agent: O=C(Cl)C(=O)Cl
Solvent: CCOCC
Product: CCN(CC)C(=[Se])c1ccccc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 66.6 %

Procedure:
To a solution of N,N-diethylbenzamide (0.18 g, 1.0 mmol) in dry diethylether (5 mL), oxalyl chloride (1.0 mmol, 0.09 mL) was added. The mixture was stirred at 0° C. for one hour under an argon atmosphere. Moreover, the reaction mixture was stirred for three hours at room temperature. The mixture was added to the solution of LiAlHSeH (1.2 mmol), prepared as described above in Example One. The reaction mixture was stirred at room temperature for three hours. The mixture was extracted with diethyl ether and washed with water. The organic layer was dried over sodium sulfate and evaporated to dryness. The residue was purified by flash chromatography on silica gel with dichloromethane to give 0.16 grams (68%) of N,N-diethylbenzselenoamide as a yellow crystal; mp 53–54° C.; C11H15NSe; 1H NMR (CDCl3) δ 1.15 (3H, t, J=6.8 Hz, CH3), 1.45 (3H, t, J=6.8 Hz, CH3), 3.43 (2H, q, J=6.8 Hz, CH2), 4.25 (2H, q, J=6.8 Hz, CH2), 7.21 (2H, d, J=7.6 Hz, Ar), 7.28 (1H, d, J=6.8 Hz, Ar), 7.33 (2H, t, J=7.2 Hz, Ar); 13C NMR (CDCl3) δ 11.2, 13.2, 48.3, 49.7, 123.7, 127.8, 128.0, 146.5, 204.0; 77Se NMR (CDCl3) δ 705.3; MS (CI): m/z=242 [M++1]; HRMS: m/z=241.0369 calcd for C11H15NSe, found 241.0368.
Reaction SMILES: [C:1]([O:5][C:6](=[O:28])[NH:7][C:8]1[CH:13]=[C:12]([C:14]2[O:15][C:16]([CH2:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=3)=[N:17][N:18]=2)[CH:11]=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[C:31]1([CH2:37][CH2:38][CH2:39]Br)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.[I-].[K+]>CN(C)C=O.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:28])[N:7]([C:8]1[CH:13]=[C:12]([C:14]2[O:15][C:16]([CH2:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=3)=[N:17][N:18]=2)[CH:11]=[CH:10][N:9]=1)[CH2:39][CH2:38][CH2:37][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: BrCCCc1ccccc1
Reactant: CC(C)(C)OC(=O)Nc1cc(-c2nnc(CCc3cccc(F)c3)o2)ccn1
Agent: [H-]
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N(CCCc1ccccc1)c1cc(-c2nnc(CCc3cccc(F)c3)o2)ccn1
Reaction time: 0.17 h
Yield: 65.9 %

Procedure:
To a suspension of tert-butyl[4-[5-[2-(3-fluorophenyl)ethyl]-1,3,4-oxadiazol-2-yl]-2-pyridyl]carbamate (270 mg, 0.70 mmol) in N,N-dimethylformamide (5 mL) was added sodium hydride (60% in oil, 34 mg, 0.84 mmol) at room temperature, and the resulting mixture was stirred for 10 min. To this reaction mixture were added 3-phenylpropyl bromide (167 mg, 0.84 mmol) and potassium iodide (10 mg), and the mixture was further stirred at room temperature for 5 hr. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=95/5-0/100) to give tert-butyl[4-[5-[2-(3-fluorophenyl)ethyl]-1,3,4-oxadiazol-2-yl]-2-pyridyl](3-phenylpropyl)carbamate (232 mg, yield 66%) as a colorless oil.
Reaction SMILES: C(OC(=O)[NH:7][CH:8]([CH2:30][C:31]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[NH:33][CH:32]=1)[C:9]([N:11]1[CH2:16][CH2:15][C:14]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)([C:17]([NH:19][N:20]([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1)=[O:10])(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:22][N:20]([CH3:21])[NH:19][C:17]([C:14]1([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:13][CH2:12][N:11]([C:9](=[O:10])[CH:8]([NH2:7])[CH2:30][C:31]2[C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[NH:33][CH:32]=2)[CH2:16][CH2:15]1)=[O:18]
Reactant: CN(C)NC(=O)C1(Cc2ccccc2)CCN(C(=O)C(Cc2c[nH]c3ccccc23)NC(=O)OC(C)(C)C)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CN(C)NC(=O)C1(Cc2ccccc2)CCN(C(=O)C(N)Cc2c[nH]c3ccccc23)CC1
Reaction time: 0.5 h
Yield: 192.8 %

Procedure:
To a solution of (2-(4-benzyl-4-(N′,N′-dimethylhydrazinocarbonyl)piperidine-1-yl)-1-(1H-indole-3-ylmethyl)-2-oxoethyl)carbamic acid tert-butyl ester (0.40 g, 0.73 mmol) in methylene chloride (3 ml) at 0° C. was added trifluoroacetic acid (3 ml) and the mixture was stirred for 30 min. The mixture was quenched with ethanol (20 ml), concentrated in vacuo and stripped three times with methylene chloride to give 0.63 g of 1-(2-amino-3-(1H-indol-3-yl)propionyl)-4-benzylpiperidine-4-carboxylic acid N′,N′-dimethylhydrazide as a colorless oil.
Reaction SMILES: C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[NH2:15][CH2:16][C:17]1[C:18]([F:34])=[C:19]([O:24][C:25]2[CH:26]=[C:27]([CH:30]=[C:31]([Cl:33])[CH:32]=2)[C:28]#[N:29])[C:20]([Br:23])=[CH:21][CH:22]=1.[N:35]([C:38]1[NH:39][C:40]([C:44](O)=[O:45])=[C:41]([Cl:43])[N:42]=1)=[N+:36]=[N-:37]>CN(C=O)C.CCOC(C)=O>[N:35]([C:38]1[NH:39][C:40]([C:44]([NH:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Br:23])=[C:19]([O:24][C:25]3[CH:26]=[C:27]([C:28]#[N:29])[CH:30]=[C:31]([Cl:33])[CH:32]=3)[C:18]=2[F:34])=[O:45])=[C:41]([Cl:43])[N:42]=1)=[N+:36]=[N-:37]
Reactant: [N-]=[N+]=Nc1nc(Cl)c(C(=O)O)[nH]1
Reactant: N#Cc1cc(Cl)cc(Oc2c(Br)ccc(CN)c2F)c1
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: ClCCCl
Solvent: CCOC(C)=O
Product: N#Cc1cc(Cl)cc(Oc2c(Br)ccc(CNC(=O)c3[nH]c(N=[N+]=[N-])nc3Cl)c2F)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 103.2 %

Procedure:
EDC (0.331 g, 1.726 mmol) and HOBT (0.233 g, 1.726 mmol) were added to a solution of 3-{[3-(aminomethyl)-6-bromo-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.558 g, 1.569 mmol) and 2-azido-4-chloro-1H-imidazole-5-carboxylic acid (0.294 g, 1.569 mmol) in DMF (7 mL). The mixture was stirred at RT overnight. The reaction mixture was diluted with EtOAc and washed with water and brine and the organic layer was dried over sodium sulfate and concentrated to give the crude title compound (0.850 g) as a light yellow solid. This crude product was taken on to the next step without further purification.
Reaction SMILES: [C:1]1([C:7]2[C:15]3[C:10](=[N:11][CH:12]=[C:13]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=4[O:22]C)[CH:14]=3)[NH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.B(Br)(Br)Br.CO>C(Cl)Cl>[C:1]1([C:7]2[C:15]3[C:10](=[N:11][CH:12]=[C:13]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=4[OH:22])[CH:14]=3)[NH:9][CH:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: COc1ccccc1-c1cnc2[nH]cc(-c3ccccc3)c2c1
Agent: BrB(Br)Br
Solvent: CO
Solvent: ClCCl
Product: Oc1ccccc1-c1cnc2[nH]cc(-c3ccccc3)c2c1
Yield: 34 %

Procedure:
To a solution of 3-phenyl-5-(2-methoxyphenyl)-1H-pyrrolo[2,3-b]pyridine (113 mg, 0.38 mmol) in CH2Cl2 (325 μl) is added BBr3 (1.1 ml of 1 N solution in CH2Cl2, 1.13 mmol). The reaction mixture is stirred for 15 hours at room temperature and neutralized at 0° C. with methanol. The solvent is evaporated under reduced pressure and the residue purified by preparative thin-layer chromatography (CH2Cl2/MeOH 94:6) to yield the expected product in the form of a white solid with a yield of 34%.