Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[CH:5]=[CH:4][C:3]([CH:6]=O)=[CH:2]1.[N+:8]([CH3:11])([O-:10])=[O:9].Cl>C(O)C.[OH-].[Na+]>[O:1]1[CH:5]=[CH:4][C:3]([CH:6]=[CH:11][N+:8]([O-:10])=[O:9])=[CH:2]1
Reactant: O=Cc1ccoc1
Reactant: C[N+](=O)[O-]
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=[N+]([O-])C=Cc1ccoc1
Yield: 64.4 %

Procedure:
To a solution of 10.035 g (104.43 mmol) of 3-furaldehyde and 6.37 g (104 mmol) of nitromethane in 200 ml of ethanol, 11.0 ml of 10 N aqueous sodium hydroxide was added dropwise under ice-cooling, after which the reaction mixture was added dropwise to about 15% aqueous hydrochloric acid; the resulting precipitate was collected by filtration, washed with water and dried to yield 2-(3-furyl)-1-nitroethylene as a brown powder (yield 9.320 g). This crude product, without purification, was used for the next reaction.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([CH3:10])=[N:7][C:6]=2[CH:11]=1.C(N(CC)CC)C.[C:19](Cl)(=[O:22])[CH:20]=[CH2:21]>O1CCCC1>[C:19]([NH:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([CH3:10])=[N:7][C:6]=2[CH:11]=1)(=[O:22])[CH:20]=[CH2:21]
Reactant: C=CC(=O)Cl
Reactant: Cc1nc2cc(N)ccc2o1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: C=CC(=O)Nc1ccc2oc(C)nc2c1
Temperature: 0 °C

Procedure:
About 150 parts of (2) are dissolved in about 1200 ml of warm tetrahydrofuran in a 3 liter three-necked flask equipped with a mechanical stirrer and dropping funnel. About 113 parts of triethylamine are added to the flask and then cooled to 0° C. using an ice bath. About 100 parts of acryloyl chloride are combined with about 300 ml of tetrahydrofuran in a dropping funnel and added dropwise to the flask while stirring under dry nitrogen. The mixture in the flask is allowed to return to room temperature while being stirred overnight and then filtered. The filter is stirred in about 1 liter of warm tetrahydrofuran for about thirty minutes and filtered again. Both filtrates are combined and about 10 ml of nitrobenzene are added to inhibit polymerization. Solvent is removed using a rotary evaporator and ethyl ether is added to solidify the product. The dark brown solid obtained after filtering is washed with methylene chloride, then ethyl ether to provide 5-acrylamido-2-methyl benzoxazole (3) as a tan solid after drying under vacuum.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([Si:8]([CH3:11])([CH3:10])[CH3:9])=[CH:4][CH:3]=1.C([Li])CCC.CCCCCC.CN([CH:26]=[O:27])C>C1COCC1>[CH3:9][Si:8]([CH3:11])([CH3:10])[C:5]1[CH:6]=[CH:7][C:2]([CH:26]=[O:27])=[CH:3][CH:4]=1
Reactant: CN(C)C=O
Reactant: C[Si](C)(C)c1ccc(Br)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: C[Si](C)(C)c1ccc(C=O)cc1
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 103.2 %

Procedure:
Bromo-4-(trimethylsilyl)benzene (1.15 g, 5 mmol) was dissolved in THF (30 ml) and cooled to −78° C. Under argon a 1.6 M solution of n-butyl lithium in hexane (3.13 ml, 5 mmol) was added dropwise keeping the temperature below −70° C. The clear colorless solution was stirred at −78° C. for 15 min and DMF (1.156 ml, 15 mmol) was added quickly. The reaction temperature increased to −68° C. The reaction was stirred for additional 15 min at −78° C., quenched with 1N aqueous hydrogen chloride solution and extracted twice with diethyl ether. The combined organic layers were washed twice with water and once with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and the solvent was evaporated to leave the product as a colorless oil (920 mg, 100%). The product was pure enough to be used directly in the next step. MS (ISP) 179.2 (M+H+). 1H NMR (CDCl3, 300 MHz): δ 10.02 (s, 1H) 7.84 (d, 2H), 7.69 (d, 2H), 0.31 (s, 9H).
Reaction SMILES: [Br:1][C:2]1[C:3]([O:15]C)=[C:4]2[C:9](=[C:10]([O:12]C)[CH:11]=1)[N:8]=[CH:7][CH:6]=[C:5]2[Cl:14].[N+]([O-])([O-])=O.[NH4+].[Ce]>C(#N)C.O>[Br:1][C:2]1[C:3](=[O:15])[C:4]2[C:5]([Cl:14])=[CH:6][CH:7]=[N:8][C:9]=2[C:10](=[O:12])[CH:11]=1
Reactant: COc1cc(Br)c(OC)c2c(Cl)ccnc12
Agent: O=[N+]([O-])[O-]
Agent: [Ce]
Agent: [NH4+]
Solvent: CC#N
Solvent: O
Product: O=C1C=C(Br)C(=O)c2c(Cl)ccnc21
Yield: 79.1 %

Procedure:
To a cooled (0° C.) solution of 6-bromo-4-chloro-5,8-dimethoxyquinoline (compound 9) (215 mg, 0.71 mmol) in acetonitrile (10 ml) was added a cooled solution of cerium ammonium nitrate (2 g, 3.67 mmol) in water (10 ml), with stirring. The solution was stirred at room temperature for 90 min, diluted with water (20 ml) and extracted with chloroform (3×60 ml). The chloroform layers were joined, dried over sodium sulphate and evaporated, yielding 153 mg (79%) of compound 10.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][CH:24]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][NH:15][CH2:16][CH:17]2[CH2:19][CH2:18]2)=[CH:9][C:8]=1[O:20][CH3:21].C(N(CC)CC)C.[CH3:32][O:33][C:34](=[O:37])[CH2:35]Br>C(#N)C>[CH3:32][O:33][C:34](=[O:37])[CH2:35][N:15]([CH2:14][CH2:13][C:10]1[CH:11]=[CH:12][C:7]([O:6][CH2:5][C:4]2[CH:22]=[CH:23][CH:24]=[C:2]([F:1])[CH:3]=2)=[C:8]([O:20][CH3:21])[CH:9]=1)[CH2:16][CH:17]1[CH2:19][CH2:18]1
Reactant: COC(=O)CBr
Reactant: COc1cc(CCNCC2CC2)ccc1OCc1cccc(F)c1
Solvent: CCN(CC)CC
Solvent: CC#N
Product: COC(=O)CN(CCc1ccc(OCc2cccc(F)c2)c(OC)c1)CC1CC1
Reaction time: 8 h
Yield: 97.2 %

Procedure:
0.271 g (0.82 mmol) of [2-[4-(3-fluoro-benzyloxy)-3-methoxy-phenyl]-ethyl]-(cyclopropylmethyl)amine, 0.140 ml (1 mmol) of triethylamine and 0.155 g (0.89 mmol) of bromo-acetic acid methyl ester were dissolved in 5 ml of acetonitrile and the reaction was carried out at 70° C. overnight. Solvent was removed under vacuum, water was added to the residue and the product was extracted with ethyl acetate. The crude product was purified by flash chromatography (hexane/ethyl acetate 100:0→80:20 gradient v:v) and 0.32 g (97% yield) of the title compound was isolated as a yellow oil.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.Br[CH2:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1.C([O-])([O-])=O.[K+].[K+]>CC#N>[CH:12]1([CH2:11][O:1][C:2]2[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=2)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1
Reactant: BrCC1CCCCC1
Reactant: O=Cc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: O=Cc1ccc(OCC2CCCCC2)cc1
Temperature: 100 °C
Yield: 82.5 %

Procedure:
A solution of 4-hydroxybenzaldehyde (0.244 g, 2.00 mmol) in CH3CN (4.0 mL) was treated with bromomethylcyclohexane (0.279 g, 2.00 mmol) and K2CO3 (0.332 g, 2.40 mmol). The reaction mixture was heated to 100° C. for 1 h in a Biotage Initiator microwave synthesizer. Additional bromomethylcyclohexane (0.279 g, 2.00 mmol) and K2CO3 (0.332 g, 2.40 mmol) were added and the reaction mixture was again heated to 100° C. for 1 h in a Biotage Initiator microwave synthesizer. Additional bromomethylcyclohexane (0.279 g, 2.00 mmol) and K2CO3 (0.332 g, 2.40 mmol) were added and the reaction mixture was again heated to 100° C. for 1 h in a Biotage Initiator microwave synthesizer. Following cooling, the reaction mixture was filtered and concentrated in vacuo. Purification via flash column chromatography (10% EtOAc/hexanes) gave the title compound as a white solid (0.360 g; 82%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.86 (s, 1 H) 7.85 (d, J=8.8 Hz, 2 H) 7.11 (d, J=8.8 Hz, 2 H) 3.89 (d, J=6.3 Hz, 2 H) 1.80 (d, J=12.6 Hz, 2 H) 1.61-1.79 (m, 4 H) 1.13-1.32 (m, 3 H) 1.07 (dd, J=12.6, 2.6 Hz, 1 H) 1.01 (dd, J=11.9, 2.5 Hz, 1 H). MS(ES+) m/e 219 [M+H]+.
Reaction SMILES: [S:1]1[CH2:5][CH2:4][N:3]=[C:2]1[C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][C:9]=2[NH2:15].[CH3:16][S:17]([C:20]1[CH:21]=[C:22]([S:26](Cl)(=[O:28])=[O:27])[CH:23]=[CH:24][CH:25]=1)(=[O:19])=[O:18]>N1C=CC=CC=1>[S:1]1[CH2:5][CH2:4][N:3]=[C:2]1[C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][C:9]=2[N:15]([S:26]([C:22]1[CH:23]=[CH:24][CH:25]=[C:20]([S:17]([CH3:16])(=[O:19])=[O:18])[CH:21]=1)(=[O:28])=[O:27])[S:26]([C:22]1[CH:23]=[CH:24][CH:25]=[C:20]([S:17]([CH3:16])(=[O:19])=[O:18])[CH:21]=1)(=[O:28])=[O:27]
Reactant: CS(=O)(=O)c1cccc(S(=O)(=O)Cl)c1
Reactant: Nc1cccc2cc(C3=NCCS3)[nH]c12
Solvent: c1ccncc1
Product: CS(=O)(=O)c1cccc(S(=O)(=O)N(c2cccc3cc(C4=NCCS4)[nH]c23)S(=O)(=O)c2cccc(S(C)(=O)=O)c2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 22.8 %

Procedure:
To a mixture of 2-(4,5-dihydro-1,3-thiazol-2-yl)-1H-indole-7-amine (100 mg) and pyridine (3 mL) was added 3-(methylsulfonyl)benzenesulfonyl chloride (140 mg) at 0° C., and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated, and the residue was subjected to silica gel column chromatography (ethyl acetate:hexane=1:1) to give the title compound (41 mg, yield 14%) as pale-yellow crystals. M+1=654.
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C@@H:21]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C@@H:20]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C@@H:19]([CH2:38][O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[O:18][C@H:10]1SC1C=CC=CC=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(S(F)(F)[F:53])CC)C.BrN1C(=O)CCC1=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:1]([O:8][C@@H:9]1[C@@H:21]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C@@H:20]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C@@H:19]([CH2:38][O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[O:18][C@@H:10]1[F:53])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCN(CC)S(F)(F)F
Reactant: c1ccc(COC[C@H]2O[C@@H](Sc3ccccc3)[C@H](OCc3ccccc3)[C@@H](OCc3ccccc3)[C@H]2OCc2ccccc2)cc1
Agent: O=C([O-])O
Agent: O=C1CCC(=O)N1Br
Agent: [Na+]
Solvent: ClCCl
Product: F[C@H]1O[C@H](COCc2ccccc2)[C@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Temperature: -15 °C
Reaction time: 0.03 h
Yield: 73.4 %

Procedure:
To a solution of 10 (10.0 g, 15.82 mmol, 1 eq) in dry CH2Cl2 (191 mL) under argon at −15° C. were added diethylaminosulfur trifluoride (3.14 mL, 23.73 mmol, 1.5 eq) and, after 2 min, N-bromosuccinimide (3.66 g, 20.57 mmol, 1.3 eq). After being stirred at −15° C. for 30 min the reaction was diluted with CH2Cl2 (420 mL) and poured into a cold saturated aqueous NaHCO3 solution (195 mL). The organic layer was dried over MgSO4 and concentrated. Purification by flash chromatography on silica gel (petroleum ether/EtOAc 94:6) afforded 11 as viscous syrup (6.3 g, 73%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:15][C:16]([CH2:18]Cl)=[CH2:17]>CC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:18][C:16]([Cl:15])=[CH2:17])=[CH:4][CH:3]=1
Reactant: Oc1ccc(Cl)cc1
Reactant: C=C(Cl)CCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: C=C(Cl)COc1ccc(Cl)cc1
Yield: 92.5 %

Procedure:
To a mixture of 4-chlorophenol (6.1 g, 47.4 mmol) and potassium carbonate (13.1 g, 94.7 mmol) in acetone (200 mL), 2,3-dichloropropene (6.6 mL, 71 mmol) was added. After heating to reflux the reaction mixture for 48 hours, the reaction mixture was cooled and filtered. The residue was washed with more acetone and the combined filtrates were concentrated in vacuo. The crude pale brown liquid (11.5 g) was purified by chromatography (silica gel, hexane/ethyl acetate, 85/15) to give 1-(4-chlorophenoxy)-2-chloro-2-propene (8.9 g, 98%) as a white liquid: Anal. Calc'd. for C9H8OCl2: C, 53.23, H, 3.97. Found: C, 53.09, H, 3.95.
Reaction SMILES: Cl.[CH2:2]([O:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[C:17]([NH2:19])[CH:16]=[CH:15][C:14]=2[Cl:20])=[CH:9][CH:8]=1)=[O:6])[CH3:3].C(N(CC)CC)C.[CH:28]1([C:34](Cl)=[O:35])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1>C1COCC1>[CH2:2]([O:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[C:17]([NH:19][C:34]([CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)=[O:35])[CH:16]=[CH:15][C:14]=2[Cl:20])=[CH:9][CH:8]=1)=[O:6])[CH3:3]
Reactant: O=C(Cl)C1CCCCC1
Reactant: CCOC(=O)c1ccc(-c2cc(N)ccc2Cl)cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CCOC(=O)c1ccc(-c2cc(NC(=O)C3CCCCC3)ccc2Cl)cc1
Reaction time: 18 h

Procedure:
A mixture of 5′-amino-2′-chloro-biphenyl-4-carboxylic acid ethyl ester hydrochloride (521 mg), triethylamine (0.49 ml) and cyclohexanecarbonyl chloride (0.26 ml) in dry THF (25 ml) was stirred at 20 C for 18 h. The mixture was then evaporated and the residue partitioned between water and dichloromethane. The organic layer was washed with water, dried (MgSO4), filtered and evaporated under reduced pressure to give the product (714 mg) as a yellow oil.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][C:10]([N:13]([CH3:20])[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:21][CH2:22][OH:23].[C:24]1([CH3:34])[CH:29]=[CH:28][C:27]([S:30](Cl)(=[O:32])=[O:31])=[CH:26][CH:25]=1.C(N(CC)CC)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][C:10]([N:13]([CH3:20])[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)=[N:4][C:3]=1[CH2:21][CH2:22][O:23][S:30]([C:27]1[CH:28]=[CH:29][C:24]([CH3:34])=[CH:25][CH:26]=1)(=[O:32])=[O:31]
Reactant: Cc1oc(-c2ccc(N(C)c3ccccc3)cc2)nc1CCO
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1ccc(S(=O)(=O)OCCc2nc(-c3ccc(N(C)c4ccccc4)cc3)oc2C)cc1
Temperature: 25 °C
Reaction time: 14 h
Yield: 86.5 %

Procedure:
A solution of 2-{5-methyl-2-[4-(methyl-phenyl-amino)-phenyl]-oxazol-4-yl}-ethanol (91 mg, 0.30 mmol) in CH2Cl2 (4.0 mL) was treated with para-toluenesulfonyl chloride (68 mg, 0.36 mmol), triethyl amine (0.20 mL) and a few crystals of DMAP. The resulting mixture was stirred at room temperature for 14 h and was quenched with water (0.2 mL). The mixture was purified directly by silica gel column chromatography (40% EtOAc/hexanes) to yield the title compound (120 mg, 83%). MS (ESI) m/z 463.1 (M+H)+.
Reaction SMILES: [CH3:1][CH:2]([S-:4])[CH3:3].[Na+].[NH2:6][C:7]1[CH:14]=[C:13](F)[C:10]([C:11]#[N:12])=[CH:9][N:8]=1>C1COCC1>[NH2:6][C:7]1[CH:14]=[C:13]([S:4][CH:2]([CH3:3])[CH3:1])[C:10]([C:11]#[N:12])=[CH:9][N:8]=1
Reactant: N#Cc1cnc(N)cc1F
Reactant: CC(C)[S-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)Sc1cc(N)ncc1C#N
Temperature: 25 °C
Reaction time: 16 h

Procedure:
Sodium propane-2-thiolate (1.59 g, 15.68 mmol) was added to 6-amino-4-fluoronicotinonitrile (intermediate 21, 2.15 g, 15.68 mmol), in THF (75 ml) and the mixture stirred for 16 h at room temperature. Additional sodium propane-2-thiolate (1.59 g, 15.68 mmol) was added and the reaction stirred at room temperature for a further 4 days, then partitioned between saturated aqueous NaHCO3 solution and EtOAc, the combined organic layers washed with brine, dried over MgSO4 and evaporated. The residue was purified by normal phase chromatography: 80 g RediSep® column, eluting with a gradient from heptane to EtOAc. Product containing fractions were combined, evaporated and recrystallised from EtOAc to give the title compound as a white solid. (UPLC-MS 3) tR 0.78; ESI-MS 194.0 [M+H]+.
Reaction SMILES: O[C:2]1([CH3:29])[CH:26]=[C:25]2[C@:20]([CH3:27])([CH2:21][CH2:22][CH2:23][CH2:24]2)[C@@H:19]2[C@@H:3]1[C@H:4]1[C@:16]([CH3:28])([CH2:17][CH2:18]2)[C@@H:7]([C@H:8]([CH3:15])[CH2:9][CH2:10][C:11]([O:13][CH3:14])=[O:12])[CH2:6][CH2:5]1.CC(C)[O-:32].[Al+3].CC(C)[O-].CC(C)[O-].CC(=O)CC.N#N>C1(C)C=CC=CC=1>[CH3:29][C:2]1[C@@H:3]2[C@@H:19]([C@:20]3([CH3:27])[C:25]([CH:26]=1)=[CH:24][C:23](=[O:32])[CH2:22][CH2:21]3)[CH2:18][CH2:17][C@@:16]1([CH3:28])[C@H:4]2[CH2:5][CH2:6][C@@H:7]1[C@H:8]([CH3:15])[CH2:9][CH2:10][C:11]([O:13][CH3:14])=[O:12]
Reactant: CC(C)[O-]
Reactant: COC(=O)CC[C@@H](C)[C@H]1CC[C@H]2[C@H]3[C@H](CC[C@]12C)[C@@]1(C)CCCCC1=CC3(C)O
Agent: N#N
Agent: [Al+3]
Solvent: CCC(C)=O
Solvent: Cc1ccccc1
Product: COC(=O)CC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3C(C)=CC4=CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C
Yield: 89.2 %

Procedure:
A mixture of methyl 7-hydroxy-7-methylchol-5-en-24-oate (8) (2.0 g, 4.78 mmoles), aluminum isopropoxide (1.17 g, 5.72 mmoles), 2-butanone (8.6 ml, 96 mmoles) in toluene (40 ml) was heated at 80° in a N2 atmosphere for 6 hrs. About 15 ml of solvent was distilled from the reaction mixture at atmospheric pressure. Toluene (30 ml) was added, and the mixture was extracted with 3N HCl (2 times), H2O (3 times) and dried with MgSO4. Evaporation in vacuo gave 1.7 g of an orange oil that was purified by flash chromatography on silica gel with hexane-EtOAc (7:2 and 2:1 ) to give 0.62 g of pure 9 as a colorless syrup. NMR (CDCl3): δ0.76 (s, 3H, 18-Me); 0.94 (d, 3H, 20-Me); 1.08 (s, 3H, 19-Me); 3.67 (s, 3H, CO2Me); 5.59 (s, 1H, 4H); 5.95 (s, 1H, 6-H).
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][NH:14][C:13](=[O:17])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[I-].[H-].[Na+].Br[CH2:22][C:23]1[CH:32]=[C:31]2[C:26]([C:27]([Cl:33])=[CH:28][CH:29]=[N:30]2)=[CH:25][CH:24]=1>C1COCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([CH2:22][C:23]2[CH:32]=[C:31]3[C:26]([C:27]([Cl:33])=[CH:28][CH:29]=[N:30]3)=[CH:25][CH:24]=2)[C:13](=[O:17])[CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1CN(C(=O)OCc2ccccc2)CCN1
Reactant: Clc1ccnc2cc(CBr)ccc12
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=C1CN(C(=O)OCc2ccccc2)CCN1Cc1ccc2c(Cl)ccnc2c1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 63 %

Procedure:
4-(Benzyloxycarbonyl)-piperazin-2-one (1.1 g, 4.6 mmol) is dissolved in THF (50 mL), cooled in an ice bath and treated with tretrabutylammonium iodide (0.18 g, mmol) and 60% sodium hydride (0.24 g, 6.0 mmol). The reaction mixture is stirred at 0° C. for 30 minutes then treated dropwise with a solution of 7-bromomethyl-4-chloroquinoline (1.2 g, 4.6 mmol), Example 14, in THF (50 mL). The resulting solution is stirred at 0° C. for 2 h then quenched with ammonium chloride solution and concentrated. Dilution with ethyl acetate is followed by a water wash; the organic layer is dried (sodium sulfate) and concentrated. The residue is chromatographed (4% methanol/methylene chloride) to yield solid 4-(benzyloxycarbonyl)-1-(4-chloroquinolin-7-ylmethyl)-piperazin-2-one (1.2 g, 2.9 mmol). A portion of this material (0.75 g, 1.8 mmol) is dissolved in acetonitrile (20 mL) and treated with iodo trimethylsilane (0.78 mL, 5.4 mmol) at room temperature for 3 hours. The reaction is quenched with methanol and concentrated to dryness. Methanol addition and concentration is repeated four times. The final residue is taken up is 2M aqueous HCl; the solution is washed with ether and concentrated. The residue is recrystallized from isopropanol and ether to yield the title compound (0.63 g, 2.3 mmol) MS m/z: M+=275; 1HNMR (CD3OD, 300 MHz) δ9.1 (d, 1H), 8.5 (d, 1H), 8.2-8.3 (m, 2H), 8.0 (d, 1H), 5.2 (s, 2H), 4.1 (s, 2H), 3.7-3.8 (m, 2H), 3.6-3.7 (m, 2H).
Reaction SMILES: Br[Zn][CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[C:9]1(/[CH:15]=[CH:16]/[C:17]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:18])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.Cl.C(OCC)(=O)C>C1COCC1>[OH:18][C:17]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)(/[CH:16]=[CH:15]/[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5]
Reactant: O=C(/C=C/c1ccccc1)c1ccccc1
Reactant: CCOC(=O)C[Zn]Br
Agent: Cl
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCOC(=O)CC(O)(/C=C/c1ccccc1)c1ccccc1
Yield: 97 %

Procedure:
Under nitrogen atmosphere, 15 mL of THF was added to 3.05 g (5 mmol, 1.0 equivalent) of (BrZnCH2COOEt.THF)2. Under argon atmosphere, a solution of 1.04 g (5 mmol) of (E)-chalcone in 2.5 mL of THF was added dropwise while stirring at 0˜5° C. The mixture was stirred at 0˜5° C. for 3 hours. 7.5 mL of 1N hydrochloric acid was added dropwise at 20° C. or lower, followed by dilution with 25 mL of ethyl acetate. Then, the layers were separated. The organic layer was washed successively with 5 mL (×2) of 1N hydrochloric acid, 5 mL of an aqueous saturated sodium chloride solution, 10 mL (×2) of an aqueous saturated sodium bicarbonate solution, and 5 mL (×2) of an aqueous saturated sodium chloride solution. After washing, the organic layer was dried with anhydrous magnesium sulfate. Concentration under reduced pressure afforded 1.44 g of the desired product (yield 97%). 1H NMR (CDCl3), (ppm): δ 1.17 (3H, t, J=7.1 Hz), 3.04 (2H, dd, J=22.8, 15.7 Hz), 4.11 (2H, q, J=7.1 Hz), 4.81 (1H, s), 6.42 (1H, d, J=16.0 Hz), 6.66 (1H, d J=16.0 Hz), 7.25-7.53 (10H, m).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:29])[CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][CH:14]([C:17]3[CH:18]=[C:19]([NH:23][C:24](=[O:28])[CH:25]([CH3:27])[CH3:26])[CH:20]=[CH:21][CH:22]=3)[CH2:13][CH2:12]2)=[CH:4][CH:3]=1.[C:30]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1O)(=[O:32])[CH3:31]>>[C:30]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[O:29][CH:8]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)[CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][CH:14]([C:17]2[CH:18]=[C:19]([NH:23][C:24](=[O:28])[CH:25]([CH3:26])[CH3:27])[CH:20]=[CH:21][CH:22]=2)[CH2:13][CH2:12]1)(=[O:32])[CH3:31]
Reactant: CC(=O)c1ccccc1O
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CCC(O)c3ccc(F)cc3)CC2)c1
Product: CC(=O)c1ccccc1OC(CCN1CCC(c2cccc(NC(=O)C(C)C)c2)CC1)c1ccc(F)cc1

Procedure:
Prepared by Procedure A and Scheme AN using N-(3-{1-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-piperidinyl}phenyl)-2-methylpropanamide and 2-acetylphenol: ESMS m/e: 517.1 (M+H)+.
Reaction SMILES: [CH2:1]([NH:5][C:6]1[CH:22]=[CH:21][CH:20]=[CH:19][C:7]=1[CH2:8][S:9][C:10]1[NH:11][C:12]2[C:13]([N:18]=1)=[N:14][CH:15]=[CH:16][CH:17]=2)[CH:2]([CH3:4])[CH3:3].ClC1C=CC=C(C(OO)=[O:31])C=1.C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl>[CH2:1]([NH:5][C:6]1[CH:22]=[CH:21][CH:20]=[CH:19][C:7]=1[CH2:8][S:9]([C:10]1[NH:11][C:12]2[C:13]([N:18]=1)=[N:14][CH:15]=[CH:16][CH:17]=2)=[O:31])[CH:2]([CH3:4])[CH3:3]
Reactant: CC(C)CNc1ccccc1CSc1nc2ncccc2[nH]1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: CC(C)CNc1ccccc1CS(=O)c1nc2ncccc2[nH]1
Temperature: 0 °C

Procedure:
In 20 ml of chloroform was dissolved 900 mg of 2-[2-(isobutylamino)benzylthio]imidazo[4,5-b]pyridine. To the resulting solution was portionwise added under chilling with ice 618 mg of m-chloroperbenzoic acid (purity: 80%) over a period of 30 min. To the mixture was added a saturated NaHCO3 solution, and the resulting mixture was then stirred. The organic phase was separated and extracted successively with 20 ml of 0.1N NaOH and 10 ml of 0.1N NaOH. The alkaline extracts were combined and neutralized by NH4Cl, and the deposited oil was extracted with chloroform. The chloroform extract was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and placed under reduced pressure to distill off the solvent. The residue was crystallized by addition of diethyl ether. The crystalline product was washed with diethyl ether to give 195 mg of 2-[2-(isobutylamino)benzylsulfinyl]imidazo[4,5-b]pyridine as a pale yellow crystalline powder. m.p.: 116° C. (decompn.)