Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[N:6][CH:7]=1.C1([O:20][C:21]([O:23][CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])=O)C=CC=CC=1>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:9][CH2:10][N:11]([C:21]([O:23][CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])=[O:20])[CH2:12][CH2:13]2)=[N:6][CH:7]=1
Reactant: CCOC(=O)COC(=O)Oc1ccccc1
Reactant: Brc1ccc(N2CCNCC2)nc1
Product: CCOC(=O)COC(=O)N1CCN(c2ccc(Br)cn2)CC1

Procedure:
The process is performed as described in Example 1 (step 1.2.). Starting with 6 g (24.80 mmol) of 1-(5-bromo-2-pyridyl)piperazine, obtained in step 3.2., and 10.88 g (48.52 mmol) of ethyl [(phenyloxycarbonyl)oxy]acetate, prepared in step 1.1. of Example 1, and after chromatography on silica gel, eluting with a 15/85 and then 30/70 mixture of ethyl acetate and cyclohexane, 6.70 g of product are obtained in the form of an oil that crystallizes to a white solid.
Reaction SMILES: Br[C:2]1[C:3]([N:24]2[CH2:28][CH2:27][C@@H:26]([OH:29])[CH2:25]2)=[N:4][CH:5]=[C:6]([CH:23]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:22])([F:21])[C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[N:30]1[CH:35]=[C:34](B(O)O)[CH:33]=[N:32][CH:31]=1>>[OH:29][C@@H:26]1[CH2:27][CH2:28][N:24]([C:3]2[C:2]([C:34]3[CH:35]=[N:30][CH:31]=[N:32][CH:33]=3)=[CH:23][C:6]([C:7]([NH:9][C:10]3[CH:11]=[CH:12][C:13]([C:16]([F:21])([F:22])[C:17]([F:18])([F:19])[F:20])=[CH:14][CH:15]=3)=[O:8])=[CH:5][N:4]=2)[CH2:25]1
Reactant: O=C(Nc1ccc(C(F)(F)C(F)(F)F)cc1)c1cnc(N2CC[C@@H](O)C2)c(Br)c1
Reactant: OB(O)c1cncnc1
Product: O=C(Nc1ccc(C(F)(F)C(F)(F)F)cc1)c1cnc(N2CC[C@@H](O)C2)c(-c2cncnc2)c1

Procedure:
The title compound was prepared in an analogous fashion to that described in Example 185 using (R)-5-bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(perfluoroethyl)phenyl)nicotinamide (Stage 208.1) and pyrimidin-5-ylboronic acid to afford a foam. HPLC (Condition 4) tR=5.11 min, UPLC-MS (Condition 3) tR=1.00 min, m/z=480.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.68-1.79 (m, 1H) 1.85 (m, J=9.00 Hz, 1H) 2.88 (d, J=11.73 Hz, 1H) 3.14-3.27 (m, 2H) 3.38 (m, J=7.00 Hz, 1H) 4.20 (m, J=2.30 Hz, 1H) 4.87 (d, J=3.52 Hz, 1H) 7.66 (d, J=8.60 Hz, 2H) 7.99 (d, J=8.60 Hz, 2H) 8.10 (d, J=2.35 Hz, 1H) 8.80 (d, J=1.96 Hz, 1H) 8.88 (s, 2H) 9.18 (s, 1H) 10.31 (s, 1H).
Reaction SMILES: [NH2:1][C:2]1[NH:7][C:6](=[O:8])[CH:5]=[C:4]([C:9]([F:12])([F:11])[F:10])[N:3]=1.C(N(CC)CC)C.[C:20]1([CH3:30])[CH:25]=[CH:24][C:23]([S:26](Cl)(=[O:28])=[O:27])=[CH:22][CH:21]=1>C(Cl)Cl>[CH3:30][C:20]1[CH:25]=[CH:24][C:23]([S:26]([O:8][C:6]2[CH:5]=[C:4]([C:9]([F:12])([F:10])[F:11])[N:3]=[C:2]([NH2:1])[N:7]=2)(=[O:28])=[O:27])=[CH:22][CH:21]=1
Reactant: Nc1nc(C(F)(F)F)cc(=O)[nH]1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)Oc2cc(C(F)(F)F)nc(N)n2)cc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of 2-amino-6-(trifluoromethyl)-4(3H)-pyrimidinone (250 mg, 1.4 mmol), triethylamine (196 μL, 1.4 mmol), N,N-dimethylaminopyridine (17 mg, 0.14 mmol), in CH2Cl2 (13 mL) cooled to 0° C. was added p-toluenesulfonyl chloride (534 mg, 2.8 mmol). The mixture was stirred at room temperature for 16 h. The mixture was diluted with CH2Cl2, washed with H2O (2×20 mL) followed by brine, dried (Na2SO4), evaporated, and dried under vacuum. Desired compound (466 mg, 1.4 mmol; 99+% yield; ES MS [M+H]+=140.
Reaction SMILES: [CH2:1]1[O:9][C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2]1.[I:10]Cl.O>CC(O)=O>[CH2:1]1[O:9][C:4]2[CH:5]=[CH:6][C:7]([I:10])=[CH:8][C:3]=2[O:2]1
Reactant: ClI
Reactant: c1ccc2c(c1)OCO2
Solvent: CC(=O)O
Solvent: O
Product: Ic1ccc2c(c1)OCO2
Reaction time: 3 h
Yield: 56.7 %

Procedure:
To a solution of 1,2-methylenedioxybenzene (24.4 g, 0.20M) in AcOH (30 ml) was added ICl (40 g, 0.250M) in AcOH (50 ml) at room temperature over 0.5 hour. The reaction mixture was stirred for an additional three hours, then poured into H2O and extracted twice with ether. The organic extracts were washed with NaHSO3, saturated NaHCO3, H2O, dried (MgSO4), and evaporated in vacuo. The product was distilled under vacuum at 70° C. to give 3,4-methylenedioxyiodobenzene as a pale orange liquid (28.1 g, 57% yield). NMR (CDCl3) δ 5.85 (s, 2H, O--CH2 --O), 6.50 (d, 1H, J=8 Hz, H6), 7.10 (m, 2H, J=8 Hz, J=2 Hz, H2 and H5); MS: 248 (M+).
Reaction SMILES: [OH:1][CH2:2][CH2:3][C:4]1[CH:5]=[C:6]([OH:10])[CH:7]=[CH:8][CH:9]=1.Br[CH2:12][C:13]1[CH:22]=[CH:21][CH:20]=[CH:19][C:14]=1[C:15]([O:17][CH3:18])=[O:16].C(=O)([O-])[O-].[K+].[K+].C(O)C(N)(CO)CO>C(#N)C>[OH:1][CH2:2][CH2:3][C:4]1[CH:5]=[C:6]([CH:7]=[CH:8][CH:9]=1)[O:10][CH2:12][C:13]1[CH:22]=[CH:21][CH:20]=[CH:19][C:14]=1[C:15]([O:17][CH3:18])=[O:16]
Reactant: OCCc1cccc(O)c1
Reactant: COC(=O)c1ccccc1CBr
Agent: NC(CO)(CO)CO
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COC(=O)c1ccccc1COc1cccc(CCO)c1
Reaction time: 8 h
Yield: 96 %

Procedure:
3-(2-Hydroxyethyl)phenol (1.0 g, 7.24 mmol) and methyl 2-(bromomethyl)benzoate (1.74 g, 7.6 mmol) were dissolved in acetonitrile (10 ml). Potassium carbonate anhydrous (2.0 g, 14.48 mmol) was added. After stirring at 60° C. for three hours PS-trisamine was added (0.3 eq) and was stirred overnight. The PS-trisamine was filtered off and the acetonitrile was removed by evaporation. EtOAc (10 ml) was added and the organic layer was washed with 3 portions of water (3×10 ml). The organic phase was dried (MgSO4) and the solvent was removed by evaporation to give 1.99 g of methyl 2-{[3-(2-hydroxyethyl)phenoxy]methyl}benzoate (yield 90%).
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:19]=[CH:18][C:7]([C:8](=[N:16][OH:17])[C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)=[CH:6][CH:5]=1.Cl[CH2:21][C:22]([NH2:24])=[O:23].O>CN(C)C=O>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([C:8](=[N:16][O:17][CH2:21][C:22]([NH2:24])=[O:23])[C:9]2[CH:10]=[CH:11][C:12]([Cl:15])=[CH:13][CH:14]=2)=[CH:18][CH:19]=1
Reactant: NC(=O)CCl
Reactant: ON=C(c1ccc(Cl)cc1)c1ccc(Cl)cc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: NC(=O)CON=C(c1ccc(Cl)cc1)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 35.4 %

Procedure:
Sodium hydride (0.5 g., 50% w/w suspension in mineral oil) was added gradually to a stirred solution of 4,4'-dichlorobenzophenone oxime (2.6 g.) in dry dimethylformamide (20 ml.) keeping the temperature below 30° C. After 30 minutes, chloroacetamide (0.9 g.) was added to the stirred solution keeping the temperature below 30° C. After 16 hours stirring at ambient temperature the mixture was poured into water (100 ml.) and the subsequent mixture extracted with ether. The combined extract was washed with water, dried (MgSO4) and evaporated. The residue (2.5 g.) was added to a column of dry chromatographic silica-gel [300 g., previously deactivated by addition of 10% w/w water and then equilibrated with 10% v/w of a mixture of toluene and acetone (10:1 v/w)]. The column was then eluted with the same mixture of toluene and acetone to give, after evaporation of solvent, a solid residue (1.5 g.). The solid was recrystallised from ethyl acetate/petrol giving di-(4-chlorophenyl)methyleneamino-oxyacetamide m.p. 141°-142° C. (1.1 g.) in 34% overall yield.
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([CH:10]2[CH2:15][CH2:14][CH2:13][O:12][CH2:11]2)[C:5]([C:16]#[N:17])=[C:4]([SH:18])[N:3]=1.Cl[CH2:20][C:21]1[N:22]=[C:23]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=2)[S:24][CH:25]=1.C(=O)(O)[O-].[Na+]>CN(C=O)C>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([CH:10]2[CH2:15][CH2:14][CH2:13][O:12][CH2:11]2)[C:5]([C:16]#[N:17])=[C:4]([S:18][CH2:20][C:21]2[N:22]=[C:23]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=3)[S:24][CH:25]=2)[N:3]=1
Reactant: N#Cc1c(N)nc(S)c(C#N)c1C1CCCOC1
Reactant: ClCc1csc(-c2ccc(Cl)cc2)n1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Product: N#Cc1c(N)nc(SCc2csc(-c3ccc(Cl)cc3)n2)c(C#N)c1C1CCCOC1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
50 mg (0.13 mmol) of the compound from Example 32A, 39 mg (0.16 mmol) of 4-(chloromethyl)-2-(4-chlorophenyl)-1,3-thiazole and 45 mg (0.54 mmol) of sodium bicarbonate are initially charged in 3 ml of dry DMF. The reaction mixture is stirred at RT for 12 h and then directly purified by preparative HPLC (column: YMC GEL ODS-AQ S-5, 15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5).
Reaction SMILES: N1C2C(=CC=CC=2)C=C1.C([N:17]1[C:29]2[C:28]([OH:30])=[C:27]3[N:31](C(OC(C)(C)C)=O)[C:32]4[CH:33]=[CH:34][C:35]([Br:38])=[CH:36][C:37]=4[C:26]3=[CH:25][C:24]=2[C:23]2[C:18]1=[CH:19][CH:20]=[C:21]([Br:46])[CH:22]=2)(OC(C)(C)C)=O.O[CH2:48][CH2:49][N:50]1[CH2:55][CH2:54][O:53][CH2:52][CH2:51]1>>[Br:38][C:35]1[CH:36]=[C:37]2[C:32](=[CH:33][CH:34]=1)[NH:31][C:27]1[C:28]([O:30][CH2:48][CH2:49][N:50]3[CH2:55][CH2:54][O:53][CH2:52][CH2:51]3)=[C:29]3[NH:17][C:18]4[CH:19]=[CH:20][C:21]([Br:46])=[CH:22][C:23]=4[C:24]3=[CH:25][C:26]2=1
Reactant: CC(C)(C)OC(=O)n1c2ccc(Br)cc2c2cc3c4cc(Br)ccc4n(C(=O)OC(C)(C)C)c3c(O)c21
Reactant: OCCN1CCOCC1
Agent: c1ccc2[nH]ccc2c1
Product: Brc1ccc2[nH]c3c(OCCN4CCOCC4)c4[nH]c5ccc(Br)cc5c4cc3c2c1

Procedure:
The title compound was prepared in a manner analogous to Example 28 except the starting indole is 5,7-diBOC-2,10-dibromo-6-hydroxyindolo[2,3-b]carbazole and the reagent is 4-(2-Hydroxyethyl)morpholine. 1H-NMR (400 MHz, CD3OD) δ ppm 8.44 (s, 1H), 8.25 (d, J=2.0 Hz, 2H), 7.42 (dd, J=8.4, 1.6 Hz, 2H), 7.41 (d, J=2.0 Hz, 2H), 4.42 (t, J=5.2 Hz, 2H), 3.81 (t, J=4.8 Hz, 4H), 2.87 (t, J=5.2 Hz, 2H), 2.70-2.60 (m, 4H); MS (ESI) m/z 542.1 (M−H)−
Reaction SMILES: ClC1C=C([C@@H](N2CC[C@H](OCOC)C2)CO)C=CC=1.[Cl:20][C:21]1[CH:22]=[C:23]([C@H:27](O)[CH2:28][N:29]2[CH2:33][CH2:32][C@H:31]([O:34][CH2:35][O:36][CH3:37])[CH2:30]2)[CH:24]=[CH:25][CH:26]=1.[CH3:39][NH:40][C:41]1[CH:50]=[CH:49][C:44]([C:45]([O:47][CH3:48])=[O:46])=[CH:43][CH:42]=1>>[Cl:20][C:21]1[CH:22]=[C:23]([C@H:27]([N:40]([C:41]2[CH:50]=[CH:49][C:44]([C:45]([O:47][CH3:48])=[O:46])=[CH:43][CH:42]=2)[CH3:39])[CH2:28][N:29]2[CH2:33][CH2:32][C@H:31]([O:34][CH2:35][O:36][CH3:37])[CH2:30]2)[CH:24]=[CH:25][CH:26]=1
Reactant: CNc1ccc(C(=O)OC)cc1
Reactant: COCO[C@H]1CCN(C[C@@H](O)c2cccc(Cl)c2)C1
Agent: COCO[C@H]1CCN([C@@H](CO)c2cccc(Cl)c2)C1
Product: COCO[C@H]1CCN(C[C@H](c2cccc(Cl)c2)N(C)c2ccc(C(=O)OC)cc2)C1
Yield: 66 %

Procedure:
This was prepared from the mixture of 2-(R)-(3-chlorophenyl)-2-(3-(S)-methoxymethoxypyrrolidin-1-yl)ethanol and 1-(S)-(3-chlorophenyl)-2-(3-(S)-methoxymethoxypyrrolidin-1-yl)ethanol and methyl 4-methylaminobenzoate in 66% yield according to a procedure similar to that described in Example 1 (i).
Reaction SMILES: CC1C=C(C)C=C(C)C=1S([O-])(=O)=O.[NH2:14][N+:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=1[NH2:22].[F:23][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][N:32]=1)[C:27](Cl)=O>>[Br:21][C:18]1[CH:19]=[CH:20][N:15]2[N:14]=[C:27]([C:26]3[CH:30]=[CH:31][N:32]=[C:24]([F:23])[CH:25]=3)[N:22]=[C:16]2[CH:17]=1
Reactant: Nc1cc(Br)cc[n+]1N
Reactant: O=C(Cl)c1ccnc(F)c1
Agent: Cc1cc(C)c(S(=O)(=O)[O-])c(C)c1
Product: Fc1cc(-c2nc3cc(Br)ccn3n2)ccn1
Yield: 77.6 %

Procedure:
The product was prepared in the same manner as described in example 1b using 1,2-diamino-4-bromopyridinium 2,4,6-trimethylbenzenesulfonate (2.2 g, 5.67 mmol) and 2-fluoroisonicotinoyl chloride (1.81 g, 11.3 mmol) as starting materials. The reaction affords 7-bromo-2-(2-fluoropyridin-4-yl)-[1,2,4]triazolo[1,5-a]pyridine (1.29 g, 77.7%) as white powder. MS: m/z=294.9 (M+H+).
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[C:6]([Cl:11])[C:3]=1[CH:4]=[O:5].C(=O)([O-])[O-].[K+].[K+].[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C)C=O>[Cl:1][C:2]1[CH:9]=[C:8]([O:10][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:7]=[C:6]([Cl:11])[C:3]=1[CH:4]=[O:5]
Reactant: O=Cc1c(Cl)cc(O)cc1Cl
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=Cc1c(Cl)cc(OCc2ccccc2)cc1Cl
Reaction time: 8 h

Procedure:
Treat a mixture of 2,6-dichloro-4-hydroxy-benzaldehyde (250 g, 1.3 mol) and potassium carbonate (361.8 g, 2.62 mol) in 2 L dimethylformamide with benzyl bromide (268.64 g, 1.57 mol). Stir the reaction at room temperature for 1 hour. Filter off solids and pour into 12 L of water. Filter off solid, wash several times with water, air dry and dissolve in ethyl acetate. Dry over magnesium sulfate, filter and concentrate under vacuum to ˜1.5 L. Allow to sit overnight then filter. Wash solid with minimal amount of hexane and vacuum dry. Concentrate the filtrate under vacuum and triturate with hexane to yield a second crop of product which when combined with the first crop equals 245 g white crystals. Repeat to obtain a third crop of 80 g as a light-tan powder (88% overall yield): 1H NMR (400 MHz, DMSO-d6) δ 10.26 (s, 1H), 7.43 (m, 5H), 7.28 (s, 2H), 5.25 (s, 2H).
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][C@@H:3]([NH:6][C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10])[CH2:2]1.Cl[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=1.C(N(C(C)C)C(C)C)C>CN(C=O)C>[CH3:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][N:1]2[CH2:5][CH2:4][C@@H:3]([NH:6][C:7](=[O:13])[O:8][C:9]([CH3:10])([CH3:12])[CH3:11])[CH2:2]2)=[CH:18][CH:17]=1
Reactant: CC(C)(C)OC(=O)N[C@@H]1CCNC1
Reactant: Cc1ccc(CCl)cc1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccc(CN2CC[C@@H](NC(=O)OC(C)(C)C)C2)cc1
Temperature: 25 °C
Yield: 75.2 %

Procedure:
To a mixture of tert-butyl (3R)-3-pyrrolidinylcarbamate (4.0 g) and 1-(chloromethyl)-4-methylbenzene (3.17 g) in DMF (40 mL) was added N-ethyl-N-isopropyl-2-propanamine (5.55 g) at ambient temperature and the resulting mixture was heated at 70 for four hours. The mixture was allowed to cool to ambient temperature and extracted with ethyl acetate (100 mL). The organic phase was washed with water (50 mL) and brine (50 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by a flash chromatography etluting with gradient solvent system (ethyl acetate-hexane from 1:4 v/v to 1:1 v/v) to give tert-butyl [(3R)-1-(4-methylbenzyl)-3-pyrrolidinyl]carbamate (4.69 g) as a pale yellow syrup.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[C:8]([Cl:10])[CH:7]=[CH:6][C:5]=1[NH:11][S:12]([C:15]([F:18])([F:17])[F:16])(=[O:14])=[O:13])(=O)[CH3:2].Cl.[F:20][C:21]([F:36])([F:35])[C:22]1[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][C:23]=1[CH2:24][O:25][NH2:26].CC([O-])=O.[Na+]>CCO>[F:20][C:21]([F:35])([F:36])[C:22]1[CH:30]=[C:29]([C:31]([F:34])([F:32])[F:33])[CH:28]=[CH:27][C:23]=1[CH2:24][O:25][N:26]=[C:1]([C:4]1[CH:9]=[C:8]([Cl:10])[CH:7]=[CH:6][C:5]=1[NH:11][S:12]([C:15]([F:18])([F:17])[F:16])(=[O:14])=[O:13])[CH3:2]
Reactant: CC(=O)c1cc(Cl)ccc1NS(=O)(=O)C(F)(F)F
Reactant: NOCc1ccc(C(F)(F)F)cc1C(F)(F)F
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: CC(=NOCc1ccc(C(F)(F)F)cc1C(F)(F)F)c1cc(Cl)ccc1NS(=O)(=O)C(F)(F)F
Yield: 88.4 %

Procedure:
A solution of N-(2-acetyl-4-chlorophenyl)trifluoromethanesulfonamide 19 (150 mg, 0.50 mmol), O-(2,4-bistrifluoromethylbenzyl)hydroxylamine hydrochloride (154 mg, 0.52 mmol) and anhydrous NaOAc (43 mg, 0.52 mmol) in EtOH (20 mL) was stirred for 15 h at RT. The reaction mixture was concentrated under vacuum and the residue filtered through a pad of silica (eluting with CH2Cl2/PE, 7:3). Purification by radial thin layer chromatography (eluting with CH2Cl2/PE, 7.5:92.5 to 1:9) afforded a pale yellow solid which was recrystallized from CH2Cl2/PE to give N-{2-[1-(2,4-bistrifluoromethylbenzyloxyimino)ethyl]-4-chlorophenyl}trifluoromethanesulfonamide 2 (240 mg, 89%), as a colorless oil. 1H n.m.r. (200 MHz, CDCl3) δ 10.96, br s, 1H; 7.96, s, 1H; 7.85, d, J=8.0 Hz, 1H; 7.72, d, J=8.0 Hz, 1H; 7.60, d, J=8.8 Hz, 1H; 7.49, d, J=2.2 Hz, 1H; 7.33, dd, J=2.2 and 8.8 Hz, 1H; 5.46, s, 2H; 2.39, s, 3H. HRMS (M+) 542.0102.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]2[CH2:15][CH2:14][C:13](=O)[CH2:12][CH2:11]2)=[CH:2]1.[NH:17]1[C:25]2[C:20](=[C:21]([N:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)[CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClCCCl>[NH:17]1[C:25]2[C:20](=[C:21]([N:26]3[CH2:31][CH2:30][N:29]([C@@H:13]4[CH2:14][CH2:15][C@H:10]([C:3]5[C:4]6[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=6)[NH:1][CH:2]=5)[CH2:11][CH2:12]4)[CH2:28][CH2:27]3)[CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18]1
Reactant: O=C1CCC(c2c[nH]c3ccccc23)CC1
Reactant: c1cc(N2CCNCC2)c2cc[nH]c2c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCCl
Product: c1cc(N2CCN([C@H]3CC[C@@H](c4c[nH]c5ccccc54)CC3)CC2)c2cc[nH]c2c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of 4-(1H-indol-3-yl)-cyclohexanone (0.53 g, 2.5 mmol), 1-(indol-4-yl)piperazine (0.5 g, 2.5 mmol), sodium triacetoxyborohydride (0.78 g, 3.5 mmol) and acetic acid (0.14 ml, 2.5 mmol) in 1,2-dichloroethane (11 ml) was allowed to stir at room temperature overnight. The reaction was quenched with 1N sodium hydroxide (10 ml), extracted with methylene chloride (3×60 ml), and washed with brine (3×60 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. Chromatography (10% methanol-ethyl acetate) afforded 0.52 g (53%) of product as a white solid: mp 85-87° C.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C@@H:7]([OH:9])[CH3:8])[CH:2]=1.[CH2:10]([O:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][C:28]([C:31](O)=[O:32])=[CH:27][CH:26]=2)=[CH:21][CH:20]=1)[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17].C1(N=C=NC2CCCCC2)CCCCC1.CN(C1C=CC=CN=1)C>C(Cl)Cl>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C@@H:7]([O:9][C:31]([C:28]2[CH:27]=[CH:26][C:25]([C:22]3[CH:23]=[CH:24][C:19]([O:18][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])=[CH:20][CH:21]=3)=[CH:30][CH:29]=2)=[O:32])[CH3:8])[CH:2]=1
Reactant: CCCCCCCCOc1ccc(-c2ccc(C(=O)O)cc2)cc1
Reactant: C[C@H](O)c1cccnc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccccn1
Solvent: ClCCl
Product: CCCCCCCCOc1ccc(-c2ccc(C(=O)O[C@@H](C)c3cccnc3)cc2)cc1
Reaction time: 15 h
Yield: 7.1 %

Procedure:
(S)-1-(3-pyridyl)ethanol (2.0 g) prepared in the above item (ii), 4-octyloxybiphenyl-4'-carboxylic acid (5.3 g), dicyclohexylcarbodiimide (5.7 g) and dimethylaminopyridine (0.2 g) were dissolved in methylene chloride (100 ml), followed by agitating the solution for 15 hours, thereafter filtering off insolubles, washing the filtrate with water, concentrating it and recrystallizing from a mixed solvent of heptane-toluene to obtain (S)-4-octyloxybiphenyl-4'-carboxylic acid-1-(3-pyridyl)ethyl ester (0.5 g). M.P.: 77.5-78.5° C. Specific angle of rotation [a]D25 =+95° (c=1.0, CHCl3). Further, the structure of this product was confirmed according to NMR spectra and the product accorded with the captioned compound.
Reaction SMILES: [CH2:1]([C:8]1[C:13]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:12][C:11]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:10][C:9]=1[OH:30])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:31]([O:38][C:39]1[CH:40]=[C:41]([CH:46]=[CH:47][C:48]=1[O:49][CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)/[CH:42]=[CH:43]/[CH2:44]O)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C(Cl)Cl>[CH2:23]([O:22][C:11]1[CH:12]=[C:13]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[C:9]([OH:30])[C:10]=1[CH2:44]/[CH:43]=[CH:42]/[C:41]1[CH:46]=[CH:47][C:48]([O:49][CH2:50][C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)=[C:39]([O:38][CH2:31][C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:40]=1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: OC/C=C/c1ccc(OCc2ccccc2)c(OCc2ccccc2)c1
Reactant: Oc1cc(OCc2ccccc2)cc(OCc2ccccc2)c1Cc1ccccc1
Solvent: ClCCl
Product: Oc1c(C/C=C/c2ccc(OCc3ccccc3)c(OCc3ccccc3)c2)c(OCc2ccccc2)cc(OCc2ccccc2)c1Cc1ccccc1
Reaction time: 8 h
Yield: 46 %

Procedure:
At rt under an N2 atmosphere, 25% H2SO4/SiO2 (1.6 g, 4 mmol) was added in one batch to the stirred mixture of 2-benzyl-3,5-bis(benzyloxy)phenol (3.96 g, 10 mmol) and (E)-3,4-bis(benzyloxy)cinnamyl alcohol (3.46 g, 10 mmol) in dry CH2Cl2 (80 mL). The resulting mixture was starred at rt overnight. After filtration and evaporation, the residue was purified by column chromatography on silica gel (EtOAc/n-hexane=1/7 v/v) and recrystallized from EtOAc and n-hexane to give a white solid, (3.4 g, 46.0% yield): mp 93-95° C.; 1H NMR (CDCl3, 400 MHz) δ 7.41-7.22 (m, 30H), 6.92 (s, 1H) 6.79 (s, 1H), 6.78 (d, J=4.0 Hz, 1H), 6.35 (A of AB, J=15.8 Hz, 1H), 6.26 (s, 1H), 6.13-6.07 (B of ABt, J=15.8, 5.0 Hz, 1H), 5.08 (s, 2H), 5.07 (s, 2H), 4.99 (s, 4H), 4.02 (s, 2H), 3.55 (d, J=5.0 Hz, 2H); 13C NMR (CDCl3, 400 MHz) δ 156.1, 155.6, 154.0, 148.9, 148.2, 141.1, 137.2, 137.1, 131.0, 130.1, 128.5, 128.4, 128.2, 127.8, 127.7, 127.6, 127.3, 127.2, 127.1, 126.5, 125.7, 119.7, 114.9, 112.4, 109.6, 107.3, 91.4, 71.1, 70.5, 70.3, 28.8, 26.6; HRMS (ESI): calcd for C50H44O5Na (M+Na) 747.3086, found 747.3096.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:5]=1[C:11]1[N:15]=[C:14]([C:16]2[CH:21]=[CH:20][C:19]([CH2:22][OH:23])=[C:18]([Cl:24])[CH:17]=2)[N:13]([CH3:25])[N:12]=1.Cl[C:27]1[C:32]([Cl:33])=[CH:31][C:30]([Cl:34])=[CH:29][N:28]=1.O>COCCOC>[Cl:24][C:18]1[CH:17]=[C:16]([C:14]2[N:13]([CH3:25])[N:12]=[C:11]([C:5]3[C:6]([F:10])=[CH:7][CH:8]=[CH:9][C:4]=3[Cl:3])[N:15]=2)[CH:21]=[CH:20][C:19]=1[CH2:22][O:23][C:27]1[C:32]([Cl:33])=[CH:31][C:30]([Cl:34])=[CH:29][N:28]=1
Reactant: Clc1cnc(Cl)c(Cl)c1
Reactant: Cn1nc(-c2c(F)cccc2Cl)nc1-c1ccc(CO)c(Cl)c1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: Cn1nc(-c2c(F)cccc2Cl)nc1-c1ccc(COc2ncc(Cl)cc2Cl)c(Cl)c1
Temperature: -5 °C
Reaction time: 0.33 h
Yield: 28.3 %

Procedure:
Sodium hydride (60%, 0.12 g) is added to 1,2-dimethoxyethane (50 ml) and a solution of 3-(2-chloro-6-fluorophenyl)-5-(3-chloro-4-hydroxymethylphenyl) 1-methyl-1H-1,2,4-triazole (1.00 g) in 1,2-dimethoxyethane (20 ml) is added dropwise thereto at -5° C. and stirred for 20 minutes. The reaction solution is added dropwise with a solution of 2,3,5-trichloropyridine (0.60 g) in 1,2-dimethoxyethane (20 ml) at -5° C. for 10 minutes with stirring. The reaction mixture is warmed to room temperature, poured into water and extracted with ethyl acetate. The organic layer is washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate is purified by silica gel column chromatography to give 0.40 g of desired compound (melting point: 153.0°-155.0° C.).
Reaction SMILES: [CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:9]([C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[CH:19][CH:18]=1)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]>C1(C)C=CC=CC=1>[CH2:1]([NH:21][C:20]1[CH:22]=[CH:23][C:17]([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])=[CH:18][CH:19]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCCCCCCCc1ccc(N)cc1
Reactant: O=Cc1ccccc1
Solvent: Cc1ccccc1
Product: CCCCCCCCc1ccc(NCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
To a solution of benzaldehyde (10 mL) in toluene (200 mL) were added, under ice-cooling, 4-octylaniline (22.5 mL) and molecular sieves 4A (20 g), and the mixture was stirred overnight at room temperature. The molecular sieves 4A was filtered off from the reaction mixture and the obtained filtrate was concentrated under reduced pressure. The residue was dissolved in methanol (200 mL) and sodium borohydride (2.3 g) was added under ice-cooling. The mixture was stirred at room temperature for 5 hr. Methanol was evaporated and water was added to the residue. The mixture was extracted with chloroform and the organic layer was washed with saturated brine, dried and concentrated under reduced pressure to give benzyl(4-octylphenyl)amine (29 g).