Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH3:7][C:8]1[CH:23]=[CH:22][CH:21]=[CH:20][C:9]=1[CH2:10][NH:11][CH2:12][CH2:13][C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1.Br[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][O:30][C:31]1[CH:32]=[C:33]2[C:38](=[CH:39][CH:40]=1)[N:37]([CH3:41])[C:36](=[O:42])[CH:35]=[CH:34]2.C(OC(=O)C)C.[ClH:49]>C(OCC)(=O)C.CN(C=O)C>[ClH:49].[ClH:49].[CH3:41][N:37]1[C:38]2[C:33](=[CH:32][C:31]([O:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][N:11]([CH2:10][C:9]3[CH:20]=[CH:21][CH:22]=[CH:23][C:8]=3[CH3:7])[CH2:12][CH2:13][C:14]3[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=3)=[CH:40][CH:39]=2)[CH:34]=[CH:35][C:36]1=[O:42]
Reactant: Cc1ccccc1CNCCc1cccnc1
Reactant: Cn1c(=O)ccc2cc(OCCCCCBr)ccc21
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Cc1ccccc1CN(CCCCCOc1ccc2c(ccc(=O)n2C)c1)CCc1cccnc1
Temperature: 60 °C
Reaction time: 8 h

Procedure:
Potassium carbonate(360 mg) and (2-methylbenzyl)-(2-pyridin-3-ylethyl)amine(591 mg) were added to a DMF solution (6.5 ml) of 6-(5-bromopentyloxy)-1-methyl-1H-quinolin-2-one(650 mg). The mixture was stirred at 60° C. for 8 hours. Ice water was added to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was washed with water and then saturated saline, dried with anhydrous sodium sulfate, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane: ethyl acetate: methanol: aqueous ammonia=70:20:10:1). The purified product was condensed under reduced pressure. A 4N-hydrogen chloride ethyl acetate solution(1.0 ml) was added to an ethyl acetate solution(20 ml) of the residue, which was stirred at room temperature. The liquid was condensed to dryness under reduced pressure to give the title compound(270 mg) as a pale yellow amorphous solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:25][C:11]3=[N:12][C:13]([N:19]([CH3:24])[S:20]([CH3:23])(=[O:22])=[O:21])=[C:14](C(C)=C)[CH:15]=[C:10]3[C:9]=2[C:26]([NH:28][CH3:29])=[O:27])=[CH:4][CH:3]=1.C[N+]1([O-])CC[O:34]CC1.[CH3:38][C:39]([CH3:41])=[O:40]>>[OH:34][CH2:38][C:39]([C:14]1[CH:15]=[C:10]2[C:9]([C:26]([NH:28][CH3:29])=[O:27])=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[O:25][C:11]2=[N:12][C:13]=1[N:19]([CH3:24])[S:20]([CH3:23])(=[O:22])=[O:21])([OH:40])[CH3:41]
Reactant: C[N+]1([O-])CCOCC1
Reactant: CC(C)=O
Reactant: C=C(C)c1cc2c(C(=O)NC)c(-c3ccc(F)cc3)oc2nc1N(C)S(C)(=O)=O
Product: CNC(=O)c1c(-c2ccc(F)cc2)oc2nc(N(C)S(C)(=O)=O)c(C(C)(O)CO)cc12

Procedure:
To 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(prop-1-en-2-yl)furo[2,3-b]pyridine-3-carboxamide (11 mg, 0.026 mmol) in acetone (1 ml) was added NMO (9.26 mg, 0.079 mmol) and potassium osmate dihydrate (0.971 mg, 2.64 μmol). After LCMS indicated predominant conversion of starting material to product, the reaction mixture was purified by HPLC to afford the title compound. MS (ESI) m/z 452.0 (M+1). 2 rotamers confirmed by 2D NMR: 1H NMR (400 MHz, CD3CN) δ ppm 8.66, 8.64 (s, 1H), 8.04-8.02 (m, 2H), 7.34-7.29 (m, 2H), 6.88 (br s, 1H), 4.16-4.13, 4.06-4.03 (m, 1H), 3.92, 3.88 (br s, 1H), 3.82-3.79 (m, 1H), 3.33, 3.32 (s, 3H), 3.29 (s, 3H), 3.15-3.02 (br s, 1H), 2.93-2.92 (d, 3H)
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[C:10]2[CH:11]=[C:12]([CH:16]=[CH:17][C:18]=2[O:19][CH3:20])[C:13]([OH:15])=O)=[CH:4][CH:3]=1.[NH2:21][CH2:22][CH2:23][O:24][CH2:25][CH2:26][OH:27]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5](/[CH:8]=[CH:9]/[C:10]2[CH:11]=[C:12]([CH:16]=[CH:17][C:18]=2[O:19][CH3:20])[C:13]([NH:21][CH2:22][CH2:23][O:24][CH2:25][CH2:26][OH:27])=[O:15])=[CH:6][CH:7]=1
Reactant: COc1ccc(C(=O)O)cc1/C=C/c1ccc(Cl)cc1
Reactant: NCCOCCO
Product: COc1ccc(C(=O)NCCOCCO)cc1/C=C/c1ccc(Cl)cc1

Procedure:
The captioned compound was synthesized from 3-[(E)-2-(4-chlorophenyl)vinyl]-4-methoxy-benzoic acid and 2-(2-aminoethoxy)-ethanol in accordance with the same procedure as in the manufacturing method described in step C of Example 1-2-3.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]3[CH:14]=[C:15]([C:18]4[O:22][C:21]([SH:23])=[N:20][N:19]=4)[CH:16]=[CH:17][C:12]=3[N:11]=[CH:10]2)=[CH:5][CH:4]=1.[CH3:24][O:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30]Br)=[CH:28][C:27]=1[C:34]([F:37])([F:36])[F:35]>>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]3[CH:14]=[C:15]([C:18]4[O:22][C:21]([S:23][CH2:30][C:29]5[CH:32]=[CH:33][C:26]([O:25][CH3:24])=[C:27]([C:34]([F:35])([F:36])[F:37])[CH:28]=5)=[N:20][N:19]=4)[CH:16]=[CH:17][C:12]=3[N:11]=[CH:10]2)=[CH:5][CH:4]=1
Reactant: COc1ccc(-n2cnc3ccc(-c4nnc(S)o4)cc32)cc1
Reactant: COc1ccc(CBr)cc1C(F)(F)F
Product: COc1ccc(-n2cnc3ccc(-c4nnc(SCc5ccc(OC)c(C(F)(F)F)c5)o4)cc32)cc1
Yield: 34 %

Procedure:
In the same manner as in Example 1 and using 5-[1-(4-methoxyphenyl)-1H-benzimidazol-6-yl]-1,3,4-oxadiazole-2-thiol instead of 5-(benzothiazol-6-yl)-1,3,4-oxadiazole-2-thiol and 4-methoxy-3-(trifluoromethyl)benzyl bromide instead of 3-(trifluoromethyl)benzyl chloride, the title compound (yield 34%) was obtained as colorless crystals.
Reaction SMILES: Cl.[NH:2]1[CH2:7][CH:6]=[C:5]([C:8]2[CH:9]=[C:10]([NH:14][C:15](=[O:17])[CH3:16])[CH:11]=[CH:12][CH:13]=2)[CH2:4][CH2:3]1.Br[CH2:19][CH2:20][CH2:21][NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1>[C:15]([NH:14][C:10]1[CH:9]=[C:8]([C:5]2[CH2:6][CH2:7][N:2]([CH2:19][CH2:20][CH2:21][NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:3][CH:4]=2)[CH:13]=[CH:12][CH:11]=1)(=[O:17])[CH3:16]
Reactant: CC(=O)Nc1cccc(C2=CCNCC2)c1
Reactant: CC(C)(C)OC(=O)NCCCBr
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Product: CC(=O)Nc1cccc(C2=CCN(CCCNC(=O)OC(C)(C)C)CC2)c1

Procedure:
A solution of N1-[3-(1,2,3,6-tetrahydro-4-pyridinyl) phenyl]acetamide hydrochloride (8.24 mmol), tert-butyl N-(3-bromopropyl)carbamate and potassium carbonate (33 mmol) in dry dioxane (30 mL) was heated at reflux temperature overnight. The solids were removed by filtration, the solution was concentrated in vacuo and the product was chromatographed, giving the desired product (110 mg). 1H NMR δ 7.65 (s, 1 H), 6.98 (s, 1 H), 7.45 (d, 1 H, J=7.8 Hz), 7.16 (apparent t, 1 H, J=7.8 Hz), 7.10 (d, 1 H, J=7.8 Hz), 6.02 (s, 1 H), 5.23 (b, 1 H), 3.40 (b, 2 H), 3.30-1.80 (m, 10 H), 2.18 (s, 3 H), 1.45 (s, 9 H)
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:10]3[CH2:12][CH:13]([CH3:16])[CH2:14][CH2:15][C:9]=3[C:8]([CH3:18])([CH3:17])[O:7][C:6]=2[CH:5]=[C:4]([CH:19]([CH:21]([CH3:27])[CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[CH3:20])[CH:3]=1.Cl.[S:29]1[CH2:34][CH2:33][N:32]([CH2:35][CH2:36][CH2:37][C:38](O)=[O:39])[CH2:31][CH2:30]1.C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl>[S:29]1[CH2:30][CH2:31][N:32]([CH2:35][CH2:36][CH2:37][C:38]([O:1][C:2]2[C:11]3[C:10]4[CH2:12][CH:13]([CH3:16])[CH2:14][CH2:15][C:9]=4[C:8]([CH3:17])([CH3:18])[O:7][C:6]=3[CH:5]=[C:4]([CH:19]([CH:21]([CH3:27])[CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[CH3:20])[CH:3]=2)=[O:39])[CH2:33][CH2:34]1
Reactant: O=C(O)CCCN1CCSCC1
Reactant: CCCCCC(C)C(C)c1cc(O)c2c(c1)OC(C)(C)C1=C2CC(C)CC1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Solvent: ClCCl
Product: CCCCCC(C)C(C)c1cc(OC(=O)CCCN2CCSCC2)c2c(c1)OC(C)(C)C1=C2CC(C)CC1

Procedure:
A mixture of 4.0 g. (10.8 mmole) of 1-hydroxy-3-(3-methyl-2-octyl)-6,6,9-trimethyl-7,8,9,10-tetrahydro-6H-dibenzo[ b,d] pyran, 2.4 g. (10.8 mmole) of γ-thiomorpholinobutyric acid hydrochloride, 2.38 g. (11.5 mmole) of dicyclohexylcarbodiimide and 250 ml. of methylene chloride was stirred and heated at reflux for 18 hours. After cooling the reaction mixture, the byproduct of dicyclohexylurea was removed by suction filtration. The solvent was evaporated to give a red-brown residue which was chromatographed using 90 g. of activated magnesium silicate (60-100 mesh) and chloroform as the solvent system. The fractions were monitored by thin layer chromatography, and the appropriate fractions were combined and evaporated to give 1.0 g. of a light yellow oil. The material was pure by thin layer chromatography, and the infrared and nuclear magnetic resonance spectra were in agreement with the designated structure.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:15])[NH:4][CH:5]1[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]1[OH:14].N[C@H:17]([C:25](O)=[O:26])CC1C=CC=CC=1.N1C=CC=CC=1.C(Cl)(=O)C>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:15])[NH:4][CH:5]1[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]1[O:14][C:25](=[O:26])[CH3:17]
Reactant: N[C@@H](Cc1ccccc1)C(=O)O
Reactant: COC(=O)NC1Cc2ccccc2C1O
Solvent: c1ccncc1
Solvent: CC(=O)Cl
Solvent: ClCCl
Product: COC(=O)NC1Cc2ccccc2C1OC(C)=O
Temperature: 0 °C
Reaction time: 1 h

Procedure:
The alcohol, (1-hydroxy-indan-2-yl)-carbamic acid methyl ester (1S-trans) prepared from L-phenylalanine (18.7 g, 0.09 mol) (J. Org. Chem. 1983, 48, 2675-2679) is suspended in methylene chloride and cooled to 0° C. Pyridine (10.7 g, 0.135 mol) is added followed by acetyl chloride (10.5 g, 0.135 mol). The mixture is stirred for 1 h. and then washed with sodium bicarbonate, 1N HCl and saturated sodium chloride. The organic layer is dried over Na2SO4, filtered and evaporated under reduced pressure to give (1-acetyloxy-indan-2-yl)-carbamic acid methyl ester (1S-trans).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[C:22]([CH3:23])=[CH:21][C:19]([NH2:20])=[C:18]([CH3:24])[CH:17]=1.Cl[C:26](Cl)([O:28][C:29](=[O:35])OC(Cl)(Cl)Cl)Cl.[CH3:37][N:38]1[CH2:43]C[CH2:41][CH:40](O)[CH2:39]1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(N(CC)CC)C.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[C:22]([CH3:23])=[CH:21][C:19]([NH:20][C:29](=[O:35])[O:28][CH:26]2[CH2:41][CH2:40][CH2:39][N:38]([CH3:43])[CH2:37]2)=[C:18]([CH3:24])[CH:17]=1
Reactant: COc1cc2nccc(Oc3cc(C)c(N)cc3C)c2cc1OC
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: CN1CCCC(O)C1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: COc1cc2nccc(Oc3cc(C)c(NC(=O)OC4CCCN(C)C4)cc3C)c2cc1OC
Yield: 40.4 %

Procedure:
4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml) and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-methyl-3-piperidinol (27 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (29 mg, yield 36%).
Reaction SMILES: N1[C:9]2[C:4](=[CH:5][C:6]([C:10]([O:12][CH3:13])=[O:11])=[CH:7][CH:8]=2)C=C1.[O-]S([C:18]([F:21])(F)F)(=O)=O.F[N+:23]1C(C)=CC(C)=C[C:24]=1C>CO>[F:21][C:18]1[C:9]2[C:4](=[CH:5][C:6]([C:10]([O:12][CH3:13])=[O:11])=[CH:7][CH:8]=2)[NH:23][CH:24]=1
Reactant: COC(=O)c1ccc2[nH]ccc2c1
Reactant: O=S(=O)([O-])C(F)(F)F
Reactant: Cc1cc(C)[n+](F)c(C)c1
Solvent: CO
Product: COC(=O)c1ccc2c(F)c[nH]c2c1

Procedure:
A solution of methyl 1H-indole-6-carboxylate 19a (2.0 g, 11.4 mmol) and N-fluoro-2,4,6-trimethylpyridinium triflate (4.3 g, 14.8 mmol) in MeOH (100 mL) was heated at reflux for 18 h. The reaction mixture was concentrated and purified by flash column chromatography (silica gel, 15-20% EtOAc/hexanes) to give compound 21a as an off-white solid.
Reaction SMILES: C(O)CCCCCCC/C=C\CCCC.[CH2:16]([OH:36])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH:26]=[CH:27][CH2:28][CH2:29][CH2:30][CH2:31]CCCC.C=CCCCC>C1COCC1>[CH2:16]([OH:36])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]/[CH:26]=[CH:27]\[CH2:28][CH2:29][CH2:30][CH3:31]
Reactant: CCCCCCCCC=CCCCCCCCCCCO
Agent: CCCC/C=C\CCCCCCCCO
Solvent: C=CCCCC
Solvent: C1CCOC1
Product: CCCC/C=C\CCCCCCCCCCO
Yield: 76 %

Procedure:
According to the procedure for compound 3, 11-eicosenol (1.3 g, 4.4 mmol) and 1-hexene (6 mL) in THF (6 mL) were reacted with 1 (0.028 g, 1 mol %) to provide 5 (0.84 g, 76% yield, 86% Z as determined by 1H-NMR) as a colorless oil; 1H NMR (CDCl3): δ 5.36 (2H, m), 3.64 (2H, td, J=6.5, 5.3 Hz), 2.02 (4H, m), 1.56 (2H, m), 1.23-1.38 (19H, m), 0.90 (3H, t, J=7.2 Hz); 13C NMR (CDCl3): δ 129.9 (2C), 63.1, 32.8, 32.0, 29.8, 29.6 (2C), 29.5, 29.4, 29.3, 27.2, 26.9, 25.8, 22.4, 14.0; HRMS (FAB): 241.2536, [C16H32O+H]+ requires 241.2531.
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[OH:17])[N:8]([CH3:18])[N:7]=1)=[O:5])C.CO.O[Li].O.Cl>C1COCC1.O>[OH:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[C:9]1[N:8]([CH3:18])[N:7]=[C:6]([C:4]([OH:5])=[O:3])[CH:10]=1
Reactant: CCOC(=O)c1cc(-c2ccccc2O)n(C)n1
Agent: Cl
Agent: [Li]O
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: Cn1nc(C(=O)O)cc1-c1ccccc1O
Reaction time: 8 h
Yield: 86.3 %

Procedure:
To a solution of 5-(2-benzyloxy-phenyl)-1H-pyrazole-3-carboxylic acid ethyl ester (0.25 g, 0.00078 mole) in DMF (5 mL) was added K2CO3 (0.225 g, 0.00163 mole) followed by methyl iodide (0.116 g, 0.00081 mole) and at the resulting mixture was stirred at ambient temperature for 1 hour. The mixture was then quenched with iced water and the resulting precipitate was isolated by filtration. The solid was recrystallized from ethyl acetate to afford 0.251 g (96%) of 5-(2-benzyloxy-phenyl)-1-methyl-1H-pyrazole-3-carboxylic acid ethyl ester. LCMS: 337.15 (M+1)+, 90.13%. To a stirred solution of 5-(2-benzyloxy-phenyl)-1-methyl-1H-pyrazole-3-carboxylic acid ethyl ester (0.251 g, 0.00075 mole) in methanol (40 mL) was added 10% Pd/C (0.05 g) and the resulting mixture was stirred under an atmosphere of hydrogen for 1 hour. The mixture was then filtered through celite and the celite was washed with methanol. The combined filtrate was concentrated under reduced pressure to afford 0.169 g (92%) of 5-(2-hydroxy-phenyl)-1-methyl-1H-pyrazole-3-carboxylic acid ethyl ester. LCMS: 247.1 (M+1)+, 99%. To a stirred solution of 5-(2-hydroxy-phenyl)-1-methyl-1H-pyrazole-3-carboxylic acid ethyl ester (0.169 g, 0.00069 mol) in a mixture of THF (10 mL), methanol (5 mL) and H2O (5 mL), was added LiOH.H2O (0.087 g, 0.00206 mol) at ambient temperature and the resulting mixture was stirred overnight. The reaction mixture was then diluted with cold water and acidified with 10% HCl. The product was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure to afford 0.13 g (87%) of 5-(2-hydroxy-phenyl)-1-methyl-1H-pyrazole-3-carboxylic acid. LCMS: 219.07 (M+1)+, 81.5%
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][CH:3]=1.[CH2:12](Br)[C:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=O.C([N:24](CC)CC)C>ClCCl>[OH:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]2[O:11][CH:12]=[C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[N:24]=2)=[CH:6][CH:7]=1
Reactant: O=C(O)Cc1ccc(O)cc1
Reactant: O=C(CBr)c1ccccc1
Reactant: CCN(CC)CC
Solvent: ClCCl
Product: Oc1ccc(Cc2nc(-c3ccccc3)co2)cc1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
In 50 ml of dichloromethane, were dissolved 6.09 g of 4-hydroxyphenyl acetic acid and 7.96 g of phenacyl bromide were dissolved, to which 5.6 ml of triethylamine was added and stirred at room temperature for 2 days. After washing the reaction solution with a 10% hydrochloric acid, it was further washed with an aqueous saturated solution of sodium hydrogen carbonate. After distilling off the dichloromethane under a reduced pressure from the solution, the residue was dissolved in 80 ml of acetic acid and refluxed for three hours with addition of 12.3 g of ammonium acetate. The acetic acid was distilled off under a reduced pressure from the solution. The residue was dissolved in dichloromethane, washed with a 10% hydrochloric acid and an aqueous saturated solution of sodium hydrogen carbonate, and then, the dichloromethane layer was collected. After drying the liquid extract over magnesium sulfate, it was concentrated under a reduced pressure, adsorbed on silica gel column, eluted with chloroform and then crystallized from isopropyl ether to obtain 3.65 g of 2-(4-hydroxybenzyl)-4-phenyloxazole having the melting point of 122° to 124° C.
Reaction SMILES: Cl[C:2]1[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][N:8]=1.[Br:9][C:10]1[CH:19]=[CH:18][CH:17]=[CH:16][C:11]=1[C:12]([NH:14][NH2:15])=[O:13].[OH-].[Na+].C(OCC)C>C1C=CC=CC=1>[N:8]1[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][C:2]=1[NH:15][NH:14][C:12](=[O:13])[C:11]1[CH:16]=[CH:17][CH:18]=[CH:19][C:10]=1[Br:9]
Reactant: NNC(=O)c1ccccc1Br
Reactant: ClC1=NCCCCC1
Agent: [Na+]
Agent: [OH-]
Solvent: c1ccccc1
Solvent: CCOCC
Product: O=C(NNC1=NCCCCC1)c1ccccc1Br
Yield: 38.7 %

Procedure:
To a solution of 7-chloro-3,4,5,6-tetrahydro-2H-azepine (1.32 g, 10 mmol, J. Med. Chem. 30, 1543-49) in benzene (20 ml) was added 2-bromo-benzoic acid hydrazide (1.08 g, 5 mmol) and the mixture was stirred at reflux temperature for 5 hrs. To the cooled reaction mixture was added 10% sodium hydroxide (10 ml) and diethyl ether (20 ml). The mixture was stirred for 30 min., the precipitate filtered off and dried in vacuo at 50° C. for 1 hr. affording 0.6 g of 2-bromo-benzoic acid-N′-(4,5,6,7-tetrahydro-3H-azepin-2-yl)-hydrazide which was dissolved in ethanol (20 ml) followed by addition of TEA (5 ml) and refluxed for 16 hrs. The volatiles were evaporated in vacuo and to the residue was added diethyl ether (10 ml) and ethyl acetate (5 ml). The precipitate was filtered off and dried in vacuo at 50° C. for 1 hr affording 0.35 g (24%) of the title compound as a solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[CH:8][C:7](OS(C(F)(F)F)(=O)=O)=[CH:6][CH:5]=1.C1COCC1.CN1CCCC1=O.[CH2:31]([Mg]Br)[CH2:32][CH2:33][CH2:34][CH2:35][CH3:36]>CCOCC>[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[CH:8][C:7]([CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])=[CH:6][CH:5]=1
Reactant: CCCCCC[Mg]Br
Reactant: COC(=O)c1ccc(OS(=O)(=O)C(F)(F)F)cc1
Solvent: CCOCC
Solvent: C1CCOC1
Solvent: CN1CCCC1=O
Product: CCCCCCc1ccc(C(=O)OC)cc1
Reaction time: 0.08 h
Yield: 92.1 %

Procedure:
A flame-dried two-necked flask is charged under argon with 4-(trifluoromethylsulfonyloxy)benzoic acid methyl ester (760 mg, 2.66 mmol), Fe(acac)3 (47 mg, 0.13 mmol), THF (30 mL) and N-methylpyrrolidone (NMP, 1.7 mL). A solution of n-hexylmagnesium bromide (2M in Et2O, 1.7 mL, 3.4 mmol) is added via syringe to the resulting red solution, causing an immediate color change to dark brown and finally to violet. The resulting mixture is stirred for 5 min, the reaction is diluted with Et2O and is carefully quenched upon addition of aq. HCl (1M, ca. 10 mL). Work-up followed by flash chromatography of the crude product as described above provides 4-hexylbenzoic acid methyl ester as a colorless syrup (540 mg, 93%). The spectroscopic and analytical data are identical to those compiled above.
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]2[C:5](=[O:14])[CH2:6][CH2:7][CH2:8][C:9]=2[C:10]=1[C:11]([OH:13])=O.[CH3:15][N:16]1[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][CH2:24][NH2:25])[CH2:18][CH2:17]1>>[CH3:1][C:2]1[NH:3][C:4]2[C:5](=[O:14])[CH2:6][CH2:7][CH2:8][C:9]=2[C:10]=1[C:11]([NH:25][CH2:24][CH2:23][CH2:22][N:19]1[CH2:18][CH2:17][N:16]([CH3:15])[CH2:21][CH2:20]1)=[O:13]
Reactant: CN1CCN(CCCN)CC1
Reactant: Cc1[nH]c2c(c1C(=O)O)CCCC2=O
Product: Cc1[nH]c2c(c1C(=O)NCCCN1CCN(C)CC1)CCCC2=O
Yield: 78.2 %

Procedure:
Similar procedure as Example 2, 2-methyl-7-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxylic acid (S4) 0.2 g (1.0 mmol) and 3-(4-methylpiperazin-1-yl)propan-1-amine 0.33 g (2.1 mmol) was reacted to give 0.26 g (78%) of the titled compound as a white solid.
Reaction SMILES: [H-].[Na+].[I-].[CH3:4][S+](C)(C)=O.[H][H].[CH3:11][C:12]1[C:13](=[O:24])[C:14]([CH3:23])([CH2:18][CH:19]=[C:20]([CH3:22])[CH3:21])[CH2:15][CH2:16][CH:17]=1>CS(C)=O.O>[CH3:11][C:12]12[CH2:4][CH:17]1[CH2:16][CH2:15][C:14]([CH3:23])([CH2:18][CH:19]=[C:20]([CH3:22])[CH3:21])[C:13]2=[O:24]
Reactant: C[S+](C)(C)=O
Reactant: CC(C)=CCC1(C)CCC=C(C)C1=O
Reactant: [H][H]
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: CC(C)=CCC1(C)CCC2CC2(C)C1=O
Temperature: 25 °C
Yield: 83 %

Procedure:
Sodium hydride (60%, 2.11 g, 52.8 mmol) was added to a suspension of trimethylsulfoxonium iodide (11.6 g, 52.8 mmol) in 60 ml of dimethyl sulfoxide. The mixture was stirred for 30 min until hydrogen evolution stopped. 2,6-Dimethyl-6-(3-methyl-but-2-enyl)-cyclohex-2-enone was added and the mixture was stirred over night at room temperature, was then diluted with water and extracted with pentane. The organic phase was washed with water and brine, dried (MgSO4) and concentrated in vacuo. The residue was distilled (bp.95° C./0.05 Torr) to yield 4.5 g (83%) of product as a mixture of two diastereomers. 1H-NMR (200 MHz, CDCl3): 5.11-4.93 (m, 1H, 2′-H), 2.45-1.32 (m, 7H), 1.75/1.70 (2s, 3H, 4′H), 1.63/1.59 (2s, 3H, 3′-CH3), 1.31-1.16 (m, 1H), 1.23/1.21 (2s, 3H), 1.01/0.99 (2s, 3H), 0.75-0.64 (m, 1H) ppm. GC/MS (EI): 206 (M+, 12), 191 (14), 163 (20), 138 (90), 123 (100), 109 (34), 95 (57), 69 (62), 41 (94). IR (ATR): 2962s, 2928s, 2866s, 1681vs, 1451s, 1375m, 1043m, 1000m cm−1.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=O)=[CH:4][CH:3]=1.C=[CH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(N(CCCC)CCCC)CCC.CC1C=CC(C)=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([CH:6]=[CH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:4][CH:3]=1
Reactant: O=C(Cl)c1ccc(Br)cc1
Reactant: C=Cc1ccccc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Solvent: Cc1ccc(C)cc1
Solvent: CCCCN(CCCC)CCCC
Product: Brc1ccc(C=Cc2ccccc2)cc1
Yield: 51 %

Procedure:
0.448 g (2 millimols) of palladium acetate, 43.88 g (0.2 mol) of 4-bromobenzoyl chloride, 26 g (0.25 mol) of styrene and 37.06 g (0.2 mol) of tri-n-butylamine in 200 mol of p-xylene are stirred for 4 hours at 120° C. After the reaction mixture has been extracted by shaking with 2 N HCl and 2 N NaOH, and dried over magnesium sulfate, the crude product is chromatographed in toluene on silica gel, and is recrystallised from n-hexane. 26.43 g (51% of theory) of 4-bromostilbene are obtained as pale yellow crystals of melting point 137.7° C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4](Br)[CH:5]=[C:6]([F:8])[CH:7]=1.[B:10](OC)([O:13]C)[O:11]C.Cl>O1CCCC1>[F:1][C:2]1[CH:3]=[C:4]([B:10]([OH:13])[OH:11])[CH:5]=[C:6]([F:8])[CH:7]=1
Reactant: COB(OC)OC
Reactant: Fc1cc(F)cc(Br)c1
Agent: Cl
Solvent: C1CCOC1
Product: OB(O)c1cc(F)cc(F)c1
Temperature: -78 °C
Reaction time: 18 h

Procedure:
In a separate reaction vessel, 40 mL of tetrahydrofuran was cooled to -78 ° C., and the Grignard reagent of 3,5-difluorophenyl bromide and a solution of 11.3 grams (0.109 mole) of trimethyl borate in 15 mL of tetrahydrofuran were added simultaneously dropwise in an effort to provide an equimolar addition of each. An additional 115 mL of tetrahydrofuran was added during the additions to dilute the thickening reaction mixture. The completion of additions required about 15 minutes. After this time the reaction mixture was allowed to warm to ambient temperature as it stirred for about 18 hours. The reaction mixture was then poured into 300 mL of an aqueous dilute solution of hydrochloric acid. The resultant mixture was extracted with two 150 mL portions of ethyl acetate. The combined extracts were dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, yielding 13.6 grams of 3,5-difluoro-phenylboronic acid. The NMR spectrum was consistent with the proposed structure.