Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](=[O:19])[N:14]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:13]([CH2:24]Cl)=[C:12]2[O:26][CH2:27][CH2:28][CH2:29][C:30]([F:33])([F:32])[F:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:34]1(=[O:44])[NH:38][C:37](=[O:39])[C:36]2=[CH:40][CH:41]=[CH:42][CH:43]=[C:35]12.[K].O>CN(C)C=O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](=[O:19])[N:14]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:13]([CH2:24][N:38]1[C:34](=[O:44])[C:35]3[C:36](=[CH:40][CH:41]=[CH:42][CH:43]=3)[C:37]1=[O:39])=[C:12]2[O:26][CH2:27][CH2:28][CH2:29][C:30]([F:33])([F:32])[F:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C1NC(=O)c2ccccc21
Reactant: CC(C)Cn1c(CCl)c(OCCCC(F)(F)F)c2cc(OCc3ccccc3)ccc2c1=O
Agent: [K]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)Cn1c(CN2C(=O)c3ccccc3C2=O)c(OCCCC(F)(F)F)c2cc(OCc3ccccc3)ccc2c1=O
Yield: 94.3 %

Procedure:
A solution of 6-benzyloxy-3-chloromethyl-2-isobutyl-4-(4,4,4-trifluorobutoxy)-1(2H)-isoquinolinone (3.37 g, 7 mmol) and potassium phthalimide (1.94 g, 10.5 mmol) in N,N-dimethylformamide (30 mL) was stirred at room temperature for 6 h. The reaction mixture was poured into water and extracted with ethyl acetate. After washing the extract with water, and the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained crystals were recrystallized from ethyl acetate-n-hexane to give 2-[[6-benzyloxy-2-isobutyl-1-oxo-4-(4,4,4-trifluorobutoxy)-1,2-dihydro-3-isoquinolinyl]methyl]-1H-isoindole-1,3(2H)-dione (3.91 g, 94.4%) as crystals.
Reaction SMILES: [H-].[Na+].[OH:3][CH2:4][CH2:5][N:6]1[CH2:10][CH2:9][CH2:8][C:7]1=[O:11].[N:12]1([CH2:17][CH2:18][O:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]3[S:30][C:29]4[CH:31]=[CH:32][CH:33]=[CH:34][C:28]=4[C:27]=3[C:35]([C:37]3[CH:42]=[CH:41][C:40](F)=[CH:39][CH:38]=3)=[O:36])=[CH:22][CH:21]=2)[CH2:16][CH2:15][CH2:14][CH2:13]1>CN(C=O)C.[Cl-].[Na+].O>[O:11]=[C:7]1[CH2:8][CH2:9][CH2:10][N:6]1[CH2:5][CH2:4][O:3][C:40]1[CH:41]=[CH:42][C:37]([C:35]([C:27]2[C:28]3[CH:34]=[CH:33][CH:32]=[CH:31][C:29]=3[S:30][C:26]=2[C:23]2[CH:22]=[CH:21][C:20]([O:19][CH2:18][CH2:17][N:12]3[CH2:16][CH2:15][CH2:14][CH2:13]3)=[CH:25][CH:24]=2)=[O:36])=[CH:38][CH:39]=1
Reactant: O=C(c1ccc(F)cc1)c1c(-c2ccc(OCCN3CCCC3)cc2)sc2ccccc12
Reactant: O=C1CCCN1CCO
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: O=C(c1ccc(OCCN2CCCC2=O)cc1)c1c(-c2ccc(OCCN3CCCC3)cc2)sc2ccccc12
Reaction time: 0.25 h

Procedure:
Sodium hydride (60% oil dispersion, 50 mg) was suspended in DMF (2.0 mL) and stirred at ambient temperature for 15 min under argon before 1-(2-hydroxyethyl)-2-pyrrolidinone (87 μL) was added. After stirring for 15 min, 4-fluorophenyl 2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]-benzo[b]thiophen-3-yl ketone (223 mg) in 1 mL of DMF was introduced and the resulting solution was stirred at ambient temperature for 3.5 h. The reaction mixture was diluted with brine (50 mL) and extracted with EtOAc (3×50 mL). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. Chromatography with Et3N:MeOH:EtOAc (5:5-10:90-85) afforded the product as a colorless oil (210 mg).
Reaction SMILES: C([O:3][C:4]([CH:6]1[CH:8]([CH:9]=[C:10]([Cl:22])[C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]([F:21])([F:20])[F:19])=[CH:13][CH:12]=2)[C:7]1([CH3:24])[CH3:23])=[O:5])C.[OH-].[Na+]>C(O)C.O>[CH3:23][C:7]1([CH3:24])[CH:8]([CH:9]=[C:10]([Cl:22])[C:11]2[CH:12]=[CH:13][C:14]([O:17][C:18]([F:20])([F:21])[F:19])=[CH:15][CH:16]=2)[CH:6]1[C:4]([OH:5])=[O:3]
Reactant: CCOC(=O)C1C(C=C(Cl)c2ccc(OC(F)(F)F)cc2)C1(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CC1(C)C(C=C(Cl)c2ccc(OC(F)(F)F)cc2)C1C(=O)O
Yield: 68.2 %

Procedure:
30.8 g (0.085 mol) of 2,2-dimethyl-3-(2-chloro-2-(4-trifluoromethoxy-phenyl)-vinyl)-cyclopropanecarboxylic acid ethyl ester were dissolved in 100 ml of ethanol, a solution of 4 g (0.1 mol) of sodium hydroxide in 100 ml of water was then added and the mixture was heated to the reflux temperature for 4 hours, while stirring. The ethanol was then distilled off under a waterpump vacuum, the residue was taken up in 300 ml of warm water and the mixture was extracted once with 300 ml of methylene chloride. The aqueous phase was separated off, acidified with concentrated hydrochloric acid and then extracted with 2 times 300 ml of methylene chloride. The organic phase was then separated off and dried over magnesium sulphate and the solvent was distilled off under a waterpump vaccum. Last residues of solvent were removed by brief incipient distillation under 2 mm Hg at a bath temperature of 60° C. 19.4 g (68.3% of theory) of 2,2-dimethyl-3-(2-chloro-2-(4-trifluoromethoxy-phenyl)-vinyl)-cyclopropanecarboxylic acid (cis and trans, E and Z isomer mixture) were then obtained as a very viscous yellow oil. The structure was confirmed by the 1H-NMR spectrum.
Reaction SMILES: CN([CH:4]=[C:5]1[C:9](=O)[CH2:8][N:7](C(OC(C)(C)C)=O)[CH2:6]1)C.[O-]CC.[Na+].[F:22][C:23]([F:28])([F:27])[C:24]([NH2:26])=[NH:25]>C(O)C.C(OCC)(=O)C.Cl>[F:22][C:23]([F:28])([F:27])[C:24]1[N:26]=[CH:4][C:5]2[CH2:6][NH:7][CH2:8][C:9]=2[N:25]=1
Reactant: CN(C)C=C1CN(C(=O)OC(C)(C)C)CC1=O
Reactant: N=C(N)C(F)(F)F
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: CCOC(C)=O
Product: FC(F)(F)c1ncc2c(n1)CNC2
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
To a solution of the product from Step A (500 mg) in anhydrous ethanol (25 mL) was added sodium ethoxide (2.33 mL, 21% in ethanol). After stirring for 5 min, trifluoroacetamidine (700 mg) was added and the resulting mixture was heated to reflux for 1 h. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The organic layer was washed sequentially with 5% aqueous citric acid solution and brine, dried over anhydrous sodium sulfate, filtered and concentrated to give a crude product which was deprotected by dissolving in 1N methanolic hydrogen chloride for 1 h. The resulting solution was concentrated and chromatographed on a Biotage® system (silica gel cartridge, gradient from 10% to 18% of 10% concentrated aqueous ammonium hydroxide in methanol/dichloromethane) to yield the title compound. LC-MS=190.0 (M+1).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([CH3:13])=[N:10][CH:9]=2)=[C:4]([O:14][CH3:15])[CH:3]=1.[Cl:16][CH2:17][CH2:18][CH2:19][C:20]#[CH:21].C(N(CC)CC)C>C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Cl:16][CH2:17][CH2:18][CH2:19][C:20]#[C:21][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([CH3:13])=[N:10][CH:9]=2)=[C:4]([O:14][CH3:15])[CH:3]=1
Reactant: COc1cc(Br)ccc1-c1cnc(C)o1
Reactant: C#CCCCCl
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: COc1cc(C#CCCCCl)ccc1-c1cnc(C)o1
Temperature: 70 °C
Reaction time: 3 h

Procedure:
A mixture of 5-(4-bromo-2-methoxyphenyl)-2-methyl-1,3-oxazole (6.00 g), 5-chloropent-1-yne (4.74 mL), dichlorobis(triphenylphosphine)palladium(II) (1.57 g), copper(I) iodide (426 mg) and triethylamine (60 mL) was stirred at 70° C. for 3 hr, and diluted with ethyl acetate, and the mixture was filtered through celite. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (4.85 g).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[N:7]=[C:6]([C@H:8]([CH2:17][CH2:18][CH2:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[O:5][N:4]=1.[CH2:26]([S:28](Cl)(=[O:30])=[O:29])[CH3:27]>>[CH:20]1([CH2:19][CH2:18][CH2:17][C@@H:8]([C:6]2[O:5][N:4]=[C:3]([CH2:2][NH:1][S:28]([CH2:26][CH3:27])(=[O:30])=[O:29])[N:7]=2)[CH2:9][C:10]([O:12][C:13]([CH3:15])([CH3:16])[CH3:14])=[O:11])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]1
Reactant: CC(C)(C)OC(=O)C[C@@H](CCCC1CCCCC1)c1nc(CN)no1
Reactant: CCS(=O)(=O)Cl
Product: CCS(=O)(=O)NCc1noc([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)n1

Procedure:
Method the same as for Preparation 6 using tert-butyl(3R)-3-[3-(aminomethyl)-1,2,4-oxadiazol-5-yl]-6-cyclohexylhexanoate (preparation 18) (200 mg, 0.57 mmol) and ethanesulphonylchloride (54 μl, 0.57 mmol) as starting materials. The reaction was carried out at 0° C.
Reaction SMILES: [CH2:1]([C:5]1[C:6]([CH3:13])=[CH:7][C:8]([C:11]#[N:12])=[N:9][CH:10]=1)[CH:2]([CH3:4])[CH3:3].C(N(CC)CC)C.Cl.[NH2:22][OH:23]>CO>[OH:23][NH:22][C:11]([C:8]1[CH:7]=[C:6]([CH3:13])[C:5]([CH2:1][CH:2]([CH3:4])[CH3:3])=[CH:10][N:9]=1)=[NH:12]
Reactant: NO
Reactant: Cc1cc(C#N)ncc1CC(C)C
Agent: Cl
Solvent: CO
Solvent: CCN(CC)CC
Product: Cc1cc(C(=N)NO)ncc1CC(C)C
Temperature: 75 °C
Reaction time: 18 h
Yield: 123 %

Procedure:
To a solution of 5-isobutyl-4-methyl-pyridine-2-carbonitrile (106 mg, 608 μmol) in methanol (3 mL), triethylamine (123 mg, 1.22 mmol) and hydroxylamine hydrochloride (63 mg, 913 μmol) is added. The mixture is stirred at 75° C. for 18 h before it is concentrated. The residue is dissolved in aq. NaHCO3 (pH 7-8) and extracted with DCM (6×50 mL). The org. extracts are combined, dried over MgSO4, filtered, concentrated and dried to give the title compound (155 mg) as a white solid; LC-MS: tR=0.67 min, [M+1]+=208.01; 1H NMR (CD3OD): δ0.97 (d, J=6.8 Hz, 6H), 1.84-1.96 (m, 1H), 2.37 (s, 3H), 2.58 (d, J=7.3 Hz, 2H), 7.67 (s, 1H), 8.26 (s, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:3]=1[CH2:4][O:5][C@@H:6]1[C@@H:12]([CH2:13][O:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=2[Cl:23])[O:11][C@H:8](OC)[C@:7]1([CH3:25])[OH:24].Br.[Na].[Cl:33][C:34]1[N:39]=[CH:38][NH:37][C:36]2=[N:40][CH:41]=[CH:42][C:35]=12.C(#N)C>ClCCl>[Cl:33][C:34]1[C:35]2[CH:42]=[CH:41][N:40]([C@@H:8]3[O:11][C@H:12]([CH2:13][O:14][CH2:15][C:16]4[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=4[Cl:23])[C@@H:6]([O:5][CH2:4][C:3]4[CH:26]=[CH:27][C:28]([Cl:30])=[CH:29][C:2]=4[Cl:1])[C@@:7]3([CH3:25])[OH:24])[C:36]=2[N:37]=[CH:38][N:39]=1
Reactant: CO[C@H]1O[C@H](COCc2ccc(Cl)cc2Cl)[C@@H](OCc2ccc(Cl)cc2Cl)[C@@]1(C)O
Reactant: Clc1nc[nH]c2nccc1-2
Agent: Br
Agent: [Na]
Solvent: CC#N
Solvent: ClCCl
Product: C[C@@]1(O)[C@H](OCc2ccc(Cl)cc2Cl)[C@@H](COCc2ccc(Cl)cc2Cl)O[C@H]1n1ccc2c(Cl)ncnc21
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of the compound from Step C (9.42 g, 19 mmol) in anhydrous dichloromethane (285 mL) at 0° C. was added HBr (5.7 M in acetic acid, 20 mL, 114 mmol) dropwise. The resulting solution was stirred at 0° C. for 1 h and then at room temperature for 3h, evaporated in vacuo and co-evaporated with anhydrous toluene (3×40 mL). The oily residue was dissolved in anhydrous acetonitrile (50 mL) and added to a solution of sodium salt of 4-chloro-1H-pyrrolo[2,3-d]pyrimidine [for preparation, see J. Chem. Soc., 131 (1960)] in acetonitrile [generated in situ from 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (8.76 g, 57 mmol) in anhydrous acetonitrile (1000 mL), and NaH (60% in mineral oil, 2.28 g, 57 mmol), after 4 h of vigorous stirring at room temperature]. The combined mixture was stirred at room temperature for 24 h, and then evaporated to dryness. The residue was suspended in water (250 mL) and extracted with EtOAc (2×500 mL). The combined extracts were washed with brine (300 mL), dried over Na2SO4, filtered and evaporated. The crude product was purified on a silica gel column (10 cm×10 cm) using ethyl acetate/hexane (1:3 and 1:2) as the eluent. Fractions containing the product were combined and evaporated in vacuo to give the desired product (5.05 g) as a colorless foam.
Reaction SMILES: [CH2:1]1[CH2:8][CH:7]([NH2:9])[C:5](=[O:6])[NH:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[CH3:17][O:18][C:19]1[CH:20]=[CH:21][C:22]2[O:26][C:25]([C:27](Cl)=[O:28])=[CH:24][C:23]=2[CH:30]=1>ClCCl>[CH3:17][O:18][C:19]1[CH:20]=[CH:21][C:22]2[O:26][C:25]([C:27]([NH:9][CH:7]3[CH2:8][CH2:1][CH2:2][CH2:3][NH:4][C:5]3=[O:6])=[O:28])=[CH:24][C:23]=2[CH:30]=1
Reactant: NC1CCCCNC1=O
Reactant: COc1ccc2oc(C(=O)Cl)cc2c1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccc2oc(C(=O)NC3CCCCNC3=O)cc2c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 61.3 %

Procedure:
To a being cooled solution of DL-α-amino-ε-caprolactam (0.83 g) and triethylamine (1.1 ml) in dichloromethane (12 ml), a solution of (5-methoxybenzofuran-2-yl)carbonyl chloride (1.37 g) in dichloromethane (5 ml) was added dropwise below 10° C. After being stirred for 3 hours at ambient temperature, the appeared precipitates was collected by filtration to give DL-α-(5-methoxybenzofuran-2-yl)carbonylamino-ε-caprolactam (1.20 g).
Reaction SMILES: C(OC1CCN([C:11]2[CH:16]=[CH:15][C:14]([B:17]3[O:21][C:20]([CH3:23])([CH3:22])[C:19]([CH3:25])([CH3:24])[O:18]3)=[CH:13][CH:12]=2)CC1)(=O)C.BrC1C=CC([O:31][CH:32]2[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]2)=CC=1>CCOC(C)=O.O>[CH3:38][N:35]1[CH2:36][CH2:37][CH:32]([O:31][C:11]2[CH:12]=[CH:13][C:14]([B:17]3[O:18][C:19]([CH3:24])([CH3:25])[C:20]([CH3:22])([CH3:23])[O:21]3)=[CH:15][CH:16]=2)[CH2:33][CH2:34]1
Reactant: CN1CCC(Oc2ccc(Br)cc2)CC1
Reactant: CC(=O)OC1CCN(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1
Solvent: O
Solvent: CCOC(C)=O
Product: CN1CCC(Oc2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1
Temperature: 25 °C

Procedure:
The title compound was synthesized according to the method described for the synthesis of 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidin-4-yl acetate, except substituting 4-(4-bromophenoxy)-1-methylpiperidine (300 mg, 1.11 mmol). The reaction was then allowed to cool to rt and was diluted with EtOAc and water was added. The resulting mixture was extracted with EtOAc and the combined organic extracts were washed with brine, dried over MgSO4 and concentrated to give the crude product. Crude product was purified by flash chromatography using MeOH/CH2Cl2 (2:98 to 15:85) to give the title compound as a brown solid (200 mg, 57%). 1H NMR (400 MHz, CD3OD) δ 7.68 (d, J=7.6 Hz, 2H), 6.94 (d, J=7.7 Hz, 2H), 4.53 (br s, 1H), 2.94-2.91 (m, 2H), 2.58-2.50 (m, 2H), 2.40 (s, 3H), 2.18-2.00 (m, 2H), 1.93-1.78 (m, 2H), 1.34 (m, 12H); MS ESI 318.1 [M+H]+, calcd for [C18H28BNO3+H]+ 318.22.
Reaction SMILES: [C:1]([O:5][C:6](=[O:17])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14]O)=[CH:10][C:9]=1[CH3:16])([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)[Br:38]>C(Cl)Cl>[C:1]([O:5][C:6](=[O:17])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][Br:38])=[CH:10][C:9]=1[CH3:16])([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1cc(CO)ccc1NC(=O)OC(C)(C)C
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: Cc1cc(CBr)ccc1NC(=O)OC(C)(C)C
Reaction time: 0.5 h
Yield: 36.4 %

Procedure:
The compound (1.035 g) obtained in Example 518 was dissolved in methylene chloride (20 ml) and to the solution, triphenylphosphine (1.38 g) and carbon tetrabromide (1.74 g) were successively added under ice cooling. The reaction mixture was stirred for 30 min under ice cooling, then stirred at room temperature for 30 min and the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent, n-hexane:ethyl acetate=5:1) to give 476.6 mg of the titled compound (yield, 36%).
Reaction SMILES: [NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[CH:5]=[CH:4][C:3]=1[NH2:18].[C:19](O)(=[O:23])[C:20](O)=[O:21].S(=O)(=O)(O)O>CN(C)C=O>[NH:1]1[C:2]2[C:15]3[C:14](=[O:16])[C:13]4[C:8]([C:7](=[O:17])[C:6]=3[CH:5]=[CH:4][C:3]=2[NH:18][C:20](=[O:21])[C:19]1=[O:23])=[CH:9][CH:10]=[CH:11][CH:12]=4
Reactant: O=C(O)C(=O)O
Reactant: Nc1ccc2c(c1N)C(=O)c1ccccc1C2=O
Agent: O=S(=O)(O)O
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)c2c1ccc1[nH]c(=O)c(=O)[nH]c21
Reaction time: 16 h

Procedure:
1,2-Diaminoanthraquinone (1.19 g, 5 mmol) is dissolved in N,N-dimethylformamide (30 mL), and oxalic acid (0.46 g, 5 mmol) and concentrated sulfuric acid (0.1 mL) is added thereinto. After reverse flow for 16 hours, the reacted mixture is transferred into icy water (200 mL) for precipitation. The precipitate is collected and washed by hot alcohol and, so as to obtain the black compound 26, and the production rate is 30%.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1B(O)O.C([O-])([O-])=O.[Cs+].[Cs+].[F:17][C:18]1[CH:26]=[CH:25][CH:24]=[CH:23][C:19]=1[C:20](Cl)=[O:21]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:20]([C:19]1[CH:23]=[CH:24][CH:25]=[CH:26][C:18]=1[F:17])=[O:21]
Reactant: OB(O)c1ccccc1F
Reactant: O=C(Cl)c1ccccc1F
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: Cc1ccccc1
Product: O=C(c1ccccc1F)c1ccccc1F
Temperature: 100 °C
Yield: 48.1 %

Procedure:
To a stirred suspension of 2-fluorobenzeneboronic acid (280 mg, 2 mmol), Cs2CO3 (1.63 g, 5 mmol) and tetrakis(triphenylphosphine)palladium(0) (40 mg, 0.02 mmol) in toluene (35 ml) under nitrogen was added dropwise 2-fluorobenzoyl chloride (634 mg, 4 mmol). The suspension was heated at 100° C. for 16 h, cooled to RT and partitioned between ethyl acetate and water. The organic layer was washed with aqueous potassium hydrogencarbonate solution, brine, dried over sodium sulfate, filtered and evaporated. Purification by flash chromatography afforded the title compound (210 mg, 46%). Colorless liquid.
Reaction SMILES: FC(F)(F)C(O)=O.[CH3:8][C:9]([NH:26]C(=O)OC(C)(C)C)([CH3:25])[CH2:10][CH2:11][N:12]1[C:16]([CH3:17])=[N:15][C:14]([C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)=[N:13]1>ClCCl>[CH3:25][C:9]([NH2:26])([CH3:8])[CH2:10][CH2:11][N:12]1[C:16]([CH3:17])=[N:15][C:14]([C:18]2[CH:19]=[CH:20][C:21]([CH3:24])=[CH:22][CH:23]=2)=[N:13]1
Reactant: Cc1ccc(-c2nc(C)n(CCC(C)(C)NC(=O)OC(C)(C)C)n2)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1ccc(-c2nc(C)n(CCC(C)(C)N)n2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A total of 11 mL trifluoroacetic acid are added dropwise to a solution of 2.97 g (8.3 mmol) of tert.butyl [1,1-dimethyl-3-(5-methyl-3-p-tolyl-[1,2,4]triazol-1-yl)-propyl]-carbamate in 80 mL dichloromethane and the mixture is stirred overnight at ambient temperature. The solvent is distilled off and the residue is combined with diethyl ether and stirred. The precipitated solid is filtered off and washed. Yield: 2.11 g (68%, trifluoroacetate); mass spectroscopy [M+H]+=259.
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[C:8](=O)([O:16]C1C=CC([N+]([O-])=O)=CC=1)[O:9][CH2:10][CH2:11][Si:12]([CH3:15])([CH3:14])[CH3:13].C(N(CC)C(C)C)(C)C>C1COCC1>[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:9][CH2:10][CH2:11][Si:12]([CH3:15])([CH3:14])[CH3:13])=[O:16])[CH2:4][CH2:3]1
Reactant: C[Si](C)(C)CCOC(=O)Oc1ccc([N+](=O)[O-])cc1
Reactant: OC1CCNCC1
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: C[Si](C)(C)CCOC(=O)N1CCC(O)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
6.9 g of 4-hydroxypiperidine were dissolved in 150 ml of THF. 19.4 g of 2-(trimethylsilyl)ethyl 4-nitrophenyl carbonate and 11.9 ml of N,N-diisopropylethylamine were successively added thereto. The mixture was stirred at room temperature for 1 h and then the solvent was removed in vacuo. The residue was taken up in 400 ml of ethyl acetate and washed once with 200 ml of 0.5 N HCl and twice with 200 ml of 1 N NaOH each time. The organic phase was dried with MgSO4, the solvent was removed in vacuo, and the residue was purified by chromatography on silica gel.
Reaction SMILES: [CH:1]1[C:11]2[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[CH2:8][N:7]([C:16](=[NH:20])[O:17][CH2:18][CH3:19])[CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[C:21]1([S:27](Cl)(=[O:29])=[O:28])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>>[C:21]1([S:27]([N:20]=[C:16]([N:7]2[CH2:6][C:5]3[CH:4]=[CH:3][CH:2]=[CH:1][C:11]=3[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[CH2:8]2)[O:17][CH2:18][CH3:19])(=[O:29])=[O:28])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: CCOC(=N)N1Cc2ccccc2-c2ccccc2C1
Product: CCOC(=NS(=O)(=O)c1ccccc1)N1Cc2ccccc2-c2ccccc2C1

Procedure:
starting from ethyl 5,7-dihydro-6H-dibenz[c,e]azepine-6-carboximidate and benzenesulfonyl chloride, there is obtained ethyl N-(phenylsulfonyl)-5,7-dihydro-6H-dibenz[c,e]azepine-6-carboximidate, m.p. 145.5°-149.5° C.
Reaction SMILES: [C:1]1([C@@H:7]([OH:9])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N+:29]([C:32]1[CH:40]=[CH:39][C:35]([C:36](O)=[O:37])=[CH:34][CH:33]=1)([O-:31])=[O:30].COCCOC(N=NC(OCCOC)=O)=O>C1COCC1.O>[N+:29]([C:32]1[CH:33]=[CH:34][C:35]([C:36]([O:9][C@@H:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH3:8])=[O:37])=[CH:39][CH:40]=1)([O-:31])=[O:30].[C:1]1([C@@H:7]([OH:9])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1
Agent: COCCOC(=O)N=NC(=O)OCCOC
Agent: C[C@H](O)c1ccccc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: C1CCOC1
Product: C[C@@H](OC(=O)c1ccc([N+](=O)[O-])cc1)c1ccccc1
Reaction time: 4 h

Procedure:
After (S)-1-phenylethyl alcohol (300 mg, 2.46 mmol), triphenylphosphine (771 mg, 2.95 mmol), 4-nitrobenzoic acid (494 mg, 2.95 mmol), and THF (12 ml) were added to a 50 ml flask, azodicarboxylic acid bis(2-methoxyethyl) ester (691 mg, 2.95 mmol) dissolved in THF (6 ml) was added dropwise thereto at 20° C., and the reaction was allowed to proceed for four hours. Water (0.5 mL) was added, and concentration was carried out. Then, water (10 ml) was added to the solution, and extraction was carried out using diethyl ether (10 ml,×2). Then, the organic layer was washed with water (10 mL) and saturated salt water (10 ml), and dehumidified with anhydrous magnesium sulfate. Subsequently, a crude product obtained by concentration was purified by column chromatography (silica gel, 5% ethyl acetate-hexane solution) to give (R)-1-(4-nitrobenzoyloxy)-1-phenylethane as a pale yellow liquid substance (559 mg, yield: 84%/(S)-1-phenylethyl alcohol).
Reaction SMILES: [H-].[Na+].[CH:3]1([S:6]([NH2:9])(=[O:8])=[O:7])[CH2:5][CH2:4]1.[CH:10]([C@@H:13]1[CH2:17][O:16][C:15](=[O:18])[N:14]1[C:19]1[CH:20]=[C:21]([CH:25]2[C:34]([CH3:36])([CH3:35])[CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[C:30]([C:37](O)=[O:38])[CH:31]=3)[NH:26]2)[CH:22]=[CH:23][CH:24]=1)([CH3:12])[CH3:11].C(N1C=CN=C1)(N1C=CN=C1)=O>CN(C)C=O>[CH:10]([C@@H:13]1[CH2:17][O:16][C:15](=[O:18])[N:14]1[C:19]1[CH:20]=[C:21]([CH:25]2[C:34]([CH3:36])([CH3:35])[CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[C:30]([C:37]([NH:9][S:6]([CH:3]4[CH2:5][CH2:4]4)(=[O:8])=[O:7])=[O:38])[CH:31]=3)[NH:26]2)[CH:22]=[CH:23][CH:24]=1)([CH3:12])[CH3:11]
Reactant: NS(=O)(=O)C1CC1
Reactant: CC(C)[C@@H]1COC(=O)N1c1cccc(C2Nc3ccc(C(=O)O)cc3CC2(C)C)c1
Agent: O=C(n1ccnc1)n1ccnc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)[C@@H]1COC(=O)N1c1cccc(C2Nc3ccc(C(=O)NS(=O)(=O)C4CC4)cc3CC2(C)C)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 19.8 %

Procedure:
To a suspension of 60% sodium hydride (290 mg, 7.3 mmol) in N,N-dimethylformamide (2.5 mL) was added cyclopropanesulfonamide (895 mg, 7.4 mmol) at room temperature. The resulting mixture was stirred at 25° C. for 1 h. A solution of 2-[3-((R)-4-isopropyl-2-oxo-oxazolidin-3-yl)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (300 mg, 0.74 mmol) and 1,1′-carbonyldiimidazole (300 mg, 1.84 mmol) in N,N-dimethylformamide (2.0 mL) was stirred at 70° C. After stirring at 70° C. for 1 h, the above suspension of cyclopropanesulfonamide and sodium hydride in N,N-dimethylformamide was added and the mixture was allowed to stir at 25° C. for 1 h. Purification by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded cyclopropanesulfonic acid {2-[3-((R)4-isopropyl-2-oxo-oxazolidin-3-yl)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carbonyl}-amide (75 mg, 20%) as a white solid: LC/MS m/e calcd for C27H33N3O5S (M+H)+: 512.65, observed: 512.1.