Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([OH:9])=[C:4]([Cl:10])[CH:3]=1.[C:11]([O-])([O-])=O.[K+].[K+].CI>CN(C=O)C>[Br:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH3:11])=[C:4]([Cl:10])[CH:3]=1
Reactant: Oc1c(Cl)cc(Br)cc1Cl
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Product: COc1c(Cl)cc(Br)cc1Cl
Temperature: 25 °C
Reaction time: 16 h
Yield: 84.4 %

Procedure:
A mixture of 4-bromo-2,6-dichlorophenol (10 g, 41.67 mmol), K2CO3 (11.5 g, 83.3 mmol) and CH3I (8.88 g, 62.5 mmol) in DMF (100 mL) was stirred at rt for 16 h. TLC (EtOAc/petroleum ether=1:2) indicated complete consumption of 4-bromo-2,6-dichlorophenol. The reaction mixture was poured into water (300 mL). The aqueous phase was extracted with EtOAc (2×100 mL). The combined organic phases were dried over anhydrous Na2SO4, and concentrated in vacuo to give crude 5-bromo-1,3-dichloro-2-methoxybenzene, which was purified by column chromatography (silica gel, EtOAc/petroleum ether=1:5) to yield the ether product (9 g, yield 84.9%) as a white solid. 1H NMR (400 MHz, CDCl3): δ 7.45 (s, H), 3.91 (s, 3H) ppm.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][C:3]=1[OH:12].C(=O)([O-])[O-].[K+].[K+].[CH:19](I)([CH3:21])[CH3:20].O>CN(C)C=O>[CH:19]([O:12][C:3]1[CH:4]=[C:5]([N+:9]([O-:11])=[O:10])[C:6]([F:8])=[CH:7][C:2]=1[Br:1])([CH3:21])[CH3:20]
Reactant: CC(C)I
Reactant: O=[N+]([O-])c1cc(O)c(Br)cc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)Oc1cc([N+](=O)[O-])c(F)cc1Br
Temperature: 50 °C
Reaction time: 1 h
Yield: 85.7 %

Procedure:
Then, 100 g (0.42 mol) of 2-bromo-4-fluoro-5-nitrophenol was dissolved in 400 ml of dimethylformamide, to which 70 g (0.50 mol) of potassium carbonate was added and after warming to 50° C., 94 g (0.55 mol) of isopropyl iodide was added dropwise, and the mixture was stirred at 45° to 50° C. for 1 hour. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer was washed with water and then with diluted hydrochloric acid, dried, and concentrated. The residue was subjected to column chromatography, which afforded 99.8 g (0.36 mol) of 2-bromo-4-fluoro-5-nitrophenyl isopropyl ether.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Mg]Br)=[CH:4][CH:3]=1.Cl[Si:11]1([CH2:16][Cl:17])[CH2:15][CH2:14][CH2:13][CH2:12]1>>[Cl:17][CH2:16][Si:11]1([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[CH2:15][CH2:14][CH2:13][CH2:12]1
Reactant: ClC[Si]1(Cl)CCCC1
Reactant: Clc1ccc([Mg]Br)cc1
Product: ClC[Si]1(c2ccc(Cl)cc2)CCCC1

Procedure:
In the same apparatus and procedures as Example 1 was reacted 83 ml of 4-chlorophenylmagnesiumbromide solution (1.0 M in diethylether) with 1-chloro-1-chloromethyl-1-silacyclopentane prepared from the above procedure i) for 5 hrs. In the same method as Example 1 was treated the reaction product to give 5.20 g of 1-chloromethyl-1-(4-chlorophenyl)-1-silacyclopentane (b.p. 108°-110° C./0.5 mmHg).
Reaction SMILES: Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[N:4](C2CCCCO2)[N:3]=1.[O:19]1[C:24]2[CH:25]=[CH:26][C:27](B(O)O)=[CH:28][C:23]=2[O:22][CH2:21][CH2:20]1.ClCCl.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl>COCCOC.O.CO>[O:19]1[C:24]2[CH:25]=[CH:26][C:27]([C:2]3[C:10]4[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=4)[NH:4][N:3]=3)=[CH:28][C:23]=2[O:22][CH2:21][CH2:20]1
Reactant: OB(O)c1ccc2c(c1)OCCO2
Reactant: N#Cc1ccc2c(c1)c(Br)nn2C1CCCCO1
Agent: Cl
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: COCCOC
Solvent: O
Product: N#Cc1ccc2[nH]nc(-c3ccc4c(c3)OCCO4)c2c1
Temperature: 45 °C
Yield: 72.1 %

Procedure:
The title compound was prepared using 3-bromo-1-perhydro-2H-pyran-2-yl-1H-indazole-5-carbonitrile (0.354 g, 1.15 mmol), in ethylene glycol dimethyl ether (20 mL), 2H,3H-benzo[e]1,4-dioxin-6-boronic acid (0.250 g, 1.39 mmol), [1,1′-bis(diphenyl phosphino-ferrocene] complex with dichloromethane (1:1) (0.094 g, 0.11 mmol) and potassium phosphate (2.40 g, 11.5 mmol). Solvent was removed using a rotary evaporator and purification of the residue by column chromatography (silica gel, 20% ethyl acetate/hexanes) gave a solid. Methanol (30 mL) and aqueous 6 N hydrochloric acid (30 mL) were added to the solid and the mixture was heated at 45° C. for 5 h. Water (30 mL) was added and the solid was filtered and dried in a vacuum oven to afford the title compound (0.230 g, 71% yield over 2 steps): ES-MS (m/z) 278 [M+1]+.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([N:10]3[CH2:15][CH2:14][CH:13]([O:16][CH2:17][C@@H:18]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH3:19])[CH2:12][CH2:11]3)=[N:7][C:6]=2[CH:28]=1.Br[CH2:30][CH2:31][CH3:32]>>[CH3:19][C@H:18]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:24])([CH3:26])[CH3:25])[CH2:17][O:16][CH:13]1[CH2:14][CH2:15][N:10]([C:8]2[O:9][C:5]3[CH:4]=[CH:3][C:2]([O:1][CH2:30][CH2:31][CH3:32])=[CH:28][C:6]=3[N:7]=2)[CH2:11][CH2:12]1
Reactant: CCCBr
Reactant: C[C@@H](COC1CCN(c2nc3cc(O)ccc3o2)CC1)NC(=O)OC(C)(C)C
Product: CCCOc1ccc2oc(N3CCC(OC[C@H](C)NC(=O)OC(C)(C)C)CC3)nc2c1

Procedure:
By a method similar to Example 6, step A, and using tert-butyl [(1S)-2-{[1-(5-hydroxy-1,3-benzoxazol-2-yl)piperidin-4-yl]oxy}-1-methylethyl]carbamate (412 mg) and 1-bromopropane (0.282 mL), the title compound (367 mg) was obtained.
Reaction SMILES: N[C:2]1[C:3]([CH3:15])=[CH:4][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[N:6][CH:7]=1.N(OCCC(C)C)=O.[I:24]CI>>[I:24][C:2]1[C:3]([CH3:15])=[CH:4][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[N:6][CH:7]=1
Reactant: Cc1cc(NC(=O)C(C)(C)C)ncc1N
Reactant: ICI
Agent: CC(C)CCON=O
Product: Cc1cc(NC(=O)C(C)(C)C)ncc1I
Temperature: 85 °C

Procedure:
A mixture of 5-amino-4-methyl-2-(trimethylacetyl)aminopyridine (1.0 g, 4.82 mmol) in 34 mL of diiodomethane containing isoamyl nitrite (4.0 mL, 29.77 mmol) was heated at 85° C. for 0.5 h, cooled to room temperature and evaporated at 60° C. under high vacuum to give a red semi-solid. The crude material was purified by silica gel column chromatography using 10% ether/hexane as eluant to give the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[O:9][C:10]2[C:15]([C:16](=[O:18])[CH:17]=1)=[C:14]([O:19]C)[CH:13]=[C:12]([O:21]C)[C:11]=2[C@@H:23]1[CH2:27][CH2:26][N:25]([CH3:28])[C@H:24]1[CH2:29][OH:30].Cl>CO>[ClH:1].[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[O:9][C:10]2[C:15]([C:16](=[O:18])[CH:17]=1)=[C:14]([OH:19])[CH:13]=[C:12]([OH:21])[C:11]=2[C@@H:23]1[CH2:27][CH2:26][N:25]([CH3:28])[C@H:24]1[CH2:29][OH:30]
Reactant: COc1cc(OC)c2c(=O)cc(-c3ccccc3Cl)oc2c1[C@@H]1CCN(C)[C@H]1CO
Agent: Cl
Solvent: CO
Product: CN1CC[C@@H](c2c(O)cc(O)c3c(=O)cc(-c4ccccc4Cl)oc23)[C@@H]1CO

Procedure:
(+)-trans-2-(2-Chlorophenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one (0.2 g, 0.48 mmol) was suspended in methanol (2 mL) and ethereal HCl (5 mL) was added. The suspension was stirred to get a clear solution. The solution was concentrated under reduced pressure to obtain the title compound.
Reaction SMILES: [CH2:1]([C@H:3]1[N:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[C@@H:4]1[C:13]([O:15][CH3:16])=[O:14])[CH3:2].[CH3:17][C@@H:18]([OH:23])[CH2:19][CH2:20][CH:21]=[CH2:22].B(F)(F)F.O(CC)CC>C(Cl)Cl>[C:9]([O:8][C:6]([NH:5][C@@H:4]([C@@H:3]([O:23][C@@H:18]([CH2:19][CH2:20][CH:21]=[CH2:22])[CH3:17])[CH2:1][CH3:2])[C:13]([O:15][CH3:16])=[O:14])=[O:7])([CH3:12])([CH3:11])[CH3:10]
Reactant: CC[C@@H]1[C@@H](C(=O)OC)N1C(=O)OC(C)(C)C
Reactant: C=CCC[C@@H](C)O
Agent: FB(F)F
Solvent: CCOCC
Solvent: ClCCl
Product: C=CCC[C@@H](C)O[C@@H](CC)[C@H](NC(=O)OC(C)(C)C)C(=O)OC
Temperature: 25 °C
Reaction time: 16 h
Yield: 42.8 %

Procedure:
To a round-bottom flask equipped with a stir bar was added (2S,3R)-1-tert-butyl 2-methyl 3-ethylaziridine-1,2-dicarboxylate (691, 3.02 mmol) and CH2Cl2 (12 mL). To the solution was added (R)-hex-5-en-2-ol (363 mg, 3.62 mmol), then BF3-OEt2 (1.0M in CH2Cl2, 0.30 mL). The solution was stirred at room temperature for 16 h. The solution was transfered to a separatory funnel and was diluted with CH2Cl2, then the solution was washed with aq. saturated NaHCO3; then brine. The organic phase was dried over Na2SO4; filtered; then concentrated in vacuo. The resulting residue was subjected to silica gel chromatography (hexanes:EtOAc 90:10 to 70:30) to afford (2S,3S)-methyl 2-((tert-butoxycarbonyl)amino)-3-((R)-hex-5-en-2-yloxy)pentanoate as a colorless oil (426 mg, 43%). 1H-NMR (500 MHz, CDCl3) δ 5.81 (ddt, J=17.0, 10.4, 6.5 Hz, 1H), 5.19 (d, J=7.7 Hz, 1H), 5.08-5.00 (m, 1H), 4.96 (dd, J=10.2, 1.7 Hz, 1H), 4.50 (dd, J=8.3, 3.5 Hz, 1H), 3.75 (s, 3H), 3.65-3.58 (m, 1H), 3.57-3.50 (m, 1H), 2.19-2.06 (m, 2H), 1.66-1.56 (m, 2H), 1.55-1.38 (m, 11H), 1.13 (d, J=6.1 Hz, 3H), 0.97 (t, J=7.3 Hz, 3H).
Reaction SMILES: [CH3:1][N:2]([CH3:9])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C1N([N+:16]([O-:18])=[O:17])CN([N+]([O-])=O)CN1[N+]([O-])=O.C(O[N+]([O-])=O)C(CO[N+]([O-])=O)(CO[N+]([O-])=O)CO[N+]([O-])=O>>[CH3:1][N:2]([CH3:9])[C:3]1[CH:8]=[CH:7][C:6]([N+:16]([O-:18])=[O:17])=[CH:5][CH:4]=1
Reactant: O=[N+]([O-])N1CN([N+](=O)[O-])CN([N+](=O)[O-])C1
Reactant: CN(C)c1ccccc1
Agent: O=[N+]([O-])OCC(CO[N+](=O)[O-])(CO[N+](=O)[O-])CO[N+](=O)[O-]
Product: CN(C)c1ccc([N+](=O)[O-])cc1

Procedure:
Considering the electrophilic nature of the NOx species generated by the photofragmentation of RDX and PETN and their resemblance to the active electrophiles in aromatic nitration reactions, reactions between electron-rich tertiary aromatic amines and the photofragments of RDX and PETN were selected. It was found that photolysis (λ=313 nm) of a mixture of N,N-dimethylaniline (DMA) and 2 equivalents of either RDX or PETN for 10 minutes in acetonitrile under anaerobic conditions afforded the formation of N,N-dimethyl-4-nitroaniline (DMNA) in 14% yield (GC yield). Higher yields of DMNA were obtained with longer photolysis times and DMNA was formed in ca. 80% yield after 1 hour. The photoreaction between DMA and either RDX or PETN under anaerobic conditions was observed to produce only a single, yellow-colored product (DMNA) and other side products were not evident by TLC or GC-MS analyses. The 1H-NMR, IR and high-resolution mass spectra of the isolated yellow product matched those obtained for an authentic commercial sample of DMNA. Conducting the photolysis under aerobic conditions resulted in partial demethylation of DMA and yielded a mixture of DMNA and its demethylated analog, N-methyl-4-nitroaniline (13) (see Scheme 1). Photolysis of DMA with ammonium nitrate was also found to produce DMNA, although relatively longer photolysis times (>30 minutes) were required and greater amounts of demethylated side products were observed (possibly due to the presence of water or other nucleophiles in the solutions).
Reaction SMILES: [Cl:1][C:2]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:3]=1[C:4]([CH:6]1[C:11](=[O:12])[CH2:10][CH2:9][CH2:8][C:7]1=[O:13])=[O:5].[N+](=[CH2:21])=[N-].CC1C=CC(S(N(N=O)C)(=O)=O)=CC=1>CCOCC>[CH3:21][O:12][C:11]1[CH2:10][CH2:9][CH2:8][C:7](=[O:13])[C:6]=1[C:4](=[O:5])[C:3]1[CH:14]=[CH:15][C:16]([Cl:18])=[CH:17][C:2]=1[Cl:1]
Reactant: O=C1CCCC(=O)C1C(=O)c1ccc(Cl)cc1Cl
Reactant: C=[N+]=[N-]
Agent: Cc1ccc(S(=O)(=O)N(C)N=O)cc1
Solvent: CCOCC
Product: COC1=C(C(=O)c2ccc(Cl)cc2Cl)C(=O)CCC1
Yield: 35 %

Procedure:
2-(2,4-Dichlorobenzoyl)cyclohexane-1,3-dione (2.85 g, 0.01 mol) was stirred as a suspension in 25 ml anhydrous ether. Diazomethane, generated from Diazald® (50 ml, 0.02 mol) was added at 0° at a rate slow enough to control effervescence. The resulting solution was stirred for an hour and the solvent allowed to evaporated under a stream of nitrogen in a beaker. The resulting oil was dissolved in ether and washed twice with saturated aqueous K2CO3. Evaporation of the solvent under reduced pressure yielded a solid (1.0 g, 35%, m.p. 81°-86° C.), the nuclear magnetic, infrared and mass spectra of which were consistent with the structure.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:7]([O:18][CH3:19])=[CH:6][C:3]=1[C:4]#[N:5].CO[CH:22](OC)[N:23]([CH3:25])[CH3:24]>C1(C)C=CC=CC=1>[CH2:11]([O:10][C:8]1[C:7]([O:18][CH3:19])=[CH:6][C:3]([C:4]#[N:5])=[C:2]([N:1]=[CH:22][N:23]([CH3:25])[CH3:24])[CH:9]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: COC(OC)N(C)C
Reactant: COc1cc(C#N)c(N)cc1OCc1ccccc1
Solvent: Cc1ccccc1
Product: COc1cc(C#N)c(N=CN(C)C)cc1OCc1ccccc1
Temperature: 105 °C
Yield: 90.2 %

Procedure:
2-amino-4-(benzyloxy)-5-methoxybenzonitrile (100 g, 394 mmol) in toluene (1400 ml) was treated with dimethylformamide dimethylacetal (100 ml, 940 mmol) at reflux with slow distillation of solvent to maintain the internal temperature at 105° C. After 3 hours the solution was cooled and filtered to remove a small amount of solid. The filtrate was evaporated in vacuo, the residue triturated with diethyl ether, the solid collected by suction filtration and dried in vacuo to yield N′-(5-(benzyloxy)-2-cyano-4-methoxyphenyl)-N,N-dimethylimidoformamide (110 g, 90% yield) as a brown solid:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[C:11]([NH:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][N:20]3[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)[CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[CH3:26].Cl[CH2:28][CH:29]([OH:32])[CH2:30][OH:31].C(N(CC)CC)C>C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[C:11]([NH:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][N:20]3[CH2:21][CH2:22][N:23]([CH2:28][CH:29]([OH:32])[CH2:30][OH:31])[CH2:24][CH2:25]3)[CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[CH3:26]
Reactant: COc1cc(NCCCCCCN2CCNCC2)c2nccc(C)c2c1
Reactant: OCC(O)CCl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: COc1cc(NCCCCCCN2CCN(CC(O)CO)CC2)c2nccc(C)c2c1
Yield: 20.3 %

Procedure:
A mixture of 3 g (0.008 mole) of 6-methoxy-4-methyl-N-[6-(1-piperazinyl)hexyl]-8-quinolinamine (Example 1) and 0.72 ml (0.008 mole) of 3-chloro-1,2-propanediol was heated at 120° for 2 hours. An additional 0.2 ml of 3-chloro-1,2-propanediol and 1 ml of triethylamine were added and the mixture was heated at 130° for 3 hr and allowed to cool. The reaction mixture was diluted with ethyl acetate, washed with water and saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and concentrated to dryness in vacuo. The residual oil was chromatographed over 200 g of silica gel, eluting first with one liter of a 1:15:84 mixture of triethylamine:methanol:ethyl acetate and then with a 1:20:79 mixture of the same solvents. That portion of the eluant containing fairly pure product Rf (silica--25 parts of methanol:75 parts of ethyl acetate:1 part of triethylamine)=0.26 was concentrated to dryness, taken up in 2-propanol and treated with an excess of a 17% solution of hydrogen chloride in 2-propanol to afford 0.7 g of product. That portion of the eluant containing contaminated product was concentrated and rechromatographed over 50 g of silica with a 1:15:84 mixture of triethyl amine:methanol:ethyl acetate and the product was isolated as described above. The two crops were combined and recrystallized from ethanol to afford 1.0 g (23%) of the title compound, mp. 237°-241° (dec) with prior sintering.
Reaction SMILES: CS(O[C:6]1[CH:11]=[CH:10][C:9]([Br:12])=[CH:8][C:7]=1[CH:13]([CH3:15])[CH3:14])(=O)=O.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.CS(C)=O.[C:56]([O:59][CH2:60]C)(=[O:58])C>CO.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[Br:12][C:9]1[CH:10]=[CH:11][C:6]([C:56]([O:59][CH3:60])=[O:58])=[C:7]([CH:13]([CH3:15])[CH3:14])[CH:8]=1
Reactant: CCOC(C)=O
Reactant: CC(C)c1cc(Br)ccc1OS(C)(=O)=O
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(CCCP(c2ccccc2)c2ccccc2)c2ccccc2)cc1
Solvent: CO
Solvent: CS(C)=O
Solvent: O
Product: COC(=O)c1ccc(Br)cc1C(C)C
Temperature: 55 °C
Reaction time: 8 h

Procedure:
A mixture of 4-bromo-2-isopropylphenyl methanesulfonate (0.71 g), palladium acetate (0.023 g), 1,3-bis(diphenyl-phosphino)propane (0.042 g) and triethylamine (0.63 mL) in methanol (6 mL)/dimethylsulfoxide (9 mL) was stirred overnight at 55° C. under an atmosphere of carbon monoxide. Water and ethyl acetate were added to the reaction mixture. The organic layer was separated, washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: diethyl ether/n-hexane=1/10) to afford the title compound (0.355 g).
Reaction SMILES: [OH-].[K+].[F:3][C:4]([F:49])([F:48])[C:5]1[CH:6]=[C:7]([C@H:15]2[O:19][C:18](=[O:20])[N:17]([CH2:21][C:22]3[C:27]([N:28]([CH2:31][C@H:32]4[CH2:37][CH2:36][C@H:35]([CH2:38][C:39]([O:41]CC)=[O:40])[CH2:34][CH2:33]4)[CH2:29][CH3:30])=[CH:26][CH:25]=[C:24]([C:44]([CH3:46])=[CH2:45])[N:23]=3)[C@H:16]2[CH3:47])[CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1.Cl.CC(O)=O>CCO.O.[Cl-].[Na+].O>[F:48][C:4]([F:3])([F:49])[C:5]1[CH:6]=[C:7]([C@H:15]2[O:19][C:18](=[O:20])[N:17]([CH2:21][C:22]3[C:27]([N:28]([CH2:31][C@H:32]4[CH2:37][CH2:36][C@H:35]([CH2:38][C:39]([OH:41])=[O:40])[CH2:34][CH2:33]4)[CH2:29][CH3:30])=[CH:26][CH:25]=[C:24]([C:44]([CH3:46])=[CH2:45])[N:23]=3)[C@H:16]2[CH3:47])[CH:8]=[C:9]([C:11]([F:13])([F:14])[F:12])[CH:10]=1
Reactant: C=C(C)c1ccc(N(CC)C[C@H]2CC[C@H](CC(=O)OCC)CC2)c(CN2C(=O)O[C@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)[C@@H]2C)n1
Agent: Cl
Agent: [Cl-]
Agent: [K+]
Solvent: O
Solvent: CC(=O)O
Solvent: CCO
Product: C=C(C)c1ccc(N(CC)C[C@H]2CC[C@H](CC(=O)O)CC2)c(CN2C(=O)O[C@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)[C@@H]2C)n1

Procedure:
Aqueous potassium hydroxide (4N, 100 μL) was added to a stirred solution of ethyl (trans-4-{[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-isopropenylpyridin-3-yl](ethyl)amino]methyl}cyclohexyl)acetate (7.3 mg, 0.0109 mmol) in EtOH (0.9 mL) and water (0.35 mL) at room temperature. After 8 h the reaction was acidified to pH 5 with 1 N HCl and then diluted with brine (10 mL). The mixture was extracted with EtOAc (3×20 mL) and the combined extracts were dried (Na2SO4) and concentrated in vacuo to afford the crude product. This was purified by flash chromatography (Si, 12×160 mm, 1% AcOH, 0-65% EtOAc in hexanes gradient) to afford (trans)-4-{[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyridin-3-yl](ethyl)amino]methyl}cyclohexyl)acetic acid. Rf=0.59 (1% AcOH, 1:2 EtOAc/hexanes). LCMS calc.=642.3; found=642.2 (M+1)+. 1H NMR (500 MHz, CDCl3): δ 7.87 (s, 1H); 7.78 (s, 2 H); 7.40 (s, 2 H); 5.85 (s, 1 H); 5.75 (d, J=8.6 Hz, 1 H); 5.25 (s, 1 H); 4.97 (d, J=16.7 Hz, 1 H); 4.43-4.35 (m, 2 H); 2.98-2.90 (m, 2 H); 2.84 (dd, J=8.5, 12.9 Hz, 1 H); 2.76 (dd, J=7.4, 12.9 Hz, 1 H); 2.20 (br s, 5 H); 1.80-1.64 (m, 5 H); 1.35-1.24 (m, 1 H); 0.99 (t, J=7.0 Hz, 3 H); 0.95-0.83 (m, 4 H); 0.72 (d, J=6.6 Hz, 3 H).
Reaction SMILES: C[O:2][C:3](=[O:31])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8]([O:27][CH:28]([F:30])[F:29])=[C:9]([CH2:19][C:20]1[CH:25]=[CH:24][C:23](Br)=[CH:22][CH:21]=1)[C:10]([CH2:17][CH3:18])=[N:11]2.[CH:32]([N:35]1[CH:39]=[CH:38][C:37](B2OC(C)(C)C(C)(C)O2)=[N:36]1)([CH3:34])[CH3:33].C(=O)([O-])[O-].[Cs+].[Cs+].Cl>CN(C)C=O>[F:30][CH:28]([F:29])[O:27][C:8]1[C:7]2[C:12](=[C:13]([F:16])[CH:14]=[CH:15][C:6]=2[O:5][CH2:4][C:3]([OH:2])=[O:31])[N:11]=[C:10]([CH2:17][CH3:18])[C:9]=1[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:37]2[CH:38]=[CH:39][N:35]([CH:32]([CH3:34])[CH3:33])[N:36]=2)=[CH:22][CH:21]=1
Reactant: CCc1nc2c(F)ccc(OCC(=O)OC)c2c(OC(F)F)c1Cc1ccc(Br)cc1
Reactant: CC(C)n1ccc(B2OC(C)(C)C(C)(C)O2)n1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CCc1nc2c(F)ccc(OCC(=O)O)c2c(OC(F)F)c1Cc1ccc(-c2ccn(C(C)C)n2)cc1
Temperature: 140 °C
Yield: 27.2 %

Procedure:
A mixture of [3-(4-bromobenzyl)-4-difluoromethoxy-2-ethyl-8-fluoroquinolin-5-yloxy]acetic acid methyl ester (0.05 g), 1-isopropyl-3-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.047 g), tetrakis(triphenylphospine)palladium (0) (0.012 g), N,N-dimethylformamide (0.3 mL) and 2.0 M aqueous cesium carbonate solution (0.2 mL) was heated by microwave irradiation at 140° C. for 6 minutes. The mixture was cooled to room temperature, acidified by the addition of 1.0 M aqueous hydrochloric acid solution and then extracted with ethyl acetate. The combined extracts were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and then concentrated under reduced pressure. Purification of the residue by preparative reverse-phase HPLC gave title compound (0.014 g).
Reaction SMILES: Br[C:2]([F:26])([F:25])[C:3](F)([F:23])[O:4][C:5]1[CH:6]=[C:7]([S:19]([F:22])(=[O:21])=[O:20])[CH:8]=[C:9]([O:11][C:12](F)([F:17])[C:13]([F:16])([F:15])Br)[CH:10]=1.C(#N)C>[Cu]Cl.[Zn].C(Cl)Cl>[F:23][C:3]([O:4][C:5]1[CH:6]=[C:7]([S:19]([F:22])(=[O:21])=[O:20])[CH:8]=[C:9]([O:11][C:12]([F:17])=[C:13]([F:16])[F:15])[CH:10]=1)=[C:2]([F:26])[F:25]
Reactant: O=S(=O)(F)c1cc(OC(F)(F)C(F)(F)Br)cc(OC(F)(F)C(F)(F)Br)c1
Agent: Cl[Cu]
Agent: [Zn]
Solvent: CC#N
Solvent: ClCCl
Product: O=S(=O)(F)c1cc(OC(F)=C(F)F)cc(OC(F)=C(F)F)c1
Temperature: 110 °C
Reaction time: 48 h
Yield: 72.2 %

Procedure:
Into a 100 mL round bottom flask in a dry box were placed 5.41 g of the 3,5-di(2-bromotetrafluoroethoxy)benzenesulfonyl fluoride, 0.5 g (0.005 mol) of copper(I) chloride and 0.65 g (0.01 mol) of activated zinc powder. Then 15 mL of well-dried acetonitrile was added to the flask. The mixture was stirred at 110° C. under dry nitrogen gas for 2 days, followed by taking a sample for 19F NMR to monitor the progress of the reaction. The spectrum of this sample showed that all of starting material had converted. After being cooled to room temperature, 75 mL of methylene chloride was added to the flask and the organic layer was stirred at room temperature overnight followed by filtration to remove the salt. The combined organic layer was washed with saturated sodium chloride water solution in a 500 mL separatory funnel three times and dried over sodium sulfate overnight. After the removal of the drying agent, the filtrate was refluxed with 5 g of active carbon for 1 day. After being cooled down to room temperature, the mixture was filtered to remove active carbon and the solvents were evaporated off under the reduced pressure. The crude product was purified first by recrystallization and then by column chromatography (silica gel, 70-230 mesh) using 2 parts by volume of petroleum ether to 1 part by volume of chloroform. A total of 2.5 g of 3,5-di(trifluorovinyloxy)benzenesulfonyl fluoride product was obtained as a transparent liquid in about 50% yield.
Reaction SMILES: [C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:9]=1[NH2:15])([CH3:4])([CH3:3])[CH3:2].C([O:21][C:22](=O)[CH2:23][C:24](=[O:37])[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([C:31]2[CH:32]=[N:33][CH:34]=[N:35][CH:36]=2)[CH:26]=1)(C)(C)C>>[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:9]=1[NH:15][C:22](=[O:21])[CH2:23][C:24](=[O:37])[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([C:31]2[CH:36]=[N:35][CH:34]=[N:33][CH:32]=2)[CH:26]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)CC(=O)c1cccc(-c2cncnc2)c1
Reactant: CC(C)(C)OC(=O)Nc1ccc(Cl)cc1N
Product: CC(C)(C)OC(=O)Nc1ccc(Cl)cc1NC(=O)CC(=O)c1cccc(-c2cncnc2)c1

Procedure:
The title compound was prepared from (2-amino-4-chloro-phenyl)-carbamic acid tert-butyl ester (Example J4) (243 mg, 1.0 mmol) and 3-oxo-3-(3-pyrimidin-5-yl-phenyl)-propionic acid tert-butyl ester (Example K13) (298 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown solid (350 mg, 75%).