Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[C:6](B2OC(C)(C)C(C)(C)O2)=[C:5]([CH3:16])[NH:4][N:3]=1.[CH2:17]([N:24]([CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C@@H:25]1[CH2:34][CH2:33][C:32]2[C:27](=[C:28](Br)[CH:29]=[CH:30][CH:31]=2)[CH2:26]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[CH2:36]([N:24]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C@@H:25]1[CH2:34][CH2:33][C:32]2[C:27](=[C:28]([C:6]3[C:2]([CH3:1])=[N:3][NH:4][C:5]=3[CH3:16])[CH:29]=[CH:30][CH:31]=2)[CH2:26]1)[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1
Reactant: Brc1cccc2c1C[C@H](N(Cc1ccccc1)Cc1ccccc1)CC2
Reactant: Cc1n[nH]c(C)c1B1OC(C)(C)C(C)(C)O1
Product: Cc1n[nH]c(C)c1-c1cccc2c1C[C@H](N(Cc1ccccc1)Cc1ccccc1)CC2
Yield: 58 %

Procedure:
The title compound was synthesized as described for Intermediate example I-4 in 58% yield, starting from 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H-pyrazole and (2R)-N,N-dibenzyl-8-bromo-1,2,3,4-tetrahydronaphthalen-2-amine (described in WO9905134A1): MS (ESI) m/z 422[M+H+].
Reaction SMILES: [CH3:1][O:2][C:3](=[O:26])/[C:4](/[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[CH:18][C:17]=1[F:25])=[CH:5]/[O:6][CH3:7].[H][H]>CO.C(OCC)(=O)C.[Pd]>[CH3:1][O:2][C:3](=[O:26])/[C:4](/[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][C:17]=1[F:25])=[CH:5]/[O:6][CH3:7]
Reactant: CO/C=C(/C(=O)OC)c1ccccc1COc1ccc([N+](=O)[O-])cc1F
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CO
Product: CO/C=C(/C(=O)OC)c1ccccc1COc1ccc(N)cc1F
Reaction time: 18 h
Yield: 93.9 %

Procedure:
1.0 g (2.7 mmol) of the compound obtained in Step 1 was dissolved in a mixture of 5 ml of methanol and 5 ml of ethyl acetate, and 200 mg of 10% palladium/carbon was added thereto. The resulting mixture was placed in a hydrogenation reactor, and hydrogen gas was introduced therein with stirring the mixture for 18 hours. The reaction mixture was filtered through Cellite, and concentrated under a reduced pressure. The residue was subjected to column chromatography using 40% ethyl acetate/hexane as an eluent to obtain 0.84 g (yield 92%) of (E)-methyl-2-[2-((2-fluoro-4-aminophenoxy)methyl)phenyl]-3-methoxyacrylate.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][C:8]([OH:10])=O.[CH2:11]([C@@H:18]1[NH:23][CH2:22][CH2:21][N:20]([C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[C:26]([O:32][CH:33]3[CH2:36][CH2:35][CH2:34]3)[CH:25]=2)[CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[CH2:11]([C@H:18]1[CH2:19][N:20]([C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[C:26]([O:32][CH:33]3[CH2:36][CH2:35][CH2:34]3)[CH:25]=2)[CH2:21][CH2:22][N:23]1[C:8](=[O:10])[CH2:7][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: O=C(O)Cc1ccccn1
Reactant: COc1ccc(N2CCN[C@@H](Cc3ccccc3)C2)cc1OC1CCC1
Product: COc1ccc(N2CCN(C(=O)Cc3ccccn3)[C@@H](Cc3ccccc3)C2)cc1OC1CCC1

Procedure:
Prepared by the method outlined for Example 189 using pyridine-2-yl-acetic acid and (S)3-benzyl-1-(3-cyclobutoxy-4-methoxy-phenyl)-piperazine (Example 7, Compound 95) as starting materials. Product as an oil. LC/MS (Method B) 2.57 min, [M+1]+ 472. Potency class A.
Reaction SMILES: [CH2:1]([C:4]1[NH:12][C:7]2=[N:8][CH:9]=[CH:10][CH:11]=[C:6]2[CH:5]=1)[CH2:2][CH3:3].[H-].[Na+].[C:15]1([C:21]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[N:22]2[C:26]([C:27]3[C:32]([C:33]4[CH:38]=[CH:37][C:36]([CH2:39]Br)=[CH:35][CH:34]=4)=[CH:31][CH:30]=[CH:29][CH:28]=3)=[N:25][N:24]=[N:23]2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.O>CN(C=O)C>[CH2:1]([C:4]1[N:12]([CH2:39][C:36]2[CH:35]=[CH:34][C:33]([C:32]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[C:26]3[N:22]([C:21]([C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=4)([C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=4)[C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)[N:23]=[N:24][N:25]=3)=[CH:38][CH:37]=2)[C:7]2=[N:8][CH:9]=[CH:10][CH:11]=[C:6]2[CH:5]=1)[CH2:2][CH3:3]
Reactant: CCCc1cc2cccnc2[nH]1
Reactant: BrCc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCc1cc2cccnc2n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Reaction time: 0.33 h

Procedure:
To a stirred mixture of 2-propyl-1H-pyrrolo-[2,3-b]pyridine (29 mg, 0.18 mmol) in DMF (1 mL) was added NaH (6.7 mg of an 80% dispersion in oil, 0.271 mmol). After 20 min, N-triphenylmethyl-5-(4'-bromomethylbiphen-2-yl)tetrazole (111 mg, 0.19 mmol) was added and the mixture was stirred for 30 min. Water was added and the mixture was extracted with EtOAc. Purification by flash chromatography (SiO2, 25% EtOAc/hexanes) gave 2-propyl-1-[[2'-(1-triphenylmethyl-1H-tetrazol-5-yl)[1,1']-biphenyl-4-yl]methyl]-1H-pyrrolo[2,3-b]pyridine as a foam.
Reaction SMILES: S(Cl)([Cl:4])(=O)=O.[Cl:6][C:7]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:8]=1[NH:9][C:10]1[C:11]([CH2:15][C:16]([OH:18])=[O:17])=[CH:12][S:13][CH:14]=1.[OH-].[Na+].S(S([O-])=O)([O-])=O.[Na+].[Na+]>C(Cl)Cl>[Cl:4][C:14]1[S:13][CH:12]=[C:11]([CH2:15][C:16]([OH:18])=[O:17])[C:10]=1[NH:9][C:8]1[C:19]([Cl:23])=[CH:20][CH:21]=[CH:22][C:7]=1[Cl:6]
Reactant: O=C(O)Cc1cscc1Nc1c(Cl)cccc1Cl
Reactant: O=S(=O)(Cl)Cl
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: O=C(O)Cc1csc(Cl)c1Nc1c(Cl)cccc1Cl
Reaction time: 0.17 h

Procedure:
1.35 g (10 mmoles) of sulfuryl chloride in 20 ml of methylene chloride are added dropwise to a solution of 3.02 g (10 mmoles) of 4-(2,6-dichloroanilino)-3-thiophenacetic acid in 15 ml of methylene chloride at -15°. After 10 minutes, 10 ml each of 2 N NaOH and 10 percent strength (aq) sodium dithionite solution are added. The aqueous phase is separated off, acidified and extracted with ethyl acetate, and the product phase is dried and concentrated. Recrystallization of the residue from cyclohexane yields pure 5-chloro-4-(2,6-dichloroanilino)-3-thiophenacetic acid (d. 141° to 142°).
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:16][CH2:17][C:18]([CH3:21])([OH:20])[CH3:19])=[C:7]([N+:13]([O-])=O)[C:8]([Cl:12])=[N:9]2)=[CH:4][CH:3]=1>[Pt].C(#N)C>[NH2:13][C:7]1[C:8]([Cl:12])=[N:9][C:10]2[C:5]([C:6]=1[NH:16][CH2:17][C:18]([CH3:21])([OH:20])[CH3:19])=[CH:4][CH:3]=[C:2]([Br:1])[CH:11]=2
Reactant: CC(C)(O)CNc1c([N+](=O)[O-])c(Cl)nc2cc(Br)ccc12
Agent: [Pt]
Solvent: CC#N
Product: CC(C)(O)CNc1c(N)c(Cl)nc2cc(Br)ccc12
Yield: 84.3 %

Procedure:
Platinum on carbon (0.2 g of 5%) was added to a solution of 1-[(7-bromo-2-chloro-3-nitroquinolin-4-yl)amino]-2-methylpropan-2-ol (1.94 g, 5.16 mmol) in acetonitrile in a Parr vessel. The mixture was placed under hydrogen pressure (40 psi, 2.8×105 Pa) for two hours and then filtered through a layer of CELITE filter agent. The filter cake was washed with methanol. The filtrate was concentrated under reduced pressure to provide 1.5 g of 1-[(3-amino-7-bromo-2-chloroquinolin-4-yl)amino]-2-methylpropan-2-ol as an oil.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:17]([F:20])([F:19])[F:18])([C:13]([F:16])([F:15])[F:14])[C:7](=[O:12])[N:8]2O)=[CH:4][CH:3]=1.CC(O)=O>C1COCC1.[Zn]>[NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:13]([F:16])([F:14])[F:15])([C:17]([F:18])([F:19])[F:20])[C:7](=[O:12])[NH:8]2)=[CH:4][CH:3]=1
Reactant: Nc1ccc2c(c1)N(O)C(=O)C2(C(F)(F)F)C(F)(F)F
Agent: [Zn]
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: Nc1ccc2c(c1)NC(=O)C2(C(F)(F)F)C(F)(F)F
Temperature: 25 °C
Reaction time: 0.67 h

Procedure:
To a solution of 1.245 g (4.151 mmol) 6-amino-1-hydroxy-3,3-bis-trifluoromethyl-1,3-dihydro-indol-2-one in 80 ml THF was added 3.565 ml (62.27 mmol) glacial AcOH and 19 g (290.6 mmol) Zinc dust (100 mesh). The reaction was stirred 40 min at RT and then 5 h at reflux. The reaction was cooled to RT. The solvent was decanted and concentrated, then dissolved in EtOAc and filtered through Celite®. The EtOAc solution was then washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4, filtered, and concentrated and dried under vacuum, to yield the titled compound, as a yellow solid.
Reaction SMILES: ClC1C=C(C=CC=1)C(OO)=[O:6].[CH2:12]([C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=1)[CH:13]=[CH2:14]>ClCCl>[N+:21]([C:18]1[CH:19]=[CH:20][C:15]([CH2:12][CH:13]2[CH2:14][O:6]2)=[CH:16][CH:17]=1)([O-:23])=[O:22]
Reactant: C=CCc1ccc([N+](=O)[O-])cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: O=[N+]([O-])c1ccc(CC2CO2)cc1
Yield: 70.8 %

Procedure:
Add allyl tri-n-butylstannane (30.10 mmol, 9.33 ml) dropwise to a stirred solution of 4-iodo-nitrobenzene (5 g, 20.07 mmol), tetrakis-(triphenylphosphine) palladium(0) (1.16 g, 1 mmol) and copper (I) iodide (306 mg, 1.6 mmol) in 50 ml of dry 1,4-dioxane under argon atmosphere. Reflux the mixture for 24 hours and then cool to room temperature. Dilute the solution with 40 ml of diethyl ether and add 20 ml of saturated solution of KF and stir for 2 hours. Filter the mixture and wash the organic layer with water (20 ml), brine (20 ml) and dry over sodium sulfate. Evaporate the solution under reduced pressure and purify the residue by flash chromatography on silica gel using hexane-ethyl acetate as eluent (20:1) to afford 1.80 g (55%) of 1-allyl-4-nitrobenzene. Add a solution of 3-chloro-peroxybenzoic acid (5.98 g, 24.28 mmol), in 20 ml of dichloromethane to a solution of 1-allyl-4-nitro-benzene (1.8 g, 11.04 mmol) in 50 ml of dichloromethane and stir the mixture at room temperature overnight. Quench with saturated NaHCO3 (15 ml), and wash the organic layer three times with saturated NaHCO3 and dry over magnesium sulfate. Evaporate under reduced pressure to afford 1.4 g (71%) of the title compound.
Reaction SMILES: [CH2:1]([NH:17][C:18]1[CH:38]=[CH:37][C:21]([C:22]([O:24][CH:25]2[CH2:30][O:29]C(C3C=CC=CC=3)[O:27][CH2:26]2)=[O:23])=[CH:20][CH:19]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].[H][H]>[Pd].C(O)(=O)C>[CH2:1]([NH:17][C:18]1[CH:19]=[CH:20][C:21]([C:22]([O:24][CH:25]([CH2:26][OH:27])[CH2:30][OH:29])=[O:23])=[CH:37][CH:38]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: [H][H]
Reactant: CCCCCCCCCCCCCCCCNc1ccc(C(=O)OC2COC(c3ccccc3)OC2)cc1
Agent: [Pd]
Solvent: CC(=O)O
Product: CCCCCCCCCCCCCCCCNc1ccc(C(=O)OC(CO)CO)cc1

Procedure:
A mixture of 2-phenyl-1,3-dioxan-5-yl 4-(n-hexadecylamino)benzoate, palladium black, and acetic acid is shaken under one atmosphere of hydrogen until hydrogen uptake ceases. The catalyst is separated by filtration and the solvent is evaporated. Crystallization from acetonitrile affords 1,3-dihydroxy-2-propyl 4-(n-hexadecylamino)benzoate as a white solid.
Reaction SMILES: [Cl:1][C:2]([Cl:21])([Cl:20])[C:3]([C:5]1[N:6]([CH2:10][C:11]([C:13]2[CH:18]=[N:17][C:16]([CH3:19])=[CH:15][N:14]=2)=[O:12])[CH:7]=[CH:8][CH:9]=1)=[O:4].[Br:22]N1C(=O)CCC1=O.[NH4+].[Cl-]>C1COCC1>[Br:22][C:8]1[CH:9]=[C:5]([C:3](=[O:4])[C:2]([Cl:1])([Cl:20])[Cl:21])[N:6]([CH2:10][C:11]([C:13]2[CH:18]=[N:17][C:16]([CH3:19])=[CH:15][N:14]=2)=[O:12])[CH:7]=1
Reactant: Cc1cnc(C(=O)Cn2cccc2C(=O)C(Cl)(Cl)Cl)cn1
Reactant: O=C1CCC(=O)N1Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: Cc1cnc(C(=O)Cn2cc(Br)cc2C(=O)C(Cl)(Cl)Cl)cn1
Reaction time: 8 h
Yield: 49.2 %

Procedure:
To a solution of 2,2,2-trichloro-1-{1-[2-(5-methylpyrazin-2-yl)-2-oxoethyl]-1H-pyrrol-2-yl}ethanone (260 mg, 0.75 mmol) in THF (4.4 mL) was added N-bromosuccinimide (144 mg, 0.81 mmol) at −15° C. The mixture was allowed at room temperature overnight. A saturated aqueous solution of NH4Cl (5 mL) was added and the mixture extracted with CH2Cl2 (3×5 mL). The organics were dried (Na2SO4), filtrated and concentrated in vacuo to give a residue that was purified by chromatography (Biotage SP4, gradient 1 CV hexanes, 0-40% EtOAc in hexanes 15 CV, 40-60% 5CV) to give 1-{4-bromo-1-[2-(5-methylpyrazin-2-yl)-2-oxoethyl]-1H-pyrrol-2-yl}-2,2,2-trichloroethanone as a yellow solid (157 mg, yield: 49%). ESI-MI m/z [M+H]+: 425.9.
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][C:7]([C:11]#N)=[CH:6][CH:5]=2.O.[PH2]([O-])=[O:15].[Na+].N1C=CC=CC=1>C(O)(=O)C.[Ni]>[CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][C:7]([CH:11]=[O:15])=[CH:6][CH:5]=2
Reactant: O=[PH2][O-]
Reactant: Cc1cc2cc(C#N)ccc2[nH]1
Agent: [Ni]
Agent: [Na+]
Solvent: O
Solvent: c1ccncc1
Solvent: CC(=O)O
Product: Cc1cc2cc(C=O)ccc2[nH]1
Temperature: 45 °C
Reaction time: 1.25 h
Yield: 80.3 %

Procedure:
A mixture of 3.9 g 2-methyl-1H-indole-5-carbonitrile [Journal of Organic Chemistry (1994), 9(21), 6372-7], 7.22 g sodium hypophosphite monohydrate and 2.60 g Raney-Nickel in 110 ml acetic acid (50%)/pyridine 1:1 was stirred at 45° C. for 75 min. After cooling down to room temperature, the reaction mixture was filtered (dicalite), then the filtrate poured into ice-water and extracted 3 times with EtOAc. The combined organic phases were washed with water, dried over magnesium sulfate and evaporated. The residue was crystallized from n-heptane to give 3.19 g of 2-methyl-1H-indole-5-carbaldehyde as light red solid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([Mg]Br)[CH:5]=[C:6]([F:9])[C:7]=1[F:8].[CH2:12]([C@H:15]1[CH2:20][CH2:19][C@H:18]([CH:21]2[CH2:24][C:23]3([CH2:27][C:26](=[O:28])[CH2:25]3)[CH2:22]2)[CH2:17][CH2:16]1)[CH2:13][CH3:14]>C(OCC)C>[CH2:12]([C@H:15]1[CH2:16][CH2:17][C@H:18]([CH:21]2[CH2:22][C:23]3([CH2:27][C:26]([OH:28])([C:4]4[CH:3]=[C:2]([F:1])[C:7]([F:8])=[C:6]([F:9])[CH:5]=4)[CH2:25]3)[CH2:24]2)[CH2:19][CH2:20]1)[CH2:13][CH3:14]
Reactant: Fc1cc([Mg]Br)cc(F)c1F
Reactant: CCC[C@H]1CC[C@H](C2CC3(CC(=O)C3)C2)CC1
Solvent: CCOCC
Product: CCC[C@H]1CC[C@H](C2CC3(C2)CC(O)(c2cc(F)c(F)c(F)c2)C3)CC1
Reaction time: 15 h

Procedure:
A mixture of 15 mmol of 3,4,5-trifluorophenylmagnesium bromide (prepared from 3,4,5-trifluorobromobenzene and magnesium turnings), 15 mmol of 4E and 50 ml of diethyl ether is stirred for 15 hours. After conventional work-up the product is obtained, which is processed further without purification.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]1([CH2:13][N:14]2[CH:18]=[N:17][CH:16]=[N:15]2)[C@H:11]([CH3:12])[O:10]1.[N:19]1([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([N:31]3[CH:35]=[N:34][NH:33][C:32]3=[O:36])=[CH:27][CH:26]=2)[CH:23]=[N:22][CH:21]=[N:20]1>>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]([OH:10])([CH2:13][N:14]1[CH:18]=[N:17][CH:16]=[N:15]1)[C@H:11]([N:33]1[C:32](=[O:36])[N:31]([C:28]2[CH:27]=[CH:26][C:25]([CH2:24][N:19]3[CH:23]=[N:22][CH:21]=[N:20]3)=[CH:30][CH:29]=2)[CH:35]=[N:34]1)[CH3:12]
Reactant: C[C@@H]1O[C@@]1(Cn1cncn1)c1ccc(F)cc1F
Reactant: O=c1[nH]ncn1-c1ccc(Cn2cncn2)cc1
Product: C[C@@H](n1ncn(-c2ccc(Cn3cncn3)cc2)c1=O)[C@](O)(Cn1cncn1)c1ccc(F)cc1F

Procedure:
(2R,3S)-2-(2,4-Difluorophenyl)-3-methyl-2-(1H-1,2,4-triazol-1-yl)methyloxirane was reacted with 4-[4-(1H-1,2,4-triazol-1-ylmethyl)phenyl]-3(2H,4H)-1,2,4-triazolone in the same manner as in Working Example 11 to give 2-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-4-[4-(1H-1,2,4-triazol-1-ylmethyl)-phenyl]-3(2H,4H)-1,2,4-triazolone (Compound 18).
Reaction SMILES: [C:1]([O:18][CH:19]([CH2:27][O:28][C:29](=[O:45])[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH3:44])[CH2:20][S:21][CH2:22][CH2:23][C:24]([OH:26])=O)(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].Cl.[C:47]([O:51][C:52](=[O:63])[CH2:53][NH:54][C:55](=[O:62])[CH2:56][NH:57][C:58](=[O:61])[CH2:59][NH2:60])([CH3:50])([CH3:49])[CH3:48].P(C#N)(OCC)(OCC)=O.O>CN(C)C=O.C(N(CC)CC)C>[C:47]([O:51][C:52](=[O:63])[CH2:53][NH:54][C:55](=[O:62])[CH2:56][NH:57][C:58](=[O:61])[CH2:59][NH:60][C:24](=[O:26])[CH2:23][CH2:22][S:21][CH2:20][CH:19]([O:18][C:1](=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH2:27][O:28][C:29](=[O:45])[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH3:44])([CH3:50])([CH3:48])[CH3:49]
Reactant: CCCCCCCCCCCCCCCC(=O)OCC(CSCCC(=O)O)OC(=O)CCCCCCCCCCCCCCC
Reactant: CC(C)(C)OC(=O)CNC(=O)CNC(=O)CN
Agent: CCOP(=O)(C#N)OCC
Agent: Cl
Solvent: CCN(CC)CC
Solvent: O
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCCCCC(=O)OCC(CSCCC(=O)NCC(=O)NCC(=O)NCC(=O)OC(C)(C)C)OC(=O)CCCCCCCCCCCCCCC
Temperature: 25 °C
Reaction time: 1 h
Yield: 20 %

Procedure:
To a solution of 6,7-bis(palmitoyloxy)-4-thiaheptanoic acid as obtained in Reference Example 4 (400 mg) and glycylglycylglycine t-butyl ester hydrochloride (149 mg) in dimethylformamide (6 ml), triethylamine (0.094 ml) and diethyl cyanophosphate (150 mg) were added at 0° C., followed by stirring at room temperature for 1 hour. After addition of water, the reaction mixture was extracted with chloroform. The extract was washed with a 5% aqueous solution of citric acid, a saturated aqueous solution of sodium hydrogen carbonate and saturated saline, and dried over anhydrous sodium sulfate, and the solvent was distilled off. The resulting residue was recrystallized (acetone-hexane) to yield the title compound (110 mg, yield 20%) as a wax-like substance.
Reaction SMILES: [C:1]([O:4][CH:5]([C:8]1[C:9]([S:14]([NH:17]C(C)(C)C)(=[O:16])=[O:15])=[N:10][CH:11]=[CH:12][CH:13]=1)[CH2:6][Cl:7])(=[O:3])[CH3:2]>FC(F)(F)C(O)=O>[C:1]([O:4][CH:5]([C:8]1[C:9]([S:14]([NH2:17])(=[O:15])=[O:16])=[N:10][CH:11]=[CH:12][CH:13]=1)[CH2:6][Cl:7])(=[O:3])[CH3:2]
Reactant: CC(=O)OC(CCl)c1cccnc1S(=O)(=O)NC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Product: CC(=O)OC(CCl)c1cccnc1S(N)(=O)=O
Temperature: 40 °C
Reaction time: 12 h
Yield: 100.1 %

Procedure:
3.6 g of 3-(1-acetoxy-2-chloroethyl)-N-(1,1-dimethylethyl)-2-pyridinesulfonamide is added to 20 ml of trifluoroacetic acid and allowed to stir at 40° C. for 12 hours. The acid is evaporated and the crude product is purified by column chromatography to give the subject compound (3 g).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[OH-].[Na+].[CH2:11](Br)[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].O>C(O)C>[CH2:11]([O:8][C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=1)[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCBr
Reactant: Oc1ccc(Br)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CCCCCCOc1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 77.8 %

Procedure:
In 200 g of ethanol were dissolved 86.5 g (0.5 mol) of 4-bromophenol and 22 g (0.55 mol) of sodium hydroxide. To the solution at 70° C., 90.8 g (0.55 mol) of n-hexyl bromide was added dropwise. The solution was allowed to ripen for 4 hours and cooled to room temperature, after which 120 g of water was added. The oily matter was separated therefrom and concentrated by a rotary evaporator, followed by vacuum distillation (boiling point 125-128° C./0.5 Torr), yielding 100 g of 4-n-hexyloxyphenyl bromide.
Reaction SMILES: CN(C)[CH:3]=[CH:4][N+:5]([O-:7])=[O:6].C(O)(C(F)(F)F)=O.[C:16]1([S:22]([C:25]2[CH:33]=[C:32]3[C:28]([CH:29]=[CH:30][NH:31]3)=[CH:27][CH:26]=2)(=[O:24])=[O:23])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>>[N+:5]([CH:4]=[CH:3][C:29]1[C:28]2[C:32](=[CH:33][C:25]([S:22]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)(=[O:23])=[O:24])=[CH:26][CH:27]=2)[NH:31][CH:30]=1)([O-:7])=[O:6]
Reactant: O=S(=O)(c1ccccc1)c1ccc2cc[nH]c2c1
Reactant: CN(C)C=C[N+](=O)[O-]
Solvent: O=C(O)C(F)(F)F
Product: O=[N+]([O-])C=Cc1c[nH]c2cc(S(=O)(=O)c3ccccc3)ccc12
Temperature: 0 °C
Reaction time: 24 h

Procedure:
Combine 1-dimethylamino-2-nitroethylene (676.9 mg, 5.83 mmol) and TFA (9.0 ml) and stir until dissolved. Add 6-benzenesulfonyl-1H-indole (1.5 g, 5.83 mmol) and stir at ambient temperature. After 24 hours, pour the reaction mixture into ice/water and adjust to pH 8. After stirring, filter the precipitate, wash with water, and dry to give the title compound as a yellow powder: mp 110° C., dec. MS (ACPI): m/e 329.0 (M+1). Analysis for C16H12N2O4S: Calcd: C, 58.53; H, 3.68; N, 8.53. found: C, 58.54; H, 3.83; N, 7.85.
Reaction SMILES: [C:1]1([C:7]2[CH:21]=[CH:20][C:10]([CH2:11][P:12](=[O:19])([O:16]CC)[O:13]CC)=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>Cl>[C:1]1([C:7]2[CH:21]=[CH:20][C:10]([CH2:11][P:12](=[O:13])([OH:19])[OH:16])=[CH:9][CH:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCOP(=O)(Cc1ccc(-c2ccccc2)cc1)OCC
Agent: Cl
Product: O=P(O)(O)Cc1ccc(-c2ccccc2)cc1
Temperature: 25 °C
Yield: 16.8 %

Procedure:
A vigorously stirred suspension of 3.5 g (12 mmol) of diethyl 4-phenylbenzylphosphonate in 35 ml of concentrated hydrochloric acid was refluxed for 45 hours and cooled to room temperature. The solids were filtered, washed with water and then recrystallized from EtOH to give 0.5 g of product; m.p. 246°-248° C.
Reaction SMILES: Cl[CH:2]([O:4][C:5](=[O:32])[N:6]([C:29](=[O:31])[CH3:30])[CH2:7][C@@H:8]1[O:12][C:11](=[O:13])[N:10]([C:14]2[CH:19]=[CH:18][C:17]([CH:20]3[CH2:25][CH2:24][S:23](=[O:27])(=[O:26])[CH2:22][CH2:21]3)=[C:16]([F:28])[CH:15]=2)[CH2:9]1)[CH3:3].[CH3:33][C:34]([CH3:39])([CH3:38])[C:35]([O-:37])=[O:36].[Cs+].[I-].[Na+].C(#N)C>O>[C:29]([N:6]([CH2:7][C@@H:8]1[O:12][C:11](=[O:13])[N:10]([C:14]2[CH:19]=[CH:18][C:17]([CH:20]3[CH2:25][CH2:24][S:23](=[O:27])(=[O:26])[CH2:22][CH2:21]3)=[C:16]([F:28])[CH:15]=2)[CH2:9]1)[C:5]([O:4][CH:2]([O:37][C:35](=[O:36])[C:34]([CH3:39])([CH3:38])[CH3:33])[CH3:3])=[O:32])(=[O:31])[CH3:30]
Reactant: CC(=O)N(C[C@H]1CN(c2ccc(C3CCS(=O)(=O)CC3)c(F)c2)C(=O)O1)C(=O)OC(C)Cl
Reactant: CC(C)(C)C(=O)[O-]
Agent: [Cs+]
Agent: [I-]
Agent: [Na+]
Solvent: CC#N
Solvent: O
Product: CC(=O)N(C[C@H]1CN(c2ccc(C3CCS(=O)(=O)CC3)c(F)c2)C(=O)O1)C(=O)OC(C)OC(=O)C(C)(C)C
Temperature: 25 °C
Yield: 30 %

Procedure:
Acetyl-{3-[4-(1,1-dioxo-hexahydro-1λ6-thiopyran-4-yl)-3-fluoro-phenyl]-2-oxo-oxazolidin-5(R)-ylmethyl}-carbamic acid 1-chloro-ethyl ester (11) (0.40 g, 0.81 mmol), cesium 2,2-dimethyl-propionate (0.38 g, 1.63 mmol), sodium iodide (0.121 g, 0.81 mmol) and acetonitrile (25 mL) are heated to reflux overnight. After cooling to RT, water is added and the reaction mixture is extracted with EtOAc and then with dichloromethane. The organic phases are washed separately with brine and then the organic layers are combined, dried over MgSO4, filtered, and conc in vacuo. The isolated residue is subjected to silica gel flash chromatography, eluting with MeOH/CH2Cl2 gradient (0-4% MeOH over 1 hour and 30 minutes) to afford the title compound. Isolated yield: 30%. 1H NMR (400 MHz, DMSO-d6): δ 7.41-7.38 (m, 1H), 7.33 (t, 1H), 7.22 (dd, 1H), 6.71-6.65 (m, 1H), 4.77-4.68 (m, 1H), 4.12-3.94 (m, 2H), 3.88-3.74 (m, 2H), 3.36-3.28 (m, 2H), 3.18-3.12 (m, 1H), 3.07-3.03 (m, 2H), 2.37 (d, 3H), 2.15-2.06 (m, 2H), 2.00-1.97 (m, 2H) 1.44 (dd, 3H); 1.08 (d, 9H),
Reaction SMILES: [ClH:1].CC(C)(OC([NH:8][C@H:9]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=O)C>CCOC(C)=O>[ClH:1].[NH2:8][C@H:9]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12]
Reactant: CCOC(=O)C[C@H](NC(=O)OC(C)(C)C)c1ccccc1
Agent: Cl
Solvent: CCOC(C)=O
Product: CCOC(=O)C[C@H](N)c1ccccc1
Reaction time: 0.5 h
Yield: 98 %

Procedure:
Dry HCl gas was bubbled through a solution of the product of example 12 (3.0 g, 10.2 mmol) in EtOAc (50 mL) at ambient temperature for 15 minutes. After stirring for an additional 30 minutes, the solvent was removed under reduced pressure affording 2.30 g (98%) of product as a yellow oil. 1H-NMR (300 MHz, d6 -DMSO) δ 1.03 (t, J=7Hz, 3H), 3.02 (dd, J=10Hz, J=15Hz, 1H), 3.25 (dd, J=6Hz, J=15Hz, 1H), 3.96 (m, 2H), 4.55 (m, 1H), 7.3-7.6 (m, 5H), 8.93 (s, 3H).