Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:17]=[C:16](I)[CH:15]=[C:14]2[C:9]=1[CH2:10][N:11]([CH2:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=1)[C:12](=[O:27])[N:13]2[C:19]1[C:24]([Cl:25])=[CH:23][CH:22]=[CH:21][C:20]=1[Cl:26].[C:37]([N:41]1[CH2:46][CH2:45][C:44](=[CH:47][Sn](C)(C)C)[CH2:43][CH2:42]1)([CH3:40])([CH3:39])[CH3:38]>>[C:37]([N:41]1[CH2:46][CH2:45][C:44](=[CH:47][C:16]2[CH:15]=[C:14]3[C:9]([CH2:10][N:11]([CH2:28][C:29]4[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=4)[C:12](=[O:27])[N:13]3[C:19]3[C:24]([Cl:25])=[CH:23][CH:22]=[CH:21][C:20]=3[Cl:26])=[C:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])[CH:17]=2)[CH2:43][CH2:42]1)([CH3:40])([CH3:39])[CH3:38]
Reactant: CC(C)(C)N1CCC(=C[Sn](C)(C)C)CC1
Reactant: COc1ccc(CN2Cc3c(-c4ccccc4Cl)cc(I)cc3N(c3c(Cl)cccc3Cl)C2=O)cc1
Product: COc1ccc(CN2Cc3c(-c4ccccc4Cl)cc(C=C4CCN(C(C)(C)C)CC4)cc3N(c3c(Cl)cccc3Cl)C2=O)cc1

Procedure:
The title compound was prepared from 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-iodo-3-(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one (EXAMPLE CCC34) and using 1-tert-butyl-4-[(trimethylstannyl)methylene]piperidine (INTERMEDIATE ABA3) as described in EXAMPLE 41, Step A. Mass spectrum (ESI): 674.5 (M+1).
Reaction SMILES: I[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15].O1CCCC1.[C:24]([C:26]1[CH:27]=[C:28]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[CH:29]=[N:30][CH:31]=1)#[CH:25]>[Cu]I.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.C(N(CC)CC)C>[C:14]([O:13][C:12]([NH:11][C:3]1[CH:4]=[CH:5][C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=1[C:25]#[C:24][C:26]1[CH:27]=[C:28]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:37])([CH3:36])[CH3:38])[CH:29]=[N:30][CH:31]=1)=[O:18])([CH3:17])([CH3:16])[CH3:15]
Reactant: CC(C)(C)OC(=O)Nc1ccc([N+](=O)[O-])cc1I
Reactant: C#Cc1cncc(NC(=O)OC(C)(C)C)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)Nc1cncc(C#Cc2cc([N+](=O)[O-])ccc2NC(=O)OC(C)(C)C)c1
Reaction time: 0.08 h
Yield: 85.9 %

Procedure:
Into the reaction flask was added tert-butyl (2-iodo-4-nitrophenyl)carbamate (1.5 g, 4.1 mmol) and copper(I) iodide (0.031 g, 0.16 mmol), bis(triphenylphosphine)palladium(II) chloride (0.12 g, 0.16 mmol), tetrahydrofuran (10 mL), and triethylamine (0.63 mL). The mixture was stirred under bubbling N2 for 5 min, and tert-butyl (5-ethynylpyridin-3-yl)carbamate (0.90 g, 4.1 mmol) was then added. The reaction mixture was stirred at 65° C. for 1 h. After concentration, the residue was diluted with EtOAc and water. The aqueous layer was extracted again with EtOAc. The organic layers were combined and dried over Na2SO4. After filtration and concentration, the crude was purified by silica gel column chromatography to give the desired product (1.6 g, 85%). LCMS for C23H27N4O6 (M+H)+: m/z=455.1.
Reaction SMILES: C([Li])CCC.C[Si](C)(C)[NH:8][C:9]1[C:10]([CH3:15])=[CH:11][CH:12]=[CH:13][CH:14]=1.[F:18][C:19]([F:26])([F:25])[C:20](OCC)=O>O>[F:18][C:19]([F:26])([F:25])[C:20]1[NH:8][C:9]2[C:10]([CH:15]=1)=[CH:11][CH:12]=[CH:13][CH:14]=2
Reactant: Cc1ccccc1N[Si](C)(C)C
Reactant: CCOC(=O)C(F)(F)F
Agent: [Li]CCCC
Solvent: O
Product: FC(F)(F)c1cc2ccccc2[nH]1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 47 %

Procedure:
A 2.5 M solution of n-butyl lithium in hexanes (8.8 mL, 22 mmole) at room temperature, under N2, is treated with N,N,N'N'-tetramethylethylenediamine (TMEDA) (3.3 mL, 22 mole), stirred at room temperature for 0.5 hour, treated with N-trimethylsilyl-o-toluidine (1.79 g, 10 mmole), heated at reflux temperature for 6 hours, cooled to -78° C., treated with ethyl trifluoroacetate (1.4 mL, 12 mmole) stirred at -78° C. for 0.25 hour, warmed to room temperature, diluted with water and extracted with diethyl ether. The combined extracts are washed sequentially with 1 N HCl and saturated NaHCO3, dried over MgSO4 and concentrated in vacuo to give a residue. The residue is chromatographed using silica gel and 4:1 hexanes:ethyl acetate as eluent to afford the title product as a light yellow solid, mp 104°-106° C. (literature mp 102° C.1), 0.81 g (47% yield), further identified by IR, 1HNMR and 19FNMR analyses.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH:4]([C:6]1[S:7][CH:8]=[CH:9][CH:10]=1)[OH:5].C1(=O)OC(=O)CC1>CC(OC)(C)C>[Cl:1][CH2:2][CH2:3][C@@H:4]([C:6]1[S:7][CH:8]=[CH:9][CH:10]=1)[OH:5]
Reactant: OC(CCCl)c1cccs1
Agent: O=C1CCC(=O)O1
Solvent: COC(C)(C)C
Product: O[C@@H](CCCl)c1cccs1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
197 g (1.16 mol) of alcohol 4, containing 10% of alcohol 5 (i.e. the reaction product obtained from Example 1), are initially introduced in 1 liter of MTBE. 64.4 g (0.64 mol) of succinic anhydride and 10 g of Burkholderia plantarii lipase are then added. The mixture is stirred at RT for 20 h and freed from the enzyme by filtration. After 1.4 l of water have been added, the mixture is adjusted to pH=9 with sodium carbonate and the aqueous phase is separated off. The organic phase is dried over sodium sulfate and freed from the solvent. 96 g of 6, which contains approx. 10% of the corresponding antipode of 5, are obtained.
Reaction SMILES: IC.[Cl:3][C:4]1[C:5]2[CH:12]=[CH:11][NH:10][C:6]=2[N:7]=[CH:8][N:9]=1.[C:13](=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[Cl:3][C:4]1[C:5]2[CH:12]=[CH:11][N:10]([CH3:13])[C:6]=2[N:7]=[CH:8][N:9]=1
Reactant: Clc1ncnc2[nH]ccc12
Reactant: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CI
Product: Cn1ccc2c(Cl)ncnc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 94.1 %

Procedure:
Iodomethane (12.2 mL, 195 mmol) was added to a solution of 4-Chloro-7H-pyrrolo[2,3-d]pyrimidine (15.0 g, 97.7 mmol) and cesium carbonate (47.7 g, 146.5 mmol) in DMF (200 mL). The reaction mixture was stirred at room temperature 1 h, quenched with H2O (500 mL), and extracted with EtOAc (3×200 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo. Purification by flash column chromatography (silica, 2:8→3:7 EtOAc:hexanes) provided the title compound as an off-white solid (15.4 g, 94%). MS: 168.5 (MH+); HPLC Rf: 3.45 min. (HPLC method 4); HPLC purity: 96%.
Reaction SMILES: Br[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1.[CH3:13][Si:14]([C:17]#[CH:18])([CH3:16])[CH3:15].C(NCC)C.O>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I.CCOCC>[CH3:13][Si:14]([C:17]#[C:18][C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1)([CH3:16])[CH3:15]
Reactant: CCOC(=O)c1ccc(Br)cc1
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOCC
Solvent: O
Solvent: CCNCC
Product: CCOC(=O)c1ccc(C#C[Si](C)(C)C)cc1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
A resealable tube was flame-dried under high vacuum. The vacuum was broken by the addition of dry argon, and the flask was allowed to cool to room temperature. The flask was charged with 5.0 g (18.1 mmol) of ethyl 4-bromobenzoate, 7.7 mL (54.3 mmol) of (trimethylsilyl)acetylene, and 65 mL of diethylamine. The solution was purged with argon for 15 minutes and bis(triphenylphosphine)palladium (II) chloride (320 mg, 0.45 mmol) and copper (I) iodide (87 mg, 0.45 mmol) were added, the tube sealed, and the solution stirred at 55° C. for 3 days. The solution was poured into a separatory funnel containing water and ether. The layers were separated and the aqueous layer was extracted 3 times with ether. The combined ether layers were washed once with brine, and dried over magnesium sulfate, and the solvents were removed under reduced pressure. The residue was purified by silica gel chromatography (95:5. hexane:ethyl acetate) to give the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[CH2:12](O)[CH3:13]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:3]=1[C:4]([O:6][CH2:12][CH3:13])=[O:5]
Reactant: CCO
Reactant: O=C(O)c1cc(Cl)ccc1Br
Agent: O=S(=O)(O)O
Product: CCOC(=O)c1cc(Cl)ccc1Br

Procedure:
A solution of 2-bromo-5-chlorobenzoic acid in ethanol (10 ml) and sulphuric acid (0.5 ml) was refluxed for 20 hours then cooled and evaporated. The residue was dissolved in diethyl ether/water and the organic layer dried (magnesium sulphate) and evaporated to give 516 mg of light brown oil.
Reaction SMILES: [OH-].[Na+].C([O:5][C:6](=[O:31])[CH2:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([CH2:17][CH:18]2[CH2:22][CH2:21][N:20]([CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)[C:19]2=[O:29])[C:11]=1[F:30])C.Cl>CO>[Cl:16][C:13]1[CH:14]=[CH:15][C:10]([CH2:9][CH2:8][CH2:7][C:6]([OH:31])=[O:5])=[C:11]([F:30])[C:12]=1[CH2:17][CH:18]1[CH2:22][CH2:21][N:20]([CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)[C:19]1=[O:29]
Reactant: CCOC(=O)CCCc1ccc(Cl)c(CC2CCN(C3CCCCC3)C2=O)c1F
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)CCCc1ccc(Cl)c(CC2CCN(C3CCCCC3)C2=O)c1F
Reaction time: 0.5 h
Yield: 54.1 %

Procedure:
Add 5 N NaOH solution (3 mL, 3 mmol) into 4-[4-chloro-3-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-2-fluoro-phenyl]-butyric acid ethyl ester (Preparation 79) (0.58 g, 1.4 mmol) in methanol (5 mL) at room temperature and stir for 30 minutes. Evaporate MeOH under reduced pressure and neutralize the residue by 1N HCl. Extract the mixture with ethyl acetate (10 mL) and separate the organic layer. Dry the organic layer with magnesium sulfate, filter and evaporate solvent under reduced pressure. Purify the residue by column chromatography to obtain the title product as white solid (300 mg, 55%): Mass spectrum (ion spray): m/z=396.0 (M+H).
Reaction SMILES: Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:3]=1.O(CCCCO)C1C=CC=CC=1.[NH:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.C([O-])([O-])=O.[K+].[K+]>>[O:13]([CH2:12][CH2:11][CH2:10][CH2:9][O:8][C:4]1[CH:5]=[N:6][CH:7]=[C:2]([N:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)[N:3]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: Clc1cncc(OCCCCOc2ccccc2)n1
Reactant: C1CNCCN1
Agent: O=C([O-])[O-]
Agent: OCCCCOc1ccccc1
Agent: [K+]
Product: c1ccc(OCCCCOc2cncc(N3CCNCC3)n2)cc1

Procedure:
The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-(4-phenoxybutoxy)pyrazine (1.99 g, 7.14 mmol; obtained according to the procedure of example 50, step 1, starting from 4-phenoxy-1-butanol*), piperazine (1.84 g, 21.4 mmol) and K2CO3 (0.99 g, 7.14 mmol). The yield of the title compound was 1.52 g (65%) which was obtained as an oil. Purity100% (HPLC). MS m/z 329 (M+H)+. HRMS m/z calcd for C18H24N4O2 (M)+ 328.1899, found 328.1894.
Reaction SMILES: [Cl:1][S:2]([C:5]1[CH:6]=[C:7]([CH:11]=[CH:12][CH:13]=1)[C:8](Cl)=[O:9])(=[O:4])=[O:3].[CH2:14]([NH:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH3:50])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31].C(N(CC)C(C)C)(C)C>C1COCC1>[CH2:33]([N:32]([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[C:8](=[O:9])[C:7]1[CH:11]=[CH:12][CH:13]=[C:5]([S:2]([Cl:1])(=[O:4])=[O:3])[CH:6]=1)[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH3:50]
Reactant: O=C(Cl)c1cccc(S(=O)(=O)Cl)c1
Reactant: CCCCCCCCCCCCCCCCCCNCCCCCCCCCCCCCCCCCC
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: CCCCCCCCCCCCCCCCCCN(CCCCCCCCCCCCCCCCCC)C(=O)c1cccc(S(=O)(=O)Cl)c1

Procedure:
To a stirred solution of 3-chlorosulfonylbenzoyl chloride (25.0 g, 1.1406 mol) in 250 ml of THF at 0° C. was added in one portion a cold suspension of dioctadecylamine (59.3 g, 0.1137 mol) and N,N-diisopropylethylamine (13.5 g, 0.1406 mol) in 500 ml of THF. The addition was exothermic to ≃10° C. The reaction was stirred without cooling overnight. The white insolubles were filtered and the filtrate poured into dilute hydrochloric acid. The aqueous mixture was extracted with ethyl acetate and the organic layer washed with water, dried over anhydrous magnesium sulfate and concentrated to dryness under aspirator pressure at 35° C. The resulting 68 g (90 percent) of yellow oil slowly crystallized. NMR was consistent for the product.
Reaction SMILES: Cl.Cl.[Br:3][C:4]1[N:9]=[CH:8][C:7]([O:10][CH2:11][CH2:12][NH2:13])=[CH:6][CH:5]=1.N1C=CC=CC=1.[C:20](Cl)(=[O:22])[CH3:21].C(=O)([O-])O.[Na+]>O1CCCC1>[Br:3][C:4]1[N:9]=[CH:8][C:7]([O:10][CH2:11][CH2:12][NH:13][C:20](=[O:22])[CH3:21])=[CH:6][CH:5]=1
Reactant: CC(=O)Cl
Reactant: NCCOc1ccc(Br)nc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: CC(=O)NCCOc1ccc(Br)nc1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
To a mixture of 2-((6-bromopyridin-3-yl)oxy)ethanamine dihydrochloride obtained in Reference Example 5 (1.00 g), pyridine (1.12 mL) and tetrahydrofuran (20 mL) was added dropwise acetyl chloride (0.368 mL) at 0° C. The reaction mixture was stirred at room temperature for 5 hr, aqueous sodium hydrogen carbonate solution was added thereto, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The precipitated solid was collected by filtration, and washed with diisopropyl ether to give the title compound (0.792 g).
Reaction SMILES: [CH2:1]([C:3]1[C:8]([NH2:9])=[C:7]([CH3:10])[C:6]([NH2:11])=[C:5]([CH2:12][CH3:13])[CH:4]=1)[CH3:2].O>[Pt].C(C(C)=O)C>[CH:1]([NH:11][C:6]1[C:5]([CH2:12][CH3:13])=[CH:4][C:3]([CH2:1][CH3:2])=[C:8]([NH:9][CH:5]([CH2:6][CH3:7])[CH3:12])[C:7]=1[CH3:10])([CH2:3][CH3:4])[CH3:2]
Reactant: CCc1cc(CC)c(N)c(C)c1N
Agent: [Pt]
Solvent: CCC(C)=O
Solvent: O
Product: CCc1cc(CC)c(NC(C)CC)c(C)c1NC(C)CC
Temperature: 130 °C
Reaction time: 0.62 h
Yield: 88.8 %

Procedure:
Diethyl(methyl)-1,3-benzenediamine, as a mixture of its 2,4-diethyl-6-methyl- and 4,6-diethyl-2-methyl-isomers (5 g; Ethacure® 100, Albemarle Corporation), Pt(S)/C (0.5 g), water (1 g) and methyl ethyl ketone (50 g) were charged into a 100 mL metal autoclave at 22° C. The autoclave was purged 3 times with 125 psig (9.63×105 Pa) of H2 at 22° C. The reaction mixture was then heated at 130° C. under 125 psig (9.63×105 Pa) of H2. After 30-45 minutes, H2 uptake was observed. The reaction mixture was stirred at 130° C. for 8 hours (until no further H2 uptake was observed). The product mixture was cooled to 22° C. and degassed. A diluted product sample was analyzed by GC (100° C. for 5 minutes at 10° C. per minute rate; final temperature, 270° C.). The GC data (normalization method) showed 100% conversion of diethyl(methyl)-1,3-benzenediamine, and an 88.8% yield of N,N′-di-sec-butyl-[diethyl(methyl)-1,3-benzenediamine].
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=O.[NH2:10][C:11]1[CH:12]=[C:13]2[C:17]3=[C:18]([CH2:20][S:21][CH2:22][CH2:23][N:16]3[C@H:15]3[CH2:24][CH2:25][N:26](C(OC(C)(C)C)=O)[CH2:27][C@@H:14]23)[CH:19]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][NH:10][C:11]1[CH:12]=[C:13]2[C:17]3=[C:18]([CH2:20][S:21][CH2:22][CH2:23][N:16]3[C@H:15]3[CH2:24][CH2:25][NH:26][CH2:27][C@@H:14]23)[CH:19]=1
Reactant: O=Cc1cccc(Cl)c1
Reactant: CC(C)(C)OC(=O)N1CC[C@H]2[C@@H](C1)c1cc(N)cc3c1N2CCSC3
Product: Clc1cccc(CNc2cc3c4c(c2)[C@@H]2CNCC[C@@H]2N4CCSC3)c1

Procedure:
Using 3-chlorobenzaldehyde and following the procedures described in EXAMPLE 126, tert-butyl (7bR,11aS)-6-amino-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate from EXAMPLE 33, Part B was converted into the title compound of EXAMPLE 156. 1H NMR(CDCl3) δ 7.37 (s, 1H), 7.29-7.20 (m, 2H), 6.34 (d, 1H, J=2.2 Hz), 6.24 (d, 1H, J=2.6 Hz), 4.25 (broad s, 2H), 3.67 (s, 2H), 3.57-3.50 (m, 1H), 3.42-3.31 (m, 2H), 3.20-2.85 (m, 6H), 2.60 (dd, 1H, J=12.8, 9.9 Hz), 2.15-1.97 (m, 2H). LRMS (ES)+: 386.3 (M+H)+.
Reaction SMILES: [F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1)[CH2:6][N:7]1[C@H:11]([CH3:12])[C@@H:10]([C:13]2[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:14]=2I)[O:9][C:8]1=[O:24].[F:34][C:35]1[C:40]([CH:41]([CH3:43])[CH3:42])=[CH:39][C:38](B(O)O)=[C:37]([O:47][CH3:48])[CH:36]=1>>[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1)[CH2:6][N:7]1[C@H:11]([CH3:12])[C@@H:10]([C:13]2[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:14]=2[C:38]2[CH:39]=[C:40]([CH:41]([CH3:43])[CH3:42])[C:35]([F:34])=[CH:36][C:37]=2[O:47][CH3:48])[O:9][C:8]1=[O:24]
Reactant: C[C@@H]1[C@@H](c2cc(C(F)(F)F)ccc2I)OC(=O)N1Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: COc1cc(F)c(C(C)C)cc1B(O)O
Product: COc1cc(F)c(C(C)C)cc1-c1ccc(C(F)(F)F)cc1[C@H]1OC(=O)N(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)[C@@H]1C

Procedure:
Following the procedure described in EXAMPLE 81, 38.5 mg of (4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-5-[2-iodo-5-(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one and 18 mg of (4-fluoro-5-isopropyl-2-methoxyphenyl)boronic acid (EXAMPLE 78) gave the title compound. Mass spectrum (ESI) 638.3 (M+1). 1H NMR signals are doubled because of atropoisomerism. 1H NMR (500 MHz, CDCl3): δ 7.55-7.80 (m, 5H), 7.29 (d, J=8 Hz, 1H), 7.00, 6.77 (d, J=8.5 Hz, 1H), 6.68, 6.63 (d, J˜12 Hz, 1H), 5.08, 5.04 (d, J˜5 Hz, 1H), 4.81, 4.75 (d, J=16 Hz, 1H), 4.26, 4.23 (d, 15.5 Hz, 1H), 3.75 (s, 2H), 3.50 (s, 1H), 3.43 (m, 0.5H), 3.12-3.24 (m, 1.5H), 1.24, 1.22 (d, J˜5 Hz, 3H), 1.17, 1.06 (d, J=7 Hz, 3H), 0.84, 0.70 (d, J=6 Hz, 3H).
Reaction SMILES: CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Si:25]([O:32][CH2:33][C@H:34]([CH3:56])[O:35][C:36]1[CH:37]=[C:38]([CH:42]=[C:43]([O:45][C:46]2[CH:51]=[CH:50][C:49]([S:52]([CH3:55])(=[O:54])=[O:53])=[CH:48][CH:47]=2)[CH:44]=1)[C:39](O)=[O:40])([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26].[NH2:57][C:58]1[S:59][CH:60]=[CH:61][N:62]=1>CN(C=O)C>[Si:25]([O:32][CH2:33][C@H:34]([CH3:56])[O:35][C:36]1[CH:37]=[C:38]([CH:42]=[C:43]([O:45][C:46]2[CH:47]=[CH:48][C:49]([S:52]([CH3:55])(=[O:53])=[O:54])=[CH:50][CH:51]=2)[CH:44]=1)[C:39]([NH:57][C:58]1[S:59][CH:60]=[CH:61][N:62]=1)=[O:40])([C:28]([CH3:31])([CH3:29])[CH3:30])([CH3:26])[CH3:27]
Reactant: C[C@@H](CO[Si](C)(C)C(C)(C)C)Oc1cc(Oc2ccc(S(C)(=O)=O)cc2)cc(C(=O)O)c1
Reactant: Nc1nccs1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Product: C[C@@H](CO[Si](C)(C)C(C)(C)C)Oc1cc(Oc2ccc(S(C)(=O)=O)cc2)cc(C(=O)Nc2nccs2)c1
Reaction time: 4 h
Yield: 69.9 %

Procedure:
HATU (513 mg, 1.35 mmol) was added to 3-((1S)-2-{[tert-Butyl(dimethyl)silyl]oxy}-1-methylethoxy)-5-[4-(methylsulfonyl)phenoxy]benzoic acid (520 mg, 1.08 mmol) followed by addition of DMF (5 mL), disopropylethylamine (0.48 mL) and 2-aminothiazole (135 mg, 1.35 mmol) and the reaction was stirred under argon for 4 h. The solvent was evaporated and the residue was dissolved in saturated aqueous sodium hydrogencarbonate (30 mL) and ethyl acetate (50 mL). The organic layer was separated, washed with saturated aqueous ammonium chloride (30 mL) then dried (MgSO4), filtered and evaporated. Purification by column chromatography, eluting with 1:2 to 2:1 ethyl acetate:hexanes, afforded the title compound as a colourless oil (425 mg, 70%).
Reaction SMILES: [CH2:1]([N:4]([CH2:17][CH2:18][CH3:19])[C:5]([C:7]1[CH:8]=[C:9]([CH:13]=[C:14]([CH3:16])[CH:15]=1)[C:10]([OH:12])=O)=[O:6])[CH2:2][CH3:3].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[NH2:34][C@@H:35]([CH2:54][C:55]1[CH:60]=[C:59]([F:61])[CH:58]=[C:57]([F:62])[CH:56]=1)[CH2:36][NH:37][C@H:38]([C:40]([NH:42][C@H:43]([C:47]([NH:49][CH2:50][CH:51]([CH3:53])[CH3:52])=[O:48])[CH:44]([CH3:46])[CH3:45])=[O:41])[CH3:39]>CN(C=O)C>[F:61][C:59]1[CH:60]=[C:55]([CH2:54][C@H:35]([NH:34][C:10](=[O:12])[C:9]2[CH:13]=[C:14]([CH3:16])[CH:15]=[C:7]([C:5]([N:4]([CH2:1][CH2:2][CH3:3])[CH2:17][CH2:18][CH3:19])=[O:6])[CH:8]=2)[CH2:36][NH:37][C@H:38]([C:40]([NH:42][C@H:43]([C:47]([NH:49][CH2:50][CH:51]([CH3:53])[CH3:52])=[O:48])[CH:44]([CH3:46])[CH3:45])=[O:41])[CH3:39])[CH:56]=[C:57]([F:62])[CH:58]=1
Reactant: CC(C)CNC(=O)[C@@H](NC(=O)[C@H](C)NC[C@@H](N)Cc1cc(F)cc(F)c1)C(C)C
Reactant: CCCN(CCC)C(=O)c1cc(C)cc(C(=O)O)c1
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: CCCN(CCC)C(=O)c1cc(C)cc(C(=O)N[C@H](CN[C@@H](C)C(=O)N[C@H](C(=O)NCC(C)C)C(C)C)Cc2cc(F)cc(F)c2)c1
Reaction time: 1 h
Yield: 69.5 %

Procedure:
3-[(Dipropylamino)carbonyl]-5-methylbenzoic acid, (90 mg, 0.34 mmol) is combined with EDC(65 mg, 0.34 mmol) and HOBT (46 mg, 0.34 mmol) in 3 mL of DMF and stirred under nitrogen for 1 h. This solution is then added to a solution of N-[(2S)-2-amino-3-(3,5-difluorophenyl)propyl]-L-alanyl-N1-isobutyl-L-valinamide (88 mg, 0.21 mmol) in 1 mL of DMF. The reaction is continued for 3 days at ambient temperature. It is then quenched with 1 N KH2PO4 and diluted with ethyl acetate containing about 1% of methanol. The organic phase is washed with water, 1 N NaHCO3, and brine, and dried over Na2SO4. Concentration and chromatography over silica gel, eluting with 4% to 6% methanol in dichloromethane, affords 96 mg (0.146 mmol, 69%) of the title compound as a light tan solid. 1H NMR (CDCl3) δ 7.75 (d, J=9 Hz, 1H), 7.54 (s, 1H), 7.37 (s, 1H), 7.21 (s, 1H), 7.16 (d, J=8 Hz, 1H), 6.84 (m, 2H), 6.70 (m, 1H), 6.64 (m, 1H), 4.19 (dd, J=7, 9 Hz, 1H), 4.05 (m, 1H), 3.5-3.4 (m, 2H), 3.33 (dd, J=6, 14 Hz, 1H), 3.19-3.02 (m, 5H), 2.88 (dd, J=6, 14 Hz, 1H), 2.68 (dd, J=4, 13.5 Hz, 1H), 2.58 (m, 1H), 2.37 (s, 3H), 1.96 (m, 1H), 1.75-1.64 (m, 4H), 1.50 (m, 2H), 1.35 (d, J=7 Hz, 3H), 0.99 (t, J=7 Hz, 3H), 0.91 (d, J=7 Hz, 3H), 0.86 (m, 9H), 0.71 (t, J=7 Hz, 3H).
Reaction SMILES: [CH2:1]([O:4][N:5]([C@H:18]1[CH2:23][N:22](C(OC(C)(C)C)=O)[C@H:21]([CH2:31][O:32][CH3:33])[CH:20]=[C:19]1[C:34](=[O:36])[NH2:35])[S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[N+:15]([O-:17])=[O:16])(=[O:8])=[O:7])[CH:2]=[CH2:3].FC(F)(F)C(O)=O>ClCCl>[CH2:1]([O:4][N:5]([C@@H:18]1[C:19]([C:34]([NH2:35])=[O:36])=[CH:20][C@@H:21]([CH2:31][O:32][CH3:33])[NH:22][CH2:23]1)[S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[N+:15]([O-:17])=[O:16])(=[O:8])=[O:7])[CH:2]=[CH2:3]
Reactant: C=CCON([C@H]1CN(C(=O)OC(C)(C)C)[C@H](COC)C=C1C(N)=O)S(=O)(=O)c1ccccc1[N+](=O)[O-]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: C=CCON([C@H]1CN[C@H](COC)C=C1C(N)=O)S(=O)(=O)c1ccccc1[N+](=O)[O-]

Procedure:
To a solution of Intermediate 112 (729 mg, 1.38 mmol) in dichloromethane (10 mL) was added trifluoroacetic acid (2133 μl, 27.69 mmol). This solution was slightly darker after addition. The reaction was placed under a nitrogen atmosphere and stirred until LCMS analysis indicated consumption of starting material (˜45 minutes). At that time, solvent was removed in vacuo. The residue was taken up in toluene and sonicated, and then toluene was removed in vacuo. This was repeated twice, affording an orange solid of high purity by proton NMR. The product was taken forward without further purification.