Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([S:7]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:13][C:12]=2I)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:22]([CH:24]1[CH2:28][CH2:27][CH2:26][O:25]1)#[CH:23].C(N(CC)CC)C.O>O1CCOCC1>[O:25]1[CH2:26][CH2:27][CH2:28][CH:24]1[C:22]1[N:10]([S:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)(=[O:9])=[O:8])[C:11]2[C:12]([CH:23]=1)=[CH:13][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:15][CH:16]=2
Reactant: C#CC1CCCO1
Reactant: CS(=O)(=O)c1ccc(NS(=O)(=O)c2ccccc2)c(I)c1
Solvent: C1COCCO1
Solvent: O
Solvent: CCN(CC)CC
Product: CS(=O)(=O)c1ccc2c(c1)cc(C1CCCO1)n2S(=O)(=O)c1ccccc1
Temperature: 60 °C
Reaction time: 3 h
Yield: 91.8 %

Procedure:
To a solution of 1-benzenesulfonylamino-2-iodo-4-methanesulfonylbenzene (256 mg) in 1,4-dioxane (6 ml), 2-ethynyltetrahydrofuran (169 mg), bistriphenylphosphine palladium dichloride (21 mg), cuprous iodide (11 mg) and triethylamine (89 mg) were added successively and the mixture was stirred in a sealed tube at 60° C. for 3 hours. After cooling the reaction solution was poured into water, extracted with dichloromethane, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was separated using silica gel preparative thin-layer chromatography (hexane:ethyl acetate=1:1) to obtain 218 mg of the desired product in a white amorphous form.
Reaction SMILES: [C:1]1([C:7]2[CH2:8][CH2:9][NH:10][CH2:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1C2C(=CC=CC=2)CCN1[C:23]([Cl:25])=[O:24]>>[C:1]1([C:7]2[CH2:12][CH2:11][N:10]([C:23]([Cl:25])=[O:24])[CH2:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C1=C(c2ccccc2)CCNC1
Reactant: O=C(Cl)N1CCc2ccccc2C1
Product: O=C(Cl)N1CC=C(c2ccccc2)CC1
Yield: 95 %

Procedure:
4-Phenyl-3,6-dihydro-2H-pyridine-1-carbonyl chloride (62A) is prepared from 4-phenyl-1,2,3,6-tetrahydropyridine as described for 24A.
Reaction SMILES: [F:1][C:2]1[CH:14]=[C:13](F)[C:12]([F:16])=[CH:11][C:3]=1[C:4]([NH:6][S:7]([CH3:10])(=[O:9])=[O:8])=[O:5].[Cl:17][C:18]1[CH:19]=[C:20]([OH:29])[CH:21]=[N:22][C:23]=1[O:24][CH:25]1[CH2:28][CH2:27][CH2:26]1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.O>[Cl:17][C:18]1[CH:19]=[C:20]([O:29][C:13]2[C:12]([F:16])=[CH:11][C:3]([C:4]([NH:6][S:7]([CH3:10])(=[O:9])=[O:8])=[O:5])=[C:2]([F:1])[CH:14]=2)[CH:21]=[N:22][C:23]=1[O:24][CH:25]1[CH2:28][CH2:27][CH2:26]1
Reactant: Oc1cnc(OC2CCC2)c(Cl)c1
Reactant: CS(=O)(=O)NC(=O)c1cc(F)c(F)cc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: CS(=O)(=O)NC(=O)c1cc(F)c(Oc2cnc(OC3CCC3)c(Cl)c2)cc1F
Temperature: 90 °C
Yield: 11.8 %

Procedure:
2,4,5-trifluoro-N-(methylsulfonyl)benzamide (Preparation 27, 0.317 g, 1.25 mmol), 5-chloro-6-cyclobutoxypyridin-3-ol (Preparation 19, 0.250 g, 1.25 mmol) and potassium carbonate (0.346 g, 2.50 mmol) were suspended in DMSO (16 mL) and heated at 90° C. for 48 hours. The reaction was diluted with water (50 mL) and extracted with EtOAc (3×20 mL). The combined organics were dried over magnesium sulfate, filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography eluting with 20% EtOAc (with 0.5% AcOH) in heptane to afford the title compound as a white solid (64 mg, 12%):
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([OH:13])[CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])([O-:3])=[O:2].Br[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17].C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[N+:1]([C:4]1[CH:5]=[C:6]([CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[O:13][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccc(O)cc1[N+](=O)[O-]
Reactant: CCOC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC#N
Product: CCOC(=O)COc1ccc([N+](=O)[O-])c([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 80 %

Procedure:
A round-bottom flask was charged with 3,4-dinitrophenol (11.04 g, 60 mmol, commercially available from Fluka-Sigma-Aldrich), ethyl bromoacetate (11.02 g, 66 mmol), acetonitrile (120 mL) and cesium carbonate (21.6 g). The mixture was stirred at room temperature overnight. The mixture was filtered, and the recovered solid was washed with ethyl acetate. The filtrate was further diluted with ethyl acetate and water. The aqueous layer was extracted with ethyl acetate and combined organic solvent was washed with saturated brine, dried and concentrated under reduced pressure. The residue was triturated with ether to give ethyl 2-(3,4-dinitrophenoxy)acetate (13.0 g, 80% yield). 1H-NMR (400 MHz, MeOH-d4): δ 8.15 (d, 1H), 7.55 (s, 1H), 7.35 (d, 1H), 4.95 (s, 2H), 4.23 (q, 2H), 1.25 (t, 3H). MS (EI): 271 (MH+).
Reaction SMILES: O[CH:2]([N:15]1[C:21](=[O:22])[C@@H:20]2[C@H:16]1[S:17][C:18]([CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=CC=1)=[N:19]2)[C:3]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1)=[O:4].O.C1(C)C=CC(S(O)(=O)=[O:38])=CC=1.BrCC([C@H]1CCCO1)=O.C(=O)([O-])[O-].[K+].[K+]>ClCCl.CC(C)=O.O>[NH2:19][C@@H:20]1[C:21](=[O:22])[N:15]2[C:2]([C:3]([O:5][CH2:6][C:7]3[CH:8]=[CH:9][C:10]([O:13][CH3:14])=[CH:11][CH:12]=3)=[O:4])=[C:23]([C@H:24]3[CH2:29][CH2:28][CH2:27][O:38]3)[CH2:18][S:17][C@H:16]12
Reactant: COc1ccc(COC(=O)C(O)N2C(=O)[C@H]3N=C(Cc4ccccc4)S[C@H]32)cc1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C(CBr)[C@H]1CCCO1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: O
Solvent: CC(C)=O
Product: COc1ccc(COC(=O)C2=C([C@H]3CCCO3)CS[C@@H]3[C@H](N)C(=O)N23)cc1

Procedure:
4-Methoxybenzyl (RS)-2-hydroxy-2-[(1R,5R)-3-benzyl-4-thia-2,6-diazabicyclo[3.2.0]hept-2-en-7-on-6-yl]acetate (4.103g) in dichloromethane (15ml) and acetone (15ml) was ring opened with 4-toluenesulphonic acid hydrate (3.33g) in water (8ml) and coupled to (R)-2-bromoacetyltetrahydrofuran (2.11g) in acetone (20ml) with potassium carbonate (0.687g) as described in Example 6(b) for the diastereoisomeric mixture. After purification by flash chromatography, the title compound was obtained as a yellow gum (2.618g, 49%); [α]D -10.7 (c 1.00 CHCl3).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][C:5](Cl)=[O:6].CN(C)C1C=CC=CC=1.[C:17]([OH:21])([CH3:20])([CH3:19])[CH3:18]>C(OCC)C>[Cl:1][CH2:2][CH2:3][CH2:4][C:5]([O:21][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:6]
Reactant: O=C(Cl)CCCCl
Reactant: CC(C)(C)O
Solvent: CN(C)c1ccccc1
Solvent: CCOCC
Product: CC(C)(C)OC(=O)CCCCl

Procedure:
A mixture of 4-chlorobutyryl chloride (93 g, 0.66 mol), N,N-dimethylaniline (80 g, 0.66 mol) and tert-butanol (0.66 mol) in ethyl ether (100 mL) was refluxed for 5 h. The reaction was cooled, diluted with ether and washed with water, 10% citric acid, saturated NaCl and dried over Na2SO4. Crude product obtained after evaporation of the solvent was distilled under vacuum (10 mmHg). Pure product (79 g, 67%) boiling at 57-58° C. was collected. 1H NMR (DMSO-d6) δ 3.64 (t, J=7 Hz, 2H), 2.35 (t, J=7 Hz, 2H), 1.93 (q, 2H), 1.41 (s, 9H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:12]=[CH:13][C:14]=1[O:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22]C)[CH:17]=1)[CH2:5][NH:6][CH2:7][CH2:8][CH:9]([CH3:11])[CH3:10].B(Br)(Br)Br.[Cl:28]CCl>>[ClH:28].[F:1][C:2]1[CH:3]=[C:4]([CH2:5][NH:6][CH2:7][CH2:8][CH:9]([CH3:11])[CH3:10])[CH:12]=[CH:13][C:14]=1[O:15][C:16]1[CH:17]=[C:18]([OH:22])[CH:19]=[CH:20][CH:21]=1
Reactant: COc1cccc(Oc2ccc(CNCCC(C)C)cc2F)c1
Reactant: ClCCl
Agent: BrB(Br)Br
Product: CC(C)CCNCc1ccc(Oc2cccc(O)c2)c(F)c1
Product: Cl
Temperature: 25 °C
Reaction time: 1 h

Procedure:
The [3-fluoro-4-(3-methoxy-phenoxy)-benzyl]-(3-methyl-butyl)-amine (460 mg, 1.45 mmol) was dissolved in dichloromethane (10 ml) and cooled to −78° C. as boron tribromide (7.25 mL of a 1.0 M in dichloromethane, 7.25 mmol) was added slowly. After 1 hour at −78° C., the reaction was allowed to warm to room temperature. After 4 hours at room temperature the reaction mixture was carefully being quenched with cold water before the pH was adjusted to 10.0 using concentrated ammonium hydroxide. The reaction mixture was extracted with dichloromethane two times and the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by preparative thin layer chromatography on silica eluting with 5% methanol in ethyl acetate. The HCl salt of the product thus isolated was formed by dissolving the free base in ethyl acetate and adding 1 ml of 4.0 M HCl in dioxane and evaporating to afford the product (2A) a solid.
Reaction SMILES: [NH2:1][C:2]1[C:7]([O:8][CH2:9][C:10]([F:13])([F:12])[F:11])=[CH:6][C:5]([CH:14]([CH2:20][CH:21]2[CH2:23][CH2:22]2)[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:4][C:3]=1Br.[F:25][C:26]([F:37])([F:36])[C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.[F-].[Cs+].CCOC(C)=O>COCCOC.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.O>[NH2:1][C:2]1[C:3]([C:30]2[CH:31]=[CH:32][C:27]([C:26]([F:37])([F:36])[F:25])=[CH:28][CH:29]=2)=[CH:4][C:5]([CH:14]([CH2:20][CH:21]2[CH2:23][CH2:22]2)[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:6][C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11]
Reactant: OB(O)c1ccc(C(F)(F)F)cc1
Reactant: CCOC(=O)C(CC1CC1)c1cc(Br)c(N)c(OCC(F)(F)F)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cs+]
Agent: [F-]
Solvent: O
Solvent: CCOC(C)=O
Solvent: COCCOC
Product: CCOC(=O)C(CC1CC1)c1cc(OCC(F)(F)F)c(N)c(-c2ccc(C(F)(F)F)cc2)c1
Yield: 54.2 %

Procedure:
A mixture of ethyl 2-(4-amino-3-bromo-5-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate (1.1, 3.3 mmol), 4-trifluoromethylphenylboronic acid (1.26 g, 6.7 mmol), CsF (1.26 g, 8.3 mmol) and Pd (PPh3)4 (0.38 g, 0.33 mmol) in 50 mL anhydrous 1,2-dimethoxy ethane was refluxed for 8 h under argon. The reaction mixture was cooled, and 50 mL of EtOAc and 50 mL of water were added. The organic phase was separated, dried over Na2SO4, filtered and concentrated under reduced pressure to give a yellow oil. The oil was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl 2-(6-amino-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate (0.85 g, 82% yield) as a white solid.
Reaction SMILES: [Mg].[OH:2][C:3]([CH2:9][C:10]([O:12][CH3:13])=[O:11])=[CH:4][C:5]([O:7][CH3:8])=[O:6].C1COCC1.[C:19](Cl)(=[O:23])[CH:20]([CH3:22])[CH3:21].Cl>C1(C)C=CC=CC=1>[C:19]([CH:9]([C:3](=[O:2])[CH2:4][C:5]([O:7][CH3:8])=[O:6])[C:10]([O:12][CH3:13])=[O:11])(=[O:23])[CH:20]([CH3:22])[CH3:21]
Reactant: CC(C)C(=O)Cl
Reactant: COC(=O)C=C(O)CC(=O)OC
Agent: Cl
Agent: [Mg]
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: COC(=O)CC(=O)C(C(=O)OC)C(=O)C(C)C
Temperature: 25 °C
Reaction time: 18 h
Yield: 167.9 %

Procedure:
A mixture of 12.15 g (0.03 mol) of product of Step A in 50 ml of toluene was refluxed using a Dean-Stark trap for 1 hour. The resulting clear solution was cooled to room temperature and 50 ml of anhydrous THF were added. To this solution 6.4 g (6.3 ml, 0.06 mol) of isobutyryl chloride was added and stirred for 18 hours. Crude was poured into 3.7% HCl, extracted with EtOAc, the EtOAc layer was washed again with 3.7% HCl and saturated NaCl. Organic layer was dried (MgSO4) and removed in vacuo affording 12.3 g of crude dimethyl 2-(isobutyryl)-3-oxo-1,5-pentanedioate. The crude was purified by HPLC using 10% EtOAc/cyclohexane as eluting solvent affording 8.87 g (61%) of this intermediate as a light yellow oil; nD25 1.4783.
Reaction SMILES: [CH3:1][CH:2]([CH3:24])[CH:3]([NH:14][CH2:15][CH2:16][NH:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:4]1[C:5]([C:10]([F:13])([F:12])[F:11])=[N:6][CH:7]=[N:8][CH:9]=1.C(N(CC)CC)C.ClCCl.[C:35](Cl)(Cl)=[O:36]>O>[CH3:1][CH:2]([CH3:24])[CH:3]([N:14]1[CH2:15][CH2:16][N:17]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:35]1=[O:36])[C:4]1[C:5]([C:10]([F:12])([F:11])[F:13])=[N:6][CH:7]=[N:8][CH:9]=1
Reactant: CC(C)C(NCCNc1ccccc1)c1cncnc1C(F)(F)F
Reactant: O=C(Cl)Cl
Solvent: ClCCl
Solvent: O
Solvent: CCN(CC)CC
Product: CC(C)C(c1cncnc1C(F)(F)F)N1CCN(c2ccccc2)C1=O
Reaction time: 1 h
Yield: 68.6 %

Procedure:
1.05 g (4.2 mol) of 5-(1-chloro-2-methylpropyl)-4-trifluoromethylpyrimidine and 0.61 (4.2 mol) of N-phenylethylenediamine were added to 10 ml of isopropyl alcohol, followed by stirring at room temperature for 6 hours. After completion of the reaction, the reaction solution was concentrated, then poured into water and extracted with ethyl acetate, and purified by silica gel column chromatography (ethyl acetate:n-hexane=1:1 to ethyl acetate) to obtain 0.38 g of N-[2-methyl-1-(4-trifluoromethylpyrimidin-5-yl)-propyl]-N′-phenylethane-1,2-diamine. Then, 0.38 g (1 mmol) of N-[2-methyl-1-(4-trifluoromethylpyrimidin-5-yl)-propyl]-N′-phenylethane-1,2-diamine and 0.5 g (5 mmol) of triethylamine were added to 10 ml of dichloromethane, and a dichloromethane solution containing 0.2 g (2 mmol) of phosgene was dropwise added under cooling with ice. After the dropwise addition, stirring was further continued at room temperature for 1 hour to terminate the reaction. After termination of the reaction, the product was poured into water, washed with an aqueous sodium hydrogencarbonate solution, dried and concentrated, and the obtained oily product was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:1 to ethyl acetate) to obtain 0.25 g (yield: 61%) of 1-[2-methyl-1-(4-trifluoromethyl-pyrimidin-5-yl)-propyl]-3-phenylimidazolin-2-one as colorless crystals (melting point: 126-128° C.).
Reaction SMILES: [CH3:1][S:2]([N:5]1[CH2:10][CH2:9][N:8]([C@@H:11]2[CH2:15][NH:14][C@H:13]([C:16]([NH:18][C:19]3[CH:31]=[CH:30][C:22]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[CH:21][CH:20]=3)=[O:17])[CH2:12]2)[CH2:7][CH2:6]1)(=[O:4])=[O:3].[CH3:32][C:33]([O:36][C:37]([NH:39][C@H:40]([C@H:42]1[CH2:47][CH2:46][C@H:45]([C:48](O)=[O:49])[CH2:44][CH2:43]1)[CH3:41])=[O:38])([CH3:35])[CH3:34]>>[CH3:32][C:33]([O:36][C:37]([NH:39][C@H:40]([C@H:42]1[CH2:43][CH2:44][C@H:45]([C:48]([N:14]2[CH2:15][C@@H:11]([N:8]3[CH2:9][CH2:10][N:5]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:6][CH2:7]3)[CH2:12][C@H:13]2[C:16]([NH:18][C:19]2[CH:31]=[CH:30][C:22]([C:23]([O:25][C:26]([CH3:28])([CH3:27])[CH3:29])=[O:24])=[CH:21][CH:20]=2)=[O:17])=[O:49])[CH2:46][CH2:47]1)[CH3:41])=[O:38])([CH3:34])[CH3:35]
Reactant: C[C@H](NC(=O)OC(C)(C)C)[C@H]1CC[C@H](C(=O)O)CC1
Reactant: CC(C)(C)OC(=O)c1ccc(NC(=O)[C@@H]2C[C@H](N3CCN(S(C)(=O)=O)CC3)CN2)cc1
Product: C[C@H](NC(=O)OC(C)(C)C)[C@H]1CC[C@H](C(=O)N2C[C@@H](N3CCN(S(C)(=O)=O)CC3)C[C@H]2C(=O)Nc2ccc(C(=O)OC(C)(C)C)cc2)CC1

Procedure:
Following the procedure described in Example 8, the compound prepared in Example 6 was treated with trans-4-[(1S)-1-({[(2-methyl-2-propanyl)oxy]carbonyl}amino)ethyl]cyclohexanecarboxylic acid to give the title compound as a light brown solid.
Reaction SMILES: C([O:8][C:9]1[CH:42]=[CH:41][C:12]2[NH:13][C:14]([C:19]3[C:20](=[O:40])[C:21]([CH2:35][CH2:36][CH:37]([CH3:39])[CH3:38])([CH2:30][CH2:31][CH:32]([CH3:34])[CH3:33])[C:22]4[C:27]([C:28]=3[OH:29])=[CH:26][CH:25]=[CH:24][CH:23]=4)=[N:15][S:16](=[O:18])(=[O:17])[C:11]=2[CH:10]=1)C1C=CC=CC=1.C(OC1C=CC2NC(C3C(=O)C(CCC)(CCC)C4C(C=3O)=CC=CC=4)=NS(=O)(=O)C=2C=1)C1C=CC=CC=1>>[OH:29][C:28]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]([CH2:35][CH2:36][CH:37]([CH3:39])[CH3:38])([CH2:30][CH2:31][CH:32]([CH3:34])[CH3:33])[C:20](=[O:40])[C:19]=1[C:14]1[NH:13][C:12]2[CH:41]=[CH:42][C:9]([OH:8])=[CH:10][C:11]=2[S:16](=[O:17])(=[O:18])[N:15]=1
Reactant: CC(C)CCC1(CCC(C)C)C(=O)C(C2=NS(=O)(=O)c3cc(OCc4ccccc4)ccc3N2)=C(O)c2ccccc21
Agent: CCCC1(CCC)C(=O)C(C2=NS(=O)(=O)c3cc(OCc4ccccc4)ccc3N2)=C(O)c2ccccc21
Product: CC(C)CCC1(CCC(C)C)C(=O)C(C2=NS(=O)(=O)c3cc(O)ccc3N2)=C(O)c2ccccc21

Procedure:
The title compound was prepared by the procedure of Example 2G, substituting the product of Example 7B for the product of Example 2F. 1H NMR (300 MHz, DMSO-d6): δ 13.69 (s, 1 H), 10.42 (s, 1 H), 8.17 (d, J=7.72 Hz, 1 H), 7.77 (m, 1 H), 7.56 (m, 3 H), 7.19 (m, 2 H), 2.12 (m, 4 H), 1.29 (m, 2 H), 0.75 (m, 14 H), 0.38 (m, 2 H).
Reaction SMILES: [CH2:1]([O:7][C:8]1[CH:9]=[N:10][C:11]([C:14]2[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=2)=[N:12][CH:13]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[F:21][C:22]([F:46])([O:27][C:28]([F:45])([F:44])[C:29]([F:43])([F:42])[O:30][C:31]([F:41])([F:40])[CH2:32][O:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38]Br)[C:23]([F:26])([F:25])[F:24]>O>[CH2:1]([O:7][C:8]1[CH:13]=[N:12][C:11]([C:14]2[CH:15]=[CH:16][C:17]([O:20][CH2:38][CH2:37][CH2:36][CH2:35][CH2:34][O:33][CH2:32][C:31]([O:30][C:29]([F:42])([F:43])[C:28]([F:44])([F:45])[O:27][C:22]([F:21])([F:46])[C:23]([F:24])([F:25])[F:26])([F:41])[F:40])=[CH:18][CH:19]=2)=[N:10][CH:9]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCCCOc1cnc(-c2ccc(O)cc2)nc1
Reactant: FC(F)(COCCCCCBr)OC(F)(F)C(F)(F)OC(F)(F)C(F)(F)F
Solvent: O
Product: CCCCCCOc1cnc(-c2ccc(OCCCCCOCC(F)(F)OC(F)(F)C(F)(F)OC(F)(F)C(F)(F)F)cc2)nc1

Procedure:
The title compound was prepared essentially as in Example 1 by combining 5-hexyloxy-2-(4-hydroxyphenyl)pyrimidine (2.26 g, 8.3 mmol) with 5-(2-(2-(pentafluoroethoxy) tetrafluoroethoxy)-2,2-difluoroethoxy)-1-bromopentane (4.08 g, 8.3 mmol; prepared by combining 1,5-dibromopentane with 2-(2-(pentafluoroethoxy)tetrafluoroethoxy)-2,2-difluoroethanol). Product was isolated by addition of water (160 mL) to the resulting mixture, followed by filtration and recrystallization from ethanol. The recrystallized precipitate was dried at about 130° C., and the resulting product was further purified by Kugelrohr distillation (b.p. 190°-205° C. at 0.3 torr; yield of 15.2 g).
Reaction SMILES: CCN(C(C)C)C(C)C.[NH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21].[CH2:25]([O:27][P:28]([CH2:33][C:34](O)=[O:35])([O:30][CH2:31][CH3:32])=[O:29])[CH3:26].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[CH2:31]([O:30][P:28]([CH2:33][C:34]([NH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[NH:17][C:18](=[O:24])[O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:35])([O:27][CH2:25][CH3:26])=[O:29])[CH3:32]
Reactant: CC(C)(C)OC(=O)Nc1ccccc1N
Reactant: CCOP(=O)(CC(=O)O)OCC
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCOP(=O)(CC(=O)Nc1ccccc1NC(=O)OC(C)(C)C)OCC
Reaction time: 6 h
Yield: 75.6 %

Procedure:
DIPEA (5.16 g, 6.90 mL, 40 mmol) and tert-butyl 2-aminophenylcarbamate (2.08 g, 10 mmol) were added to a solution of 2-(diethoxyphosphoryl)acetic acid (2.15 g, 11 mmol) in DCM (120 mL). After the mixture was stirred for ten minutes, HATU (4.56 g, 12 mmol) was added to the reaction and stirring was prolonged for 6 h at room temperature under a nitrogen atmosphere. After completion of the reaction as indicated by HPLC, the reaction mixture was washed with saturated NaHCO3 and brine. It was dried over Na2SO4 and filtered. The filtrate was evaporated in vacuo to get the crude product, which was triturated with 30% v/v hexanes in EtOAc for 30 min. The solid was filtered, washed with 30% hexanes in EtOAc and dried to get 2.92 g of tert-butyl (2-(2-(diethoxyphosphoryl)acetamido)phenyl)carbamate as an off-white solid in 76% yield.
Reaction SMILES: [OH:1][CH2:2][C:3]1[NH:4][C:5]2[CH:6]=[CH:7][CH:8]=[C:9]([C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[O:13])[C:10]=2[CH:11]=1.N1C=CN=C1.[Si:27](Cl)([C:40]([CH3:43])([CH3:42])[CH3:41])([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>CN(C)C=O.C(OCC)(=O)C>[Si:27]([O:1][CH2:2][C:3]1[NH:4][C:5]2[CH:6]=[CH:7][CH:8]=[C:9]([C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[O:13])[C:10]=2[CH:11]=1)([C:40]([CH3:43])([CH3:42])[CH3:41])([C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Reactant: O=C(OCc1ccccc1)c1cccc2[nH]c(CO)cc12
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C)(C)[Si](OCc1cc2c(C(=O)OCc3ccccc3)cccc2[nH]1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 96.1 %

Procedure:
To a solution of benzyl 2-hydroxymethylindole-4-carboxylate (456 mg) and imidazole (364 mg) in N,N-dimethylformamide (10 ml) was added tert-butyldiphenylsilyl chloride (802 mg) and the solution was stirred at ambient temperature for 2 hours. The resulting mixture was diluted with ethyl acetate (30 ml) and washed successively with water and brine. The organic layer was dried over magnesium sulfate and concentrated in vacuo. The residue was purified be silica gel column chromatography (eluent; n-hexane:ethyl acetate=15:1) to give benzyl 2-tert-butyldiphenylsilyloxymethylindole-4-carboxylate (810 mg).
Reaction SMILES: [C:1]([Si:5]([CH3:26])([CH3:25])[O:6][C@@H:7]([C@@H:9]1[C@@H:12]([C@H:13]([C:15]([S:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[S:16])[CH3:14])[NH:11][C:10]1=[O:24])[CH3:8])([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.Cl[C:34](=[O:41])[C:35]([O:37][CH2:38][CH:39]=[CH2:40])=[O:36]>ClCCl>[CH2:38]([O:37][C:35](=[O:36])[C:34]([N:11]1[C@H:12]([C@H:13]([C:15]([S:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[S:16])[CH3:14])[C@@H:9]([C@H:7]([O:6][Si:5]([C:1]([CH3:4])([CH3:2])[CH3:3])([CH3:26])[CH3:25])[CH3:8])[C:10]1=[O:24])=[O:41])[CH:39]=[CH2:40]
Reactant: C=CCOC(=O)C(=O)Cl
Reactant: C[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]1C(=O)N[C@@H]1[C@@H](C)C(=S)Sc1ccccc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: C=CCOC(=O)C(=O)N1C(=O)[C@H]([C@@H](C)O[Si](C)(C)C(C)(C)C)[C@H]1[C@@H](C)C(=S)Sc1ccccc1
Reaction time: 2 h

Procedure:
To a mixture of (3S,4S)-3-[(1R)-1-(tertbutyldimethylsilyloxy)ethyl] -4-[(1R)-1-{(phenylthio)thiocarbonyl}ethyl]-2-oxoazetidine (5.12 g) in dichloromethane (50 ml) were added pyridine (1.8 ml) and allyl chloroglyoxylate (2.3 ml) successively at 0° C. After stirring for 2 hours at the same temperature, to the solution were added pyridine (0.9 ml) and allyl chloroglyoxylate (0.75 ml). After stirring for 1 hour at 0° C., the solution was washed with water, 1N hydrochloric acid and brine, and dried. The solvent was removed under reduced pressure and the residue was purified by column chromatography (ethyl acetate:hexane=1:9) to afford (3S,4S)-1-(allyloxyoxalyl)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[(1R)-1-{(phenylthio)thiocarbonyl}ethyl]-2-oxoazetidine (4.77 g).
Reaction SMILES: [CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9]([O:13][CH3:14])(=[O:12])[CH:10]=[CH2:11]>C(O)C>[CH3:14][O:13][C:9]([CH2:10][CH2:11][N:8]([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH2:11][CH2:10][C:9]([O:13][CH3:14])=[O:12])=[O:12]
Reactant: NCc1ccccc1
Reactant: C=CC(=O)OC
Solvent: CCO
Product: COC(=O)CCN(CCC(=O)OC)Cc1ccccc1
Reaction time: 312 h

Procedure:
107 g of benzylamine in 200 ml of ethanol are cooled in an ice bath and 172.2 g of methyl acrylate in 250 ml of ethanol are slowly added. After 13 days at RT, the solvent is evaporated under vacuum and a part of the oily residue is then distilled.