Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl-].[Cl:2][CH:3]=[N+:4]([CH3:6])[CH3:5].C([Si](C(C)C)(C(C)C)[N:11]1[CH:15]=[CH:14][CH:13]=[CH:12]1)(C)C>C(Cl)Cl>[Cl-:2].[CH3:5][N+:4]([CH3:6])=[CH:3][C:14]1[CH:13]=[CH:12][NH:11][CH:15]=1
Reactant: C[N+](C)=CCl
Reactant: CC(C)[Si](C(C)C)(C(C)C)n1cccc1
Agent: [Cl-]
Solvent: ClCCl
Product: C[N+](C)=Cc1cc[nH]c1
Temperature: 60 °C
Reaction time: 0.5 h
Yield: 127.8 %

Procedure:
10.60 g of (chloromethylene)dimethylammonium chloride and 6.25 g of N-(triisopropylsilyl)-pyrrole are suspended in 200 ml of CH2Cl2 under nitrogen at 0-5° C. The suspension is warmed to 60° C. and stirred for 30 minutes. Afterwards the mixture is cooled to ambient temperature. The suspension is filtered and washed with diethylether to give 5.67 g of the title compound as grey solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH2:15][CH2:16][CH3:17])=[CH:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1.[H][H]>[Pd].C(O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([CH2:15][CH2:16][CH3:17])[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:6][CH:7]=1
Reactant: [H][H]
Reactant: CCCC(=CC(=O)OCC)c1ccc(F)cc1
Agent: [Pd]
Solvent: CCO
Product: CCCC(CC(=O)OCC)c1ccc(F)cc1
Yield: 99.6 %

Procedure:
A mixture of ethyl 3-(4-fluorophenyl)hexenoate (58.12 g, 0.246 mol) and 10% palladium on carbon (1.1 g, Aldrich) in 95% ethanol was shaken in a Parr hydrogenator under a pressure of 2-4 atm of hydrogen for 0.75 hr. The mixture was filtered and concentrated by spin evaporation in vacuo to give 58.4 g (99.6%) of ethyl 3-(4-fluorophenyl)hexanoate as a clear liquid, NMR (DMSO-d6): d 7.27-7.20 (m, 2H), 7.12-7.04 (m, 2H), 3.91 (q, 2H, J=7.2 Hz), 2.99 (m, 1H), 2.66-2.59 (m, 1H), 2.52-2.44 (m, 1H, partially obscured by DMSO), 1.59-1.46 (m, 2H), 1.13-1.07 (m, 2H), 1.02 (t, 3H, J=7.2Hz), 0.78 (t, 3H, J=7.5 Hz).
Reaction SMILES: Cl[C:2]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][CH:7]=1)=[O:3].OCC[N:18]1[CH2:23][CH2:22][N:21]([C:24]([C@@H:26]2[CH2:30][C@H:29]([S:31][CH2:32][C:33]3[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=3)[CH2:28][N:27]2[C:41]([O:43][CH2:44][C:45]2[CH:50]=[CH:49][C:48]([N+:51]([O-:53])=[O:52])=[CH:47][CH:46]=2)=[O:42])=[O:25])[CH2:20][CH2:19]1.[C:54](OCC)(=[O:56])[CH3:55]>CN(C)C1C=CN=CC=1.C(Cl)Cl>[N+:12]([C:9]1[CH:10]=[CH:11][C:6]([CH2:5][O:4][C:2]([O:56][CH2:54][CH2:55][C:26]2([C:24]([N:21]3[CH2:20][CH2:19][NH:18][CH2:23][CH2:22]3)=[O:25])[CH2:30][CH:29]([S:31][CH2:32][C:33]3[CH:34]=[CH:35][C:36]([O:39][CH3:40])=[CH:37][CH:38]=3)[CH2:28][N:27]2[C:41]([O:43][CH2:44][C:45]2[CH:46]=[CH:47][C:48]([N+:51]([O-:53])=[O:52])=[CH:49][CH:50]=2)=[O:42])=[O:3])=[CH:7][CH:8]=1)([O-:14])=[O:13]
Reactant: CCOC(C)=O
Reactant: O=C(Cl)OCc1ccc([N+](=O)[O-])cc1
Reactant: COc1ccc(CS[C@H]2C[C@@H](C(=O)N3CCN(CCO)CC3)N(C(=O)OCc3ccc([N+](=O)[O-])cc3)C2)cc1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: COc1ccc(CSC2CN(C(=O)OCc3ccc([N+](=O)[O-])cc3)C(CCOC(=O)OCc3ccc([N+](=O)[O-])cc3)(C(=O)N3CCNCC3)C2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
5.86 g of 4-dimethylaminopyridine and a solution of 10.35 g of p-nitrobenzyl chloroformate in 40 ml of anhydrous methylene chloride were added to a solution of 22.35 g of (2S,4S)-2-[4-(2-hydroxyethyl)-1-piperazinylcarbonyl]-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (prepared as described in Preparation 7) in 160 ml of anhydrous methylene chloride, and the resulting mixture was stirred at room temperature for 1 hour. At the end of this time, the reaction mixture was diluted with 300 ml of ethyl acetate and washed with 100 ml of water, with 100 ml of a saturated aqueous solution of sodium hydrogencarbonate and with 100 ml of a saturated aqueous solution of sodium chloride, in that order. The solvents were removed by distillation under reduced pressure, and the resulting residue was purified by column chromatography through silica gel. Those fractions eluted with ethyl acetate were collected and concentrated by evaporation under reduced pressure, to give 26.35 g of the title compound as a colorless powder.
Reaction SMILES: [CH2:1]([Li])[CH2:2][CH2:3][CH3:4].CCCCCC.[CH3:12][C:13]([CH3:32])([CH3:31])[C:14]#[C:15]/[CH:16]=[CH:17]/[CH2:18][N:19]([CH2:21]C1C=C(C(=O)C)C=CC=1)[CH3:20].[CH:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>[Br-].C([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)C>[CH3:12][C:13]([CH3:31])([CH3:32])[C:14]#[C:15]/[CH:16]=[CH:17]\[CH2:18][N:19]([CH2:21][C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([C:2]([CH3:1])=[CH:3][CH3:4])[CH:34]=1)[CH3:20]
Reactant: CC(=O)c1cccc(CN(C)C/C=C/C#CC(C)(C)C)c1
Reactant: c1ccccc1
Reactant: [Li]CCCC
Agent: CC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Solvent: CCCCCC
Product: CC=C(C)c1cccc(CN(C)C/C=C\C#CC(C)(C)C)c1
Temperature: 25 °C
Yield: 25 %

Procedure:
Ethyl triphenylphosphonium bromide (0.98 g; 2.65 mmol) was added to benzene (15 ml). While the mixture was stirred under nitrogen atmosphere at room temperature, n-butyl lithium in n-hexane (1.56 M: 1.70 ml; 2.65 mmol) was added dropwise. The mixture was stirred for 5 minutes, and Compound 1 (0.50 g; 1.76 mmol) in benzene (5 ml) was added dropwise thereto, followed by heating under reflux for 3 hours. Subsequently, the mixture was left to cool to room temperature, and reaction was stopped by pouring the mixture into ice/water, followed by extraction with benzene (100 ml). The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=20:1), to thereby yield 0.13 g of the target compound (yield: 25.0%).
Reaction SMILES: Br[CH2:2][C:3]1[CH:7]=[C:6]([C:8]([CH3:11])([CH3:10])[CH3:9])[S:5][C:4]=1[C:12]([O:14][CH3:15])=[O:13].[Br:16][C:17]1[C:18]([CH3:24])=[C:19]([CH:21]=[CH:22][CH:23]=1)[NH2:20].C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[Br:16][C:17]1[C:18]([CH3:24])=[C:19]([NH:20][CH2:2][C:3]2[CH:7]=[C:6]([C:8]([CH3:11])([CH3:10])[CH3:9])[S:5][C:4]=2[C:12]([O:14][CH3:15])=[O:13])[CH:21]=[CH:22][CH:23]=1
Reactant: COC(=O)c1sc(C(C)(C)C)cc1CBr
Reactant: Cc1c(N)cccc1Br
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC#N
Product: COC(=O)c1sc(C(C)(C)C)cc1CNc1cccc(Br)c1C
Temperature: 25 °C
Reaction time: 16 h
Yield: 70.1 %

Procedure:
A 250-mL single-necked round-bottomed flask equipped with a magnetic stirrer was purged with nitrogen and charged with 101c (1.09 g, 4.68 mmol), 3-bromo-2-methyl-aniline (2.61 g, 14.0 mmol) and acetonitrile (25 mL). Cesium carbonate (1.67 g, 5.15 mmol) was added and the mixture was stirred at room temperature for 16 h. The reaction mixture was then concentrated under reduced pressure. Purification of the resulting residue by column chromatography afforded a 70% yield (1.30 g) of 101d as a yellow oil: 1H NMR (300 MHz, CDCl3) δ 6.92 (m, 2H), 6.85 (s, 1H), 6.57 (dd, 1H, J=4.8, 2.1 Hz), 4.60 (s, 2H), 3.86 (s, 3H), 2.29 (s, 3H), 1.37 (s, 9H); MS (ESI+) m/z 396.2 (M+H).
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:5]=1[C:6](Cl)=[O:7])([O-:3])=[O:2].[CH3:14][C:15]1([CH3:26])[C:20](=[O:21])[C:19]([CH3:23])([CH3:22])[C:18](=[O:24])[CH2:17][C:16]1=[O:25].C(N(CC)CC)C.CC(C)=O>C(Cl)Cl>[N+:1]([C:4]1[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:5]=1[C:6]([CH:17]1[C:16](=[O:25])[C:15]([CH3:26])([CH3:14])[C:20](=[O:21])[C:19]([CH3:23])([CH3:22])[C:18]1=[O:24])=[O:7])([O-:3])=[O:2]
Reactant: O=C(Cl)c1ccc(Cl)cc1[N+](=O)[O-]
Reactant: CC1(C)C(=O)CC(=O)C(C)(C)C1=O
Solvent: ClCCl
Solvent: CC(C)=O
Solvent: CCN(CC)CC
Product: CC1(C)C(=O)C(C(=O)c2ccc(Cl)cc2[N+](=O)[O-])C(=O)C(C)(C)C1=O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 60.1 %

Procedure:
2-Nitro-4-chlorobenzoyl chloride (2.2 g, 10 mmol) and 4,4,6,6-tetramethyl-1,3,5-cyclohexanetrione (1.8 g, 10 mmol) were dissolved in methylene chloride. Triethylamine was added and the resulting solution stirred at room temperature for 30 minutes. The solution was washed with 1 normal hydrochloric acid (1N HCl), and saturated sodium chloride (brine), dried over anhydrous magnesium sulfate (MgSO4) and concentrated under vacuum. The residue was dissolved in 20 ml acetonitrile. Triethylamine (5 ml, 3.5 equivalents) and acetone cyanohyrdin (0.5 g, 0.6 equivalent) were added and the mixture stirred at room temperature for 4 hours. After dilution with ether, the solution was washed with 1N HCl and extracted with 5% K2CO3. The basic extract was acidified with HCl and extracted with ether. The ether extract was washed with brine, dried over MgSO4 and concentrated under vacuum, yielding 2.2 g of crude product.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[CH3:12].[Br:13]N1C(=O)CCC1=O>N(C(C)(C)C#N)=NC(C)(C)C#N.C(Cl)(Cl)(Cl)Cl>[Br:13][CH2:12][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:2]=1[Cl:1])[C:6]([O:8][CH3:9])=[O:7]
Reactant: COC(=O)c1ccc(Cl)c(C)c1
Reactant: O=C1CCC(=O)N1Br
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)c1ccc(Cl)c(CBr)c1
Temperature: 25 °C
Yield: 59.5 %

Procedure:
40.4 g of methyl 4-chloro-3-methylbenzoate, 39 g of N-bromosuccinimide and 1 g of azobisisobutyronitrile were added to 300 ml of carbon tetrachloride, followed by reflux under heating for 4 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, insoluble matters were collected by filtration and the filtrate was concentrated. The obtained crude crystals were washed with hexane to obtain 34.3 g of methyl 3-bromomethyl-4-chlorobenzoate as white crystals.
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[S:10][C:9]([CH2:11][NH2:12])=[CH:8][C:6]=2[N:7]=1.[CH3:19][O:20][C:21]1[CH:22]=[C:23]([CH2:27][C:28](Cl)=[O:29])[CH:24]=[CH:25][CH:26]=1.CC1(C)C(C)(C)OB([C:39]2[CH:47]=[CH:46][CH:45]=[C:44]3[C:40]=2[CH:41]=[N:42][NH:43]3)O1>>[NH:43]1[C:44]2[C:40](=[C:39]([C:2]3[N:3]=[C:4]([N:13]4[CH2:18][CH2:17][O:16][CH2:15][CH2:14]4)[C:5]4[S:10][C:9]([CH2:11][NH:12][C:28](=[O:29])[CH2:27][C:23]5[CH:24]=[CH:25][CH:26]=[C:21]([O:20][CH3:19])[CH:22]=5)=[CH:8][C:6]=4[N:7]=3)[CH:47]=[CH:46][CH:45]=2)[CH:41]=[N:42]1
Reactant: CC1(C)OB(c2cccc3[nH]ncc23)OC1(C)C
Reactant: NCc1cc2nc(Cl)nc(N3CCOCC3)c2s1
Reactant: COc1cccc(CC(=O)Cl)c1
Product: COc1cccc(CC(=O)NCc2cc3nc(-c4cccc5[nH]ncc45)nc(N4CCOCC4)c3s2)c1
Yield: 33 %

Procedure:
(2-Chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methanamine 27 from Example 11 (53.2 mg, 0.19 mM) was reacted with 3-methoxyphenylacetyl chloride (2.2 eq) followed by Suzuki coupling of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)1H-indazole 7 as per General Procedure K. Complete reaction was confirmed by LCMS and the reaction was concentrated in vacuo to give 16.0 mg of 377 after RP-HPLC purification (33% yield). MS (Q1) 515.3 (M)+
Reaction SMILES: [OH:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][O:15][C:16]1[CH:24]=[CH:23][C:19]([C:20]([OH:22])=[O:21])=[C:18]([OH:25])[C:17]=1[CH2:26][CH2:27][CH3:28].[CH2:29](I)[CH2:30][CH2:31][CH2:32][CH2:33][CH3:34].C(=O)(O)[O-].[Na+]>CN(C)C=O>[CH2:29]([O:21][C:20](=[O:22])[C:19]1[CH:23]=[CH:24][C:16]([O:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][C:3]2[CH:4]=[CH:5][CH:6]=[C:7]([OH:8])[C:2]=2[OH:1])=[C:17]([CH2:26][CH2:27][CH3:28])[C:18]=1[OH:25])[CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]
Reactant: CCCc1c(OCCCCCCc2cccc(O)c2O)ccc(C(=O)O)c1O
Reactant: CCCCCCI
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCCCOC(=O)c1ccc(OCCCCCCc2cccc(O)c2O)c(CCC)c1O
Yield: 83.2 %

Procedure:
A mixture of 1.00 g (2.57 mmol) of 4-[6-(2,3-dihydroxyphenyl)hexyloxy]-2-hydroxy-3-propylbenzoic acid, 0.76 mL (5.15 mmol) of n-hexyl iodide and 0.26 g (3.36 mmol) of sodium bicarbonate in 15 mL of anhydrous dimethylformamide was stirred and heated at 70° for 16 hours. The solvent was removed on the oil pump, water was added and the product was extracted with ethyl acetate. The dried extract was concentrated under reduced pressure to an oil which was purified by chromatography on silica gel using 5% ethyl acetate-toluene to give 1.01 g (83% yield) of 4-[6-(2,3-dihydroxyphenyl)hexyloxy]-2-hydroxy-3-propylbenzoic acid hexyl ester as an oil.
Reaction SMILES: [N+](C1C=CC=CC=1O[C:11](=[O:35])[C@@H:12]([CH2:21][CH2:22][CH2:23][NH:24][C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])[NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])([O-])=O.[OH:36][C:37]1[CH:45]=[CH:44][C:40]([C@H:41]([NH2:43])[CH3:42])=[CH:39][CH:38]=1>C(Cl)Cl.CCOC(C)=O>[C:14]([NH:13][C@@H:12]([C:11]([NH:43][C@@H:41]([C:40]1[CH:44]=[CH:45][C:37]([OH:36])=[CH:38][CH:39]=1)[CH3:42])=[O:35])[CH2:21][CH2:22][CH2:23][NH:24][C:25]([O:27][CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)=[O:26])([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15]
Reactant: C[C@@H](N)c1ccc(O)cc1
Reactant: CC(C)(C)OC(=O)N[C@H](CCCNC(=O)OCc1ccccc1)C(=O)Oc1ccccc1[N+](=O)[O-]
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: C[C@@H](NC(=O)[C@@H](CCCNC(=O)OCc1ccccc1)NC(=O)OC(C)(C)C)c1ccc(O)cc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
Nα -Boc-Nδ -Cbz-(R)-ornithine o-nitrophenyl ester (33 g; 66.8 mmol; from step (a) above) and (R)-4-hydroxy-α-methylbenzylamine (9.3 g; 68.2 mmol) were combined in CH2Cl2 (600 mL). The resulting yellow solution was stirred at room temperature for 4 hours. When the coupling was complete, as determined by TLC, the solution was concentrated under vacuum to give the crude product. The crude material was dissolved in EtOAc, washed with 0.5N NaOH (2×300 mL), saturated KHSO4 (2×300 mL), brine (2×300 mL), dried over Na2SO4, filtered and concentrated to yield 30.1 g (61.9 mmol; 93%) of the sub-title compound.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:10]([C:29](O)=[O:30])=[N:11][C:12]([CH2:16][C:17]2([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)=[N:13][C:14]=1[OH:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Si:32]([O:39][CH2:40][CH2:41][NH:42][CH:43]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[CH3:44])([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33].O=P(Cl)(Cl)Cl.C(O)CO.C(=O)=O>N1C=CC=CC=1>[CH2:1]([O:8][C:9]1[C:10]([C:29]([N:42]([CH2:41][CH2:40][O:39][Si:32]([C:35]([CH3:36])([CH3:38])[CH3:37])([CH3:34])[CH3:33])[CH:43]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[CH3:44])=[O:30])=[N:11][C:12]([CH2:16][C:17]2([C:22]3[CH:23]=[CH:24][C:25]([Cl:28])=[CH:26][CH:27]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)=[N:13][C:14]=1[OH:15])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(NCCO[Si](C)(C)C(C)(C)C)c1ccccc1
Reactant: O=C(O)c1nc(CC2(c3ccc(Cl)cc3)CCCC2)nc(O)c1OCc1ccccc1
Agent: O=C=O
Solvent: OCCO
Solvent: c1ccncc1
Solvent: O=P(Cl)(Cl)Cl
Product: CC(c1ccccc1)N(CCO[Si](C)(C)C(C)(C)C)C(=O)c1nc(CC2(c3ccc(Cl)cc3)CCCC2)nc(O)c1OCc1ccccc1
Temperature: 0 °C
Reaction time: 2 h
Yield: 81.1 %

Procedure:
To a solution of 5-(benzyloxy)-2-((1-(4-chlorophenyl)cyclopentyl)methyl)-6-hydroxypyrimidine-4-carboxylic acid (28-02) (170 mg, 387 μmol, Eq: 1.00) and 2-(tert-butyldimethylsilyloxy)-N-(1-phenylethyl)ethanamine (34) (108 mg, 387 μmol, Eq: 1.00) in pyridine (2.00 ml) was added POCl3 (178 mg, 108 μl, 1.16 mmol, Eq: 3.00) at −10° C. (ethylene glycol-dry-ice bath), then the reaction mixture was stirred at 0° C. for 2 hr. The reaction mixture was quenched with ice cooled-water (0.5 ml), concentrated, and chromatographed (silica gel, gradient 5 to 30% ethyl acetate-hexane) to obtain 5-(benzyloxy)-N-(2-(tert-butyldimethylsilyloxy)ethyl)-2-((1-(4-chlorophenyl)cyclopentyl)methyl)-6-hydroxy-N-(1-phenylethyl)pyrimidine-4-carboxamide (35) (220 mg, 314 μmol, 81.1% yield).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[C:13]([C:18]([F:21])([F:20])[F:19])[CH:14]=[CH:15][CH:16]=3)[N:11]=[CH:10][C:9]=2[C:22]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:23])[CH:5]=[CH:6][CH:7]=1.Br[CH2:31][C:32]1[CH:41]=[CH:40][C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[N:33]=1>>[C:24]1([C:22]([C:9]2[CH:10]=[N:11][C:12]3[C:17]([C:8]=2[C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([O:1][CH2:31][C:32]4[CH:41]=[CH:40][C:39]5[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=5)[N:33]=4)[CH:3]=2)=[CH:16][CH:15]=[CH:14][C:13]=3[C:18]([F:21])([F:19])[F:20])=[O:23])[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: BrCc1ccc2ccccc2n1
Reactant: O=C(c1ccccc1)c1cnc2c(C(F)(F)F)cccc2c1-c1cccc(O)c1
Product: O=C(c1ccccc1)c1cnc2c(C(F)(F)F)cccc2c1-c1cccc(OCc2ccc3ccccc3n2)c1

Procedure:
The title compound was prepared from [4-(3-hydroxyphenyl)-8-(trifluoromethyl)quinolin-3-yl](phenyl)methanone and 2-Bromomethyl-quinoline following the procedure of Example 478: MS (ES) m/z 535.3.
Reaction SMILES: C1C(=O)N(OC(CCCCCN[C:17]([CH2:19][CH2:20][CH2:21][CH2:22][C@@H:23]2[S:27][CH2:26][C@@H:25]3[NH:28][C:29]([NH:31][C@H:24]23)=[O:30])=[O:18])=O)C(=O)C1.CN(C=[O:36])C>>[OH:36][C:17]([CH2:19][CH2:20][CH2:21][CH2:22][C@H:23]1[C@@H:24]2[C@@H:25]([NH:28][C:29]([NH:31]2)=[O:30])[CH2:26][S:27]1)=[O:18]
Reactant: O=C(CCCC[C@@H]1SC[C@@H]2NC(=O)N[C@@H]21)NCCCCCC(=O)ON1C(=O)CCC1=O
Reactant: CN(C)C=O
Product: O=C(O)CCCC[C@@H]1SC[C@@H]2NC(=O)N[C@@H]21
Reaction time: 3 h

Procedure:
Purified antibodies or their fragments, obtained as described in paragraph A at 1 mg/ml in PBS, were biotinylated for 3 hours at 25° C. (ambient temperature) by adding 37 μl of 10 mg/ml solution of NHS-LC-Biotin, Product #21335; Pierce, Rockford, Ill) in anhydrous DMF. Subsequently, the derivatized antibody was buffer-exchanged on a G25F column into PBS and stored at 0-4° C.
Reaction SMILES: [H-].[Na+].[Br:3][C:4]1[C:17]([CH3:18])=[CH:16][CH:15]=[CH:14][C:5]=1[C:6]([NH:8][CH2:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:7].I[CH3:20]>C1COCC1>[Br:3][C:4]1[C:17]([CH3:18])=[CH:16][CH:15]=[CH:14][C:5]=1[C:6]([N:8]([CH3:20])[CH2:9][C:10]([CH3:12])([CH3:13])[CH3:11])=[O:7]
Reactant: Cc1cccc(C(=O)NCC(C)(C)C)c1Br
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1cccc(C(=O)N(C)CC(C)(C)C)c1Br
Reaction time: 0.33 h

Procedure:
To a slurry of NaH (60% in mineral oil) (0.122 mL, 2.81 mmol) in THF (5 ml) was added dropwise a solution of 2-bromo-3-methyl-N-neopentylbenzamide (400 mg, 1.407 mmol) in THF (1 ml) at RT. After 20 min, iodomethane (0.096 mL, 1.548 mmol) was added and the reaction was allowed to stir for 48 h. The reaction was quenched by the addition of water and EtOAc. The organic phase was separated and dried over MgSO4. The solvent was removed under reduced pressure and the residue was purified by flash chromatography (6-48% EtOAc/hexanes). 2-Bromo-N,3-dimethyl-N-neopentylbenzamide was isolated as a clear colorless viscous oil.
Reaction SMILES: [Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=4[Cl:22])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH2:23]SCC)=[CH:4][CH:3]=1.Cl[C:28]1C=CC=C(C(OO)=O)[CH:29]=1.[S:38]([O-:42])([O-])(=[O:40])=S.[Na+].[Na+]>C(#N)C>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=4[Cl:22])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH2:23][S:38]([CH2:28][CH3:29])(=[O:42])=[O:40])=[CH:4][CH:3]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCSCc1ccc(Cl)c2nc3n(c12)CCCN3c1ccc(Cl)cc1Cl
Reactant: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: CC#N
Product: CCS(=O)(=O)Cc1ccc(Cl)c2nc3n(c12)CCCN3c1ccc(Cl)cc1Cl
Temperature: 0 °C
Reaction time: 1 h
Yield: 82 %

Procedure:
To a solution of 9-Chloro-1-(2,4-dichlorophenyl)-6-[(ethylsulfanyl)methyl]-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole (216 mg, 0.506 mmol) in acetonitrile (10 mL) was added 3-chloroperbenzoic acid (70%, 0.274 g, 1.11 mmol) at 0° C. The mixture was stirred at 0° C. for 1 hr. Aqueous sodium thiosulfate was added to the reaction mixture at 0° C. and the mixture was stirred at room temperature. The mixture was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogen carbonate and brine. The organic layer was concentrated in vacuo and the precipitated solid was collected by filtration. The solid was washed with water, 2-propanol and diisopropyl ether to give the title compound (190 mg, 0.414 mmol, 82%) as a colorless solid.
Reaction SMILES: [Cl:1][C:2]1[C:14]([Cl:15])=[C:13](/[CH:16]=[C:17](/[N+:20]([O-:22])=[O:21])\[CH2:18][CH3:19])[CH:12]=[CH:11][C:3]=1[O:4][CH2:5][CH2:6][CH2:7][C:8]([OH:10])=[O:9].O.C(=O)(O)[O-].[Na+:28]>>[Cl:1][C:2]1[C:14]([Cl:15])=[C:13](/[CH:16]=[C:17](/[N+:20]([O-:22])=[O:21])\[CH2:18][CH3:19])[CH:12]=[CH:11][C:3]=1[O:4][CH2:5][CH2:6][CH2:7][C:8]([O-:10])=[O:9].[Na+:28]
Reactant: CC/C(=C\c1ccc(OCCCC(=O)O)c(Cl)c1Cl)[N+](=O)[O-]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Product: CC/C(=C\c1ccc(OCCCC(=O)[O-])c(Cl)c1Cl)[N+](=O)[O-]

Procedure:
250 mg of (E)-4-[2,3-dichloro-4-(2-nitro-1-butenyl)phenoxy]butyric acid is dissolved in 3.1 ml of 0.1 N sodium bicarbonate and sufficient isotonic buffer to make a final volume of 10 ml. The water from all sources was pyrogen-free. The solution is sterilized by filtration.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[OH:9].[C:10]([Si:14](Cl)([CH3:16])[CH3:15])([CH3:13])([CH3:12])[CH3:11].N1C=CN=C1>>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[O:9][Si:14]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:16])[CH3:15]
Reactant: Oc1c(F)cccc1F
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Product: CC(C)(C)[Si](C)(C)Oc1c(F)cccc1F
Yield: 83.2 %

Procedure:
2,6-Difluorophenol (8.6 g, 66 mmol) was treated with tert-butylchlorodimethylsilane (17.4 g, 0.12 mol) and imidazole (13.1 g, 0.19 mol) by the method in Example 1 to give 13.41 g (83%) of tert-butyldimethylsilyl 2,6-difluorophenyl ether.
Reaction SMILES: [CH3:1][CH:2]([C:11](=[O:21])[CH2:12][C:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=O)[C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=O.[Cl:22][C:23]1[C:29]([CH3:30])=[C:28]([Cl:31])[CH:27]=[CH:26][C:24]=1[NH2:25].C1(C)C=CC(S(O)(=O)=O)=CC=1>ClC1C=CC=CC=1>[Cl:22][C:23]1[C:29]([CH3:30])=[C:28]([Cl:31])[CH:27]=[CH:26][C:24]=1[N:25]1[C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:12][C:11](=[O:21])[C:2]([CH3:1])=[C:3]1[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: CC(C(=O)CC(=O)c1ccccc1)C(=O)c1ccccc1
Reactant: Cc1c(Cl)ccc(N)c1Cl
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Clc1ccccc1
Product: Cc1c(Cl)ccc(-n2c(-c3ccccc3)cc(=O)c(C)c2-c2ccccc2)c1Cl

Procedure:
In 170 ml of chlorobenzene were dissolved 3.4 g (0.012 mole) of 2-methyl-1,5-diphenyl-1,3,5-pentanetrione and 10.6 g (0.06 mole) of 2,4-dichloro-3-methylaniline, followed by further addition of 4.1 g (0.022 mole) of para-toluenesulfonic acid and 35.0 g of Molecular Sieves 5A to the solution. After heating the reaction mixture under reflux for 2 hours, solid matter was removed from the reaction mixture, followed by an addition of 200 ml of chloroform. The resultant mixture was washed first with 100 ml of 10% hydrochloric acid and then with 100 ml of a 10% aqueous solution of sodium hydroxide. The mixture was washed further with water and was then dried over anhydrous sodium sulfate. Subsequent to removal of the sodium sulfate, the solvent was distilled off and the residue was purified by chromatography on a silica gel column (eluent: ethyl acetate). Upon recrystallization of the resultant crystals from a 2:1 mixed solvent of acetone and hexane, 0.7 g of 1-(2,4-dichloro-3-methylphenyl)-3-methyl-2,6-diphenyl-4(1H)-pyridinone having a melting point of 237°-238° C. was obtained.