2-tritylsulfanylethanamine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-bromoacetyl-S-Triphenylmethyl-L-cysteine ethyl ester (1.0 g, 1.98 mmol.) and triethylamine (0.4 mL, 2.9 mmol.) in methylene chloride (10 mL) was added S-triphenylmethyl-2-aminoethanethiol (0.64 g, 2.0 mmol.). The reaction mixture allowed to stir at room temperature for seven days. Water (10 mL) was added. The organic layer was washed with NaHCO3 (2×10 mL), water (2×10 mL), and brine (10 mL), dried (magnesium sulfate), and concentrated in vacuo to give a foamy product. Flash chromatography using ethyl acetate:hexane (3:1) gave the product in 22% yield. MS (M+H)=751, calculated 751.3. The organic layer was washed with NaHCO3 (2×10 mL), water (2×10 mL), and brine (10 mL) dried (magnesium sulfate) concentrated in vacuo to give a foamy product gave the product in 22% yield

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2-aminoethanethiol.HCl 80 (11.4 g, 100 mmol), triphenylmethanol (TrOH, 26.0 g, 100 mmol) in HCl (37%, 44.8 mL) and acetic acid (280 mL) was stirred for 5 h at 40° C. The reaction mixture was concentrated in vacuo and the resulting white solid was washed with ether and dissolved in H2O/CH2Cl2 (1:1). After adjusting the pH of the aqueous layer to ca. 14 with 1 N NaOH, the desired compound was removed by extraction. The combined organic layers were dried (K2CO3), filtered, and concentrated in vacuo to provide a white solid, S-(triphenylmethyl) 2-aminoethanethiol (28.8 g, 90.0 mmol, 90% from 80). Rf =0.50 (1:9 MeOH/CH2Cl2); 1H NMR (DMSO-d6) δ7.35-7.20 (m, 15H), 2.43 (t, J=6.1, 2H), 2.15 (t, J=5.9, 2H). To a solution of S-(triphenylmethyl) 2-aminoethanethiol (3.00 g, 9.40 mmol) and triethylamine (951 mg, 9.40 mmol) in dry CH2Cl2 (30 mL) was added bromoacetyl bromide (1.90 g, 9.40 mmol) over 15-20 min at -20°. The reaction mixture was stirred at -20° for 30 min and at room temperature for 1 h. To this mixture was added an additional equivalent of S-(triphenylmethyl) 2-amninoethanethiol (3.00 g, 9.40 mmol) and triethylamine (951 mg, 9.40 mmol). After stirring for 16 h at room temperature, the reaction mixture was concentrated under reduced pressure. The crude product was purified by flash chromatography (1:99 MeOH/CH2Cl2) to give compound 81 as a white foam (4.64 g, 6.95 mmol, 67% from amine 80). Rf 0.60 (1:9 MeOH/CH2Cl2); 1H NMR (DMSO-d6) δ7.77 (t, J=6.1, 1H), 7.35-7.20 (m, 30H), 2.97 (dd, J=6.0, 5.9, 2H), 2.86 (s, 2H), 2.35 (t, J=6.1, 2H), 2.18 (m, 4H). See Photaki et al., J. Chem. Soc. (c) 2683-2687 (1970); Bryson, N. J., Neutral technetium (v) complexes with N,S-donor chelates. Ph.D. thesis, Massachusetts Institute of Technology, Cambridge, Mass. (1988). The reaction mixture was concentrated in vacuo the resulting white solid was washed with ether dissolved in H2O/CH2Cl2 (1:1) the desired compound was removed by extraction The combined organic layers were dried (K2CO3) filtered concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Triphenylmethanol (22.9 g, 88 mmol) was added to a solution of 2-aminoethanethiol hydrochloride in trifluroacetic acid (TFA, 40 mL). The resulting solution was stirred at room temperature for about 40 min. The TFA was then removed under reduced pressure and the residue was triturated with diethyl ether. The white precipitate that formed was filtered, partitioned with aqueous NaOH (40 mL, 1N), and extracted with ethyl acetate (3×50 mL). The combined organic layers were dried over Na2SO4. The product was obtained as a white solid after solvent evaporation (23.8 g, yield 85%). ESI-MS(m/z): 320 (M+H+). 1H NMR δD (CDCl3): 7.21˜7.43 (m, 15H, phenyl), 2.58 (t, 2H, SCH2), 2.32 (t, 2H, CH2N). The TFA was then removed under reduced pressure the residue was triturated with diethyl ether The white precipitate that formed was filtered partitioned with aqueous NaOH (40 mL, 1N) extracted with ethyl acetate (3×50 mL) The combined organic layers were dried over Na2SO4 The product was obtained as a white solid after solvent evaporation (23.8 g, yield 85%)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 5-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-1H-pyrrole-2-carboxylic acid (940 mg, 2.1 mmol) synthesized in Example (18a), 2-(tritylthio)ethaneamine (1.01 g, 3.17 mmol) synthesized in Example (25a) and 4-dimethylaminopyridine (13 mg, 0.1 mmol) were added, followed by dissolution in dichloromethane (50 mL), and subsequently WSCI•HCl (445 mg, 2.3 mmol) was added at room temperature, and stirring was carried out for 1 hour under nitrogen atmosphere. The reaction solution was diluted with dichloromethane (150 mL), washed with 1N hydrochloric acid, a saturated aqueous sodium hydrogencarbonate solution and saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=10%-55%) to afford the desired product (1.08 g, yield 69%) as a white solid. washed with 1N hydrochloric acid a saturated aqueous sodium hydrogencarbonate solution and saturated brine, and subsequently dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure the resulting residue was purified silica gel column chromatography (elution solvent: ethyl acetate/hexane=10%-55%)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 5-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-1H-pyrrole-2-carboxylic acid (940 mg, 2.1 mmol) synthesized in Example (18a), 2-(tritylthio)ethaneamine (1.01 g, 3.17 mmol) synthesized in Example (25a) and 4-dimethylaminopyridine (13 mg, 0.1 mmol) were added, followed by dissolution in dichloromethane (50 mL), and subsequently WSCI•HCl (445 mg, 2.3 mmol) was added at room temperature, and stirring was carried out for 1 hour under nitrogen atmosphere. The reaction solution was diluted with dichloromethane (150 mL), washed with 1N hydrochloric acid, a saturated aqueous sodium hydrogencarbonate solution and saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=10%-55%) to afford the desired product (1.08 g, yield 69%) as a white solid. washed with 1N hydrochloric acid a saturated aqueous sodium hydrogencarbonate solution and saturated brine, and subsequently dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure the resulting residue was purified silica gel column chromatography (elution solvent: ethyl acetate/hexane=10%-55%)