AMEBA resin

Preparation of AMEBA Resin A from SASRIN Resin,... 

A total of 10.0 g (8.9 mmol) SASRIN resin2 (note 1) was washed with N,N-dimethyIfonnamide (DMF 2 x 25 mL), methanol (MeOH 2 x 25 mL), and dichloromethane (DCM note 2 2 x 25 mL), and dried under vacuum (0.5 torr) at 70°C overnight. To a suspension of the dried SASRIN resin in lOOmL of methyl sulfoxide (DMSO note 2) and 25 mL of DCM was added 12.4 mL (89 mmol, 10.0 Eq.) triethylamine (note 2) followed by 7.1 g (44.5 mmol, 5.0 Eq.) sulfur trioxide-pyridine complex (note 2). The suspension was shaken on a radial arm at room temperature overnight (note 3) filtered on a glass frit and washed with DCM (3 x 100mL), DMSO (3 x lOOmL), DCM (3 x lOOmL), and tetrahydrofuran (THF 3 x 100 mL) and dried under vacuum (0.5 torr) at room temperature to give 10.0 g Ameba resin (notes 4 and 5). 

Preparation of Ameba Resins Ba-Bd from Merrifield Resin3... 

Ameba resin Bb (Table 10.1) was prepared from 1.00 g (1.10 mmol) Merrifield resin (HL, 100-200 mesh note 6) in... 

TABLE 10.1. Ameba Resin Loading Values and Yields for Sulfonamide (1)... 

Prepared Starting Resin Loading (mmol/g) Calculated Loading of AMEBA Resin (mmol/g) Sulfonamide Yield (%) ... 

For the preparation of N- 2-(methoxyphenyl)cthyl ]-4-mcthylbcn-zenesulfonamide (1) from Ameba resins A and Ba-Bd, 100 mg (0.089 mmol) Ameba resin A was added to a glass peptide reaction vessel, suspended in 3.0 mL 1,2-dichloroethane (DCE note 2), and treated with 26 pL (0.18 mmol, 2.0 Eq.) 2-(4-methoxy-phenyl)ethylamine (note 2) and 38 mg (0.178 mmol, 2.0 Eq.) sodium triacetoxyborohydride (note 2). The suspension was shaken for 1 h treated with 5 mL MeOH filtered on a glass frit and washed with DCM (2x5 mL), DMF (2x5 mL), MeOH (2 x 5 mL), and DCM (2x5 mL). The resin was dried under vacuum (0.5 torr) at room temperature overnight. The resin was suspended in 1.5 mL DCM, treated with 155 pL (0.89 mmol, 10.0 Eq.) N,N-diisopropylethylamine (note 2) and 85 mg (0.445 mmol, 5.0 Eq.) p-toluenesulfonyl chloride (note 2), and shaken for 3.5 h. The reaction mixture was filtered on a glass frit, washed with DCM (2 x 5 mL), DMF (2x5 mL), MeOH (2x5 mL), and DCM (2 x 5 mL), and dried under vacuum (0.5 torr) at room temperature for 2h. The resin was treated with 2.5 mL of a solution of 5% trifluoroacetic acid (note 2) in DCM, shaken for 15 min, filtered on a glass frit, and washed with DCM (3x5 mL). The combined filtrate and washings were concentrated and dried under vacuum (0.5 torr) at room temperature overnight to afford 18.0 mg (66%) N- [2-(methoxyphenyl)ethyl] -4-methylbenzenesulfonamide (1). 

Ameba resin A loading was assumed to be 0.89 mmol/g, based on the loading of the starting SASRIN resin. 

Ameba resin was characterized by the diagnostic aldehyde signal at 10.5 ppm using Nanoprobe JH NMR.4 Checkers characterized Ameba resin by the diagnostic aldehyde signals at 1675-1684 cm 1 using IR. 

A solid-phase synthetic approach using 2,3-dichloro-6-aminoquinoxaUne whose 6-substutuent links on AMEBA resin facilitates the displacement of chlorine with amines, alkoxides, or other nucleophiles <2005TL4979>. 

The authors used commercially available Ameba resin ° for their investigations that upon reaction with ttimethyl orthoformate (4 equiv) and a suitably decorated benzylamine (4 equiv)... 

Kauhaluoma and Samanta used miinchnone as the key intermediate to obtain a triazole core (Scheme 9.41). Starting with Ameba resin 351, 3.84 equiv of amino acid ester 352 and 25 equiv of NaBHaCN were employed for the reductive alkylation in 1% acetic acid in DMF at room temperature for 12 h. Resin 353 was treated with 10 equiv of carboxylic acid chloride 354 in the presence of 12 equiv of A,A-diisopropylethylamine in DCM at room temperature for 12h to form amide 355, which was treated with 5% KOH in dioxane H20 (3 1) for 4h to give the corresponding carboxylic acid. Resin 356 was treated with 23.5 equiv of acetic acid anhydride, 3 equiv of DEAD (diethyl azodicarboxylate) 357, and 3 equiv of 4-phenyl-4/f-l,2,4-triazoline-3,5-dione 358 in DCM at room temperature for 5-10 h, giving the miinchnone intermediate 359, which reacted with compound 357 or 358 to form resin 360. Treatment of this with 30% TFA in DCM at room temperature for 1.5 h resulted in cleavage from the resin, producing 361. 

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