Patent Application: US-69435303-A

Abstract:
nitrophenol resins based upon various support materials . the nitrophenol resins are prepared by amide bond formation between a hydroxyl nitro benzoic acid and an aminoalkyl polymer support .

Description:
the water compatible properties of tantagel , polyethylene glycol dimethacrylamide copolymer , and silica gel resin makes it possible to conduct the amination reaction in aqueous media . active benzoyl esters ( tantagel , polyethylene glycol dimethacryalamide copolymer , silica gel ) were prepared by a base catalyzed reaction with benzoyl chloride as described above . amide couplings in aqueous solution were carried out using 0 . 1 m glycine in 0 . 1 m nahco 3 or k 2 co 3 condition , as shown in scheme 4 ( corbett et al ., 2002 ). the nitrophenol resin 2 is also useful in preparing sulfonamides . sulfonyl halides were loaded onto resin 2 to form active sulfonic ester in the presence of pyridine base . the sulfonamide synthesis was performed by amine addition to resin 6 a , and the resulting product was determined by liquid chromatography - mass spectroscopy . in a 50 ml polystyrene cartridge , to an amino polystyrene resin ( 1 g , 1 . 2 mmol ) in dmf ( 15 ml ) were added 4 - hydroxy - 3 - nitrobenzoic acid ( 1 a ) ( 1 g , 5 . 46 mmol ), hobt ( 1 g , 7 . 4 mmol ), and dic ( 1 , 3 - diisopropylcarbodiimide , 1 ml , 6 . 4 mmol ). after overnight shaking , the reaction mixture was washed with dmf ( 20 ml , 5 times ), methylene chloride , and methanol ( 20 ml , 5 times each ). to remove any undesirable side product , dmf ( 5 ml ) and piperidine ( 0 . 5 ml ) were added to the cartridge and allowed to shake for 1 . 5 h . the resin was filtered and washed with dmf . the resulting piperidine salt was removed via the addition of a 10 % hcl solution ( in dmf , 20 ml ) to the resin that was allowed to shake for 1 . 5 h . the mixture was then filtered , washed with dmf ( 20 ml , 5 times ), methanol , and methylene chloride ( 20 ml , 5 times each ) and dried by nitrogen gas flow . in a 50 ml polystyrene cartridge , to an amino tantagel ( 1 g , 0 . 45 mmol ) in dmf ( 15 ml ) were added 4 - hydroxy - 3 - nitrobenzoic acid ( 1 a ) ( 1 g , 5 . 46 mmol ), hobt ( 1 g , 7 . 4 mmol ), and dic ( 1 , 3 - diisopropylcarbodiimide , 1 ml , 6 . 4 mmol ). after overnight shaking , the reaction mixture was washed with dmf ( 20 ml , 5 times ), methylene chloride , and methanol ( 20 ml , 5 times each ). to remove any undesirable side product , dmf ( 5 ml ) and piperidine ( 0 . 5 ml ) were - added to the cartridge and allowed to shake for 1 . 5 h . the resin was filtered and washed with dmf . the resulting piperidine salt was removed via the addition of a 10 % hcl solution ( in dmf , 20 ml ) to the resin that was allowed to shake for 1 . 5h . the mixture was then filtered , washed with dmf ( 20 ml , 5 times ), methanol , and methylene chloride ( 20 ml , 5 times each ) and dried by nitrogen gas flow . this material was prepared from 4 - hydroxy - 3 - nitrobenzoic acid ( 1 a ) ( 1 g , 5 . 46 mmol ), hobt ( 1 g 7 . 4 mmol ), dic ( 1 , 3 - diisopropylcarbodiimide , 1 ml , 6 . 4 mmol ), an amino pega resin ( 1 g , 0 . 40 mmol ) using a procedure similar to polystyrene resin ( ps - 2 a ). this material was prepared from 4 - hydroxy - 3nitrobenzoic acid ( 1 a ) ( 1 g , 5 . 46 mmol ), hobt ( 1 g 7 . 4 mmol ), dic ( 1 , 3 - diisopropylcarbodiimide , 1 ml , 6 . 4 mmol ), and a mp resin ( 1 g , 0 . 99 mmol ) using a procedure similar to polystyrene resin ( ps - 2 a ). this material was prepared from 3 - hydroxy - 4 - nitrobenzoic acid ( 1 b ) ( 1 g , 5 . 46 mmol ), hobt ( 1 g , 7 . 4 mmol ), dic ( 1 , 3 - diisopropylcarbodiimide , 1 ml , 6 . 4 mmol ), and an amino polystyrene resin ( 1 g , 1 . 2 mmol ) using a procedure similar to polystyrene resin ( ps - 2 a ). this material was prepared from 3 - hydroxy - 4nitrobenzoic acid ( 1 b ) ( 1 g , 5 . 46 mmol ), hobt ( 1 g , 7 . 4 mmol ), dic ( 1 , 3 - diisopropylcarbodiimide , 1 ml , 6 . 4 mmol ), and an amino tantagel resin ( 1 g , 0 . 45 mmol ) using a procedure similar to polystyrene resin ( ps - 2 a ). this material was prepared from 3 - hydroxy - 4 - nitrobenzoic acid ( 1 b ) ( 1 g , 5 . 46 mmol ), hobt ( 1 g , 7 . 4 mmol ), dic ( 1 , 3 - diisopropylcarbodiimide , 1 ml , 6 . 4 mmol ), and an amino pega resin ( 1 g , 0 . 4 mmol ) using a procedure similar to polystyrene resin ( ps - 2 a ). this material was prepared from 3 - hydroxy - 4 - nitrobenzoic acid ( 1 b ) ( 1 g , 5 . 46 mmol ), hobt ( 1 g , 7 . 4 mmol ), dic ( 1 , 3 - diisopropylcarbodiimide , 1 ml , 6 . 4 mmol ), and an amino macroporous resin ( 1 g , 0 . 99 mmol ) using a procedure similar to polystyrene resin ( ps - 2 a ). this material was prepared from 5 - nitrosalicylic acid ( 1 c ) ( 1 g , 5 . 46 mmol ), hobt ( 1 g , 7 . 4 mmol ), dic ( 1 , 3 - diisopropylcarbodiimide , 1 ml , 6 . 4 mmol ), and an amino polystyrene resin ( 1 g , 1 . 2 mmol ) using a procedure similar to polystyrene resin ( ps - 2 a ). this material was prepared from 5 - nitrosalicylic acid ( 1 c ) ( 1 g , 5 . 46 mmol ), hobt ( 1 g , 7 . 4 mmol ), dic ( 1 , 3 - diisopropylcarbodiimide , 1 ml , 6 . 4 mmol ), and an amino tantagel resin ( 1 g , 0 . 45 mmol ) using a procedure similar to polystyrene resin ( ps - 2 a ). this material was prepared from 5 - nitrosalicylic acid ( 1 c ) ( 1 g , 5 . 46 mmol ), hobt ( 1 g , 7 . 4 mmol ), dic ( 1 , 3 - diisopropylcarodiimide , 1 ml , 6 . 4 mmol ), and an amino pega resin ( 1 g , 0 . 4 mmol ) using a procedure similar to polystyrene resin ( ps - 2 a ). this material was prepared from 5 - nitrosalicylic acid ( 1 c ) ( 1 g , 5 . 46 mmol ), hobt ( 1 g , 7 . 4 mmol ), dic ( 1 , 3 - diisopropylcarodiimide , 1 ml , 6 . 4 mmol ), and an amino macroporous resin ( 1 g , 0 . 99 mmol ) using a procedure similar to polystyrene resin ( ps - 2 a ). this material was prepared from 3 , 5 - dinitrosalicylic acid ( 1 c ) ( 1 g , 4 . 4 mmol ), hobt ( 1 g , 7 . 4 mmol ), dic ( 1 , 3 - diisopropylcarodiimide , 1 ml , 6 . 4 mmol ), and an amino polystyrene resin ( 1 g , 1 . 2 mmol ) using a procedure similar to polystyrene resin ( ps - 2 a ). this material was prepared from 3 , 5 - dinitrosalicylic acid ( 1 d ) ( 1 g , 4 . 4 mmol ), hobt ( 1 g , 7 . 4 mmol ), dic ( 1 , 3 - diisopropylcarodiimide , 1 ml , 6 . 4 mmol ), and an amino tantagel resin ( 1 g , 0 . 45 mmol ) using a procedure similar to polystyrene resin ( ps - 2 a ). this material was prepared from 3 , 5 - dinitrosalicylic acid ( 1 d ) ( 1 g , 4 . 4 mmol ), hobt ( 1 g , 7 . 4 mmol ), dic ( 1 , 3 - diisopropylcarodiimide , 1 ml , 6 . 4 mmol ), and an amino pega resin ( 1 g , 0 . 4 mmol ) using a procedure similar to polystyrene resin ( ps - 2 a ). this material was prepared from 3 , 5 - dinitrosalicylic acid ( 1 d ) ( 1 g , 4 . 4 mmol ), hobt ( 1 g , 7 . 4 mmol ), dic ( 1 , 3 - diisopropylcarodiimide , 1 ml , 6 . 4 mmol ), and an amino macroporous resin ( 1 g , 0 . 4 mmol ) using a procedure similar to polystyrene resin ( ps - 2 a ). preparation of nitrophenol resin ( ps - 2 a ) by hydrolysis of chlorobenzene in a 250 ml round - bottom flask , to an amino resin ( 4 g , 4 . 52 mmol ) in nmp ( 100 ml ) were added 4 - chloro - 3 - nitrobenzoic acid ( 2 g , 9 . 92 mmol ), dic ( 1 , 3 - diisopropylcarbodiimide , 2 ml , 12 . 8 mmol ), and hobt ( 2 g , 13 . 0 mmol ). after overnight shaking , the reaction mixture was filtered and washed with dioxane . benzyltrimethylammonium hydroxide 40 % in water ( 50 ml ), water ( 50 ml ), and dioxane ( 100 ml ) was added to the reaction mixture ( 3 a ). the reaction mixture was allowed to heat for 8 hours at 90 ° c . the resin ( 2 b ) was washed with 4 portions of warm ( 60 ° c .) dioxane , acetic acid ( 30 ml ) was added with stirring for 15 min . the polymer was washed with dioxane until the washings were neutral , fallowed by 6 portions of 300 ml of methylene chloride - methanol ( 2 : 1 ) and dried by nitrogen gas flow . the nitrophenol resin ( ps - 2 a ) ( 100 mg , 0 . 121 mmol ) was suspended in nmp ( 10 ml ), and benzoyl chloride ( 0 . 1 ml ) and pyridine ( 0 . 1 ml ) were added to the reaction mixture . the reaction mixture was allowed to shake overnight . the resins were filtered and washed with dmf ( 10 ml , 3 times ), methanol , and methylene chloride ( 10 ml , 5 times each ) and dried by nitrogen gas flow . this material was prepared from nitrophenol resin ( tg - 2 a ) ( 100 mg , 0 . 045 mmol ), benzoyl chloride ( 0 . 1 ml ), and pyridine ( 0 . 1 ml ) using a procedure similar to that for benzoyl active ester resin ( ps - 4 a ). this material was prepared from nitrophenol resin ( pega - 2 a ) ( 100 mg , 0 . 04 mmol ), benzoyl chloride ( 0 . 1 ml ), and pyridine ( 0 . 1 ml ) using a procedure similar to that for benzoyl active ester resin ( ps - 4 a ). this material was prepared from nitrophenol resin ( mp - 2 a ) ( 100 mg , 0 . 09 mmol ), benzoyl chloride ( 0 . 1 ml ), and pyridine ( 0 . 1 ml ) using a procedure similar to that for benzoyl active ester resin ( ps - 4 a ). this material was prepared from nitrophenol resin ( ps - 2 b ) ( 100 mg , 0 . 121 mmol ), benzoyl chloride ( 0 . 1 ml ), and pyridine ( 0 . 1 ml ) using a procedure similar to that for benzoyl active ester resin ( ps - 4 a ). this material was prepared from nitrophenol resin ( tg - 2 b ) ( 100 mg , 0 . 045 mmol ), benzoyl chloride ( 0 . 1 ml ), and pyridine ( 0 . 1 ml ) using a procedure similar to that for benzoyl active ester resin ( ps - 4 a ). this material was prepared from nitrophenol resin ( pega - 2 b ) ( 100 mg , 0 . 04 mmol ), benzoyl chloride ( 0 . 1 ml ), and pyridine . ( 0 . 1 ml ) using a procedure similar to that for benzoyl active ester resin ( ps - 4 a ). this material was prepared from nitrophenol resin ( mp - 2 b ) ( 100 mg , 0 . 09 mmol ), benzoyl chloride ( 0 . 1 ml ), and pyridine ( 0 . 1 ml ) using a procedure similar to that for benzoyl active ester resin ( ps - 4 a ). this material was prepared from nitrophenol resin ( ps - 2 c ) ( 100 mg , 0 . 121 mmol ), benzoyl chloride ( 0 . 1 ml ), and pyridine ( 0 . 1 ml ) using a procedure similar to that for benzoyl active ester resin ps - 4 a . this material was . prepared from nitrophenol resin . ( tg - 2 c ) ( 100 mg , 0 . 045 mmol ), benzoyl chloride ( 0 . 1 ml ), and pyridine ( 0 . 1 ml ) using a procedure similar to that for benzoyl active ester resin ( ps - 4 a ). this material was prepared from nitrophenol resin ( pega - 2 c ) ( 100 mg , 0 . 04 mmol ), benzoyl chloride ( 0 . 1 ml ), and pyridine ( 0 . 1 ml ) using a procedure similar to that for benzoyl active ester resin ( ps - 4 a ). this material was prepared from nitrophenol resin ( mp - 2 c ) ( 100 mg , 0 . 09 mmol ), benzoyl chloride ( 0 . 1 ml ), and pyridine ( 0 . 1 ml ) using a procedure similar to that for benzoyl active ester resin ( ps - 4 a ). this material was prepared from nitrophenol resin ( ps - 2 d ) ( 100 mg , 0 . 121 mmol ), benzoyl chloride ( 0 . 1 ml ), and pyridine ( 0 . 1 ml ) using a procedure similar to that for benzoyl active ester resin ( ps - 4 a ). this material was prepared from nitrophenol resin ( tg - 2 d ) ( 100 mg , 0 . 045 mmol ), benzoyl chloride ( 0 . 1 ml ), and pyridine ( 0 . 1 ml ) using a procedure similar to that for benzoyl active ester resin ps - 4 a . this material was prepared from nitrophenol resin ( pega - 2 d ) ( 100 mg , 0 . 04 mmol ), benzoyl chloride ( 0 . 1 ml ), and pyridine ( 0 . 1 ml ) using a procedure similar to that for benzoyl active ester resin ( ps - 4 a ). this material was prepared from nitrophenol resin ( mp - 2 d ) ( 100 mg , 0 . 09 mmol ), benzoyl chloride ( 0 . 1 ml ), and pyridine ( 0 . 1 ml ) using a procedure similar to that for benzoyl active ester resin ( ps - 4 a ). to a mixture of nitrophenol resin ( ps - 2 a ) ( 80 mg , 0 . 07 mmol ) in nmp ( 1 ml ) was added 4 - chlorobutyryl chloride ( 4 . 5 eq ) and pyridine ( 0 . 1 ml ). the reaction mixture was allowed to stir overnight . the resin was filtered and washed with dmf ( 5 ml , 5 times ), methylene chloride and methanol ( 5 ml , 5 times each ), and dried by nitrogen gas flow . to a mixture of nitrophenol resin ( ps - 2 a ) ( 80 mg , 0 . 07 mmol ) in nmp ( 1 ml ) was added propionyl chloride ( 4 . 5 eq ) and pyridine ( 0 . 1 ml ). the reaction mixture was allowed to stir overnight . the resin was filtered and washed with dmf ( 5 ml , 5 times ), methylene chloride and methanol ( 5 ml , 5 times each ), and dried by nitrogen gas flow . to a mixture of nitrophenol resin ( ps - 2 a ) ( 80 mg , 0 . 07 mmol ) in nmp ( 1 ml ) was added 3 - methyl butyryl chloride ( 4 . 5 eq ) and pyridine ( 0 . 1 ml ). the reaction mixture was allowed to stir overnight . the resin was filtered and washed with dmf ( 5 ml , 5 times ), methylene chloride and methanol ( 5 ml , 5 times each ), and dried by nitrogen gas flow . to a mixture of nitrophenol resin ( ps - 2 a ) ( 80 mg , 0 . 07 mmol ) in nmp ( 1 ml ) was added hexanoyl chloride ( 4 . 5 eq ) and pyridine ( 0 . 1 ml ). the reaction mixture was allowed to stir overnight . the resin was filtered and washed with dmf ( 5 ml , 5 times ), methylene chloride and methanol ( 5 ml , 5 times each ), and dried by nitrogen gas flow . to a mixture of nitrophenol resin ( ps - 2 a ) ( 80 mg , 0 . 07 mmol ) in nmp ( 1 ml ) was added pentanoyl chloride ( 4 . 5 eq ) and pyridine ( 0 . 1 ml ). the reaction mixture was allowed to stir overnight . the resin was filtered and washed with dmf ( 5 ml , 5 times ), methylene chloride and methanol ( 5 ml , 5 times each ), and dried by nitrogen gas flow . to a mixture of nitrophenol resin ( ps - 2 a ) ( 80 mg , 0 . 07 mmol ) in nmp ( 1 ml ) was added phenylacetyl chloride ( 4 . 5 eq ) and pyridine ( 0 . 1 ml ). the reaction mixture was allowed to stir overnight . the resin was filtered and washed with dmf ( 5 ml , 5 times each ), methylene chloride and methanol ( 5 ml , 5 times each ), and dried by nitrogen gas flow . to a mixture of nitrophenol resin ( ps - 2 a ) ( 80 mg , 0 . 07 mmol ) in nmp ( 1 ml ) was added 3 - phenylpropionyl chloride ( 4 . 5 eq ) and pyridine ( 0 . 1 ml ). the reaction mixture was allowed to stir overnight . the resin was filtered and washed with dmf ( 5 ml , 5 times ), methylene chloride and methanol ( 5 ml , 5 times each ), and dried by nitrogen gas flow . to a mixture of nitrophenol resin ( ps - 2 a ) ( 80 mg , 0 . 07 mmol ) in nmp ( 1 ml ) was added adamantine - 1 - carbonyl chloride ( 4 . 5 eq ) and pyridine ( 0 . 1 ml ). the reaction mixture was allowed to stir overnight . the resin was filtered and washed with dmf ( 5 ml , 5 times ), methylene chloride and methanol ( 5 ml , 5 times each ), and dried by nitrogen gas flow . to a mixture of nitrophenol resin ( ps - 2 a ) ( 80 mg , 0 . 07 mmol ) in nmp ( 1 ml ) was added 4 - fluorophenylacetyl chloride ( 4 . 5 eq ) and pyridine ( 0 . 1 ml ). the reaction mixture was allowed to stir overnight . the resin was filtered and washed with dmf ( 5 ml , 5 times ), methylene chloride and methanol ( 5 ml , 5 times each ), and dried by nitrogen gas flow . to a mixture of nitrophenol resin ( ps - 2 a ) ( 80 mg , 0 . 07 mmol ) in nmp ( 1 ml ) was added 4 - methoxyphenylacetyl chloride ( 4 . 5 eq ) and pyridine ( 0 . 1 ml ). the reaction mixture was allowed to stir overnight . the resin was filtered and washed with dmf ( 5 ml , 5 times ), methylene chloride and methanol ( 5 ml , 5 times each ), and dried by nitrogen gas flow . to a mixture of nitrophenol resin ( ps - 2 a ) ( 80 mg , 0 . 07 mmol ) in nmp ( 1 ml ) was added 4 - chlorophenylacetyl chloride ( 4 . 5 eq ) and pyridine ( 0 . 1 ml ). the reaction mixture was allowed to stir overnight . the resin was filtered and washed with dmf ( 5 ml , 5 times ), methylene chloride and methanol ( 5 ml , 5 times each ), and dried by nitrogen gas flow . to a mixture of nitrophenol resin ( ps - 2 a ) ( 80 mg , 0 . 07 mmol ) in nmp ( 1 ml ) was added 3 - cyclopentylpropionyl chloride ( 4 . 5 eq ) and pyridine ( 0 . 1 ml ). the reaction mixture was allowed to stir overnight . the resin was filtered and washed with dmf ( 5 ml , 5 times ), methylene chloride and methanol ( 5 ml , 5 times each ), and dried by nitrogen gas flow . to a mixture of nitrophenol resin ( ps - 2 a ) ( 80 mg , 0 . 07 mmol ) in nmp ( 1 ml ) was added 4 - chlorobenzoyl chloride ( 4 . 5 eq ) and pyridine ( 0 . 1 ml ). the reaction mixture was allowed to stir overnight . the resin was filtered and washed with dmf ( 5 ml , 5 times ), methylene chloride and methanol ( 5 ml , 5 times each ), and dried by nitrogen gas flow . the mixture of benzoyl active ester resin ( example 18 ) ( 40 mg ) in thf ( 1 ml ) was treated with 2 -( aminomethyl ) pyridine 0 . 3 μl . the reaction mixture was stirred at room temperature overnight . ei - ms m / z 213 . 1 [ m + h ] + . lc area ( uv 250 )= 99 % lc retention time ( uv 250 )= 1 . 51 . this material was prepared from 4 - chlorobutyryl active ester resin ( example 34 ) using a procedure similar to n - pyridin - 2 - ylmethyl benzamide . ei - ms m / z 213 . 1 [ m + h ] + . lc area ( uv 250 )= 89 . 6 % lc retention time ( uv 250 )= 0 . 74 . this material was prepared from propionyl active ester resin ( example 35 ) resin using a procedure similar to n - pyridin - 2 - ylmethyl benzamide . ei - ms m / z 165 . 1 [ m + h ] + . lc area ( uv 250 )= 95 . 6 % lc retention time ( uv 250 )= 0 . 23 . this material was prepared from 3 - methylbutyryl active ester resin ( example 36 ) using a procedure similar to n - pyridin - 2 - ylmethyl benzamide . ei - ms m / z 193 . 1 [ m + h ] + . lc area ( uv 250 )= 95 % lc retention time ( uv 250 )= 1 . 37 . this material was prepared from n - hexanoyl active ester resin ( example 37 ) using a procedure similar to n - pyridin - 2 - ylmethyl benzamide . ei - ms m / z 207 . 2 [ m + h ] + . lc area ( uv 250 )= 93 % lc retention time ( uv 250 )= 1 . 71 . this material was prepared from n - pentanoyl active ester resin ( example 38 ) using a procedure similar to n - pyridin - 2 - ylmethyl benzamide . ei - ms m / z 193 . 1 [ m + h ] + . lc area ( uv 250 )= 94 . 5 % lc retention time ( uv 250 )= 1 . 43 . this material was prepared from 2 - phenylacetyl active ester resin ( example 39 ) using a procedure similar to n - pyridin - 2 - ylmethyl benzamide . ei - ms m / z 227 . 1 [ m + h ] + . lc area ( uv 250 )= 60 % lc retention time ( uv 250 )= 1 . 61 . this material was prepared from 3 - pheny propionyl active ester resin ( example 40 ) using a procedure similar to n - pyridin - 2 - ylmethyl benzamide . ei - ms m / z 241 . 1 [ m + h ] + . lc area ( uv 250 )= 92 . 4 % lc retention time ( uv 250 )= 1 . 72 . this material was prepared from adamantine - 1 - carboyl active ester resin ( example 41 ) using a procedure similar to n - pyridin - 2 - ylmethyl benzamide . ei - ms m / z 271 . 2 [ m + h ] + . lc area ( uv 250 )= 97 % lc retentin time ( uv 250 )= 2 . 05 . this material was prepared from 4 - fluorophenylacetyl active ester resin ( example 42 ) using a procedure similar to n - pyridin - 2 - ylmethyl benzamide . ei - ms m / z 245 . 1 ( m + h ] + . lc area ( uv 250 )= 70 % lc retention time ( uv 250 )= 1 . 67 . this material was prepared from 4 - methoxyphenylacetyl active ester resin ( example 43 ) using a procedure similar to n - pyridin - 2 - ylmethyl benzamide . ei - ms m / z 245 . 1 [ m + h ] + . lc area ( uv 250 )= 70 % lc retention time ( uv 250 )= 1 . 67 . this material was prepared from 4 - chlorophenylacetyl active ester resin ( example 44 ) using a procedure similar to n - pyridin - 2 - ylmethyl benzamide . ei - ms m / z 261 . 1 [ m + h ] + . lc area ( uv 250 )= 80 % lc retention time ( uv 250 )= 1 . 83 . this material was prepared from cyclopentypropionyl active ester resin ( example 45 ) using a procedure similar to n - pyridin - 2 - ylmethyl benzamide . ei - ms m / z 233 . 1 [ m + h ] + . lc area ( uv 250 )= 97 % lc retention time ( uv 250 )= 1 . 91 . this material was prepared from 2 - chlorobenzoyl active ester resin ( example 46 ) using a procedure similar to n - pyridin - 2 - ylmethyl benzamide . ei - ms m / z 247 . 0 [ m + h ] + . lc area ( uv 250 )= 99 % lc retention time ( uv 250 )= 1 . 84 . to a nitrophenol resin ( tg - 2 a ) ( 10 mg , 3 . 5 μmol ) was added 0 . 1 m glycin in 0 . 1 m nahco 3 . the reaction was stirred for 18 hours . the reaction mixture was filtered and washed with h 2 o . the washer was combined and acidified with acetic acid . ei - ms m / z 180 . 0 [ m + h ] + lc area ( uv 230 )= 95 % lc retention time ( uv 230 )= 1 . 55 . to a nitrophenol resin ( tg - 2 a ) ( 10 mg , 3 . 5 μmol ) was added 0 . 1 m glycin in 0 . 1 m k 2 co 3 . the reaction was stirred for 18 hours . the reaction mixture was filtered and washed with h 2 o . the washer was combined and acidified with acetic acid . ei - ms m / z 180 . 0 [ m + h ] + lc area ( uv 230 )= 96 % lc retention time ( uv 230 )= 1 . 50 . a silica gel ( 1 g ) in toluene ( 10 ml ) was refluxed with aminopropyltriethoxysilane ( 1 . 2 ml ). the reaction mixture was refluxed for 6 hours with stirring . the reaction mixture was filtered using 3 ml filter cartridges , washed thoroughly with methanol and methylene chloride . it was the dried by blowing nitrogen gas . 32 , 33 . preparation of 4 - hydroxyl nitrobenzamidopropyl silica gel ( sg - 2 a ) in 100 ml round - bottom flask , to aminopropyl silica gel ( 1 g ) in nmp ( 10 ml ) was added 4 - hydroxyl - 3 - nitrobenzoic acid ( 2 g , 10 . 9 mmol ). hobt ( 2 g , 14 . 8 mmol ) and dic ( 1 , 3 - diisopropylcarbodiimide , 2 ml , 12 . 8 mmol ) were added to the reaction mixture . the reaction mixture was allowed to stir overnight , followed by filtering . it was washed with dmf ( 10 ml , 5 times ), methylene chloride , and methanol ( 10 ml , 5 times each ). the amino silica gel was washed with piperidine ( 0 . 2 ml ) in thf ( 2 ml ) and shaken for 10 min . the silica gel was filtered and washed with dmf ( 10 ml , 5 times ) and mc ( 10 ml , 5 times ). the silica gel was dried with a nitrogen gas flow . the silica - gel resin ( example 61 ) ( 1 g ) was stirred with benzoyl chloride ( 1 ml , 8 . 53 mmol ) in a 1 : 10 solution of pyridine : mc ( 10 ml ). after 1 hour stirring , the resin was filtered , washed with thf ( 10 ml , 5 times ) and mc ( 10 ml , 5 times ), and dried by nitrogen flow . a benzoyl active ester resin ( ps - 4 a , tg - 4 a , pega - 74 a , mp - 4 a , or sg - 4 a , 50 mg , 75 μmol ) was added to 10 kinds of amine ( 0 . 3 μmol ) in thf ( 1 ml ) and agitated on a rocker overnight at room temperature . the reaction mixture was filtered and washed with a portion of thf ( 1 ml ), and the filtrates were combined and dried . completion of the reaction was confirmed by tlc with ninhydrin staining and analyzed by lc - ms . a 1 ei - ms m / z 273 . 1 [ m + h ] + lc retention time ( uv 250 )= 1 . 41 a 2 ei - ms m / z 268 . 1 [ m + h ] + lc retention time ( uv 250 )= 1 . 54 a 3 ei - ms m / z 172 . 1 [ m + na ] + lc retention time ( uv 250 )= 1 . 75 a 4 ei - ms m / z 244 . 1 [ m + na ] + lc retention time ( uv 250 )= 1 . 85 a 5 ei - ms m / z 244 . 1 [ m + na ] + lc retention time ( uv 250 )= 2 . 03 a 6 ei - ms m / z 200 . 1 [ m + na ] + lc retention time ( uv 250 )= 2 . 15 a 7 ei - ms m / z 248 . 1 [ m + na ] + lc retention time ( uv 250 )= 2 . 28 a 8 ei - ms m / z 298 . 1 [ m + na ] + lc retention time ( uv 250 )= 2 . 54 a 9 ei - ms m / z 256 . 1 [ m + na ] + lc retention time ( uv 250 )= 2 . 75 a 10 ei - ms m / z 284 . 1 [ m + na ] + lc retention time ( uv 250 )= 3 . 01 preparation of sulfonic acid active ester resin ( ps - 6 a ) a nitrophenol resin 2 a ( 1 g , 2 . 2 mmol ) was added to a 100 ml polypropylene reaction vessel . the resin was swelled with thf ( 20 ml ) for 10 min with mild agitation . pyridine ( 1 ml ) was added to the reaction . a p - toluenesulfonyl chloride ( 1 . 2 mg , 6 . 3 mmol ) was added to the resin mixture and agitated vigorously until all of the sulfonyl chloride dissolved . the polypropylene reaction vessel was capped and gently agitated for 16 hours at room temperature . the reaction mixture was filtered and washed with dmf ( 10 ml , 5 times ), mc and methanol ( 10 ml , 5 times each ) and dried by nitrogen gas flow . a p - toluenesulfonyl active ester resin ( 50 mg , 0 . 055 mmol ) was added to a 10 ml polypropylene reaction vessel . the resin was swelled in thf ( 1 ml ) for 10 min . piperidine ( 3 . 7 mg , 0 . 044mmol ) was added and the mixture was filtered , then washed with mc . the filtrates were combined and evaporated . ei - ms m / z 262 . 1 [ m + na ] + lc area ( uv 230 )= 95 % lc retention time ( uv 230 )= 2 . 58 . a p - toluenesulfonyl active ester resin ( 50 mg , 0 . 055 mmol ) was added to a 10 ml polypropylene reaction vessel . the resin was swelled in thf ( 1 ml ) for 10 min . 1 - cyclohexylpiperazine ( 7 . 4 mg , 0 . 044 mmol ) was added and the mixture was filtered , and then washed with mc . the filtrates were combined and evaporated . ei - ms m / z 323 . 2 [ m + h ] + lc area ( uv 230 )= 99 % lc retention time ( uv 230 )= 1 . 63 . a p - toluenesulfonyl active ester resin ( 50 mg , 0 . 055 mmol ) was added to a 10 ml polypropylene reaction vessel . the resin was swelled in thf ( 1 ml ) for 10 min . 2 - pyridyl - piperazine ( 7 . 2 mg , 0 . 044mmol ) was added and the mixture was filtered , and then washed with mc . the filtrates were combined and evaporated . ei - ms m / z 318 . 1 [ m + h ] + lc area ( uv 230 )= 99 % lc retention time ( uv 230 )= 2 . 12 . for the nitrophenols of the present invention , the oh and the no 2 groups can be at any position on the benzene ring . as used herein , alkyl carbon chains , if not specified , contain from 1 to 20 carbon atoms , preferably from 1 to 16 carbon atoms , and are straight or branched . the alkyl groups may be optionally substituted , with one or more groups , preferably alkyl group substituents that may be the same or different . as used herein , lower alkyl , refers to carbon chains having fewer than or equal to about 6 carbon atoms . as used herein an alkyl group substituent includes halo , haloalkyl , preferably halo lower alkyl , aryl , hydroxy , alkoxy , aryloxy , alkoxy , alkylthio , arylthio , aralkyloxy , aralkylthio , carboxy , alkoxycarbonyl , oxo , and cycloalkyl . the term “ aryl ” herein refers to aromatic cyclic compounds having up to 10 atoms , including carbon atoms , oxygen atoms , sulfur atoms , selenium atoms , etc . aryl groups include , but are not limited to , groups such as phenyl , substituted phenyl , naphthyl , substituted naphthyl , in which the substituent is preferably lower alkyl , halogen , or lower alkyl . “ aryl ” may also refer to fused rings systems having aromatic unsaturation . the fused ring systems can contain up to about 7 rings . an “ aryl group substituent ” as used herein includes alkyl , cycloalkyl , cycloaryl , aryl , heteroaryl , optionally substituted with 1 or more , preferably 1 to 3 , substituents selected from halo , haloalkyl , and alkyl , arylalkyl , heteroarylalkyl , alkenyl containing 1 to 2 double bonds , alkynyl containing 1 to 2 triple bonds , halo , hydroxy , polyhaloalkyl , preferably trifluoromethyl , formyl , alkylcarbonyl , arylcarbonyl , optionally substituted with 1 or more , preferably 1 to 3 , substituents selected from halo , haloalkyl , alkyl , heteroarylcarbonyl , carboxyl , alkoxycarbonyl , aryloxycarbonyl , aminocarbonyl , alkylaminocarbonyl , dialkylaminocarbonyl , arylalkylaminocarbonyl , alkoxy , aryloxy , perfluoroalkoxy , alkenyloxy , alkynyloxy , arylalkoxy , aminoalkyl , alkylaminoalkyl , dialkylaminoalkyl , arylaminoalkyl , amino , alkylamino , dialkylamino , arylamino , alkylarylamino , alkylcarbonylamino , arylcarbonylamino , amido , nitro , mercapto , alkylthio , arylthio , perfluoroalkylthio , thiocyano , isothiocyano , alkylsufinyl , alkylsulfonyl , arylsulfinyl , arylsulfonyl , aminosulfonyl , alkylaminosulfinyl , dialkylaminosulfonyl , and arylaminosulfonyl . the term “ arylalkyl ” as used herein refers to an alkyl group which is substituted with one or more aryl groups . examples of arylalkyl groups include benzyl , 9 - fluorenylmethyl , naphthylmethyl , diphenylmethyl , and triphenylmethyl . “ cycloalkyl ” as used herein refers to a saturated mono - or multicyclic ring system , preferably of 3 to 10 carbon atoms , more preferably from 3 to 6 carbon atoms . cycloalkenyl and cycloalkynyl refer to mono - or multicyclic ring systems that respectively include at least one double bond and at least one triple bond . cycloalkenyl and cycloalkynyl groups may preferably contain 3 to 10 carbon atoms , with cycloalkenyl groups more preferably containing 4 to 7 carbon atoms and cycloalkynyl groups more preferably containing 8 to 10 carbon atoms . the ring systems of the cycloalkyl , cycloalkenyl and cycloalkynyl groups may be composed of one ring or two or more rings which may be joined together in a fused , bridged , or spiro - connected fashion , and may be optionally substituted with one or more alkyl group substituents . the term “ heteroaryl ” for purposes of the present application refers to a monocyclic or multicyclic ring system , preferably about 5 to about 15 members , in which at least one atom , preferably 1 to 3 atoms , is a heteroatom , that is , an element other than carbon , including nitrogen , oxygen , or sulfur atoms . the heteroaryl may be optionally substituted with one or more , preferably 1 to 3 , aryl group substituents . exemplary heteroaryl groups include , for example , furanyl , thienyl , pyridyl , pyrrolyl , n - methylpyrrolyl , quinolyinyl and isoquinolinyl . the term “ heterocyclic ” refers to a monocyclic or multicyclic ring system , preferably of 3 to 10 members , more preferably 4 to 7 members , where one or more , preferably 1 to 3 , of the atoms in the ring system is a heteroatom , i . e ., an atom that is other than carbon , such as nitrogen , oxygen , or sulfur . the heterocycle may be optionally substituted with one or more , preferably 1 to 3 , aryl group substituents . preferred substituents of the heterocyclic group include hydroxy , alkoxy , halo lower alkyl . the term heterocyclic may include heteroaryl . exemplary heterocyclics include , for example , pyrrolidinyl , piperidinyl , alkylpiperidinyl , morpholinyl , oxadiazolyl , or triazolyl . the nomenclature alkyl , alkoxy , carbonyl , etc , is used as is generally understood by those of skilled this art . as used herein , alkyl refers to saturated carbon chains that contain one or more carbon atoms ; the chains may be straight or branched or include cyclic portions or may be cyclic . the term “ halogen ” or “ halide ” includes f , cl , br , and i . this can include pseudohalides , which are anions that behave substantially similarly to halides . these compounds can be used in the same manner and treated in the same manner as halides . pseudohalides include , but are not limited to , cyanide , cyanate , thiocyanate , selenocyanate , trifluoromethyl , and azide . the term “ haloalkyl ” refers to a lower alkyl radical in which one or more of the hydrogen atoms are replaced by halogen , including but not limited to , chloromethyl , trifluoromethyl , 1 - chloro - 2 - fluoroethyl , and the like . “ haloalkoxy ” refers to ro — in which r is a haloalkyl group . the term “ arylene ” as used herein refers to a monocyclic or polycyclic bivalent aromatic group preferably having from 1 to 20 carbon atoms and at least one aromatic ring . the arylene group is optionally substituted with one or more alkyl group substituents . there may be optionally inserted around the arylene group one or more oxygen , sulfur , or substituted or unsubstitued nitrogen atoms , where the nitrogen substituent is alkyl . “ heteroarylene ” refers to a bivalent monocyclic or multicyclic ring system , preferably of about 5 to about 15 members , wherein one or more of the atoms in the ring system is a heteroatom . the heteroarylene may be optionally substituted with one or more aryl group substituents . as used herein , “ alkylidene ” refers to a bivalent group , such as ═ cr ′ r ″, which is attached to one atom of another group , forming a double bond . “ arylalkylidene ” refers to an alkylidene group in which either r ′ or r ″ is an aryl group . as used herein , when any particular group , such as phenyl or pyridyl , is specified , this means that the group is substituted or unsubstituted . preferred substituents , where not specified , are halo , halo lower alkyl , and lower alkyl . thus , according to the present invention , new polymer - bound nitrophenol resins were prepared by coupling alkylamine - resin with a hydroxynitrobenzoic acid . active esters and sulfonic acid esters react with a diverse set of amino nucleophiles to generate arrays of amides and sulfonamides that are useful in drug discovery . the novel active ester resins based upon a variety of resin compositions have broad applications , particularly because previously used resins had limited usage in organic solvents because of their poor swelling properties in hydrophilic solvents . the resins of the present invention can be used in most conventionally used solvents , including aqueous media . additionally , production expenses are much lower than for comparable tetrafluorophenol resins . thus , the present invention makes it possible to synthesize arrays of highly pure amide and sulfonamide libraries by providing reactive acylating and sulfonylating reagents . active carboxylic esters and sulfonic acid esters react with a diverse set of amine nucleophiles to generate arrays of amides and sulfonamides that are useful in drug discovery . any primary or secondary amine can be used as the amine nucleophie to react with a carboxylic ester or sulfonic acid ester . among the primary and secondary amines that can be used in the present invention are the following : the resins of the present invention will be used as tools in amide / sulfonamide library synthesis , and eventually for drug discovery . these resins will also be used as labeling reagents for biologically important amines and proteins in various conditions , including aqueous media , which is important in the field of proteomics . the foregoing description of the specific embodiments will so fully reveal the general nature of the invention that others can , by applying current knowledge , readily modify and / or adapt for various applications such specific embodiments without departing from the generic concept , and , therefore , such adaptions and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments . it is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation . 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