H-LYS(BOC)OME

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (S)-6-tert-Butoxycarbonylamino-2-(2-{[1-methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carbonyl]-amino}-acetylamino)-hexanoic acid methyl ester (300 mg) was prepared by following General Procedure F starting from 1-methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (392 mg), (S)-2-amino-6-tert-butoxycarbonylamino-hexanoic acid methyl ester (280 mg), HBTU (400 mg), and DIEA (400 uL) in DMF (2 mL).

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Following General Procedure A and using N-(3,5-difluorophenylacetyl)-L-alanine (from Example B2 above) and Nε-(tert-butoxycarbonyl)-L-lysine methyl ester (Bachem), the title compound was prepared as an oil. The reaction was monitored by tlc (Rf=0.40 in 50% EtOAc/hexanes) and the product was purified by flash chromotography using 50% EtOAc/hexanes as the eluent. the product was purified by flash chromotography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of S-benzyl-N-(3-benzylthio-2,2-dimethylpropionyl)-L-cysteine (4.01 g), Nε -t-butoxycarbonyl-L-lysine methyl ester (2.08 g) and NMM (1.1 ml) in DMF (20 ml), HOBt (2.16 g) and then a solution of DCC (1.82 g) in DMF (10 ml) were added slowly under ice cooling. The mixture was stirred for 1 hr. under ice cooling and for 18 hr. at room temperature. After an addition of a mixture of ethyl acetate and benzene (2:1, 500 ml), the mixture was washed with 10% citric acid solution, water, saturated sodium bicarbonate solution, water and then saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The oily residue was purified by a silica gel column chromatography to give 3.22 g (61%) of the titled compound. under ice cooling and for 18 hr at room temperature the mixture was washed with 10% citric acid solution, water, saturated sodium bicarbonate solution, water The organic layer was dried over anhydrous sodium sulfate concentrated in vacuo The oily residue was purified by a silica gel column chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of S-benzyl-N-(3-benzylthio-2,2-dimethylpropionyl)-L-cysteine (4.01 g), Nε -t-butoxycarbonyl-L-lysine methyl ester (2.08 g) and NMM (1.1 ml) in DMF (20 ml), HOBt (2.16 g) and then a solution of DCC (1.82 g) in DMF (10 ml) were added slowly under ice cooling. The mixture was stirred for 1 hr. under ice cooling and for 18 hr. at room temperature. After an addition of a mixture of ethyl acetate and benzene (2:1, 500 ml), the mixture was washed with 10% citric acid solution, water, saturated sodium bicarbonate solution, water and then saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The oily residue was purified by a silica gel column chromatography to give 3.22 g (61%) of the titled compound. under ice cooling and for 18 hr at room temperature the mixture was washed with 10% citric acid solution, water, saturated sodium bicarbonate solution, water The organic layer was dried over anhydrous sodium sulfate concentrated in vacuo The oily residue was purified by a silica gel column chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: DOTA-alkyl-biotin was synthesized following the procedure of Takenouchi et al. (J. Organic Chem. 58:1955-1958, 1993) starting with the compound H-Lys(Boc)-OMe (Bachem, E-1620). H-Lys(Boc)-OMe was treated stepwise with methyl bromoacetate and diethylenetriamine to obtain tert-butyl 4-(3,12-dioxo-1,4,7,10-tetraazacyclododecan-2-yl)butylcarbamate. Borane-THF complex was used to reduce the carboxylic amides followed by trifluoroacetic acid Boc deprotection to obtain 4-(1,4,7,10-tetraazacyclododecan-2-yl)butan-1-amine. This compound was subsequently reacted with biotin-xx, SSE (Invitrogen, B-6352) in DMSO with a 10 fold molar excess of triethylamine for 3 hours vortexing at room temperature. In all synthesis steps compounds were purified by HPLC and confirmed by mass spectrometry with a Waters (Milford, Mass.) LCT electrospray time-of-flight (ES-TOF) liquid chromatography mass spectrometry (LC/MS) or by MALDI-TOF as described above.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: DOTA-alkyl-biotin was synthesized following the procedure of Takenouchi et al. (J. Organic Chem. 58:1955-1958, 1993) starting with the compound H-Lys(Boc)-OMe (Bachem, E-1620). H-Lys(Boc)-OMe was treated stepwise with methyl bromoacetate and diethylenetriamine to obtain tert-butyl 4-(3,12-dioxo-1,4,7,10-tetraazacyclododecan-2-yl)butylcarbamate. Borane-THF complex was used to reduce the carboxylic amides followed by trifluoroacetic acid Boc deprotection to obtain 4-(1,4,7,10-tetraazacyclododecan-2-yl)butan-1-amine. This compound was subsequently reacted with biotin-xx, SSE (Invitrogen, B-6352) in DMSO with a 10 fold molar excess of triethylamine for 3 hours vortexing at room temperature. In all synthesis steps compounds were purified by HPLC and confirmed by mass spectrometry with a Waters (Milford, Mass.) LCT electrospray time-of-flight (ES-TOF) liquid chromatography mass spectrometry (LC/MS) or by MALDI-TOF as described above.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Following General Procedure A and using N-(3,5-Difluorophenylacetyl)-L-alanine (from Example B2 above) and Nε-(tert-butoxycarbonyl)-L-lysine methyl ester (Bachem), the title compound was prepared as an oil. The reaction was monitored by tlc (Rf=0.40 in 50% EtOAc/hexanes) and the product was purified by flash chromotography using 50% EtOAc/hexanes as the eluent. the product was purified by flash chromotography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Following General Procedure A and using N-(3,5-difluorophenylacetyl)-L-alanine (from Example B2 above) and Nε-(tert-butoxycarbonyl)-L-lysine methyl ester (Bachem), the title compound was prepared as an oil. The reaction was monitored by tlc (Rf=0.40 in 50% EtOAc/hexanes) and the product was purified by flash chromatography using 50% EtOAc/hexanes as the eluent. the product was purified by flash chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (S)-6-tert-Butoxycarbonylamino-2-(2-{[1-methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carbonyl]-amino}-acetylamino)-hexanoic acid methyl ester (300 mg) was prepared by following General Procedure F starting from 1-methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (392 mg), (S)-2-amino-6-tert-butoxycarbonylamino-hexanoic acid methyl ester (280 mg), HBTU (400 mg), and DIEA (400 uL) in DMF (2 mL).

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (S)-6-tert-Butoxycarbonylamino-2-(2-{[1-methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carbonyl]-amino}-acetylamino)-hexanoic acid methyl ester (300 mg) was prepared by following General Procedure F starting from 1-methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (392 mg), (S)-2-amino-6-tert-butoxycarbonylamino-hexanoic acid methyl ester (280 mg), HBTU (400 mg), and DIEA (400 uL) in DMF (2 mL).

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Following General Procedure A and using N-(3,5-difluorophenylacetyl)-L-alanine (from Example B2 above) and Nε-(tert-butoxycarbonyl)-L-lysine methyl ester (Bachem), the title compound was prepared as an oil. The reaction was monitored by tlc (Rf=0.40 in 50% EtOAc/hexanes) and the product was purified by flash chromotography using 50% EtOAc/hexanes as the eluent. the product was purified by flash chromotography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Following General Procedure A and using N-(3,5-difluorophenylacetyl)-L-alanine (from Example B2 above) and Nε-(tert-butoxycarbonyl)-L-lysine methyl ester (Bachem), the title compound was prepared as an oil. The reaction was monitored by tlc (Rf=0.40 in 50% EtOAc/hexanes) and the product was purified by flash chromotography using 50% EtOAc/hexanes as the eluent. the product was purified by flash chromotography