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Chemical Structure| 80366-85-4
Chemical Structure| 80366-85-4
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Product Details of [ 80366-85-4 ]

CAS No. :80366-85-4 MDL No. :MFCD18382162
Formula : C11H16N2O7 Boiling Point : -
Linear Structure Formula :- InChI Key :ZZBOTLREHORFCK-UHFFFAOYSA-N
M.W : 288.25 Pubchem ID :12098210
Synonyms :

Safety of [ 80366-85-4 ]

Signal Word:Warning Class:
Precautionary Statements:P210-P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P332+P313-P337+P313-P362-P370+P378-P403+P233-P403+P235-P405-P501 UN#:
Hazard Statements:H315-H319-H335 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 80366-85-4 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 80366-85-4 ]

[ 80366-85-4 ] Synthesis Path-Downstream   1~85

  • 1
  • cyclo-<K(Fmoc)-P-G-K(Dde)-A-K-P-G-K(AlocHNOCH2CO)-A> [ No CAS ]
  • [ 80366-85-4 ]
  • cyclo-<K(Fmoc)-P-G-K(Dde)-A-K(BocHNOCH2CO)-P-G-K(AlocHNOCH2CO)-A> [ No CAS ]
  • 2
  • [ 6066-82-6 ]
  • [ 42989-85-5 ]
  • [ 80366-85-4 ]
YieldReaction ConditionsOperation in experiment
92% With diisopropyl-carbodiimide; In dichloromethane; at 20℃; for 4h;Inert atmosphere; Initially, a slurry of (boc-aminooxy)acetic acid (4.42g, 23.12mmol) and N-hydroxysuccinimide (2.79g, 24.28mmol) in 55mL dry DCM was prepared. N,N?-Diisopropylcarbodiimide (3.06g, 3.76mL, 24.88mmol) was added under argon and the clear solution was stirred for 2h. Subsequently, additional N,N?-Diisopropylcarbodiimide (244mg, 300muL, 1.99mmol) was added and the reaction mixture was stirred for further 2h. Afterwards, the precipitated urea was removed by filtration and washed with a small amount of DCM. The obtained solution was diluted with DCM to a final volume of 300mL and washed four times with water. The organic layer was dried with magnesium sulfate and the solvent was removed under reduced pressure. Thus, the product was obtained as colorless solid (6.13g, 21.27mmol, 92%). 1H NMR (300MHz, DMSO-d6): delta=10.36 (1H, s, NH), 4.82 (2H, s, O-CH2), 2.84 (4H, s, CH2-CH2), 1.42 (9H, s, 3xCH3); 13C NMR (75MHz, DMSO-d6): delta=170.0, 165.1, 156.6, 80.6, 69.9, 27.9, 25.5; m/z (MALDI-TOF): 357.04 [M+3Na]+.
92% With diisopropyl-carbodiimide; In dichloromethane; at 20℃; for 4h;Inert atmosphere; A slurry of N-hydroxysuccinimide (2.79 g, 24.28 mmol) as well as (Boc-aminooxy)acetic acid (4.42 g, 23.12 mmol, 3) was prepared in 55 mL dry dichloromethane (DCM). Subsequently, N,N?-diisopropylcarbodiimide (3.06 g, 3.76 mL, 24.88 mmol) was added and the clear solution was stirred for 2 h under argon. Afterwards, another volume N,N?diisopropylcarbodiimide (244 mg, 300 muL, 1.99 mmol) was added and the reaction mixture was stirred for further 2 h at room temperature. The precipitated urea was removed by filtration and washed with a small amount of DCM. After that, the obtained solution was diluted with 200 mL DCM and washed four times with water. The organic layer was dried with magnesium sulfate and the solvent was removed in vacuo, to obtain the product as a colorless solid (6.13 g, 21.27 mmol, 92%). m/z (MALDI-TOF) 357.04 [M+3Na]+; 1H NMR (300 MHz, DMSO-d6, 298 K) delta (ppm) = 10.36 (s, 1H), 4.82 (s, 2H), 2.84 (s, 4H), 1.42 (s, 9 H); 13C NMR (75 MHz, DMSO-d6, 298 K) delta (ppm) = 169.95, 165.14, 156.57, 80.60, 69.90, 27.93, 25.47.
90% With dicyclohexyl-carbodiimide; In 1,4-dioxane; ethyl acetate; at 20℃; for 5h;Cooling with ice; To a stirred solution of N-Boc-aminooxyacetic acid (0.500 g, 2.6 mmol) in ethyl acetate/dioxane (1: 1 , 10 mL) cooled on an ice bath were added N-hydroxysuccmirnide (0.310 g, 2.7 mmol) and DCC (0.563 g, 2.7 mmol) (Foillard et al., 2008). The resulting mixture was stirred at room temperature for 5 hours and was then filtered through a pad of Celite, and the filtrate was concentrated under vacuum. The obtained residue was redissolved in ethyl acetate (35 mL) and washed with 5% aqueous NaHC03(3 x 5 mL), water (2 x 10 mL), and brine (10 mL). The organic phase was dried over Na2S04and evaporated in vacuo to give product as a white solid (0.68 g, 90%).
With dicyclohexyl-carbodiimide; Lambda/-succinimidyl BOC-3-(Aminooxy)acetate is obtained from BOC-3-(aminoxy)acetic acid according to the method described by S. Deroo et al. [Tetr. Lett. 44 (2003) 8379]. The /V-succinimidyl ester is reacted with 7-aminoheptanoic acid (1.1 equivalents) and diisopropylethyl amine (3 equivalents) in dichloromethane for 16 hours at room temperature. The coupling product, Compound 3, is purified by flash chromatography on silica.
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; 2-(((tert-Butoxycarbonyl)amino)-oxy)acetic acid (1.50 mmol, 287 mg) and N-hydroxysuccinimide (1.65 mmol, 190 mg) were dissolved in drydimethylformamide (DMF). 3-(Ethyliminomethyleneamino)-N,N-dimethylpropan-1-amine hydrochloride (EDC-HCl)(1.80 mmol, 227 mg) was added and the reaction was stirred overnight at room temperature. The mixture was diluted with water and extracted with ethylacetate. The organic layer was dried and concentrated to yield the product as a yellow liquid with some DMF impurities (?59%, 255 mg). The product was applied in the next reaction step without further purification.
With dicyclohexyl-carbodiimide; In dichloromethane; at 20℃; for 0.0833333h; Synthesis of tert-butyl 2-(3-(2-methylprop-2-enamido)propylamino)-2-oxoethoxycarbamate (MEPO) (S7) The synthesis of this monomer was adapted from a previously published procedure. See Esser-Kahn & Francis, Angew. Chem. Int. Ed. 2008, 47, 3751-3754. A 250 mL round-bottom flask was charged with a mixture of S6 (3.2 g, 16.68 mmol) and N-hydroxysuccinimide (2.3 g, 19.98 mmol) in CH2Cl2 (100 mL). The mixture was sonicated to dissolve the solids. To the solution was added N,N'-dicyclohexylcarbodiimide (4.15 g, 20.11 mmol) directly while stirring. The reaction mixture was stirred for 5 min at rt, then cooled to 0 C. for 10 min to precipitate the urea byproduct. The mixture was filtered through Celite, the precipitate washed with CH2Cl2 (50 mL), and the filtrate taken directly to the next step. A 500 mL round-bottom flask was charged with the filtrate and cooled to 0 C. Directly to this was added N-(3-aminopropyl)methacrylamide hydrochloride (1.5 g, 8.39 mmol) (Polysciences Inc.; Warrington, Pa., www.polysciences.com), followed by N,N-diisopropylethylamine (6.1 mL, 35 mmol) dropwise while stirring. The reaction mixture was allowed to come to room temperature over 1 h, then continued at rt for 3 h. The solution was diluted with 50 mL of CH2Cl2 and washed with three 150 mL portions of water followed by 100 mL of brine. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. Purification by flash chromatography with EtOAc:MeOH, 19:1, afforded a clear, viscous oil (1.65 g, 62.4%). TLC: (EtOAc) Rf=0.2. 1H NMR (400 MHz, CD3OD): delta, 1.48 (s, 9H), 1.76 (p, 2H, J=6.8), 1.95 (s, 3H), 3.31 (q, 4H, J=6.9), 4.27 (s, 2H), 5.38 (s, 1H), 5.73 (s, 1H). 13C NMR (100 MHz, CD3OD): delta, 17.5, 27.2, 28.7, 36.0, 36.5, 75.0, 81.7, 119.2, 139.9, 158.3, 169.8, 170.2.
With dicyclohexyl-carbodiimide; In dichloromethane; M. Kurono, M. Isobe Chem. Lett. 2004, 33, 452-453; M. Kurono, A. Shimomura, N. Chikusa Tetrahedron 2004, 60, 1773-1780 and S. Deroo, E. Defrancq, C. Moucheron, A. Kirsch-De Mesmaecker, P. Dumy Tetrahedron Lett. 2003, 44, 8379-8382, by protection of commercial of O-carboxymethyl-hydroxylamine hemihydrochloride ((H2NOCH2COOH)2. HCl) with di-t-butyl dicarbonate (Boc2O) in dioxane in a basic medium (NaOH) (80%) followed by reaction of the acid obtained as an intermediate product (BocNHOCH2COOH) with N-hydroxysuccinimide in the presence of dicyclohexylcarbodiimide (DCC) in CH2Cl2 (yield: 90%);

  • 3
  • [ 80366-85-4 ]
  • (S)-5-(Acetyl-hydroxy-amino)-2-{(S)-5-(acetyl-hydroxy-amino)-2-[(S)-5-(acetyl-hydroxy-amino)-2-amino-pentanoylamino]-pentanoylamino}-pentanoic acid; compound with ethyl-dipropyl-amine [ No CAS ]
  • [ 246218-05-3 ]
  • 4
  • [ 80366-85-4 ]
  • cyclo(-Asp(OtBu)-Phe-Lys-Arg(Pmc)Gly-) [ No CAS ]
  • C52H78N10O14S [ No CAS ]
  • 5
  • [ 80366-85-4 ]
  • [ 152572-68-4 ]
  • [ 635709-48-7 ]
  • 6
  • [ 80366-85-4 ]
  • [ 679406-27-0 ]
  • [ 679406-28-1 ]
  • 7
  • [ 35060-08-3 ]
  • [ 80366-85-4 ]
  • [ 697755-36-5 ]
  • 8
  • c-(L-Lys(X)-L-Lys-L-Lys(X)-L-Pro-Gly-L-Lys(X)-L-Ala-L-Lys(X)-L-Pro-Gly), X = β-D-galactopyranosyl(1->4)-β-D-glucopyranosyloxyiminomethylcarbonyl [ No CAS ]
  • [ 80366-85-4 ]
  • c-(L-Lys(X)-L-Lys(Y)-L-Lys(X)-L-Pro-Gly-L-Lys(X)-L-Ala-L-Lys(X)-L-Pro-Gly), X = β-D-galactopyranosyl(1->4)-β-D-glucopyranosyloxyiminomethylcarbonyl, Y = t-butyloxycarbonylaminooxymethylcarbonyl [ No CAS ]
  • 9
  • cyclo(-Gly-Lys(CO-CH(CH2Ot-Bu)NHBoc)-Lys-Lys(CO-CH(CH2Ot-Bu)NHBoc)-Pro-Gly-Lys(CO-CH(CH2Ot-Bu)NHBoc)-Lys-Lys(CO-CH(CH2Ot-Bu)NHBoc)-Pro-) [ No CAS ]
  • [ 80366-85-4 ]
  • cyclo(-Gly-Lys(CO-CH(CH2Ot-Bu)NHBoc)-Lys(CO-CH2ONHBoc)-Lys(CO-CH(CH2Ot-Bu)NHBoc)-Pro-Gly-Lys(CO-CH(CH2Ot-Bu)NHBoc)-Lys(CO-CH2ONHBoc)-Lys(CO-CH(CH2Ot-Bu)NHBoc)-Pro-) [ No CAS ]
  • 10
  • [ 80366-85-4 ]
  • [ 696660-77-2 ]
  • [ 696660-79-4 ]
  • 11
  • 9-(glycylamino)-1,4,5,8-tetraazaphenanthrene [ No CAS ]
  • [ 80366-85-4 ]
  • TAP'' [ No CAS ]
  • 12
  • [ 960607-70-9 ]
  • [ 80366-85-4 ]
  • C24H36N10O14S2 [ No CAS ]
  • C26H39N11O16S2 [ No CAS ]
  • 13
  • [ 960607-68-5 ]
  • [ 80366-85-4 ]
  • C24H41N7O12 [ No CAS ]
  • C26H44N8O14 [ No CAS ]
  • 14
  • [ 80366-85-4 ]
  • BocSer(t-Bu)-Lys[BocSer(t-Bu)-]-Lys{BocSer(t-Bu)-Lys[BocSer(t-Bu)-]-Ala-Lys-(Rink amide resin) [ No CAS ]
  • C41H79N15O15 [ No CAS ]
  • 15
  • [ 80366-85-4 ]
  • H-Gly-Leu-Ser(t-Bu)-Asp(t-Bu)-Val-Gly-(Sasrin resin) [ No CAS ]
  • C24H41N7O12 [ No CAS ]
  • C26H44N8O14 [ No CAS ]
  • 17
  • [ 107-15-3 ]
  • [ 80366-85-4 ]
  • [ 186345-92-6 ]
  • 18
  • [ 929087-15-0 ]
  • [ 80366-85-4 ]
  • C29H43N5O14 [ No CAS ]
YieldReaction ConditionsOperation in experiment
55% In dimethyl sulfoxide; for 72h; Example 56General procedures preparations of N-2-(tert-butoxycarbonylamιnooxy)acetate -liqandsDA-IaA 50-mL flask was charged with Aminobenzyl-ligand N-Ia (95 7 mg, O 187 mmol) and dimethyl sulfoxide (DMSO) (12 mL) To this, the above 2,5-dιoxopyrrolιdιn-1 -yl 2-(tert-butoxycarbonylaminooxy)acetate (81 9 mg, 0 284 mmol) was added, and the mixture was stirred for 72 h The DMSO was removed by high vacuum rotary evaporation to yield a clear, colorless oil Acetonitϖle (25 mL) was added and the mixture was placed at -20 C for 24 h The acetonitϖle was decanted and the product vacuum dried to yield a powder DA-Ia (57 5 mg, 55%)
  • 19
  • [ 80366-85-4 ]
  • [ 60-32-2 ]
  • [ 879898-82-5 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 16h; Λ/-succinimidyl BOC-3-(Aminooxy)acetate is obtained from BOC-3-(aminoxy)acetic acid according to the method described by S. Deroo et al. [Tetr. Lett. 44 (2003) 8379]. The /V-succinimidyl ester is reacted with 7-aminoheptanoic acid (1.1 equivalents) and diisopropylethyl amine (3 equivalents) in dichloromethane for 16 hours at room temperature. The coupling product, Compound 3, is purified by flash chromatography on silica.
  • 21
  • C44H78N14O10 [ No CAS ]
  • [ 80366-85-4 ]
  • C72H122N18O26 [ No CAS ]
  • 22
  • [ 80366-85-4 ]
  • N-(3-aminopropyl)methacrylamide hydrochloride [ No CAS ]
  • [ 1037313-35-1 ]
YieldReaction ConditionsOperation in experiment
1.65 g With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; for 4h; Synthesis of tert-butyl 2-(3-(2-methylprop-2-enamido)propylamino)-2-oxoethoxycarbamate (MEPO) (S7) The synthesis of this monomer was adapted from a previously published procedure. See Esser-Kahn & Francis, Angew. Chem. Int. Ed. 2008, 47, 3751-3754. A 250 mL round-bottom flask was charged with a mixture of S6 (3.2 g, 16.68 mmol) and N-hydroxysuccinimide (2.3 g, 19.98 mmol) in CH2Cl2 (100 mL). The mixture was sonicated to dissolve the solids. To the solution was added N,N'-dicyclohexylcarbodiimide (4.15 g, 20.11 mmol) directly while stirring. The reaction mixture was stirred for 5 min at rt, then cooled to 0 C. for 10 min to precipitate the urea byproduct. The mixture was filtered through Celite, the precipitate washed with CH2Cl2 (50 mL), and the filtrate taken directly to the next step. A 500 mL round-bottom flask was charged with the filtrate and cooled to 0 C. Directly to this was added N-(3-aminopropyl)methacrylamide hydrochloride (1.5 g, 8.39 mmol) (Polysciences Inc.; Warrington, Pa., www.polysciences.com), followed by N,N-diisopropylethylamine (6.1 mL, 35 mmol) dropwise while stirring. The reaction mixture was allowed to come to room temperature over 1 h, then continued at rt for 3 h. The solution was diluted with 50 mL of CH2Cl2 and washed with three 150 mL portions of water followed by 100 mL of brine. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. Purification by flash chromatography with EtOAc:MeOH, 19:1, afforded a clear, viscous oil (1.65 g, 62.4%). TLC: (EtOAc) Rf=0.2. 1H NMR (400 MHz, CD3OD): δ, 1.48 (s, 9H), 1.76 (p, 2H, J=6.8), 1.95 (s, 3H), 3.31 (q, 4H, J=6.9), 4.27 (s, 2H), 5.38 (s, 1H), 5.73 (s, 1H). 13C NMR (100 MHz, CD3OD): δ, 17.5, 27.2, 28.7, 36.0, 36.5, 75.0, 81.7, 119.2, 139.9, 158.3, 169.8, 170.2.
  • 23
  • [ 526196-33-8 ]
  • [ 80366-85-4 ]
  • [ 1180490-95-2 ]
  • 24
  • C54H52N3O9Pol [ No CAS ]
  • [ 29022-11-5 ]
  • [ 13734-38-8 ]
  • [ 71989-31-6 ]
  • [ 150629-67-7 ]
  • [ 80366-85-4 ]
  • [ 174653-61-3 ]
  • [ 882051-18-5 ]
  • 25
  • C36H45N3O10*H(1+) [ No CAS ]
  • [ 80366-85-4 ]
  • C43H56N4O14 [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% With triethylamine; In dichloromethane; at 20℃; for 0.5h; EXAMPLE I l[0107] Synthesis of 2-(3-{l-carboxy-5-[2-(4-fluoro-benzylideneaminooxy)- acetylamino]-pentyl}-ureido)-pentanedioic acid (9).; To a solution of compound 1 (0.062 g, 0.073 mmol) in CH2Cl2 (2 mL) was added triethylamine (0.045 mL, 0.320 mmol), followed by 7V-tert-butyloxycarbonyl-O-(carboxymethyl)hydroxyamine hydroxysuccinimidyl ester (0.025 g, 0.087 mmol, Bioconjugate Chemistry 1993, 4, 515-20). After stirring for 30 min at room temperature, the solvent was evaporated. The crude material was purified by a silica column using methanol/methylene chloride (5:95) to afford 0.055 g (89%) of compound 10. 1H NMR (400 MHz5 CDCl3) £7.98 (bs, IH), 7.91 (s, IH), 7.25-7.27 (m, 6H), 6.85-6.88 (m, 6H), 5.56- 5.63 (m, 2H), 5.01-5.11 (m, 6H), 4.47-4.53 (m, IH), 4.27-4.38 (m, 3H), 3.79 (m, 9H), 3.30-3.38 (m, IH), 3.15-3.21 (m, IH), 2.36-2.41 (m, 2H), 2.10-2.15 (m, IH), 1.89-1.95 (m, IH), 1.74-1.81 (m, IH), 1.23-1.61 (m, 14H). ESI-Mass calcd for C43H57N4O14 [M + H]+ 853.4, found 853.5.
  • 26
  • [ 957486-82-7 ]
  • [ 80366-85-4 ]
  • [ 1246614-10-7 ]
  • 27
  • C42H80N8O12 [ No CAS ]
  • [ 80366-85-4 ]
  • [ 1358996-32-3 ]
  • 28
  • C58H112N8O20 [ No CAS ]
  • [ 80366-85-4 ]
  • C65H123N9O24 [ No CAS ]
  • 29
  • [ 13472-00-9 ]
  • [ 80366-85-4 ]
  • C15H23N3O4 [ No CAS ]
  • 30
  • C20H33N5O5S2 [ No CAS ]
  • [ 80366-85-4 ]
  • C27H44N6O9S2 [ No CAS ]
  • 31
  • [ 1616794-43-4 ]
  • [ 80366-85-4 ]
  • [ 1616794-27-4 ]
  • 32
  • C18H35N7O2*C2HF3O2 [ No CAS ]
  • [ 80366-85-4 ]
  • [ 1616794-35-4 ]
  • 33
  • C13H26N2O6 [ No CAS ]
  • [ 80366-85-4 ]
  • C20H37N3O10 [ No CAS ]
  • 34
  • C18H33N3O11 [ No CAS ]
  • [ 80366-85-4 ]
  • C25H44N4O15 [ No CAS ]
  • 35
  • [ 80366-85-4 ]
  • 2-aminoethyl α-D-galactopyranosyl-(1-> 3)-β-D-galactopyranosyl-(1-> 4)-β-D-glycopyranoside [ No CAS ]
  • C27H48N2O20 [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% With triethylamine; In dimethyl sulfoxide; at 20℃; for 2h; To a solution of amino linker 24 (30 mg, 55 umol) in DMSO (1.0 mL) was added activated acid 25 (19 mg, 66 umol) and Et3N (11.5 μ, 82 umol). After been stirred at room temperature for 2 hours, the product was precipitated with acetone/ether (1 :2, 10 mL). And the residue was washed with acetone/ether (1 : 1, 10 mL), and dried in vacuo. The crude product was purified by flash column chromatography (32:68 MeOH/EtOAc) to give product (55 mg, 84%). ).() 400 MHz: 1.46 (s, 9H), 3.31-3.36 (m, 2H), 3.44-3.88 (m, 14H), 3.90-4.04 (m, 4H), 4.16- 4.19 (m, 2H), 4.37 (s, 21 1 ;·. 4.46-4.55 (m, 2H), 5.13 (d, 1 H, ./ 3.8 Hz).
  • 36
  • C25H46N2O17 [ No CAS ]
  • [ 80366-85-4 ]
  • C32H57N3O21 [ No CAS ]
YieldReaction ConditionsOperation in experiment
56% With triethylamine; In dimethyl sulfoxide; at 20℃; for 2h; To a solution of amino linker 30 (35 nig, 54 umol) in DMSO (1.0 mL) was added, activated acid 25 (23 mg, 81 umol) and Et N (15 μ, 108 umol). After being stirred at room temperature for 2 hours, the product was precipitated with acetone/ether (1 :2, 10 mL), And the residue was washed with acetone/ether (1 : 1 , 10 mL), and dried in vacuo. The crude product was purified by bio-gel P2 column to give product (25 mg, 56%). D20 400 MHz: 1.41 -1.66 (m, 6H), 1.47 (s, 9H), 2.29 (t, 2H, ./ 7.1 Hz), 3.23-3.50 (m, 5H), 3.56-3.89 (m, 1 1H), 3.91 -4.04 (m, 41 1 ). 4.15-4.24 (m, 2H), 4.35 (s, 2H), 4.49 (d, 1 H, J = 7.9 Hz), 4.51 (d, 1H, J = 7.9 Hz), 5.14 (d, 1H, J = 3.9 Hz).
  • 37
  • [ 1206451-84-4 ]
  • [ 80366-85-4 ]
  • C15H28N2O9 [ No CAS ]
  • 38
  • C22H22N2OS [ No CAS ]
  • [ 80366-85-4 ]
  • C29H33N3O5S [ No CAS ]
  • 39
  • [ 80366-85-4 ]
  • [ 183896-00-6 ]
  • C27H49N5O9S [ No CAS ]
  • 40
  • C51H70ClN17O18S3 [ No CAS ]
  • [ 80366-85-4 ]
  • C58H81ClN18O22S3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 8h; Previously prepared compound 6 (Exemplary Scheme 3) (20 mg, 0.015 mmol) was mixed with <strong>[80366-85-4]t-Boc-aminooxyacetic acid N-hydroxysuccinimide ester</strong> (8.6 mg, 0.03 mmol) in 10 mL anhydrous DMF, along with 50 uL DIPEA. The solution was stirred for eight hours at room temperature to allow for a complete conversion of compound 6 (Exemplary Scheme 3). The mixture was then vacuum -concentrated and purified via HPLC. The eluted fraction with the correct UV absorption and mass spectrometry was dried to yield the desired compound 7 (12mg, yield 53%). 1HNMR (600MHz, D20): δ 8.21(s, 1H), 7.44(m, 1H), 7.35-7.33(m, 2H), 6.44(s, 1H), 4.48-3.02(m, 26H), 2.87-2.79(m, 6H), 2.64(s, 3H), 2.49-2.44(m, 2H), 2.30(s, 3H), 2.18-1.98(m, 4H), 1.83-1.60(m, 4H), 1.47(s, 9H); 13CNMR (151MHz, D20): 176.2, 173.6, 173.4, 172.8, 172.4, 171.9, 171.4, 171.3, 171.0, 164.4, 163.9, 161.7, 159.9, 158.4, 157.9, 157.8, 156.2, 138.9, 138.4, 131.8, 130.7(2), 129.0, 128.9, 126.9, 83.6, 77.4, 74.1, 61.1, 58.1, 55.8, 53.9, 53.1, 52.7, 52.4, 51.7, 50.6, 49.8, 49.7, 49.6, 42.1, 41.4, 39.9, 38.1, 36.4, 34.7, 34.4, 33.2, 27.2, 27.0, 26.9(3),25.9, 24.7, 17.3 HRMS calculated for C58H8iClN18022S3 [MH]+ 1513.4702, observed 1513.4694; [M+2H]2+ 757.2390, observed 757.2372
  • 41
  • C57H95N21O12S [ No CAS ]
  • [ 80366-85-4 ]
  • C71H117N23O20S [ No CAS ]
  • 42
  • C34H39NO3S [ No CAS ]
  • [ 80366-85-4 ]
  • C41H50N2O7S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In dichloromethane; [0111] The amino linker alcohol (Example 1) is treated with 2-(Boc-aminooxy)acetic acid succinimidyl ester (1.2 eq) and DIPEA (2 eq) in CH2C12 to produce the intermediate Bocaminooxy-acetamido linker alcohol. This is converted to the succinimidyl carbonate using standard procedures, first converting to the chloroformate using triphosgene/pyridine then to the succinimidyl carbonate using N-hydroxy-succinimide/pyridine (Santi, et al., Proc. Nail. A cad. Sci. USA (2011)109:6211-6216). The carbonate is used to derivatize Boc-protected octreotide analogously to Example 3 and Example 4. Final treatment with 1:1 CH2C12/CF3CO2H provides the aminooxy-linker-octreotide as the bis(trifluoroacetate) salt.
  • 43
  • [ 80366-85-4 ]
  • C43H49Cl3N2O9S [ No CAS ]
  • 44
  • [ 80366-85-4 ]
  • C46H53N3O11S [ No CAS ]
  • 45
  • [ 80366-85-4 ]
  • [ 76-05-1 ]
  • [ 138529-46-1 ]
  • N-(2-(2-(2-(2-(aminooxy)acetamido)ethoxy)ethoxy)ethyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide trifluoroacetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
30.7 mg Biotin derivative 4 (0.24 mmol, 115 mg) was dissolved in CH2Cl2/TFA (4:1) and stirred for 1 h. The mixture was concentrated and dried under vacuum. The residue was redissolved in dry DMF with compound 5 (0.48 mmol, 1.40 mg) and triethylamine (0.58 mmol, 58.9 mg) and stirred at room temperature overnight. Concentration and purification by column chromatography (CH2Cl2 + MeOH (slowly increasing from 0%to 7%); Rf(CH2Cl2:MeOH; 9:1) 0.3) yielded the Boc-protected product. The compound was then redissolved in CH2Cl2/TFA (4:1) and stirred for 1 h. The mixture was concentrated and dried under vaccum to yield the desired product 1 as TFA salt (1:1.16) in 22 % (53.0 mumol, 30.7 mg) as a white sticky solid.
  • 46
  • 2,2',2"-(10-(5-amino-1-carboxypentyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid [ No CAS ]
  • [ 80366-85-4 ]
  • 2,2',2"-(10-(14-carboxy-2,2-dimethyl-4,8-dioxo-3,6-dioxa-5,9-diazatetradecan-14-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; for 24h; 2,2',2"-(10-(14-carboxy-2,2-dimethyl-4,8-dioxo-3,6-dioxa-5,9-diazatctradccan-14-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triaceticacid(10-7)2, 2', 2"-( 10-(5- Amino- 1 -carboxypentyl)- 1 ,4,7, 10-tetraazacyclododecane- l,4,7-triyl)triacetic acid (10-5) (0.572g, 1.20 mmol) and diisopropylethylamine (1.05 mL, 1.26 mmol) were dissolved in dry DMF (10 mL). After 5 min, 2,5- dioxopyrrolidin-l-yl 2-(((tert-butoxycarbonyl)amino)oxy)acetate (10-6) (0.416g, 1.44 mmol) was added and stirring continued for 24h. The solvent was evaporated and the residue purified by preparative HPLC to yield 0.652 g (1.00 mmol, 84%) of white solid product: NMR (< 6-DMSO): δ 4.15 (s, 2H), 3.79 (m, 4H), 3.61 (m, 2H), 3.56 (dd, 1H), 3.20-2.93 (m, 18H), 1.76 (m, 1H), 1.60 (m, 1H), 1.56-1.38 (m, 13H); LC/MS (ESI+): C27H48N6Oi2: m/z calcd 649.34 [MH+], found 649.6 (MH+).
  • 47
  • biotinyl-3,6-dioxaoctanediamine [ No CAS ]
  • [ 80366-85-4 ]
  • C23H41N5O8S [ No CAS ]
  • 48
  • 2-((((S)-1-(chloromethyl)-3-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-2,3-dihydro-1H-benzo[e]indol-5-yloxy)(hydroxy)phosphoryloxy)(hydroxy)phosphoryloxy)ethylamine trifluoroacetate [ No CAS ]
  • [ 80366-85-4 ]
  • tert-butyl 2-(2-((((S)-1-(chloromethyl)-3-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-2,3-dihydro-1H-benzo[e]indol-5-yloxy)(hydroxy)phosphoryloxy)(hydroxy)phosphoryloxy)ethylamino)-2-oxoethoxycarbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0℃; for 0.166667h; A solution of 20-3 mono TFA salt (10 mg, 0.0128 mmol) in DMF (0.5 mL) was treated with 2,5-dioxopyrrolidin-l-yl 2-(tert-butoxycarbonylaminooxy)acetate (7.35 mg, 0.0256 mmol) and diisopropylethyl amine (8.9 μ, 0.0512 mmol) at 0C for 10 min. The reaction mixture was purified by RP-HPLC (Phenomenex Gemini -NX CI 8 5 μηι 100 x 30mm; MeCN/water with 0.05% TFA) to obtain a white powder as compound 20-4 (8.6 mg, 80 %). MS m z 843 (M+H)+.
  • 49
  • (8S)-methyl 4-(((2-aminoethoxy)(hydroxy)phosphoryloxy)(hydroxy)phosphoryloxy)-8-(chloromethyl)-6-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-2-carboxylate trifluoroacetate [ No CAS ]
  • [ 80366-85-4 ]
  • (8S)-methyl 8-(chloromethyl)-4-(((2,2-dimethyl-4,8-dioxo-3,6-dioxa-5,9-diazaundecan-11-yloxy)(hydroxy)phosphoryloxy)(hydroxy)phosphoryloxy)-6-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With triethylamine; In dichloromethane; at 0℃; for 0.166667h; A solution of 21-3 (16 mg, 0.019 mmol) in dichloromethane (2 mL) was treated with 2,5-dioxopyrrolidin-l-yl 2-(tert-butoxycarbonylaminooxy)acetate (1 1.0 mg, 0.038 mmol) and triethylamine (10.1 μ, 0.076 mmol) at 0C for 10 min. The reaction mixture directly purified by RP-HPLC (Phenomenex Gemini -NX C18 5 μιη 100 x 30mm; MeCN/water with 0.05% TFA) to obtain a white powder 21-4 (14 mg, 83 %). MS m z 890 (M+H)+.
  • 50
  • (S)-2-((bis(dimethylamino)methylene)amino)-1-(((3R,4S,5S)-1-((S)-2-((1R,2R)-3-(((S)-N-1-(3-aminopropylsulfonamido)-1-oxo-3-phenylpropan-2-yl)amino)-1-methoxy-2-methyl-3-oxopropyl)pyrrolidin-1-yl)-3-methoxy-5-methyl-1-oxoheptan-4-yl)(methyl)amino)-3-methyl-1-oxobutane [ No CAS ]
  • [ 80366-85-4 ]
  • [ 76-05-1 ]
  • ((bis(dimethylamino)methylene)amino)-1-(((3R,4S,5S)-1-((S)-2-((1R,2R)-3-(((S)-N-1-(3-(N-(t-butoxycarbonyl)aminoxyacetyl)aminopropylsulfonamido)-1-oxo-3-phenylpropan-2-yl)amino)-1-methoxy-2-methyl-3-oxopropyl)pyrrolidin-1-yl)-3-methoxy-5-methyl-1-oxoheptan-4-yl)(methyl)amino)-3-methyl-1-oxobutane trifluoroacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Step 1A solution of (S)-2-((bis(dimethylamino)methylene)amino)-1 -(((3R,4S,5S)-1 -((S)- 2-((1 R,2R)-3-(((S)-N-1 -(3-aminopropylsulfonamido)-1 -oxo-3-phenylpropan-2-yl)amino)-1 - methoxy-2-methyl-3-oxopropyl)pyrrolidin-1 -yl)-3-methoxy-5-methyl-1 -oxoheptan-4- yl)(methyl)amino)-3-methyl-1 -oxobutane (CL-31) (25 mg, 30 Pmol) and DIEA (26 Pl) in DMF (1.5 ml) was combined with a solution of 2,5-dioxopyrrolidin-1 -yl 2-(((tert- butoxycarbonyl)amino)oxy)acetate (8.6 mg, 30 Pmol) and DIEA (26 Pl) in DMF (1.5 ml). The reaction mixture was stirred for 1 h at rt, and then purified by preparative HPLC (20- 70% acetonitrile-H2O containing 0.05% TFA) to obtain (0847) ((bis(dimethylamino)methylene)amino)-1 -(((3R,4S,5S)-1 -((S)-2-((1 R,2R)-3-(((S)-N-1 -(3- (N-(t-butoxycarbonyl)aminoxyacetyl)aminopropylsulfonamido)-1 -oxo-3-phenylpropan-2- yl)amino)-1 -methoxy-2-methyl-3-oxopropyl)pyrrolidin-1 -yl)-3-methoxy-5-methyl-1 - oxoheptan-4-yl)(methyl)amino)-3-methyl-1 -oxobutane, as a TFA salt. MS m/z 101 1.5(M+1 ). Retention time 1 .079 min
  • 51
  • [ 88192-19-2 ]
  • [ 80366-85-4 ]
  • 2-(Boc-aminooxy)-N-(3-azidopropyl)acetamide [ No CAS ]
  • 52
  • [ 80366-85-4 ]
  • [ 2450-71-7 ]
  • [ 203435-40-9 ]
  • 53
  • (S)-2,6-Diamino-hexanoic acid [2-(pyridin-2-yldisulfanyl)-ethyl]-amide [ No CAS ]
  • [ 80366-85-4 ]
  • C27H44N6O9S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 3h;Inert atmosphere; 7 (1.10g, 2.14mmol) was dissolved in 15mL dry DCM and the equal amount of TFA was added. The initially prepared solution was vigorously stirred for 1hat room temperature. Afterwards, the solvent and reagent were removed and the obtained residue was dried for further 24h in high vacuum. The oily substance was dissolved in 25mL DMF and DIPEA (2.76g, 3.63mL, 21.37mmol) and 5 (1.23g, 4.27mmol) were added, consecutively. Subsequently, the solution was stirred for 3hat room temperature in an argon atmosphere. The reaction mixture was diluted with 300mL ethyl acetate and washed two times with 0.2M hydrochloric acid as well as brine. Afterwards, the organic layer was dried with magnesium sulfate and the solvent was removed in vacuo. The obtained residue was purified by silica gel column chromatography using ethyl acetate/methanol (15:1) as eluent, whereby, the product was isolated as colorless solid (1.14g, 1.73mmol, 81%). 1H NMR (300MHz, DMSO-d6): δ=10.32 (1H, s, CONHO), 10.29 (1H, s, CONHO), 8.50-8.41 (1H, m, NCH), 8.24 (1H, t, J=5.4Hz, CHCONH), 8.10 (1H, d, J=8.1Hz, CHNH), 7.98 (1H, t, J=5.4Hz, OCH2CONH), 7.89-7.70 (2H, m, SCCHCH), 7.29-7.18 (1H, m, NCHCH), 4.38-4.08 (3H, m, CHNH, NHOCH2), 4.12 (2H, s, NHOCH2), 3.49-3.19 (2H, m, CH2CH2S), 3.08 (2H, q, J=6.6Hz, NHCH2CH2CH2), 2.89 (2H, t, J=6.6Hz, CH2CH2S), 1.71-1.48 (2H, m, CHCH2), 1.47-1.34 (2H, m, NHCH2CH2CH2), 1.33-1.21 (2H, m, NHCH2CH2CH2), 1.40 (18H, s, 6xCH3); 13C NMR (75MHz, DMSO-d6): δ=171.3, 167.9, 167.7, 159.1, 157.0, 156.9, 149.6, 137.8, 121.2, 119.3, 80.6, 80.6, 74.8, 74.6, 52.0, 38.0, 37.8, 37.3, 31.8, 28.7, 27.9, 22.7; m/z (MALDI-TOF): 661.11 [M+H]+.
  • 54
  • C67H110N20O31 [ No CAS ]
  • [ 80366-85-4 ]
  • C74H121N21O35 [ No CAS ]
  • 55
  • C103H169N19O58 [ No CAS ]
  • [ 80366-85-4 ]
  • C110H180N20O62 [ No CAS ]
  • 56
  • C87H141N23O38 [ No CAS ]
  • [ 80366-85-4 ]
  • C94H152N24O42 [ No CAS ]
  • 57
  • C33H55N7O4 [ No CAS ]
  • [ 80366-85-4 ]
  • C35H58N8O6 [ No CAS ]
  • 58
  • C97H144FN35O19S2*6C2HF3O2 [ No CAS ]
  • [ 80366-85-4 ]
  • C104H155FN36O23S2*6C2HF3O2 [ No CAS ]
  • 59
  • C76H135N17O20 [ No CAS ]
  • [ 80366-85-4 ]
  • C90H157N19O28 [ No CAS ]
  • 60
  • C71H123N21O18 [ No CAS ]
  • [ 80366-85-4 ]
  • C78H134N22O22 [ No CAS ]
  • 61
  • [ 159857-79-1 ]
  • [ 80366-85-4 ]
  • tert-butyl (2-(((S)-1-(((S)-1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)amino)-2-oxoethoxy)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In methanol; dichloromethane; for 18h;Inert atmosphere; To a solution of (S)-2-((S)-2-amino-3-methylbutanamido)-N-(4-(hydroxymethyl)phenyl)-5- ureidopentanamide (152 mg, 0.4 mmol, CAS159857-79-1 ) and 2,5-dioxopyrrolidin-1 -yl 2- (((tert-butoxycarbonyl)amino)oxy)acetate (127 mg, 0.44 mmol) in 2:1 CH2CI2/MeOH (6 mL) was added DIEA (77 uL, 0.44 mmol). After stirring for 2 hours additional 2,5-dioxopyrrolidin-1 -yl 2- (((tert-butoxycarbonyl)amino)oxy)acetate (40 mg, 0.1 mmol) was added. After stirring for 16 hours the reaction was directly purified by ISCO S1O2 chromatography (eluting with 5-30% MeOH/CH2CI2) to yield tert-butyl (2-(((S)-1 -(((S)-1 -((4-(hydroxymethyl)phenyl)amino)-1 -oxo-5- ureidopentan-2-yl)amino)-3-methyl-1 -oxobutan-2-yl)amino)-2-oxoethoxy)carbamate (MH+=553.2).
  • 62
  • [ 80366-85-4 ]
  • tert-butyl (2-(((S)-3-methyl-1-(((S)-1-((4-((((4-nitrophenoxy)carbonyl)oxy)methyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)amino)-1-oxobutan-2-yl)amino)-2-oxoethoxy)carbamate [ No CAS ]
  • 63
  • [ 80366-85-4 ]
  • tert-butyl (2-(((S)-3-methyl-1-oxo-1-(((S)-1-oxo-1-((4-(((prop-2-yn-1-ylcarbamoyl)oxy)methyl)phenyl)amino)-5-ureidopentan-2-yl)amino)butan-2-yl)amino)-2-oxoethoxy)carbamate [ No CAS ]
  • 64
  • (S)-2-amino-N-((S)-1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)-4-methylpentanamide [ No CAS ]
  • [ 80366-85-4 ]
  • tert-butyl (2-(((S)-1-(((S)-1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)amino)-2-oxoethoxy)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In methanol; dichloromethane; for 76h;Inert atmosphere; To a solution of (S)-2-amino-N-((S)-1 -((4-(hydroxymethyl)phenyl)amino)-1 -oxo-5- ureidopentan-2-yl)-4-methylpentanamide (500 mg, 1 .27 mmol) and 2,5-dioxopyrrolidin-1 -yl 2- (((tert-butoxycarbonyl)amino)oxy)acetate (476 mg, 1 .65 mmol) in 2:1 CH2CI2/MeOH (8 mL) was added DIEA (0.289 mL, 1 .65 mmol). After stirring for 60 hours additional 2,5-dioxopyrrolidin-1 - yl 2-(((tert-butoxycarbonyl)amino)oxy)acetate (120 mg, 0.3 mmol) was added. After stirring for 16 hours the reaction was directly purified by ISCO Si02 chromatography (eluting with 5-30% MeOH/CH2CI2) to yield tert-butyl (2-(((S)-1 -(((S)-1 -((4-(hydroxymethyl)phenyl)amino)-1 -oxo-5- ureidopentan-2-yl)amino)-4-methyl-1 -oxopentan-2-yl)amino)-2-oxoethoxy)carbamate (MH+=567.2).
  • 65
  • tert-butyl (1-(9H-fluoren-9-yl)-3,8,11,14-tetraoxo-2-oxa-4,7,10,13-tetraazapentadecan-15-yl)carbamate [ No CAS ]
  • [ 80366-85-4 ]
  • (9H-fluoren-9-yl)methyl (2,2-dimethyl-4,8,11,14,17-pentaoxo-3,6-dioxa-5,9,12,15,18-pentaazaicosan-20-yl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
tert-butyl (1 -(9H-fluoren-9-yl)-3,8,1 1 ,14-tetraoxo-2-oxa-4,7,10,13-tetraazapentadecan-15- yl)carbamate (1 gram, 1 .81 mmol) was treated with 25%TFA/CH2CI2 (20 mL) for 1 .5 hours at which time the volatiles were removed in vacuo. The residue was dissolved in CH2CI2 (20 mL) and to about 0.905 mmoles was add DIEA (0.788 mL, 4.51 mmol) and 2,5-dioxopyrrolidin-1 -yl 2-(((tert-butoxycarbonyl)amino)oxy)acetate (295 mg, 1 .08 mmol). After stirring for 21 hours MeOH (5 mL) was added to make the solution homogeneous and the reaction was directly purified by ISCO Si02 chromatography (eluting with 0-30% MeOH/CH2CI2) to yield (9H-fluoren- 9-yl)methyl (2,2-dimethyl-4,8,1 1 ,14,17-pentaoxo-3,6-dioxa-5,9,12,15,18-pentaazaicosan-20- yl)carbamate (MH+=627.3). To a 1 :1 MeOH/CH2CI2 (60 mL) solution of (9H-fluoren-9-yl)methyl (2,2-dimethyl-4,8,1 1 ,14,17-pentaoxo-3,6-dioxa-5,9, 12,15,18-pentaazaicosan-20-yl)carbamate (assumed 0.90 mmol) was added 2N dimethylamine in MeOH (13.55 mL, 27.1 mmol). After standing for 16 hours the volatiles were removed in vacuo, the residue was dissolved in DMSO (7 mL) and was purified by RP-HPLC to yield after lyophilization tert-butyl ((14-amino-2,5,8,1 1 - tetraoxo-3,6,9,12-tetraazatetradecyl)oxy)carbamate (MH+=405.2) as the TFA salt.
  • 66
  • 2-chlorotrityl resin [ No CAS ]
  • C31H38N4O6S [ No CAS ]
  • [ 80366-85-4 ]
  • [ 166108-71-0 ]
  • C32H56N8O13S [ No CAS ]
  • 67
  • 2-chlorotrityl resin [ No CAS ]
  • [ 80366-85-4 ]
  • N-α-Fmoc-N-ε-[5-(dimethylamino)naphthalene-1-sulfonyl]-L-lysine [ No CAS ]
  • [ 166108-71-0 ]
  • C34H53N7O13S [ No CAS ]
  • 68
  • 2-(pyridin-2-yldisulfanyl)ethan-1-amine hydrochloride [ No CAS ]
  • [ 80366-85-4 ]
  • 2-((tert-butoxycarbonylaminooxy)-N-(2-(2-pyridyldithio)))ethylacetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 3h;Inert atmosphere; The active ester 4 (3.88 g, 13.47 mmol) and 2-(2-pyridyldithio)ethylamine hydrochloride (3.00 g, 13.47 mmol) were dissolved in 60 mL dry N,N-dimethylformamide (DMF). Afterwards, N,N-diisopropylethylamine (DIPEA) (6.96 g, 9.16 mL, 53.87 mmol) was added and the reaction mixture was stirred at room temperature under argon for 3 h. Subsequently, the reaction mixture was diluted with 250 mL ethyl acetate and washed three times with water. The organic layer was dried with magnesium sulfate and the solvent was removed in vacuo. The residue was purified by silica gel column chromatography (ethyl acetate-hexane 2:1), whereby the product was obtained as colorless oil (3.53 g, 9.83 mmol, 73%). m/z (FD) 357.8 [M]+; 1H NMR (300 MHz, DMSO-d6, 298 K) δ (ppm) = 10.29 (s, 1H), 8.52 8.40 (m, 1H), 8.23 (t, 1 H, J = 5.7 Hz), 7.91 7.70 (m, 2H), 7.30 7.17 (m, 1H), 4.16 (s, 2H), 3.43 (q, 2 H, J = 6.5 Hz), 2.93 (t, 2 H, J = 6.5 Hz), 1.40 (s, 9 H); 13C NMR (75 MHz, DMSO-d6, 298 K) δ (ppm) = 168.05, 158.98, 156.78, 149.62, 137.77, 121.20, 119.31, 80.60, 74.68, 37.37, 37.25, 27.92.
  • 69
  • (x)C2HF3O2*C19H25N5O2S4 [ No CAS ]
  • [ 80366-85-4 ]
  • (S)-tert-butyl ((1,5-dioxo-1,5-bis((2-(2-pyridinyldithio)ethyl)amino)pentan-2-yl)amino)-2-oxoethoxycarbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
187.2 mg With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 3h;Inert atmosphere; The modified glutamic acid 10 (250 mg, 428.2 µmol) was gradually dissolved in 10 mL dry DCM and the same amount of TFA was added. The reaction mixture was stirred for 1 h at room temperature followed by removal of solvent and reagent in vacuum. Afterwards, the obtained oil was dissolved in 5 mL dry DMF and consecutively DIPEA (387.4 mg, 509.8 μL, 3 mmol) as well as 4 (135.8 mg, 471 μmol) were added. The solution was stirred for 3 h under argon at room temperature and was subsequently diluted with 250 mL ethyl acetate. The organic layer was washed three times with brine, dried over magnesium sulfate and the solvent was removed under reduced pressure. After that, the residue was purified by silica gel column chromatography (ethyl acetate-methanol 15:1), whereby the product was obtained as yellow oil (187.2 mg, 284.9 μmol, 78%). m/z (MALDI-TOF) 695.22 [M+K]+; 1H NMR (300 MHz, DMSO-d6, 298 K) δ (ppm) = 10.30 (s, 1H), 8.51 8.40 (m, 2H), 8.24 (t, 1H, J = 5.7 Hz), 8.12 (d, 1H, J = 8.0 Hz), 8.05 (t, 1H, J = 5.7 Hz), 7.88 7.70 (m, 4H), 7.28 7.19 (m, 2H), 4.33 4.09 (m, 1H), 3.43 3.24 (m, 4H), 2.89 (t, 2H, J = 7.0 Hz), 2.87 (t, 2H, J = 7.0 Hz), 2.09 (t, 2H, J = 8.0 Hz), 1.97 1.69 (m, 2H), 1.38 (s, 9H); 13C NMR (75 MHz, DMSO-d6, 298 K) δ (ppm) = 171.40, 170.88, 167.91, 159.08, 159.04, 156.86, 149.58, 137.76, 121.17, 119.25, 80.61, 74.64, 51.80, 37.84, 37.78, 37.43, 37.27, 31.59, 28.04, 27.91.
  • 70
  • (2R,5S,8S,11S,14S,19S)-19-amino-5,8,14-tris(carboxymethyl)-11-(3-guanidinopropyl)-2-(((2-(methyl(2-(4-(4-(4-(6-methylpyridin-2-yl)-1H-pyrazol-3-yl)pyridin-2-yl)phenoxy)ethyl)carbamoyloxy)ethyl)disulfanyl)methyl)-4,7,10,13,16-pentaoxo-3,6,9,12,15-pentaazaicosane-1,20-dioic acid [ No CAS ]
  • [ 80366-85-4 ]
  • (2R,5S,8S,11S,14S,19S)-19-(2-(tert-butoxycarbonylaminooxy)acetamido)-5,8,14-tris(carboxymethyl)-11-(3-guanidinopropyl)-2-(((2-(methyl(2-(4-(4-(4-(6-methylpyridin-2-yl)-1H-pyrazol-3-yl)pyridin-2-yl)phenoxy)ethyl)carbamoyloxy)ethyl)disulfanyl)methyl)-4,7,10,13,16-pentaoxo-3,6,9,12,15-pentaazaicosane-1,20-dioic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
33% With triethylamine; In N,N-dimethyl-formamide; at 21℃; for 16h;Inert atmosphere; To a solution of L13 (32 mg, 0.025mmol) in DMF (3ml) was added 2,5- dioxopyrrolidin-1-yl2-(tert-butoxycarbonylaminooxy)acetate (L14) (28mg, 0.097 mmol) followed by TEA (0.5ml). The reaction mixture was stirred at approximately 21 C under N2 atmosphere for 16 hr to provide L15. The crude L15 was purified by preparative HPLC to provide 12 mg of purified L15 as white solid (yield 33%)
  • 71
  • (2R,5S,8S,11S,14S,19S)-19-amino-5,8,14-tris(carboxy methyl)-11-(3-guanidinopropyl)-2-(((2-(methyl(2-(4-(4-(4-(6-methylpyridin-2-yl)-1H-pyrazol-3-yl)pyridin-2-yl)phenoxy)ethyl)carbamoyloxy)ethyl)disulfanyl)methyl)-4,7,10,13,16-pentaoxo-3,6,9,12,15-pentaazaicosane-1,20-dioic acid [ No CAS ]
  • [ 80366-85-4 ]
  • (2R,5S,8S,11S,14S,19S)-19-(2-(tert-butoxycarbonylaminooxy)acetamido)-5,8,14-tris(carboxymethyl)-11-(3-guanidinopropyl)-2-(((2-(methyl(2-(4-(4-(4-(6-methylpyridin-2-yl)-1H-pyrazol-3-yl)pyridin-2-yl)phenoxy)ethyl)carbamoyloxy)ethyl)disulfanyl)methyl)-4,7,10,13,16-pentaoxo-3,6,9,12,15-pentaazaicosane-1,20-dioic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
33% With triethylamine; In N,N-dimethyl-formamide; at 21℃; for 16h;Inert atmosphere; To a solution of L13 (32 mg, 0.025 mmol) in DMF (3 ml) was added 2,5-dioxopyrrolidin-1-yl2-(tert-butoxycarbonylaminooxy)acetate (L14) (28 mg, 0.097 mmol) followed by TEA (0.5 ml). The reaction mixture was stirred at approximately 21 C. under N2 atmosphere for 16 hr to provide L15. The crude L15 was purified by preparative HPLC to provide 12 mg of purified L15 as white solid (yield 33%)
33% With triethylamine; In N,N-dimethyl-formamide; at 21℃; for 16h;Inert atmosphere; To a solution of L13 (32 mg, 0.025mmol) in DMF (3ml) was added 2,5-dioxopyrrolidin-1- yl2-(tert-butoxycarbonylaminooxy)acetate (L14) (28mg, 0.097 mmol) followed by TEA (0.5ml).The reaction mixture was stirred at approximately 21 C under N2 atmosphere for 16 hr to provide L15. The crude L15 was purified by preparative HPLC to provide 12 mg of purified L15 as white solid (yield 33%)
  • 72
  • {4-[(2S)-2-[(2S)-2-amino-3-methylbutanamido]-5-(carbamoylamino)pentanamido]phenyl}methyl N-[(1S)-1-[(1S)-1-[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-2-[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]carbamoyl}-1-methoxy-2-methylethyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl](methyl)carbamoyl}-2-methylpropyl]carbamoyl}-2-methylpropyl]-N-methylcarbamate [ No CAS ]
  • [ 80366-85-4 ]
  • C73H119N13O18 [ No CAS ]
YieldReaction ConditionsOperation in experiment
MMAE 3 was dissolved in 2 mL DMF and left stirring under N2. 21 mg of NHS-activated aminoxy cross linker were weighed in a glass vial and dissolved in 1 mL of DMF. This solution was then added to the reaction vessel. Finally, 20 pL of DIPEA/DMF (0545) (50:50 v/v%) were added to the reaction mixture. The reaction was left stirring at RT under N2 for 18 hours. The reaction was monitored by normal phase TLC. After 18 hours of reaction, the reaction solvent was evaporated under vacuum to obtain a solid product. The product MMAE 4 was washed with diethyl ether three times.
  • 73
  • 6-amino-9-(4-(aminomethyl)benzyl)-2-butoxy-7H-purin-8(9H)-one [ No CAS ]
  • [ 80366-85-4 ]
  • N-(4-((6-amino-2-butoxy-8-oxo-7H-purin-9(8H)-yl)methyl)benzyl)-2-(aminooxy)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% To a solution of compound 118 (5 mg, 0.007 mmol) and 2,5- dioxopyrrolidin-l-yl 2-(tert-butoxycarbonylaminooxy)acetate (3 mg, 0.010 mmol) in DMF (1 mL) was added DIEA (5 uL, 0,057 mmol) at 23 C. After 10 min, the solvent was removed in vacuo. To the residue was added DCM (1 mL) and TFA (1 mL) at 23 C. After 10 min, the mixture was purified by Prep-LC to obtain compound 119 (3.6 mg, 0.005 mmol, 65%). MS m/z 41 (M+H)+.
  • 74
  • 6-amino-9-((6-(4-(2-aminoethyl)piperazin-1-yl)pyridin-3-yl)methyl)-2-(butylamino)-7H-purin-8(9H)-one trifluoroacetic acid [ No CAS ]
  • [ 80366-85-4 ]
  • [ 76-05-1 ]
  • N-(2-(4-(5-((6-amino-2-(butylamino)-8-oxo-7H-purin-9(8H)-yl)methyl)pyridin-2-yl)piperazin-1-yl)ethyl)-2-(aminooxy)acetamide trifluoroacetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% To a solution of compound 126 (9 mg, 0.010 mmol) and 2,5-dioxopyrrolidin-l-yl 2-(tert-butoxycarbonylaminooxy)acetate (2.5 mg, 0.011 mmol) in DMF (l mL) was added DIEA (10 uL, 0.060 mmol) at 23 C. After 15 min, the solvent was removed in vacuo, To the residue was added DCM (1 mL) and TFA (1 mL). After 5 min, the solvent was removed in vacuo. The residue was purified by Prep-LC to obtain compound 127 (8mg, 0.008 mmol, 82%) as TFA salt. MS m/z 514 (M+H) h,
  • 75
  • 6-amino-9-((6-(2-((2-aminoethyl)(methyl)amino)ethylamino)pyridin-3-yl)methyl)-2-(butylamino)-7H-purin-8(9H)-one [ No CAS ]
  • [ 80366-85-4 ]
  • N-(2-((2-(5-((6-amino-2-(butylamino)-8-oxo-7H-purin-9(8H)-yl)methyl)pyridin-2-ylamino)ethyl)(methyl)amino)ethyl)-2-(aminooxy)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
54% General procedure: To a solution of compound 126 (9 mg, 0.010 mmol) and 2,5-dioxopyrrolidin-l-yl 2-(tert-butoxycarbonylaminooxy)acetate (2.5 mg, 0.011 mmol) in DMF (l mL) was added DIEA (10 uL, 0.060 mmol) at 23 C. After 15 min, the solvent was removed in vacuo, To the residue was added DCM (1 mL) and TFA (1 mL). After 5 min, the solvent was removed in vacuo. The residue was purified by Prep-LC to obtain compound 127 (8mg, 0.008 mmol, 82%) as TFA salt. MS m/z 514 (M+H) h,
  • 76
  • 6-amino-9-(4-((4-(2-aminoethyl)piperidin-1-yl)methyl)benzyl)-2-butoxy-7H-purin-8(9H)-one trifluoroacetic acid [ No CAS ]
  • [ 80366-85-4 ]
  • N-(2-(1-(4-((6-amino-2-butoxy-8-oxo-7H-purin-9(8H)-yl)methyl)benzyl)piperidin-4-yl)ethyl)-2-(aminooxy)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% To a solution of compound 126 (9 mg, 0.010 mmol) and 2,5-dioxopyrrolidin-l-yl 2-(tert-butoxycarbonylaminooxy)acetate (2.5 mg, 0.011 mmol) in DMF (l mL) was added DIEA (10 uL, 0.060 mmol) at 23 C. After 15 min, the solvent was removed in vacuo, To the residue was added DCM (1 mL) and TFA (1 mL). After 5 min, the solvent was removed in vacuo. The residue was purified by Prep-LC to obtain compound 127 (8mg, 0.008 mmol, 82%) as TFA salt. MS m/z 514 (M+H) h,
  • 77
  • (S)-2-amino-N-(2-(1-(4-((6-amino-2-butoxy-8-oxo-7H-purin-9(8H)-yl)methyl)benzyl)piperidin-4-yl)ethyl)propanamide [ No CAS ]
  • [ 80366-85-4 ]
  • (S)-N-(2-(1-(4-((6-amino-2-butoxy-8-oxo-7H-purin-9(8H)-yl)methyl)benzyl)piperidin-4-yl)ethyl)-2-(2-(aminooxy)acetamido)propanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
58% General procedure: To a solution of compound 126 (9 mg, 0.010 mmol) and 2,5-dioxopyrrolidin-l-yl 2-(tert-butoxycarbonylaminooxy)acetate (2.5 mg, 0.011 mmol) in DMF (l mL) was added DIEA (10 uL, 0.060 mmol) at 23 C. After 15 min, the solvent was removed in vacuo, To the residue was added DCM (1 mL) and TFA (1 mL). After 5 min, the solvent was removed in vacuo. The residue was purified by Prep-LC to obtain compound 127 (8mg, 0.008 mmol, 82%) as TFA salt. MS m/z 514 (M+H) h,
  • 78
  • (S)-2-amino-N-(2-(1-(4-((6-amino-2-butoxy-8-oxo-7H-purin-9(8H)-yl)methyl)benzyl)piperidin-4-yl)ethyl)-5-guanidinopentanamide [ No CAS ]
  • [ 80366-85-4 ]
  • (S)-N-(2-(1-(4-((6-amino-2-butoxy-8-oxo-7H-purin-9(8H)-yl)methyl)benzyl)piperidin-4-yl)ethyl)-2-(2-(aminooxy)acetamido)-5-guanidinopentanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
42% General procedure: To a solution of compound 126 (9 mg, 0.010 mmol) and 2,5-dioxopyrrolidin-l-yl 2-(tert-butoxycarbonylaminooxy)acetate (2.5 mg, 0.011 mmol) in DMF (l mL) was added DIEA (10 uL, 0.060 mmol) at 23 C. After 15 min, the solvent was removed in vacuo, To the residue was added DCM (1 mL) and TFA (1 mL). After 5 min, the solvent was removed in vacuo. The residue was purified by Prep-LC to obtain compound 127 (8mg, 0.008 mmol, 82%) as TFA salt. MS m/z 514 (M+H) h,
  • 79
  • 9-(4-(4,4'-bipiperidin-1-ylmethyl)benzyl)-6-amino-2-butoxy-7H-purin-8(9H)-one [ No CAS ]
  • [ 80366-85-4 ]
  • 6-amino-9-(4-((1'-(2-(aminooxy)acetyl)-4,4'-bipiperidin-1-yl)methyl)benzyl)-2-butoxy-7H-purin-8(9H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
18% General procedure: To a solution of compound 126 (9 mg, 0.010 mmol) and 2,5-dioxopyrrolidin-l-yl 2-(tert-butoxycarbonylaminooxy)acetate (2.5 mg, 0.011 mmol) in DMF (l mL) was added DIEA (10 uL, 0.060 mmol) at 23 C. After 15 min, the solvent was removed in vacuo, To the residue was added DCM (1 mL) and TFA (1 mL). After 5 min, the solvent was removed in vacuo. The residue was purified by Prep-LC to obtain compound 127 (8mg, 0.008 mmol, 82%) as TFA salt. MS m/z 514 (M+H) h,
  • 80
  • N-(2-(1-(4-((4-amino-6-butoxy-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-1-yl)methyl)benzyl)piperidin-4-yl)ethyl)-4-(2-aminoethyl)benzamide [ No CAS ]
  • [ 80366-85-4 ]
  • N-(2-(1-(4-((4-amino-6-butoxy-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-1-yl)methyl)benzyl)piperidin-4-yl)ethyl)-4-(2-(2-(aminooxy)acetamido)ethyl)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
94% General procedure: To a solution of compound 126 (9 mg, 0.010 mmol) and 2,5-dioxopyrrolidin-l-yl 2-(tert-butoxycarbonylaminooxy)acetate (2.5 mg, 0.011 mmol) in DMF (l mL) was added DIEA (10 uL, 0.060 mmol) at 23 C. After 15 min, the solvent was removed in vacuo, To the residue was added DCM (1 mL) and TFA (1 mL). After 5 min, the solvent was removed in vacuo. The residue was purified by Prep-LC to obtain compound 127 (8mg, 0.008 mmol, 82%) as TFA salt. MS m/z 514 (M+H) h,
  • 81
  • [ 13734-28-6 ]
  • [ 80366-85-4 ]
  • Boc-Lys(Boc-aminooxyacetyl)-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 23℃; for 2h; To 2,5-dioxopyrrolidin-l-yl 2-(tert- butoxycarbonylaminooxy) acetate (399 mg, 1,384 mmol) and Boc-Lys-OH (335 mg, 1.360 mmol) in DMF (5 mL), was added DIEA (750 ul, 4.306 mmol) at 23 C. After 2h, the solvent was removed in vacuo. The residue was dissolved in EtOAc (50 ml) and washed with IN HC1 (50 ml) and brine (20 mL). The organic layer was dried over MgSCL, filtered, and the solvent removed in vacuo. The residue was purified by flash chromatography to obtain compound 215 (480 mg, 1.144 mmol, 83%) as a white solid. MS m/z 420 (M+H)+.
  • 82
  • N-(2-(2-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)ethoxy)ethyl)piperazine-1-carboxamide [ No CAS ]
  • [ 80366-85-4 ]
  • C25H36N8O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
22% Compound 7 (22 g, 0.02 mmol) was dissolved in DCM (1 mL) and treated with DIPEA (3.5 uL, 0.02 mmol), followed by 2,5- dioxopyrrolidin-l-yl 2-(tert~butoxycarbonylaminooxy)acetate (3.3 mg, 0.011 mmol). The reaction was kept at room temperature for 17h. To the mixture was added TFA (0.3 mL), and stirred for 15 min. After drying in vacuo, the residue was purified by Prep-HPLC to obtain compound 9 (15 g, 22% from 7). MS m/z 918 (M+H)+.
  • 83
  • [ 80366-85-4 ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • C64H99N15O16S3 [ No CAS ]
  • 84
  • (2R,5S,8S,11S,14S,19S)-19-amino-5,8,14-tris(carboxymethyl)-11-(3-guanidinopropyl)-2-(((2-(methyl(2-(4-(4-(4-(6-methylpyridin-2-yl)-1H-pyrazol-3-yl)pyridin-2-yl)phenoxy)ethyl)carbamoyloxy)ethyl)disulfanyl)methyl)-4,7,10,13,16-pentaoxo-3,6,9,12,15-pentaazaicosane-1,20-dioic acid [ No CAS ]
  • [ 80366-85-4 ]
  • (2R,5S,8S,11S,14S,19S)-19-(2-(tert-butoxycarbonylaminooxy)acetamido)-5,8,14-tris(carboxymethyl)-11-(3-guanidinopropyl)-2-(((2-(methyl(2-(4-(4-(4-(6-methylpyridin-2-yl)-1H-pyrazol-3-yl)pyridin-2-yl)phenoxy)ethyl)carbamoyloxy)ethyl)disulfanyl)methyl)-4,7,10,13,16-pentaoxo-3,6,9,12,15-pentaazaicosane-1,20-dioic acid [ No CAS ]
  • 85
  • [ 105047-45-8 ]
  • [ 80366-85-4 ]
  • [ 757960-24-0 ]
YieldReaction ConditionsOperation in experiment
65% With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 50℃; for 1h; 3 tert-butyl (S)-(2-((5-amino-6-((2-(l-(4-((6-amino-2-butoxy-8-oxo-7,8-dihydro- 9H-purin-9-yl)methyl)benzyl)piperidin-4-yl)ethyl)amino)-6-oxohexyl)amino)-2- oxoethoxy)carbamate (249): To a solution of 2,5-dioxopyrrolidin-l-yl 2-(((tert- butoxycarbonyl)amino)oxy)acetate (380 mg, 1.318 mmol) and Fmoc-L-Lys-OH (444 mg, 1.205 mmol) in DMF (5 mL) was added DIEA (660 pL, 3.789 mmol) at 50°C. After 1 h, the solvent was removed in vacuo, the residue dissolved in EtOAc (50 mL), and washed with IN HC1 (50 mL) and brine (20 mL). The organic layer was dried over MgSCh then filtered. The solvent was removed in vacuo. The residue was purified by flash chromatography with MeOH/DCM gradient (0-10%) to obtain compound 249 (466 mg, 0.860 mmol, 65%).MS m/z 542 (M+H)+.
65% With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 50℃; for 1h; 3 tert-butyl (S)-(2-((5-amino-6-((2-(l-(4-((6-amino-2-butoxy-8-oxo-7,8-dihydro- 9H-purin-9-yl)methyl)benzyl)piperidin-4-yl)ethyl)amino)-6-oxohexyl)amino)-2- oxoethoxy)carbamate (249): To a solution of 2,5-dioxopyrrolidin-l-yl 2-(((tert- butoxycarbonyl)amino)oxy)acetate (380 mg, 1.318 mmol) and Fmoc-L-Lys-OH (444 mg, 1.205 mmol) in DMF (5 mL) was added DIEA (660 pL, 3.789 mmol) at 50°C. After 1 h, the solvent was removed in vacuo, the residue dissolved in EtOAc (50 mL), and washed with IN HC1 (50 mL) and brine (20 mL). The organic layer was dried over MgSCh then filtered. The solvent was removed in vacuo. The residue was purified by flash chromatography with MeOH/DCM gradient (0-10%) to obtain compound 249 (466 mg, 0.860 mmol, 65%).MS m/z 542 (M+H)+.
Same Skeleton Products
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