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[ CAS No. 163437-14-7 ] {[proInfo.proName]}

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Cat. No.: {[proInfo.prAm]}
Chemical Structure| 163437-14-7
Chemical Structure| 163437-14-7
Structure of 163437-14-7 * Storage: {[proInfo.prStorage]}
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Product Details of [ 163437-14-7 ]

CAS No. :163437-14-7 MDL No. :MFCD00153361
Formula : C20H21NO6S Boiling Point : -
Linear Structure Formula :- InChI Key :KJLKPACOHZKRFM-SFHVURJKSA-N
M.W :403.45 Pubchem ID :7016362
Synonyms :

Calculated chemistry of [ 163437-14-7 ]

Physicochemical Properties

Num. heavy atoms : 28
Num. arom. heavy atoms : 12
Fraction Csp3 : 0.3
Num. rotatable bonds : 9
Num. H-bond acceptors : 6.0
Num. H-bond donors : 2.0
Molar Refractivity : 103.75
TPSA : 118.15 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -7.04 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.59
Log Po/w (XLOGP3) : 2.42
Log Po/w (WLOGP) : 3.49
Log Po/w (MLOGP) : 1.83
Log Po/w (SILICOS-IT) : 2.19
Consensus Log Po/w : 2.31

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.56

Water Solubility

Log S (ESOL) : -3.59
Solubility : 0.104 mg/ml ; 0.000258 mol/l
Class : Soluble
Log S (Ali) : -4.54
Solubility : 0.0115 mg/ml ; 0.0000286 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -5.57
Solubility : 0.0011 mg/ml ; 0.00000272 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 2.0
Synthetic accessibility : 4.21

Safety of [ 163437-14-7 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 163437-14-7 ]

* 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 [ 163437-14-7 ]

[ 163437-14-7 ] Synthesis Path-Downstream   1~15

  • 1
  • [ 73731-37-0 ]
  • [ 163437-14-7 ]
  • [ 2502290-01-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h 1.2: 0.5 h 2.1: sodium cyanoborohydride; acetic acid / methanol / 20 °C / pH 4 - 5
  • 2
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 35661-40-6 ]
  • [ 71989-14-5 ]
  • [ 71989-35-0 ]
  • [ 163437-14-7 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Stage #1: Fmoc-Leu-OH With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate for 0.75h; Automated synthesizer; Stage #2: With piperidine In N,N-dimethyl-formamide Automated synthesizer; Stage #3: N-(fluoren-9-ylmethoxycarbonyl)glycine; Fmoc-Leu-OH; N-Fmoc L-Phe; Fmoc-(tBu)Asp-OH; Fmoc-Thr(tBu)-OH; Fmoc-L-Met(O2)-OH; Fmoc-Glu(Pg)-OH Further stages; General procedure: The amino acids (5eq) were activated with equimolar amounts of HATU and a 2-fold molar excess of DIPEA and acylated for 45min over the resin free amino groups. Fmoc deprotection in each coupling step and the end of the linear assembly was performed with 20% piperidine in (DMF). Acetylation of the N-terminus was performed by treating the resin in DMF with acetic anhydride (10eq) for 15min. The dry peptide-resin was treated with the cleavage mixture, 92.5% TFA, 2.5% TIPS and 5% H2O for 1h at RT. The resin was filtered off, the volatiles were evaporated by SpeedVac and the peptide precipitated by addition of cold MTBE. After removal of the supernatant, the peptide pellets were washed twice with MTBE, dried, taken into ACN/H2O and lyophilized. Lyophilization afforded crude peptides in yields ranging between 80 and 90%. The overall purity of the crude peptide was >90% as assessed by UPLC-MS analysis (Column: C18 ACQUITY BEH 1.7µm, 2.1x100 mm, 100Å, gradient: 10%-10% (1.5min)-60% (4min)-80% (1min) %B where A=H2O+0.1%TFA and B=ACN+0.1%TFA). The crude peptides were purified by RP-HPLC on an automated Waters FractionLynx RP-HPLC/MS using a Waters XBridge BEH C18 OBD Prep Column (130Å, 5µm, 30mm×150mm) at a flow rate of 30mL/min, λ=214nm, with a 10-10% (5min)-60%(20min) %B linear gradient (A=H2O+0.1%TFA and B=ACN+0.1%TFA). Purified peptides were recovered by lyophilization of pooled fractions with a purity>95% and yields ranging between 35 and 55%.
  • 3
  • [ 50-00-0 ]
  • [ 163437-14-7 ]
  • [ 2642726-11-0 ]
YieldReaction ConditionsOperation in experiment
With camphor-10-sulfonic acid In toluene at 95℃; for 4h; 1-1 Compound aa092-a ((2S) -2- [9H-fluorene-9-ylmethoxycarbonylamino] -4-methylsulfonylbutanoic acid,Fmoc-Met (O2) -OH) (5.0 g, 12.39 mmol), paraformaldehyde (1.12 g, 37.2 mmol)) And CSA (0.144 g, 0.62 mmol) were suspended in toluene (83 mL) and stirred at 95 ° C. for 4 hours. After cooling the reaction solution to room temperature and diluting the filtrate with ethyl acetate (100 mL), saturated aqueous sodium hydrogen carbonate solution / water (1/1) and saturated saline solution / water (1/1).) Was washed. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give compound aa092-b as a crude product.(4.2g)
  • 4
  • (2S)-4-[[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl]amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]butanoic acid [ No CAS ]
  • [ 6089-09-4 ]
  • [ 929-10-2 ]
  • [ 71989-35-0 ]
  • [ 125238-99-5 ]
  • 1‐fluorenylmethoxycarbonyl-(2S,3aS,7aS)‐octahydroindole‐2‐carboxylic acid [ No CAS ]
  • [ 135112-27-5 ]
  • (2S)-2-[9H-fluorene-9-ylmethoxycarbonylamino]-4-methylsulfonylbutanoic acid [ No CAS ]
  • 2-([(9H-fluoren-9-yl)methoxy]carbonyl}amino)-3-(4-benzoylphenyl)propanoic acid [ No CAS ]
  • C68H101N9O16S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: (2S)-4-[[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl]amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]butanoic acid With O‑(6‑chlorobezotriazol‑1‑yl)‑N,N,N,N‑tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 2h; Stage #2: With piperidine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #3: 4-pentynoic acid; isooctanoic acid; Fmoc-Thr(tBu)-OH; (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid; 1‐fluorenylmethoxycarbonyl-(2S,3aS,7aS)‐octahydroindole‐2‐carboxylic acid; (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)butanoic acid; (2S)-2-[9H-fluorene-9-ylmethoxycarbonylamino]-4-methylsulfonylbutanoic acid; 2-([(9H-fluoren-9-yl)methoxy]carbonyl}amino)-3-(4-benzoylphenyl)propanoic acid Further stages;
  • 5
  • (2S)-4-[[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl]amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]butanoic acid [ No CAS ]
  • [ 6089-09-4 ]
  • [ 929-10-2 ]
  • [ 71989-35-0 ]
  • [ 125238-99-5 ]
  • 1‐fluorenylmethoxycarbonyl-(2S,3aS,7aS)‐octahydroindole‐2‐carboxylic acid [ No CAS ]
  • [ 135112-27-5 ]
  • (2S)-2-[9H-fluorene-9-ylmethoxycarbonylamino]-4-methylsulfonylbutanoic acid [ No CAS ]
  • 2-([(9H-fluoren-9-yl)methoxy]carbonyl}amino)-3-(4-benzoylphenyl)propanoic acid [ No CAS ]
  • C68H101N9O16S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid With O‑(6‑chlorobezotriazol‑1‑yl)‑N,N,N,N‑tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 2h; Stage #2: With piperidine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #3: (2S)-4-[[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl]amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]butanoic acid; 4-pentynoic acid; isooctanoic acid; Fmoc-Thr(tBu)-OH; 1‐fluorenylmethoxycarbonyl-(2S,3aS,7aS)‐octahydroindole‐2‐carboxylic acid; (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)butanoic acid; (2S)-2-[9H-fluorene-9-ylmethoxycarbonylamino]-4-methylsulfonylbutanoic acid; 2-([(9H-fluoren-9-yl)methoxy]carbonyl}amino)-3-(4-benzoylphenyl)propanoic acid Further stages;
  • 6
  • [ 235788-61-1 ]
  • [ 6089-09-4 ]
  • [ 929-10-2 ]
  • [ 35661-60-0 ]
  • [ 71989-35-0 ]
  • [ 114360-54-2 ]
  • [ 125238-99-5 ]
  • [ 130309-37-4 ]
  • [ 135112-27-5 ]
  • [ 163437-14-7 ]
  • [ 117666-96-3 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Stage #1: Fmoc-Thr(tBu)-OH With O‑(6‑chlorobezotriazol‑1‑yl)‑N,N,N,N‑tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 2h; Stage #2: With piperidine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #3: (2S)-4-[[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl]amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]butanoic acid; 4-pentynoic acid; isooctanoic acid; Fmoc-Leu-OH; Fmoc-Thr(tBu)-OH; N-(9-fluorenylmethoxycarbonyl)-D-leucine; (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid; 1‐fluorenylmethoxycarbonyl-(2S,3aS,7aS)‐octahydroindole‐2‐carboxylic acid; (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)butanoic acid; (2S)-2-[9H-fluorene-9-ylmethoxycarbonylamino]-4-methylsulfonylbutanoic acid; 2-([(9H-fluoren-9-yl)methoxy]carbonyl}amino)-3-(4-benzoylphenyl)propanoic acid Further stages;
  • 7
  • [ 235788-61-1 ]
  • [ 6089-09-4 ]
  • [ 929-10-2 ]
  • [ 35661-60-0 ]
  • [ 71989-35-0 ]
  • [ 114360-54-2 ]
  • [ 125238-99-5 ]
  • [ 130309-37-4 ]
  • [ 135112-27-5 ]
  • [ 163437-14-7 ]
  • [ 117666-96-3 ]
  • [ 2823428-20-0 ]
YieldReaction ConditionsOperation in experiment
Stage #1: Fmoc-Thr(tBu)-OH With O‑(6‑chlorobezotriazol‑1‑yl)‑N,N,N,N‑tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 2h; Stage #2: With piperidine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #3: (2S)-4-[[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl]amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]butanoic acid; 4-pentynoic acid; isooctanoic acid; Fmoc-Leu-OH; Fmoc-Thr(tBu)-OH; N-(9-fluorenylmethoxycarbonyl)-D-leucine; (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid; 1‐fluorenylmethoxycarbonyl-(2S,3aS,7aS)‐octahydroindole‐2‐carboxylic acid; (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)butanoic acid; (2S)-2-[9H-fluorene-9-ylmethoxycarbonylamino]-4-methylsulfonylbutanoic acid; 2-([(9H-fluoren-9-yl)methoxy]carbonyl}amino)-3-(4-benzoylphenyl)propanoic acid Further stages;
  • 8
  • [ 235788-61-1 ]
  • [ 6089-09-4 ]
  • [ 929-10-2 ]
  • [ 35661-60-0 ]
  • [ 71989-35-0 ]
  • [ 114360-54-2 ]
  • [ 125238-99-5 ]
  • [ 130309-37-4 ]
  • [ 135112-27-5 ]
  • [ 163437-14-7 ]
  • [ 117666-96-3 ]
  • [ 2823428-24-4 ]
YieldReaction ConditionsOperation in experiment
Stage #1: Fmoc-Thr(tBu)-OH With O‑(6‑chlorobezotriazol‑1‑yl)‑N,N,N,N‑tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 2h; Stage #2: With piperidine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #3: (2S)-4-[[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl]amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]butanoic acid; 4-pentynoic acid; isooctanoic acid; Fmoc-Leu-OH; Fmoc-Thr(tBu)-OH; N-(9-fluorenylmethoxycarbonyl)-D-leucine; (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid; 1‐fluorenylmethoxycarbonyl-(2S,3aS,7aS)‐octahydroindole‐2‐carboxylic acid; (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)butanoic acid; (2S)-2-[9H-fluorene-9-ylmethoxycarbonylamino]-4-methylsulfonylbutanoic acid; 2-([(9H-fluoren-9-yl)methoxy]carbonyl}amino)-3-(4-benzoylphenyl)propanoic acid Further stages;
  • 9
  • [ 235788-61-1 ]
  • [ 6089-09-4 ]
  • [ 71989-35-0 ]
  • [ 130309-37-4 ]
  • [ 135112-27-5 ]
  • [ 163437-14-7 ]
  • [ 117666-96-3 ]
  • [ 2823428-43-7 ]
YieldReaction ConditionsOperation in experiment
Stage #1: Fmoc-Thr(tBu)-OH With O‑(6‑chlorobezotriazol‑1‑yl)‑N,N,N,N‑tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 2h; Stage #2: With piperidine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #3: (2S)-4-[[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl]amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]butanoic acid; 4-pentynoic acid; 1‐fluorenylmethoxycarbonyl-(2S,3aS,7aS)‐octahydroindole‐2‐carboxylic acid; (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)butanoic acid; (2S)-2-[9H-fluorene-9-ylmethoxycarbonylamino]-4-methylsulfonylbutanoic acid; 2-([(9H-fluoren-9-yl)methoxy]carbonyl}amino)-3-(4-benzoylphenyl)propanoic acid Further stages;
  • 10
  • [ 235788-61-1 ]
  • [ 6089-09-4 ]
  • [ 71989-35-0 ]
  • [ 125238-99-5 ]
  • [ 130309-37-4 ]
  • [ 135112-27-5 ]
  • [ 163437-14-7 ]
  • [ 117666-96-3 ]
  • [ 2823428-39-1 ]
YieldReaction ConditionsOperation in experiment
Stage #1: Fmoc-Thr(tBu)-OH With O‑(6‑chlorobezotriazol‑1‑yl)‑N,N,N,N‑tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 2h; Stage #2: With piperidine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #3: (2S)-4-[[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl]amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]butanoic acid; 4-pentynoic acid; (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid; 1‐fluorenylmethoxycarbonyl-(2S,3aS,7aS)‐octahydroindole‐2‐carboxylic acid; (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)butanoic acid; (2S)-2-[9H-fluorene-9-ylmethoxycarbonylamino]-4-methylsulfonylbutanoic acid; 2-([(9H-fluoren-9-yl)methoxy]carbonyl}amino)-3-(4-benzoylphenyl)propanoic acid Further stages;
  • 11
  • [ 235788-61-1 ]
  • [ 6089-09-4 ]
  • [ 35661-60-0 ]
  • [ 71989-35-0 ]
  • [ 114360-54-2 ]
  • [ 125238-99-5 ]
  • [ 130309-37-4 ]
  • [ 135112-27-5 ]
  • [ 163437-14-7 ]
  • [ 117666-96-3 ]
  • [ 2823428-16-4 ]
YieldReaction ConditionsOperation in experiment
Stage #1: Fmoc-Thr(tBu)-OH With O‑(6‑chlorobezotriazol‑1‑yl)‑N,N,N,N‑tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 2h; Stage #2: With piperidine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #3: (2S)-4-[[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl]amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]butanoic acid; 4-pentynoic acid; Fmoc-Leu-OH; N-(9-fluorenylmethoxycarbonyl)-D-leucine; (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid; 1‐fluorenylmethoxycarbonyl-(2S,3aS,7aS)‐octahydroindole‐2‐carboxylic acid; (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)butanoic acid; (2S)-2-[9H-fluorene-9-ylmethoxycarbonylamino]-4-methylsulfonylbutanoic acid; 2-([(9H-fluoren-9-yl)methoxy]carbonyl}amino)-3-(4-benzoylphenyl)propanoic acid Further stages;
  • 12
  • [ 6089-09-4 ]
  • [ 130309-37-4 ]
  • [ 135112-27-5 ]
  • [ 163437-14-7 ]
  • [ 117666-96-3 ]
  • [ 2823427-84-3 ]
YieldReaction ConditionsOperation in experiment
16.7% Stage #1: (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)butanoic acid With O‑(6‑chlorobezotriazol‑1‑yl)‑N,N,N,N‑tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine at 20℃; for 2h; Stage #2: With piperidine In N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #3: 4-pentynoic acid; 1‐fluorenylmethoxycarbonyl-(2S,3aS,7aS)‐octahydroindole‐2‐carboxylic acid; (2S)-2-[9H-fluorene-9-ylmethoxycarbonylamino]-4-methylsulfonylbutanoic acid; 2-([(9H-fluoren-9-yl)methoxy]carbonyl}amino)-3-(4-benzoylphenyl)propanoic acid Further stages;
  • 13
  • [ 2497586-03-3 ]
  • [ 163437-14-7 ]
  • [ 2717499-28-8 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 0.5h; 10 Compound N : HATU (12 mg, 0.032 mmol, 1.1 equiv.) was added to a solution of amino acid M (12 mg, 0.029 mmol, 1.0 equiv.), Intermediate 3 (20 mg, 0.029 mmol, 1.0 equiv.) and DIEA (0.032 mL, 0.18 mmol, 6 equiv.) in DMF (1.0 mL), and the resultant mixture was stirred at room temperature for 30 min. The residual crude product was purified by HPLC (MeCN/fhO 65%-100%, 35 min, 40 mL/min, the product came out when MeCN is 77.1%) to afford compound N.
  • 14
  • [ CAS Unavailable ]
  • [ 163437-14-7 ]
YieldReaction ConditionsOperation in experiment
60% With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 0.5h; 10 Compound M : Fmoc-L-methionine (compound L) (100 mg, 0.27 mmol, 1.0 equiv.) was dissolved in DCM (2.0 mL) and mcpba (77%, 133 mg, 0.59 mmol, 2.2 equiv.). The resulting mixture was stirred at r.t. for 30 min until LC-MS showed that the reaction was finished. The solvents were removed under vacuum and the residue was purified by HPLC (MeCN/HzO 30%-100%, 70 min, 40 mL/min, the product came out when MeCN is 46.5%) to yield compound M (65 mg, 60% yield).
  • 15
  • [ 146368-11-8 ]
  • [ 625845-42-3 ]
  • [ CAS Unavailable ]
  • [ 163437-14-7 ]
  • [ 2446045-36-7 ]
YieldReaction ConditionsOperation in experiment
Stage #1: Fmoc-Oic-OH With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; Stage #2: With piperidine In N,N-dimethyl-formamide Stage #3: 1-(5-carboxypentyl)-2-[3,3-dimethyl-5-sulfo-1-(4-sulfobutyl)-2,3-dihydro-1H-indol-2-yliden]-1,3-pentadienyl-3,3-dimethyl-3H-indolium-5-sulfonate; C28H29NO5; Fmoc-L-Met(O2)-OH Further stages; 1 Example 1: Synthesis of sulfoCy5-Nle(OBzl)-Met(O)2-Oic-OH Synthesis of the protected linear peptide (Cy5-Nle(OBzl)-Met(O)2-Oic-OH) was carried out using manual peptide synthesis with standard Fmoc solid phase peptide chemistry. Synthesis was undertaken using Chlorotrityl chloride resin (loading 1.0 mmol/g from Chem-Impex) on a 0.2 mmol scale (0.3 g of resin). Coupling of the first amino acid was performed with Fmoc-Oic-OH (1.2 mol eq relative to resin loading) in dichloromethane (DCM) activated with 3 mol eq of diisopropylethylamine (DIPEA). This was carried out overnight at room temperature. The resin was then washed with DMF (3×5 mL×2 min each and then DCM 2×5 mL×2 min each) and then exposed to the deprotection solution 20% piperidine in DMF (3×5 mL×5 min each) and after the third deprotection step a positive bromophenol blue test resulted. (0326) Coupling of subsequent Fmoc-amino acids was performed using the 1.5 mol eq. (relative to resin loading) of Fmoc amino acid, PyBOP (1H-Benzotriazol-1-yloxy)(tri-1-pyrrolidinyl)phosphonium hexafluorophosphate in DMF (5 mL/g of resin) with activation in situ, using 3 mol equiv of DIPEA. This was carried out for 1 h at room temperature (RT). At this stage the TNBS test was used to monitor peptide coupling providing a negative result. The resin was then washed with DMF (3×5 mL×2 min each and then DCM 2×5 mL×2 min each). The resin was then exposed to the deprotection solution 20% piperidine in DMF (3×5 mL×5 min each) and after the third deprotection step a positive TNBS test resulted. The resin was washed with DMF (3×5 mL×2 min each and then DCM 2×5 mL×2 min each) and the coupling process continued with the next Fmoc amino acid until the sequence was completed. (0327) The final amino acid on the peptide resin was Fmoc deprotected with 20% piperidine in DMF (3×5 mL×5 min each) and then thoroughly washed with DMF then DCM. A portion of the resin (30 mg, 0.03 mmol) was suspended in 4:1 DMF:DMSO and sulfoCy5 acid (30 mg, 0.046 mmol) was added to the mixture followed by PyBOP (0.1 mmol) and finally DIPEA (0.6 mmol). The mixture was left for 24 h with intermittent agitation and then thoroughly washed with DMSO (until a colorless filtrate was obtained), followed by DMF, DCM, MeOH and finally Ether. The dried resin was taken up in 5 mL of HFIP (hexafluoroisopropanol):DCM:TIPS (v:v:v, 30:69:1) and left to stand for 2 h. The filtrate was filtered from the resin and the resin washed with HFIP until colorless. The combined filtrate and washings were concentrated to a residue (10.1 mg) and then purified by RP-HPLC providing 3 mg of the intermediate sulfoCy5-Nle(OBzl)-Met(O)2-Oic-OH as a blue powder. The compound was checked for purity by HPLC absorbance measurement at 214 nm (0329) (FIG. 1A) and confirmed as having the correct molecular weight by API-ES analysis: m/z calculated; C60H79N5O14S3 [M-H]- 1189.5, [M-2H]2- 593.7; observed: [M-H]- 1189.0, [M-2H]2- 593.6 (FIG. 1B).
Stage #1: Fmoc-Oic-OH With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; Stage #2: With piperidine In N,N-dimethyl-formamide Stage #3: 1-(5-carboxypentyl)-2-[3,3-dimethyl-5-sulfo-1-(4-sulfobutyl)-2,3-dihydro-1H-indol-2-yliden]-1,3-pentadienyl-3,3-dimethyl-3H-indolium-5-sulfonate; C28H29NO5; Fmoc-L-Met(O2)-OH Further stages; 1 Example 1: Synthesis of sulfoCy5-Nle(OBzl)-Met(O)2-Oic-OH Synthesis of the protected linear peptide (Cy5-Nle(OBzl)-Met(O)2-Oic-OH) was carried out using manual peptide synthesis with standard Fmoc solid phase peptide chemistry. Synthesis was undertaken using Chlorotrityl chloride resin (loading 1.0 mmol/g from Chem-Impex) on a 0.2 mmol scale (0.3 g of resin). Coupling of the first amino acid was performed with Fmoc-Oic-OH (1.2 mol eq relative to resin loading) in dichloromethane (DCM) activated with 3 mol eq of diisopropylethylamine (DIPEA). This was carried out overnight at room temperature. The resin was then washed with DMF (3×5 mL×2 min each and then DCM 2×5 mL×2 min each) and then exposed to the deprotection solution 20% piperidine in DMF (3×5 mL×5 min each) and after the third deprotection step a positive bromophenol blue test resulted. (0326) Coupling of subsequent Fmoc-amino acids was performed using the 1.5 mol eq. (relative to resin loading) of Fmoc amino acid, PyBOP (1H-Benzotriazol-1-yloxy)(tri-1-pyrrolidinyl)phosphonium hexafluorophosphate in DMF (5 mL/g of resin) with activation in situ, using 3 mol equiv of DIPEA. This was carried out for 1 h at room temperature (RT). At this stage the TNBS test was used to monitor peptide coupling providing a negative result. The resin was then washed with DMF (3×5 mL×2 min each and then DCM 2×5 mL×2 min each). The resin was then exposed to the deprotection solution 20% piperidine in DMF (3×5 mL×5 min each) and after the third deprotection step a positive TNBS test resulted. The resin was washed with DMF (3×5 mL×2 min each and then DCM 2×5 mL×2 min each) and the coupling process continued with the next Fmoc amino acid until the sequence was completed. (0327) The final amino acid on the peptide resin was Fmoc deprotected with 20% piperidine in DMF (3×5 mL×5 min each) and then thoroughly washed with DMF then DCM. A portion of the resin (30 mg, 0.03 mmol) was suspended in 4:1 DMF:DMSO and sulfoCy5 acid (30 mg, 0.046 mmol) was added to the mixture followed by PyBOP (0.1 mmol) and finally DIPEA (0.6 mmol). The mixture was left for 24 h with intermittent agitation and then thoroughly washed with DMSO (until a colorless filtrate was obtained), followed by DMF, DCM, MeOH and finally Ether. The dried resin was taken up in 5 mL of HFIP (hexafluoroisopropanol):DCM:TIPS (v:v:v, 30:69:1) and left to stand for 2 h. The filtrate was filtered from the resin and the resin washed with HFIP until colorless. The combined filtrate and washings were concentrated to a residue (10.1 mg) and then purified by RP-HPLC providing 3 mg of the intermediate sulfoCy5-Nle(OBzl)-Met(O)2-Oic-OH as a blue powder. The compound was checked for purity by HPLC absorbance measurement at 214 nm (0329) (FIG. 1A) and confirmed as having the correct molecular weight by API-ES analysis: m/z calculated; C60H79N5O14S3 [M-H]- 1189.5, [M-2H]2- 593.7; observed: [M-H]- 1189.0, [M-2H]2- 593.6 (FIG. 1B).
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