Dapt

Base Information

• Chemical Name: Dapt
• CAS No.: 208255-80-5
• Molecular Formula: C23H26F2N2O4
• Molecular Weight: 432.467
• Hs Code.: 29242990
• DSSTox Substance ID: DTXSID00415519
• Nikkaji Number: J1.588.805I
• Wikipedia: DAPT_(chemical)
• Wikidata: Q27158972
• ChEMBL ID: CHEMBL255682
• Mol file: 208255-80-5.mol

Synonyms:DAPT butylester;DAPT peptide;GSI-IX cpd;N-(2FPhAc)Ala-phenyl-Gly t-butyl ester;N-(N-(3,5-difluorophenacetyl)alanyl)-S-phenylglycine t-butyl ester;N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine t-butyl ester;N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester;N-(N-(3,5-difluorophenylacetyl)alanyl)phenyloglycine t-butyl ester

Chemical Property of Dapt

Chemical Property:

• Appearance/Colour: white solid
• Vapor Pressure: 6.31E-15mmHg at 25°C
• Refractive Index: 1.534
• Boiling Point: 612.2 °C at 760 mmHg
• PKA: 12.82±0.46(Predicted)
• Flash Point: 324.1 °C
• PSA: 84.50000
• Density: 1.213 g/cm³
• LogP: 3.99300
• Storage Temp.: 2-8°C
• Sensitive.: Light Sensitive
• Solubility.: DMSO: ~18 mg/mL
• XLogP3: 3.7
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 9
• Exact Mass: 432.18606364
• Heavy Atom Count: 31
• Complexity: 622

Purity/Quality:

99% ^*data from raw suppliers

DAPT ^*data from reagent suppliers

Safty Information:

• Safety Statements: 24/25

MSDS Files:

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: CC(C(=O)NC(C1=CC=CC=C1)C(=O)OC(C)(C)C)NC(=O)CC2=CC(=CC(=C2)F)F
• Isomeric SMILES: C[C@@H](C(=O)N[C@@H](C1=CC=CC=C1)C(=O)OC(C)(C)C)NC(=O)CC2=CC(=CC(=C2)F)F
• Recent ClinicalTrials: Antithrombotic Therapy After Coronary Artery Bypass Grafting Combined With Coronary Endarterectomy
• Description: DAPT (208255-80-5) is an inhibitor of γ-secretase (IC50 in human primary neurons = 115 nM for total Aβ or 200 nM for Aβ42 specifically).1?Oral administration of DAPT has been shown to reduce levels of Aβ in brain extract, cerebrospinal fluid and plasma from mice and rats.2,3?DAPT blocks Notch signaling which promotes neuronal differentiation of precursor cells.4?Enhances iPS cells without oncogenes KLF4 and CMYC5. Cell permeable.
• Uses: DAPT (GSI-IX) is a novel γ-secretase inhibitor, which inhibits Aβ production with IC50 of 20 nM in HEK 293 cells A potent and specific inhibitor of γ-secretase. DAPT is used in the study of β-amyloid formation. DAPT has been shown to inhibit Notch signaling in studies of autoimmune and lymphoproliferative diseases, such as ALPS and lupus erythematosus, as well as in cancer cell growth, angiogenesis, and differentiation of human induced pluripotent stem cells.

Technology Process of Dapt

There total 5 articles about Dapt which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 88.0%

3,5-difluorophenyl acetic acid (105184-38-1) + N-(L-alanyl)-(2S)-2-phenylglycine tert-butyl ester (327052-53-9) → ((S)-tert-butyl 2-((S)-2-(2-(3,5-difluorophenyl)acetamido)propanamido)-2-phenylacetate) (208255-80-5)

Guidance literature:

3,5-difluorophenyl acetic acid; With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20 ℃; for 1h;

N-(L-alanyl)-(2S)-2-phenylglycine tert-butyl ester; With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20 ℃;

DOI:10.1039/b504988a

Reference yield:

N-(N-carbobenzyloxy-L-alanyl)-(2S)-2-phenylglycine tert-butyl ester (860013-16-7) → ((S)-tert-butyl 2-((S)-2-(2-(3,5-difluorophenyl)acetamido)propanamido)-2-phenylacetate) (208255-80-5)

Guidance literature:

Multi-step reaction with 2 steps

1: 96 percent / H₂ / Pd(OH)2 on activated charcoal / methanol / 20 °C

2: 88 percent / BOP; ethyldiisopropylamine / CH₂Cl₂ / 0 - 20 °C

With hydrogen; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; palladium hydroxide - carbon; In methanol; dichloromethane;

DOI:10.1071/CH05102

Reference yield:

tert-butyl (S)-2-amino-2-phenylacetate hydrochloride → ((S)-tert-butyl 2-((S)-2-(2-(3,5-difluorophenyl)acetamido)propanamido)-2-phenylacetate) (208255-80-5)

Guidance literature:

Multi-step reaction with 3 steps

1: 3.70 g / BOP; ethyldiisopropylamine / CH₂Cl₂ / 20 °C

2: 96 percent / H₂ / Pd(OH)2 on activated charcoal / methanol / 20 °C

3: 88 percent / BOP; ethyldiisopropylamine / CH₂Cl₂ / 0 - 20 °C

With hydrogen; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; palladium hydroxide - carbon; In methanol; dichloromethane;

DOI:10.1071/CH05102

upstream raw materials:

3,5-difluorophenyl acetic acid

N-(L-alanyl)-(2S)-2-phenylglycine tert-butyl ester

N-(N-carbobenzyloxy-L-alanyl)-(2S)-2-phenylglycine tert-butyl ester

(S)-2-phenylglycine

Downstream raw materials:

(2S)-({N-[(3,5-difluorophenyl)acetyl]-L-alanyl}amino)(phenyl)acetic acid

Refernces

• 1、 Pietrancosta, Nicolas,Quelever, Gilles,Laras, Younes,Garino, Cedrik,Burlet, Stephane,Kraus, Jean Louis. "Design of β-secretase inhibitors by introduction of a mandelyl moiety in DAPT analogues". . p. 585 - 594. Retrieved 2007/10/03.