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Chemical Structure| 195514-23-9 Chemical Structure| 195514-23-9
Chemical Structure| 195514-23-9

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AP1867 is a synthetic FKBP12F36V-directed ligand, used as a warhead in a series of heterobifunctional degraders (PROTACs) targeting FKBP12F36V.

4.5 *For Research Use Only! Not for Human Use. We Do Not Sell to Patients.

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Product Details of AP1867

CAS No. :195514-23-9
Formula : C38H47NO11
M.W : 693.78
SMILES Code : O=C([C@H]1N(C([C@H](C2=CC(OC)=C(OC)C(OC)=C2)CC)=O)CCCC1)O[C@@H](C3=CC=CC(OCC(O)=O)=C3)CCC4=CC=C(OC)C(OC)=C4
English Name :2-(3-((R)-3-(3,4-Dimethoxyphenyl)-1-(((S)-1-((S)-2-(3,4,5-trimethoxyphenyl)butanoyl)piperidine-2-carbonyl)oxy)propyl)phenoxy)acetic acid
MDL No. :MFCD31813776

Safety of AP1867

Application In Synthesis of AP1867

* 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 [ 195514-23-9 ]

[ 195514-23-9 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 195202-06-3 ]
  • [ 195514-23-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: PyBroP; diisopropylethylamine / CH2Cl2 / 20 °C 2: TFA / CH2Cl2 / 2 h / 20 °C
Multi-step reaction with 3 steps 1.1: Cinchonidin / acetonitrile / 20 °C 2.1: 2-chloro-1-methyl-pyridinium iodide; triethylamine / dichloromethane / 2 h / 20 °C 2.2: 20 °C 3.1: dmap; dicyclohexyl-carbodiimide / dichloromethane / 20 °C
  • 2
  • [ 1957235-98-1 ]
  • [ 195514-23-9 ]
  • [ 1957235-19-6 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 17h; 90.1 Synthesis of dFKBP13 - dFKBP21 and dFKBP24 - dFKBP38 4-((6-aminohexyl)oxy)-2-(2,6-dioxopiperidin-3-yl)isoindoline-l,3-dione (5.59 mg, 0.015 mmol, leq) as a solution in 151.63 μ DMF (0.1 M) is added to FKBP acid (10.52 mg, 0.015 mmol, leq). DIPEA (7.43 μ, 0.045 mmol, 3 eq) is added, followed by HATU (5.70 mg, 0.015 mmol, 1 eq). The mixture is stirred for 17 hours at room temperature. The mixture is then diluted with EtOAc and washed with saturated sodium bicarbonate, water then brine. The organic layer is dried over sodium sulfate, filtered and condensed. The crude material is purified by column chromatography.
  • 3
  • [ 1957235-99-2 ]
  • [ 195514-23-9 ]
  • [ 1957235-19-6 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 23h; 93 4-((6-aminohexyl)oxy)-2-(2,6-dioxopiperidin-3-yl)isoindoline-l ,3-dione trifluoroacetate salt (9.7 mg, 0.020 mmol, 1 eq) is added to 2-(3-((i?)-3-(3,4- dimethoxy phenyl)- 1 -(((
  • 4
  • [ 890091-43-7 ]
  • [ 195514-23-9 ]
  • [ 3080923-25-4 ]
YieldReaction ConditionsOperation in experiment
80% 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℃; 1 Synthesis of 11 To t-Boc-N-amido-PEG9-amine (17 mg, 0.031 mmol, 1.0 equiv.) was added AP1867 (21 mg, 0.031 mmol), HATU (18 mg, 0.046 mmol, 1.6 equiv.), DMF (0.5 mL), and DIPEA (27 μL, 0.155 mmol, 5.0 equiv.). The reaction mixture was stirred overnight at room temperature, then diluted with ethyl acetate (5 mL) washed with water (2 x 5 mL), saturated NaHCO3(1 x 5 mL), brine (5 mL), dried over Mg2SO4and filtered. The filtrate was concentrated under reduced pressure and purified by flash column chromatography (0-10% MeOH in CH2CI2), to yield a colorless residue (30.8 mg, 80% yield). 'H NMR (600 MHz, CDC13) 87.17 (t, J= 7.8 Hz, 1H), 7.12 - 6.94 (m, 1H), 6.94 - 6.82 (m, 1H), 6.82 - 6.73 (m, 2H), 6.73 - 6.58 (m, 3H), 6.41 (s, 2H), 5.62 (dd, J = 8.2, 5.5 Hz, 1H), 5.50 - 5.38 (m, 1H), 5.04 (s, 1H), 4.57 - 4.38 (m, 2H), 3.99 - 3.80 (m, 9H), 3.78 (s, 2H), 3.68 (s, 3H), 3.67 - 3.42 (m, 36H), 3.30 (q, J = 5.3 Hz, 2H), 2.79 (td, J = 13.4, 3.1 Hz, 1H), 2.63 - 2.40 (m, 2H), 2.34 - 2.15 (m, 1H), 2.13 - 1.97 (m, 2H), 1.99 - 1.84 (m, 2H), 1.75 - 1.65 (m, 2H), 1.65 - 1.49 (m, 1H), 1.43 (s, 9H), 0.89 (t, J = 7.3 Hz, 3H).
 

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