ChemicalBook CAS DataBase List PROTAC RAR Degrader-1

PROTAC RAR Degrader-1 synthesis

12synthesis methods

Product Name:PROTAC RAR Degrader-1
CAS Number:1351169-27-1
Molecular formula:C51H72N4O11
Molecular Weight:917.14

12,15,18-Trioxa-2,6,9,21-tetraazatetracosanoic acid, 24-[5-[(1E)-3-[3,5-bis(1,1-dimethylethyl)phenyl]-3-oxo-1-propen-1-yl]-2-(methoxycarbonyl)phenoxy]-4-hydroxy-7-(2-methylpropyl)-5,8,20-trioxo-3-(phenylmethyl)-, 9H-fluoren-9-ylmethyl ester, (3R,4S,7S)-

1351169-42-0
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1351169-27-1
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Yield:1351169-27-1 64%

Reaction Conditions:

Stage #1: methyl 2-(3-{2-[2-(2-{2-[(S)-2-((2S,3R)-3-{[(9H-fluoren-9-yl)methoxy]carbonylamino}-2-hydroxy-4-phenylbutanamido)-4-methylpentanamido]ethoxy}ethoxy)ethoxy]acetamido}propoxy)-4-[(E)-3-(3,5-di-tert-butylphenyl)-3-oxoprop-1-enyl]benzoatewith lithium hydroxide monohydrate in methanol;water at 20; for 2 h;
Stage #2: in methanol;water;Acidic conditions;

Steps:

5.1.12. 2-[3-(2-{2-[2-(2-{(S)-2-[(2S,3R)-3-Amino-2-hydroxy-4-phenylbutanamido]-4-methylpentanamido}ethoxy)ethoxy]ethoxy}acetamido)propoxy]-4-[(E)-3-(3,5-di-tert-butylphenyl)-3-oxoprop-1-enyl]benzoic acid (9)

LiOH·H₂O (36.0 mg, 0.858 mmol) was added to a solution of 30a (16.0 mg, 0.0139 mmol) in MeOH/H₂O (1.0 mL/0.25 mL) and the resulting mixture was stirred at room temperature for 2 h. The reaction mixture was neutralized and concentrated in vacuo. The residue was extracted with AcOEt. The organic solution was washed with brine, concentrated in vacuo and purified by PTLC (CHCl₃/MeOH/25% NH₃ aqueous solution = 6/1/1) to give 683 mg (64%) of 9 as a colorless solid; ¹H NMR (CDCl₃, 500 MHz, δ; ppm): 8.19 (1H, br), 7.90 (2H, m), 7.82 (2H, d, J = 1.8 Hz), 7.76 (1H, m), 7.69 (1H, d, J = 15.8 Hz), 7.67 (1H, t, J = 1.8 Hz), 7.48 (1H, d, J = 15.8 Hz), 7.32-7.18 (5H, m), 7.14 (1H, s), 4.30 (2H, m), 4.14 (3H, m), 4.00-3.40 (21H, m), 3.26 (1H, m), 3.13 (1H, m), 2.04 (2H, m), 1.80 (1H, m), 1.61 (2H, m), 1.38 (18H, s), 0.90 (3H, d, J = 6.7 Hz) 0.89 (3H, d, J = 6.7 Hz); ¹³C NMR (CDCl₃, 125 MHz, δ; ppm): 191.49, 172.61, 171.91, 169.91, 169.74, 151.33, 143.48, 137.76, 129.36, 128.99, 127.74, 127.29, 127.23, 122.75, 120.51, 119.27, 113.92, 70.96, 70.10, 70.02, 69.69, 69.03, 69.39, 68.04, 67.02, 55.01, 52.79, 40.08, 39.12, 36.39, 36.22, 35.03, 31.41, 29.69, 24.81, 23.04, 21.57; MS (FAB) m/z: 917 (MH⁺); HRMS (FAB) calcd for , 917.5276; found 917.5297.

References:

Itoh, Yukihiro;Kitaguchi, Risa;Ishikawa, Minoru;Naito, Mikihiko;Hashimoto, Yuichi [Bioorganic and Medicinal Chemistry,2011,vol. 19,# 22,p. 6768 - 6778] Location in patent:experimental part

Ethanone, 1-[3,5-bis(1,1-dimethylethyl)phenyl]-2-bromo-

717915-17-8
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1351169-27-1
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Phosphonic acid, P-[2-[3,5-bis(1,1-dimethylethyl)phenyl]-2-oxoethyl]-, diethyl ester

1351169-32-8
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1351169-27-1
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References

12,15,18-Trioxa-2,6,9-triazaeicosanedioic acid, 4-hydroxy-7-(2-methylpropyl)-5,8-dioxo-3-(phenylmethyl)-, 20-(1,1-dimethylethyl) 1-(9H-fluoren-9-ylmethyl) ester, (3R,4S,7S)-

1351169-38-4
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1351169-27-1
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Benzoic acid, 4-[(1E)-3-[3,5-bis(1,1-dimethylethyl)phenyl]-3-oxo-1-propen-1-yl]-2-[3-[[(1,1-dimethylethoxy)carbonyl]amino]propoxy]-, methyl ester

1351169-36-2
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1351169-27-1
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