Home Cart 0 Sign in  

[ CAS No. 159858-21-6 ]

{[proInfo.proName]} ,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
2D
Chemical Structure| 159858-21-6
Chemical Structure| 159858-21-6
Structure of 159858-21-6 *Storage: {[proInfo.prStorage]}

Quality Control of [ 159858-21-6 ]

Related Doc. of [ 159858-21-6 ]

SDS
Alternatived Products of [ 159858-21-6 ]
Alternatived Products of [ 159858-21-6 ]

Product Details of [ 159858-21-6 ]

CAS No. :159858-21-6MDL No. :MFCD28139060
Formula : C26H32N4O6 Boiling Point : -
Linear Structure Formula :-InChI Key :N/A
M.W :496.56Pubchem ID :-
Synonyms :

Computed Properties of [ 159858-21-6 ]

TPSA : - H-Bond Acceptor Count : -
XLogP3 : - H-Bond Donor Count : -
SP3 : - Rotatable Bond Count : -

Safety of [ 159858-21-6 ]

Signal Word:WarningClass:N/A
Precautionary Statements:P280-P305+P351+P338UN#:N/A
Hazard Statements:H302Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 159858-21-6 ]

  • Upstream synthesis route of [ 159858-21-6 ]
  • Downstream synthetic route of [ 159858-21-6 ]

[ 159858-21-6 ] Synthesis Path-Upstream   1~4

  • 1
  • [ 159858-21-6 ]
  • [ 623-04-1 ]
  • [ 159858-22-7 ]
YieldReaction ConditionsOperation in experiment
88% With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline In methanol; dichloromethane at 20℃; for 48 h; Darkness DCM/MeOH=2/1 mixed solvent 60 ml was added to the reaction flask, followed by addition of Fmoc-vc2g (4.2 mmol) and1.04 g (2 eq) of PABOH was added. After stirring the dissolved portion, 2.0 g (2 eq) of EEDQ was added. The reaction system is protected from light at room temperatureStir the reaction for 2.0 days. After completion of the reaction, the mixture was concentrated under reduced pressure at 40°C to give a white solid. Collect white solids and add methyl tert-butylEthyl ether (100 ml) was stirred and filtered, and the filter cake was washed with methyl tert-butyl ether. The resulting white solid was dried at 40 °C under reduced pressure to give 2.2 g.About 88percent
85% With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline In methanol; dichloromethane at 20℃; for 36 h; Darkness; Inert atmosphere Fmoc-Val-Cit-PABOH 2. To a solution of Fmoc-protected dipeptide 1 (0.30 g, 0.60 mmol) in CH2Cl2/MeOH (2: 1 , 9 mL) was added P-aminobenzyl alcohol (0.12 g, 0.98 mmol ) and EEDQ (0.24 g, 0.98 mmol), and the reaction mixture was stirred in the dark for 1.5 d. The solvents were evaporated, and the resultant was triturated with Et20 (25 mL). The resulting suspension was sonicated for 20 min and left to stand for 30 min. The crude product was collected by filtration and then purified by flash chromatography using a pre-packed 50 g silica column [solvent A: MeOH; solvent B: CH2C12; gradient: 0percentA / 100percentB (1 CV), 0percentA / 100percentB -→ 20percentA / 80percentB (10 CV), 20percentA / 80percentB (2 CV); flow rate: 40 mL/min; monitored at 254 and 280 nm] to afford Fmoc-protected compound 2 (0.31 g, 0.51 mmol, 85percent yield) as a brown solid. [000188] NMR (500 MHz, DMSO-d6) 6 10.00 (1 H, s), 8.13 (1 H, d, J = 7.7 Hz), 7.92 (2H, d, J = 7.5 Hz), 7.81 - 7.71 (2H, m), 7.57 (2H, d, J= 8.4 Hz), 7.49 - 7.40 (3H, m), 7.35 (2H, t, J= 7.4 Hz), 7.26 (2H, d, J = 8.3 Hz), 5.99 (1 H, t, J = 6.5 Hz), 5.43 (2H, s), 5.12 (1 H, t, J= 5.6 Hz), 4.45 (2H, d, J= 5.4 Hz), 4.32 (1H, d,J= 10.1 Hz), 4.29 - 4.19 (3H, m), 4.00 - 3.88 (1H, m), 3.12 - 2.91 (2H, m), 2.09 - 1.94 (1H, m), 1.80-1.31 (4H, m), 0.90 (3H, d, .7=6.6 Hz), 0.88 (3H, d,J=6.7 Hz). [000189] I3C NMR (125 MHz, DMSO-d6) δ 171.7, 170.9, 159.3, 156.6, 144.4, 144.2, 141.2, 138.0, 137.9, 128.1, 127.6, 127.4, 125.8, 120.6, 119.3, 66.2, 63.1, 60.6, 47.2,30.9,30.0, 27.3, 19.7, 18.8, 15.0.
82% With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline In methanol at 20℃; for 36 h; Fmoc-val-cit (1 eq),Add 2 eq of p-aminobenzyl alcohol (2 eq) to DMC / MeOH (2: 1), add EEDQ (2 eq) and shake for 1.5 days at room temperature.After completion of the reaction, the solvent is dried and precipitated with ether. Repeat after filtering with Ether. Yield: yellow solid 82percent.
77% With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline In methanol; dichloromethane at 40℃; Step 3
Synthesis of (9H-fluoren-9-yl)methyl ((S)-1-(((S)-1-((4-(hydroxymethyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)carbamate (92)
To the suspension of compound 90 (70 g, 0.141 mol) in DCM/MeOH (1 L/500 mL) was added compound 91 (34.7 g, 0.282 mol) followed by EEDQ (69.7 g, 0.282 mol).
The mixture was stirred at 40° C. overnight.
The reaction mixture was filtered and the wet cake was suspended in EtOAc/TBME (500 mL/200 mL) and stirred for 30 min, then filtered.
The solid was washed with EtOAc/TBME to provide compound 92 as off-white solid 65 g (77percent).
1H NMR (400 MHz, DMSO-d6) δ=9.98 (s, 1H), 8.11 (d, 1H), 7.87 (d, 2H), 7.77 (m, 2H), 7.52 (d, 2H), 7.39 (m, 3H), 7.30 (m, 2H), 7.21 (d, 2H), 5.97 (m, 1H), 5.41 (s, 2H), 5.10 (m, 1H), 4.42 (m, 3H), 4.22 (m, 3H), 3.90 (m, 1H), 2.93 (m, 2H), 1.98 (m, 1H), 1.50 (m, 2H), 1.30 (m, 2H), 0.84 (m, 6H).
76% With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline In methanol; dichloromethane at 20℃; A solution of compound 28 (1 g, 2.01 mmol, leq) andp-aminobenzyl alcohol (273 mg, 2.21 mmol, 1.1 eq) in a mixture of DCM/MeOH (20 mL/10 mL) was treated with EEDQ (996 mg, 4.03 mmol, 2 eq). The mixture was stirred in the dark at room temperature overnight. The solvents were removed under vacuum and the resulting solid residue was triturated with 10 mL of ethyl ether. The solid was collected by filtration and washed with ethyl ether to yield the product (925 mg, 76percent yield): 1H NMR (DMSO-5 d, J -8.5 Hz), 7.74 (2H, t, J = 6.7 Hz), 7.89 (2H, d, J = 7.6 Hz)5 8.12 (IH, d, J = 7.3 Hz); 13 C NMR (DMSO-c^) δ 18.34, 19.28, 26.84, 29.56, 30.47, 46.67, 53.05, 60.05, 62.55, 65.65, 118.71, 119.98, 125.23, 126.79, 126.94, 127.51, 137.27, 137.36, 140.55, 143.60, 143.73, 155.93, 158.69, 170.17, 171.06.
65% With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline In methanol; dichloromethane at 20℃; for 16 h; Darkness EEDQ (840 mg, 3.4 mmol) is added to a solution containing compound [12] (870 mg, 1 .7 mmol) and p-aminobenzyl alcohol (227 mg, 1 .8 mmol) in dichloro- methane/methanol 2:1 (15 mL). The reaction is left in the dark at room temperature for 16 hours. The solvents are removed, and the resulting solid residue filtrated using diethyl ether to give product [14] as a white solid, 660 mg (65percent yield). MS: m/z 624 [M+Na]+.1H NMR (400 MHz, DMSO) δ 10.00 (bs, 1 H), 8.13 (m, 4H), 7.92 (d, J = 7.3 Hz, 2H), 7.76 (d, J = 7.6 Hz, 2H), 7.58 (d, J = 8.1 Hz, 2H), 7.51 - 7.10 (m, 2H), 6.02 (s, 1 H), 5.43 (m, 4H), 5.13 (s, 1 H), 4.47 (s, 3H), 4.31 (m 4H), 3.13 - 2.74 (m, 2H), 2.03 (s, 1 H), 1 .83 - 1 .55 (m, 2H), 1 .43 (s, 2H), 0.90 (d, J = 6.7 Hz, 6H).13C NMR (101 MHz, DMSO) δ 171 .2, 170.4, 158.93, 156.15, 144.6, 143.8, 140.7, 137.5, 127.6, 127.2 (2C) 125.3, 120.1 (2C), 1 18.9, 65.7, 62.6, 60.1 , 53.0, 46.7, 31 .0, 30.5, 26.7, 19.6, 18.7.

Reference: [1] International Journal of Molecular Sciences, 2017, vol. 18, # 9,
[2] Patent: CN107789630, 2018, A, . Location in patent: Paragraph 0073; 0074; 0075
[3] Patent: WO2017/66668, 2017, A1, . Location in patent: Paragraph 000187-000189
[4] Journal of Controlled Release, 2012, vol. 160, # 3, p. 618 - 629
[5] Patent: KR2017/41562, 2017, A, . Location in patent: Paragraph 0431-0432
[6] Patent: US2016/271270, 2016, A1, . Location in patent: Paragraph 0379; 0382
[7] Patent: WO2008/34124, 2008, A2, . Location in patent: Page/Page column 79
[8] Patent: WO2018/178060, 2018, A1, . Location in patent: Page/Page column 64; 65; 67
[9] Patent: WO2014/80251, 2014, A1, . Location in patent: Sheet 16/23
[10] Bioconjugate Chemistry, 2015, vol. 26, # 11, p. 2261 - 2278
[11] Nature Communications, 2017, vol. 8, # 1,
  • 2
  • [ 159858-21-6 ]
  • [ 159857-81-5 ]
Reference: [1] Patent: WO2017/66668, 2017, A1,
[2] Patent: WO2017/66668, 2017, A1,
[3] International Journal of Molecular Sciences, 2017, vol. 18, # 9,
[4] Patent: CN107789630, 2018, A,
[5] Patent: CN108743968, 2018, A,
  • 3
  • [ 159858-21-6 ]
  • [ 159857-79-1 ]
Reference: [1] Patent: WO2014/80251, 2014, A1,
[2] Patent: WO2017/66668, 2017, A1,
[3] International Journal of Molecular Sciences, 2017, vol. 18, # 9,
[4] Patent: CN107789630, 2018, A,
[5] Patent: WO2018/178060, 2018, A1,
[6] Patent: CN108743968, 2018, A,
  • 4
  • [ 159858-21-6 ]
  • [ 863971-53-3 ]
Reference: [1] Patent: US2016/271270, 2016, A1,
Historical Records