Acetic Acid → HCID 86636763, compound

HRID 1910405Notes

Reaction equation

HRID 1910405 reaction equation
[C:1]([NH:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]([NH:14][NH2:15])=[O:13])(=[O:5])[C:2]([CH3:4])=[CH2:3].[CH3:16][C@@H:17]1[O:22][C@@H:21]([O:23][C@@H:24]2[C:29]3=[C:30]([OH:47])[C:31]4[C:43](=[O:44])[C:42]5[C:37](=[CH:38][CH:39]=[CH:40][C:41]=5[O:45][CH3:46])[C:35](=[O:36])[C:32]=4[C:33]([OH:34])=[C:28]3[CH2:27][C@@:26]([OH:52])([C:48]([CH2:50][OH:51])=[O:49])[CH2:25]2)[CH2:20][C@H:19]([NH2:53])[C@@H:18]1[OH:54].Cl.C(O)(=O)C>CO.CO.C(Cl)(Cl)Cl.C(O)(=O)C>[C:1]([NH:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]([NH:14][NH2:15])=[O:13])(=[O:5])[C:2]([CH3:4])=[CH2:3].[CH3:16][C@@H:17]1[O:22][C@@H:21]([O:23][C@@H:24]2[C:29]3=[C:30]([OH:47])[C:31]4[C:43](=[O:44])[C:42]5[C:37](=[CH:38][CH:39]=[CH:40][C:41]=5[O:45][CH3:46])[C:35](=[O:36])[C:32]=4[C:33]([OH:34])=[C:28]3[CH2:27][C@@:26]([OH:52])([C:48]([CH2:50][OH:51])=[O:49])[CH2:25]2)[CH2:20][C@H:19]([NH2:53])[C@@H:18]1[OH:54]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 31703DoxorubicinHCID 71445139N-(6-Hydrazinyl-6-oxohexyl)-2-methylprop-2-enamide

Product 1

HCID 86636763HCID 86636763, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 21866353chloroform methanol HOAcSolvent

Procedure

6-(Methacryloylamino)hexanoylhydrazine (40 mg, 0.188 mmol) was dissolved in 6 ml of methanol at room temperature. The solution was poured into a reaction vessel in which doxorubicin.HCl (115 mg, 0.198 mmol) was placed and the suspension was stirred vigorously. 310 μl of acetic acid was added to the suspension and the reaction mixture stirred at room temperature for 24 hours. The reaction process was monitored by TLC-Silicagel 60 F254 plates (methanol:chloroform:acetic acid 2:8:1, Rf(DOX)=0.75, Rf(MA-AH-NHN=DOX)=0.9). 100 mg of copolymer 1 was then added to the homogenous reaction mixture (to bind the residual free DOX) and the reaction mixture was stirred at room temperature for another 4 hours. The product was purified from polymeric and low-molecular impurities by means of gel chromatography in a column (30 cm×3 cm) filled with Sephadex LH-20 in methanol. The filtrate was concentrated to 2 ml and the product precipitated into 30 ml of diethyl ether. The product was sucked off, washed with a small amount of diethyl ether, and vacuum dried to constant weight. The yield was 110 mg of product (79%) with the melting point of 172 to 175° C. TLC (methanol:chloroform:acetic acid 2:8:1): one stain at Rf=0.9. MALDI-TOF MS: 762 (M+Na).

Workup

  1. stirringthe reaction mixture stirred at room temperature for 24 hours
  2. stirringwas stirred at room temperature for another 4 hours
  3. customThe product was purified from polymeric and low-molecular impurities by means of gel chromatography in a column (30 cm×3 cm)
  4. additionfilled with Sephadex
  5. concentrationThe filtrate was concentrated to 2 ml
  6. customthe product precipitated into 30 ml of diethyl ether
  7. washwashed with a small amount of diethyl ether, and vacuum
  8. customdried to constant weight

Sources & evidence

ORD record
ord-4ee038d854aa41dab69057bd2c3aab4d
Source dataset
uspto-grants-2013_12
Patent number
US08603990B2

Reaction notes

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