Disodium methylenebis(2-hydroxy-3-naphthoate) → HCID 178465153, compound

HRID 539416Notes

Reaction equation

HRID 539416 reaction equation
[CH3:1][CH2:2][NH:3][C:4]([C@H:6]1[N:10]([C:11]([C@@H:13]([NH:21][C:22]([C@@H:24]([NH:29][C:30]([C@H:32]([NH:37][C:38]([C@@H:40]([NH:49][C:50]([C@@H:52]([NH:55][C:56]([C@@H:58]([NH:69][C:70]([C@@H:72]([NH:79][C:80]([C@H:82]2[NH:87][C:85](=[O:86])[CH2:84][CH2:83]2)=[O:81])[CH2:73][C:74]2[N:78]=[CH:77][NH:76][CH:75]=2)=[O:71])[CH2:59][C:60]2[C:64]3[CH:65]=[CH:66][CH:67]=[CH:68][C:63]=3[NH:62][CH:61]=2)=[O:57])[CH2:53][OH:54])=[O:51])[CH2:41][C:42]2[CH:43]=[CH:44][C:45]([OH:48])=[CH:46][CH:47]=2)=[O:39])[CH2:33][CH:34]([CH3:36])[CH3:35])=[O:31])[CH2:25][CH:26]([CH3:28])[CH3:27])=[O:23])[CH2:14][CH2:15][CH2:16][NH:17][C:18]([NH2:20])=[NH:19])=[O:12])[CH2:9][CH2:8][CH2:7]1)=[O:5].CC(O)=O.C1C=C2C=C(C(O)=O)C(O)=C(CC3C4C(=CC=CC=4)C=C(C(O)=O)C=3O)C2=CC=1.[Na+]>C(Cl)Cl.C(O)C1C=CC=CC=1>[CH3:1][CH2:2][NH:3][C:4]([C@H:6]1[N:10]([C:11]([C@@H:13]([NH:21][C:22]([C@@H:24]([NH:29][C:30]([C@H:32]([NH:37][C:38]([C@@H:40]([NH:49][C:50]([C@@H:52]([NH:55][C:56]([C@@H:58]([NH:69][C:70]([C@@H:72]([NH:79][C:80]([C@H:82]2[NH:87][C:85](=[O:86])[CH2:84][CH2:83]2)=[O:81])[CH2:73][C:74]2[N:78]=[CH:77][NH:76][CH:75]=2)=[O:71])[CH2:59][C:60]2[C:64]3[CH:65]=[CH:66][CH:67]=[CH:68][C:63]=3[NH:62][CH:61]=2)=[O:57])[CH2:53][OH:54])=[O:51])[CH2:41][C:42]2[CH:47]=[CH:46][C:45]([OH:48])=[CH:44][CH:43]=2)=[O:39])[CH2:33][CH:34]([CH3:36])[CH3:35])=[O:31])[CH2:25][CH:26]([CH3:28])[CH3:27])=[O:23])[CH2:14][CH2:15][CH2:16][NH:17][C:18]([NH2:20])=[NH:19])=[O:12])[CH2:9][CH2:8][CH2:7]1)=[O:5]

Participants

5

Reactant 2

HCID 10179807Disodium methylenebis(2-hydroxy-3-naphthoate)HCID 178476396HCID 178476396, compound

Product 1

HCID 178465153HCID 178465153, compoundYield 78.5%

Reagents, catalysts & solvents 2

HCID 244Benzyl AlcoholSolventHCID 6344DichloromethaneSolvent

Procedure

PLGA polymer (MW 24,000,160 mg) was dissolved in CH2Cl2 (1000 μL). Leuprolide acetate (40 mg) was dissolved in BnOH (1000 μL) and added to the polymer solution yielding a homogeneous organic phase. The resulting organic phase was combined with a 1% PVA aqueous phase containing 10 mM disodium pamoate to provide an emulsion. The emulsion was collected directly into a 0.3% PVA solvent extraction solution (100 mL) and stirred for 10 minutes. A secondary extraction solution consisting of 2% isopropanol (200 mL) was added and stirred for an additional four hours. Hardened microparticles were collected by filtration, washed with water, air dried and stored at 4° C. This provided formulation BJ (157 mg, 78.5% yield) with a median particle size 54.0 μm. The core load (9.4%), encapsulation efficiency (47.0%) and in vitro burst (5.31%) were determined by RP-HPLC assay.

Workup

  1. additionadded to the polymer solution
  2. customyielding a homogeneous organic phase
  3. customto provide an emulsion
  4. customThe emulsion was collected directly into a 0.3% PVA solvent extraction solution (100 mL)
  5. additionwas added
  6. stirringstirred for an additional four hours
  7. filtrationHardened microparticles were collected by filtration
  8. washwashed with water, air
  9. customdried
  10. customstored at 4° C

Sources & evidence

ORD record
ord-0bbb04e8f0204ade89a9e3cc7a441dcf
Source dataset
uspto-grants-2014_10
Patent number
US08871269B2

Reaction notes

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