Hydrochloric Acid → HCID 44219107, compound

HRID 41834

Reaction equation

HRID 41834 reaction equation
[OH-:1].[K+].[C:3]([NH:6][C:7]1[C:8]([I:33])=[C:9]([C:24]([N:26]([CH2:28][CH:29]([OH:32])[CH2:30][OH:31])[CH3:27])=[O:25])[C:10]([I:23])=[C:11]([C:21]=1[I:22])[C:12]([N:14]([CH2:16][CH:17]([OH:20])[CH2:18][OH:19])[CH3:15])=[O:13])(=[O:5])[CH3:4].B(O)(O)O.[O:38]1[CH2:40][CH:39]1[CH2:41][O:42][CH2:43][CH2:44][O:45][CH2:46][CH:47]1[CH2:49][O:48]1.Cl>C(#N)C.O.O.CO>[OH:38][CH:39]([CH2:41][O:42][CH2:43][CH2:44][O:45][CH2:46][CH:47]([OH:48])[CH2:49][N:6]([C:7]1[C:21]([I:22])=[C:11]([C:12]([N:14]([CH3:15])[CH2:16][CH:17]([OH:20])[CH2:18][OH:19])=[O:13])[C:10]([I:23])=[C:9]([C:8]=1[I:33])[C:24]([N:26]([CH3:27])[CH2:28][CH:29]([OH:32])[CH2:30][OH:31])=[O:25])[C:3](=[O:1])[CH3:4])[CH2:40][N:6]([C:7]1[C:21]([I:22])=[C:11]([C:12]([N:14]([CH2:16][CH:17]([OH:20])[CH2:18][OH:19])[CH3:15])=[O:13])[C:10]([I:23])=[C:9]([C:8]=1[I:33])[C:24]([N:26]([CH2:28][CH:29]([OH:32])[CH2:30][OH:31])[CH3:27])=[O:25])[C:3](=[O:5])[CH3:4]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 7628Boric AcidHCID 14797Potassium HydroxideHCID 16683Glycol diglycidyl etherHCID 198101Compound 17

Product 1

HCID 44219107HCID 44219107, compoundYield 5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

To a stirred solution of water/methanol (4.9 ml, 2.5 ml) and potassium hydroxide (0.47 g, 8.4 mmol) at 40° C. was added 5-acetylamino-N,N′-bis-(2,3-dihydroxypropyl)-2,4,6-triiodo-N,N′-dimethyl isophthalamide (5.0 g, 6.5 mmol). To the clear solution was then added boric acid (0.28 g, 4.5 mmol). The mixture was cooled to room temperature and pH adjusted to 12.6. 2-{[2-(oxiran-2-ylmethoxy)-ethoxy]methyl}oxirane (0.382 g, 2.22 mmol) was added. The pH of the solution was adjusted to the interval 12.6-13. The reaction was left over weekend. To the solution was added HCl (18%) to pH 4. Salts were removed by treatment with ion exchanger AMB200C and IRA67. The solution was filtered from the resin and evaporated. The product was purified by preparative HPLC (column YMC amino 21.2×250 mm, solvents: A=water and B=acetonitrile; gradient 85-65% B over 25 min; flow 25.0 ml/min, UV detection at 214 nm and 254 nm), and obtained in 180 mg after lyophilisation, 5% yield. Analysis by LC-MS (column Agilent Zorbax SB-Aq 3.5 μm 3.0×100 mm, solvents: A=water/0.1% formic acid and B=acetonitrile/0.1% formic acid; gradient 0-30% B over 20 min; flow 0.3 ml/min, UV detection at 214 and 254 nm, ESI-MS) gave one broad peak centred at 9.6 minutes with m/z 1724.6 (MH+) corresponding to the structure.

Workup

  1. waitThe reaction was left over weekend
  2. customSalts were removed by treatment with ion exchanger AMB200C and IRA67
  3. filtrationThe solution was filtered from the resin
  4. customevaporated
  5. customThe product was purified by preparative HPLC (column YMC amino 21.2×250 mm, solvents
  6. customobtained in 180 mg after lyophilisation, 5% yield
  7. waitgradient 0-30% B over 20 min
  8. customgave one broad peak centred at 9.6 minutes with m/z 1724.6 (MH+) corresponding to the structure

Sources & evidence

ORD record
ord-8e8c25af5c89490ebb7e58afb2f717ea
Source dataset
uspto-grants-2013_09
Patent number
US08535642B2

Linked notes

Loading…