Hydrochloric Acid → 5.5'-(2,3-dihydroxybutane-1,4-diyl)bis(formylazanediyl)bis(N1,N3-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide)

HRID 1408283

Reaction equation

HRID 1408283 reaction equation
[OH-:1].[K+].[OH:3][CH:4]([CH2:29][OH:30])[CH2:5][NH:6][C:7](=[O:28])[C:8]1[C:21]([I:22])=[C:20]([NH:23][CH:24]=[O:25])[C:19]([I:26])=[C:10]([C:11]([NH:13][CH2:14][CH:15]([OH:18])[CH2:16][OH:17])=[O:12])[C:9]=1[I:27].B(O)(O)O.[CH2:35]1[O:37][CH:36]1[CH:38]1[O:40][CH2:39]1.Cl>CO.O>[OH:40][CH:38]([CH:36]([OH:37])[CH2:35][N:23]([C:20]1[C:21]([I:22])=[C:8]([C:7]([NH:6][CH2:5][CH:4]([OH:3])[CH2:29][OH:30])=[O:28])[C:9]([I:27])=[C:10]([C:19]=1[I:26])[C:11]([NH:13][CH2:14][CH:15]([OH:18])[CH2:16][OH:17])=[O:12])[CH:24]=[O:1])[CH2:39][N:23]([C:20]1[C:19]([I:26])=[C:10]([C:11]([NH:13][CH2:14][CH:15]([OH:18])[CH2:16][OH:17])=[O:12])[C:9]([I:27])=[C:8]([C:21]=1[I:22])[C:7]([NH:6][CH2:5][CH:4]([OH:3])[CH2:29][OH:30])=[O:28])[CH:24]=[O:25]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 7628Boric Acid2×HCID 11254DiepoxybutaneHCID 14797Potassium Hydroxide2×HCID 86649138N1,N3-bis(2,3-dihydroxypropyl)-5-formylamino-2,4,6-triiodoisophthalamide

Product 1

HCID 252221725.5'-(2,3-dihydroxybutane-1,4-diyl)bis(formylazanediyl)bis(N1,N3-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide)Yield 43%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a stirred solution of water (10 ml), methanol (5 ml) and potassium hydroxide (1.0 g, 16.4 mmol) was added N1,N3-bis(2,3-dihydroxypropyl)-5-formylamino-2,4,6-triiodoisophthalamide (Example 1a) (10.0 g, 13.6 mmol). To the clear solution was then added boric acid (0.59 g, 9.5 mmol). The pH was continuously maintained at pH 12.6 by addition of potassium hydroxide (10 M) and 1,3-butadiene diepoxide (0.40 g, 4.7 mmol) was added. The pH of the solution was continuously maintained within the interval from 12.6 to 13 by addition of solid boric acid for 5 hours and then left over the weekend. The solution was neutralized by addition of hydrochloric acid (18% w) and then treated with ion exchangers (AMB200C, 20 ml) and (IRA67, 20 ml). The resins were removed by filtration and rinsed with water and the combined aqueous volume was reduced in vacuo. The crude product was purified by preparative HPLC (column Phenomenex Luna C18 10 μm 250×50.0 mm, solvents: A=water and B=acetonitrile; gradient 0-10% B over 60 min; flow 50.0 ml/ min, UV detection at 214 nm and 254 nm). After freeze drying 3.1 g 5.5′-(2,3-dihydroxybutane-1,4-diyl)bis(formylazanediyl)bis(N1,N3-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide) (43% yield) was obtained.

Workup

  1. additionwas added
  2. waitleft over the weekend
  3. additiontreated with ion exchangers (AMB200C, 20 ml) and (IRA67, 20 ml)
  4. customThe resins were removed by filtration
  5. washrinsed with water
  6. customThe crude product was purified by preparative HPLC (column Phenomenex Luna

Sources & evidence

ORD record
ord-4caf1daa53b54a60bd48eaef394ce998
Source dataset
uspto-grants-2014_12
Patent number
US08920780B2

Linked notes

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