Iodine → 5-(N-(3-(N-(3,5-bis(2,3-dihydroxypropylcarbamoyl)-2,4,6-triiodophenyl)acetamido)-2-hydroxypropyl)formamido)-N1,N3-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide

HRID 1408287Notes

Reaction equation

HRID 1408287 reaction equation
[CH2:1]([N:4]([C:8]1[C:9]([I:32])=[C:10]([C:24]([NH:26][CH2:27][CH:28]([OH:31])[CH2:29][OH:30])=[O:25])[C:11]([I:23])=[C:12]([C:21]=1[I:22])[C:13]([NH:15][CH2:16][CH:17]([OH:20])[CH2:18][OH:19])=[O:14])[C:5](=[O:7])[CH3:6])[CH:2]=[CH2:3].[I-].[K+].II.[OH:37][CH:38]([CH2:63][OH:64])[CH2:39][NH:40][C:41](=[O:62])[C:42]1[C:55]([I:56])=[C:54]([NH:57][CH:58]=[O:59])[C:53]([I:60])=[C:44]([C:45]([NH:47][CH2:48][CH:49]([OH:52])[CH2:50][OH:51])=[O:46])[C:43]=1[I:61].[OH-:65].[K+]>O.CO>[OH:20][CH:17]([CH2:18][OH:19])[CH2:16][NH:15][C:13]([C:12]1[C:21]([I:22])=[C:8]([N:4]([CH2:1][CH:2]([OH:65])[CH2:3][N:57]([C:54]2[C:53]([I:60])=[C:44]([C:45]([NH:47][CH2:48][CH:49]([OH:52])[CH2:50][OH:51])=[O:46])[C:43]([I:61])=[C:42]([C:55]=2[I:56])[C:41]([NH:40][CH2:39][CH:38]([OH:37])[CH2:63][OH:64])=[O:62])[CH:58]=[O:59])[C:5](=[O:7])[CH3:6])[C:9]([I:32])=[C:10]([C:24](=[O:25])[NH:26][CH2:27][CH:28]([OH:31])[CH2:29][OH:30])[C:11]=1[I:23])=[O:14]

Participants

8

Reactant 5

HCID 807IodineHCID 4875Potassium IodideHCID 14797Potassium HydroxideHCID 596228935-(N-allylacetamido)-N1,N3-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamideHCID 86649138N1,N3-bis(2,3-dihydroxypropyl)-5-formylamino-2,4,6-triiodoisophthalamide

Product 1

HCID 468316225-(N-(3-(N-(3,5-bis(2,3-dihydroxypropylcarbamoyl)-2,4,6-triiodophenyl)acetamido)-2-hydroxypropyl)formamido)-N1,N3-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent3×

Conditions

Temperature
10 °C

Procedure

To a stirred solution of water (10 ml) and methanol (7 ml) is added 5-(N-allylacetamido)-N1,N3-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (5.0 g 6.35 mmol). pH is adjusted to pH 2 and a solution of potassium iodide (1.05 g, 6.35 mmol) and iodine 1.61 g, 6.35 mmol) in water (5 ml) and methanol (5 ml) is added drop wise at 50° C. The mixture is stirred over night. The solution is cooled to 10° C. and N,N′-Bis-(2,3-dihydroxy-propyl)-5-formylamino-2,4,6-triiodo-isophthalamide (Example 1a)(4.65 g 6.35 mmol) is added. Potassium hydroxide (10 M) is added drop wise to maintain a stable pH of 11.6 and the mixture is stirred for 24 hours. The solution is diluted with water (50 ml) and treated with ion exchangers (AMB200C, 20 ml) and (IRA67, 20 ml). The resins are filtered off and rinsed with water. The combined aqueous phases are reduced in vacuo and the crude product is 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.

Workup

  1. temperatureto maintain a stable pH of 11.6
  2. stirringthe mixture is stirred for 24 hours
  3. additiontreated with ion exchangers (AMB200C, 20 ml) and (IRA67, 20 ml)
  4. filtrationThe resins are filtered off
  5. washrinsed with water
  6. customthe crude product is purified by preparative HPLC (column Phenomenex Luna

Sources & evidence

ORD record
ord-d4231570eb3b400fbdcef0ad3d6fdb5e
Source dataset
uspto-grants-2014_12
Patent number
US08920780B2

Reaction notes

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