Iodine → HCID 178478694, compound

To a 250 ml round-bottomed flask equipped with a stir bar and addition funnel was added 4.0 g (21.7 mmol) of histamine dihydrochloride and 6.0 ml of distilled water and the pH adjusted to 8.0 with concentrated NaOH. The addition funnel was charged with a solution of 2.76 g (10.86 mmol, 0.5 equivalent) of I2 in 100 ml of ethanol (abs.) and the solution added slowly dropwise with stirring at room temperature over 6 hours. The pH was periodically monitored and maintained at an apparent pH=8.0 with concentrated NaOH. The dark suspension was then stirred overnight, readjusted to pH=8.0 and allowed to stir an additional 3 hours. The suspension was filtered and evaporated to a red oil. Purification of this material was accomplished by electrophoresis using a 1M HOAc buffer titrated to pH 5 with pyridine. Approximately 400 mg of crude material, dissolved in methanol, was applied in a 1 cm band to an 8"×16" paper which was run for 1 hour at 20 V/cm and 150-180 mA. A thin strip was then removed from the paper and visualized with ninhydrin spray. The iodohistamine band was then cut out of the remaining sheet and eluted with several portions of methanol. The methanol extracts were acidified (con.HCl) and evaporated in vacuo. The remaining residue was re-evaporated with one volume of absolute ethanol followed by recrystallization from absolute ethanol. In this manner 620 mg (19%) of the analytically pure title compound was isolated, m.p. 210° C. with decomposition. The mother liquor was pooled, evaporated, and the residue recrystallized to yield an additional 205 mg of somewhat inferior material.

1. customTo a 250 ml round-bottomed flask equipped with a stir bar and addition funnel
2. additionthe solution added slowly dropwise
3. stirringThe dark suspension was then stirred overnight
4. stirringto stir an additional 3 hours
5. filtrationThe suspension was filtered
6. customevaporated to a red oil
7. customPurification of this material
8. dissolutionApproximately 400 mg of crude material, dissolved in methanol
9. waitwas run for 1 hour at 20 V/cm and 150-180 mA
10. customA thin strip was then removed from the paper
11. washeluted with several portions of methanol
12. customHCl) and evaporated in vacuo
13. customThe remaining residue was re-evaporated with one volume of absolute ethanol
14. customfollowed by recrystallization from absolute ethanol

ORD record

ord-304ebe36d1bd40398f47b8cea17ef53e

Source dataset

uspto-grants-1991_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05047549