تفاعل #70113

معادلة التفاعل

triethylamine

5-Amino-2,4,6-triiodo-isophthalic acid dichloride

1-amino-2,3-dihydroxypropane

serinol

→

5-amino-N1-(1,3-dihydroxypropan-2-yl)-N3-(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide

المردود 57.0%

المذيبات

DMA

DMA

water

DMA

ظروف التفاعل

المعالجة

1. 1
   أخرىAt 2° C. a mantled reactor with mechanical stirrer, dropping
2. 2
   أخرىthe inner temperature below −19° C
3. 3
   workup.STIRRINGThe mixture was stirred at a temperature gradient from −24° C. to 0° C. in 24 h
4. 4
   workup.STIRRINGthe mixture was stirred at a temperature gradient from 0° C. to 40° C. in 20 h
5. 5
   workup.STIRRINGThe mixture was stirred at 22° C. for 1 day
6. 6
   أخرىprecipitated triethylamine hydrochloride
7. 7
   ترشيحwas filtered off
8. 8
   أخرىEvaporation at 60° C./25 mbar
9. 9
   workup.WAITleft a viscous liquid residue (586 g) which
10. 10
    workup.ADDITIONwas diluted with water (350 ml)
11. 11
    أخرىSalts and excess amines were removed by treatment with ion exchangers Amberlite200C (143 ml), IRA67 (148 ml)
12. 12
    ترشيحIRA900 (56 ml) followed by filtration
13. 13
    غسيلThe ion exchangers were washed with water (2×400 ml)
14. 14
    workup.ADDITIONSome seeding crystals were added to the combined aqueous phase
15. 15
    workup.STIRRINGthe solution was stirred slowly at 22° C. for 9 days
16. 16
    أخرىThe precipitate was isolated by filtration
17. 17
    workup.STIRRINGstirred for 1 day
18. 18
    ترشيحThe suspension was filtered
19. 19
    أخرىthe filter cake was dried in air (216 g, 57% yield, 88.6% HPLC purity)
20. 20
    أخرىThe crude product was purified by preparative HPLC (column
21. 21
    workup.WAIThold 10 min
22. 22
    أخرىfreeze dried

الإجراء التجريبي

At 2° C. a mantled reactor with mechanical stirrer, dropping funnel and inner thermometer was charged with DMA (640 ml), triethylamine (224 ml, 161.3 g, 1.59 mol) and 5-Amino-2,4,6-triiodo-isophthalic acid dichloride (320 g, 537 mmol). The mixture was stirred and cooled to −24° C. A solution of 1-amino-2,3-dihydroxypropane (49.92 g, 548 mmol) in DMA (160 ml) was added slowly to keep the inner temperature below −19° C. The mixture was stirred at a temperature gradient from −24° C. to 0° C. in 24 h. A solution of serinol (60 g, 658 mmol) in DMA (160 ml) was added slowly and the mixture was stirred at a temperature gradient from 0° C. to 40° C. in 20 h. The mixture was stirred at 22° C. for 1 day and precipitated triethylamine hydrochloride was filtered off. Evaporation at 60° C./25 mbar left a viscous liquid residue (586 g) which was diluted with water (350 ml). Salts and excess amines were removed by treatment with ion exchangers Amberlite200C (143 ml), IRA67 (148 ml) and IRA900 (56 ml) followed by filtration. The ion exchangers were washed with water (2×400 ml). Some seeding crystals were added to the combined aqueous phase and the solution was stirred slowly at 22° C. for 9 days. The precipitate was isolated by filtration. The filter cake was re-suspended in water (240 ml) and stirred for 1 day. The suspension was filtered and the filter cake was dried in air (216 g, 57% yield, 88.6% HPLC purity). The crude product was purified by preparative HPLC (column: selfpacked Luna C18, 10 μm 250×100 mm, solvents: A=water and B=acetonitrile; gradient 5-10% B over 10 min, hold 10 min; flow 350 ml/min, UV detection at 244 nm and 254 nm). Relevant fractions were combined and freeze dried to yield 5-amino-N1-(1,3-dihydroxypropan-2-yl)-N3-(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide.

المصدر