반응 #327483

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DIPEA

HOAt

DIC

3-(1-Trityl-1H-imidazol-4-yl)-propyl amine

DIPEA

Dimethylmalonic acid

2-Chlorotrityl chloride resin

→

title compound

2,2-Dimethyl-N-[3-(1-trityl-1H-imidazol-4-yl)-propyl]-malonamic acid

용매

DCM

DMF

DMF

DCM DMF

DCM

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후처리

1. 1
   여과filtered
2. 2
   workup.ADDITIONadded to the resin
3. 3
   여과The resin was filtered
4. 4
   세척washed with DCM:MeOH:DIPEA (17:2:1), DCM, NMP og DCM (2×25 mL of each)
5. 5
   workup.WAITThe resin was swelled in DMF for 20 mins
6. 6
   여과filtered
7. 7
   workup.STIRRINGthe resin was shaken for 90 min at RT
8. 8
   workup.STIRRINGThe resin was shaken for 2 days
9. 9
   여과The resin was filtered
10. 10
    세척washed with NMP (5×20 mL) and DCM (10×20 mL)
11. 11
    workup.ADDITION2,2,2-Trifluoroethanol/dichlormethan 1:1 (20 mL) was added to the resin and it
12. 12
    workup.WAITwas shaked for 2 hrs
13. 13
    세척The resin was washed with 2,2,2-Trifluoroethanol/dichlormethan 1:1 (10 mL)
14. 14
    기타the combined filtrates were collected
15. 15
    농축concentrated in vacuo

실험 절차

2-Chlorotrityl chloride resin (2.3 g, 3.0 mmol) was swelled in DCM for 20 mins and filtered. Dimethylmalonic acid (2 eq; 6.0 mmol; 793 mg) was dissolved i DCM:DMF 1:1 (10 mL) and added to the resin followed by DIPEA (6 eq; 18.0 mmol; 3.14 mL) and DCM (10 mL). The resin was shaken overnight at RT. The resin was filtered and washed with DCM:MeOH:DIPEA (17:2:1), DCM, NMP og DCM (2×25 mL of each). The resin was swelled in DMF for 20 mins and filtered. HOAt (3 eq; 9.0 mmol; 1.23 g), DIC (3 eq; 9.0 mmol; 1.40 mL) and DMF (25 mL) was added and the resin was shaken for 90 min at RT. The resin was filtrered and 3-(1-Trityl-1H-imidazol-4-yl)-propyl amine (1.8 eq; 5.40 mmol; 1.84 g), DIPEA (4 eq; 6.0 mmol; 2.09 mL), and DMF (10 mL) was added. The resin was shaken for 2 days. The resin was filtered and washed with NMP (5×20 mL) and DCM (10×20 mL). 2,2,2-Trifluoroethanol/dichlormethan 1:1 (20 mL) was added to the resin and it was shaked for 2 hrs. The resin was washed with 2,2,2-Trifluoroethanol/dichlormethan 1:1 (10 mL) and the combined filtrates were collected and concentrated in vacuo to yield the title compound.

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