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

HRID 240301

반응식

HRID 240301 반응식
C1C=CC(C(Cl)(C2C(Cl)=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH3:22][C:23]([CH3:30])([C:27](O)=[O:28])[C:24]([OH:26])=[O:25].CCN(C(C)C)C(C)C.C1C=NC2N(O)N=NC=2C=1.CC(C)N=C=NC(C)C.[C:59]([N:78]1[CH:82]=[C:81]([CH2:83][CH2:84][CH2:85][NH2:86])[N:80]=[CH:79]1)([C:72]1[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=1)([C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1)[C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1>C(Cl)Cl.CN(C=O)C.C(Cl)Cl.CN(C=O)C>[CH3:22][C:23]([CH3:30])([C:27]([NH:86][CH2:85][CH2:84][CH2:83][C:81]1[N:80]=[CH:79][N:78]([C:59]([C:72]2[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=2)([C:66]2[CH:67]=[CH:68][CH:69]=[CH:70][CH:71]=2)[C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)[CH:82]=1)=[O:28])[C:24]([OH:26])=[O:25]

참가 물질

10

반응물 6

HCID 11686Dimethylmalonic acidHCID 12734DiisopropylcarbodiimideHCID 81531Diisopropylethylamine2회HCID 945242-Chlorotrityl chlorideHCID 181649HOAtHCID 153458253-(1-trityl-1H-imidazol-4-yl)propan-1-amine

생성물 1

HCID 583390552,2-Dimethyl-N-[3-(1-trityl-1H-imidazol-4-yl)-propyl]-malonamic acid

시약·촉매·용매 3

HCID 6228Dimethylformamide용매2회HCID 6344Dichloromethane용매2회HCID 22350042dichloromethane N,N-dimethylformamide용매

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.

후처리

  1. filtrationfiltered
  2. additionadded to the resin
  3. filtrationThe resin was filtered
  4. washwashed with DCM:MeOH:DIPEA (17:2:1), DCM, NMP og DCM (2×25 mL of each)
  5. waitThe resin was swelled in DMF for 20 mins
  6. filtrationfiltered
  7. stirringthe resin was shaken for 90 min at RT
  8. stirringThe resin was shaken for 2 days
  9. filtrationThe resin was filtered
  10. washwashed with NMP (5×20 mL) and DCM (10×20 mL)
  11. addition2,2,2-Trifluoroethanol/dichlormethan 1:1 (20 mL) was added to the resin and it
  12. waitwas shaked for 2 hrs
  13. washThe resin was washed with 2,2,2-Trifluoroethanol/dichlormethan 1:1 (10 mL)
  14. customthe combined filtrates were collected
  15. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-51fb02d2b3e44d059f9206863699f7d7
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08648041B2

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