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

HRID 2408307

反応式

HRID 2408307 の反応式
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]

参加物

10

反応物 6

HCID 11686Dimethylmalonic acidHCID 12734DiisopropylcarbodiimideHCID 81531Diisopropylethylamine2 回HCID 945242-Chlorotrityl chlorideHCID 181649HOAtHCID 153458253-(1-trityl-1H-imidazol-4-yl)propan-1-amine

生成物 1

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

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒2 回HCID 6344Dichloromethane溶媒2 回HCID 22350042dichloromethane N,N-dimethylformamide溶媒

実験手順

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 filtered 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.

後処理

  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. filtrationThe resin was filtered
  9. stirringThe resin was shaken for 2 days
  10. filtrationThe resin was filtered
  11. washwashed with NMP (5×20 mL) and DCM (10×20 mL)
  12. addition2,2,2-Trifluoroethanol/dichlormethan 1:1 (20 mL) was added to the resin and it
  13. waitwas shaked for 2 hrs
  14. washThe resin was washed with 2,2,2-Trifluoroethanol/dichlormethan 1:1 (10 mL)
  15. customthe combined filtrates were collected
  16. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-3306912c49294a66b56590c7f04378e8
出典データセット
uspto-grants-2014_08
特許番号
US08815802B2

関連ノート

読み込み中…