Dimethylformamide → Ac-VAD-pNA

HRID 54165

반응식

HRID 54165 반응식
[NH:1]([C:31]([O:33]C(C)(C)C)=O)[C@H:2]([C:6]([NH:8][C@H:9]([C:11]([NH:13][C@H:14]([C:19]([NH:21][C:22]1[CH:30]=[CH:29][C:25]([N+:26]([O-:28])=[O:27])=[CH:24][CH:23]=1)=[O:20])[CH2:15][C:16](=[O:18])[OH:17])=[O:12])[CH3:10])=[O:7])[CH:3]([CH3:5])[CH3:4].[CH3:38]C(ON1C(=O)CCC1=O)=O.C([O-])(O)=O.[Na+].CN(C=O)C>C(O)(C(F)(F)F)=O.Cl>[NH:1]([C:31]([CH3:38])=[O:33])[C@H:2]([C:6]([NH:8][C@H:9]([C:11]([NH:13][C@H:14]([C:19]([NH:21][C:22]1[CH:30]=[CH:29][C:25]([N+:26]([O-:28])=[O:27])=[CH:24][CH:23]=1)=[O:20])[CH2:15][C:16](=[O:18])[OH:17])=[O:12])[CH3:10])=[O:7])[CH:3]([CH3:4])[CH3:5]

참가 물질

7

반응물 4

HCID 6228DimethylformamideHCID 84460Acetic acid N-hydroxysuccinimide esterHCID 516892Sodium BicarbonateHCID 10459430t-BOCValAlaAsp-p-nitroanilide

생성물 1

HCID 10367219Ac-VAD-pNA

시약·촉매·용매 2

HCID 313Hydrochloric Acid용매HCID 6422Trifluoroacetic acid용매

실험 절차

t-BOCValAlaAsp-p-nitroanilide (174 mg, 0.33 mmole) was dissolved in neat TFA (5 mL) and stirred at room temperature for 1 hour. The TFA was removed in vacuo and the residue was then dissolved in 5 mL of CH2Cl2 which was then evaporated in vacuo. This dissolution with CH2Cl2 and subsequent evaporation repeated two more times. The residue was dissolved in dioxane/water (5 mL, 4:1) and treated with acetic acid N-hydroxysuccinimide ester (63 mg, 0.40 mmole) and NaHCO3 (139 mg, 1.65 mmole). After 18 hours, the mixture was diluted with 1N HCl (25 mL) and extracted three times with ethyl acetate. The combined extracts were dried with MgSO4, filtered and concentrated to a yellow solid which was recrystallized from ethyl acetate/ethanol to give 33 mg (21%) of light yellow powder: mp 196°-200° C. (dec.); 1H NMR (DMSO-d6) δ 0.80 (d, J=6.6 Hz, 3H), 0.82 (d, J=5.1 Hz, 3H), 1.20 (d, J=7.2 Hz, 3H), 1.85 (s, 3H), 1.85-2.0 (m, 1H), 2.60 (dd, J=7.5, 16.6 Hz, 1H), 2.75 (dd, J=6.2, 16.6 Hz, 1H), 4.1-4.2 (m, 1H), 4.2-4.3 (m, 1H), 4.6-4.7 (m, 1H), 7.8-7.9 (m, 3H), 8.11 (d, J=6.8 Hz, 1H), 8.21 (d, J=9.3 Hz, 2H), 8.27 (d, J=7.2 Hz, 1H), 10.51 (s, 1H), 12.45 (br s, 1H); MS (LSIMS) m/e 488 (6, M+ +Na), 466 (23, M+ +1), 449 (7) 328 (15), 213 (44), 142 (100); [α]D20 -24.9° (c=1.0, DMF); Analysis calculated for C20H27N5O8 : C, 51.60; H, 5.85; N, 15.05; found: C, 50.16; H, 5.79; N, 14.06.

후처리

  1. customThe TFA was removed in vacuo
  2. dissolutionthe residue was then dissolved in 5 mL of CH2Cl2 which
  3. customwas then evaporated in vacuo
  4. dissolutionThis dissolution
  5. customwith CH2Cl2 and subsequent evaporation
  6. dissolutionThe residue was dissolved in dioxane/water (5 mL, 4:1)
  7. waitAfter 18 hours
  8. extractionextracted three times with ethyl acetate
  9. dry with materialThe combined extracts were dried with MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated to a yellow solid which
  12. customwas recrystallized from ethyl acetate/ethanol
  13. customto give 33 mg (21%) of light yellow powder

출처 및 근거

ORD 기록
ord-b5a95e385cf348d1a359ec9fd1973e2f
출처 데이터셋
uspto-grants-1997_04
특허 번호
US05622830

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