Dimethylformamide → Ac-VAD-pNA

HRID 54165

Reaction equation

HRID 54165 reaction equation
[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]

Participants

7

Reactant 4

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

Product 1

HCID 10367219Ac-VAD-pNA

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-b5a95e385cf348d1a359ec9fd1973e2f
Source dataset
uspto-grants-1997_04
Patent number
US05622830

Linked notes

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