Reacción #475346

Ecuación de reacción

(S)-5-(benzyloxy)-2-(tert-butoxycarbonylamino)-5-oxopentanoic acid

benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate

N,N-diisopropyl-ethyl-amine

NaOH

trans-farnesyl-L-cysteine

→

(S)-4-(tert-butoxycarbonylamino)-5-((R)-1-carboxy-2-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienylthio)ethylamino)-5-oxopentanoic acid

Disolventes

THF

MeOH

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe reaction was quenched by 1 N HCl and pH of the solution
2. 2
   ExtracciónThe mixture was extracted by ethyl acetate (15 mL×3)
3. 3
   SecadoThe organic layer was dried over Na2SO4
4. 4
   Concentraciónconcentrated in vacuo
5. 5
   Otroto afford crude Compound N-66
6. 6
   Otroobtained
7. 7
   workup.WAITThe reaction was left at room temperature for 10 min
8. 8
   OtroThe reaction was quenched by 1 N HCl and pH of the solution
9. 9
   ExtracciónThe mixture was extracted by ethyl acetate (15 mL×3)
10. 10
    SecadoThe organic layer was dried over Na2SO4
11. 11
    Concentraciónconcentrated in vacuo
12. 12
    OtroThe residue was then further purified by preparative HPLC (164 mg, 30%)
13. 13
    Otroto yield Compound N-66

Procedimiento

In a 100 mL round bottom flask, to a solution of (S)-5-(benzyloxy)-2-(tert-butoxycarbonylamino)-5-oxopentanoic acid (674 mg, 2 mmol) and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBop, 1040 mg, 2 mmol) and in THF (5 mL) was added N,N-diisopropyl-ethyl-amine (1.04 mL, 6 mmol) dropwise. After 10 min, S-trans, trans-farnesyl-L-cysteine (650 mg, 2 mmol) was added slowly. The solution was stirred at room temperature for 4 h. The reaction was quenched by 1 N HCl and pH of the solution was adjusted to 3.0. The mixture was extracted by ethyl acetate (15 mL×3). The organic layer was dried over Na2SO4 and concentrated in vacuo. Half of the residue was used directly for next step to afford crude Compound N-66. To this crude Compound N-66 obtained above dissolved in MeOH (1 mL), was added 5 N NaOH (2 mL, 10 mmol). The reaction was left at room temperature for 10 min. The reaction was quenched by 1 N HCl and pH of the solution was adjusted to 2.0. The mixture was extracted by ethyl acetate (15 mL×3). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was then further purified by preparative HPLC (164 mg, 30%) to yield Compound N-66. 1H-NMR (500 MHz, CDCl3): δ 1.45 (s, 9H), 1.62 (s, 6H), 1.68 (s, 3H), 1.70 (s, 3H), 1.95-2.09 (m, 10H), 2.46-2.54 (m, 2H), 2.91 (dd, J=5.0, 15.0 Hz, 1H), 3.04 (dd, J=5.0, 15.0 Hz, 1H), 3.17-3.25 (m, 2H), 4.56 (dd, J=10.0, 15.0 Hz, 1H), 4.77-4.81 (m, 1H), 5.12 (m, 2H), 5.23 (t, J=10.0 Hz, 1H), 5.64 (d, J=10.0 Hz, 1H), 7.66 (d, J=10.0 Hz, 1H), 8.40 (broad, 2H). 13C-NMR (125 MHz, CDCl3): δ 16.06, 16.15, 17.75, 25.77, 26.52, 26.74, 28.01, 28.33, 29.73, 29.89, 32.60, 39.70, 39.74, 52.22, 52.95, 80.91, 119.57, 123.83, 124.35, 131.38, 135.34, 140.04, 156.06, 172.18, 174.00, 177.16; ES-MS: mass calcd for Chemical Formula: C28H46N2O2S 554.74. Found (M+Na) m/z 577.4.

Fuente