Acetonitrile → HCID 10253214, compound

HRID 1744963Notes

Reaction equation

HRID 1744963 reaction equation
C(O[CH:5]([C:24]1(Br)[C:30](=[O:31])[N:29]2[C@@H:25]1[S:26][CH:27]=[C:28]2[C:32]([O:34]CC1C=CC([N+]([O-])=O)=CC=1)=[O:33])[C:6]1[N:23]=[C:9]2[N:10]=[CH:11][C:12]3[CH2:17][N:16]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:15][CH2:14][C:13]=3[N:8]2[N:7]=1)(=O)C.C(#N)C>C1COCC1.[Pd]>[CH2:21]([O:20][C:18]([N:16]1[CH2:15][CH2:14][C:13]2[N:8]3[N:7]=[C:6](/[CH:5]=[C:24]4\[C@@H:25]5[N:29]([C:30]\4=[O:31])[C:28]([C:32]([OH:34])=[O:33])=[CH:27][S:26]5)[N:23]=[C:9]3[N:10]=[CH:11][C:12]=2[CH2:17]1)=[O:19])[CH3:22]

Participants

5

Reactant 2

HCID 6342AcetonitrileHCID 21019556HCID 21019556, compound

Product 1

HCID 10253214HCID 10253214, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
3 °C

Procedure

ethyl 2-[(acetyloxy)((5R)-6-bromo-2-{[(4-nitrobenzyl)oxy]carbonyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-en-6-yl)methyl]-8,9-dihydropyrido[3,4-e][1,2,4]triazolo[1,5-a]pyrimidine-7(6H)-carboxylate (220 mg, 0.28 mmol) was dissolved in THF (20 mL) and acetonitrile (20 mL) and phophate buffer (6.5 pH) (20 ml) and hydrogenated over Pd/C (10%) (200 mg) under 40 psi pressure. At the end, reaction mixture was filtered, cooled to 3° C., and 0.1 N NaOH was added to adjust the pH to 8.5. The filtrate was washed with ethyl acetate and the aqueous layer was separated. The aqueous layer was concentrated under high vacuum at 35° C. to give a yellow precipitate. The product was purified by HP21 resin reverse phase column chromatography. Initially the column was eluted with deionized water (2 L) and latter with 10% acetonitrile:water. The fractions containing the product were collected and concentrated under reduced pressure at room temperature. The yellow solid was washed with acetone, filtered and dried. Yield: 15 mg, 2%; Yellow crystals; mp>250° C. (Dec); (M+H+Na) 449. 1H NMR (DMSO-d6) δ 8.61 (s, 1H), 7.01 (s, 1H), 6.90(s, 1H), 6.44(s, 1H), 4.74(m, 2H, CH2), 4.13 (q, 2H, J=5.4 Hz), 3.84(s, m, 2H, CH2), 1.22(t, 3H, CH3, J=5.7 Hz).

Workup

  1. customAt the end, reaction mixture
  2. filtrationwas filtered
  3. addition0.1 N NaOH was added
  4. washThe filtrate was washed with ethyl acetate
  5. customthe aqueous layer was separated
  6. concentrationThe aqueous layer was concentrated under high vacuum at 35° C.
  7. customto give a yellow precipitate
  8. customThe product was purified by HP21 resin reverse phase column chromatography
  9. washInitially the column was eluted with deionized water (2 L) and latter with 10% acetonitrile
  10. additionThe fractions containing the product
  11. customwere collected
  12. concentrationconcentrated under reduced pressure at room temperature
  13. washThe yellow solid was washed with acetone
  14. filtrationfiltered
  15. customdried

Sources & evidence

ORD record
ord-496e29885b124dc58799f2e1eef858b7
Source dataset
uspto-grants-2006_03
Patent number
US07018997B2

Reaction notes

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