Acetonitrile → (5R,6Z)-6-[(5-methyl-6,7,8,9-tetrahydro[1,2,4]triazolo[1,5-a]quinazolin-2-yl)methylene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

HRID 1744967ノート

反応式

HRID 1744967 の反応式
C(O[CH:5]([C:28]1[N:41]=[C:31]2[N:32]=[C:33]([CH3:40])[C:34]3[CH2:35][CH2:36][CH2:37][CH2:38][C:39]=3[N:30]2[N:29]=1)[C:6]1(Br)[C:12](=[O:13])[N:11]2[C@@H:7]1[S:8][CH:9]=[C:10]2[C:14]([O:16]CC1C=CC([N+]([O-])=O)=CC=1)=[O:15])(=O)C.C(#N)C>C1COCC1.[Pd]>[CH3:40][C:33]1[C:34]2[CH2:35][CH2:36][CH2:37][CH2:38][C:39]=2[N:30]2[N:29]=[C:28](/[CH:5]=[C:6]3\[C@@H:7]4[N:11]([C:12]\3=[O:13])[C:10]([C:14]([OH:16])=[O:15])=[CH:9][S:8]4)[N:41]=[C:31]2[N:32]=1

参加物

5

反応物 2

HCID 6342AcetonitrileHCID 696085554-nitrobenzyl(5R)-6-[(acetyloxy)(5-methyl-6,7,8,9-tetrahydro[1,2,4]triazolo[1,5-a]quinazolin-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate

生成物 1

HCID 10408127(5R,6Z)-6-[(5-methyl-6,7,8,9-tetrahydro[1,2,4]triazolo[1,5-a]quinazolin-2-yl)methylene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
3 °C

実験手順

4-nitrobenzyl (5R)-6-[(acetyloxy)(5-methyl-6,7,8,9-tetrahydro[1,2,4]triazolo[1,5-a]quinazolin-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (600 mg, 0.93 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: 37 mg, 11%; as yellow crystals; mp 250° C. (Dec); (M+H+Na) 392.

後処理

  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

出典と根拠

ORDレコード
ord-43623cfd81e14a9497c819731208bc94
出典データセット
uspto-grants-2006_03
特許番号
US07018997B2

反応ノート

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