Hydrochloric Acid → HCID 67051623、化合物

HRID 1717598ノート

反応式

HRID 1717598 の反応式
[F:1][C:2]1[C:3]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([I:32])=[CH:28][C:27]=2[F:33])=[C:4]([C:9]([N:11]2[CH2:14][C:13]([CH2:16][NH:17]/[C:18](/SC)=[CH:19]/[N+:20]([O-:22])=[O:21])([OH:15])[CH2:12]2)=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[NH4+:35].[ClH:36].O1CCOCC1>C(O)C.CO>[ClH:36].[NH2:35]/[C:18](/[NH:17][CH2:16][C:13]1([OH:15])[CH2:14][N:11]([C:9]([C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([F:1])[C:3]=2[NH:25][C:26]2[CH:31]=[CH:30][C:29]([I:32])=[CH:28][C:27]=2[F:33])=[O:10])[CH2:12]1)=[CH:19]\[N+:20]([O-:22])=[O:21]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 14923Ammonium HydroxideHCID 312751,4-DioxaneHCID 67051949HCID 67051949、化合物

生成物 1

HCID 67051623HCID 67051623、化合物収率 87%

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 887Methanol溶媒

反応条件

温度
70 °C

実験手順

To a solution of (0.05 g 0.08 mmol) 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[(Z)-1-(methylthio)-2-nitroethenyl]amino}methyl)azetidin-3-ol in ethanol (2 mL) was added ammonium hydroxide (0.1 mL, 0.8 mmol) and the reaction mixture was stirred at 70° C. for 16 hours. The reaction mixture was concentrated in vacuo. The crude product was purified by reverse phase preparative HPLC. The fractions were collected and the solvent was concentrated. The residue was partitioned with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, brine and dried over anhydrous sodium sulfate. Filtration and concentration resulted in an amorphous residue, which was dissolved in methanol, and 4 N HCl in dioxane (40 μL, 0.16 mmol) was added to the solution. A white precipitate formed and was collected by vacuum filtration. The solid was washed with hexane, and dried to afford 42 mg (87%) 3-({[(E)-1-amino-2-nitroethenyl]amino}methyl)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol hydrochloride. 1H NMR (400 MHz, d4-MeOH): 7.58 (t, 0.5H), 7.44 (t, 0.5H), 7.36 (m, 1H), 7.31 (m, 1H), 7.04 (m, 1H), 6.63 (m, 1H), 3.90-4.30 (m, 4H) 3.72 (s, 2H); MS (EI) for C19H17F3IN5O4: 564 (MH+).

後処理

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customThe crude product was purified by reverse phase preparative HPLC
  3. customThe fractions were collected
  4. concentrationthe solvent was concentrated
  5. customThe residue was partitioned with ethyl acetate
  6. washThe organic layer was washed with saturated aqueous sodium bicarbonate, brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationFiltration and concentration
  9. customresulted in an amorphous residue, which
  10. customA white precipitate formed
  11. filtrationwas collected by vacuum filtration
  12. washThe solid was washed with hexane
  13. customdried

出典と根拠

ORDレコード
ord-db0f2b1c452b48f48f48605c236abe61
出典データセット
uspto-grants-2010_09
特許番号
US07803839B2

反応ノート

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