Sodium Iodide → Butyric acid (R)-3-[N-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-(3-methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionyloxymethyl Ester

HRID 541521ノート

反応式

HRID 541521 の反応式
[C:1]([O:6][CH2:7]Cl)(=[O:5])[CH2:2][CH2:3][CH3:4].[Na+].[I-].[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([F:42])=[C:16]([C:18]2[CH:23]=[CH:22][C:21]([CH2:24][N:25]([CH2:36][C@@H:37]([OH:41])[C:38]([OH:40])=[O:39])[NH:26][C:27]([C:29]3[O:33][N:32]=[C:31]([O:34][CH3:35])[CH:30]=3)=[O:28])=[CH:20][CH:19]=2)[CH:17]=1.CCN(C(C)C)C(C)C>CC(C)=O.C(O)(=O)C>[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([F:42])=[C:16]([C:18]2[CH:19]=[CH:20][C:21]([CH2:24][N:25]([CH2:36][C@@H:37]([OH:41])[C:38]([O:40][CH2:7][O:6][C:1](=[O:5])[CH2:2][CH2:3][CH3:4])=[O:39])[NH:26][C:27]([C:29]3[O:33][N:32]=[C:31]([O:34][CH3:35])[CH:30]=3)=[O:28])=[CH:22][CH:23]=2)[CH:17]=1

参加物

7

反応物 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 2725008Chloromethyl butanoateHCID 67972936(R)-3-[N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-(3-methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic Acid

生成物 1

HCID 86705099Butyric acid (R)-3-[N-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-(3-methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionyloxymethyl Ester収率 26.7%

試薬・触媒・溶媒 2

HCID 176Acetic Acid溶媒HCID 180Acetone溶媒2 回

反応条件

温度
65 °C

実験手順

A mixture of chloromethyl butyrate (16.2 μL, 129 μmol) and NaI (19.4 mg, 129 μmol) in acetone (0.7 mL, 10 mmol) was heated at 65° C. for 1 hour. The mixture was then cooled to room temperature and a mixture of (R)-3-[N-(5′-Chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3-methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid (20.0 mg) and DIPEA (15.0 mL, 0.1 mmol) in acetone (0.3 mL) was added. The resulting mixture was stirred at room temperature for 1 hour then concentrated. The residue was dissolved in AcOH (2.0 mL), filtered, and purified by reverse phase preparative HPLC. The desired fractions were combined and freeze dried to yield a white solid. The solid was dissolved in acetic acid (1.5 mL), filtered and purified by reverse phase preparative HPLC to yield the title compound (6.5 mg, purity 100%). MS m/z [M+H]+ calc'd for C26H27ClFN3O8, 564.15. found. 564.

後処理

  1. temperatureThe mixture was then cooled to room temperature
  2. additionwas added
  3. concentrationthen concentrated
  4. dissolutionThe residue was dissolved in AcOH (2.0 mL)
  5. filtrationfiltered
  6. custompurified by reverse phase preparative HPLC
  7. customfreeze dried
  8. customto yield a white solid
  9. filtrationfiltered
  10. custompurified by reverse phase preparative HPLC

出典と根拠

ORDレコード
ord-3fca85e3727b40fd9c479850b42643c4
出典データセット
uspto-grants-2014_10
特許番号
US08871792B2

反応ノート

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