Acetone → (R)-3-{N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-[3-(2-fluorophenyl)-isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic Acid Acetoxymethyl Ester

HRID 541510ノート

反応式

HRID 541510 の反応式
[C:1]([O:4][CH2:5]Br)(=[O:3])[CH3:2].[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([F:43])=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][N:21]([CH2:37][C@@H:38]([OH:42])[C:39]([OH:41])=[O:40])[NH:22][C:23]([C:25]3[O:29][N:28]=[C:27]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=4[F:36])[CH:26]=3)=[O:24])=[CH:16][CH:15]=2)[CH:13]=1.CCN(CC)CC.CC(C)=O>>[C:1]([O:4][CH2:5][O:41][C:39](=[O:40])[C@H:38]([OH:42])[CH2:37][N:21]([CH2:20][C:17]1[CH:18]=[CH:19][C:14]([C:12]2[CH:13]=[C:8]([Cl:7])[CH:9]=[CH:10][C:11]=2[F:43])=[CH:15][CH:16]=1)[NH:22][C:23]([C:25]1[O:29][N:28]=[C:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[F:36])[CH:26]=1)=[O:24])(=[O:3])[CH3:2]

参加物

5

反応物 4

HCID 180AcetoneHCID 8471TriethylamineHCID 68536Bromomethyl acetateHCID 67973214(R)-3-{N-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-[3-(2-fluorophenyl)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic acid

生成物 1

HCID 86705090(R)-3-{N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-[3-(2-fluorophenyl)-isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic Acid Acetoxymethyl Ester収率 18.6%

実験手順

Bromomethyl acetate (11.9 mL, 121 μmol) was added to a mixture of (R)-3-{N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-[3-(2-fluorophenyl)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic acid (40.0 mg, 76 μmol) and Et3N (21.1 mL, 152 μmol) in acetone (1.0 mL, 14 mmol). The resulting mixture was stirred at room temperature for 1 hour. The mixture was then concentrated and the residue was dissolved in AcOH (2 mL), filtered, and purified by reverse phase prep HPLC. The desired fractions were frozen and lyophilized to yield the title compound (8.5 mg, purity 98.5%) as a TFA salt. MS m/z [M+H]+ calc'd for C29H24ClF2N3O7, 600.13. found 600.1.

後処理

  1. concentrationThe mixture was then concentrated
  2. dissolutionthe residue was dissolved in AcOH (2 mL)
  3. filtrationfiltered
  4. custompurified by reverse phase prep HPLC
  5. temperatureThe desired fractions were frozen

出典と根拠

ORDレコード
ord-0e15cc7e23f24cb597fdfab65e01a7a2
出典データセット
uspto-grants-2014_10
特許番号
US08871792B2

反応ノート

読み込み中…