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

HRID 541510노트

반응식

HRID 541510 반응식
[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]

참가 물질

5

반응물 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

생성물 1

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

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-0e15cc7e23f24cb597fdfab65e01a7a2
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08871792B2

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