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

HRID 541513노트

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HRID 541513 반응식
[C:1](=[O:9])([O:5][CH:6]([CH3:8])[CH3:7])[O:2][CH2:3]Cl.[Na+].[I-].[Cl:12][C:13]1[CH:14]=[CH:15][C:16]([F:48])=[C:17]([C:19]2[CH:24]=[CH:23][C:22]([CH2:25][N:26]([CH2:42][C@@H:43]([OH:47])[C:44]([OH:46])=[O:45])[NH:27][C:28]([C:30]3[O:34][N:33]=[C:32]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=4[F:41])[CH:31]=3)=[O:29])=[CH:21][CH:20]=2)[CH:18]=1.CCN(CC)CC>CC(C)=O>[CH:6]([O:5][C:1]([O:2][CH2:3][O:46][C:44](=[O:45])[C@H:43]([OH:47])[CH2:42][N:26]([CH2:25][C:22]1[CH:23]=[CH:24][C:19]([C:17]2[CH:18]=[C:13]([Cl:12])[CH:14]=[CH:15][C:16]=2[F:48])=[CH:20][CH:21]=1)[NH:27][C:28]([C:30]1[O:34][N:33]=[C:32]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[F:41])[CH:31]=1)=[O:29])=[O:9])([CH3:8])[CH3:7]

참가 물질

6

반응물 4

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 14787051Chloromethyl isopropyl carbonateHCID 67973214(R)-3-{N-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-[3-(2-fluorophenyl)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic acid

생성물 1

HCID 86705092(R)-3-{N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-[3-(2-fluorophenyl)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic Acid Isopropoxycarbonyloxymethyl Ester수율 7.4%

시약·촉매·용매 1

HCID 180Acetone용매2회

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온도
60 °C

실험 절차

Chloromethyl isopropyl carbonate (17.3 mg, 114 μmol) and NaI 17.0 mg, 114 μmol) were combined in acetone (1.0 mL, 14 mmol) and heated at 60° C. for 1 hour. The mixture was then cooled to room temperature. A mixture of (R)-3-{N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-[3-(2-fluorophenyl)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic acid (20.0 mg, 38 μmol) dissolved in acetone (1.0 mL) and treated with Et3N (10.6 μL, 76 μmol) was added and the resulting mixture was stirred at room temperature for 5 hours. The mixture was concentrated and the residue was dissolved in AcOH (2.0 mL), filtered and purified by reverse phase preparative HPLC. The product was freeze dried and purified by reverse phase preparative HPLC to yield the title compound (1.8 mg, purity 100%). MS m/z [M+H]+ calc'd for C31H28ClF2N3O8, 644.15. found 644.1.

후처리

  1. temperatureThe mixture was then cooled to room temperature
  2. additionwas added
  3. concentrationThe mixture was concentrated
  4. dissolutionthe residue was dissolved in AcOH (2.0 mL)
  5. filtrationfiltered
  6. custompurified by reverse phase preparative HPLC
  7. customdried
  8. custompurified by reverse phase preparative HPLC

출처 및 근거

ORD 기록
ord-476d623d819e434891baf300001b46c2
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08871792B2

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