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

HRID 541511ノート

反応式

HRID 541511 の反応式
CC.[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([F:39])=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:17]([CH2:33][C@@H:34]([OH:38])[C:35]([OH:37])=[O:36])[NH:18][C:19]([C:21]3[O:25][N:24]=[C:23]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[F:32])[CH:22]=3)=[O:20])=[CH:12][CH:11]=2)[CH:9]=1.CCN([CH2:45][CH3:46])CC.C[C:48](C)=[O:49]>>[CH3:48][O:49][CH2:45][CH2:46][O:36][C:35](=[O:37])[C@H:34]([OH:38])[CH2:33][N:17]([CH2:16][C:13]1[CH:14]=[CH:15][C:10]([C:8]2[CH:9]=[C:4]([Cl:3])[CH:5]=[CH:6][C:7]=2[F:39])=[CH:11][CH:12]=1)[NH:18][C:19]([C:21]1[O:25][N:24]=[C:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[F:32])[CH:22]=1)=[O:20]

参加物

5

反応物 4

HCID 180AcetoneHCID 6324EthaneHCID 8471TriethylamineHCID 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 86705091(R)-3-{N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-[3-(2-fluorophenyl)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic Acid 2-methoxyethyl Ester収率 48.1%

反応条件

温度
50 °C

実験手順

Ethane, 1-bromo-2-methoxy (5.7 mL, 0.1 mmol) 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 (20.0 mg, 38 μmol) and Et3N (13.2 μL, 0.1 mmol) in acetone (1.0 mL, 14 mmol), and resulting mixture was stirred at 50° C. overnight. The mixture was concentrated, and the residue was dissolved in AcOH (1.5 mL), filtered, and purified by reverse phase preparative HPLC to yield the title compound (10.7 mg, purity 95.7%) as a TFA salt. MS m/z [M+H]+ calc'd for C29H26ClF2N3O6, 586.15. found 585.8.

後処理

  1. customresulting mixture
  2. concentrationThe mixture was concentrated
  3. dissolutionthe residue was dissolved in AcOH (1.5 mL)
  4. filtrationfiltered
  5. custompurified by reverse phase preparative HPLC

出典と根拠

ORDレコード
ord-4673afd8f71a4d6e9168e8a516660024
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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