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

HRID 541515Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 541515
N1C(C)=CC=CC=1C.[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([F:45])=[C:14]([C:16]2[CH:21]=[CH:20][C:19]([CH2:22][N:23]([CH2:39][C@@H:40]([OH:44])[C:41]([OH:43])=[O:42])[NH:24][C:25]([C:27]3[O:31][N:30]=[C:29]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=4[F:38])[CH:28]=3)=[O:26])=[CH:18][CH:17]=2)[CH:15]=1.[CH2:46]([O:48][C:49](=[O:53])[O:50][CH2:51]Cl)[CH3:47].[Na+].[I-]>CN(C=O)C.O>[CH2:46]([O:48][C:49]([O:50][CH2:51][O:42][C:41](=[O:43])[C@H:40]([OH:44])[CH2:39][N:23]([CH2:22][C:19]1[CH:20]=[CH:21][C:16]([C:14]2[CH:15]=[C:10]([Cl:9])[CH:11]=[CH:12][C:13]=2[F:45])=[CH:17][CH:18]=1)[NH:24][C:25]([C:27]1[O:31][N:30]=[C:29]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[F:38])[CH:28]=1)=[O:26])=[O:53])[CH3:47]

Komponenten

7

Edukt 4

HCID 5238Sodium IodideHCID 79372,6-LutidineHCID 5325479Chloromethyl Ethyl CarbonateHCID 67973214(R)-3-{N-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-[3-(2-fluorophenyl)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic acid

Produkt 1

HCID 86705094(R)-3-{N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-[3-(2-fluorophenyl)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic Acid Ethoxycarbonyloxymethyl EsterAusbeute 11,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

2,6-Lutidine (407 mg, 3.8 mmol) was added to a solution of (R)-3-{N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-[3-(2-fluorophenyl)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic acid (200 mg, 380 mmol), carbonic acid chloromethyl ester ethyl ester (105 mg, 760 μmol) and NaI (114 mg, 760 μmol) in DMF (10 mL). The mixture was stirred overnight at room temperature. Water (30 mL) was added and the mixture was extracted with EtOAc (3×40 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by preparative HPLC (MeCN—H2O (0.1% TFA); Gradient 60-70) to yield the title compound as a white solid (56 mg). LC-MS: 630.1 [M+H]+. 1H-NMR: (CD3OD-d4, 400 MHz) δ 1.24 (t, J=5.9 Hz, 3H), 3.30-3.33 (m, 2H), 4.17-4.32 (m, 4H), 4.45 (t, J=4.2 Hz, 1H), 5.78 (br, 2H), 7.20-7.28 (m, 1H), 7.57-7.29 (m, 10H), 7.92-7.95 (m, 1H).

Aufarbeitung

  1. extractionthe mixture was extracted with EtOAc (3×40 mL)
  2. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by preparative HPLC (MeCN—H2O (0.1% TFA); Gradient 60-70)

Quellen und Nachweise

ORD-Eintrag
ord-66aeefae8dd74906b15e4035ef1a3e90
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08871792B2

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