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 541515노트

반응식

HRID 541515 반응식
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]

참가 물질

7

반응물 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

생성물 1

HCID 86705094(R)-3-{N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-[3-(2-fluorophenyl)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic Acid Ethoxycarbonyloxymethyl Ester수율 11.7%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-66aeefae8dd74906b15e4035ef1a3e90
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08871792B2

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