Ethyl alpha-oxobenzenebutanoate → N-[1-(R,S)-carboxy-3-phenylpropyl]-L-lysyl-(S)-2-pyrrolidineacetic acid

HRID 979838노트

반응식

HRID 979838 반응식
C([O:3][C:4](=[O:27])[CH2:5][C@@H:6]1[CH2:10][CH2:9][CH2:8][N:7]1[C:11](=[O:26])[C@H:12]([CH2:21][CH2:22][CH2:23][CH2:24][NH2:25])[NH:13]C(OC(C)(C)C)=O)C.C([O:30][C:31](=[O:42])[C:32](=O)[CH2:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)C>>[C:31]([CH:32]([NH:13][C@H:12]([C:11]([N:7]1[CH2:8][CH2:9][CH2:10][C@H:6]1[CH2:5][C:4]([OH:27])=[O:3])=[O:26])[CH2:21][CH2:22][CH2:23][CH2:24][NH2:25])[CH2:33][CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)([OH:30])=[O:42]

참가 물질

3

반응물 2

HCID 562087Ethyl alpha-oxobenzenebutanoateHCID 53706975N--BOC-L-lysyl-(S)-2-pyrrolidineacetic acid ethyl ester

생성물 1

HCID 131715010N-[1-(R,S)-carboxy-3-phenylpropyl]-L-lysyl-(S)-2-pyrrolidineacetic acid

실험 절차

The product of Step A above is condensed with 2-oxo-4-phenylbutyric acid ethyl ester by the procedure of Example 1, Step E. The diastereomers are separated by silica gel chromatography. The individual diastereomers are converted into the corresponding diacids by saponification as in Example 2 and the -BOC group is removed in hydrogen chloride in ethyl acetate by the procedure of Example 1, Step D. The resulting hydrochloride salt is converted to the free base by absorbing on a strong acid ion exchange resin (Dowex 50W; H+ cycle) and eluting with 3% pyridine in water. Freeze drying affords the desired product, and the S,S,S and R,S,S, diastereomers are separated using reverse phase HPLC.

후처리

  1. customThe diastereomers are separated by silica gel chromatography
  2. customthe -BOC group is removed in hydrogen chloride in ethyl acetate by the procedure of Example 1, Step D
  3. customby absorbing on a strong acid ion exchange resin (Dowex 50W; H+ cycle)
  4. washeluting with 3% pyridine in water
  5. customFreeze drying

출처 및 근거

ORD 기록
ord-59581d7069e54c00a22610ee723059fd
출처 데이터셋
uspto-grants-1987_01
특허 번호
US04634716

반응 노트

불러오는 중…