(S)-2-Methoxy-1-phenylethanamine → (2R)-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-N-[(1S)-2,2-dimethyl-1-({[(1S)-2-methoxy-1-phenylethyl]amino}carbonyl)propyl]-5-[(3'-methoxy-2-methylbiphen-4-yl)propyl]pentanamide

HRID 1700970노트

반응식

HRID 1700970 반응식
[C:1]([C@@H:4]([NH:9][C:10](=[O:41])[C@@H:11]([C@H:33]1[C:37](=[O:38])[O:36][C:35]([CH3:40])([CH3:39])[O:34]1)[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]1[CH:23]=[C:22]([CH3:24])[C:21]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([O:31][CH3:32])[CH:26]=2)=[CH:20][CH:19]=1)[C:5]([CH3:8])([CH3:7])[CH3:6])(O)=[O:2].[CH3:42][O:43][CH2:44][C@@H:45]([NH2:52])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1>C(OCC)(=O)C>[CH3:39][C:35]1([CH3:40])[O:34][C@@H:33]([C@@H:11]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]2[CH:23]=[C:22]([CH3:24])[C:21]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([O:31][CH3:32])[CH:26]=3)=[CH:20][CH:19]=2)[C:10]([NH:9][C@H:4]([C:1]([NH:52][C@@H:45]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH2:44][O:43][CH3:42])=[O:2])[C:5]([CH3:6])([CH3:7])[CH3:8])=[O:41])[C:37](=[O:38])[O:36]1

참가 물질

4

반응물 2

HCID 11768756(S)-2-Methoxy-1-phenylethanamineHCID 131723127(2R)-N-[(1S)-1-(carboxy)-2,2-dimethylpropyl]-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-5-[(3'-methoxy-2-methylbiphen-4-yl)propyl]pentanamide

생성물 1

HCID 131723128(2R)-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-N-[(1S)-2,2-dimethyl-1-({[(1S)-2-methoxy-1-phenylethyl]amino}carbonyl)propyl]-5-[(3'-methoxy-2-methylbiphen-4-yl)propyl]pentanamide수율 69%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

According to the method of Example 25(a), (2R)-N-[(1S)1-(carboxy)-2,2-dimethylpropyl]-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-5-[(3′-methoxy-2-methylbiphen-4-yl)propyl]pentanamide (Preparation 34)(220 mg, 0.42 mmol) was reacted with (1S)-2-methoxy-1-phenylethylamine (63 mg, 0.42 mmol) at room temperature for 2.5 h. The mixture was poured into ethyl acetate (75 mL) and washed with 0.5M aqueous sodium dihydrogenphosphate (2×50 mL) and 5% aqueous sodium bicarbonate (50 mL)(solid sodium chloride was added to give phase separation). The organic solution was dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by flash chromatography (gradient elution with hexane:ethyl acetate=30:70 to 60:40) to give a white solid which was purified again by flash chromatography (sorbsil C60, (20-40μ) silica gel, eluting with hexane:ethyl acetate 35:65) to give (2R)-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-N-[(1S)-2,2-dimethyl-1-({[(1S)-2-methoxy-1-phenylethyl]amino}carbonyl)propyl]-5-[(3′-methoxy-2-methylbiphen-4-yl)propyl]pentanamide as a white solid (191 mg, 69%).

후처리

  1. washwashed with 0.5M aqueous sodium dihydrogenphosphate (2×50 mL) and 5% aqueous sodium bicarbonate (50 mL)(solid sodium chloride was added to give phase separation)
  2. dry with materialThe organic solution was dried (Na2SO4)
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by flash chromatography (gradient elution with hexane:ethyl acetate=30:70 to 60:40)
  5. customto give a white solid which
  6. customwas purified again by flash chromatography (sorbsil C60, (20-40μ) silica gel, eluting with hexane:ethyl acetate 35:65)

출처 및 근거

ORD 기록
ord-875aaf0b7e184b7f9f49c52fe8138c6f
출처 데이터셋
uspto-grants-2002_02
특허 번호
US06350907B1

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