Hydrazine hydrate (1:1) → (2S)-N-((1R)-2-amino-1-[4-((S)-2-methylbutoxy)phenyl]-ethyl)-2-phenylpropionamide

HRID 1874641노트

반응식

HRID 1874641 반응식
O=C1C2C(=CC=CC=2)C(=O)[N:3]1[CH2:12][C@H:13]([NH:26][C:27](=[O:36])[C@H:28]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH3:29])[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][C@@H:22]([CH3:25])[CH2:23][CH3:24])=[CH:16][CH:15]=1.O.NN>C(O)C>[NH2:3][CH2:12][C@H:13]([NH:26][C:27](=[O:36])[C@H:28]([C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[CH3:29])[C:14]1[CH:15]=[CH:16][C:17]([O:20][CH2:21][C@@H:22]([CH3:25])[CH2:23][CH3:24])=[CH:18][CH:19]=1

참가 물질

4

반응물 2

HCID 24654Hydrazine hydrate (1:1)HCID 67085677(S)-N-((R)-2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-1-(4-((S)-2-methyl-butoxy)-phenyl)-ethyl)-2-phenyl-propionamide

생성물 1

HCID 51354470(2S)-N-((1R)-2-amino-1-[4-((S)-2-methylbutoxy)phenyl]-ethyl)-2-phenylpropionamide수율 52%

시약·촉매·용매 1

HCID 702Ethanol용매

반응 조건

온도
60 °C

실험 절차

A mixture of (S)-N-((R)-2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-1-(4-((S)-2-methyl-butoxy)-phenyl)-ethyl)-2-phenyl-propionamide (320 mg, 0.66 mmol) and ethanol (20 mL) was treated dropwise with hydrazine monohydrate (0.32 mL, 6.6 mmol), and the resulting reaction was maintained at 60° C. overnight. The mixture was allowed to cool to room temperature and the solids were removed by filtration. The filtrate was concentrated to dryness, and triturated with ethyl acetate (15 mL), and the mixture was filtered. The collected solids were air dried, then dissolved in diethyl ether (5 mL). The resulting solution was treated with concentrated HCl (0.05 mL), and the precipitate was collected by filtration to afford (2S)-N-((1R)-2-amino-1-[4-((S)-2-methylbutoxy)phenyl]-ethyl)-2-phenylpropionamide (120 mg, 52% yield) as a white solid: 1H NMR (400 MHz, MeOD) δ 7.21-7.31 (m, 5H), 7.09 (d, J=8.6 Hz, 2H), 6.84 (d, J=8.8 Hz, 2H), 5.12 (dd, J=8.8, 5.8 Hz, 1H), 3.81 (dd, J=9.3, 6.1 Hz, 1H), 3.70-3.77 (m, 2H), 3.23-3.30 (m, 2H), 1.81 (s, 1H), 1.57 (ddd, J=13.4, 7.6, 5.8 Hz, 1H), 1.47 (d, J=6.8 Hz, 3H), 1.24-1.33 (m, 1H), 1.02 (d, J=6.8 Hz, 3H), 0.96 (t, J=7.5 Hz, 3H); LRMS (ESI) m/e 355.1 [(M+H)+, calcd for C22H31N2O2 355.5].

후처리

  1. customthe resulting reaction
  2. temperatureto cool to room temperature
  3. customthe solids were removed by filtration
  4. concentrationThe filtrate was concentrated to dryness
  5. customtriturated with ethyl acetate (15 mL)
  6. filtrationthe mixture was filtered
  7. customdried
  8. dissolutiondissolved in diethyl ether (5 mL)
  9. additionThe resulting solution was treated with concentrated HCl (0.05 mL)
  10. filtrationthe precipitate was collected by filtration

출처 및 근거

ORD 기록
ord-ba6afdd89f7f4205aa0426b4ce704a6e
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08304577B2

반응 노트

불러오는 중…