HCID 10131699, 화합물 → benzyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamate

HRID 1391710노트

반응식

HRID 1391710 반응식
[F:1][C:2]1[CH:3]=[C:4]([CH2:9][C@H:10]([NH:14][C:15](=[O:24])[O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@H:11]2[CH2:13][O:12]2)[CH:5]=[C:6]([F:8])[CH:7]=1.[CH2:25]([O:28][C@@H:29]1[C:37]2[C:32](=[CH:33][C:34]([O:38][CH3:39])=[CH:35][CH:36]=2)[C@H:31]([NH2:40])[CH2:30]1)[CH:26]=[CH2:27].[Cl-].[Na+].O.C([O-])(O)=O.[Na+]>CC#N>[CH2:25]([O:28][C@H:29]1[C:37]2[C:32](=[CH:33][C:34]([O:38][CH3:39])=[CH:35][CH:36]=2)[C@@H:31]([NH:40][CH2:13][C@@H:11]([OH:12])[C@@H:10]([NH:14][C:15](=[O:24])[O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:9][C:4]2[CH:3]=[C:2]([F:1])[CH:7]=[C:6]([F:8])[CH:5]=2)[CH2:30]1)[CH:26]=[CH2:27]

참가 물질

5

반응물 3

HCID 10131699HCID 10131699, 화합물HCID 69314472cis-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-amineHCID 129703874Sodium hydrogencarbonate brine

생성물 1

HCID 59676145benzyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamate수율 16%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

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온도
30 °C

실험 절차

Step E (1): A mixture of benzyl (S)-2-(3,5-difluorophenyl)-1-((S)-oxiran-2-yl)ethylcarbamate (1.0 g, 3.0 mmol), cis-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-amine (657 mg, 3.0 mmol) and LiClO4 (1.60 g, 15 mmol) in CH3CN (10 mL) with was stirred at 30° C. for 2.5 days. The resulting mixture was poured into brine/NaHCO3 solution and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (1-20% MeOH (containing 0.1% triethylamine)/chloroform linear gradient) to give two pure diastereomers 265 mg (16% yield) of benzyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamate (diastereomer A, first to elute) and 270 mg (16% yield)of benzyl (2S,3R)-4-((1R,3S)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamate (diastereomer B, second to elute). Data for diastereomer A: HRMS (M+H)+=553.2534; 1H NMR (500 MHz, DMSO-d6) δ 7.21-7.35 (m, 4H), 7.14-7.21 (m, 2 H), 7.03 (t, J=9.46 Hz, 1H), 6.87-6.99 (m, 3H), 6.83 (dd, J=8.24, 2.14 Hz, 1H), 5.88-6.00 (m, 1H), 5.30 (dd, J=17.09, 1.83 Hz, 1H), 5.14 (dd, J=10.53, 1.98 Hz, 1H), 4.96-5.02 (m, 1H), 4.83-4.95 (m, 2H), 4.75 (t, J=6.41 Hz, 1H), 4.01-4.13 (m, 2H), 3.91-4.00 (m, 1H), 3.72-3.76 (m, 3H), 3.64-3.72 (m, 1H), 3.44-3.53 (m, 1H), 3.06 (dd, J=13.73, 3.05 Hz, 1H), 2.65-2.75 (m, 1H), 2.54-2.65 (m, 2H), 1.92-2.02 (m, 1H), 1.57-1.67 (m, 1H). Data for diastereomer B: HRMS (M+H)+=553.2509; 1H NMR (500 MHz, DMSO-d6) δ 7.20-7.37 (m, 4H), 7.12-7.22 (m, 2H), 6.98-7.13 (m, 1H), 6.86-7.00 (m, 3H), 6.82 (dd, J=8.24, 2.14 Hz, 1H), 5.80-6.05 (m, 1H), 5.30 (dd, J=17.40, 1.83 Hz, 1H), 5.14 (d, J=10.38 Hz, 1H), 4.80-5.03 (m, 3H), 4.74 (t, J=5.95 Hz, 1H), 3.99-4.15 (m, 2H), 3.95 (t, J=6.10 Hz, 1H), 3.62-3.77 (m, 3H), 3.49 (d, J=4.88 Hz, 1H), 3.03 (dd, J=13.89, 3.20 Hz, 1H), 2.54-2.80 (m, 4H), 2.01-2.18 (m, 1H), 1.59-1.76 (m, 1H).

후처리

  1. extractionextracted with EtOAc
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel chromatography (1-20% MeOH (containing 0.1% triethylamine)/chloroform linear gradient)

출처 및 근거

ORD 기록
ord-56027b74e7cf414cbba1fee859bc26df
출처 데이터셋
uspto-grants-2008_03
특허 번호
US07338974B2

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