HCID 10131699、化合物 → 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 1391710ノート

反応式

HRID 1391710 の反応式
[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]

参加物

5

反応物 3

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

生成物 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-ylcarbamate収率 16%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
30 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-56027b74e7cf414cbba1fee859bc26df
出典データセット
uspto-grants-2008_03
特許番号
US07338974B2

反応ノート

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