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 → HCID 59676141, 화합물

HRID 1391711노트

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HRID 1391711 반응식
[CH2:1]([O:4][C@H:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[C@@H:7]([NH:16][CH2:17][C@@H:18]([OH:40])[C@@H:19]([NH:29]C(=O)OCC2C=CC=CC=2)[CH2:20][C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[C:23]([F:28])[CH:22]=2)[CH2:6]1)[CH:2]=[CH2:3]>COCCOC.O>[CH2:1]([O:4][C@H:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[C@@H:7]([NH:16][CH2:17][C@@H:18]([OH:40])[C@@H:19]([NH2:29])[CH2:20][C:21]2[CH:22]=[C:23]([F:28])[CH:24]=[C:25]([F:27])[CH:26]=2)[CH2:6]1)[CH:2]=[CH2:3]

참가 물질

3

반응물 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

생성물 1

HCID 59676141HCID 59676141, 화합물수율 38%

시약·촉매·용매 1

HCID 18180031Water 1,2-dimethoxyethane용매

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온도
110 °C

실험 절차

Step E (2): Ba(OH)2.H2O (267 mg, 1.41 mmol) was added to a vial charged with 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, 260 mg, 0.471 mmol) from stepE(1), DME/H2O (3 mL/2 mL). The sealed vial was heated at 110° C. for 18 h. Filtered the reaction mixture through a Pasture pipette/Kimwipe plug to remove solids. Rinsed the vessel and solids with fresh DME. The filtrate was evaporated in vacuo. Residual solvents were removed under high vacuum. The crude residue was purified by silica gel chromatography (1-20% MeOH (containing 0.1% triethylamine)/chloroform linear gradient) to give 74 mg (38% yield) the of the title compound as a clear viscous oil. LC-MS (M+H)+=419.24; 1H NMR (500 MHz, CDCl3) δ 7.32 (d, J=8.24 Hz, 1H), 6.92 (d, J=2.14 Hz, 1H), 6.85 (dd, J=8.24, 2.44 Hz, 1H), 6.71-6.80 (m, 2H), 6.60-6.71 (m, 1H), 5.84-6.03 (m, 1H), 5.30 (dd, J=17.24, 1.68 Hz, 1H), 5.18 (dd, J=10.38, 1.53 Hz, 1H), 4.77 (dd, J=6.10, 3.97 Hz, 1H), 4.08-4.12 (m, 2H), 4.05 (dd, J=6.87, 4.43 Hz, 1H), 3.79 (s, 3H), 3.47-3.52 (m, 1H), 3.04-3.10 (m, 1H), 2.90-3.00 (m, 2H), 2.75 (dd, J=11.90, 8.55 Hz, 1H), 2.61-2.68 (m, 1H), 2.49 (dd, J=13.43, 9.77 Hz, 1H), 1.94-2.00 (m, 1H).

후처리

  1. filtrationFiltered the reaction mixture through a Pasture pipette/Kimwipe plug
  2. customto remove solids
  3. washRinsed the vessel and solids with fresh DME
  4. customThe filtrate was evaporated in vacuo
  5. customResidual solvents were removed under high vacuum
  6. customThe crude residue was purified by silica gel chromatography (1-20% MeOH (containing 0.1% triethylamine)/chloroform linear gradient)

출처 및 근거

ORD 기록
ord-693111dae74a40908959414ba0dac6fc
출처 데이터셋
uspto-grants-2008_03
특허 번호
US07338974B2

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