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, compound

HRID 1391711Notes

Reaction equation

HRID 1391711 reaction equation
[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]

Participants

3

Reactant 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

Product 1

HCID 59676141HCID 59676141, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
110 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-693111dae74a40908959414ba0dac6fc
Source dataset
uspto-grants-2008_03
Patent number
US07338974B2

Reaction notes

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