Acetyl chloride → Ly-2874455

HRID 41516Notes

Reaction equation

HRID 41516 reaction equation
C(Cl)(=O)C.[Cl:5][C:6]1[CH:7]=[N:8][CH:9]=[C:10]([Cl:46])[C:11]=1[C@H:12]([O:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[N:20](C1CCCCO1)[N:19]=[C:18]2/[CH:30]=[CH:31]/[C:32]1[CH:33]=[N:34][N:35]([CH2:37][CH2:38][O:39]C2CCCCO2)[CH:36]=1)[CH3:13]>CO>[Cl:46][C:10]1[CH:9]=[N:8][CH:7]=[C:6]([Cl:5])[C:11]=1[C@H:12]([O:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[NH:20][N:19]=[C:18]2/[CH:30]=[CH:31]/[C:32]1[CH:33]=[N:34][N:35]([CH2:37][CH2:38][OH:39])[CH:36]=1)[CH3:13]

Participants

4

Reactant 2

HCID 6367Acetyl chlorideHCID 666468355-((R)-1-(3,5-Dichloropyridin-4-yl)ethoxy)-1-(tetrahydro-2H-pyran-2-yl)-3-((E)-2-(1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-pyrazol-4-yl)vinyl)-1H-indazole

Product 1

HCID 46944259Ly-2874455

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

Charge a 3-neck, 250 mL round bottom flask equipped with an addition funnel, nitrogen inlet, internal temperature probe and magnetic stirrer with methanol (57 mL) and cool in an ice bath. To the resulting solution, add acetyl chloride (20 mL, 281.03 mmol) slowly through an addition funnel. To the solution, add 5-((R)-1-(3,5-dichloropyridin-4-yl)ethoxy)-1-(tetrahydro-2H-pyran-2-yl)-3-((E)-2-(1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-pyrazol-4-yl)vinyl)-1H-indazole (7.1 g, 11.59 mmol) dissolved in methanol (40 mL) via addition funnel. After addition is complete, remove the ice bath, warm to RT and stir the mixture for 4 hours. Concentrate the reaction mixture in vacuo to a yellow foam. Dissolve the yellow foam in methanol (10 mL) and add slowly to a saturated aqueous sodium bicarbonate solution (120 mL). Stir the mixture at RT for 30 minutes. Filter the mixture, wash the solid with water (100 mL), and dry under vacuum. Recrystallize the solid from hot EA/methanol/hexanes to give the title compound as a white solid. Yield: 2.1 g (41%). MS (ES) m/z 444 [M+1]+.

Workup

  1. additionCharge a 3-neck, 250 mL round bottom flask
  2. customequipped with an addition funnel, nitrogen inlet
  3. additionAfter addition
  4. customremove the ice bath
  5. concentrationConcentrate the reaction mixture in vacuo to a yellow foam
  6. dissolutionDissolve the yellow foam in methanol (10 mL)
  7. additionadd slowly to a saturated aqueous sodium bicarbonate solution (120 mL)
  8. stirringStir the mixture at RT for 30 minutes
  9. filtrationFilter the mixture
  10. washwash the solid with water (100 mL)
  11. customdry under vacuum
  12. customRecrystallize the solid from hot EA/methanol/hexanes

Sources & evidence

ORD record
ord-1ba7e3bd721b4ebda30006a79a5dbb07
Source dataset
uspto-grants-2013_09
Patent number
US08530665B2

Reaction notes

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