Lithium Hydroxide → HCID 24822033, compound

HRID 1929528Notes

Reaction equation

HRID 1929528 reaction equation
F[C:2](F)(F)[C:3]([O-])=[O:4].[CH2:8]([C:10]1[C:15](=[O:16])[NH:14][N:13]=[C:12]([CH2:17][C:18]2[CH:19]=[CH:20][C:21]([F:33])=[C:22]([CH:32]=2)[C:23]([N:25]2[CH2:31][CH2:30][CH2:29][NH2+:28][CH2:27][CH2:26]2)=[O:24])[CH:11]=1)[CH3:9].CCN(C(C)C)C(C)C.C(Cl)(C)=O.[Li+].[OH-]>C(Cl)Cl.CN(C=O)C>[C:3]([N:28]1[CH2:29][CH2:30][CH2:31][N:25]([C:23]([C:22]2[CH:32]=[C:18]([CH:19]=[CH:20][C:21]=2[F:33])[CH2:17][C:12]2[CH:11]=[C:10]([CH2:8][CH3:9])[C:15](=[O:16])[NH:14][N:13]=2)=[O:24])[CH2:26][CH2:27]1)(=[O:4])[CH3:2]

Participants

6

Reactant 4

HCID 3939Lithium HydroxideHCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 68505928HCID 68505928, compound

Product 1

HCID 24822033HCID 24822033, compound

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To a solution Example 1, A4 (1 eq) in DCM:DMF (2:1, 0.5 M), it was added DIPEA (3 eq), followed by AcCl (1.2 eq). After stirring 30 min at RT, the solvent was removed under reduced pressure and the crude redissolved in EtOAc, washed with 1M HCl, dried (Na2SO4), and concentrated under reduced pressure. The resulting crude was dissolved in THF:H2O (1:1) and LiOH (2 eq) was added, after stirring for 40 min at RT the reaction mixture was extracted with EtOAc. The combined organic fractions were washed with brine, dried (Na2SO4) and concentrated under reduced pressure, to afford the title compound as yellow powder. 1H NMR (400 MHz, DMSO-d6) δ: 12.6 (1H, s), 7.38 (1H, m), 7.28-7.17 (3H, m), 3.92 (2H, m), 3.82-3.66 (3H, m), 3.60-3.48 (3H, m), 3.43-3.30 (2H, m), 2.46 (2H, q, J=7.3 Hz), 2.05 (1.5H, s), 1.89 (1.5H, s), 1.88-1.49 (2H, m), 1.12 (3H, t, J=7.3 Hz). MS (ES) C21H25FN4O3 required: 400. found: 401 (M+H)+.

Workup

  1. customthe solvent was removed under reduced pressure
  2. dissolutionthe crude redissolved in EtOAc
  3. washwashed with 1M HCl
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe resulting crude was dissolved in THF:H2O (1:1)
  7. stirringafter stirring for 40 min at RT the reaction mixture
  8. extractionwas extracted with EtOAc
  9. washThe combined organic fractions were washed with brine
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1066cd32190b486084fbb1c46009f91f
Source dataset
uspto-grants-2012_05
Patent number
US08188084B2

Reaction notes

Loading…