1-Acetylpiperazine → HCID 9848246, compound

HRID 2120351Notes

Reaction equation

HRID 2120351 reaction equation
[Cl:1][C:2]1[C:7](F)=[C:6]([S:9]([CH2:12][CH3:13])(=[O:11])=[O:10])[CH:5]=[CH:4][C:3]=1[NH:14][C:15](=[O:23])[C@:16]([OH:22])([CH3:21])[C:17]([F:20])([F:19])[F:18].[C:24]([N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1)(=[O:26])[CH3:25]>CN1C(=O)CCC1>[Cl:1][C:2]1[C:7]([N:30]2[CH2:31][CH2:32][N:27]([C:24](=[O:26])[CH3:25])[CH2:28][CH2:29]2)=[C:6]([S:9]([CH2:12][CH3:13])(=[O:11])=[O:10])[CH:5]=[CH:4][C:3]=1[NH:14][C:15](=[O:23])[C@:16]([OH:22])([CH3:21])[C:17]([F:20])([F:19])[F:18]

Participants

4

Reactant 2

HCID 837951-AcetylpiperazineHCID 57348891(2R)-N-[2-Chloro-4-(ethanesulfonyl)-3-fluorophenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide

Product 1

HCID 9848246HCID 9848246, compoundYield 34.8%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
147 °C

Procedure

(R)-N-[2-Chloro-3-fluoro-4-(ethylsulphonyl)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide (Example 15; 2.0 g) was added to a solution of 1-acetylpiperazine (2.0 g, 3 eq) in anhydrous NMP (3 ml) under argon and the mixture was stirred and heated to 147° C. for 24 hours. The reaction mixture was cooled and partitioned between a saturated aqueous solution of ammonium chloride (80 ml) and ether (4×200 ml). The combined ether extracts were washed with brine (200 ml), dried and concentrated to give a gum. The residue was purified by chromatography on a Mega Bond Elut column (50 g) eluting with 0-4% MeOH/DCM to give the title compound (0.895 g) as a white foam. NMR: 1.14 (t, 3H), 1.61 (s, 3H), 2.05 (s, 3H), 2.75-2.82 (m, 1H), 2.94 (brm, 2H), 3.25-3.44 (m, 3H), 3.49-3.56 (q, 2H), 3.85 (d, 1H), 4.39 (d, 1H), 7.94 (d, 1H), 8.07 (brs, 1H), 8.26 (d, 1H), 9.94 (brs, 1H); m/z: 484.

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between a saturated aqueous solution of ammonium chloride (80 ml) and ether (4×200 ml)
  3. washThe combined ether extracts were washed with brine (200 ml)
  4. customdried
  5. concentrationconcentrated
  6. customto give a gum
  7. customThe residue was purified by chromatography on a Mega Bond Elut column (50 g)
  8. washeluting with 0-4% MeOH/DCM

Sources & evidence

ORD record
ord-0607d35746b04e40b362c596bf0b4f3c
Source dataset
uspto-grants-2004_02
Patent number
US06689909B1

Reaction notes

Loading…