Sodium hydride → HCID 53830736, compound

HRID 1432933Notes

Reaction equation

HRID 1432933 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][NH:14][C:13](=[O:17])[C@@H:12]1[CH3:18])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[I-].[H-].[Na+].Br[CH2:23][C:24]1[CH:33]=[C:32]2[C:27]([C:28]([Cl:34])=[CH:29][CH:30]=[N:31]2)=[CH:26][CH:25]=1>C1COCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([CH2:23][C:24]2[CH:33]=[C:32]3[C:27]([C:28]([Cl:34])=[CH:29][CH:30]=[N:31]3)=[CH:26][CH:25]=2)[C:13](=[O:17])[C@@H:12]1[CH3:18])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 30165Iodide IonHCID 217084447-Bromomethyl-4-chloroquinolineHCID 542270461-Piperazinecarboxylic acid, 2-methyl-3-oxo-, phenylmethyl ester, (2S)-

Product 1

HCID 53830736HCID 53830736, compoundYield 77.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

4-(Benzyloxycarbonyl)-3-(S)-methylpiperazin-2-one (1.0 g, 4.0 mmol), EXAMPLE 46, is dissolved in THF (60 mL), cooled in an ice bath and treated with tretrabutylammonium iodide (0.10 g, 0.27 mmol) and 60% sodium hydride (0.18 g, 4.4 mmol). The reaction mixture is stirred at 0° C. for 30 minutes then treated dropwise with a solution of 7-bromomethyl-4-chloroquinoline (1.12 g, 4.4 mmol), EXAMPLE 14, in THF (5 mL). The resulting solution warmed to room temperature over approximately 1 h then quenched with sodium bicarbonate solution and concentrated. The residue is partitioned between ethyl acetate and water; the organic layer is dried (sodium sulfate) and concentrated. The residue is chromatographed (5% methanol/methylene chloride) to yield solid 4-(Benzyloxycarbonyl)-1-(4-chloroquinolin-7-ylmethyl)-3-(S)-methyl-piperazin-2-one (1.32 g, 3.1 mmol). A portion of this material (0.10 g, 0.23 mmol) is dissolved in acetonitrile (6 mL) and treated with iodotrimethyl-silane (0.1 mL, 0.75 mmol) at room temperature for 2 hours. The reaction is quenched with methanol and concentrated to dryness. Methanol addition and concentration is repeated six times. The final residue is taken up is 2M aqueous HCl; the solution is washed with ether and concentrated to yield the title compound. MS m/z: M+=289; 1H NMR (CD3OD, 300 MHz) δ9.2 (d, 1H), 8.6 (d, 1H), 8.2-8.3 (m, 2H), 8.0 (d, 1H), 5.1 (q, 1H), 4.3-4.4 (m, 1H), 3.8-4.0 (m, 2H), 3.6-3.8 (m, 3H), 1.75 (d, 3H).

Workup

  1. temperaturecooled in an ice bath
  2. temperatureThe resulting solution warmed to room temperature over approximately 1 h
  3. customthen quenched with sodium bicarbonate solution
  4. concentrationconcentrated
  5. customThe residue is partitioned between ethyl acetate and water
  6. dry with materialthe organic layer is dried (sodium sulfate)
  7. concentrationconcentrated
  8. customThe residue is chromatographed (5% methanol/methylene chloride)

Sources & evidence

ORD record
ord-fdb07ba2bcdd47d89688c2cdbc9d31d7
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

Loading…