Triethylamine → 5-Bromo-3-(4-((S)-1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-1-methylpyrazin-2(1H)-one

HRID 1363498Notes

Reaction equation

HRID 1363498 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH3:8])[CH:4]([C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][CH:10]=2)[C:3]1=[O:16].Br[C:18]1[C:19](=[O:26])[N:20]([CH3:25])[CH:21]=[C:22]([Br:24])[N:23]=1.C(N(CC)CC)C>CC(O)C>[Br:24][C:22]1[N:23]=[C:18]([NH:15][C:12]2[CH:13]=[CH:14][C:9]([C@H:4]3[C:3](=[O:16])[N:2]([CH3:1])[CH2:7][CH2:6][N:5]3[CH3:8])=[CH:10][CH:11]=2)[C:19](=[O:26])[N:20]([CH3:25])[CH:21]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 130629693,5-Dibromo-1-methyl-1H-pyrazin-2-oneHCID 576251203-(4-Aminophenyl)-1,4-dimethylpiperazin-2-one

Product 1

HCID 576250965-Bromo-3-(4-((S)-1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-1-methylpyrazin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

To a single-necked 250 mL round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged (−)-1,4-dimethyl-3-(4-aminophenyl)piperazin-2-one (8.2 g, 37.3 mmol), 3,5-dibromo-1-methylpyrazin-2(1H)-one (10.0 g, 37.3 mmol), and i-PrOH (100 mL). Triethylamine (5.72 mL, 41 mmol, 1.1 eq) was then added and the resulting suspension was heated at 80° C. for 16 hrs. A thick slurry was observed the following day. The reaction was cooled to room temperature then concentrated in vacuo to ˜20 mL total volume. At that point 20 mL of 2M Na2CO3 solution was added followed by 100 mL of water. The mixture was then allowed to slurry for 2 hrs at room temperature. The off-white solid was then collected on a fritted funnel and allowed to air dry for ˜1 hr. The solids were returned to the reaction flask and 100 mL of diethyl ether/hexanes (1:1) was added and the suspension was triturated at room temperature for 1 hr. The white solid was then collected on a fritted funnel, dried on the filter with vacuum for 1 hr, then transferred to a round-bottomed flask and vacuum-dried overnight. White solids were obtained, 12.88 g (85%).

Workup

  1. customTo a single-necked 250 mL round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser
  3. temperatureThe reaction was cooled to room temperature
  4. concentrationthen concentrated in vacuo to ˜20 mL total volume
  5. additionAt that point 20 mL of 2M Na2CO3 solution was added
  6. customThe off-white solid was then collected on a fritted funnel
  7. customto air dry for ˜1 hr
  8. additionwas added
  9. customthe suspension was triturated at room temperature for 1 hr
  10. customThe white solid was then collected on a fritted funnel
  11. customdried on the
  12. filtrationfilter with vacuum for 1 hr
  13. customtransferred to a round-bottomed flask
  14. customvacuum-dried overnight
  15. customWhite solids were obtained

Sources & evidence

ORD record
ord-803fca32d59f436da447cd951b4eb7ba
Source dataset
uspto-grants-2011_02
Patent number
US07884108B2

Reaction notes

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