D-Camphorsulfonic Acid → 5-Bromo-3-(4-(1-ethyl-3-oxopiperazin-2-yl)phenylamino]-1-methylpyrazin-2(1H)-one

HRID 1363510Notes

Reaction equation

HRID 1363510 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[N:13]([CH2:14][CH3:15])[CH2:12][CH2:11][NH:10][C:9]2=[O:16])=[CH:4][CH:3]=1.Br[C:18]1[C:19](=[O:26])[N:20]([CH3:25])[CH:21]=[C:22]([Br:24])[N:23]=1.CC1(C)[C@]2(CS(O)(=O)=O)C(C[C@H]1CC2)=O>C(O)(C)C>[Br:24][C:22]1[N:23]=[C:18]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([CH:8]3[C:9](=[O:16])[NH:10][CH2:11][CH2:12][N:13]3[CH2:14][CH3:15])=[CH:6][CH:7]=2)[C:19](=[O:26])[N:20]([CH3:25])[CH:21]=1

Participants

5

Reactant 3

HCID 65617D-Camphorsulfonic AcidHCID 130629693,5-Dibromo-1-methyl-1H-pyrazin-2-oneHCID 576251673-(4-Aminophenyl)-4-ethylpiperazin-2-one

Product 1

HCID 576251865-Bromo-3-(4-(1-ethyl-3-oxopiperazin-2-yl)phenylamino]-1-methylpyrazin-2(1H)-oneYield 79%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 33 (450 mg, 2.05 mmol), isopropanol (5 mL), 13 (603 mg, 2.26 mmol) and DL-10-camphorsulfonic acid (813 mg, 3.50 mmol), and the reaction mixture was then stirred at reflux for 16 h. After this time, the reaction mixture was cooled to room temperature, filtered and the filter cake washed with isopropanol (10 mL). The resulting solid was dissolved in methylene chloride/methanol (3:1), absorbed onto silica gel and purified by flash chromatography to afford 34 in 79% yield (654 mg) as an orange solid: mp 152-153° C.; 1H NMR (500 MHz, CDCl3) δ8.28 (bs, 1H7.73 (d, 2H, J=8.5 Hz), 7.43 (d, 2H, J=8.5 Hz), 6.74 (s, 1H), 5.90 (d, 1H, J=3.5 Hz), 4.12 (s, 1H), 3.60 (m, 1H), 3.52 (s, 3H), 3.36 (m, 1H), 3.12 (m, 1H), 2.60 (m, 2H), 2.28 (m, 1H), 1.00 (t, 3H, J=7.0 Hz); MS (ESI+) m/z 406.0 (M+H).

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser
  3. temperatureat reflux for 16 h
  4. filtrationfiltered
  5. washthe filter cake washed with isopropanol (10 mL)
  6. dissolutionThe resulting solid was dissolved in methylene chloride/methanol (3:1)
  7. customabsorbed onto silica gel
  8. custompurified by flash chromatography

Sources & evidence

ORD record
ord-c3575206149f4cdca70f66066758f0a8
Source dataset
uspto-grants-2011_02
Patent number
US07884108B2

Reaction notes

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