Diisopropylethylamine → 7-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-4-isopropyl-3,4-dihydropyrido[2,3-b]pyrazin-2(1H)-one

HRID 69671

Reaction equation

HRID 69671 reaction equation
O[CH2:2][C:3]1[CH:16]=[N:15][C:6]2[N:7]([CH:12]([CH3:14])[CH3:13])[CH2:8][C:9](=[O:11])[NH:10][C:5]=2[CH:4]=1.[I-].C(C[P+](C)(C)C)#N.CCN(C(C)C)C(C)C.Cl.[Cl:35][C:36]1[CH:41]=[CH:40][C:39]([N:42]2[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]2)=[CH:38][CH:37]=1>C(#N)CC>[Cl:35][C:36]1[CH:37]=[CH:38][C:39]([N:42]2[CH2:47][CH2:46][N:45]([CH2:2][C:3]3[CH:16]=[N:15][C:6]4[N:7]([CH:12]([CH3:14])[CH3:13])[CH2:8][C:9](=[O:11])[NH:10][C:5]=4[CH:4]=3)[CH2:44][CH2:43]2)=[CH:40][CH:41]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 30847201-(4-Chlorophenyl)piperazine HydrochlorideHCID 10514344(Cyanomethyl)trimethylphosphanium iodideHCID 583244367-(hydroxymethyl)-4-isopropyl-3,4-dihydropyrido[2,3-b]pyrazin-2(1H)-one

Product 1

HCID 468644807-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-4-isopropyl-3,4-dihydropyrido[2,3-b]pyrazin-2(1H)-oneYield 26%

Reagents, catalysts & solvents 1

HCID 7854PropionitrileSolvent

Conditions

Temperature
90 °C

Procedure

The 7-(hydroxymethyl)-4-isopropyl-3,4-dihydropyrido[2,3-b]pyrazin-2(1H)-one (100 mg, 0.452 mmol) was weighed into a vial and taken up as a suspension in propiononitrile (1 mL). Next was added (cyanomethyl)trimethylphosphonium iodide (132 mg, 0.542 mmol) followed by DIEA (0.237 mL, 1.356 mmol). To the stirred white suspension was then added the 1-(4-chlorophenyl)piperazine hydrochloride (116 mg, 0.50 mmol). The reaction was stirred overnight at 90° C. The crude reaction was cooled to room temperature and concentrated to a residue, then taken up in DMSO (3 mL) and purified via HPLC (55-90% acetonitrile in water, ammonium bicarbonate buffer). The fractions were combined and concentrated until a white solid precipitated. The precipitate was filtered off and dried in vacuum to afford the title compound (46.6 mg, 26%) as a white solid. 1H NMR (DMSO-d6) δ (ppm): 10.49 (s, 1H), 7.63 (d, J=2.0 Hz, 1H), 7.21 (d, J=9.1 Hz, 2H), 6.97 (d, J=1.8 Hz, 1H), 6.92 (d, J=9.1 Hz, 2H), 4.74-4.87 (m, 1H), 3.81 (s, 2H), 3.33 (d, J=2.0 Hz, 2H), 3.01-3.15 (m, 4H), 2.41-2.48 (m, 4H), 1.12 (d, J=6.8 Hz, 6H). [M+H] calc'd for C21H26ClN5O, 400; found, 400.

Workup

  1. customThe crude reaction
  2. temperaturewas cooled to room temperature
  3. concentrationconcentrated to a residue
  4. custompurified via HPLC (55-90% acetonitrile in water, ammonium bicarbonate buffer)
  5. concentrationconcentrated until a white solid
  6. customprecipitated
  7. filtrationThe precipitate was filtered off
  8. customdried in vacuum

Sources & evidence

ORD record
ord-bac62cf7585a4c8aa9296b63c48cb881
Source dataset
uspto-grants-2014_09
Patent number
US08822470B2

Linked notes

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