Acetone → 1-{2-[4-(2,4-difluorophenoxy)piperidin-1-yl]-3-{[(3S)-oxolan-3-yl]amino}-5H,6H,7H,8H-pyrido[3,4-b]pyrazin-6-yl}ethan-1-one

HRID 713373Notes

Reaction equation

HRID 713373 reaction equation
[F:1][C:2]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[N:12]=[C:13]3[CH:26]=[CH:25][N:24]=[CH:23][C:14]3=[N:15][C:16]=2[NH:17][C@H:18]2[CH2:22][CH2:21][O:20][CH2:19]2)[CH2:7][CH2:6]1.[CH3:32][C:33](C)=[O:34].CC(OC(C)=O)=O>O1CCOCC1.[Pd]>[F:1][C:2]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[N:12]=[C:13]3[CH2:26][CH2:25][N:24]([C:33](=[O:34])[CH3:32])[CH2:23][C:14]3=[N:15][C:16]=2[NH:17][C@H:18]2[CH2:22][CH2:21][O:20][CH2:19]2)[CH2:7][CH2:6]1

Participants

6

Reactant 3

HCID 180AcetoneHCID 7918Acetic AnhydrideHCID 118159379HCID 118159379, compound

Product 1

HCID 1181591641-{2-[4-(2,4-difluorophenoxy)piperidin-1-yl]-3-{[(3S)-oxolan-3-yl]amino}-5H,6H,7H,8H-pyrido[3,4-b]pyrazin-6-yl}ethan-1-one

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (S)-2-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-N-(tetrahydrofuran-3-yl)pyrido[3,4-b]pyrazin-3-amine (2.0 g, 4.68 mmol) in dioxane:acetone (50 ml; 1.5:1) was added Ac2O (4.8 mL, 50.9 mmol) and Pd/C (400 mg, 3.76 mmol); then, the reaction was stirred at 60° C. under H2 atmosphere (345 kPa) for 72 h. The mixture was filtered through a pad of Celite™ and washed with EtOAc. The reaction solution was diluted with EtOAc (50 mL) and poured into sat. aqueous NaHCO3 (50 ml), then washed with brine (2×30 mL). The organic layer was dried over Na2SO4 and concentrated to give the crude product, which was purified by flash column chromatography to yield the title compound (193.4 mg) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.88-1.89 (m, 4H), 2.05-2.09 (m, 4H), 2.60-2.90 (m, 4H), 3.30-3.40 (m, 4H), 3.55-3.57 (m, 1H), 3.68-3.74 (m, 2H), 3.85-3.95 (m, 2H), 4.38-4.51 (m, 4H), 5.91 (dd, J=6.0, 4.4 Hz, 1H), 7.01 (m, 1H), 7.25-7.31 (m, 2H); ESI-MS m/z [M+H]+ 474.3.

Workup

  1. filtrationThe mixture was filtered through a pad of Celite™
  2. washwashed with EtOAc
  3. additionThe reaction solution was diluted with EtOAc (50 mL)
  4. additionpoured into sat. aqueous NaHCO3 (50 ml)
  5. washwashed with brine (2×30 mL)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. concentrationconcentrated
  8. customto give the crude product, which
  9. customwas purified by flash column chromatography

Sources & evidence

ORD record
ord-2a5c0da5ac6943668a3815f4589c2df8
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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