Morpholine → 1-(2-Chloro-3,6-difluorobenzyl)-7-(2-morpholin-4-yl-pyridin-4-yl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazine

HRID 659433Notes

Reaction equation

HRID 659433 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Cl:7][C:8]1[C:31]([F:32])=[CH:30][CH:29]=[C:28]([F:33])[C:9]=1[CH2:10][N:11]1[CH2:16][CH2:15][NH:14][C:13]2[N:17]=[CH:18][C:19]([C:21]3[CH:26]=[CH:25][N:24]=[C:23](Cl)[CH:22]=3)=[CH:20][C:12]1=2>>[Cl:7][C:8]1[C:31]([F:32])=[CH:30][CH:29]=[C:28]([F:33])[C:9]=1[CH2:10][N:11]1[CH2:16][CH2:15][NH:14][C:13]2[N:17]=[CH:18][C:19]([C:21]3[CH:22]=[CH:23][N:24]=[C:25]([N:1]4[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)[CH:26]=3)=[CH:20][C:12]1=2

Participants

3

Reactant 2

HCID 8083MorpholineHCID 578858211-(2-Chloro-3,6-difluorobenzyl)-7-(2-chloropyridin-4-yl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazine

Product 1

HCID 578860981-(2-Chloro-3,6-difluorobenzyl)-7-(2-morpholin-4-yl-pyridin-4-yl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazineYield 21%

Procedure

Morpholine (2 mL) was added to 1-(2-chloro-3,6-difluorobenzyl)-7-(2-chloropyridin-4-yl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazine (61 mg), and the mixture was heated in a microwave oven for two (2) hours at 180° C. The mixture was then concentrated, and the residue was purified through silica gel chromatography followed by preparative reversed-phase HPLC. The trifluoroacetic acid salt was neutralized with saturated sodium bicarbonate, and the free base extracted into methylene chloride, washed with brine and dried with magnesium sulfate. The solution was concentrated to give the title compound as a yellow solid (21% yield). M.p.=157° C., LCMS: m/z=458.07 (M+H+), 1H-NMR (CDCl3, 400 MHz) δ 3.38 (2H, t, J=4.7 Hz), 3.56 (4H, t, J=4.8 Hz), 3.62 (2H, t, J=4.5 Hz), 3.86 (4H, t, J=4.8 Hz), 4.58 (2H, s), 6.65 (1H, s), 6.76 (1H, d, J=5.1 Hz), 7.06 (2H, m), 7.16 (1H, m), 7.59 (2H, m), 8.22 (1H, d, J=5.1 Hz).

Workup

  1. concentrationThe mixture was then concentrated
  2. customthe residue was purified through silica gel chromatography
  3. extractionthe free base extracted into methylene chloride
  4. washwashed with brine
  5. dry with materialdried with magnesium sulfate
  6. concentrationThe solution was concentrated

Sources & evidence

ORD record
ord-a936eeb905c249acad969c03b868b090
Source dataset
uspto-grants-2011_12
Patent number
US08080561B2

Reaction notes

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