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

HRID 659430Notes

Reaction equation

HRID 659430 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:6][C:7]1[C:30]([F:31])=[CH:29][CH:28]=[C:27]([F:32])[C:8]=1[CH2:9][N:10]1[CH2:15][CH2:14][NH:13][C:12]2[N:16]=[CH:17][C:18]([C:20]3[CH:25]=[CH:24][N:23]=[C:22](Cl)[CH:21]=3)=[CH:19][C:11]1=2>>[Cl:6][C:7]1[C:30]([F:31])=[CH:29][CH:28]=[C:27]([F:32])[C:8]=1[CH2:9][N:10]1[CH2:15][CH2:14][NH:13][C:12]2[N:16]=[CH:17][C:18]([C:20]3[CH:21]=[CH:22][N:23]=[C:24]([N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)[CH:25]=3)=[CH:19][C:11]1=2

Participants

3

Reactant 2

HCID 31268PyrrolidineHCID 578858211-(2-Chloro-3,6-difluorobenzyl)-7-(2-chloropyridin-4-yl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazine

Product 1

HCID 578857961-(2-Chloro-3,6-difluorobenzyl)-7-(2-pyrrolidin-1-yl-pyridin-4-yl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazineYield 35%

Conditions

Temperature
87 °C

Procedure

Pyrrolidine (1 mL) was added to 1-(2-chloro-3,6-difluorobenzyl)-7-(2-chloropyridin-4-yl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazine (32 mg). The reaction mixture was stirred at 87° C. for 72 hours and then concentrated. The residue was purified by normal phase column chromatography eluting with 5% methanol in CH2Cl2 to give the title compound as a yellow solid (35% yield). LCMS: m/z=442.21 (M+H+), 1H-NMR (CDCl3, 400 MHz) δ 2.03 (4H, m), 3.33 (2H, m), 3.53 (6H, m), 4.53 (2H, d, J=1.3 Hz), 5.06 (1H, bs), 6.43 (1H, d, J=0.8 Hz), 6.68 (1H, dd, J=5.4, 1.4 Hz), 7.02 (1H, m), 7.12 (2H, m), 7.79 (1H, d, J=1.8 Hz), 8.15 (1H, d, J=5.6 Hz).

Workup

  1. concentrationconcentrated
  2. customThe residue was purified by normal phase column chromatography
  3. washeluting with 5% methanol in CH2Cl2

Sources & evidence

ORD record
ord-5996396c32d04cf1ac5c141dfdc13c07
Source dataset
uspto-grants-2011_12
Patent number
US08080561B2

Reaction notes

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