Pyrrolidine → 1-(2,5-Dichlorobenzyl)-7-(6-pyrrolidin-1-yl-pyridin-3-yl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazine

HRID 659417Notes

Reaction equation

HRID 659417 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[C:7]1[N:12]=[CH:11][C:10]([C:13]2[CH:31]=[N:30][C:16]3[NH:17][CH2:18][CH2:19][N:20]([CH2:21][C:22]4[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:23]=4[Cl:29])[C:15]=3[CH:14]=2)=[CH:9][CH:8]=1>>[Cl:29][C:23]1[CH:24]=[CH:25][C:26]([Cl:28])=[CH:27][C:22]=1[CH2:21][N:20]1[CH2:19][CH2:18][NH:17][C:16]2[N:30]=[CH:31][C:13]([C:10]3[CH:11]=[N:12][C:7]([N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)=[CH:8][CH:9]=3)=[CH:14][C:15]1=2

Participants

3

Reactant 2

HCID 31268PyrrolidineHCID 578860757-(6-Chloropyridin-3-yl)-1-(2,5-dichlorobenzyl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazine

Product 1

HCID 578858811-(2,5-Dichlorobenzyl)-7-(6-pyrrolidin-1-yl-pyridin-3-yl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazineYield 36%

Conditions

Temperature
87 °C

Procedure

Pyrrolidine (1 mL) was added to 7-(6-chloropyridin-3-yl)-1-(2,5-dichlorobenzyl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazine (49 mg), and the mixture was stirred at 87° C. for 16 hours. The reaction mixture was then concentrated, and CH2Cl2 and H2O were added. The organic phase was isolated, dried with magnesium sulfate, filtered and then purified by normal phase column chromatography eluting with 3% methanol in CH2Cl2 to give the title compound as a yellow solid (36% yield). M.p.>200° C., LCMS: m/z=440.19 (M+H+), 1H-NMR (CDCl3, 400 MHz) δ 1.99 (4H, m), 3.47 (6H, m), 3.64 (2H, t, J=4.0 Hz), 4.47 (2H, s), 4.98 (1H, bs), 6.35 (1H, d, J=8.8 Hz), 6.52 (1H, d, J=1.8 Hz), 7.18 (1H, dd, J=8.3, 2.5 Hz), 7.26 (1H, m), 7.32 (1H, d, J=8.6 Hz), 7.48 (1H, dd, J=8.7, 2.4 Hz), 7.62 (1H, d, J=1.8 Hz), 8.17 (1H, d, J=2.3 Hz).

Workup

  1. concentrationThe reaction mixture was then concentrated
  2. additionCH2Cl2 and H2O were added
  3. customThe organic phase was isolated
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. custompurified by normal phase column chromatography
  7. washeluting with 3% methanol in CH2Cl2

Sources & evidence

ORD record
ord-21532aba43d34b37965b074b443b26d7
Source dataset
uspto-grants-2011_12
Patent number
US08080561B2

Reaction notes

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