Lithium diisopropylamide → (+/-)-1-[1-(6-chloropyridin-2-yl)-2,2-dipyridin-3-ylethyl]pyridin-2(1H)-one

HRID 1360130Notes

Reaction equation

HRID 1360130 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][N:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]2=[O:15])[CH:5]=[CH:4][CH:3]=1.[Li+].CC([N-]C(C)C)C.Cl[CH:25]([C:32]1[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=1)[C:26]1[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=1>C1COCC1>[Cl:1][C:2]1[N:7]=[C:6]([CH:8]([N:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]2=[O:15])[CH:25]([C:32]2[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=2)[C:26]2[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=2)[CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 574257801-[(6-chloropyridin-2-yl)methyl]pyridin-2(1H)-oneHCID 574257823,3'-(Chloromethylene)dipyridine

Product 1

HCID 59706213(+/-)-1-[1-(6-chloropyridin-2-yl)-2,2-dipyridin-3-ylethyl]pyridin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To the solution of 1-[(6-chloropyridin-2-yl)methyl]pyridin-2(1H)-one (0.3 g, 1.36 mmol) in THF (6 mL) at −78° C. was added LDA(0.83 mL, 1.8 M) and stirred at −78° C. for 1 h. The solution of 3-[chloro(pyridin-3-yl)methyl]pyridine (0.278 g, 1.36 mmol) in THF (3 mL) was added and the mixture was warmed to 0° C. and stirred at 0° C. for 1 h. The reaction was quenched with water and extracted with CH2Cl2. The combined organic layer was dried, filtered, and concentrated. The residue was purified by silica gel chromatography (3% MeOH in CH2Cl2) to give (±)-1-[1-(6-chloropyridin-2-yl)-2,2-dipyridin-3-ylethyl]pyridin-2(1H)-one. 1H-NMR (500 MHz, CDCl3) δ 8.58 (d, 1H, J=2.2), 8.53 (d, 1H, J=2.0), 8.42 (dd, 1H, J=4.6, 1.2), 8.35 (dd, 1H, J=4.6, 1.2), 7.92 (d, 1H, 3=6.6), 7.84 (d, 1H, J=8.0), 7.64 (d, 1H, J=8.0), 7.48 (t, 1H, J=7.7), 7.25-7.09 (m, 6H), 6.41 (d, 1H, J=9.0), 6.09 (t, 1H, J=6.7), 5.30 (d, 1H, J=12.2). LRMS m/z (M+H) Calcd: 389.8. found: 389.0.

Workup

  1. temperaturethe mixture was warmed to 0° C.
  2. stirringstirred at 0° C. for 1 h
  3. customThe reaction was quenched with water
  4. extractionextracted with CH2Cl2
  5. customThe combined organic layer was dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (3% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-3973c8fd5d6e460091391ec1c77f5d0d
Source dataset
uspto-grants-2011_02
Patent number
US07879839B2

Reaction notes

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