HCID 22941953, compound → HCID 131721103, compound

HRID 361596Notes

Reaction equation

HRID 361596 reaction equation
[N:1]1([CH2:6]/[CH:7]=[C:8](/[C:16]2[N:21]=[C:20](/[CH:22]=[CH:23]/[CH:24]=[O:25])[CH:19]=[CH:18][CH:17]=2)\[C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:26]([Mg]Cl)[CH2:27][CH3:28]>C1COCC1>[N:1]1([CH2:6]/[CH:7]=[C:8](/[C:16]2[N:21]=[C:20](/[CH:22]=[CH:23]/[CH:24]([OH:25])[CH2:26][CH2:27][CH3:28])[CH:19]=[CH:18][CH:17]=2)\[C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 22941953HCID 22941953, compoundHCID 178455855HCID 178455855, compound

Product 1

HCID 131721103HCID 131721103, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of 3-(6-[3-pyrrolidin-1-yl-1-{4-tolyl}-prop-1E-enyl]-pyridin-2-yl)-prop-2E-enal (925 mg, 2.78 mmol) in anhydrous THF (30 ml) at -78° C. was treated dropwise with a solution of n-propyl magnesium chloride (1.53 ml, 2.0 M in diethylether, 3.06 mmol). The reaction mixture was allowed to warm slowly to room temperature (~2 hours). The reaction was quenched with water (3 ml) and THF removed under reduced pressure. The residue was taken up in 1M HCl and then basified with solid sodium bicarbonate to pH 8. The product was extracted with ethyl acetate (×3). The organics were combined, dried over sodium sulphate, filtered and concentrated under reduced pressure. The product was purified by column chromatography eluting with 5-8% methanol in DCM. Product containing fractions were combined and solvent removed to provide 1-(6-[3-pyrrolidin-1-yl-1-{4-tolyl}-prop-1E-enyl]-pyridin-2-yl)-hex-1E-en-3-ol as a pale pink foam (593 mg, 57%). 1H-NMR; δ (CDCl3), 7.44 (1H, t, J=7.7 Hz), 7.24-7.18 (3H, m), 7.12-7.07 (3H, m), 6.89 (1H, dd, J=15.7, 6.2 Hz), 6.68 (2H, m), 4.38 (1H, m), 3.35 (2H, d, J=7.1 Hz), 2.41 (4H, bs), 1.86 (3H, s), 1.71-1.61 (2H, m), 1.58-1.42 (2H, m), 1.47 (3H, t, J=7.0 Hz).

Workup

  1. customThe reaction was quenched with water (3 ml) and THF
  2. customremoved under reduced pressure
  3. extractionThe product was extracted with ethyl acetate (×3)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe product was purified by column chromatography
  8. washeluting with 5-8% methanol in DCM
  9. additionProduct containing fractions
  10. customsolvent removed

Sources & evidence

ORD record
ord-589baee531b046caadb5567029310643
Source dataset
uspto-grants-1999_02
Patent number
US05866588

Reaction notes

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