Diisopropylamine → HCID 67518348, compound

HRID 2173376Notes

Reaction equation

HRID 2173376 reaction equation
[C:1]([O:5][C:6](=[O:24])[CH2:7][C:8]1[CH:9]=[N:10][C:11]([NH:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:12][C:13]=1[CH2:14][CH2:15]Br)([CH3:4])([CH3:3])[CH3:2].C([N-]C(C)C)(C)C.[Li+].C(NC(C)C)(C)C.C([Li])CCC>O1CCCC1>[CH3:20][C:19]([CH3:22])([CH3:21])[C:18]([NH:17][C:11]1[N:10]=[CH:9][C:8]2[CH:7]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:24])[CH2:15][CH2:14][C:13]=2[CH:12]=1)=[O:23]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 2724682Lithium diisopropylamideHCID 86727103HCID 86727103, compoundHCID 178418339Butyllithium

Product 1

HCID 67518348HCID 67518348, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of tert-butyl{4-(2-bromoethyl)-6-[(2,2-dimethylpropanoyl)amino]pyridin-3-yl}acetate (6.5 g, 16.3 mmol) in tetrahydrofuran (50 mL) cooled in a dry ice-acetone bath was treated with a solution of lithium diisopropylamide in tetrahydrofuran (50 mL) (prepared from diisopropylamine (3.79 g, 34.7 mmol) and n-butyllithium (2.5 M, 13.7 mL) dropwise via addition funnel over 1 h. After complete addition, the reaction stirred an additional 1 h, then was quenched with saturated sodium bicarbonate solution and allowed to warm to room temperature. The resulting mixture was diluted with ethyl acetate and water and transferred to a reparatory funnel. The layers were separated and the aqueous extracted with ethyl acetate (2×). The combined organics were washed with brine, dried (Na2SO4), filtered and concentrated. Purification of the resulting residue (2−>25% EtOAc/hexanes eluent) provided tert-butyl 3-[(2,2-dimethylpropanoyl)amino]-6,7-dihydro-5H-cyclopenta[c]pyridine-7-carboxylate. 1H NMR (500 MHz, CDCl3), δ 8.27 (s, 1H), 8.16 (s, 1H), 8.06 (br s, 1H), 3.96 (dd, J=5.0, 5.5 Hz, 1H), 3.06 (m, 1H), 2.90 (m, 1H), 2.45 (m, 1H), 2.32 (m, 1H)-1), 1.47 (s, 9H), 1.32 (s, 9H); LC/MS (M+1)+=319.0;

Workup

  1. additionAfter complete addition
  2. customwas quenched with saturated sodium bicarbonate solution
  3. additionThe resulting mixture was diluted with ethyl acetate and water
  4. customtransferred to a reparatory funnel
  5. customThe layers were separated
  6. extractionthe aqueous extracted with ethyl acetate (2×)
  7. washThe combined organics were washed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification of the resulting residue (2−>25% EtOAc/hexanes eluent)

Sources & evidence

ORD record
ord-5cf0650ee61842bab11db83ee64c782e
Source dataset
uspto-grants-2015_06
Patent number
US09056859B2

Reaction notes

Loading…