Diisopropylethylamine → HCID 58554157, compound

HRID 1631004Notes

Reaction equation

HRID 1631004 reaction equation
Cl[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][N:3]=1.[C:10]([O:14][C:15](=[O:18])[CH2:16][NH2:17])([CH3:13])([CH3:12])[CH3:11].CCN(C(C)C)C(C)C>O1CCOCC1>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([NH:17][CH2:16][C:15]([O:14][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:18])=[N:3][CH:4]=1)#[N:7]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 151417Glycine tert-butyl ester2×HCID 51520946-Chloro-3-pyridinecarbonitrile

Product 1

HCID 58554157HCID 58554157, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 6-chloronicotinonitrile (1.00 g, 7.2 mmol), glycine tert-butyl ester (1.04 g, 7.9 mmol) and DIEA (4.9 mL, 29 mmol) in anhydrous dioxane (20 mL) was heated at reflux. After 24 hours, an additional amount of glycine tert-butyl ester (0.5 g, 3.8 mmol) was added. After 24 additional hours at reflux, the reaction mixture was concentrated under reduced pressure. The residue was taken up with EtOAc (50 mL) and washed with water (20 mL). The organic layer was dried (MgSO4) and the solvent was removed under reduced pressure. After precipitation from EtOAc/Et2O/heptane, the title compound was obtained as an off-white powder (1.55 g, 92%). HPLC (Method A), Rt: 3.1 min (purity: 95.1%). UPLC/MS, M+(ESI): 178.0 ([M-tBu+2H]+), M−(ESI): 232.1. 1H NMR (DMSO-d6, 300 MHz) δ 8.39 (d, J=2.1 Hz, 1H), 7.91 (m, 1H), 7.72 (dd, J=8.8, 2.1 Hz, 1H), 6.66 (d, J=8.8 Hz, 1H), 3.98 (d, J=6.1 Hz, 2H), 1.39 (s, 9H).

Workup

  1. temperatureat reflux
  2. temperatureAfter 24 additional hours at reflux
  3. concentrationthe reaction mixture was concentrated under reduced pressure
  4. washwashed with water (20 mL)
  5. dry with materialThe organic layer was dried (MgSO4)
  6. customthe solvent was removed under reduced pressure
  7. customAfter precipitation from EtOAc/Et2O/heptane

Sources & evidence

ORD record
ord-ee1e5a1ed96549359fd88fde2ff4b644
Source dataset
uspto-grants-2014_07
Patent number
US08791142B2

Reaction notes

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