Diisopropylethylamine → Tert-butyl 4-[(5-cyanopyridin-2-yl)amino]butanoate

HRID 1631006Notes

Reaction equation

HRID 1631006 reaction equation
Cl[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][N:3]=1.Cl.[C:11]([O:15][C:16](=[O:21])[CH2:17][CH2:18][CH2:19][NH2:20])([CH3:14])([CH3:13])[CH3:12].CCN(C(C)C)C(C)C>O1CCOCC1.CCOCC>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([NH:20][CH2:19][CH2:18][CH2:17][C:16]([O:15][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:21])=[N:3][CH:4]=1)#[N:7]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 51520946-Chloro-3-pyridinecarbonitrileHCID 24750478Tert-butyl 4-aminobutanoate hydrochloride2×

Product 1

HCID 58170046Tert-butyl 4-[(5-cyanopyridin-2-yl)amino]butanoate

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 6-chloronicotinonitrile (1.0 g, 7.2 mmol), 4-aminobutyric acid tert-butyl ester hydrochloride (2.12 g, 10.8 mmol, Sennchem 09600) and DIEA (4.9 mL, 28.9 mmol) in anhydrous dioxane (20 mL) was heated at 80° C. After 48 hours, an additional amount of 4-aminobutyric acid tert-butyl ester hydrochloride (0.55 g, 2.80 mmol) was added. After 24 additional hours at 80° C., the reaction mixture was diluted with Et2O (100 mL) and washed with water (2×50 mL) and brine (50 mL). The organic layer was dried (MgSO4) and the solvents were removed under reduced pressure. After purification by flash chromatography (silica, EtOAc/cHex), the title compound was obtained as a beige powder. HPLC (Method A), Rt: 3.3 min (purity: 91%). UPLC/MS, M+(ESI): 262.1, M−(ESI): 260.2. 1H NMR (DMSO-d6, 300 MHz) δ 8.37 (d, J=2.2 Hz, 1H), 7.63 (m, 2H), 6.52 (d, J=8.9 Hz, 1H), 3.29 (m, 2H), 2.26 (t, J=7.4 Hz, 2H), 1.73 (tt, J=7.4, 7.0 Hz, 2H), 1.38 (s, 9H).

Workup

  1. washwashed with water (2×50 mL) and brine (50 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. customthe solvents were removed under reduced pressure
  4. customAfter purification by flash chromatography (silica, EtOAc/cHex)

Sources & evidence

ORD record
ord-e126c8b36c114bc59ece2c4f0cafa7b0
Source dataset
uspto-grants-2014_07
Patent number
US08791142B2

Reaction notes

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