Diisopropylamine → HCID 117925936, compound

HRID 1054207Notes

Reaction equation

HRID 1054207 reaction equation
C([Li])CCC.[CH:6]([NH:9][CH:10](C)C)(C)C.[CH2:13]([N:15]([CH2:24][CH3:25])[C:16](=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1)[CH3:14].[O:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1>>[CH2:24]([N:15]([CH2:13][CH3:14])[C:16](=[O:23])[C:17]1[C:22]([C:30](=[O:26])[C:29]2[CH:6]=[N:9][CH:10]=[CH:27][CH:28]=2)=[CH:21][CH:20]=[CH:19][N:18]=1)[CH3:25]

Participants

5

Reactant 4

HCID 7912DiisopropylamineHCID 8028Tetrahydrofuran2×HCID 410739HCID 410739, compoundHCID 178418339Butyllithium

Product 1

HCID 117925936HCID 117925936, compound

Conditions

Temperature
0 °C

Procedure

A solution of n-butyllithium (1.6M in hexane, 3.65 mL, 5.85 mmol) was added dropwise over a 5-minute period to a solution of diisopropylamine (818 μL, 5.85 mmol) in 20 mL of anhydrous tetrahydrofuran held at −78° C. and under nitrogen. The reaction was warmed to 0° C., held at that temperature for 15 min, and then cooled to −78° C. The resulting solution was added dropwise over a 10 minute period to a solution of N,N-diethylpicolinamide 14 (2.09 g, 11.7 mmol) in 20 mL of anhydrous tetrahydrofuran under nitrogen at −78° C. The reaction was then allowed to warm slowly overnight to ambient temperature and then quenched with 10 mL of water and 10 mL of saturated brine. The reaction mixture was extracted with 3×30 mL of ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting oil was crystallized from ethanol/hexanes to give N,N-diethyl-3-picolinoylpicolinamide 12 (750 mg, 2.64 mmol). 1H NMR (400 MHz, DMSO-d6) δ 8.69-8.60 (m, 1H), 8.62-8.53 (m, 1H), 8.09-7.95 (m, 3H), 7.66-7.53 (m, 2H), 3.43-3.24 (m, 2H), 3.07 (q, J=7.1 Hz, 2H), 1.22 (t, J=7.0 Hz, 2H), 0.55 (t, J=7.1 Hz, 2H). LCMS: (M+H)+, 284.

Workup

  1. customheld at −78° C. and under nitrogen
  2. temperaturecooled to −78° C
  3. temperatureto warm slowly overnight to ambient temperature
  4. customquenched with 10 mL of water and 10 mL of saturated brine
  5. extractionThe reaction mixture was extracted with 3×30 mL of ethyl acetate
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting oil was crystallized from ethanol/hexanes

Sources & evidence

ORD record
ord-e92b4001d35e435d9a03abf0369cfac9
Source dataset
uspto-grants-2016_07
Patent number
US09394299B2

Reaction notes

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