Diisopropylamine → 2-Chloro-6-(2-hydroxybutylamino)-4-(trifluoromethyl)pyridine-3-carbonitrile

HRID 2276000

Reaction equation

HRID 2276000 reaction equation
[C:1]([C:3]1[C:4]([Cl:14])=[N:5][C:6](Cl)=[CH:7][C:8]=1[C:9]([F:12])([F:11])[F:10])#[N:2].N[CH:16]([CH2:19]C)[CH2:17][OH:18].[CH:21]([NH:24]C(C)C)(C)C.ClCl>>[Cl:14][C:4]1[C:3]([C:1]#[N:2])=[C:8]([C:9]([F:12])([F:11])[F:10])[CH:7]=[C:6]([NH:24][CH2:21][CH:17]([OH:18])[CH2:16][CH3:19])[N:5]=1

Participants

5

Reactant 4

HCID 7912DiisopropylamineHCID 221292-Amino-1-butanolHCID 24526ChlorineHCID 27367262,6-Dichloro-4-(trifluoromethyl)nicotinonitrile

Product 1

HCID 866534212-Chloro-6-(2-hydroxybutylamino)-4-(trifluoromethyl)pyridine-3-carbonitrileYield 55%

Procedure

Neat 3-cyano-2,6-dichloro-4-trifluoromethylpyridine (0.641 g, 6 mmol) was added by pipette at a dropwise rate over 3 minutes to 2-aminobutanol (1.5 g, 6 mmol). Di-isopropylamine (0.9 g, 7 mmol) was added after 10 minutes and the resultant mixture was heated in a sealed tube at 70° C. for 30 minutes to selectively displace the chlorine at position 6 before quenching in ice-cold water and extracted with dichloromethane. Organic extracts were washed twice with water, dried over sodium sulfate and concentrated under reduced pressure. The residue was washed with diethylether and the resultant solid was used in the next step without further purification. 2-Chloro-6-(2-hydroxybutylamino)-4-(trifluoromethyl)pyridine-3-carbonitrile was isolated in 55% yield.

Workup

  1. custombefore quenching in ice-cold water
  2. extractionextracted with dichloromethane
  3. washOrganic extracts were washed twice with water
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. washThe residue was washed with diethylether
  7. customthe resultant solid was used in the next step without further purification

Sources & evidence

ORD record
ord-6dfd08c581e74732b0ee67d9ccb2f6a6
Source dataset
uspto-grants-2015_09
Patent number
US09131694B2

Linked notes

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