Diisopropylamine → 2-Chloro-6-[[1-(hydroxymethyl)-2-methyl-propyl]amino]-4-(trifluoromethyl)pyridine-3-carbonitrile
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].[NH2:15][CH:16]([CH:19]([CH3:21])[CH3:20])[CH2:17][OH:18].C(NC(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:15][CH:16]([CH2:17][OH:18])[CH:19]([CH3:21])[CH3:20])[N:5]=1Participants
Procedure
Neat 3-cyano-2,6-dichloro-4-trifluoromethylpyridine (0.641 g, 6 mmol) (Compound 14) was added by pipette at a dropwise rate over 3 minutes to 2-amino-3-methyl-butan-1-ol (1.5 g, 6 mmol) (Compound 15). 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-[[1-(hydroxymethyl)-2-methyl-propyl]amino]-4-(trifluoromethyl) pyridine-3-carbonitrile (Compound 13) was isolated in 50% yield.
Workup
- custombefore quenching in ice-cold water
- extractionextracted with dichloromethane
- washOrganic extracts were washed twice with water
- dry with materialdried over sodium sulfate
- concentrationconcentrated under reduced pressure
- washThe residue was washed with diethylether
- customthe resultant solid was used in the next step without further purification
Sources & evidence
- ORD record
- ord-aeb529a6033640ed874ea6b5c4412dad
- Source dataset
- uspto-grants-2013_12
- Patent number
- US08604199B2
Reaction notes
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