Hydrochloric Acid → 1-methyl-6-(4-(pyridin-2-yl-methoxy)-3-(trifluoromethyl)phenyl)-1H-[1,2,3]triazolo[4,5-c]pyridine-4-carbonitrile

HRID 517964Notes

Reaction equation

HRID 517964 reaction equation
[NH2:1][C:2]1[C:3]([C:28]#[N:29])=[N:4][C:5]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)=[C:12]([C:24]([F:27])([F:26])[F:25])[CH:11]=2)=[CH:6][C:7]=1[NH:8][CH3:9].Cl.[N:31]([O-])=O.[Na+].C(OCC)(=O)C>CN1C(=O)CCC1.O>[CH3:9][N:8]1[C:7]2[CH:6]=[C:5]([C:10]3[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=4)=[C:12]([C:24]([F:27])([F:26])[F:25])[CH:11]=3)[N:4]=[C:3]([C:28]#[N:29])[C:2]=2[N:1]=[N:31]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 23668193Sodium NitriteHCID 672942713-Amino-4-(methylamino)-6-(4-(pyridin-2-ylmethoxy)-3-(trifluoromethyl)phenyl)picolinonitrile

Product 1

HCID 533300421-methyl-6-(4-(pyridin-2-yl-methoxy)-3-(trifluoromethyl)phenyl)-1H-[1,2,3]triazolo[4,5-c]pyridine-4-carbonitrileYield 27.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
7.5 °C

Procedure

To 3-amino-4-(methylamino)-6-(4-(pyridin-2-ylmethoxy)-3-(trifluoromethyl)-phenyl)picolinonitrile (1.7 g) in NMP (20 ml) was added 1M hydrochloric acid (22 ml) and cooled to 5-10° C. with an ice bath. To above solution was then added dropwise a solution of sodium nitrite (0.59 g) in water (5 ml) during 5 minutes. The mixture was stirred at room temperature for another 1 hour. After adding ethyl acetate (200 ml), the mixture washed with water (4×100 ml), brine (50 ml), solvent removed under reduced pressure. Upon addition of methanol (20 ml) to the residue, the desired product precipitated and collected by filtration to give 1-methyl-6-(4-(pyridin-2-yl-methoxy)-3-(trifluoromethyl)phenyl)-1H-[1,2,3]triazolo[4,5-c]pyridine-4-carbonitrile (480 mg) as a white solid. 1H NMR (CDCl3) δ: 8.61 (d, 1H), 8.35 (s, 1H), 8.29 (d, 1H), 7.98 (s, 1H), 7.78 (t, 1H), 7.60 (d, 1H), 7.27 (t, 1H), 7.22 (d, 1H), 5.40 (s, 2H), 4.44 (s, 3H). MS m/z 411 (M+H).

Workup

  1. washthe mixture washed with water (4×100 ml), brine (50 ml), solvent
  2. customremoved under reduced pressure
  3. additionUpon addition of methanol (20 ml) to the residue
  4. customthe desired product precipitated
  5. filtrationcollected by filtration

Sources & evidence

ORD record
ord-f23fecf460d04d538e062e3fc125d312
Source dataset
uspto-grants-2015_08
Patent number
US09115126B2

Reaction notes

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