Sodium Nitrite → 6-(4-(3-hydroxypropoxy)-3-(trifluoromethyl)phenyl)-1-methyl-1H-[1,2,3]triazolo[4,5-c]pyridine-4-carbonitrile

HRID 517986Notes

Reaction equation

HRID 517986 reaction equation
[N:1]([O-])=O.[Na+].[NH2:5][C:6]1[C:7]([C:29]#[N:30])=[N:8][C:9]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH2:23][OH:24])=[C:16]([C:25]([F:28])([F:27])[F:26])[CH:15]=2)=[CH:10][C:11]=1[NH:12][CH3:13]>O.Cl.CN1C(=O)CCC1.C(OCC)(=O)C>[OH:24][CH2:23][CH2:22][CH2:21][O:20][C:17]1[CH:18]=[CH:19][C:14]([C:9]2[N:8]=[C:7]([C:29]#[N:30])[C:6]3[N:5]=[N:1][N:12]([CH3:13])[C:11]=3[CH:10]=2)=[CH:15][C:16]=1[C:25]([F:28])([F:26])[F:27]

Participants

7

Reactant 2

HCID 23668193Sodium NitriteHCID 672942663-Amino-6-(4-(3-hydroxypropoxy)-3-(trifluoromethyl)phenyl)-4-(methylamino)picolinonitrile

Product 1

HCID 533303906-(4-(3-hydroxypropoxy)-3-(trifluoromethyl)phenyl)-1-methyl-1H-[1,2,3]triazolo[4,5-c]pyridine-4-carbonitrileYield 20.2%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of sodium nitrite (13.07 g) in water (40 ml) was added to 3-amino-6-(4-(3-hydroxypropoxy)-3-(trifluoromethyl)phenyl)-4-(methylamino)picolinonitrile (49.6 g) in 2M hydrochloric acid (203 ml) and NMP (180 ml). The mixture was stirred at room temperature for 2 hours then diluted with ethyl acetate (50 mml), and the mixture washed with water (300 ml+100 ml×4), the organic layer was dried over magnesium sulphate, solvent removed under reduced pressure. The residue was then columned on silica gel using DCM then DCM-MeOH (199:1) as eluant to give expected product (10.34 g). 1H NMR (CD3OD) δ: 8.55 (s, 1H), 8.39-8.45 (m, 2H), 7.35 (d, 1H), 4.45 (s, 3H), 4.30 (t, 2H), 3.80 (t, 2H), 2.06 (quin, 2H). MS m/z 378 (M+H).

Workup

  1. washthe mixture washed with water (300 ml+100 ml×4)
  2. dry with materialthe organic layer was dried over magnesium sulphate, solvent
  3. customremoved under reduced pressure

Sources & evidence

ORD record
ord-10d0617cc32c4af2997bc61cd3e06984
Source dataset
uspto-grants-2015_08
Patent number
US09115126B2

Reaction notes

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