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

HRID 517967Notes

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:19]=[N:20][CH:21]=[CH:22][CH:23]=3)=[C:12]([C:24]([F:27])([F:26])[F:25])[CH:11]=2)=[CH:6][C:7]=1[NH:8][CH3:9].[N:30]([O-])=O.[Na+]>O.O1CCOCC1.Cl>[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:19]=[N:20][CH:21]=[CH:22][CH:23]=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:30]1

Participants

Conditions

Temperature: 0 °C

Procedure

To a suspension of 3-amino-4-(methylamino)-6-(4-(pyridin-3-ylmethoxy)-3-(trifluoromethyl)phenyl)picolinonitrile (1.33 g) in water (15 ml) and 1,4-dioxane (15 ml), 2N hydrochloric acid (2.5 ml) was added at 0° C. and sodium nitrite (0.332 g) in water (3 ml) was added then stirred at 0° C. for 10 min then at 20° C. for 70 h. The reaction mixture was filtered, washed with water, dried in vacuum oven to give 1.14 g brown solid. Purified by Biotage SNAP cartridge KP-Sil column (100 g, heptane:ethyl acetate=1:0, 2:1, 1:1, 1:2 to 0:1 then ethyl acetate:methanol=25:1, 20:1 to 15:1 then dichloromethane:methanol=15:1, 10:1), fractions were passed through Strata SCX column (5 g) to give 560.7 mg light brown solid as 1-methyl-6-(4-(pyridin-3-ylmethoxy)-3-(trifluoromethyl)phenyl)-1H-[1,2,3]triazolo[4,5-c]pyridine-4-carbonitrile (41%).

Workup

additionwas added at 0° C.
waitat 20° C. for 70 h
filtrationThe reaction mixture was filtered
washwashed with water
customdried in vacuum oven

Sources & evidence

ORD record: ord-1c078fea30794ec99c4304bdf9eeb869
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115126B2

Reaction notes

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