2-Methoxypyridine-4-carbaldehyde → HCID 59276493, compound

HRID 2070896Notes

Reaction equation

HRID 2070896 reaction equation
[F:1][C:2]([F:22])([F:21])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[N:20]=[C:13]3[CH:14]=[CH:15][CH:16]=[C:17](CO)[N:12]3[N:11]=2)=[CH:5][CH:4]=1.C([Li])CCC.C[O:29][C:30]1[CH:31]=[C:32]([CH:35]=[CH:36][N:37]=1)[CH:33]=O>O1CCCC1>[F:21][C:2]([F:1])([F:22])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[N:20]=[C:13]3[CH:14]=[CH:15][CH:16]=[C:17]([CH2:33][C:32]4[CH:35]=[CH:36][NH:37][C:30](=[O:29])[CH:31]=4)[N:12]3[N:11]=2)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 27629962-Methoxypyridine-4-carbaldehydeHCID 68587983HCID 68587983, compoundHCID 178418339Butyllithium

Product 1

HCID 59276493HCID 59276493, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

2-Methoxypyridin-4-yl)(2-(4-(trifluoromethyl)phenylamino)-[1,2,4]triazolo[1,5-a]pyridin-5-yl)methanol. The reaction was performed in two batches of starting material (0.397 g and 0.310 g) according to the following procedure and recombined for work-up and purification. A suspension of 5-bromo-N-(4-(trifluoromethyl)phenyl)-[1,2,4]triazolo[1,5-c]pyridin-2-amine (0.397 g, 1.111 mmol) in dry tetrahydrofuran (6.0 mL) was cooled to −78° C. The mixture was then reacted with n-butyl lithium (0.933 mL, 2.333 mmol, 2.5 M in hexanes). The reaction was stirred at low temperature for 1 h. A solution of 2-methoxyisonicotinaldehyde (0.32 g, 2.333 mmol) in dry tetrahydrofuran (3 mL) was then added dropwise. Low temperature was maintained for 2 h. Checked after 30 min, the reaction had progressed to a mixture of desired product contaminated with de-halogenated starting material. The reaction was quenched with water and the crude was extracted with ethyl acetate. The combined extracts were dried over magnesium sulfate and evaporated to dryness. The residue was purified by biotage column chromatography using the following gradient: 800 mL gradient 10-50% ethyl acetate in hexanes, then 1.100 L at 50% ethyl acetate in hexanes. Desired fractions were combined and evaporated to dryness. (2-Methoxypyridin-4-yl)(2-(4-(trifluoromethyl)phenylamino)-[1,2,4]triazolo[1,5-c]pyridin-5-yl)methanol (0.574 g, 1.382 mmol, 69.8% yield) was collected as a yellow oil. 1H NMR (400 MHz, METHANOL-d4) δ (ppm) 8.04 (d, J=5.47 Hz, 1H), 7.63-7.70 (m, 3H), 7.54 (d, J=8.59 Hz, 2H), 7.47 (d, J=9.37 Hz, 1H), 7.32 (d, J=7.03 Hz, 1H), 7.04 (s, 1H), 7.01 (d, J=5.47 Hz, 1H), 6.32 (s, 1H), 3.86 (s, 3H); MS (ESI): m/z 416.2 [M+1]+.

Workup

  1. customrecombined for work-up and purification
  2. temperatureLow temperature was maintained for 2 h
  3. waitChecked after 30 min

Sources & evidence

ORD record
ord-73a6c19cb7e14bbca168780072ad1d40
Source dataset
uspto-grants-2012_10
Patent number
US08299056B2

Reaction notes

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