Hydrochloric Acid → 2-([1,2,4]Triazolo[1,5-a]pyridin-6-yl)-1-(6-methylpyridin-2-yl)ethanone

HRID 1432421Notes

Reaction equation

HRID 1432421 reaction equation
[N:1]1[CH:2]=[N:3][N:4]2[CH:9]=[C:8]([CH:10]=O)[CH:7]=[CH:6][C:5]=12.C1(OP([CH:28]([C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([CH3:42])[N:37]=2)NC2C=CC=CC=2)(=O)OC2C=CC=CC=2)C=CC=CC=1.C([O-])([O-])=[O:44].[Cs+].[Cs+].Cl>C1COCC1.CC(O)C.C(OC)(C)(C)C>[CH3:42][C:38]1[N:37]=[C:36]([C:28](=[O:44])[CH2:10][C:8]2[CH:7]=[CH:6][C:5]3[N:4]([N:3]=[CH:2][N:1]=3)[CH:9]=2)[CH:41]=[CH:40][CH:39]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 45083592[1,2,4]Triazolo[1,5-a]pyridine-6-carbaldehydeHCID 58748142Diphenyl ((6-methylpyridin-2-yl)(phenylamino)methyl)phosphonate

Product 1

HCID 666325662-([1,2,4]Triazolo[1,5-a]pyridin-6-yl)-1-(6-methylpyridin-2-yl)ethanone

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

To a solution of [1,2,4]triazolo[1,5-a]pyridine-6-carbaldehyde (3 g, 20 mmol; see subpart (a) above) and [(6-methyl-pyridin-2-yl)-phenylamino-methyl]-phosphonic acid diphenyl ester (8.8 g, 20 mmol; prepared from 6-methyl-pyridine-2-carboxaldehyde (Aldrich-Sigma, St. Louis, Mo.) according to Tetrahedron Lett. 39:1717-1720 (1998)) in a mixture of THF (40 mL) and iPrOH (10 mL) was added Cs2CO3 (8.6 g, 26 mmol) and the mixture was stirred at room temperature for overnight. A solution of 3N HCl (30 mL) was added dropwise to the above mixture and stirred for 1 hour. It was then diluted with MTBE (methyl t-butyl ether) and extracted with 1N HCl twice. The aqueous extracts were neutralized with ca. 50% KOH until pH 7-8 was reached and precipitates formed. The precipitates were collected, washed with water, and dried to yield 1-(6-methyl-pyridin-2-yl)-2-[1,2,4]triazolo[1,5-a]pyridin-6-yl-ethanone as an offwhite solid (2.9 g). The filtrates were extracted with EtOAc and dried over MgSO4 and concentrated. The residue was recrystalized with iPrOH/H2O to yield more desired product (0.6 g). ESP+, m/e 253. 1H NMR (CDCl3, 300 MHz), δ 8.6 (s, 1H), 8.29 (s, 1H), 7.87 (d, 1H), 7.72 (t, 1H),7.70 (d, 1H), 7.53 (dd, 1H), 7.36 (d, 1H), 4.61 (s, 2H), 2.66 (s, 3H).

Workup

  1. stirringstirred for 1 hour
  2. extractionextracted with 1N HCl twice
  3. customprecipitates
  4. customformed
  5. customThe precipitates were collected
  6. washwashed with water
  7. customdried

Sources & evidence

ORD record
ord-50874ce7c9124426bf61d505217ff268
Source dataset
uspto-grants-2009_11
Patent number
US07612094B2

Reaction notes

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