Acetic Acid → ethyl (8R)-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]-8-(3,4,5-trifluorophenoxy)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-carboxylate

HRID 1398218Notes

Reaction equation

HRID 1398218 reaction equation
CS[C:3]1[C@@:8]([O:14][C:15]2[CH:20]=[C:19]([F:21])[C:18]([F:22])=[C:17]([F:23])[CH:16]=2)([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:7][CH2:6][CH2:5][N:4]=1.[CH3:24][O:25][C:26]1[N:31]=[C:30]([C:32]([NH:34][NH2:35])=O)[CH:29]=[CH:28][C:27]=1[N:36]1[CH:40]=[C:39]([CH3:41])[N:38]=[CH:37]1.C(O)(=O)C>C(OCC)(=O)C>[CH3:24][O:25][C:26]1[N:31]=[C:30]([C:32]2[N:4]3[CH2:5][CH2:6][CH2:7][C@:8]([O:14][C:15]4[CH:20]=[C:19]([F:21])[C:18]([F:22])=[C:17]([F:23])[CH:16]=4)([C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:3]3=[N:35][N:34]=2)[CH:29]=[CH:28][C:27]=1[N:36]1[CH:40]=[C:39]([CH3:41])[N:38]=[CH:37]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 66608186ethyl (3S)-2-(methylsulfanyl)-3-(3,4,5-trifluorophenoxy)-3,4,5,6-tetrahydropyridine-3-carboxylateHCID 666083826-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridine-2-carbohydrazide

Product 1

HCID 66608299ethyl (8R)-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]-8-(3,4,5-trifluorophenoxy)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-carboxylateYield 95.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To ethyl (3S)-2-(methylsulfanyl)-3-(3,4,5-trifluorophenoxy)-3,4,5,6-tetrahydropyridine-3-carboxylate (702 mg) and 6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridine-2-carbohydrazide (500 mg) was added acetic acid (3 ml), and the mixture was stirred at 100° C. for 3 hr. The reaction mixture was diluted with ethyl acetate, and the mixture was washed with 10% aqueous potassium carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and purified by silica gel column chromatography (NH, ethyl acetate). The crudely-purified product was purified by silica gel column chromatography (methanol/ethyl acetate) to give the title compound (1.02 g).

Workup

  1. washthe mixture was washed with 10% aqueous potassium carbonate solution and saturated brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. custompurified by silica gel column chromatography (NH, ethyl acetate)
  4. customThe crudely-purified product was purified by silica gel column chromatography (methanol/ethyl acetate)

Sources & evidence

ORD record
ord-fa5adc5644304637a45de2b572943761
Source dataset
uspto-grants-2014_12
Patent number
US08901309B2

Reaction notes

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