Triethylamine → 4-(azetidine-1-carbonyl)-1-methyl-N-(6-methyl-2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-1H-pyrazole-5-carboxamide

HRID 1802160Notes

Reaction equation

HRID 1802160 reaction equation
Cl.[CH3:2][C:3]1[C:4]([NH2:18])=[CH:5][C:6]2[N:7]([N:9]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:11]=2)[CH:8]=1.C(N(CC)CC)C.C[Al](C)C.[N:30]1([C:34]([C:36]2[CH:37]=[N:38][N:39]([CH3:46])[C:40]=2[C:41](OCC)=[O:42])=[O:35])[CH2:33][CH2:32][CH2:31]1.C(N(C(C)C)C(C)C)C>O1CCOCC1>[N:30]1([C:34]([C:36]2[CH:37]=[N:38][N:39]([CH3:46])[C:40]=2[C:41]([NH:18][C:4]2[C:3]([CH3:2])=[CH:8][N:7]3[N:9]=[C:10]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=4)[N:11]=[C:6]3[CH:5]=2)=[O:42])=[O:35])[CH2:31][CH2:32][CH2:33]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 81531DiisopropylethylamineHCID 16682925Trimethylaluminum2×HCID 67041800ethyl 4-(azetidine-1-carbonyl)-1-methyl-1H-pyrazole-5-carboxylateHCID 677760476-Methyl-2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-amine hydrochloride

Product 1

HCID 573773054-(azetidine-1-carbonyl)-1-methyl-N-(6-methyl-2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-1H-pyrazole-5-carboxamideYield 24.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
25 °C

Procedure

To an argon purged solution of 6-methyl-2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-amine hydrochloride (147 mg, 564 μmol) and triethylamine (78.6 μl, 564 μmol) in dioxane (8 ml) is added trimethylaluminum (2M solution in toluene, 705 μl, 1.41 mmol). The resulting mixture is stirred for 1 hour at 25° C., then ethyl 4-(azetidine-1-carbonyl)-1-methyl-1H-pyrazole-5-carboxylate (134 mg, 564 μmol) is added; the mixture is heated to 100° C. and stirred for 18 hours. As no conversion is detected N-ethyl diisopropylamine (246 μl, 1.41 mmol) and another portion of trimethylaluminum (2M solution in toluene, 705 μl, 1.41 mmol) are added, the mixture is stirred for 1 hours at 25° C. and then for further 20 hours at 100° C. The crude material is loaded on silica and purified by flash chromatography on a 20 g silica column using heptane/ethyl acetate 10-100% as eluent affording 4-(azetidine-1-carbonyl)-1-methyl-N-(6-methyl-2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-1H-pyrazole-5-carboxamide (57 mg, 24.3%) as a light yellow solid. mp.: 226-8° C. MS: m/z=416.2 (M+H+).

Workup

  1. temperaturethe mixture is heated to 100° C.
  2. stirringstirred for 18 hours
  3. stirringthe mixture is stirred for 1 hours at 25° C.
  4. waitfor further 20 hours at 100° C
  5. custompurified by flash chromatography on a 20 g silica column

Sources & evidence

ORD record
ord-129b1e3a7d944007bcbab532fd6e8c26
Source dataset
uspto-grants-2013_01
Patent number
US08349824B2

Reaction notes

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