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

HRID 1802152Notes

Reaction equation

HRID 1802152 reaction equation
Cl.[O:2]1[CH2:7][CH2:6][N:5]([C:8]2[N:17]=[C:11]3[CH:12]=[C:13]([NH2:16])[CH:14]=[CH:15][N:10]3[N:9]=2)[CH2:4][CH2:3]1.C[Al](C)C.[N:22]1([C:26]([C:28]2[CH:29]=[N:30][N:31]([CH3:38])[C:32]=2[C:33](OCC)=[O:34])=[O:27])[CH2:25][CH2:24][CH2:23]1>O1CCOCC1>[N:22]1([C:26]([C:28]2[CH:29]=[N:30][N:31]([CH3:38])[C:32]=2[C:33]([NH:16][C:13]2[CH:14]=[CH:15][N:10]3[N:9]=[C:8]([N:5]4[CH2:4][CH2:3][O:2][CH2:7][CH2:6]4)[N:17]=[C:11]3[CH:12]=2)=[O:34])=[O:27])[CH2:23][CH2:24][CH2:25]1

Participants

5

Reactant 3

HCID 16682925TrimethylaluminumHCID 67041800ethyl 4-(azetidine-1-carbonyl)-1-methyl-1H-pyrazole-5-carboxylateHCID 677759312-Morpholino-[1,2,4]triazolo[1,5-a]pyridin-7-amine hydrochloride

Product 1

HCID 573773034-(azetidine-1-carbonyl)-1-methyl-N-(2-morpholino-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-1H-pyrazole-5-carboxamideYield 82.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To an nitrogene purged suspension of 2-morpholino-[1,2,4]triazolo[1,5-a]pyridin-7-amine hydrochloride (80 mg, 0.313 mmol) and N-ethyldiisoppropylamine (120 ul, 0.688 mmole) in dioxane (3 ml) is added trimethyl aluminium (2 M solution in toluene, 0.47 ml, 0.94 mmol). The resulting solution is stirred for ½ hour at room temperature. Then ethyl 4-(azetidine-1-carbonyl)-1-methyl-1H-pyrazole-5-carboxylate (75 mg, 0.313 mmol) in dioxane (0.7 ml) is added and the mixture is heated to reflux in a sealed vessel and stirred for 19 hours. Purification of the reaction mixture by chromatography on a 12 g RediSep silica cartridge (eluent dichloromethane+4% methanol) affords 4-(azetidine-1-carbonyl)-1-methyl-N-(2-morpholino-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-1H-pyrazole-5-carboxamide (106 mg, 82.5%) as an off-white solid. mp.: 232-4° C. MS: m/z=411.3 (M+H+).

Workup

  1. customTo an nitrogene purged
  2. temperaturethe mixture is heated
  3. temperatureto reflux in a sealed vessel
  4. stirringstirred for 19 hours
  5. customPurification of the reaction mixture by chromatography on a 12 g RediSep silica cartridge (eluent dichloromethane+4% methanol)

Sources & evidence

ORD record
ord-d4490b4982304286a4e0bdefd2f96c6e
Source dataset
uspto-grants-2013_01
Patent number
US08349824B2

Reaction notes

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