Morpholine → Gemlapodect

HRID 1802161Notes

Reaction equation

[CH3:1][N:2]1[C:6]([C:7](=[O:24])[NH:8][C:9]2[CH:14]=[CH:13][N:12]3[N:15]=[C:16]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[N:17]=[C:11]3[CH:10]=2)=[C:5]([C:25](O)=[O:26])[CH:4]=[N:3]1.[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1.CCCP(=O)=O>O1CCCC1.C(OCC)(=O)C>[CH3:1][N:2]1[C:6]([C:7]([NH:8][C:9]2[CH:14]=[CH:13][N:12]3[N:15]=[C:16]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[N:17]=[C:11]3[CH:10]=2)=[O:24])=[C:5]([C:25]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)=[O:26])[CH:4]=[N:3]1

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of 1-methyl-5-(2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-ylcarbamoyl)-1H-pyrazole-4-carboxylic acid (100 mg, 276 μmol), morpholine (240 μl, 2.76 mmol) and propylphosphonic anhydride (50% in ethyl acetate, 407 μl, 690 μmol) in tetrahydrofurane (7 ml) is stirred for 3 hours at 70° C. The mixture is diluted with ethyl acetate and washed with sat. aqueous sodium hydrogencarbonate solution and brine. The organic layer is separated, dried with magnesium sulfate and the solvent is evaporated. The residue (76 mg white foam) is triturated with diethylether and ethyl acetate affording 1-methyl-4-(morpholine-4-carbonyl)-N-(2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-1H-pyrazole-5-carboxamide (53 mg, 44.5%) as a white solid. mp.: 203-207° C. MS: m/z=432.4 (M+H+).

Workup

washwashed with sat. aqueous sodium hydrogencarbonate solution and brine
customThe organic layer is separated
dry with materialdried with magnesium sulfate
customthe solvent is evaporated
customThe residue (76 mg white foam) is triturated with diethylether and ethyl acetate

Sources & evidence

ORD record: ord-03f0cea4dc424e95a880d89ecd109dad
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08349824B2

Reaction notes

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