Morpholine → HCID 57377743, compound

HRID 1802189Notes

Reaction equation

[F:1][C:2]1[C:3]([NH:17][C:18]([C:20]2[N:24]([CH3:25])[N:23]=[CH:22][C:21]=2[C:26](O)=[O:27])=[O:19])=[CH:4][C:5]2[N:6]([N:8]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[N:10]=2)[CH:7]=1.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.CCCP(=O)=O.C(N(C(C)C)CC)(C)C>O1CCCC1>[F:1][C:2]1[C:3]([NH:17][C:18]([C:20]2[N:24]([CH3:25])[N:23]=[CH:22][C:21]=2[C:26]([N:29]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)=[O:27])=[O:19])=[CH:4][C:5]2[N:6]([N:8]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[N:10]=2)[CH:7]=1

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of 5-(6-fluoro-2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-ylcarbamoyl)-1-methyl-1H-pyrazole-4-carboxylic acid (138 mg, 363 μmol), morpholine (253 μl, 2.9 mmol), propylphosphonic anhydride (50% in ethyl acetate, 534 μl, 907 μmol) and diisopropylethylamine (190 μl, 1.09 mmol) in tetrahydrofuran (10 ml) was stirred for 2.5 days (weekend) at 70° C. under nitrogen atmosphere. The solvent was evaporated, the residue was triturated with saturated aqueous sodium hydrogencarbonate solution and the precipitated solid was filtered off and dried in vacuum. The crude material was applied on silica and purified by flash chromatography over a 20 g silica column using heptane/ethyl acetate 10-100% as eluent, affording 2-methyl-4-(morpholine-4-carbonyl)-2H-pyrazole-3-carboxylic acid (6-fluoro-2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-amide (67 mg, 41.1%) as white solid. Mp.: 224-225° C. MS: m/z=450.0 (M+H+).

Workup

customThe solvent was evaporated
customthe residue was triturated with saturated aqueous sodium hydrogencarbonate solution
filtrationthe precipitated solid was filtered off
customdried in vacuum
custompurified by flash chromatography over a 20 g silica column

Sources & evidence

ORD record: ord-d05ae50f844a463191bd0824475da6f2
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08349824B2

Reaction notes

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