Pyrrolidine → HCID 57377742, compound

HRID 1802188Notes

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]([OH:28])=O)=[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[CH2:33][CH2:32][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[CH2:33][CH2:32][CH2:31][CH2:30]2)=[O:28])=[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), pyrrolidine (240 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 at 70° C. The solvent was evaporated; the residue was triturated with saturated aqueous sodium hydrogencarbonate solution and the precipitated solid was filtered off and dried in vacuo. The material was applied on silica and purified by flash chromatography over a 20 g silica column using heptane/EtOAc 10-100% as eluent, affording N-(6-fluoro-2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-1-methyl-4-(pyrrolidine-1-carbonyl)-1H-pyrazole-5-carboxamide (83 mg, 52.8%) as white solid. Mp. 250-251° C. MS: m/z=434.4 (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 vacuo
custompurified by flash chromatography over a 20 g silica column

Sources & evidence

ORD record: ord-552e9c989eaf4251bf62d6d1a26b7f1b
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08349824B2

Reaction notes

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