2-Amino-5-chloropyridine → N-(5-chloropyridin-2-yl)-2-(1,4-dioxa-8-azaspiro[4.5]decan-8-ylcarbonyl)aminobenzamide

HRID 1373712Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][N:3]=1.C[Mg]Br.[O:12]1[C:16]2([CH2:21][CH2:20][N:19]([C:22]3[O:27][C:26](=[O:28])[C:25]4[CH:29]=[CH:30][CH:31]=[CH:32][C:24]=4[N:23]=3)[CH2:18][CH2:17]2)[O:15][CH2:14][CH2:13]1>O1CCCC1>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:26](=[O:28])[C:25]2[CH:29]=[CH:30][CH:31]=[CH:32][C:24]=2[NH:23][C:22]([N:19]2[CH2:18][CH2:17][C:16]3([O:12][CH2:13][CH2:14][O:15]3)[CH2:21][CH2:20]2)=[O:27])=[N:3][CH:4]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a stirred solution of 2-amino-5-chloropyridine (573 mg, 4.51 mmol) in tetrahydrofuran (25 mL) at 0° C. under nitrogen was added methylmagnesium bromide (3.0 M in ether, 1.50 mL, 4.51 mmol) dropwise via a syringe. After stirring at 0° C. for 10 min, 2-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-4H-3,1-benzoxazin-4-one (1.30 g, 4.51 mmol) was added. After stirring 15 h at room temperature, the solvent was removed in vacuo. The residue was partitioned between ethyl acetate and saturated aqueous sodium chloride and the layers separated. The organic phase was washed with water, dried (magnesium sulfate), filtered, and concentrated in vacuo to give, after recrystallization from EtOAc, 880 mg (47%) of the title compound.

Workup

stirringAfter stirring 15 h at room temperature
customthe solvent was removed in vacuo
customThe residue was partitioned between ethyl acetate and saturated aqueous sodium chloride
customthe layers separated
washThe organic phase was washed with water
dry with materialdried (magnesium sulfate)
filtrationfiltered
concentrationconcentrated in vacuo
customto give
customafter recrystallization from EtOAc, 880 mg (47%) of the title compound

Sources & evidence

ORD record: ord-85b31b7d1c844ff081e6584a3b9c7753
Source dataset: uspto-grants-2007_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07163938B2

Reaction notes

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