3-Methylpyridine → 2-(3-Bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-6-chloro-8-methyl-4H-benzo[d][1,3]oxazin-4-one

HRID 1178693Notes

Reaction equation

[Br:1][C:2]1[CH:6]=[C:5]([C:7]([OH:9])=O)[N:4]([C:10]2[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][N:11]=2)[N:3]=1.[Cl:17][C:18]1[CH:29]=[C:28]([CH3:30])[C:21]2[NH:22]C(=O)[O:24][C:25](=O)[C:20]=2[CH:19]=1.N1C=CC=C(C)C=1.CS(Cl)(=O)=O>C(#N)C.O>[Br:1][C:2]1[CH:6]=[C:5]([C:7]2[O:9][C:25](=[O:24])[C:20]3[CH:19]=[C:18]([Cl:17])[CH:29]=[C:28]([CH3:30])[C:21]=3[N:22]=2)[N:4]([C:10]2[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][N:11]=2)[N:3]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a mixture of 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (see WO 03/015519 for preparation) (93.6% purity, 16.16 g, 50.0 mmol), 6-chloro-8-methyl-1H-benzo[d][1,3]oxazine-2,4-dione (99.0% purity, 11.22 g, 52.5 mmol), and 3-picoline (16.5 mL, 15.8 g, 170 mmol) in acetonitrile (65 mL) at about −5° C. was added dropwise methanesulfonyl chloride (5.0 mL, 7.4 g, 65 mmol) in acetonitrile (15 mL). After 15 minutes at −5 to 0° C., the reaction mixture was heated to 50° C. for 4 hours. The reaction mixture was then cooled to room temperature, water (20 mL) was added dropwise, and the reaction mixture was stirred 15 minutes. The mixture was filtered, and the solids were washed sequentially with 4:1 acetonitrile-water (2×35 mL) and acetonitrile (3×35 mL), and dried under nitrogen to afford the title product as a light yellow powder, 20.55 g (94.4% purity by HPLC, 85.8% yield calculated based on the purity).

Workup

temperatureThe reaction mixture was then cooled to room temperature
filtrationThe mixture was filtered
washthe solids were washed sequentially with 4:1 acetonitrile-water (2×35 mL) and acetonitrile (3×35 mL)
customdried under nitrogen

Sources & evidence

ORD record: ord-f38876a7b62349b8851d34dfeb823445
Source dataset: uspto-grants-2007_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07276601B2

Reaction notes

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