Water → 4-bromo-5-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1H-pyrrole-2-carbonitrile
Reaction equation
[CH3:1][C:2]1([CH3:20])[O:7][C:6](=[O:8])[NH:5][C:4]2[CH:9]=[CH:10][C:11]([C:13]3[NH:14][C:15]([C:18]#[N:19])=[CH:16][CH:17]=3)=[CH:12][C:3]1=2.C1C(=O)N([Br:28])C(=O)C1.O>C1COCC1>[Br:28][C:17]1[CH:16]=[C:15]([C:18]#[N:19])[NH:14][C:13]=1[C:11]1[CH:10]=[CH:9][C:4]2[NH:5][C:6](=[O:8])[O:7][C:2]([CH3:20])([CH3:1])[C:3]=2[CH:12]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To 4,4-dimethyl-6-(5-cyano-1H-pyrrol-2-yl)-1,4-dihydrobenzo[d][1,3]oxazin-2-one (0.625 g, 2.3 mmol, 1 eq) in THF (anhydrous, 60 mL) was added NBS (0.46 g, 2.5 mmol, 1.1 eq) at −78° C. After 1 hour, the reaction was warmed to room temperature, poured into water (100 mL) and extracted with ethyl acetate (2×100 mL). The organic layers were combined, washed with aqueous 10% sodium bisulfite solution (50 mL), water (50 mL) and brine (50 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Crystallization from 20% ethyl acetate/hexane gave the product (40 mg, 5%) as a white solid. The filtrate (0.5 g) was placed aside. 1H NMR (300 MHz, d6-DMSO): δ 1.64 (s, 6H), 6.98 (d, 1H, J=8.2 Hz), 7.19 (d, 1H, J=1.4 Hz), 7.57 (s, 1H), 7.62 (dd, 1H, J=1.4, 8.3 Hz), 10.43 (s, 1H), 12.91 (s, 1H). MS (ESI) [M−H]−m/z 344/346. Anal. calcd. for C15H12BrN3O2: C, 52.04; H, 3.49; N, 12.14. Found: C, 51.4; H, 3.57; N, 11.59.
Workup
- extractionextracted with ethyl acetate (2×100 mL)
- washwashed with aqueous 10% sodium bisulfite solution (50 mL), water (50 mL) and brine (50 mL)
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
- customCrystallization from 20% ethyl acetate/hexane
Sources & evidence
- ORD record
- ord-536bb3998e8e4931a51c503a1acb384c
- Source dataset
- uspto-grants-2013_07
- Patent number
- US08476262B2
Reaction notes
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