Brofoxine → 5-(4,4-Dimethyl-oxo-1,4-dihydro-2H-3,1-benzoxazine-6-yl)-1H-pyrrole-carbonitrile

HRID 269399Notes

Reaction equation

HRID 269399 reaction equation
C[N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:7]#[N:8].[B].[CH3:10][C:11]1([CH3:23])[O:21][C:19](=[O:20])[NH:18][C:17]2[CH:16]=[CH:15][C:14](Br)=[CH:13][C:12]1=2>>[CH3:10][C:11]1([CH3:23])[C:12]2[CH:13]=[C:14]([C:6]3[NH:2][C:3]([C:7]#[N:8])=[CH:4][CH:5]=3)[CH:15]=[CH:16][C:17]=2[NH:18][C:19](=[O:20])[O:21]1

Participants

4

Reactant 3

HCID 30630BrofoxineHCID 20641111-Methylpyrrole-2-carbonitrileHCID 5462311Boron

Product 1

HCID 102209945-(4,4-Dimethyl-oxo-1,4-dihydro-2H-3,1-benzoxazine-6-yl)-1H-pyrrole-carbonitrile

Procedure

In still a further embodiment, 5-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1H-pyrrole-2-carbonitrile is prepared according to the present invention. This process includes reacting 1-methyl-pyrrole-2-carbonitrile and a boron agent; coupling the boronated carbonitrile with 6-bromo-4,4-dimethyl-1,4-dihydro-2H-3,1-benzoazin-2-one (the Brofoxine™ reagent) to give 5-(4,4-dimethyl-2-oxo-1,4- dihydro -2H-3,1-benzoxazin-6-yl)-1H-pyrrole-2-carbonitrile. See, Scheme 8. Desirably, the boron agent is tri-isopropylborate. The boron agent is typically reacted with the carbonitrile in the presence of lithium di-isopropylamide (LDA) and tri-isopropylborate to give a boronate/borinate mixture which is not isolated. The coupling is typically performed in situ in the presence of a soluble palladium (0) catalyst to give 5-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1H-pyrrole-2-carbonitrile in an unpurified form.

Workup

  1. customIn still a further embodiment, 5-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1H-pyrrole-2-carbonitrile is prepared

Sources & evidence

ORD record
ord-6f2be007aef04207b27728488b9a9235
Source dataset
uspto-grants-2008_11
Patent number
US07446211B2

Reaction notes

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