Potassium Carbonate → 5-(4,4-diethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1-methyl-1H-pyrrole-2-carbonitrile

HRID 915898Notes

Reaction equation

HRID 915898 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:7]#[N:8].C(OB(OC(C)C)OC(C)C)(C)C.C([N-]C(C)C)(C)C.[Li+].Br[C:31]1[CH:45]=[CH:44][C:34]2[NH:35][C:36](=[O:43])[O:37][C:38]([CH2:41][CH3:42])([CH2:39][CH3:40])[C:33]=2[CH:32]=1.C(=O)([O-])[O-].[K+].[K+].[Cl-].[NH4+]>C1COCC1.O>[CH2:41]([C:38]1([CH2:39][CH3:40])[C:33]2[CH:32]=[C:31]([C:6]3[N:2]([CH3:1])[C:3]([C:7]#[N:8])=[CH:4][CH:5]=3)[CH:45]=[CH:44][C:34]=2[NH:35][C:36](=[O:43])[O:37]1)[CH3:42]

Participants

9

Reactant 6

HCID 11430Potassium CarbonateHCID 21531Triisopropyl borateHCID 25517Ammonium ChlorideHCID 20641111-Methylpyrrole-2-carbonitrileHCID 2724682Lithium diisopropylamideHCID 112775676-Bromo-4,4-diethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one

Product 1

HCID 112553235-(4,4-diethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1-methyl-1H-pyrrole-2-carbonitrileYield 55.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-methyl-1H-pyrrole-2-carbonitrile (4.1 g, 35 mmol) and triisopropylborate (8.9 mL, 38.5 mmol) in THF (80 mL) at 0° C. was added lithium diisopropylamide (22.8 mL, 45.5 mmol). The reaction mixture was allowed to warm to room temperature. Upon completion by TLC, the reaction was added dropwise to a 65° C. solution of 6-bromo-4,4-diethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one (2.0 g, 7.0 mmol), potassium carbonate (2.9 g, 21 mmol) dissolved in (25 mL water), and tetrakistriphenylphosphine palladium (0) (0.4 g, 0.35 mmol) in tetrahydrofuran (20 mL). Upon completion by TLC of the reaction, it was poured into a saturated solution of ammonium chloride (200 mL), extracted with ethyl acetate (100 mL), dried with magnesium sulfate, and concentrated. Trituration of the residue with ethyl acetate/dichloromethane gave 5-(4,4-diethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1-methyl-1H-pyrrole-2-carbonitrile (1.2 g, 55%) as an off-white solid. 1H NMR (DMSO-d6): δ 10.26 (s, 1H), 7.37 (d, 1H, J=8.2, 1.6 Hz), 7.31 (d, 1H, J=1.8 Hz), 7.03 (d, 1H, J=4.0 Hz), 6.96 (d, 1H, J=8.2 Hz), 6.32 (d, 1H, J=4.0 Hz), 3.69 (s, 3H), 2.02 (m, 2H, J=7.3 Hz), 1.88 (m, 2H, J=7.3 Hz), 0.78 (t, 6H, J=7.3 Hz). MS (ESI) m/z 310 ([M+H]+); MS (ESI) m/z 308 ([M−H]−). HRMS: calcd for C18H19N3O2, 309.1477; found (ESI_FT), 310.15488;

Workup

  1. customUpon completion by TLC of the reaction, it
  2. extractionextracted with ethyl acetate (100 mL)
  3. dry with materialdried with magnesium sulfate
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-c1e7f4ea1b534fd993058af7d81f7117
Source dataset
uspto-grants-2007_09
Patent number
US07268149B2

Reaction notes

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