Potassium Carbonate → 1-methyl-5-(2-oxo-1,2-dihydrospiro [3,1-benzoxazine-4,1'-cyclobutan]-6-yl)-1H-pyrrole-2-carbonitrile

HRID 915896Notes

Reaction equation

HRID 915896 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:32]=[CH:33][C:34]2[NH:43][C:42](=[O:44])[O:41][C:37]3([CH2:40][CH2:39][CH2:38]3)[C:35]=2[CH:36]=1.C(=O)([O-])[O-].[K+].[K+].[Cl-].[NH4+]>C1COCC1.O>[CH3:1][N:2]1[C:6]([C:31]2[CH:32]=[CH:33][C:34]3[NH:43][C:42](=[O:44])[O:41][C:37]4([CH2:40][CH2:39][CH2:38]4)[C:35]=3[CH:36]=2)=[CH:5][CH:4]=[C:3]1[C:7]#[N:8]

Participants

9

Reactant 6

HCID 11430Potassium CarbonateHCID 21531Triisopropyl borateHCID 25517Ammonium ChlorideHCID 20641111-Methylpyrrole-2-carbonitrileHCID 2724682Lithium diisopropylamideHCID 112426146-bromospiro[3,1-benzoxazine-4,1'-cyclobutan]-2(1H)-one

Product 1

HCID 113583221-methyl-5-(2-oxo-1,2-dihydrospiro [3,1-benzoxazine-4,1'-cyclobutan]-6-yl)-1H-pyrrole-2-carbonitrileYield 80.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-methyl-1H-pyrrole-2-carbonitrile (0.84 g, 7.1 mmol) and triisopropylborate (1.8 mL, 7.8 mmol) in THF (15 mL) at 0° C. was added lithium diisopropylamide (4.6 mL, 9.2 mmol). The reaction was allowed to warm to room temperature. Upon completion by TLC, the reaction was added dropwise to a 65° C. solution of 6-bromospiro[3,1-benzoxazine-4,1′-cyclobutan]-2(1H)-one (0.38 g, 1.4 mmol), potassium carbonate (0.58 g, 4.2 mmol) dissolved in (5 mL water), and tetrakistriphenylphosphine palladium (0) (0.081 g, 0.07 mmol) in tetrahydrofuran (10 mL). Upon completion by TLC of the reaction the reaction mixture was poured into a saturated solution of ammonium chloride (100 mL), extracted with ethyl acetate (50 mL), dried with magnesium sulfate, and purified on a silica gel column (40% ethyl acetate/hexane) to give 1-methyl-5-(2-oxo-1,2-dihydrospiro[3,1-benzoxazine-4,1′-cyclobutan]-6-yl)-1H-pyrrole-2-carbonitrile (0.33 g, 79%) as a light red solid. 1H NMR (DMSO-d6): δ 10.41 (s, 1H), 7.58 (d, 1H, J=2 Hz), 7.43 (dd, 1H, J=8.2, 1.8 Hz), 7.04 (d, 1H, J=4.0 Hz), 6.39 (d, 1H, J=8.2 Hz), 6.39 (d, 1H, J=4.0 Hz), 3.73 (s, 3H), 2.55-2.49 (m, 2H), 2.05-1.90 (m, 2H), 1.88-1.83 (m, 2H). MS (ESI) m/z 294 ([M+H]+); MS (ESI) m/z 292 ([M−H]−). High resolution mass spectrometry (HRMS): calcd for C17H15N3O2, 293.1164; found (ESI_FT), 294.12311.

Workup

  1. customUpon completion by TLC of the reaction the reaction mixture
  2. extractionextracted with ethyl acetate (50 mL)
  3. dry with materialdried with magnesium sulfate
  4. custompurified on a silica gel column (40% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-28a12cc7ef4f4d18b0c593656d240a26
Source dataset
uspto-grants-2007_09
Patent number
US07268149B2

Reaction notes

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