Acetic Acid → 2-(2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-(dipyridin-3-ylmethyl)-N-methylpyridine-3-amine

HRID 1661133Notes

Reaction equation

HRID 1661133 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]([C:11]2[C:16]([NH:17][CH:18]([C:25]3[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=3)[C:19]3[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=3)=[CH:15][CH:14]=[CH:13][N:12]=2)[CH2:3][CH2:2]1.[H-].[Na+].[C:33](O)(=O)C>CN(C=O)C.CI.C(OCC)(=O)C>[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]([C:11]2[C:16]([N:17]([CH:18]([C:19]3[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=3)[C:25]3[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=3)[CH3:33])=[CH:15][CH:14]=[CH:13][N:12]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 24758Sodium hydrideHCID 166780742-(2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-(dipyridin-3-ylmethyl)pyridine-3-amine

Product 1

HCID 247601922-(2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-(dipyridin-3-ylmethyl)-N-methylpyridine-3-amine

Reagents, catalysts & solvents 3

HCID 6328Methyl iodideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-(dipyridin-3-ylmethyl)pyridine-3-amine (82 mg, 0.207 mmol) in dry DMF (1.5 mL) was added 60% sodium hydride/mineral oil (16 mg, 0.40 mmol) and let stir at ambient temperature for 15 minutes. Over a one hour period methyl iodide (3 drops) was added. The reaction was diluted with ethyl acetate, neutralized with acetic acid, and washed with water (3×). The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent evaporated. The residue was purified by chromatography on silica gel eluting with a 20-90% acetone/hexane gradient to give the title compound as a white solid. 1H-NMR (500 MHz, CDCl3): δ 8.50 (2H, d, J=4.6 Hz), 8.19 (2H, s), 8.16 (1H, d, J=4.4 Hz), 7.25 (2H, d, J=6.4 Hz), 7.15-7.17 (2H, m), 7.01 (21H, m), 6.75-6.84 (4H, m), 6.57 (1H, d, J=7.8 Hz), 6.01 (1H, s), 4.16 (2H, t, J=4.4 Hz), 3.86 (2H, t, J=4.4 Hz), 2.53 (3H, s). m/e (m+1): 410.2

Workup

  1. washwashed with water (3×)
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. customthe solvent evaporated
  5. customThe residue was purified by chromatography on silica gel eluting with a 20-90% acetone/hexane gradient

Sources & evidence

ORD record
ord-6c157cbee59a4fcaa0ba30d648ba68f9
Source dataset
uspto-grants-2011_10
Patent number
US08030332B2

Reaction notes

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