Sodium Iodide → 4-(2-(1-Methylpyrrolidin-2-yl)ethyl)-7-nitro-2H-benzo[b][1,4]oxazin-3(4H)-one

HRID 1917121Notes

Reaction equation

HRID 1917121 reaction equation
[N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[NH:12][C:11](=[O:13])[CH2:10][O:9][C:8]=2[CH:14]=1)([O-:3])=[O:2].Cl.Cl[CH2:17][CH2:18][CH:19]1[CH2:23][CH2:22][CH2:21][N:20]1[CH3:24].[Na+].[I-].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[CH3:24][N:20]1[CH2:21][CH2:22][CH2:23][CH:19]1[CH2:18][CH2:17][N:12]1[C:11](=[O:13])[CH2:10][O:9][C:8]2[CH:14]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=[CH:6][C:7]1=2

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 27638307-nitro-3,4-dihydro-2H-1,4-benzoxazin-3-oneHCID 3017050Pyrrolidine, 2-(2-chloroethyl)-1-methyl-, hydrochloride (1:1)

Product 1

HCID 591441764-(2-(1-Methylpyrrolidin-2-yl)ethyl)-7-nitro-2H-benzo[b][1,4]oxazin-3(4H)-oneYield 67%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A suspension of 7-nitro-2H-benzo[b][1,4]oxazin-3(4H)-one (0.5 g, 2.575 mmol), 2-(2-chloroethyl)-1-methylpyrrolidine hydrochloride (0.94 g, 5.150 mmol), NaI (0.19 g, 1.287 mmol), and K2CO3 (2.13 g, 15.452 mmol) in dry DMF (10 mL) was stirred at room temperature overnight (18 hours). The reaction was diluted with water (150 mL), and the product was extracted into ethyl acetate (2×25 mL). The combined ethyl acetate layers were washed with brine (20 mL) and dried (Na2SO4). The solvent was evaporated, and the crude material was purified by column chromatography (3:97 (2M NH3 in MeOH):CH2Cl2) to obtain the title compound (0.525 g, 67%) as a yellow solid. 1H NMR (DMSO-d6) δ 1.47-1.65 (m, 4H), 1.79-2.13 (m, 4H), 2.18 (s, 3H), 2.89-2.95 (m, 1H), 3.98 (t, 2H, J=7.8 Hz), 4.79 (s, 2H), 7.40 (d, 1H, J=9.0 Hz), 7.80 (d, 1H, J=2.7 Hz), 7.98 (dd, 1H, J=2.4, 9.0 Hz); ESI-MS (m/z, %): 306 (MH+, 100).

Workup

  1. extractionthe product was extracted into ethyl acetate (2×25 mL)
  2. washThe combined ethyl acetate layers were washed with brine (20 mL)
  3. dry with materialdried (Na2SO4)
  4. customThe solvent was evaporated
  5. customthe crude material was purified by column chromatography (3:97 (2M NH3 in MeOH):CH2Cl2)

Sources & evidence

ORD record
ord-812758f6345b4a1c8170973c4846029c
Source dataset
uspto-grants-2013_12
Patent number
US08618286B2

Reaction notes

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