HCID 10680516, compound → HCID 178483710, compound

HRID 1917149Notes

Reaction equation

HRID 1917149 reaction equation
[CH3:1][N:2]([CH3:16])[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][O:8][C:7]2[CH:11]=[CH:12][C:13]([NH2:15])=[CH:14][C:6]1=2.I.[S:18]1[CH:22]=[CH:21][CH:20]=[C:19]1[C:23](SC)=[NH:24]>>[CH3:1][N:2]([CH3:16])[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][O:8][C:7]2[CH:11]=[CH:12][C:13]([NH:15][C:23]([C:19]3[S:18][CH:22]=[CH:21][CH:20]=3)=[NH:24])=[CH:14][C:6]1=2

Participants

3

Reactant 2

HCID 10680516HCID 10680516, compoundHCID 66704664Methyl thiophene-2-carbimidothioate hydroiodide

Product 1

HCID 178483710HCID 178483710, compound

Procedure

To a stirred ethanolic solution of 4-(2-(dimethylamino)ethyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine (0.088 g, 0.398 mmol) under an argon atmosphere was added methyl thiophene-2-carbimidothioate hydroiodide (0.227 g, 0.795 mmol). The resulting faintly cloudy yellow mixture stirred overnight at room temperature. After 20 hours, argon was bubbled through the mixture, which was then concentrated to afford a residue. The residue was then partitioned between EtOAc (100 mL) and saturated NaHCO3 (˜10 mL) solution. The aqueous layer (pH˜9) was further extracted with EtOAc, and the combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated to yield a yellow residue. Purification on silica gel (dry chromatography, eluting with 5-7.5% (2M NH3MeOH)/CH2Cl2) yielded the title compound 9 as a yellow residue (70 mg, 53.3%). 1H NMR (DMSO-d6) δ 7.70 (d, 1H, J=2.7 Hz), 7.57 (d, 111, J=5.0 Hz), 7.07 (dd, 1H, J=5.0, 3.7 Hz), 6.59 (d, 1H, J=8.2 Hz), 6.30 (brs, 2H), 6.14 (s, 1H), 6.00 (d, 1H, J=8.1 Hz), 4.18-4.02 (m, 2H), 3.41-3.25 (m, 4H+H2O), 2.41 (t, 2H, J=6.7 Hz), 2.17 (s, 6H); ESI-MS (m/z, %): 331 (MH+, 100).

Workup

  1. waitAfter 20 hours
  2. customargon was bubbled through the mixture, which
  3. concentrationwas then concentrated
  4. customto afford a residue
  5. customThe residue was then partitioned between EtOAc (100 mL) and saturated NaHCO3 (˜10 mL) solution
  6. extractionThe aqueous layer (pH˜9) was further extracted with EtOAc
  7. washthe combined organic layers were washed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto yield a yellow residue
  12. customPurification on silica gel (dry chromatography, eluting with 5-7.5% (2M NH3MeOH)/CH2Cl2)

Sources & evidence

ORD record
ord-95d14114a6734e30be1478906e8589c3
Source dataset
uspto-grants-2013_12
Patent number
US08618286B2

Reaction notes

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