N,N-Dimethyl-2-(7-nitro-2H-benzo[b][1,4]oxazin-4(3H)-yl)ethanamine → 4-(2-(dimethylamino)ethyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-amine

HRID 424475Notes

Reaction equation

HRID 424475 reaction equation
[CH3:1][N:2]([CH3:18])[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][O:8][C:7]2[CH:11]=[C:12]([N+:15]([O-])=O)[CH:13]=[CH:14][C:6]1=2>[Pd]>[CH3:1][N:2]([CH3:18])[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][O:8][C:7]2[CH:11]=[C:12]([NH2:15])[CH:13]=[CH:14][C:6]1=2

Participants

3

Reactant 1

HCID 66704389N,N-Dimethyl-2-(7-nitro-2H-benzo[b][1,4]oxazin-4(3H)-yl)ethanamine

Product 1

HCID 283221974-(2-(dimethylamino)ethyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-amine

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

A suspension of N,N-dimethyl-2-(7-nitro-2H-benzo[b][1,4]oxazin-4(3H)-yl)ethanamine (210 mg, 0.836 mmol) and Pd—C (10% wt, 89 mg, 0.084 mmol) in dry EtOH (15 mL) was purged with hydrogen gas. The reaction was stirred at room temperature for 3 hours under hydrogen atmosphere (balloon pressure). The reaction mixture was then filtered through a Celite pad and washed with EtOH (15 mL). The light purple filtrate was concentrated to give crude 4-(2-(dimethylamino)ethyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-amine. A solution of this crude 4-(2-(dimethylamino)ethyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-amine (185 mg, 0.836 mmol) in dry EtOH (10 mL) was treated with methyl thiophene-2-carbimidothioate hydroiodide (477 mg, 1.672 mmol) and stirred overnight at room temperature. The reaction was diluted with saturated NaHCO3 solution (50 mL) and the product was extracted into CH2Cl2 (3×25 mL). The combined organic layers were dried (Na2SO4) and concentrated. The residue was subjected to flash chromatography on silica gel using 2:98 MeOH:CH2Cl2, followed by 5:95 (2M NH3 in MeOH):CH2Cl2, to give a yellow solid (150 mg, 54%). 1H-NMR (DMSO-d6) δ 7.69 (dd, J=3.6, 0.9 Hz, 1H), 7.56 (dd, J=5.1, 0.9 Hz, 1H), 7.07 (dd, J=5.1, 3.9 Hz, 1H), 6.64 (d, J=8.4 Hz, 1H), 6.35-6.26 (m, 4H), 4.14 (t, J=3.9 Hz, 2H), 3.33-3.29 (m, 4H), 2.42 (t, J=6.9 Hz, 2H), 2.19 (s, 6H); ESI-MS (m/z, %): 331 (MH+, 100), 260 (25); ESI-HRMS calculated for C17H23N4OS (MH+): 331.1587, Observed: 331.1594; HPLC purity: 99.0% by area.

Workup

  1. custom89 mg, 0.084 mmol) in dry EtOH (15 mL) was purged with hydrogen gas
  2. filtrationThe reaction mixture was then filtered through a Celite pad
  3. washwashed with EtOH (15 mL)
  4. concentrationThe light purple filtrate was concentrated

Sources & evidence

ORD record
ord-b524609296da4e19a390c01c4ff7ed76
Source dataset
uspto-grants-2012_01
Patent number
US08106043B2

Reaction notes

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