7-Amino-4-(2-(pyrrolidin-1-yl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one → N-(3-Oxo-4-(2-(pyrrolidin-1-yl)ethyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl) thiophene-2-carboximidamide

HRID 424467Notes

Reaction equation

HRID 424467 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[N:10]([CH2:11][CH2:12][N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[C:9](=[O:18])[CH2:8][O:7][C:6]=2[CH:19]=1.I.[S:21]1[CH:25]=[CH:24][CH:23]=[C:22]1[C:26](SC)=[NH:27]>C(O)C.C([O-])(O)=O.[Na+]>[O:18]=[C:9]1[CH2:8][O:7][C:6]2[CH:19]=[C:2]([NH:1][C:26]([C:22]3[S:21][CH:25]=[CH:24][CH:23]=3)=[NH:27])[CH:3]=[CH:4][C:5]=2[N:10]1[CH2:11][CH2:12][N:13]1[CH2:14][CH2:15][CH2:16][CH2:17]1

Participants

5

Reactant 2

HCID 591441107-Amino-4-(2-(pyrrolidin-1-yl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-oneHCID 66704664Methyl thiophene-2-carbimidothioate hydroiodide

Product 1

HCID 178511897N-(3-Oxo-4-(2-(pyrrolidin-1-yl)ethyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl) thiophene-2-carboximidamideYield 90.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A solution of 7-amino-4-(2-(pyrrolidin-1-yl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (0.125 g, 0.478 mmol) in dry ethanol (5 mL) was treated with methyl thiophene-2-carbimidothioate hydroiodide (0.27 g, 0.956 mmol) at room temperature. The resulting mixture was stirred for 2 days. The reaction was then diluted with saturated NaHCO3 solution (20 mL), and the product was extracted into CH2Cl2 (2×20 mL). The combined CH2Cl2 layers were washed with brine (15 mL) and dried (Na2SO4). The solvent was evaporated, and the crude material was purified by column chromatography (3:97 (2 M NH3 in MeOH):CH2Cl2) to obtain the title compound 3 (0.16 g, 90%) as a solid. 1H NMR (DMSO-d6) δ 1.64-1.72 (m, 4H), 2.46-2.54 (m, 4H, merged with DMSO-d6 resonance), 2.60 (t, 2H, J=7.2 Hz), 3.99 (t, 2H, J=7.2 Hz), 4.58 (s, 2H), 6.47-6.57 (m, 4H), 7.06-7.12 (m, 2H), 7.60 (d, 1H, J=4.2 Hz), 7.73 (d, 1H, J=3.3 Hz); ESI-MS (m/z, %): 371 (MH+, 66), 150 (63), 128 (100); ESI-HRMS calculated for C19H23N4O2S (MH+), calculated: 371.1536, observed: 371.1548; HPLC purity 93.17% by area.

Workup

  1. extractionthe product was extracted into CH2Cl2 (2×20 mL)
  2. washThe combined CH2Cl2 layers were washed with brine (15 mL)
  3. dry with materialdried (Na2SO4)
  4. customThe solvent was evaporated
  5. customthe crude material was purified by column chromatography (3:97 (2 M NH3 in MeOH):CH2Cl2)

Sources & evidence

ORD record
ord-dfe7aab7c36f4932a154cc19d6c6792b
Source dataset
uspto-grants-2012_01
Patent number
US08106043B2

Reaction notes

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