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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 1917126
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HRID 1917126 반응식
[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
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HCID 591441107-Amino-4-(2-(pyrrolidin-1-yl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-oneHCID 66704664Methyl thiophene-2-carbimidothioate hydroiodide

생성물 1

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

시약·촉매·용매 2

HCID 702Ethanol용매HCID 516892
Sodium Bicarbonate
용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-9d3d1eab51934ccbb5f193e4f9de5c1b
출처 데이터셋
uspto-grants-2013_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08618286B2

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