N,N-Dimethyl-2-(6-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)ethanamine → N-(4-(2-(dimethylamino)ethyl)-3,4-dihydro-2H-benzo[b][1,4]thiazin-6-yl)thiophene-2-carboximidamide

HRID 1917225ノート

反応式

HRID 1917225 の反応式
[CH3:1][N:2]([CH3:18])[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][S:8][C:7]2[CH:11]=[CH:12][C:13]([N+:15]([O-])=O)=[CH:14][C:6]1=2.I.[S:20]1[CH:24]=[CH:23][CH:22]=[C:21]1[C:25](SC)=[NH:26]>C(O)C.ClCCl.[Pd]>[CH3:1][N:2]([CH3:18])[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][S:8][C:7]2[CH:11]=[CH:12][C:13]([NH:15][C:25]([C:21]3[S:20][CH:24]=[CH:23][CH:22]=3)=[NH:26])=[CH:14][C:6]1=2

参加物

6

反応物 2

HCID 59144147N,N-Dimethyl-2-(6-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)ethanamineHCID 66704664Methyl thiophene-2-carbimidothioate hydroiodide

生成物 1

HCID 178483713N-(4-(2-(dimethylamino)ethyl)-3,4-dihydro-2H-benzo[b][1,4]thiazin-6-yl)thiophene-2-carboximidamide収率 62.8%

試薬・触媒・溶媒 3

HCID 23938Palladium触媒HCID 702Ethanol溶媒HCID 6344Dichloromethane溶媒

実験手順

A suspension of N,N-dimethyl-2-(6-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)ethanamine (75 mg, 0.281 mmol) and palladium, 10 wt. % on activated carbon (29.9 mg, 0.028 mmol) in ethanol (5 mL) was stirred at room temperature under an atmosphere of hydrogen (balloon pressure) for 90 minutes. During this time, the yellow color of the reaction dissipated. To this mixture was then added methyl thiophene-2-carbimidothioate hydroiodide (160 mg, 0.561 mmol), and the resulting suspension was stirred overnight at room temperature. The mixture was then diluted with dichloromethane and filtered to remove palladium. The organic filtrate was further diluted with water and saturated sodium carbonate (1:1). The organic layer was separated, and the aqueous layer was extracted again with dichloromethane. The combined organics were dried, filtered, concentrated, and then chromatographed in 1:19 (2M NH3 in methanol):ethyl acetate, giving the desired product 27 (61 mg, 62.8%). 1H NMR (DMSO-d6) δ 7.71 (d, J=3.3 Hz, 1H), 7.58 (d, J=5.1 Hz, 1H), 7.10-7.06 (m, 1H), 6.83 (d, J=8.1 Hz, 1H), 6.37 (brs, 2H), 6.17 (s, 1H), 6.08 (d, J=7.8 Hz, 1H), 3.63-3.58 (m, 2H), 3.39-3.32 (m, 2H), 3.01-2.96 (m, 2H), 2.42 (t, J=6.9 Hz, 2H), 2.10 (s, 6H); ESI-MS (m/z, %): 347 (MH+, 100), 276 (74); ESI-HRMS calculated for C17H23N4S2 (MH+), calculated: 347.1358, observed: 347.1349; HPLC purity: 95% by area.

後処理

  1. customDuring this time, the yellow color of the reaction dissipated
  2. filtrationfiltered
  3. customto remove palladium
  4. additionThe organic filtrate was further diluted with water and saturated sodium carbonate (1:1)
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted again with dichloromethane
  7. customThe combined organics were dried
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customchromatographed in 1:19 (2M NH3 in methanol)

出典と根拠

ORDレコード
ord-323543d7a9404d18a632bc0f9d1953f8
出典データセット
uspto-grants-2013_12
特許番号
US08618286B2

反応ノート

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