Diisopropylethylamine → N-(3-(isothiazolo[5,4-b]pyridin-3-ylamino)propyl)-N-((4'-methoxybiphenyl-4-yl)methyl)-1,2-dimethyl-1H-imidazole-4-sulfonamide

HRID 502597ノート

反応式

HRID 502597 の反応式
[S:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3]([NH:10][CH2:11][CH2:12][CH2:13][NH:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)=[CH:18][CH:17]=2)=[N:2]1.C(N(C(C)C)CC)(C)C.[CH3:39][N:40]1[CH:44]=[C:43]([S:45](Cl)(=[O:47])=[O:46])[N:42]=[C:41]1[CH3:49]>C(Cl)Cl>[S:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3]([NH:10][CH2:11][CH2:12][CH2:13][N:14]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:23]=[CH:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=3)=[CH:18][CH:17]=2)[S:45]([C:43]2[N:42]=[C:41]([CH3:49])[N:40]([CH3:39])[CH:44]=2)(=[O:47])=[O:46])=[N:2]1

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 27362561,2-Dimethylimidazole-4-sulfonyl chlorideHCID 58726876N1-(isothiazolo[5,4-b]pyridin-3-yl)-N3-((4'-methoxybiphenyl-4-yl)methyl)propane-1,3-diamine

生成物 1

HCID 58727123N-(3-(isothiazolo[5,4-b]pyridin-3-ylamino)propyl)-N-((4'-methoxybiphenyl-4-yl)methyl)-1,2-dimethyl-1H-imidazole-4-sulfonamide収率 32%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

N1-(Isothiazolo[5,4-b]pyridin-3-yl)-N3-((4′-methoxybiphenyl-4-yl)methyl)propane-1,3-diamine (100 mg, 0.25 mmol) was dissolved in anhydrous methylene chloride with diisopropylethylamine (0.11 mL, 0.63 mmol). The mixture was cooled in an ice-bath under nitrogen and a solution of 1,2-dimethylimidazole-4-sulfonyl chloride (58.4 mg, 0.30 mmol) in methylene chloride (5 mL) was added dropwise. After the addition was completed the ice-bath was removed and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with methylene chloride and then washed successively with saturated sodium bicarbonate solution and brine. The organic solution was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by prep-scale reverse phase high performance liquid chromatography to yield N-(3-(isothiazolo[5,4-b]pyridin-3-ylamino)propyl)-N-((4′-methoxybiphenyl-4-yl)methyl)-1,2-dimethyl-1H-imidazole-4-sulfonamide (45 mg). 1H NMR (300 MHz, DMSO-d6): 8.64-8.66 (d, 1H), 8.45-8.50 (d, 1H), 7.52-7.75 (m, 8H), 7.28 (s, 1H), 6.95 (s, 1H), 6.82 (s, 1H), 3.99 (s, 2H), 3.89 (s, 3H), 3.55-3.65 (m, 5H), 2.88-2.90 (t, 2H), 2.50 (s, 3H), 1.99-2.10 ppm (t, 2H). MW=563 confirmed by LC-MS, tr=4.31 min (Method E) MH+=564.

後処理

  1. temperatureThe mixture was cooled in an ice-bath under nitrogen
  2. additionAfter the addition
  3. customwas removed
  4. additionThe reaction mixture was diluted with methylene chloride
  5. washwashed successively with saturated sodium bicarbonate solution and brine
  6. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by prep-scale reverse phase high performance liquid chromatography

出典と根拠

ORDレコード
ord-1ec7c370ef8b4ed9a0cd6c93e4b01192
出典データセット
uspto-grants-2010_08
特許番号
US07776847B2

反応ノート

読み込み中…