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 502597노트

반응식

HRID 502597 반응식
[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

참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-1ec7c370ef8b4ed9a0cd6c93e4b01192
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07776847B2

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