3,4-Difluoro-2-(2-fluoro-4-iodoanilino)benzoyl fluoride → 1-({3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(1-methylethyl)amino]methyl}azetidin-3-amine

HRID 1672918노트

반응식

HRID 1672918 반응식
Cl.[CH3:2][CH:3]([NH:5][CH2:6][C:7]1([NH2:11])[CH2:10][NH:9][CH2:8]1)[CH3:4].[F:12][C:13]1[C:14]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([I:30])=[CH:26][C:25]=2[F:31])=[C:15]([CH:19]=[CH:20][C:21]=1[F:22])[C:16](F)=[O:17]>C(=O)(O)[O-].[Na+].O1CCOCC1.O>[F:12][C:13]1[C:14]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([I:30])=[CH:26][C:25]=2[F:31])=[C:15]([C:16]([N:9]2[CH2:10][C:7]([CH2:6][NH:5][CH:3]([CH3:4])[CH3:2])([NH2:11])[CH2:8]2)=[O:17])[CH:19]=[CH:20][C:21]=1[F:22]

참가 물질

6

반응물 2

HCID 594691583,4-Difluoro-2-(2-fluoro-4-iodoanilino)benzoyl fluorideHCID 670519473-{[(1-Methylethyl)amino]methyl}azetidin-3-amine hydrochloride

생성물 1

HCID 162230231-({3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(1-methylethyl)amino]methyl}azetidin-3-amine수율 37%

시약·촉매·용매 3

HCID 962Water용매HCID 312751,4-Dioxane용매HCID 516892Sodium Bicarbonate용매

실험 절차

To a mixture of the 3-{[(1-methylethyl)amino]methyl}azetidin-3-amine hydrochloride (20 mg, 0.079 mmol) in saturated sodium bicarbonate solution (1.0 mL) and dioxane (1.0 mL) was added 3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzoyl fluoride (31 mg, 0.079 mmol), prepared using procedures similar to those described in Reference 1, and the resulting mixture was stirred at room temperature for 18 h. The reaction mixture was diluted with water (5 mL) and extracted with ethyl acetate (3×5 mL). The combined extract was washed with water then brine solution (5 mL each), dried over sodium sulfate, filtered and concentrated to give an oily residue which was purified by reverse phase HPLC to afford 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(1-methylethyl)amino]methyl}azetidin-3-amine (15 mg, 37% yield). 1H NMR (400 MHz, d4-Methanol): 7.46-7.43 (dd, 1H), 7.35-7.33 (dd, 1H), 7.31-7.27 (m, 1H), 7.08-7.01 (dd, 1H), 6.63, 6.58 (td, 1H), 4.09-4.07 (d, 1H), 3.91-3.85 (dd, 2H), 3.76-3.73 (d, 1H), 2.80-2.74 (m, 1H), 2.73 (s, 2H), 1.07-1.05 (d, 6H); MS (EI) for C20H22F3IN4O: 519 (MH+).

후처리

  1. customprepared
  2. extractionextracted with ethyl acetate (3×5 mL)
  3. extractionThe combined extract
  4. washwas washed with water
  5. dry with materialbrine solution (5 mL each), dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give an oily residue which
  9. customwas purified by reverse phase HPLC

출처 및 근거

ORD 기록
ord-c09eb007a8a445e5a05e4d3571f13cf7
출처 데이터셋
uspto-grants-2011_08
특허 번호
US07999006B2

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