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 605721ノート

反応式

HRID 605721 の反応式
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]

参加物

6

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 312751,4-Dioxane溶媒HCID 516892Sodium Bicarbonate溶媒

実験手順

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+).

後処理

  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

出典と根拠

ORDレコード
ord-064bd70f570c414fb0ae621dafe3aad8
出典データセット
uspto-grants-2011_03
特許番号
US07915250B2

反応ノート

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