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Diisopropylethylamine → 1,1-dimethylethyl {(1R)-1-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3-yl]ethyl}carbamate

HRID 1717604
ノート
印刷プレビュー

反応式

HRID 1717604 の反応式
[OH:1][C:2]1([C@H:6]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH3:7])[CH2:5][NH:4][CH2:3]1.C(N(C(C)C)CC)(C)C.[F:25][C:26]1[C:27]([NH:36][C:37]2[CH:42]=[CH:41][C:40]([I:43])=[CH:39][C:38]=2[F:44])=[C:28]([CH:32]=[CH:33][C:34]=1[F:35])[C:29](F)=[O:30]>ClCCl>[F:25][C:26]1[C:27]([NH:36][C:37]2[CH:42]=[CH:41][C:40]([I:43])=[CH:39][C:38]=2[F:44])=[C:28]([C:29]([N:4]2[CH2:3][C:2]([C@H:6]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH3:7])([OH:1])[CH2:5]2)=[O:30])[CH:32]=[CH:33][C:34]=1[F:35]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 594691583,4-Difluoro-2-(2-fluoro-4-iodoanilino)benzoyl fluorideHCID 86621270HCID 86621270、化合物

生成物 1

HCID 689021591,1-dimethylethyl {(1R)-1-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3-yl]ethyl}carbamate収率 61%

試薬・触媒・溶媒 1

HCID 6344
Dichloromethane
溶媒

実験手順

To a solution of 1,1-dimethylethyl [(1R)-1-(3-hydroxyazetidin-3-yl)ethyl]carbamate (200 mg, 0.92 mmol) in dichloromethane (5 mL) was added diisopropylethylamine (228 μL, 1.38 mmol) and 3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzoyl fluoride (prepared according to the procedures described in Reference 1) (363 mg, 0.92 mmol). The mixture was stirred at rt for 16 h, after which the volatile materials were removed in vacuo. The residue was purified by column chromatography (50% hexanes: 50% ethyl acetate) to provide 1,1-dimethylethyl {(1R)-1-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3-yl]ethyl}carbamate as a colorless film (333 mg, 0.56 mmol, 61% yield). 1H NMR (400 MHz, CDCl3) δ 8.47 (br s, 1H), 7.40 (dd, 1H), 7.32 (d, 1H), 7.12 (m, 1H), 6.81 (m, 1H), 6.61 (m, 1H), 4.74 (br d, 1H), 4.22 (d, 1H), 4.15-4.07 (m, 2H), 3.96 (br s, 1H), 3.77 (m, 1H), 1.43 (s, 9H), 1.18 (d, 3H); MS (EI) for C23H25F3IN3O4: 536 (M-tert-butyl+H).

後処理

  1. customprepared
  2. customafter which the volatile materials were removed in vacuo
  3. customThe residue was purified by column chromatography (50% hexanes: 50% ethyl acetate)

出典と根拠

ORDレコード
ord-aeb6f6a1c87c418d9e602a60aba1bff6
出典データセット
uspto-grants-2010_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07803839B2

反応ノート

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