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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 1672946
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HRID 1672946 반응식
[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]
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참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6344
Dichloromethane
용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-12e950e2372447d9b8908bc93d0d64eb
출처 데이터셋
uspto-grants-2011_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07999006B2

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