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 1672946Notes

Reaction equation

HRID 1672946 reaction equation
[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]

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-12e950e2372447d9b8908bc93d0d64eb
Source dataset
uspto-grants-2011_08
Patent number
US07999006B2

Reaction notes

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