Triethylamine → 1-[1-({3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3-yl]-2-(1,3-dioxolan-2-yl)ethyl 2,4,6-tris(1-methylethyl)benzenesulfonate

HRID 1672964Notes

Reaction equation

HRID 1672964 reaction equation
[F:1][C:2]1[C:3]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([I:31])=[CH:27][C:26]=2[F:32])=[C:4]([C:9]([N:11]2[CH2:14][C:13]([CH:16]([OH:23])[CH2:17][CH:18]3[O:22][CH2:21][CH2:20][O:19]3)([OH:15])[CH2:12]2)=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].C(N(CC)CC)C.[CH:40]([C:43]1[CH:48]=[C:47]([CH:49]([CH3:51])[CH3:50])[CH:46]=[C:45]([CH:52]([CH3:54])[CH3:53])[C:44]=1[S:55](Cl)(=[O:57])=[O:56])([CH3:42])[CH3:41].C(OCC)(=O)C>ClCCl.CN(C)C1C=CN=CC=1>[CH3:42][CH:40]([C:43]1[CH:48]=[C:47]([CH:49]([CH3:50])[CH3:51])[CH:46]=[C:45]([CH:52]([CH3:54])[CH3:53])[C:44]=1[S:55]([O:23][CH:16]([C:13]1([OH:15])[CH2:12][N:11]([C:9]([C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([F:1])[C:3]=2[NH:24][C:25]2[CH:30]=[CH:29][C:28]([I:31])=[CH:27][C:26]=2[F:32])=[O:10])[CH2:14]1)[CH2:17][CH:18]1[O:22][CH2:21][CH2:20][O:19]1)(=[O:56])=[O:57])[CH3:41]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 810422,4,6-Tris(1-methylethyl)benzenesulfonyl chloride2×HCID 670518421-({3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[2-(1,3-dioxolan-2-yl)-1-hydroxyethyl]azetidin-3-ol

Product 1

HCID 866212721-[1-({3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3-yl]-2-(1,3-dioxolan-2-yl)ethyl 2,4,6-tris(1-methylethyl)benzenesulfonateYield 14%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
35 °C

Procedure

1-({3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[2-(1,3-dioxolan-2-yl)-1-hydroxyethyl]azetidin-3-ol (148 mg, 0.262 mmol), was dissolved in dichloromethane (10 mL) and treated with 4-(dimethylamino)pyridine (38 mg, 0.31 mmol), triethylamine (0.036 mL, 0.262 mmol) and 2,4,6-triisopropylbenzenesulfonyl chloride (303 mg, 1.0 mmol) at 35° C. for 15 h. 2,4,6-Triisopropylbenzenesulfonyl chloride (100 mg, 0.33 mmol) was added and the mixture was stirred at 35° C. for 3.5 h. The mixture was adsorbed on to silica and purified by column chromatography (silica gel, 40-50% ethyl acetate in hexanes and then 100% ethyl acetate) to give 1-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3-yl]-2-(1,3-dioxolan-2-yl)ethyl 2,4,6-tris(1-methylethyl)benzenesulfonate (30 mg, 0.0361 mmol, 14% yield): MS (EI) for C36H42F3IN2O7S: 831 (MH+).

Workup

  1. custompurified by column chromatography (silica gel, 40-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-56cb8f02f60947bda9a734a091610cb4
Source dataset
uspto-grants-2011_08
Patent number
US07999006B2

Reaction notes

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