Diisopropylethylamine → 1,1-Dimethylethyl {[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidine-3-yl]methyl}carbamate

HRID 1672904Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1672904
[CH3:1][C:2]([O:5][C:6]([NH:8][CH2:9][C:10]1([OH:24])[CH2:13][N:12]([C:14]([O:16]CC2C=CC=CC=2)=O)[CH2:11]1)=[O:7])([CH3:4])[CH3:3].CCN(C(C)C)C(C)C.[F:34][C:35]1[C:36]([NH:45][C:46]2[CH:51]=[CH:50][C:49]([I:52])=[CH:48][C:47]=2[F:53])=[C:37]([CH:41]=[CH:42][C:43]=1[F:44])C(F)=O>[Pd].CO>[F:34][C:35]1[C:36]([NH:45][C:46]2[CH:51]=[CH:50][C:49]([I:52])=[CH:48][C:47]=2[F:53])=[C:37]([C:14]([N:12]2[CH2:11][C:10]([CH2:9][NH:8][C:6](=[O:7])[O:5][C:2]([CH3:1])([CH3:3])[CH3:4])([OH:24])[CH2:13]2)=[O:16])[CH:41]=[CH:42][C:43]=1[F:44]

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 594691583,4-Difluoro-2-(2-fluoro-4-iodoanilino)benzoyl fluorideHCID 67051555Benzyl 3-({[(tert-butoxy)carbonyl]amino}methyl)-3-hydroxyazetidine-1-carboxylate

Produkt 1

HCID 685160531,1-Dimethylethyl {[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidine-3-yl]methyl}carbamateAusbeute 66 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 23938PalladiumKatalysatorHCID 887MethanolLösungsmittel

Versuchsvorschrift

Phenylmethyl 3-[({[(1,1-dimethylethyl)oxy]carbonyl}amino)methyl]-3-hydroxyazetidine-1-carboxylate (16.5 mg, 0.05 mmol) and 10% Pd/C (8 mg) were taken into methanol (2 mL) and hydrogenated at ambient pressure over 12 hours. The catalyst was removed by filtration and the filtrate concentrated and dried in vacuo. The residue was taken into THF (1 mL) followed by addition of DIPEA (10 μL, 0.06 mmol) and 3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzoyl fluoride (19.8 mg, 0.05 mmol), prepared using procedures similar to those described in Reference 1, and the solution was stirred at room temperature for 30 minutes. Concentration and purification of the residue by silica gel flash chromatography using hexanes:ethyl acetate (1:1.5) afforded 1,1-dimethylethyl {[1-({3,4-difluoro-2[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidine-3-yl]methyl}carbamate (19 mg, 66% yield).

Aufarbeitung

  1. customThe catalyst was removed by filtration
  2. concentrationthe filtrate concentrated
  3. customdried in vacuo
  4. customprepared
  5. concentrationConcentration and purification of the residue by silica gel flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-2771084366db4b28a83d8ad148675230
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US07999006B2

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