Potassium Phosphate, Tribasic → 2,6-Difluoro-3-[4-(4-methoxy-phenyl)-5-pyridin-3-yl-thiazol-2-ylmethoxy]-benzamide

HRID 415588Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 415588
Br[C:2]1[S:6][C:5]([CH2:7][O:8][C:9]2[C:10]([F:19])=[C:11]([C:15]([F:18])=[CH:16][CH:17]=2)[C:12]([NH2:14])=[O:13])=[N:4][C:3]=1[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1.[N:28]1[CH:33]=[CH:32][CH:31]=[C:30](B(O)O)[CH:29]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O.[Pd+2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:19][C:10]1[C:9]([O:8][CH2:7][C:5]2[S:6][C:2]([C:30]3[CH:29]=[N:28][CH:33]=[CH:32][CH:31]=3)=[C:3]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[N:4]=2)=[CH:17][CH:16]=[C:15]([F:18])[C:11]=1[C:12]([NH2:14])=[O:13]

Komponenten

6

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 27343783-Pyridinylboronic acidHCID 594026583-[5-Bromo-4-(4-methoxy-phenyl)-thiazol-2-ylmethoxy]-2,6-difluoro-benzamide

Produkt 1

HCID 594028712,6-Difluoro-3-[4-(4-methoxy-phenyl)-5-pyridin-3-yl-thiazol-2-ylmethoxy]-benzamideAusbeute 551,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 21584511triphenylphosphine palladium (II)KatalysatorHCID 21962138N,N-Dimethylformamide--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a solution of 3-[5-bromo-4-(4-methoxy-phenyl)-thiazol-2-ylmethoxy]-2,6-difluoro-benzamide (0.1 g, 0.02 mmol) in DMF:H2O (2:1), 3-pyridine boronic acid (0.054 g, 0.04 mmol), potassium phosphate (0.056 g, 0.025 mmol) was added. The reaction mixture was degassed for 10 min and then dichlorobis [(triphenylphosphine)-Palladium (II) (0.023 g, 0.003 mmol) was added and again degassed for 10 min. The reaction mixture was heated at 120° C. for 12 h under the nitrogen atmosphere. DMF was distilled off, after cooling to r.t., water was added into reaction mixture and extracted with ethyl acetate, The combined organic layers were dried over anhydrous Na2SO4, and evaporated to dryness under reduced pressure. The compound was purified by chromatography on silica (230-400μ) using ethyl acetate/hexane (50:50) as the eluent to provide the title compound as yellow solid (0.050 g, 50%). 1H NMR (DMSO-d6, 400 MHz): δ 3.75 (s, 3H), 5.59 (s, 2H), 6.92 (d, 2H, J=8.8 Hz (o-coupling), 7.14 (dt, 1H, J=9.2 Hz (o-coupling), 7.36 (d, 2H, J=8.4 Hz (o-coupling), 7.45 (dt, 2H, J=9.2 Hz (o-coupling) J=5.2 Hz (o-coupling), 7.79 (m, 1H), 7.88 (broad s, 1H), 8.16 (broad s, 1H), 8.53 (d, 1H, J=2.0 Hz (m-coupling), 8.57 (d, 1H, J=4.8 Hz). MS ES+ (454.10), HPLC (method 5) Rt=15.26 min.

Aufarbeitung

  1. customThe reaction mixture was degassed for 10 min
  2. additionwas added
  3. customagain degassed for 10 min
  4. distillationDMF was distilled off
  5. temperatureafter cooling to r.t.
  6. additionwater was added into reaction mixture
  7. extractionextracted with ethyl acetate
  8. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  9. customevaporated to dryness under reduced pressure
  10. customThe compound was purified by chromatography on silica (230-400μ)

Quellen und Nachweise

ORD-Eintrag
ord-b5777d64c19a4c16ad2c3c340c2ae5b6
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08088791B2

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