Triphenylphosphine → (2,5-Dichloro-pyrimidin-4-yl)-{2-fluoro-6-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-amine

HRID 1041709

Reaktionsgleichung

Reaktionsgleichung von HRID 1041709
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=2[OH:16])[C:5]([Cl:17])=[CH:4][N:3]=1.[O:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]1[O:24][CH2:25][CH2:26]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>C(Cl)Cl>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[C:10]([O:16][CH2:26][CH2:25][O:24][CH:19]3[CH2:20][CH2:21][CH2:22][CH2:23][O:18]3)=[CH:11][CH:12]=[CH:13][C:14]=2[F:15])[C:5]([Cl:17])=[CH:4][N:3]=1

Komponenten

6

Edukt 4

HCID 11776Triphenylphosphine2×HCID 97268Di-tert-butyl azodicarboxylate2×HCID 41668332-(Oxan-2-yloxy)ethan-1-ol2×HCID 866339952-(2,5-Dichloro-pyrimidin-4-ylamino)-3-fluoro-phenol

Produkt 1

HCID 86634071(2,5-Dichloro-pyrimidin-4-yl)-{2-fluoro-6-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-amineAusbeute 44,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a suspension of 2-(2,5-Dichloro-pyrimidin-4-ylamino)-3-fluoro-phenol (0.150 g, 0.547 mmol), 2-(Tetrahydro-pyran-2-yloxy)-ethanol (0.0960 g, 0.657 mmol), and Triphenylphosphine (0.230 g, 0.876 mmol) in Methylene chloride (6 mL) cooled to 0° C. on an ice bath was slowly added Di-tert-butyl azodicarboxylate (0.202 g, 0.876 mmol), at which time a solution formed. The reaction mixture was stirred at rt overnight. The reaction did not go to completion so equal amounts of 2-(Tetrahydro-pyran-2-yloxy)-ethanol, Triphenylphosphine, Methylene chloride, and Di-tert-butyl azodicarboxylate were added as were at the start of the reaction and stirred. The reaction mixture was then concentrated and dissolved in minimal amounts of DCM. It was then purified by silica gel chromatography (ISCO, 0-30% EtOAc) to give (2,5-Dichloro-pyrimidin-4-yl)-{2-fluoro-6-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-amine as a clear oil (98 mg, 44%). 1H-NMR (CDCl3): 8.17 (s, 1H), 7.22 (m, 1H), 6.93 (s, 1H), 6.82 (m, 2H), 4.63 (s, 1H), 4.22 (m, 2H), 3.98 (m, 1H), 3.74 (m, 2H), 3.47 (m, 1H), 1.67 (m, 2H), 1.55 (m, 2H) 1.49 (m, 2H)

Aufarbeitung

  1. customat which time a solution formed
  2. additionwere added
  3. customas were at the start of the reaction
  4. stirringstirred
  5. concentrationThe reaction mixture was then concentrated
  6. dissolutiondissolved in minimal amounts of DCM
  7. customIt was then purified by silica gel chromatography (ISCO, 0-30% EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-6847a5510b3842dca6f95e47b36458a3
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08552186B2

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