Nitrogen → 2-(2-Chloro-5-cyclopropyl-pyridin-4-ylamino)-N-methoxy-benzamide

HRID 62513Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 62513
N#N.Br[C:4]1[C:5]([NH:11][C:12]2[CH:22]=[CH:21][CH:20]=[CH:19][C:13]=2[C:14]([NH:16][O:17][CH3:18])=[O:15])=[CH:6][C:7]([Cl:10])=[N:8][CH:9]=1.[CH:23]1(B(O)O)[CH2:25][CH2:24]1.[Na+].[Br-].[F-].[K+]>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[Cl:10][C:7]1[CH:6]=[C:5]([NH:11][C:12]2[CH:22]=[CH:21][CH:20]=[CH:19][C:13]=2[C:14]([NH:16][O:17][CH3:18])=[O:15])[C:4]([CH:23]2[CH2:25][CH2:24]2)=[CH:9][N:8]=1

Komponenten

9

Edukt 5

HCID 947NitrogenHCID 253881Sodium BromideHCID 522689Potassium FluorideHCID 2760897Cyclopropylboronic acidHCID 575169052-[(5-bromo-2-chloro-4-pyridinyl)amino]-N-methoxyBenzamide

Produkt 1

HCID 575169062-(2-Chloro-5-cyclopropyl-pyridin-4-ylamino)-N-methoxy-benzamideAusbeute 53 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel2×HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

In a sealable tube toluene (50 mL) was degassed with N2 at 50° C. for 15 min and to this 2-(5-bromo-2-chloro-pyridin-4-ylamino)-N-methoxy-benzamide (1.5 g, 4.21 mmole, 1 eq), cyclopropylboronic acid (1.4 g, 16.85 mmole, 4 eq) and Pd(PPh3)4 (0.24 g, 0.21 mmole, 0.05 eq) were added and resulting mixture was degassed for 30 min. To this NaBr (0.44 g, 4.33 mmole, 1.03 eq) and a solution of KF (0.8 g, 13.90 mmole, 3.3 eq) in H2O (3 mL) were added; again degassed with N2 for 15 min. The tube was sealed and the resulting mixture was heated at 100° C. for 24 h. After completion of reaction, reaction mixture was allowed to cool at room temperature, poured into water (100 mL) and extracted with toluene (2×50 mL). Combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude compound was purified by washing with 0.5% DCM-Et2O to give titled compound as pale yellow solid (0.7 g, 53%). 1H-NMR (400 MHz, DMSO-d6): δ 0.57-072 (m, 2H), 0.97-1.10 (m, 2H), 1.62-1.75 (m, 1H), 3.68 (s, 3H), 7.02 (s, 1H), 7.11-7.20 (m, 1H), 7.51-7.67 (m, 3H), 7.94 (s, 1H), 9.62 (s, 1H), 11.92 (brs, 1H). LC-MS [M+H]+=318.2.

Aufarbeitung

  1. additionwere added
  2. customresulting mixture
  3. customwas degassed for 30 min
  4. customagain degassed with N2 for 15 min
  5. customThe tube was sealed
  6. customAfter completion of reaction, reaction mixture
  7. temperatureto cool at room temperature
  8. extractionextracted with toluene (2×50 mL)
  9. dry with materialCombined organic layer was dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe crude compound was purified
  13. washby washing with 0.5% DCM-Et2O

Quellen und Nachweise

ORD-Eintrag
ord-6f1cd5ff86f74161b75a638967f9a947
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09446034B2

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