Sodium hydride → 5-bromo-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine

HRID 872055Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 872055
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C@H:9]2[CH2:11][C@@H:10]2[CH2:12][OH:13])=[N:7][CH:8]=1.[H-].[Na+].[Br:16][C:17]1[C:18](Cl)=[N:19][C:20]([CH3:23])=[N:21][CH:22]=1.C(=O)(O)[O-].[Na+]>C1COCC1>[Br:16][C:17]1[C:18]([O:13][CH2:12][C@H:10]2[CH2:11][C@@H:9]2[C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][N:7]=2)=[N:19][C:20]([CH3:23])=[N:21][CH:22]=1

Komponenten

6

Edukt 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 249038115-Bromo-4-chloro-2-methylpyrimidineHCID 66834134((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methanol

Produkt 1

HCID 710613855-bromo-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a solution of [(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]methanol (S,S-DD3, ent2) (1.1 g, 6.1 mmol) in THF (25 mL) was added sodium hydride (300 mg, 7.4 mmol). The reaction mixture stirred at ambient temperature for 30 minutes. Next, a solution of 5-bromo-4-chloro-2-methylpyrimidine (MM2) (1.5 g, 7.4 mmol) in THF (5 mL) was added and the reaction mixture was stirred at ambient temperature for two hours. Aqueous sodium bicarbonate (20 mL) was carefully added and the mixture was extracted with EtOAc (2×50 mL). The combined organics were dried over MgSO4, filtered and concentrated to afford the title compound as a yellow oil, which was sufficiently pure to use in the subsequent step without further purification. 1H NMR (500 MHz, DMSO): δ 8.60 (s, 1 H), 8.12 (d, J=3.0 Hz, 1 H), 7.30-7.22 (m, 2 H), 4.42 (d, J=7.1 Hz, 2 H), 3.78 (s, 3 H), 2.50 (s, 3 H), 2.19 (dt, J=8.6, 4.6 Hz, 1 H), 1.75 (s, 1 H), 1.14 (dt, J=8.8, 4.7 Hz, 1 H), 1.04 (dt, J=8.9, 4.7 Hz, 1 H); LRMS m/z (M+H) 350.3 found, 350.2 required.

Aufarbeitung

  1. stirringthe reaction mixture was stirred at ambient temperature for two hours
  2. extractionthe mixture was extracted with EtOAc (2×50 mL)
  3. dry with materialThe combined organics were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-a2c7f09a4a924f00a325f448b1457725
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08975261B2

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