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

HRID 872055Notes

Reaction equation

HRID 872055 reaction equation
[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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-a2c7f09a4a924f00a325f448b1457725
Source dataset
uspto-grants-2015_03
Patent number
US08975261B2

Reaction notes

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