Tetrahydrofuran → 5-bromo-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine
Reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([C@H:11]2[CH2:13][C@@H:12]2[CH2:14][OH:15])=[N:9][CH:10]=1.[Br:16][C:17]1[C:18](Cl)=[N:19][C:20](Cl)=[N:21][CH:22]=1.[CH2:25]1COCC1>>[Br:16][C:17]1[C:18]([O:15][CH2:14][C@H:12]2[CH2:13][C@@H:11]2[C:8]2[CH:7]=[CH:6][C:5]([O:4][CH3:3])=[CH:10][N:9]=2)=[N:19][C:20]([CH3:25])=[N:21][CH:22]=1Participants
Procedure
NaH (78 mg, 1.95 mmol, 60% disp.) was added to a stirring solution of [(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]methanol (S,S-DD3, ent2) (350 mg, 1.953 mmol) and 5-bromo-2,4-dichloropyrimidine (445 mg, 1.953 mmol) in THF (9.77 mL). The reaction mixture was stirred at room temperature for 1 hour, and then quenched by dropwise addition of saturated aqueous NaHCO3. The reaction mixture was diluted with EtOAc (50 mL), and washed with saturated aqueous NaHCO3 (50 mL) and brine (50 mL). The organics were dried over MgSO4, filtered, and concentrated in vacuo to afford the title compound as an orange gum. The unpurified product was sufficiently pure to use in the subsequent step without further purification. LRMS m/z (M+H) 372.2 found, 372.0 required.
Workup
- customquenched by dropwise addition of saturated aqueous NaHCO3
- additionThe reaction mixture was diluted with EtOAc (50 mL)
- washwashed with saturated aqueous NaHCO3 (50 mL) and brine (50 mL)
- dry with materialThe organics were dried over MgSO4
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-ef668a5f107a4b8ca7fcc0b2709c4cf5
- Source dataset
- uspto-grants-2015_03
- Patent number
- US08975261B2
Reaction notes
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