Diisopropylamine → N-(1-Adamantylmethyl)-5-bromo-2-methoxyisonicotinamide

HRID 1247610Notes

Reaction equation

C([Li])CCC.C(NC(C)C)(C)C.[Br:13][C:14]1[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[N:18][CH:19]=1.[C:22]12([CH2:32][N:33]=[C:34]=[O:35])[CH2:31][CH:26]3[CH2:27][CH:28]([CH2:30][CH:24]([CH2:25]3)[CH2:23]1)[CH2:29]2>O1CCCC1.[Cl-].[Na+].O>[C:22]12([CH2:32][NH:33][C:34](=[O:35])[C:15]3[C:14]([Br:13])=[CH:19][N:18]=[C:17]([O:20][CH3:21])[CH:16]=3)[CH2:31][CH:26]3[CH2:27][CH:28]([CH2:30][CH:24]([CH2:25]3)[CH2:23]1)[CH2:29]2

Participants

Conditions

Temperature: 0 °C

Procedure

n-Butyllithium (2.51 ml of a 2.5M solution in hexanes) was added to diisopropylamine (0.88 ml) in dry tetrahydrofuran,(15 ml) at 65° C. To this solution was added a solution of 5-bromo-2-methoxypyridine (0.82 ml) in dry tetrahydrofuran (10 ml) dropwise over 30 minutes at −65° C. A solution of 1-adamantylmethylisocyanate (1 g) in dry tetrahydrofuran (10 ml) was then added in small portions over 30 minutes at −65° C. The reaction mixture was allowed to warm to 0° C., diluted with saturated brine (20 ml) and extracted into ethyl acetate (3×20 ml). The combined extracts were dried over anhydrous sodium sulphate, filtered and concentrated. The residue was purified by chromatography on silica gel eluting with dichloromethane:acetone (19:1 to 2.5:1) to afford the sub-titled compound (1.1 g) as a colourless powder.

Workup

extractionextracted into ethyl acetate (3×20 ml)
dry with materialThe combined extracts were dried over anhydrous sodium sulphate
filtrationfiltered
concentrationconcentrated
customThe residue was purified by chromatography on silica gel eluting with dichloromethane:acetone (19:1 to 2.5:1)

Sources & evidence

ORD record: ord-7e64bf878b994329b227bd253c067cb8
Source dataset: uspto-grants-2006_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07129246B2

Reaction notes

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