Sodium hydride → HCID 68456809, compound

HRID 2387520Notes

Reaction equation

HRID 2387520 reaction equation
[C:1]12([CH2:11][OH:12])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[H-].[Na+].Cl[C:16]1[CH:21]=[CH:20][N+:19]([O-:22])=[CH:18][CH:17]=1>CN(C=O)C>[C:1]12([CH2:11][O:12][C:16]3[CH:21]=[CH:20][N+:19]([O-:22])=[CH:18][CH:17]=3)[CH2:8][CH:7]3[CH2:6][CH:5]([CH2:4][CH:3]([CH2:9]3)[CH2:2]1)[CH2:10]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 64556Tricyclo(3.3.1.1'3,7)dec-1-ylmethanolHCID 707244-chloropyridine N-oxide

Product 1

HCID 68456809HCID 68456809, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of adamantanemethanol (1.2 g, 7.4 mmol) in DMF (8 mL) was added NaH (0.3 g, 7.4 mmol) in a single portion. After gas evolution subsided, 4-chloropyridine N-oxide (0.8 g, 6.17 mmol) was added. The reaction mixture was stirred at room temperature under Ar until the reaction was complete. The mixture was quenched with water and extracted with CH2Cl2. The organic layer was washed with H2O and 5% LiCl, dried over Na2SO4, filtered and concentrated to dryness. Purification by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2) gave 4-(adamantylmethoxy)pyridine N-oxide (1.55 g, 97%) as a yellow solid. This material was suspended in Ac2O (5 mL), heated to 140° C. and stirred at 140° C. for 4 h. After cooling, the mixture was diluted with CH3OH and H2O (10 mL, 1:1 mixture) and stirred at room temperature for 1 h. The mixture was concentrated, and the residue was purified by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2) to give 4-(adamantylmethoxy)pyridin-2(1H)-one (1.08 g, 70%) as a brown solid. Following the procedure of Example 62 (step f), but substituting 5-bromo-1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazole for 4-(2-(5-iodo-1H-indazol-1-yl)ethyl)morpholine, 4-(adamantylmethoxy)pyridin-2(1H)-one for 4-phenethylpyridin-2(1H)-one, and 1,2-trans-cyclohexyldiamine for 8-hydroxyquinoline, the title compound (142 mg, 79%) was obtained as a yellow powder: mp 252-254° C.; 1H NMR (500 MHz, CD3OD) δ 8.24 (s, 1H), 7.82 (d, J=2.0 Hz, 1H), 7.78 (d, J=9.0 Hz, 1H), 7.58 (d, J=7.5 Hz, 1H), 7.46 (dd, J=9.0, 2.0 Hz, 1H), 6.29 (dd, J=7.5, 3.0 Hz, 1H), 6.04 (d, J=2.5 Hz, 1H), 4.87 (t, J=6.5 Hz, 2H), 3.86 (t, J=5.5 Hz, 2H), 3.69-3.72 (m, 2H), 3.63 (s, 2H), 3.16-3.20 (m, 2H), 2.16-2.19 (m, 2H), 2.00-2.03 (m, 3H), 1.71-1.84 (m, 12H), 1.24-1.31 (m, 2H); ESI MS m/z 473 [M+H]+; HPLC (Method D) 98.9% (AUC), tR=15.4 min.

Workup

  1. customThe mixture was quenched with water
  2. extractionextracted with CH2Cl2
  3. washThe organic layer was washed with H2O and 5% LiCl
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customPurification by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-1225da2c318845de9892b510e644c71e
Source dataset
uspto-grants-2012_09
Patent number
US08268868B2

Reaction notes

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