Sodium hydride → 2-(1-[(benzyloxy)methyl]-5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)-5-bromopyridine

HRID 1881858Notes

Reaction equation

HRID 1881858 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[NH:9][C:10]([CH:13]([C:21]3[CH:26]=[CH:25][C:24]([S:27]([CH:30]4[CH2:32][CH2:31]4)(=[O:29])=[O:28])=[CH:23][CH:22]=3)[CH2:14][CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[CH:11][CH:12]=2)=[N:6][CH:7]=1.[H-].[Na+].Cl[CH2:36][O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.[Cl-].[NH4+]>CN(C)C=O>[CH2:38]([O:37][CH2:36][N:9]1[C:10]([CH:13]([C:21]2[CH:22]=[CH:23][C:24]([S:27]([CH:30]3[CH2:31][CH2:32]3)(=[O:29])=[O:28])=[CH:25][CH:26]=2)[CH2:14][CH:15]2[CH2:16][CH2:17][O:18][CH2:19][CH2:20]2)=[CH:11][CH:12]=[C:8]1[C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][N:6]=1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 137983Benzyl chloromethyl etherHCID 593312485-bromo-2-(5-[1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl]-1H-pyrrol-2-yl)pyridine

Product 1

HCID 593313122-(1-[(benzyloxy)methyl]-5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)-5-bromopyridineYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5-bromo-2-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)pyridine (3.00 g) in N,N-dimethylformamide (25 mL) was added sodium hydride (60%, oil, 279 mg) under ice-cooling, and the mixture was stirred at 0° C. for 10 min. To the reaction solution was added [(chloromethoxy)methyl]benzene (0.970 mL), and the mixture was stirred at 0° C. for 3 hr. A saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=10:90-50:50, volume ratio) to give the title compound (2.91 g, yield 79%) as a colorless amorphous solid.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at 0° C. for 3 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed successively with water and saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=10:90-50:50, volume ratio)

Sources & evidence

ORD record
ord-e2dc8e2f2e404cd89ee94252aa15663e
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

Loading…