Sodium hydride → Delamanid

HRID 2221403Notes

Reaction equation

HRID 2221403 reaction equation
[F:1][C:2]([F:25])([F:24])[O:3][C:4]1[CH:23]=[CH:22][C:7]([O:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=3)[CH2:11][CH2:10]2)=[CH:6][CH:5]=1.[H-].[Na+].Br[C:29]1[N:30]([CH2:37][C@:38]2([CH3:41])[CH2:40][O:39]2)[CH:31]=[C:32]([N+:34]([O-:36])=[O:35])[N:33]=1>CN(C)C=O>[CH3:40][C@@:38]1([CH2:41][O:21][C:18]2[CH:19]=[CH:20][C:15]([N:12]3[CH2:11][CH2:10][CH:9]([O:8][C:7]4[CH:22]=[CH:23][C:4]([O:3][C:2]([F:1])([F:24])[F:25])=[CH:5][CH:6]=4)[CH2:14][CH2:13]3)=[CH:16][CH:17]=2)[O:39][C:29]2=[N:33][C:32]([N+:34]([O-:36])=[O:35])=[CH:31][N:30]2[CH2:37]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10467858(R)-2-bromo-4-nitro-1-(2-methyl-2-oxiranylmethyl)imidazoleHCID 11653258SS-3227

Product 1

HCID 6480466DelamanidYield 33%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
72.5 °C

Procedure

4-[4-(4-Trifluoromethoxyphenoxy)piperidin-1-yl]phenol (693 mg) was dissolved in N,N-dimethylformamide (3 ml), then under ice-cooling condition, sodium hydride (86 mg) was added, the reaction mixture was stirred at 70-75° C. for 20 minutes. The reaction mixture was ice-cooled, a solution prepared by dissolving (R)-2-bromo-4-nitro-1-(2-methyl-2-oxiranylmethyl)imidazole (720 mg) prepared in example 6 in N,N-dimethylformamide (3 ml) was added and stirred at 70-75° C. for 20 minutes. The reaction mixture was turned back to a room temperature, ice-water (25 ml) was added, and extracted 3 times with dichloromethane (50 ml). The organic layers were combined, after being washed with water 3 times, the organic layer was dried over anhydrous magnesium sulfate. After being filterated under a reduced pressure, the filtrate was concentrated, and the obtained residue was purified by use of a silica gel column chromatography (eluent: dichloromethane/ethyl acetate=3/1). Recrystallized from ethyl acetate/diisopropyl ether, there was obtained (R)-2-methyl-6-nitro-2-{4-[4-(4-trifluoromethoxyphenoxy)piperidin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole (343 mg, yield: 33%) as pale yellow powder product.

Workup

  1. additionwas added
  2. temperaturecooled
  3. customa solution prepared
  4. additionwas added
  5. stirringstirred at 70-75° C. for 20 minutes
  6. customwas turned back to a room temperature
  7. extractionextracted 3 times with dichloromethane (50 ml)
  8. washafter being washed with water 3 times
  9. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  10. concentrationthe filtrate was concentrated
  11. customthe obtained residue was purified by use of a silica gel column chromatography (eluent: dichloromethane/ethyl acetate=3/1)
  12. customRecrystallized from ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-6c76033b9b9d4b3f96ccbaec2a3c16b2
Source dataset
uspto-grants-2008_05
Patent number
US07368579B2

Reaction notes

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