Sodium hydride → Tert-butyl 4-{2-[(3,5-bis-trifluoromethyl-benzyl)-(2-bromo-4,5-dimethoxy-benzyl)-amino]-pyrimidin-5-yloxy}-butyrate

HRID 604167Notes

Reaction equation

HRID 604167 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1)[CH2:6][NH:7][C:8]1[N:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:10][N:9]=1.[H-].[Na+].[Br:36][C:37]1[CH:42]=[C:41]([O:43][CH3:44])[C:40]([O:45][CH3:46])=[CH:39][C:38]=1[CH2:47]Cl.[Cl-].[NH4+]>CN(C=O)C.C(OCC)(=O)C>[F:33][C:2]([F:1])([F:32])[C:3]1[CH:4]=[C:5]([CH:25]=[C:26]([C:28]([F:29])([F:30])[F:31])[CH:27]=1)[CH2:6][N:7]([CH2:47][C:38]1[CH:39]=[C:40]([O:45][CH3:46])[C:41]([O:43][CH3:44])=[CH:42][C:37]=1[Br:36])[C:8]1[N:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:12][N:13]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 49622811-Bromo-2-(chloromethyl)-4,5-dimethoxybenzeneHCID 86626523Tert-butyl 4-[2-(3,5-bis-trifluoromethyl-benzylamino)-pyrimidin-5-yloxy]-butyrate

Product 1

HCID 86626904Tert-butyl 4-{2-[(3,5-bis-trifluoromethyl-benzyl)-(2-bromo-4,5-dimethoxy-benzyl)-amino]-pyrimidin-5-yloxy}-butyrateYield 78.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Tert-butyl 4-[2-(3,5-bis-trifluoromethyl-benzyl-amino)-pyrimidin-5-yloxy]-butyrate (100 mg) is dissolved in DMF (1 ml) and thereto is added sodium hydride (60%) (10.8 mg) under ice-cooling, and the mixture is stirred under ice-cooling for 15 minutes. Thereto is added 1-bromo-2-chloromethyl-4,5-dimethoxybenzene (83.1 mg) and the mixture is stirred under ice-cooling for 1 hour. To the reaction solution are added aqueous ammonium chloride solution and ethyl acetate, and the mixture is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (hexane:ethyl acetate=10:1→14:1) to give tert-butyl 4-{2-[(3,5-bis-trifluoromethyl-benzyl)-(2-bromo-4,5-dimethoxy-benzyl)-amino]-pyrimidin-5-yloxy}-butyrate (116 mg). MS (m/z): 708/710 [M+H]+

Workup

  1. temperaturecooling
  2. temperaturecooling for 15 minutes
  3. stirringthe mixture is stirred under ice-
  4. temperaturecooling for 1 hour
  5. customthe mixture is separated
  6. washthe organic layer is washed with a saturated brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue is purified by silica gel column chromatography (hexane:ethyl acetate=10:1→14:1)

Sources & evidence

ORD record
ord-c0527b9686724134915bd0235262482c
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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