Sodium hydride → Tert-butyl 4-{2-[(3,5-dichloro-benzyl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyrate

HRID 604149Notes

Reaction equation

HRID 604149 reaction equation
[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([O:39][CH3:40])=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:11]=2[CH2:20][NH:21][C:22]2[N:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[CH:24][N:23]=2)[CH:9]=1)([CH3:3])[CH3:2].[Cl:41][C:42]1[CH:47]=[C:46]([CH2:48]Cl)[CH:45]=[C:44]([Cl:50])[CH:43]=1.[H-].[Na+]>CN(C)C=O.[Cl-].[Na+].O>[Cl:41][C:42]1[CH:47]=[C:46]([CH:45]=[C:44]([Cl:50])[CH:43]=1)[CH2:48][N:21]([CH2:20][C:11]1[CH:12]=[C:13]([C:16]([F:19])([F:17])[F:18])[CH:14]=[CH:15][C:10]=1[C:8]1[CH:9]=[C:4]([CH:1]([CH3:3])[CH3:2])[CH:5]=[CH:6][C:7]=1[O:39][CH3:40])[C:22]1[N:23]=[CH:24][C:25]([O:28][CH2:29][CH2:30][CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[CH:26][N:27]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 1378803,5-Dichlorobenzyl chlorideHCID 66603218Tert-butyl 4-{2-[(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyrate

Product 1

HCID 66603221Tert-butyl 4-{2-[(3,5-dichloro-benzyl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyrateYield 79.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Tert-butyl 4-{2-[(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyrate (180 mg) is dissolved in N,N-dimethylformamide (1.0 ml), and thereto is added 1,3-dichloro-5-chloromethyl-benzene (252 mg), followed by an addition of sodium hydride (60%) (34 mg) under ice-cooling and the mixture is stirred at room temperature for 3 hours. To the reaction solution are added a saturated brine, and the mixture is extracted with ethyl acetate, and the organic layer is dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=19:1→9:1) to give tert-butyl 4-{2-[(3,5-dichloro-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyrate (184 mg). MS (m/z): 720/718 [M+H]+

Workup

  1. temperaturecooling
  2. extractionthe mixture is extracted with ethyl acetate
  3. dry with materialthe organic layer is dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=19:1→9:1)

Sources & evidence

ORD record
ord-14c9f15c673a44328a32423f2a56bb27
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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