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

HRID 604191Notes

Reaction equation

HRID 604191 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.[CH2:34]([O:41][C:42]1[CH:47]=[CH:46][C:45]([C:48]2[CH:53]=[C:52]([CH:54]([CH3:56])[CH3:55])[CH:51]=[CH:50][C:49]=2[O:57][CH3:58])=[C:44]([CH2:59]Cl)[CH:43]=1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.[H-].[Na+].[Cl-].[NH4+]>CN(C)C=O.C(OCC)(=O)C>[CH2:34]([O:41][C:42]1[CH:47]=[CH:46][C:45]([C:48]2[CH:53]=[C:52]([CH:54]([CH3:56])[CH3:55])[CH:51]=[CH:50][C:49]=2[O:57][CH3:58])=[C:44]([CH2:59][N:7]([CH2:6][C:5]2[CH:25]=[C:26]([C:28]([F:29])([F:30])[F:31])[CH:27]=[C:3]([C:2]([F:1])([F:32])[F:33])[CH:4]=2)[C:8]2[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]=2)[CH:43]=1)[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 670872924-Benzyloxy-2-chloromethyl-5'-isopropyl-2'-methoxy-biphenylHCID 86626523Tert-butyl 4-[2-(3,5-bis-trifluoromethyl-benzylamino)-pyrimidin-5-yloxy]-butyrate

Product 1

HCID 86626920Tert-butyl 4-{2-[(4-benzyloxy-5'-isopropyl-2'-methoxy-biphenyl-2-ylmethyl)-(3,5-bis-trifluoromethyl-benzyl)-amino]-pyrimidin-5-yloxy}-butyrateYield 65.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Tert-butyl 4-[2-(3,5-bis-trifluoromethyl-benzylamino)-pyrimidin-5-yloxy]-butyrate (1.11 g) and 4-benzyloxy-2-chloromethyl-5′-isopropyl-2′-methoxy-biphenyl (805 mg) are dissolved in N,N-dimethylformamide (10 ml) and thereto is added sodium hydride (60%) (120 mg) under ice-cooling, and the mixture is stirred under ice-cooling for 2 hours, and then is stirred at room temperature for 30 minutes. Thereto are added a saturated 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 resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=1:0→4:1) to give tert-butyl 4-{2-[(4-benzyloxy-5′-isopropyl-2′-methoxy-biphenyl-2-ylmethyl)-(3,5-bis-trifluoromethyl-benzyl)-amino]-pyrimidin-5-yloxy}-butyrate (1.14 g). MS (m/z): 824 [M+H]+.

Workup

  1. temperaturecooling
  2. temperaturecooling for 2 hours
  3. stirringis stirred at room temperature for 30 minutes
  4. customthe mixture is separated
  5. washthe organic layer is washed with a saturated brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=1:0→4:1)

Sources & evidence

ORD record
ord-ad66a500b35c41c4b6eb0b1b20a471ae
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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