Sodium hydride → ((R)-2-{3-(2,6-difluoro-benzyl)-4-methyl-5-[4-(3-nitro-benzyl)-3-oxo-piperazin-1-yl]-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl}-1-phenyl-ethyl)-carbamic acid tert-butyl ester

HRID 574254Notes

Reaction equation

HRID 574254 reaction equation
[C:1]([O:5][C:6](=[O:41])[NH:7][C@H:8]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[CH2:9][N:10]1[C:15](=[O:16])[C:14]([N:17]2[CH2:22][CH2:21][NH:20][C:19](=[O:23])[CH2:18]2)=[C:13]([CH3:24])[N:12]([CH2:25][C:26]2[C:31]([F:32])=[CH:30][CH:29]=[CH:28][C:27]=2[F:33])[C:11]1=[O:34])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[N+:44]([C:47]1[CH:48]=[C:49]([CH:52]=[CH:53][CH:54]=1)[CH2:50]Br)([O-:46])=[O:45].[Cl-].[NH4+]>C1COCC1.ClCCl>[C:1]([O:5][C:6](=[O:41])[NH:7][C@H:8]([C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)[CH2:9][N:10]1[C:15](=[O:16])[C:14]([N:17]2[CH2:22][CH2:21][N:20]([CH2:50][C:49]3[CH:52]=[CH:53][CH:54]=[C:47]([N+:44]([O-:46])=[O:45])[CH:48]=3)[C:19](=[O:23])[CH2:18]2)=[C:13]([CH3:24])[N:12]([CH2:25][C:26]2[C:31]([F:32])=[CH:30][CH:29]=[CH:28][C:27]=2[F:33])[C:11]1=[O:34])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 77568Benzene, 1-(bromomethyl)-3-nitro-HCID 67142728HCID 67142728, compound

Product 1

HCID 67142935((R)-2-{3-(2,6-difluoro-benzyl)-4-methyl-5-[4-(3-nitro-benzyl)-3-oxo-piperazin-1-yl]-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl}-1-phenyl-ethyl)-carbamic acid tert-butyl esterYield 45.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

{(R)-2-[3-(2,6-difluoro-benzyl)-4-methyl-2,6-dioxo-5-(3-oxo-piperazin-1-yl)-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethyl}-carbamic acid tert-butyl ester (50 mg, 0.0878 mmol) was dissolved in 1 mL of THF, with nitrogen purge. While on ice, 60% NaH (10 mg, 0.263 mmol) was added to the solution which was then stirred at room temperature for 10 min. Again, while being cooled on ice, 3-nitrobenzyl bromide (23 mg, 0.105 mmol) was added, followed by stirring at room temperature for 1 hr. A little amount of a saturated ammonium chloride solution was added before extraction with dichloromethane. After concentration, the resulting residue was purified by column chromatography eluting with an EtOAc/hexane/dichloromethane (2/1/0.5) eluent to afford 28 mg of the compound (42%).

Workup

  1. custompurge
  2. additionwas added
  3. stirringby stirring at room temperature for 1 hr
  4. concentrationAfter concentration
  5. customthe resulting residue was purified by column chromatography
  6. washeluting with an EtOAc/hexane/dichloromethane (2/1/0.5) eluent

Sources & evidence

ORD record
ord-ec00808f0b5f4cf5b2d1acdb86f092ef
Source dataset
uspto-grants-2015_05
Patent number
US09034850B2

Reaction notes

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