Chloroacetyl chloride → {(R)-2-[5-(2-chloro-acetylamino)-3-(2,6-difluoro-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethyl}-carbamic acid tert-butyl ester

HRID 574250Notes

Reaction equation

HRID 574250 reaction equation
[C:1]([O:5][C:6](=[O:34])[NH:7][C@H:8]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:9][N:10]1[C:15](=[O:16])[C:14]([NH2:17])=[CH:13][N:12]([CH2:18][C:19]2[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=2[F:26])[C:11]1=[O:27])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[Cl:42][CH2:43][C:44](Cl)=[O:45]>ClCCl>[C:1]([O:5][C:6](=[O:34])[NH:7][C@H:8]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:9][N:10]1[C:15](=[O:16])[C:14]([NH:17][C:44](=[O:45])[CH2:43][Cl:42])=[CH:13][N:12]([CH2:18][C:19]2[C:20]([F:26])=[CH:21][CH:22]=[CH:23][C:24]=2[F:25])[C:11]1=[O:27])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6577Chloroacetyl chloride2×HCID 8471TriethylamineHCID 67143363HCID 67143363, compound

Product 1

HCID 67143301{(R)-2-[5-(2-chloro-acetylamino)-3-(2,6-difluoro-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethyl}-carbamic acid tert-butyl esterYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of {(R)-2-[5-amino-3-(2,6-difluoro-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethyl}-carbamic acid tert-butyl ester (50 mg, 0.11 mmol) in dichloromethane (2 mL) were added triethylamine (29 μl, 0.22 mmol) and chloro-acetyl chloride (9.3 μl, 0.12 mmol) in that order, followed by stirring at room temperature for 2 hrs. Again, chloro-acetyl chloride (5.0 μl, 0.06 mmol) was added to the solution which was then stirred at room temperature for 1 hr. The solution was washed with an aqueous saturated sodium bicarbonate solution to separate an organic layer which was then concentrated. The residue was purified using silica gel chromatography (eluent: hexane/ethyl acetate, 2/1) and dried in a vacuum to afford 44 mg of the compound as a colorless oil (yield 76%).

Workup

  1. stirringwas then stirred at room temperature for 1 hr
  2. washThe solution was washed with an aqueous saturated sodium bicarbonate solution
  3. customto separate an organic layer which
  4. concentrationwas then concentrated
  5. customThe residue was purified
  6. customdried in a vacuum

Sources & evidence

ORD record
ord-48fa37b720e24f1484311439efb9984f
Source dataset
uspto-grants-2015_05
Patent number
US09034850B2

Reaction notes

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