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

HRID 574251Notes

Reaction equation

HRID 574251 reaction equation
[C:1]([O:5][C:6](=[O:38])[NH:7][C@H:8]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH2:9][N:10]1[C:15](=[O:16])[C:14]([NH:17][C:18](=[O:21])[CH2:19]Cl)=[CH:13][N:12]([CH2:22][C:23]2[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=2[F:30])[C:11]1=[O:31])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[NH2:46][CH2:47][CH2:48][OH:49]>C(#N)C>[C:1]([O:5][C:6](=[O:38])[NH:7][C@H:8]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH2:9][N:10]1[C:15](=[O:16])[C:14]([NH:17][C:18](=[O:21])[CH2:19][NH:46][CH2:47][CH2:48][OH:49])=[CH:13][N:12]([CH2:22][C:23]2[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=2[F:30])[C:11]1=[O:31])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 700EthanolamineHCID 8471TriethylamineHCID 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 ester

Product 1

HCID 67143503((R)-2-{3-(2,6-difluoro-benzyl)-5-[2-(2-hydroxy-ethylamino)-acetylamino]-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl}-1-phenyl-ethyl)-carbamic acid tert-butyl esterYield 80.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of {(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 (44 mg, 0.08 mmol) in acetonitrile (2 mL) were added triethylamine(30 μl, 0.22 mmol) and 2-amino-ethanol (60 μl, 0.96 mmol) in that order. The solution was stirred at 60° C. for 4 hrs, cooled to room temperature, and washed with an aqueous saturated sodium bicarbonate solution to separate an organic layer. The organic layer was concentrated, and the residue was purified using silica gel chromatography (eluent: dichloromethane/methanol, 10/1) and dried in a vacuum to afford 37 mg of the compound as a colorless oil (yield 80%).

Workup

  1. temperaturecooled to room temperature
  2. washwashed with an aqueous saturated sodium bicarbonate solution
  3. customto separate an organic layer
  4. concentrationThe organic layer was concentrated
  5. customthe residue was purified
  6. customdried in a vacuum

Sources & evidence

ORD record
ord-9359df1abec641e0b70feea240be14ea
Source dataset
uspto-grants-2015_05
Patent number
US09034850B2

Reaction notes

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