Triethylamine → {(R)-2-[5-(4-chloro-butyrylamino)-3-(2,6-difluoro-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethyl}-carbamic acid tert-butyl ester

HRID 574262Notes

Reaction equation

HRID 574262 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][CH2:44][CH2:45][C:46](Cl)=[O:47]>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:46](=[O:47])[CH2:45][CH2:44][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 8471TriethylamineHCID 783704-Chlorobutyryl chlorideHCID 67143363HCID 67143363, compound

Product 1

HCID 67144080{(R)-2-[5-(4-chloro-butyrylamino)-3-(2,6-difluoro-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethyl}-carbamic acid tert-butyl esterYield 78%

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 (42 mg, 0.089 mmol) in dichloromethane (2 mL) were added triethylamine (25 μl, 0.178 mmol) and 4-chloro-butyryl chloride (11 μl, 0.097 mmol) in the order. The solution was stirred at room temperature for 2 hrs and concentrated. The residue was purified using silica gel chromatography (eluent: hexane/ethyl acetate/dichloromethane, 2/1/1) and dried in a vacuum to afford 40 mg of the compound as a colorless oil (yield 78%). 1H NMR (300 MHz, CDCl3) δ 1.33 (9H, s), 2.17 (2H, p), 2.57 (2H, t), 3.63 (2H, t), 4.10 (1H, m), 4.34 (1H, t), 4.99-5.14 (3H, m), 5.47 (1H, d), 6.96 (2H, m), 7.24-7.39 (6H, m), 7.72 (1H, s), 8.65 (1H, s)

Workup

  1. concentrationconcentrated
  2. customThe residue was purified
  3. customdried in a vacuum

Sources & evidence

ORD record
ord-a60bc7d3cdb04b6daefae0698a0dae24
Source dataset
uspto-grants-2015_05
Patent number
US09034850B2

Reaction notes

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