Trifluoroacetic acid → 3-((R)-2-Amino-2-phenyl-ethyl)-1-(2-fluoro-6-trifluoromethyl-benzyl)-6-methyl-5-[4-(3-nitro-benzyl)-3-oxo-piperazin-1-yl]-1H-pyrimidine-2,4-dione

HRID 574255Notes

Reaction equation

HRID 574255 reaction equation
C(OC(=O)[NH:7][C@H:8]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[CH2:9][N:10]1[C:15](=[O:16])[C:14]([N:17]2[CH2:22][CH2:21][N:20]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([N+:30]([O-:32])=[O:31])[CH:25]=3)[C:19](=[O:33])[CH2:18]2)=[C:13]([CH3:34])[N:12]([CH2:35][C:36]2C(F)=[CH:40][CH:39]=[CH:38][C:37]=2[F:43])[C:11]1=[O:44])(C)(C)C.[F:52][C:53]([F:58])([F:57])[C:54](O)=O.C([O-])(O)=O.[Na+]>ClCCl>[NH2:7][C@H:8]([C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1)[CH2:9][N:10]1[C:15](=[O:16])[C:14]([N:17]2[CH2:22][CH2:21][N:20]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([N+:30]([O-:32])=[O:31])[CH:25]=3)[C:19](=[O:33])[CH2:18]2)=[C:13]([CH3:34])[N:12]([CH2:35][C:36]2[C:54]([C:53]([F:58])([F:57])[F:52])=[CH:40][CH:39]=[CH:38][C:37]=2[F:43])[C:11]1=[O:44]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 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 ester

Product 1

HCID 671437763-((R)-2-Amino-2-phenyl-ethyl)-1-(2-fluoro-6-trifluoromethyl-benzyl)-6-methyl-5-[4-(3-nitro-benzyl)-3-oxo-piperazin-1-yl]-1H-pyrimidine-2,4-dioneYield 45.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of ((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 (28 mg, 0.0371 mmol) in 1 mL of dichloromethane was added trifluoroacetic acid (0.1 ml, 1.29 mmol) under ice cooling, followed by stirring at room temperature for 2 hrs. The solution was neutralized with sat. NaHCO3, extracted with dichloromethane and concentrated in a vacuum. The residue was purified by column chromatography eluting with a dichloromethane/methanol (20/1) eluent to afford 11 mg of compound 9-1 (45%). 1H NMR (300 MHz, CDCl3) δ 2.42 (3H, s), 2.81 (1H, m), 3.12 (1H, m), 3.30-3.49 (2H, m), 3.72 (1H, m), 4.02-4.22 (3H, m), 4.33 (1H, dd), 4.55 (1H, m), 4.91 (1H, m), 5.23 (2H, dd), 6.92 (2H, t), 7.20-7.37 (6H, m), 7.53 (1H, t), 7.65 (1H, d), 8.13 (1H, s), 8.15 (1H, m).

Workup

  1. extractionextracted with dichloromethane
  2. concentrationconcentrated in a vacuum
  3. customThe residue was purified by column chromatography
  4. washeluting with a dichloromethane/methanol (20/1) eluent

Sources & evidence

ORD record
ord-234992cdf53149a88a29c87177817ed8
Source dataset
uspto-grants-2015_05
Patent number
US09034850B2

Reaction notes

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