Dimethylformamide → (4-{[6-Amino-1-cyclopropylmethyl-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-ylcarbamoyl]-methyl}-phenyl)-carbamic acid tert-butyl ester

HRID 858039Notes

Reaction equation

HRID 858039 reaction equation
[C:1]([O:5][C:6](=[O:35])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][C:15](=[O:34])[NH:16][C:17]2[C:18](=[O:33])[N:19]([CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[F:32])[C:20](=[O:24])[NH:21][C:22]=2[NH2:23])=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].CN(C)C=O.C(=O)([O-])[O-].[K+].[K+].[CH:47]1([CH2:50]Br)[CH2:49][CH2:48]1>>[C:1]([O:5][C:6](=[O:35])[NH:7][C:8]1[CH:9]=[CH:10][C:11]([CH2:14][C:15](=[O:34])[NH:16][C:17]2[C:18](=[O:33])[N:19]([CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[F:32])[C:20](=[O:24])[N:21]([CH2:50][CH:47]3[CH2:49][CH2:48]3)[C:22]=2[NH2:23])=[CH:12][CH:13]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 81503BromomethylcyclopropaneHCID 58762847HCID 58762847, compound

Product 1

HCID 58762834(4-{[6-Amino-1-cyclopropylmethyl-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-ylcarbamoyl]-methyl}-phenyl)-carbamic acid tert-butyl esterYield 52%

Conditions

Temperature
25 °C

Procedure

A solution of (4-{[6-amino-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-ylcarbamoyl]-methyl}-phenyl)-carbamic acid tert-butyl ester in N,N-dimethylformamide (2.5 g, 5.17 mmol) at 25° C. under argon was treated with potassium carbonate (6.43 g, 46.53 mmol) followed by cyclopropyl methyl bromide (752 mg, 7.76 mmol). The suspension was stirred at 25° C. overnight. At this time, the reaction was concentrated in vacuo. The residue was diluted with a solution of water (100 mL) and a 1.0N aqueous hydrochloric acid solution (31 mL). The resulting suspension was diluted with chloroform and neutralized with a 1.0N aqueous hydrochloric acid solution. The layers were separated. The aqueous layer was extracted with chloroform. The organics layers were washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 97/3 methylene chloride/methanol) afforded (4-{[6-amino-1-cyclopropylmethyl-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-ylcarbamoyl]-methyl}-phenyl)-carbamic acid tert-butyl ester (1.45 g, 52%) as an orange foam; EI-HRMS m/e calculated for C28H32FN5O5 (M+) 537.2387. found 537.2387.

Workup

  1. concentrationAt this time, the reaction was concentrated in vacuo
  2. additionThe residue was diluted with a solution of water (100 mL)
  3. additionThe resulting suspension was diluted with chloroform
  4. customThe layers were separated
  5. extractionThe aqueous layer was extracted with chloroform
  6. washThe organics layers were washed with a saturated aqueous sodium chloride solution
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-38c36a53240546128c0df04e258da1ac
Source dataset
uspto-grants-2006_12
Patent number
US07148229B2

Reaction notes

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