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 858039ノート

反応式

HRID 858039 の反応式
[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]

参加物

5

反応物 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 81503BromomethylcyclopropaneHCID 58762847(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

生成物 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 ester収率 52%

反応条件

温度
25 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-38c36a53240546128c0df04e258da1ac
出典データセット
uspto-grants-2006_12
特許番号
US07148229B2

反応ノート

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