Imidazole → HCID 58109239、化合物

HRID 2037537ノート

反応式

HRID 2037537 の反応式
CS(O[CH2:6][CH2:7][C@@:8]1([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=2)[O:13][C:12](=[O:14])[N:11]([C@H:15]([C:17]2[CH:22]=[CH:21][C:20]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[F:30])=[CH:19][CH:18]=2)[CH3:16])[CH2:10][CH2:9]1)(=O)=O.[NH:38]1[CH:42]=[CH:41][N:40]=[CH:39]1.C([O-])([O-])=O.[K+].[K+]>C(#N)C>[F:30][C:24]1[CH:25]=[C:26]([F:29])[CH:27]=[CH:28][C:23]=1[C:20]1[CH:21]=[CH:22][C:17]([C@@H:15]([N:11]2[CH2:10][CH2:9][C@@:8]([C:31]3[CH:32]=[CH:33][C:34]([F:37])=[CH:35][CH:36]=3)([CH2:7][CH2:6][N:38]3[CH:42]=[CH:41][N:40]=[CH:39]3)[O:13][C:12]2=[O:14])[CH3:16])=[CH:18][CH:19]=1

参加物

5

反応物 3

HCID 795ImidazoleHCID 11430Potassium CarbonateHCID 86649947HCID 86649947、化合物

生成物 1

HCID 58109239HCID 58109239、化合物収率 1.2%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

A mixture of 2-((S)-3-((S)-1-(2′,4′-difluorobiphenyl-4-yl)ethyl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)ethyl methanesulfonate (230 mg, 0.43 mmol), imidazole (44 mg, 0.65 mmol), K2CO3 (178.7 mg, 1.29 mmol) in acetonitrile (4 mL) was heated to reflux overnight. The solvent was removed and the residue was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc and the combined organic layer was washed with brine, dried over Na2SO4, filtered and concentrated to give the crude product, which was purified by preparative HPLC to give (R)-3-[(S)-1-(2′,4′-difluoro-biphenyl-4-yl)-ethyl]-6-(4-fluoro-phenyl)-6-(2-imidazol-1-yl-ethyl)-[1,3]oxazinan-2-one (2.5 mg, 1.2%). LC-MS Method 2 tR=2.14, min, m/z=506; 1H NMR (CDCl3): 1.51 (d, 3H), 2.16-2.63 (m, 7H), 2.94 (m, 2H), 3.91 (m, 1H), 4.32 (m, 1H), 5.66 (m, 1H), 6.25 (m, 1H), 6.81-6.90 (m, 2H), 6.94-7.08 (m, 5H), 7.14-7.26 (m, 6H).

後処理

  1. temperaturewas heated
  2. temperatureto reflux overnight
  3. customThe solvent was removed
  4. customthe residue was partitioned between EtOAc and water
  5. extractionThe aqueous layer was extracted with EtOAc
  6. washthe combined organic layer was washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give the crude product, which
  11. customwas purified by preparative HPLC

出典と根拠

ORDレコード
ord-bab89b01d6d24903bf81ff5962f4e746
出典データセット
uspto-grants-2013_11
特許番号
US08575156B2

反応ノート

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