Dichloromethane → 7-bromo-6-((S)-2-methyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid [(R)-1-(6-trifluoromethyl-pyridin-3-yl)-propyl]-amide

HRID 926403ノート

反応式

HRID 926403 の反応式
[F:1][C:2]([F:33])([F:32])[C:3]1[N:8]=[CH:7][C:6]([C@H:9]([NH:12][C:13]([C:15]2[CH:16]=[C:17]([C:24]([N:26]3[CH2:30][CH2:29][CH2:28][C@@H:27]3[CH3:31])=[O:25])[N:18]3[CH2:23][CH2:22][O:21][CH2:20][C:19]=23)=[O:14])[CH2:10][CH3:11])=[CH:5][CH:4]=1.[Br:34]N1C(=O)CCC1=O.ClCCl>C(Cl)(Cl)Cl>[F:33][C:2]([F:1])([F:32])[C:3]1[N:8]=[CH:7][C:6]([C@H:9]([NH:12][C:13]([C:15]2[C:16]([Br:34])=[C:17]([C:24]([N:26]3[CH2:30][CH2:29][CH2:28][C@@H:27]3[CH3:31])=[O:25])[N:18]3[CH2:23][CH2:22][O:21][CH2:20][C:19]=23)=[O:14])[CH2:10][CH3:11])=[CH:5][CH:4]=1

参加物

5

反応物 3

HCID 6344DichloromethaneHCID 67184N-bromobutanimideHCID 716961286-((S)-2-methyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid [(R)-1-(6-trifluoromethyl-pyridin-3-yl)-propyl]-amide

生成物 1

HCID 897341547-bromo-6-((S)-2-methyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid [(R)-1-(6-trifluoromethyl-pyridin-3-yl)-propyl]-amide収率 86%

試薬・触媒・溶媒 1

HCID 6212Chloroform溶媒

反応条件

温度
25 °C

実験手順

To a solution of 6-((S)-2-methyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid [(R)-1-(6-trifluoromethyl-pyridin-3-yl)-propyl]-amide (Comp. No. 16e) (200 mg, 0.43 mmol) in chloroform (5 ml) was added N-bromo-succinimide (76 mg, 0.43 mmol) and the mixture was stirred for 18 h at 25° C. Then excess dichloromethane was added and the mixture was washed consecutively with water, aqueous sodium hydrogencarbonate and brine. The organic layer was evaporated to dryness. The crude product was purified by reverse phase HPLC to give 200 mg (86%) of 7-bromo-6-((S)-2-methyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid [(R)-1-(6-trifluoromethyl-pyridin-3-yl)-propyl]-amide. LC/MS (method 3): Rt=1.81 min; m/z=543.1 (M+H+).

後処理

  1. washthe mixture was washed consecutively with water, aqueous sodium hydrogencarbonate and brine
  2. customThe organic layer was evaporated to dryness
  3. customThe crude product was purified by reverse phase HPLC

出典と根拠

ORDレコード
ord-45a8442f1708440f8a7551e943ce7836
出典データセット
uspto-grants-2016_03
特許番号
US09284333B2

反応ノート

読み込み中…