Diisopropylethylamine → 5-Chloro-6-fluoro-1H-indole-7-carboxylic acid (4-cyclopropyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide

HRID 855394ノート

反応式

HRID 855394 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:12]([OH:14])=O)[C:10]=1[F:11])[NH:7][CH:6]=[CH:5]2.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)C(C)C)(C)C.[CH:46]1([C:49]2[CH:68]=[CH:67][C:52]([CH2:53][NH:54][CH2:55][CH2:56][C:57]3[CH:62]=[CH:61][CH:60]=[C:59]([C:63]([F:66])([F:65])[F:64])[CH:58]=3)=[CH:51][CH:50]=2)[CH2:48][CH2:47]1>CN(C=O)C.O>[CH:46]1([C:49]2[CH:68]=[CH:67][C:52]([CH2:53][N:54]([CH2:55][CH2:56][C:57]3[CH:62]=[CH:61][CH:60]=[C:59]([C:63]([F:66])([F:65])[F:64])[CH:58]=3)[C:12]([C:9]3[C:10]([F:11])=[C:2]([Cl:1])[CH:3]=[C:4]4[C:8]=3[NH:7][CH:6]=[CH:5]4)=[O:14])=[CH:51][CH:50]=2)[CH2:48][CH2:47]1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 251136475-chloro-6-fluoro-1H-indole-7-carboxylic acidHCID 68695622(4-Cyclopropyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amine

生成物 1

HCID 866030855-Chloro-6-fluoro-1H-indole-7-carboxylic acid (4-cyclopropyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide収率 49.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒2 回

実験手順

To a solution of 37 mg (0.17 mmol) 5-chloro-6-fluoro-1H-indole-7-carboxylic acid and 54 mg of TBTU (0.17 mmol) in 2 ml DMF, were added 0.148 ml (0.87 mmol) of N,N-diisopropylethyl amine. After stirring for 5 min at rt, 51 mg (0.17 mmol) (4-cyclopropyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amine in 1 ml DMF was added. After stirring for 17 h at rt, the reaction mixture was diluted with 30 ml water and extracted with EtOAc (2×). The combined organic phases were washed with water and brine, dried with magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (8 g silica gel; diethylether/heptane 1:1; then 8 g silicagel DCM/heptane 70:30 to 90:10) to give 43 mg white foam (48%). MS (EI) 514.1 (M)+.

後処理

  1. stirringAfter stirring for 17 h at rt
  2. extractionextracted with EtOAc (2×)
  3. washThe combined organic phases were washed with water and brine
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (8 g silica gel

出典と根拠

ORDレコード
ord-33c8978a17784a31977e777b73d212cc
出典データセット
uspto-grants-2007_08
特許番号
US07259183B2

反応ノート

読み込み中…