Ethyl Acetate → HCID 71115218、化合物

HRID 1502480ノート

反応式

HRID 1502480 の反応式
[F:1][C@@H:2]1[CH2:4][C@@H:3]1[C:5]([OH:7])=O.CN(C(O[N:16]1N=N[C:18]2[CH:19]=[CH:20][CH:21]=[N:22][C:17]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([N:35]([CH2:39][CH3:40])[CH:36]([CH3:38])C)(C)C.C(O[CH2:45][CH3:46])(=O)C>CN(C=O)C>[F:1][C@@H:2]1[CH2:4][C@@H:3]1[C:5]([NH:16][C:17]1[N:22]=[CH:21][C:20]2[C:19]([CH:18]=1)=[CH:17][N:22]=[C:21]([C:40]1[CH:39]=[N:35][CH:36]=[CH:38][C:45]=1[CH3:46])[CH:20]=2)=[O:7]

参加物

6

反応物 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10011855(1R,2R)-2-fluorocyclopropane-1-carboxylic acid

生成物 1

HCID 71115218HCID 71115218、化合物収率 46%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
70 °C

実験手順

A mixture of (1R,2R)-2-fluorocyclopropanecarboxylic acid (35 mg, 0.34 mmol), HATU (139 mg, 0.36 mmol), and N,N-diisopropylethylamine (89 mg, 0.68 mmol) in DMF (1 mL) was heated at 70° C. for 8 hours. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (25 mL). The organic layer was separated, dried over sodium sulfate, filtered and concentrated in vacuo to provide a residue that was purified by reverse phase HPLC purification (5-85% ACN in water w/0.1% NH4OH, 14 min). Desired fractions were combined and evaporated in vacuo to afford the title compound as an off-white solid (25 mg, 46%). 1H NMR (400 MHz, DMSO) δ 11.20 (s, 1H), 9.50 (s, 1H), 9.34 (s, 1H), 8.68 (s, 1H), 8.68 (s, 1H), 8.50 (d, J=5.0 Hz, 1H), 8.19 (s, 1H), 7.39 (d, J=5.0 Hz, 1H), 5.08-4.85 (m, 1H), 2.44 (s, 3H), 2.30 (m, 1H), 1.72 (m, 1H), 1.23 (m, 1H). LCMS (Method E): RT=3.166 min, M+H+=323.2.

後処理

  1. washwashed with water (25 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto provide a residue that
  7. customwas purified by reverse phase HPLC purification (5-85% ACN in water w/0.1% NH4OH, 14 min)
  8. customevaporated in vacuo

出典と根拠

ORDレコード
ord-2ce9b4c3a88440998429ca082ad5a0b4
出典データセット
uspto-grants-2015_12
特許番号
US09206175B2

反応ノート

読み込み中…