Diisopropylethylamine → (1S,2S)-2-fluoro-N-(7-(5-fluoro-4-methylpyridin-3-yl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide

HRID 468957ノート

反応式

HRID 468957 の反応式
[F:1][C:2]1[C:3]([CH3:19])=[C:4]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([NH2:18])[N:14]=[CH:15]3)=[CH:10][N:9]=2)[CH:5]=[N:6][CH:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:44][C@H:45]1[CH2:47][C@H:46]1[C:48](O)=[O:49].C(N(CC)C(C)C)(C)C>CN(C=O)C.C(OCC)(=O)C>[F:44][C@H:45]1[CH2:47][C@H:46]1[C:48]([NH:18][C:13]1[N:14]=[CH:15][C:16]2[C:11]([CH:12]=1)=[CH:10][N:9]=[C:8]([C:4]1[CH:5]=[N:6][CH:7]=[C:2]([F:1])[C:3]=1[CH3:19])[CH:17]=2)=[O:49]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 9793716cis-2-Fluorocyclopropanecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 679743607-(5-Fluoro-4-methylpyridin-3-yl)-2,6-naphthyridin-3-amine

生成物 1

HCID 71115274(1S,2S)-2-fluoro-N-(7-(5-fluoro-4-methylpyridin-3-yl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide収率 43%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
70 °C

実験手順

A mixture of 7-(5-fluoro-4-methyl-3-pyridyl)-2,6-naphthyridin-3-amine (35 mg, 0.14 mmol), HATU (113 mg, 0.29 mmol), (1S,2S)-2-fluorocyclopropanecarboxylic acid (29 mg, 0.28 mmol), and N,N-diisopropylethylamine (0.10 mL, 0.55 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 (20 mg, 43%). 1H NMR (400 MHz, DMSO) δ 11.22 (s, 1H), 9.35 (s, 1H), 8.70 (s, 1H), 8.59 (sz, 1H), 8.58 (s, 1H), 8.24 (s, 1H), 4.98 (m, 1H), 2.37 (d, J=1.9 Hz, 3H), 2.31 (m, 1H), 1.72 (m, 1H), 1.23 (m, 1H). LCMS (Method E): RT=3.978 min, M+H+=341.2.

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-9eae322a7bbc486f8f39b70ee4ad199c
出典データセット
uspto-grants-2014_01
特許番号
US08623889B2

反応ノート

読み込み中…