Ammonium fluoride → 1-cyclopropyl-3-((3-(4-hydroxybutyl)imidazo[1,2-a]pyrazin-2-yl)methyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one

HRID 80632

反応式

HRID 80632 の反応式
[Si]([O:8][CH2:9][CH2:10]/[CH:11]=[CH:12]/[C:13]1[N:17]2[CH:18]=[CH:19][N:20]=[CH:21][C:16]2=[N:15][C:14]=1[CH2:22][N:23]1[C:27]2[CH:28]=[N:29][CH:30]=[CH:31][C:26]=2[N:25]([CH:32]2[CH2:34][CH2:33]2)[C:24]1=[O:35])(C(C)(C)C)(C)C.[F-].[NH4+]>CO.[Pd]>[CH:32]1([N:25]2[C:26]3[CH:31]=[CH:30][N:29]=[CH:28][C:27]=3[N:23]([CH2:22][C:14]3[N:15]=[C:16]4[CH:21]=[N:20][CH:19]=[CH:18][N:17]4[C:13]=3[CH2:12][CH2:11][CH2:10][CH2:9][OH:8])[C:24]2=[O:35])[CH2:33][CH2:34]1

参加物

5

反応物 2

HCID 25516Ammonium fluorideHCID 86704031(E)-3-((3-(4-(tert-butyldimethylsilyloxy)but-1-enyl)imidazo[1,2-a]pyrazin-2-yl)methyl)-1-cyclopropyl-1H-imidazo[4,5-c]pyridin-2(3H)-one

生成物 1

HCID 574102501-cyclopropyl-3-((3-(4-hydroxybutyl)imidazo[1,2-a]pyrazin-2-yl)methyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one収率 87%

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 887Methanol溶媒

反応条件

温度
60 °C

実験手順

A mixture of (E)-3-((3-(4-(tert-butyldimethylsilyloxy)but-1-enyl)imidazo[1,2-a]pyrazin-2-yl)methyl)-1-cyclopropyl-1H-imidazo[4,5-c]pyridin-2(3H)-one 11-a (480 mg, 0.978 mmole) and Pd/C 10% (52 mg, 0.05 eq) in MeOH (20 mL) was hydrogenated for 2 h. The reaction mixture was then filtered over dicalite and concentrated to dryness. The resulting white solid (480 mg, 84%) was used directly in the next step. It was redissolved in MeOH and ammonium fluoride (39 mg, 1.1 eq) was added. The reaction mixture was then heated at 60° C. overnight. After concentration, the crude was purified by Prep HPLC on (RP Vydac Denali C18-10 μm, 250 g, 5 cm), with the following mobile phase (0.25% NH4HCO3 solution in water, CH3CN), to give the targeted product P17 in 87% yield (320 mg). m/z=491 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ ppm 0.82-0.94 (m, 2H), 0.99-1.10 (m, 2H), 1.36-1.46 (m, 2H), 1.46-1.59 (m, 2H), 2.96 (tdd, J=6.96, 6.96, 3.64, 3.51 Hz, 1H), 3.08 (t, J=7.53 Hz, 2 H), 3.34-3.43 (m, 2H), 4.38 (t, J=5.14 Hz, 1H), 5.22 (s, 2H), 7.23 (dd, J=5.27, 0.75 Hz, 1H), 7.88 (d, J=4.52 Hz, 1H), 8.22 (d, J=5.27 Hz, 1H), 8.40 (s, 1H), 8.44 (dd, J=4.64, 1.38 Hz, 1H), 8.97 (d, J=1.51 Hz, 1H).

後処理

  1. filtrationThe reaction mixture was then filtered over dicalite
  2. concentrationconcentrated to dryness
  3. dissolutionIt was redissolved in MeOH
  4. concentrationAfter concentration
  5. customthe crude was purified by Prep HPLC on (RP Vydac Denali C18-10 μm, 250 g, 5 cm), with the following mobile phase (0.25% NH4HCO3 solution in water, CH3CN)
  6. customto give the targeted product P17 in 87% yield (320 mg)

出典と根拠

ORDレコード
ord-a9c3d403fff64a98a3aaed3720c1747c
出典データセット
uspto-grants-2014_09
特許番号
US08846672B2

関連ノート

読み込み中…