Diisopropylethylamine → HCID 178461975、化合物

HRID 243418

反応式

HRID 243418 の反応式
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH2:12])[CH3:11])[N:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:6]=2[CH:19]=1.Cl[C:21]1[N:29]=[C:28]([NH2:30])[N:27]=[C:26]2[C:22]=1[N:23]=[CH:24][NH:25]2.CCN(C(C)C)C(C)C>C(O)CCC.CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH:12][C:21]3[N:29]=[C:28]([NH2:30])[N:27]=[C:26]4[C:22]=3[N:23]=[CH:24][NH:25]4)[CH3:11])[N:7]([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:6]=2[CH:19]=1

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 58459302(1S)-1-(6-Fluoro-1-phenyl-1H-benzimidazol-2-yl)ethan-1-amineHCID 1785084356-chloro-1H-purin-2-amine

生成物 1

HCID 178461975HCID 178461975、化合物収率 23%

試薬・触媒・溶媒 2

HCID 2631-Butanol溶媒HCID 887Methanol溶媒

実験手順

A mixture of (S)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine.2HCl (195 mg, 0.59 mmol), 6-chloro-9H-purin-2-ylamine (106 mg, 0.62 mmol) and DIPEA (415 μL, 2.38 mmol) in n-butanol (1 mL) was heated at 100° C. in a sealed vial for 24 h. After cooling to RT, the reaction mixture was diluted with MeOH and loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined, concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18 on a gradient 5-60%, 0.1% NH4OH in acetonitrile/water) to afford 310 as a white solid (52 mg, 23%). LCMS (Method K): RT 2.89 min [M+H]+ 389.02. 1H NMR (CDCl3, 400 MHz): δ 7.67 (1H, dd, J=8.67, 4.59 Hz), 7.62-7.38 (5H, m), 7.20 (1H, s), 7.00 (1H, td, J=9.19, 2.45 Hz), 6.79 (1H, dd, J=8.61, 2.46 Hz), 5.65 (1H, s), 4.92 (1H, s), 1.64 (3H, d, J=6.94 Hz)

後処理

  1. washThe cartridge was washed with MeOH
  2. concentrationconcentrated in vacuo
  3. customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM)

出典と根拠

ORDレコード
ord-a8073b19c8f84c87ae2be10dd3af45c1
出典データセット
uspto-grants-2014_02
特許番号
US08653089B2

関連ノート

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