Diisopropylethylamine → (S)-N-(1-(6-fluoro-1-phenyl-1H-benzo[d]imidazol-2-yl)propyl)-7H-purin-6-amine

HRID 243339ノート

反応式

HRID 243339 の反応式
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH2:13])[CH2:11][CH3:12])[N:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:6]=2[CH:20]=1.Cl[C:22]1[N:30]=[CH:29][N:28]=[C:27]2[C:23]=1[N:24]=[CH:25][N:26]2C1CCCCO1.CCN(C(C)C)C(C)C>C(O)CCC>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH:13][C:22]3[N:30]=[CH:29][N:28]=[C:27]4[C:23]=3[NH:24][CH:25]=[N:26]4)[CH2:11][CH3:12])[N:7]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:6]=2[CH:20]=1

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68157917(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)propylamine

生成物 1

HCID 60161900(S)-N-(1-(6-fluoro-1-phenyl-1H-benzo[d]imidazol-2-yl)propyl)-7H-purin-6-amine収率 21%

試薬・触媒・溶媒 1

HCID 2631-Butanol溶媒

反応条件

温度
90 °C

実験手順

A mixture of (S)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)propylamine from Example 28 (42 mg, 0.16 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (37 mg, 0.16 mmol) and DIPEA (0.14 mL, 0.8 mmol) in n-butanol (1 mL) was stirred in a sealed vial for 16 h at 90° C. After cooling to RT, the crude reaction mixture was loaded into an Isolute® SCX-2 which was washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM) affording 160 as a white solid (13 mg, 21%). LCMS: RT 3.61 min [M+H]+ 388.1. 1H NMR (DMSO, 400 MHz): δ 8.22-8.03 (2H, m), 7.80 (1H, s), 7.71-7.43 (6H, m), 7.09 (1H, t, J=9.42 Hz), 6.85 (1H, d, J=8.93 Hz), 5.38 (1H, s), 2.08-1.88 (2H, m), 0.83 (3H, t, J=7.34 Hz)

後処理

  1. temperatureAfter cooling to RT
  2. customthe crude reaction mixture
  3. washwas washed with MeOH
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was 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-f55a484bb2414ca3ac3db595ae9ad86c
出典データセット
uspto-grants-2014_02
特許番号
US08653089B2

反応ノート

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