Hydrochloric Acid → N-(5-((4-methoxybenzyloxy)methyl)-3-(2-methyl-9H-purin-6-yl)pyridin-2-yl)-1H-indol-4-amine

HRID 1811854ノート

反応式

HRID 1811854 の反応式
F[C:2]1[C:7]([C:8]2[N:16]=[C:15]([CH3:17])[N:14]=[C:13]3[C:9]=2[N:10]=[CH:11][N:12]3C2CCCCO2)=[CH:6][C:5]([CH2:24][O:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)=[CH:4][N:3]=1.[NH2:35][C:36]1[CH:44]=[CH:43][CH:42]=[C:41]2[C:37]=1[CH:38]=[CH:39][NH:40]2.Cl>CCO.CO.N>[CH3:34][O:33][C:30]1[CH:29]=[CH:28][C:27]([CH2:26][O:25][CH2:24][C:5]2[CH:6]=[C:7]([C:8]3[N:16]=[C:15]([CH3:17])[N:14]=[C:13]4[C:9]=3[N:10]=[CH:11][NH:12]4)[C:2]([NH:35][C:36]3[C:37]4[CH:38]=[CH:39][NH:40][C:41]=4[CH:42]=[CH:43][CH:44]=3)=[N:3][CH:4]=2)=[CH:32][CH:31]=1

参加物

7

反応物 3

HCID 313Hydrochloric AcidHCID 5834314-AminoindoleHCID 595483946-(2-fluoro-5-((4-methoxybenzyloxy)methyl)pyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

生成物 1

HCID 178491393N-(5-((4-methoxybenzyloxy)methyl)-3-(2-methyl-9H-purin-6-yl)pyridin-2-yl)-1H-indol-4-amine収率 7.2%

試薬・触媒・溶媒 3

HCID 222Ammonia溶媒HCID 702Ethanol溶媒HCID 887Methanol溶媒2 回

反応条件

温度
100 °C

実験手順

6-(2-Fluoro-5-((4-methoxybenzyloxy)methyl)pyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (171.2 mg, 0.3694 mmol) and 4-aminoindole (Aldrich, St. Louis, Mo., 69.2 mg, 0.524 mmol) were suspended in EtOH (2.0 mL) and hydrochloric acid (J.T. Baker, Phillipsburg, N.J., 5 N, 0.090 mL, 0.45 mmol) was added. The flask was fitted with a reflux condenser and placed in a preheated oil bath (100° C.) and stirred for about 105 minutes. Then, the reaction was cooled to room temperature and diluted with MeOH and 2 N ammonia in MeOH. The reaction was concentrated and treated with DMF and DCM and filtered. The filtrate was filtered again, and the solid was again washed with DCM. This filtrate was concentrated and purified by HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 ml/min). The fractions with product were collected, concentrated, and filtered through a silica gel filter (about 1 inch, 10:1 DCM/2 N ammonia in MeOH) to give N-(5-((4-methoxybenzyloxy)methyl)-3-(2-methyl-9H-purin-6-yl)pyridin-2-yl)-1H-indol-4-amine (13.1 mg, 7% yield). MS (ESI pos. ion) m/z 492 (M+H)+. 1H NMR (d6-DMSO, 400 MHz) δ 12.49 (s, 1H), 11.17 (s, 1H), 9.84 (s, 1H), 8.64 (s, 1H), 8.33 (s, 1H), 8.04 (d, J=6.85 Hz, 1H), 7.38-7.32 (m, 3H), 7.12-7.04 (m, 2H), 6.93 (d, J=8.80 Hz, 2H), 6.72 (s, 1H), 4.53 (s, 2H), 4.51 (s, 2H), 3.75 (s, 3H), 2.92 (s, 3H).

後処理

  1. customThe flask was fitted with a reflux condenser
  2. customplaced in a preheated oil bath
  3. temperatureThen, the reaction was cooled to room temperature
  4. concentrationThe reaction was concentrated
  5. additiontreated with DMF and DCM
  6. filtrationfiltered
  7. filtrationThe filtrate was filtered again
  8. washthe solid was again washed with DCM
  9. concentrationThis filtrate was concentrated
  10. custompurified by HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 ml/min)
  11. customThe fractions with product were collected
  12. concentrationconcentrated
  13. filtrationfiltered through a silica gel
  14. filtrationfilter (about 1 inch, 10:1 DCM/2 N ammonia in MeOH)

出典と根拠

ORDレコード
ord-083fed959b274af8b1430bc3087132c3
出典データセット
uspto-grants-2013_01
特許番号
US08362241B2

反応ノート

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