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

HRID 1811854노트

반응식

HRID 1811854 반응식
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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 222Ammonia용매HCID 702Ethanol용매HCID 887Methanol용매2회

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온도
100 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-083fed959b274af8b1430bc3087132c3
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08362241B2

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