Lithium hydroxide, monohydrate → 2,4-Diamino-6-ethyl-5-(3-(7-fluoro-2-methylquinolin-4-yloxy)propoxy)pyrimidine

HRID 40809노트

반응식

HRID 40809 반응식
[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([OH:9])=[C:4]([CH2:10][CH3:11])[N:3]=1.O.[OH-].[Li+].[F:15][C:16]1[CH:25]=[C:24]2[C:19]([C:20]([O:27][CH2:28][CH2:29][CH2:30]Br)=[CH:21][C:22]([CH3:26])=[N:23]2)=[CH:18][CH:17]=1>CN(C=O)C>[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([O:9][CH2:30][CH2:29][CH2:28][O:27][C:20]2[C:19]3[C:24](=[CH:25][C:16]([F:15])=[CH:17][CH:18]=3)[N:23]=[C:22]([CH3:26])[CH:21]=2)=[C:4]([CH2:10][CH3:11])[N:3]=1

참가 물질

5

반응물 3

HCID 168937Lithium hydroxide, monohydrateHCID 205093882,4-Diamino-6-ethylpyrimidin-5-olHCID 685750043-(7-Fluoro-2-methylquinolin-4-yloxy)propyl bromide

생성물 1

HCID 252627632,4-Diamino-6-ethyl-5-(3-(7-fluoro-2-methylquinolin-4-yloxy)propoxy)pyrimidine수율 51%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
25 °C

실험 절차

A mixture of 2,4-diamino-6-ethyl-5-hydroxypyrimidine (0.5395 g, 3.5 mmol) and lithium hydroxide monohydrate (0.294 g, 7.0 mmol) in DMF (10 mL) was stirred at 25° C. for 1 hour after that 3-(7-fluoro-2-methylquinolin-4-yloxy)propyl bromide (1.043 g, 3.5 mmol) was added to the reaction mixture and the reaction mixture was left to stir at 25° C. overnight. Two thirds of the DMF was evaporated under vacuum and reaction mixture was poured in water, solid was separated by filtration and dried in oven at 80° C. The crude product was purified by column chromatography on silica gel (4% MeOH: 96% CH2Cl2 as eluent). The product was obtained as white crystalline solid (0.6629 g, 51%). 1H NMR (400 MHz, DMSO-d6): 0.89 (3H, t, J=7.5 Hz), 2.28 (4H, m), 2.60 (3H, s), 3.85 (2H, t, J=5.9 Hz), 4.42 (2H, t, J=5.9 Hz), 5.57 (2H, s), 6.15 (2H, s), 6.99 (1H, s), 7.39 (1H, dt, J=8.8, 2.5 Hz), 7.57 (1H, dd, J=10.8, 2.5 Hz), 8.15 (1H, dd, J=9.1, 6.4 Hz).

후처리

  1. additionwas added to the reaction mixture
  2. waitthe reaction mixture was left
  3. customTwo thirds of the DMF was evaporated under vacuum and reaction mixture
  4. additionwas poured in water
  5. customsolid was separated by filtration
  6. customdried in oven at 80° C
  7. customThe crude product was purified by column chromatography on silica gel (4% MeOH: 96% CH2Cl2 as eluent)

출처 및 근거

ORD 기록
ord-e4ad3480d9094ed8b2e30f8b48a9aac7
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08530491B2

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