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

HRID 40809Notes

Reaction equation

[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

Participants

Conditions

Temperature: 25 °C

Procedure

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).

Workup

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

Sources & evidence

ORD record: ord-e4ad3480d9094ed8b2e30f8b48a9aac7
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530491B2

Reaction notes

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