Dichloromethane → 2,4-Diamino-6-ethyl-5-(3-(6-chloroquinolin-4-yloxy)propoxy)pyrimidine

HRID 40801Notes

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

Participants

Conditions

Temperature: 25 °C

Procedure

2,4-Diamino-6-ethyl-5-hydroxypyrimidine (1.39 g, 9 mmol) was added to a stirred solution of lithium hydroxide monohydrate (1.32 g, 31.50 mmol) in DMF (5 mL) and the reaction mixture was stirred at 25° C. for 1 hour. A solution of 3-(6-chloroquinolin-4-yloxy)propyl bromide (2.71 g, 9 mmol) in DMF (3 mL) was added and the reaction mixture was left stirring at 25° C. overnight. DMF was partially removed under reduced pressure to give residue. The residue was digested with dichloromethane and filtered to give white solid. Recrystallization with aqueous methanol and hot water afforded the desired diaminopyrimidine as white solid (1.85 g, 55%, m.p. 230-231° C. (dec.)). 1H NMR (500 MHz, DMSO-d6): 0.91 (3H, t, J=7.6 Hz), 2.26 (2H, q, J=7.6 Hz), 2.31 (2H, m), 3.86 (2H, t, J=6 Hz), 4.45 (2H, t, J=5.9 Hz), 5.59 (2H, s), 6.17, (2H, s), 7.15 (1H, d, J=5.3 Hz), 7.76 (1H, dd, J=9.0, 2.4 Hz), 7.98 (1H, d, J=9.0 Hz), 8.14 (1H, d, J=2.4 Hz), 8.77 (1H, d, J=5.2 Hz).

Workup

waitthe reaction mixture was left
stirringstirring at 25° C. overnight
customDMF was partially removed under reduced pressure
customto give residue
filtrationfiltered
customto give white solid
customRecrystallization with aqueous methanol and hot water

Sources & evidence

ORD record: ord-4b116ecee37545d8ae00883982414f58
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530491B2

Reaction notes

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