1-[4-(6-Chloro-pyrimidin-4-yloxy)-phenyl]-3-p-tolyl-urea → 1-[4-(6-Ethyl-pyrimidin-4-yloxy)phenyl]-3-p-tolyl-urea

HRID 1993534Notes

Reaction equation

Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=3)=[O:17])=[CH:11][CH:10]=2)[CH:3]=1.C([Cu])#N.[CH3:29][CH2:30][Mg+].[Br-]>C1COCC1>[CH2:29]([C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=3)=[O:17])=[CH:11][CH:10]=2)[CH:3]=1)[CH3:30]

Participants

Conditions

Temperature: -78 °C

Procedure

1-[4-(6-Chloro-pyrimidin-4-yloxy)-phenyl]-3-p-tolyl-urea (Example 97; 106 mg, 0.3 mmol) is dissolved in THF (10 mL) under an argon atmosphere and CuCN (215 mg, 2.4 mmol) is added. The mixture is then cooled to −78° C. and EtMgBr (1.8 ml of a 3 M solution in THF) is added via a canula. The reaction mixture is allowed to stir for 30 min at −78° C. and then warmed to rt resulting in a brown suspension. It Is stirred for additional 30 min at rt and then the solvent is removed in vacuo. The residual crude product is re-dissloved in CH2Cl2/MeOH 1:1 and purified by flash chromatography (SiO2, gradient hexanes/ethyl acetate 1:1 to 3:7) to give the title compound which is further purified by preparative TLC (SiO2, hexanes/AcOEt 3:7): m.p.=160-162° C.; C20H20N4O2: M+=349.1; 1H-NMR (DMSO-d6): 9.55 (s, 1H, HN), 9.45 (s, 1H, HN), 8.64 (s, 1H), 7.55 (d, 2H); 7.40 (d, 2H), 7.10-7.06 (m, 4H), 6.92 (s, 1H), 2.70 (q, 2H), 2.24 (s, 3H), 1.22 (t, 3H).

Workup

temperaturewarmed to rt
customresulting in a brown suspension
stirringIt Is stirred for additional 30 min at rt
customthe solvent is removed in vacuo
custompurified by flash chromatography (SiO2, gradient hexanes/ethyl acetate 1:1 to 3:7)

Sources & evidence

ORD record: ord-fc5f308ea1564e71906f0d4564306715
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07652022B2

Reaction notes

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