N,N'-Dimethylethylenediamine → 1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-4-(methylthio)pyrimidin-2(1H)-one

HRID 2059841Notes

Reaction equation

CNCCNC.[CH3:7][S:8][C:9]1[CH:14]=[CH:13][NH:12][C:11](=[O:15])[N:10]=1.Br[C:17]1[CH:28]=[CH:27][C:20]([O:21][CH2:22][C:23]([CH3:26])([OH:25])[CH3:24])=[C:19]([O:29][CH3:30])[CH:18]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(Cl)Cl.[Cu]I.O1CCOCC1.CN(C=O)C>[OH:25][C:23]([CH3:26])([CH3:24])[CH2:22][O:21][C:20]1[CH:27]=[CH:28][C:17]([N:12]2[CH:13]=[CH:14][C:9]([S:8][CH3:7])=[N:10][C:11]2=[O:15])=[CH:18][C:19]=1[O:29][CH3:30]

Participants

Conditions

Temperature: 105 °C

Procedure

After addition of N,N′-Dimethylethane-1,2-diamine (1.6 g, 18.15 mmol) to a stirred mixture of 4-(methylthio)pyrimidin-2(1H)-one Part A (430 mg, 3.02 mmol), 1-(4-bromo-2-methoxyphenoxy)-2-methylpropan-2-ol Part B (1.0 g, 3.63 mmol), copper(I)iodide (346 mg, 1.82 mmol) and potassium phosphate, tribasic (3.85 g, 18.15 mmol) in 3:1 dioxane-DMF (80 mL), the mixture was stirred at 105° C. for 7 h. The reaction mixture was diluted with CH2Cl2, washed with saturated NaHCO3, dried (MgSO4) and concentrated. The crude product was subjected to flash chromatography (silica gel/hexane-EtOAc 100:0 to 0:100 gradient) to afford 1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-4-(methylthio)pyrimidin-2(1H)-one 1C (0.375 g, 37% yield). 1H NMR (400 MHz, chloroform-D) δ 7.37 (1H, d, J=7.03 Hz), 6.95 (1H, d, J=8.53 Hz), 6.92 (1H, d, J=2.51 Hz), 6.85 (1H, dd, J=8.53, 2.51 Hz), 6.28 (1H, d, J=7.03 Hz), 3.85 (3H, s), 3.84 (2H, s), 2.61 (3H, s), 2.59 (1H, s), 1.35 (6H, s).

Workup

washwashed with saturated NaHCO3
dry with materialdried (MgSO4)
concentrationconcentrated

Sources & evidence

ORD record: ord-75d52f83c5c04a188d27ed75da4806e3
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278316B2

Reaction notes

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