Potassium Carbonate → 5-bromo-6-((2,4-difluorobenzyl)oxy)-3-(5-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2-methylphenyl)-2-methylpyrimidin-4(3H)-one

HRID 2172593Notes

Reaction equation

[Br:1][C:2]1[C:3](=[O:30])[N:4]([C:19]2[CH:24]=[C:23]([C:25](=O)[C:26]#[CH:27])[CH:22]=[CH:21][C:20]=2[CH3:29])[C:5]([CH3:18])=[N:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].Cl.[OH:32][C:33]([CH3:38])([CH3:37])[C:34]([NH2:36])=[NH:35].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Br:1][C:2]1[C:3](=[O:30])[N:4]([C:19]2[CH:24]=[C:23]([C:25]3[CH:26]=[CH:27][N:36]=[C:34]([C:33]([OH:32])([CH3:38])[CH3:37])[N:35]=3)[CH:22]=[CH:21][C:20]=2[CH3:29])[C:5]([CH3:18])=[N:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]

Participants

Conditions

Temperature: 75 °C

Procedure

To a solution of the 5-bromo-6-(2,4-difluoro-benzyloxy)-2-methyl-3-(2-methyl-5-propynoyl-phenyl)-3H-pyrimidin-4-one of Step E (80 mg, 0.17 mmol) in acetonitrile (3 mL) was added 2-hydroxy-2-methylpropionamidine HCl (35 mg, 0.25 mmol) and potassium carbonate (70 mg, 0.50 mmol) and the slurry was heated at 75° C. for eighteen hours. The reaction was returned to ambient temperature and filtered to remove excess salts. The filtrate was concentrated and purified via normal phase chromatography (ethyl acetate/heptane) to provide the title compound as a white solid (58 mg, 61% yield). MS (M, M+2): 557, 559; 1H NMR (400 MHz, chloroform-d) δ ppm, 1.64 (s, 6H), 2.17 (s, 3H), 2.20 (s, 3H), 5.50-5.60 (m, 2H), 6.87-6.94 (m, 2H), 7.54-7.58 (m, 3H), 7.92 (s, 1H), 8.13 (d, J=7.04 Hz, 1H), 8.77 (d, J=4.30, 1H).

Workup

customwas returned to ambient temperature
filtrationfiltered
customto remove excess salts
concentrationThe filtrate was concentrated
custompurified via normal phase chromatography (ethyl acetate/heptane)

Sources & evidence

ORD record: ord-dd9b846445844abda352019818a8c978
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09056110B2

Reaction notes

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