Potassium Carbonate → 5-bromo-3-(5-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2-methylphenyl)-2-methyl-6-((6-methylpyridin-2-yl)methoxy)pyrimidin-4(3H)-one

HRID 2172624Notes

Reaction equation

HRID 2172624 reaction equation
[Br:1][C:2]1[C:3](=[O:29])[N:4]([C:18]2[CH:23]=[C:22]([C:24](=O)[C:25]#[CH:26])[CH:21]=[CH:20][C:19]=2[CH3:28])[C:5]([CH3:17])=[N:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([CH3:16])[N:11]=1.Cl.[OH:31][C:32]([CH3:37])([CH3:36])[C:33]([NH2:35])=[NH:34].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Br:1][C:2]1[C:3](=[O:29])[N:4]([C:18]2[CH:23]=[C:22]([C:24]3[CH:25]=[CH:26][N:35]=[C:33]([C:32]([OH:31])([CH3:37])[CH3:36])[N:34]=3)[CH:21]=[CH:20][C:19]=2[CH3:28])[C:5]([CH3:17])=[N:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([CH3:16])[N:11]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 426142842-Hydroxy-2-methylpropanimidamide hydrochlorideHCID 715815755-bromo-2-methyl-3-(2-methyl-5-propynoyl-phenyl)-6-(6-methyl-pyridin-2-ylmethoxy)-3H-pyrimidin-4-one

Product 1

HCID 715825045-bromo-3-(5-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2-methylphenyl)-2-methyl-6-((6-methylpyridin-2-yl)methoxy)pyrimidin-4(3H)-oneYield 42%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 5-bromo-2-methyl-3-(2-methyl-5-propynoyl-phenyl)-6-(6-methyl-pyridin-2-ylmethoxy)-3H-pyrimidin-4-one of Step D (54 mg, 0.12 mmol) in acetonitrile (1 mL) was added 2-hydroxy-2-methylpropionamidine HCl (25 mg, 0.18 mmol) and potassium carbonate (50 mg, 0.36 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 light yellow solid (27 mg, 42% yield). MS (M, M+2): 536, 538; 1H NMR (400 MHz, chloroform-d) δ ppm, 1.64 (s, 6H), 2.14 (s, 3H), 2.21 (s, 3H), 2.61 (s, 3H), 4.78 (s, 1H), 5.61-5.72 (m, 2H), 7.14 (d, J=7.83 Hz, 1H), 7.43 (d, J=7.44 Hz, 1H), 7.54-7.58 (m, 2H), 7.70 (s, 1H), 7.92 (s, 1H), 8.13 (d, J=7.82 Hz, 1H), 8.77 (d, J=5.09 Hz, 1H).

Workup

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

Sources & evidence

ORD record
ord-8eb98988d96b4e21b71f39ad4cec5c36
Source dataset
uspto-grants-2015_06
Patent number
US09056110B2

Reaction notes

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