Potassium Carbonate → 5-chloro-3-(5-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2-methylphenyl)-2-methyl-6-((3-methylbenzyl)oxy)pyrimidin-4(3H)-one

HRID 2172605Notes

Reaction equation

HRID 2172605 reaction equation
[Cl: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])[CH: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>[Cl: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])[CH:11]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 426142842-Hydroxy-2-methylpropanimidamide hydrochlorideHCID 715826495-chloro-2-methyl-6-(3-methyl-benzyloxy)-3-(2-methyl-5-propynoyl-phenyl)-3H-pyrimidin-4-one

Product 1

HCID 715823365-chloro-3-(5-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2-methylphenyl)-2-methyl-6-((3-methylbenzyl)oxy)pyrimidin-4(3H)-oneYield 26%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 5-chloro-2-methyl-6-(3-methyl-benzyloxy)-3-(2-methyl-5-propynoyl-phenyl)-3H-pyrimidin-4-one from Example 4, Step E (25 mg, 0.06 mmol) in acetonitrile (2 mL) was added 2-hydroxy-2-methyl propionamidine HCl (13 mg, 0.09 mmol) and potassium carbonate (25 mg, 0.18 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 (7.6 mg, 26% yield). MS (M+H): 491; 1H NMR (400 MHz, chloroform-d) δ ppm, 1.65 (s, 6H), 2.17 (s, 3H), 2.21 (s, 3H), 2.40 (s, 3H), 5.47-5.56 (m, 2H), 7.17 (s, 1H), 7.26-7.31 (m, 3H), 7.54-7.58 (m, 2H), 7.92 (s, 1H), 8.14 (d, J=7.43 Hz, 1H), 8.76 (d, J=5.08 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-9b1ba3b8a0af457382a649dd96c34e70
Source dataset
uspto-grants-2015_06
Patent number
US09056110B2

Reaction notes

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