Potassium Carbonate → 5-chloro-3-(5-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2-methylphenyl)-2-methyl-6-((6-(trifluoromethyl)pyridin-2-yl)methoxy)pyrimidin-4(3H)-one

HRID 2172632Notes

Reaction equation

HRID 2172632 reaction equation
[Cl:1][C:2]1[C:3](=[O:32])[N:4]([C:21]2[CH:26]=[C:25]([C:27](=O)[C:28]#[CH:29])[CH:24]=[CH:23][C:22]=2[CH3:31])[C:5]([CH3:20])=[N:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[N:11]=1.Cl.[OH:34][C:35]([CH3:40])([CH3:39])[C:36]([NH2:38])=[NH:37].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Cl:1][C:2]1[C:3](=[O:32])[N:4]([C:21]2[CH:26]=[C:25]([C:27]3[CH:28]=[CH:29][N:38]=[C:36]([C:35]([OH:34])([CH3:40])[CH3:39])[N:37]=3)[CH:24]=[CH:23][C:22]=2[CH3:31])[C:5]([CH3:20])=[N:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[N:11]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 426142842-Hydroxy-2-methylpropanimidamide hydrochlorideHCID 715816405-chloro-2-methyl-3-(2-methyl-5-propynoyl-phenyl)-6-(6-trifluoromethyl-pyridin-2-ylmethoxy)-3H-pyrimidin-4-one

Product 1

HCID 715824095-chloro-3-(5-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2-methylphenyl)-2-methyl-6-((6-(trifluoromethyl)pyridin-2-yl)methoxy)pyrimidin-4(3H)-oneYield 32%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 5-chloro-2-methyl-3-(2-methyl-5-propynoyl-phenyl)-6-(6-trifluoromethyl-pyridin-2-ylmethoxy)-3H-pyrimidin-4-one of Step C (50 mg, 0.11 mmol) in acetonitrile (1 mL) was added 2-hydroxy-2-methylpropionamidine HCl (23 mg, 0.16 mmol) and potassium carbonate (45 mg, 0.33 mmol) and the slurry heated at 75° C. for eighteen hours. After cooling to room temperature the reaction was 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 yellow oil (19 mg, 32% yield). MS (M+H): 546; 1H NMR (400 MHz, chloroform-d) δ ppm, 1.64 (s, 6H), 2.15 (s, 3H), 2.21 (s, 3H), 5.69-5.78 (m, 2H), 7.56-7.59 (m, 2H), 7.66 (d, J=7.43 Hz, 1H), 7.82 (d, J=7.82 Hz, 1H), 7.94-8.00 (m, 2H), 8.14 (d, J=7.43 Hz, 1H), 8.78 (d, J=5.08 Hz, 1H).

Workup

  1. temperatureAfter cooling to room temperature the reaction
  2. filtrationwas filtered
  3. customto remove excess salts
  4. concentrationThe filtrate was concentrated
  5. custompurified via normal phase chromatography (ethyl acetate/heptane)

Sources & evidence

ORD record
ord-f12c3ebcf8764b928b0f32530f17d782
Source dataset
uspto-grants-2015_06
Patent number
US09056110B2

Reaction notes

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