Potassium Carbonate → 1-[2-Fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-5-isopropyl-6-(2,3,5-trimethyl-phenoxy)-1H-pyrimidine-2,4-dione

HRID 426261Notes

Reaction equation

HRID 426261 reaction equation
[CH:1]([C:4]1[C:5](=[O:21])[NH:6][C:7](=[O:20])[NH:8][C:9]=1[O:10][C:11]1[CH:16]=[C:15]([CH3:17])[CH:14]=[C:13]([CH3:18])[C:12]=1[CH3:19])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[F:28][C:29]1[CH:34]=[C:33]([CH2:35]OS(C)(=O)=O)[CH:32]=[C:31]([NH:41][CH2:42][C:43]2[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][CH:44]=2)[N:30]=1.[I-].[Li+]>CN(C=O)C.C(OCC)(=O)C>[F:28][C:29]1[CH:34]=[C:33]([CH2:35][N:8]2[C:9]([O:10][C:11]3[CH:16]=[C:15]([CH3:17])[CH:14]=[C:13]([CH3:18])[C:12]=3[CH3:19])=[C:4]([CH:1]([CH3:3])[CH3:2])[C:5](=[O:21])[NH:6][C:7]2=[O:20])[CH:32]=[C:31]([NH:41][CH2:42][C:43]2[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][CH:44]=2)[N:30]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 66321Lithium iodideHCID 59184646Methanesulfonic acid 2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl esterHCID 591848065-Isopropyl-6-(2,3,5-trimethyl-phenoxy)-1H-pyrimidine-2,4-dione

Product 1

HCID 591848531-[2-Fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-5-isopropyl-6-(2,3,5-trimethyl-phenoxy)-1H-pyrimidine-2,4-dioneYield 42%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-Isopropyl-6-(2,3,5-trimethyl-phenoxy)-1H-pyrimidine-2,4-dione (39 mg, 0.135 mmol) was dissolved in 1.5 mL DMF. Potassium carbonate (31 mg, 2 eq.) was added and the reaction was stirred at room temperature for 10 minutes. Methanesulfonic acid 2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl ester (0.135 mmol) and lithium iodide (15 mg, 1 eq.) were added. The reaction was stirred at room temperature overnight. Ethyl acetate was added to the reaction mixture, followed by washing with brine. The organic layer was concentrated down and purified (silica gel, 0-80% EtOAC/hexane) to give white powder (25 mg, 42%). LC-MS shows 533.1 (M+1). 1H NMR (300 MHz, CDCl3): δ 8.68 (b, 1H), 7.22 (d, 2H), 6.86 (d, 2H), 6.75 (s, 1H), 6.18 (s, 1H), 5.95 (d, 2H), 4.94 (d, 1H), 4.45 (d, 1H), 4.37 (s, 2H), 3.80 (s, 3H), 2.68 (m, 1H), 2.23 (s, 3H), 2.19 (s, 3H), 2.06 (s, 3H), 1.15 (dd, 6H).

Workup

  1. stirringThe reaction was stirred at room temperature overnight
  2. washby washing with brine
  3. concentrationThe organic layer was concentrated down
  4. custompurified (silica gel, 0-80% EtOAC/hexane)

Sources & evidence

ORD record
ord-1ef665098f6c4832837b03d14e71cfd1
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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