Potassium Carbonate → 3-[[3-(2-Fluoro-pyridin-4-ylmethyl)-5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yl]-(4-methoxy-benzyloxyimino)-methyl]-5-methyl-benzonitrile

HRID 426257Notes

Reaction equation

HRID 426257 reaction equation
[CH:1]([C:4]1[C:9](=[O:10])[NH:8][C:7](=[O:11])[NH:6][C:5]=1[C:12](=[N:22][O:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=1)[C:13]1[CH:14]=[C:15]([CH:18]=[C:19]([CH3:21])[CH:20]=1)[C:16]#[N:17])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:40][C:41]1[CH:46]=[CH:45][N:44]=[C:43]([F:47])[CH:42]=1.[I-].[Li+]>CN(C=O)C.C(OCC)(=O)C>[F:47][C:43]1[CH:42]=[C:41]([CH2:40][N:6]2[C:5]([C:12](=[N:22][O:23][CH2:24][C:25]3[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=3)[C:13]3[CH:14]=[C:15]([CH:18]=[C:19]([CH3:21])[CH:20]=3)[C:16]#[N:17])=[C:4]([CH:1]([CH3:3])[CH3:2])[C:9](=[O:10])[NH:8][C:7]2=[O:11])[CH:46]=[CH:45][N:44]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 66321Lithium iodideHCID 139851684-Bromomethyl-2-fluoropyridineHCID 866192353-[(5-Isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yl)-(4-methoxybenzyloxyimino)-methyl]-5-methyl-benzonitrile

Product 1

HCID 866192343-[[3-(2-Fluoro-pyridin-4-ylmethyl)-5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yl]-(4-methoxy-benzyloxyimino)-methyl]-5-methyl-benzonitrile

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-[(5-Isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yl)-(4-methoxybenzyloxyimino)-methyl]-5-methyl-benzonitrile (71 mg, 0.164 mmol, 1.2 eq.) was dissolved in 2.0 mL DMF. Potassium carbonate (19 mg, 0.137 mmol, 1 eq.) and 4-bromomethyl-2-fluoro-pyridine (26 mg, 1 eq.) were added to the reaction, followed by lithium iodide (18 mg, 1 eq.) 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, 20-80% EtOAc/hexane) to white powder (32 mg, 36%). LC-MS shows 542.2 (M+1). 1H NMR (300 MHz, CDCl3): δ 8.80 (br, 1H), 7.93 (d, 1H), 7.62 (s, 1H), 7.42 (s, 1H), 7.32 (d, 2H), 7.21 (s, 1H), 6.92 (d, 2H), 6.72 (d, 1H), 6.40 (s, 1H), 5.08 (dd, 2H), 4.90 (d, 1H), 4.22 (d, 1H), 3.80 (s, 3H), 2.32 (s, 3H), 2.20 (m, 1H), 1.16 (d, 3H), 1.12 (d, 3H).

Workup

  1. washby washing with brine
  2. concentrationThe organic layer was concentrated down
  3. custompurified (silica gel, 20-80% EtOAc/hexane) to white powder (32 mg, 36%)

Sources & evidence

ORD record
ord-b4b0368736674c7da089d1dc3c4f05e2
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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