Potassium Carbonate → 3-{5-Cyclopropyl-3-[2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl}-5-methyl-benzonitrile

HRID 426256Notes

Reaction equation

HRID 426256 reaction equation
[CH:1]1([C:4]2[C:9](=[O:10])[NH:8][C:7](=[O:11])[N:6]([CH2:12][C:13]3[CH:18]=[C:17]([F:19])[N:16]=[C:15](F)[CH:14]=3)[C:5]=2[C:21]([C:23]2[CH:24]=[C:25]([CH:28]=[C:29]([CH3:31])[CH:30]=2)[C:26]#[N:27])=[O:22])[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].FC1C=C(COS(C)(=O)=O)C=C([NH:51][CH2:52][C:53]2[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[CH:55][CH:54]=2)N=1.[I-].[Li+]>CN(C=O)C.C(OCC)(=O)C>[CH:1]1([C:4]2[C:9](=[O:10])[NH:8][C:7](=[O:11])[N:6]([CH2:12][C:13]3[CH:14]=[C:15]([NH:51][CH2:52][C:53]4[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[CH:55][CH:54]=4)[N:16]=[C:17]([F:19])[CH:18]=3)[C:5]=2[C:21]([C:23]2[CH:24]=[C:25]([CH:28]=[C:29]([CH3:31])[CH:30]=2)[C:26]#[N:27])=[O:22])[CH2:2][CH2:3]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 66321Lithium iodideHCID 250296833-[5-Cyclopropyl-3-(2,6-difluoro-pyridin-4-ylmethyl)-2,6-dioxo 1,2,3,6tetrahydro-pyrimidine-4-carbonyl]-5-methyl-benzonitrileHCID 59184646Methanesulfonic acid 2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl ester

Product 1

HCID 591847693-{5-Cyclopropyl-3-[2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl}-5-methyl-benzonitrileYield 34%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-[5-Cyclopropyl-3-(2,6-difluoro-pyridin-4-ylmethyl)-2,6-dioxo-1,2,3,6tetrahydro-pyrimidine-4-carbonyl]-5-methyl-benzonitrile (16 mg, 0.054 mmol) was dissolved in 0.5 mL DMF. Potassium carbonate (7.5 mg, 1 eq.) and methanesulfonic acid 2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl ester (1 eq.) were added to the reaction, followed by lithium iodide (7.2 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 give light yellow oil (10 mg, 34%). LC-MS shows 540.0 (M+1). 1H NMR (300 MHz, CDCl3): δ 7.81 (s, 1H), 7.63 (s, 1H), 7.59 (s, 1H), 7.23 (s, 1H), 7.21 (s, 2H), 6.91 (s, 1H), 6.88 (s, 1H), 5.80 (s, 1H), 5.78 (s, 1H), 4.26 (d, 2H), 3.80 (s, 2H), 2.39 (s, 3H), 0.9 (m, 1H), 0.62 (m, 3H), 0.41 (m, 1H).

Workup

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

Sources & evidence

ORD record
ord-fa8d926c66304df9b295e64d9ca65fb2
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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